The nematode Caenorhabditis elegans, with its highly sensitive olfactory system, has emerged as a promising tool for testing chemotaxis. In the field of cancer diagnostics, there is a growing interest in the development of non-invasive screening methods for the detection of volatile organic compounds in a patient's urine. The objective of this study was to contribute to the existing body of knowledge by evaluating the ability of a Caenorhabditis elegans-based chemotaxis assay to discriminate between urine samples from healthy individuals and patients diagnosed with breast or colon cancer. Following synchronization of the developmental stages of C. elegans, nematodes were exposed to the urine of cancer patients and healthy individuals. Subsequently, chemotactic indices were calculated for each urine sample. Our results demonstrated a statistically significant difference in the chemotactic response of C. elegans to urine samples from cancer patients compared to healthy volunteers (p < 0.001). Moreover, the test exhibited promising diagnostic utility, with a sensitivity of 98%, a specificity of 62%, and a detection rate of 78%. Our findings expand on previous observations, confirming the remarkable sensitivity of C. elegans hermaphrodites to discriminating cancer-related volatile organic compounds in urine samples.

Introduction: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph-nodes, instead para-aortic lymph-nodes are considered as distant metastases. Aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Material/methods: This is a retrospective analysis. De-novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; pattern of recurrence was evaluated too. A propensity score matching (PSM) was applied to create comparable cohorts. Primary end-point was the progression-free survival (PFS). Secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS) and pattern of relapse. Results: 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. Median PFS was 20 and 11 months in pelvic and para-aortic patients respectively (p=0.042). The difference was not confirmed at the multivariate analysis (p=0.06). Median BRFS was 16 and 9 months respectively in pelvic and para-aortic group (p=0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-years LPFS was 90.5%. At PSM no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have PFS comparable to pelvic disease; local control is high in both cohorts. Our results support the use of SBRT also to para-aortic metastases.

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. We also used multivariable analyses to identify factors associated with patient interest in test use. In 2023, we surveyed 159 (32%) of 500 identified patients. Among respondents, 125 (79%) reported a high level of interest in having an MCED test. Interest was not associated with personal background characteristics, but was positively associated with the following expectations: testing would be recommended for cancer screening, be convenient, and be effective in finding early-stage disease (OR=11.70, 95% CI: 4.02, 34.04, p < 0.001). Research is needed to assess patient interest and actual uptake when detailed information on testing is presented in routine care.

Objectives: The aim of this study is to understand the rationale for the lack of interest to perform regular opportunistic oral cancer screening (OCS) by primary care providers (PCPs) and the challenges they have in incorporating OCS into their annual examination protocol. Method: Sequential exploratory mixed methods were used. Both qualitative and quantitative data from PCPs working at Nebraska Medicine were obtained. One-on-one in-depth interviews were performed to identify PCP's perceptions and challenges in performing OCS. The themes identified in the qualitative study were used as a guide in the development of survey questionnaires. The survey was emailed to all the PCPs (N=100), whose information was available on the Nebraska Medicine publicly accessible website. Results: The response rate was 34%. Approximately 60% of the participants mentioned that they currently perform oral cancer screening, but only 3.8% of the providers answered that they were performing comprehensive oral cancer screening every time. Forty-eight percent of the providers identified time as the biggest challenge. Over 35.3% of the providers answered that they perform screenings for patients with a history of tobacco (i.e., smoking) or alcohol use. Conclusion: Around half of the participants identified lack of time as their primary challenge in performing OCS and lack of knowledge as their second main obstacle. Very few provided comprehensive OCS and visual examination of the oral cavity is the only step performed often.

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Despite the latest advances, a major clinical issue in EOC is the disappointing prognosis related to chemoresistance in almost one-third of cases. Drug resistance relies on heterogeneous cancer stem cells (CSCs), endowed with tumor-initiating potential, leading to relapse. No biomarkers of chemoresistance have been validated yet. Recently, major signaling pathways, micro ribonucleic acids (miRNAs), and circulating tumor cells (CTCs) have been advocated as putative biomarkers and potential therapeutic targets for drug resistance. However, further investigation is mandatory before their routine implementation. In accordance with the increasing rate of therapeutic efforts in EOC, the need for biomarker-driven personalized therapies is growing. This review aims to discuss the emerging hallmarks of drug resistance with an in-depth insight into the underlying molecular mechanisms lacking so far. Finally, a glimpse of novel therapeutic avenues and future challenges will be provided.

Language barriers exacerbate health disparities among minorities. This study highlights the efficacy of simple interventions in mitigating language barriers, optimizing clinic efficiency, and enhancing preparedness for surgical procedures in Spanish-speaking (SS) females diagnosed with breast cancer in a safety net community hospital. A bilingual questionnaire was given to English and SS patients during their initial clinic visit. Additionally, a bilingual handout on surgical options and postoperative care was provided to selected surgical patients. Among the 41 patients studied, those who completed the questionnaire had an average encounter time of 27.06 minutes, compared to 45.26 minutes for those who did not. For SS patients, the average encounter time with the questionnaire was 34.07 minutes versus 46.54 minutes without it. The average cost of a medical interpreter was $17.04 with the questionnaire, versus $23.27 without. All SS patients who received the educational handout expressed greater satisfaction and understanding of their treatment plans and were less likely to require additional pre-surgery visits. This study demonstrated how the simple implementation of a translated questionnaire can reduce interpretation cost, encounter time, and improve clinic flow. Furthermore, utilizing a bilingual surgical educational handout enhances patient understanding, surgery readiness and reduces unnecessary additional visits.

The COVID-19 pandemic has led to numerous delays in cancer-related care and cancer-specific screening, but the extent is not fully understood. For those that experience a delay or disruption in care, health related self-management is required to re-engage in care pathways and the role of health literacy in this pathway has not been explored. The purpose of this analysis is to (1) report the frequency of self-reported delays in cancer treatment and preventative screening services at an academic, NCI-designated center during the COVID-19 pandemic and (2) investigate cancer-related care and screening delays among those with adequate and limited health literacy. A cross-sectional survey was administered from an NCI-designated Cancer Center with a rural catchment area during November 2020 through March 2021. Nearly 19 percent of participants were categorized as having limited health literacy. Twenty percent of those with a cancer diagnosis reported a delay in cancer-related care; and 23-30% of the sample reported a delay in cancer screening. In general, the proportions of delays among those with adequate and limited health literacy were similar with the exception of colorectal cacner screening. There was also a notable difference in the ability to re-engage in cervical cancer screening among those with adequate and limited health literacy. Thus, there is a role for those engaged in cancer-related education and outreach to offer additional navigation resources for those at risk to cancer-related care and screening disruptions. Future study is warranted to investigate the role of health literacy on cancer care engagement.

New strategies for enhancing drug delivery to the blood–brain barrier (BBB) represents a major challenge in treating cerebral diseases. Nano-emulsion based nanocarriers represent an ideal candidate to improve drug delivery thanks to their versatility in functionalization and cargo protection. In this work, a paclitaxel loaded nano-emulsion has been firstly functionalized and stabilized with two layers constituted of chitosan and hyaluronic acid, and, secondly, the latter has been conjugated to the CRT peptide. CRT is a bioactive peptide that selectively recognizes bEnd.3 cells, model of the BBB, thanks to its interactions with transferrin (Tf) and its receptor (TfR). Cytotoxic results showed a higher uptake of CRT functionalized nano-emulsion 41.5 % more than the negative control, demonstrating the ability of this novel tool to be accumulated on the brain endothelium tissue. Thanks to these results, our approach can be fully generalizable to the design of multifunctional nanocarriers for delivery of therapeutic agents to the central nervous systems.

Most head and neck cancers are diagnosed in advanced stages, when the curative interventions are no longer possible. The assessment and the multidisciplinary therapeutic approach of the locally advanced cases are difficult since the onset of the disease becomes a significant challenge for the whole attending team (including both the patient and his family) because they have to deal with to an extensive symptomatology (abundant secretions, refractory pain, mutilations predominantly in the cephalic area), with the cure of stomas (tracheostomy, gastrostomy) and with various post-therapeutic sequelae. The present paper reflects the impact of late diagnosis, the complexity of the multimodal specific oncological treatment (chemotherapy, radiotherapy, immunotherapy, pal-liative and terminal treatment), the adaptation of medical care to the psycho-emotional structure, having as an example the case of 54-year old patient (with his consent) diagnosed with pharyn-golaryngeal neoplasm who presented himself to “St. Luca” Chronic Disease Hospital, the Oncol-ogy-Palliative Care Department, in September 2021. In patients with locally advanced head and neck cancers, besides the specifically oncological therapeutic decisions, the empathic-emotional connection between the medical team with the patient and his family plays a key role in the ther-apeutic conduct.

The coronavirus disease 2019 (COVID-19) pandemic has caused considerable global disruption to clinical practice. This article will review the impact that the pandemic has had on oncology clinical trials. It will assess the effect of the COVID-19 situation on the initial presentation and investigation of patients with suspected cancer. It will also discuss the impact of the pandemic on the subsequent management of cancer patients and how clinical trial approval, recruitment and conduct were affected during the pandemic. An intriguing aspect of the pandemic is that clinical trials investigating treatments for COVID-19 and vaccinations against the causative virus, SARS-CoV-2, have been approved and conducted at unprecedented speed. In light of this, this re-view will also discuss the potential that this enhanced regulatory environment could have on the running of oncology clinical trials in the future.

(1)Background: When the COVID-19 pandemic arrived, changes had to be made to several management aspects at our Pediatric Oncology Center. We investigated how the families per-ceived these changes. (2) Methods: Two questionnaires were developed at the Pediatric Oncology Unit of the Istituto Nazionale dei Tumori in Milan, to explore how the pandemic has affected the experience of patients who had been or were being treated at our hospital, and their families. These were administered to three samples of individuals. (3) Results: Between July and October 2020, 120 questionnaires were administered to parents of patients. The impact of school closures and the impossibility of attending sports and social activities outside the hospital were regarded as im-portant. 77.5% of parents judged the social distancing to have affected their children. Regarding the changes introduced in the management of the ward and outpatient clinic, most parents’ opinions were positive. Differences in the opinions expressed by Groups 2 and 3 were statistically significant on the topic of relationships on the ward and staff workload. The aspect most negatively affected by the pandemic was the support that patients’ parents were able to give each other. Regardless of whether patients were treated before the pandemic or after the first lockdown, their parents of all indicated a strong degree of satisfaction with the care received, and with the organizational ar-rangements. (4) Conclusions: The results of our study point us in the right direction to further improve our daily work and better respond to the needs of our patients and their families.

Radiological imaging is essential for acute patient management in Intensive Care Units (ICUs); however, it introduces the risk of exposure to ionizing radiation. This review synthesizes research on radiation exposure in intensive care unit (ICU) settings, highlighting its rise during the COVID-19 pandemic and repetitive imaging. Our analysis extends to radiation safety thresholds, revealing that some ICU patients exceed annual occupational limits, emphasizing the need to balance diagnostic utility against potential long-term risks, such as cancer. Prospective studies have demonstrated an increase in the median Cumulative Effective Dose (CED) in patients with trauma over time, prompting calls for improved awareness and monitoring. Moreover, innovative dose-reduction strategies and optimized protocols, especially in neuro-ICU units, promise to mitigate these risks. This review highlights the essential but risky role of radiological imaging in critical care. It advocates rigorous radiation management protocols to safeguard patient health, while ensuring the continuity of high-quality medical care.

Cancer patients and their family caregivers experience various losses when patients become terminally ill, yet little is known about the grief experienced by patients and caregivers and factors that influence grief as patients approach death. Additionally, few, if any, studies have explored associations between advance care planning (ACP) and grief resolution among cancer patients and caregivers. To fill this knowledge gap, the current study examined changes in grief over time in patients and their family caregivers and whether changes in patient grief are associated with changes in caregiver grief. We also sought to determine how grief changed following completion of advance directives. The sample included advanced cancer patients and caregivers (n=98 dyads) from Coping with Cancer III, a federally funded, multi-site prospective longitudinal study of end-stage cancer care. Participants were interviewed at baseline and at follow-up roughly 2 months later. Results suggest synchrony, whereby changes in patient grief were associated with changes in caregiver grief. We also found that patients who completed a living will (LW) experienced increases in grief, while caregivers of patients who completed a do-not-resuscitate (DNR) order experienced reductions in grief, suggesting that ACP may prompt “grief work” in patients while promoting grief resolution in caregivers.

Background: In 2023, ChatGPT-4 has been impactful across several sectors including healthcare, where it aids in medical information analysis and education. Electronic Patient-Reported Outcomes (ePROs) play a crucial role in monitoring cancer patients’ post-treatment symptoms, enabling early in-terventions. However, managing the voluminous ePRO data presents significant challenges. This study assesses the feasibility of utilizing ChatGPT-4 for analyzing side effect data from ePROs. Methods: Thirty cancer patients were consecutively collected via a web-based ePRO platform, reporting side effects over 4 weeks. ChatGPT-4, simulating oncologists, dietitians, and nurses, analyzed this data and offered improvement suggestions, which were then reviewed by professionals in those fields. Results: Two oncologists, two dieticians and two nurses evaluated the AI’s performance across roles with 540 reviews. ChatGPT-4 excelled in data accuracy and completeness, and was noted for its empathy and support, enhancing communication and reducing caregiver stress. It was particularly effective as a dietician. Discussion: ChatGPT-4 shows promise in processing ePRO data with high accuracy, suggesting that AI can enhance clinical decision-making. Nevertheless, its limitations in emotional engagement highlight the need for AI to supplement, not replace, human care. Emphasizing the role of dietitians underscores the importance of nutritional advice in cancer care. Future studies will further explore the feasible application of AI and ePRO in cancer care clinical processes.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.

Introduction Prostate Cancer (PCa) exhibits one of the widest racial and socioeconomic disparities. PCa disparities have also been widely linked to location as living in more deprived regions was associated with lower healthcare access and worse outcomes. This study aims to examine PCa survival across various US counties in function of different socioeconomic profiles and discuss the role of potential intermediary factors. Methods The SEER database linked to county-level SES was utilized. Five-year PCa-specific survival using the Kaplan Meier method was performed for 5 racial/ethnic categories in function of SES quintiles. Multilevel Cox proportional hazards regression was performed to assess the relationship between county-level SES and PCa survival. Multivariate regression analysis was performed to examine the role of healthcare utilization and severity. Results 279,000 PCa records were extracted, 5-year PCa-specific survival was 94%. Overall, living in counties with worst poverty/income quintile and highest proportions of foreign-born/language-isolated increased PCa mortality by 23% each. No association was observed with county-level High-School education, while Bachelor’s-level education decreased mortality risk by 23%. Associations varied considerably upon racial/ethnic stratification. Multilevel analyses showed varying contributions of individual and area-level factors to survival within minorities. The relationship between SES and PCa survival appeared to be influenced by healthcare utilization and disease stage/grade. Discussion Racial/ethnic categories responded differently under similar county-level SES and individual-level factors to the point where disparities reversed in Hispanics. The inclusion of Healthcare utilization and severity factors may provide partial early support for their role as intermediaries. Healthcare access (insurance) might not necessarily be associated with better PCa survival, through performing biopsy and or/surgery. County-level education plays an important role in PCa decision-making as it might elucidate discussions of other non-invasive management options. Conclusion Findings of this study demonstrate that interventions need to be tailored according to each group's needs. This potentially informs the focus of public health efforts in terms of planning and prioritizing. This study could also direct further research delving into pathways between area-level characteristics with PCa survival.

Pharmacists must acquire the necessary knowledge to provide better drug therapy to patients. In other words, educational programs need to facilitate behavioral changes among pharmacists. Therefore, this study aimed to evaluate how the behavior of pharmacists changed after attending a palliative care educational program. We conducted a web-based questionnaire survey examining the behavior of pharmacists regarding palliative care before participating in the program, two months after participating in the program, and eight months after participating in the program, to determine the behavior and changes over time. For all questions, scores were higher at two and eight months after attending the program than before attending the program (P &lt;0.05). In addition, no significant difference was observed between two and eight months after attending the program for all questions (P =0.504-1.000). The knowledge gained from the educational program was used to repeatedly intervene with patients with cancer, to address the various symptoms they experienced and maintain their behavior. The proven effectiveness of this program serves as a stepping stone for a nationwide rollout across Japan’s 47 prefectures.

BRCA1 and 2 pathogenic variants increase lifetime risks of breast (50-75%) and ovarian cancer (15-20%). Guidelines recommend breast screening (MRI and mammogram) or risk-reducing mastectomy with salpingo-oophorectomy for ovarian cancer prevention. We sought to 1) characterize the population of BRCA1/2 carriers in Newfoundland and Labrador (NL) 2) evaluate risk-reducing interventions 3) identify factors influencing screening and prevention adherence. Methods: This is a retrospective study from a population-based provincial cohort of BRCA1/2 carriers. Eligibility criteria for risk-reducing interventions were defined for each case and patients were categorized based on their level of adherence with recommended screening or prevention. Chi-squared and regression analyses were used to determine which factors influenced uptake and level of adherence. Results: 276 BRCA1/2 carriers were identified; 156 living NL females composed the study population. Unaffected females were younger at testing than those with a cancer diagnosis (44.4 y versus 51.7 y; p=0.002). Categorized by eligibility, 61.0%, 61.6%, 39.0% and 75.7% of patients underwent MRI, mammogram, risk-reducing mastectomy, and risk-reducing salpingo-oophorectomy, respectively. Individuals with breast cancer were more likely to have risk-reducing mastectomy (64.7% versus 35.3%; p<0.001), and those who attended specialty hereditary cancer clinic were more likely to be adherent with breast/ovarian cancer recommendations (73.2% versus 13.4%; p<0.001) and to undergo risk-reducing salpingo-oophorectomy(84.1% versus 15.9%; p<0.001). Conclusions: Nearly 40% of female BRCA1/2 carriers were not receiving breast surveillance according to evidence-based recommendations. Cancer risk reduction and uptake of breast imaging and prophylactic breast and pelvic surgeries are significantly higher in patients who receive dedicated specialty care. Organized hereditary cancer prevention programs will be a valuable component of Canadian health care systems and have the potential to reduce the burden of disease country-wide.

Histone changes that are adjustable and transmitted without altering the DNA sequence are part of epigenetic control. In many disorders, most famously malignancy, abnormal genetic information is seen as a result of mismanagement of typical epigenetic mechanisms. A paradigm change in the diagnosis and treatment of cancer has been brought about by recent discoveries about the processes of epigenetic modifications, chromatin remodeling, and noncoding RNAs implicated in the changed expression patterns of tumor cells. There is a significant increase in the search for drugs that could alter the epigenetic environment altered by tumor cells and benefit from their therapeutic potential. Phytochemicals with a high concentration of naturally produced phenol molecules known as flavonoids can regulate genomic processes. Understanding the precise epigenetic alterations brought on by flavonoid-mediated mechanisms is necessary to develop combination therapy techniques and genomic therapies for cancer. This article aims to thoroughly examine the epigenetic modifications of flavonoids, including their anticancer properties.

Sexual issues and treatment side effects are not routinely discussed with men receiving treatment for prostate cancer and support to address these concerns is not consistent across settings. This study evaluates a brief e-learning resource designed to improve sexual wellbeing support and examine its effects on healthcare professionals’ sexual attitudes and beliefs. Healthcare professionals (n=44) completed an online questionnaire at baseline which included a modified 12-item sexual attitudes and beliefs survey (SABS). Follow-up questionnaires were completed immediately after the e-learning and at 4 weeks. Data were analysed using one-way, repeat measures ANOVAs to assess change in attitudes and beliefs over time. Significant improvements were observed at follow-up for a number of survey statements including ‘knowledge and understanding’, ‘confidence in discussing sexual wellbeing’ and the extent to which participants felt ‘equipped with the language to initiate conversations’. The resource was seen as concise, relevant to practice, and as providing useful information on potential side effects of treatment. Brief, e-learning has potential to address barriers to sexual wellbeing communication and promote delivery of support for prostate cancer survivors. Practical methods and resources should be included with these interventions to support implementation of learning and long-term changes in clinical behaviour.

Severe cancer pain significantly diminishes patients' quality of life, leading to increased reliance on caregivers. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD) with symptoms such as nausea, vomiting, drowsiness, and constipation. While controlled-release oxycodone is a viable option, its prolonged use can lead to opi-oid-induced constipation (OIC). Addressing this, a relative novel formulation - a fixed 2:1 ratio of oxycodone and naloxone in prolonged release - aims to provide analgesia while alleviating OIC. This review critically assesses the evidence on the efficacy, safety, and patient experience of ox-ycodone/naloxone prolonged release in managing severe cancer pain, emphasizing the necessity for a targeted approach in this patient population.

Locally advanced rectal cancer requires multimodal treatment. Radiotherapy is being explored for intensification to improve rates of pathological complete responses (ypCR-rates) that correlates with better outcomes. This study reports a comparison between standard versus escalated dose in preoperative scenario. YpCR-rates, toxicity, postoperative complications, disease-free and overall survival at 5 years have been described. From 2012 to 2019, 99 patients were analyzed retrospectively: standard arm (mean 47.5Gy) vs. dose-escalated arm (mean 54.3Gy). All patients were treated with 3DRT in 25 fractions, concomitantly capecitabine and surgery performed according to total mesorectal excision principles in both arms. YpCR was reported by “College of American Pathologist grades”; gastrointestinal (GI) and genitourinary (GU) toxicity using the “Common Terminology Criteria for Adverse Events” (CTCAE 4.0). YpCR-rates were higher in the dose-escalated group (25% vs. 10.64%; p = 0.07) with a lower rate of non-treatment response (61.36% vs. 38.64%; p = 0.11). No statistical differences between arms were found in terms of oncological outcomes, all postoperative complications (p = 0.15), second surgeries (p = 0.62), or deaths (p = 0.62). CTCAE acute-GI and GU toxicity were grade I or II in both arms. Our study shows that the dose-escalated scheme is safer and obtains higher ypCR-rates.

Dietary supplements are widely embraced by cancer patients seeking complementary and integrative approaches to their care. Unfortunately, many patients do not discuss supplement use with physicians, often due to perceptions of physician indifference or negativity toward supplements. This communication gap exposes patients to unreliable information sources and, potentially, unnecessary risk. As the healthcare landscape evolves, patients increasingly value physicians who recognize their pivotal role in shaping healthcare decisions. This patient-centered perspective emphasizes the provision of evidence-based information tailored to individual needs, open discussions on potential risks, and shared decision-making. It underscores the importance of respecting patient autonomy, offering alternative options, documenting preferences, and ensuring ongoing support while coordinating with the healthcare team. To address these needs, healthcare providers should transform their perspectives and become expert guides who embrace patients as informed, empowered participants. This approach prioritizes open dialogue that considers both facts and uncertainties regarding dietary supplement use, allowing for mutually informed decision-making. Here, we review the literature and present a practical approach emphasizing open discussions, transparency, and respect for patient autonomy. Following this approach, healthcare providers can empower patients to navigate the complexities of dietary supplement use in the context of cancer care, ultimately safeguarding patient safety and well-being.

Background: There are limited evidence-based data to guide treatment recommendations for breast cancer (BC) patients ≥ 80 years (P80+). Identifying and addressing unmet needs are critical. Aims: Advocate-BREAST80+ compared the needs of P80+ vs. patients < 80 years (P80-). Methods: In 12/2021, a REDCap survey was circulated electronically to 6,918 persons enrolled in the Mayo Clinic Breast Disease Registry. The survey asked about concerns and satisfaction with multiple aspects of BC care. Results: 2,437 participants responded (35 % response rate); 202 (8.3%) were P80+. P80+ were less likely to undergo local regional and systemic therapies vs. P80- (p

Telehealth is the delivery of many health care services and technologies to individuals at different geographical areas and is categorized as asynchronously or synchronously. The coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions in health care delivery to breast cancer (BCa) patients and there is increasing demand for telehealth services. Globally, telehealth has become an essential means of communication between patient and health care provider. The application of telehealth to the treatment of BCa patients is evolving and increasingly research has demonstrated its feasibility and effectiveness in improving clinical, psychological and social outcomes. Two areas of telehealth that have significantly grown in the past decade and particularly since the beginning of the COVID-19 pandemic are telerehabilitation and teleoncology. There two technological systems provides opportunities at every stage of the cancer care continuum for BCa patients. We conducted a systematic literature review that examined the use of telehealth services via its various modes of delivery among BCa patients particularly in areas of screening, diagnosis, treatment modalities, as well as satisfaction among patients and health care professionals. The advantages of telehealth models of service and delivery challenges in delivery to patients in remote arears are discussed.

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher’s exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) were susceptible to HBV, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.

Abstract Background In tumors, somatic mutagenesis presumably drives DNA damage response (DDR) via altered regulatory pathways increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation activated DNA repair pathways of tumors. Purpose Justifying that cancer cells are not enemies to be killed, but rather they are ill human cells having the remnants of physiologic regulatory pathways. Results 1. Genomic instability and cancer development may be originated from the flaw of estrogen signal rather than excessive estrogen signaling. 2. Healthy cells with genomic instability exhibit somatic mutations helping DNA restitution. 3. Somatic mutations in tumor cells aim the restoration of DNA damage rather than further genomic derangement. 4. In tumors, estrogen signal drives the pathways of DNA stabilization leading to apoptotic death. 5. In the peritumoral cellular infiltration, the genomic damage of tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, increased growth factor receptor (GFR) signal confers unliganded activation of estrogen receptors (ERs). 6. In tumor cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signal and consequential apoptosis. In tumors non responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathway, are exhausted leading to farther genomic instability and unrestrained proliferation. Conclusion Understanding the real character and behavior of human tumors at molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy rather than provoking additional genomic damages.

Background: Although several studies have been conducted on the use of Artificial Intelligence (AI) in mammography (MG), research focusing on the diagnosis of metachronous bilateral breast cancer (BC), which is typically more challenging to diagnose, remains limited. This study assessed whether AI could enhance the detection of BC, achieving earlier or more accurate diagnoses than radiologists in cases of metachronous contralateral BC. Methods: The study included patients who underwent unilateral BC surgery and subsequently developed contralateral BC during follow-up. We evaluated the capability of the AI-supported MG diagnostic system FxMammo™ (FathomX Pte Ltd, Singapore) to diagnose BC more accurately or earlier than radiologists' assessments. This evaluation was supplemented by reviewing MG readings by radiologists. Results: Out of 1,101 patients who underwent surgery, 10 patients who had initially received a partial mastectomy and later developed contralateral BC were analyzed. The AI system identified malignancies in 6 cases (60%), while radiologists identified 5 cases (50%). Notably, two cases (20%) were diagnosed solely by the AI system. Additionally, for these cases, the AI system had identified malignancies a year prior to the conventional diagnosis. Conclusions: This study highlights the AI system's effectiveness in diagnosing metachronous contralateral BC via MG. In some cases, the AI system consistently diagnosed cancer at earlier than radiological assessments.

(1) Context: Cancer triggers significant changes in family dynamics. It is noteworthy that coping and problem-solving skills, particularly in situations involving cancer in children and adolescents, have not been adequately explored in the context of family adaptation. This study aims to analyze the effectiveness of family interventions in coping to improve problem-solving skills in parents and/or caregivers of children and adolescents during and after oncological treatment. (2) Methods: This is a scoping review following the recommendations of the Joanna Briggs Institute and the Systematic Reviews and Meta-Analyses Extension for Scoping Review (PRISMA-ScR), from 2014 to 2024, in the databases LILACS, CINAHL, SCOPUS, Web of Science, and PUBMED. (3) Results: Forty-five studies were eligible. Coping strategies were categorized as follows: (1) positive attitudes (including a sense of courage and hope, family support to enhance resilience, and future planning), (2) caregiver empowerment (involving acceptance of diagnosis, emotional distancing, and coping through religiosity), and (3) communication skills (encompassing professional communication, horizontal dialogue with healthcare teams, and sincere communication with friends and family). (4) Conclusions: Over time, families develop coping and problem-solving strategies that influence changes in family functioning patterns, aiding them in accepting, reinterpreting, and reframing ideas and feelings associated with neoplasia.

The shortage of physicians in rural communities contributes to increased mortality rates among Medicare beneficiaries. This increase in mortality risk is commonly due to diseases such as heart disease and cancer, including melanoma and non-melanoma skin cancer (NMSC). Mohs micrographic surgery (MMS) is considered the gold-standard treatment for NMSC tumors, however, due to a shortage of dermatologists and Mohs surgeons in rural areas, access to MMS is limited. In these areas, image guided superficial radiation therapy (IGSRT) serves as a viable option for the treatment of NMSC lesions, with fewer recurrences and 99% cure rates, which are comparable to MMS cure rates. IGSRT is performed in dermatology clinics with support from a multidisciplinary team, including radiation therapists, medical physicists, radiation oncologists, and dermatologists. As IGSRT is able to be performed by general dermatologists, Medicare beneficiaries in rural communities will have an increase in access to treatment options and a decrease in delayed skin cancer treatment.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Tspo is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of TSPO makes it a good diagnostic biomarker and TSPO could serve as a target for anticancer drug development.

The microbiome, once considered peripheral, is emerging as a relevant player in the intricate web of factors contributing to cancer development and progression. These often overlooked microorganisms, in the context of urological malignancies, have been investigated primarily focusing on the gut microbiome, while exploration of urogenital microorganisms remains limited. In light of this, our systematic review delves into the complex role of these understudied actors in various neoplastic conditions, including prostate, bladder, kidney, penile, and testicular cancers. Our analysis found a total of 37 studies, with prostate cancer-12, bladder cancer-20, kidney cancer-4, penile/testicular cancer-1, which reveals distinct associations specific to each condition, hinting at potential therapeutic avenues and future biomarker discoveries. It becomes evident that further research is imperative to unravel the complexities of this domain and provide a more comprehensive understanding.

Cigarette smoke (CS) is a major driver of many respiratory diseases including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco causes oxidative stress, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression in the lungs of smokers. MicroRNAs (miRNAs) are small non-coding RNAs that influence several bi-ological processes and interfere with several regulatory pathways. The purpose of this study was to assess the effect of active CS on miRNAs expression in AMs obtained from bronchoalveolar lavage (BAL) of ever- or never-smoker subjects and patients with COPD or NSCLC. BAL specimens were collected from 43 sex-matched subjects to determine the expression of has-miR-34a-5p, 17-5p, 16-5p, 106a-5p, 223-5p, and 20a-5p before and after in vitro CS exposure by RT-PCR. In addition, bioin-formatic analysis of miRNAs target genes linked to inflammation was performed. Distinct and common miRNA expression profiles were identified in response to CS, suggesting their possible role in smoking-related diseases. It is noteworthy that, following exposure to CS, the expression levels of hsa-miR-34a-5p and 17-5p in both ever- or never-smokers, 106a-5p in never-smokers and 20a-5p in ever-smokers, shifted towards those found in individuals with COPD, suggesting them like a risk factor in developing this lung condition. Moreover, we identified miRNA targets involved in the immune system or AMs property regulation using in silico analysis. In conclusion, our study iden-tified miRNA signatures in AMs exposed to CS, indicating that CS is an important driver of epige-netic changes that contribute to the onset of various lung diseases.

Neurotensin (NT) is a peptide involved in digestion, neuromodulation, and cancer progression. NT and its receptors (NTR1 and SORT1 mainly) have been widely studied in oncology. Data show NT expression is under the control of sex steroid hormones, in particular estradiol. We focused on its involvement in three main female hormone-sensitive cancers: breast, ovarian, and endometrial cancer in a narrative review. NT, NTR1 and SORT1 are mostly expressed in these three cancers and their involvement in oncologic processes such as proliferation and invasion seems to match, as does their impact on prognosis for most. The development of NT receptor-targeted therapies, including theranostics and radioligand treatments, presents a promising avenue for personalized cancer treatment.

Inherited mutations in BRCA1 and BRCA2 genes increase risks for breast, ovarian, and other cancers. Both genes encode proteins for accurately repairing chromosome breaks. If mutations inactivate this function, broken chromosomes may not be restored correctly, allowing breaks to persist or rearrange chromosomes. These abnormalities are potentially catastrophic events that can originate from viral infections. I used bioinformatic analyses of publicly available breast cancer patient data to show that the distribution of chromosome breaks in hereditary breast cancers differs markedly from sporadic breast cancers. Then I tested hereditary breast cancer sequence data around chromosome breaks for DNA similarity to all known viruses. Human DNA flanking breakpoints usually had decisive matches to Epstein-Barr virus (EBV / HHV4) tumor variants HKHD40 and HKNPC60. Many breakpoints were near EBV genome anchor sites, human EBV tumor-like sequences, EBV-associated epigenetic marks, and some fragile sites. On chromosomes 2 and 12, sequences near EBV genome anchor sites accounted for 90% and 88% of breakpoints (p<0.0001), respectively. On chromosome 4, 51/52 inter-chromosomal breakpoints were close to EBV-like sequences in 19 hereditary breast cancers. In contrast, 19 sporadic breast cancers only had 12 interchromosomal breakpoint regions on chromosome 4 near EBV-like sequences. On various other chromosomes, five EBV genome anchor sites were near hereditary breast cancer breakpoints at precisely defined, disparate gene or LINE locations. Independent evidence further implicating EBV in hereditary breast cancer breakpoints is that 25 breast cancer break positions are within 1.25% of breakpoints in model EBV cancers. In addition to BRCA1 or BRCA2 mutations, all the hereditary breast cancers had mutated genes essential for immune responses. This compromise facilitates reactivation of herpes viruses which produce nucleases capable of breaking chromosomes. EBV also causes other deleterious effects: anchored EBV episomes can interfere with normal replication and obstruct DNA break repairs; even very early infection causes massive transcription changes. The results, therefore, imply proactive treatment and prevention of herpes viral infections may prevent some chromosome breaks and benefit BRCA mutation carriers.

Urological cancers include a spectrum of malignancies affecting organs of the reproductive and/or urinary systems, such as prostate, kidney, bladder, and testis. Despite improved primary prevention, detection and treatment, urological cancers are still characterized by an increasing incidence and mortality worldwide and although advances have been made toward understanding the molecular basis of these diseases, a complete insight of the pathogenic mechanisms is still a research challenge for defining safer pharmacological therapies and prognostic factors, especially for the metastatic stage of these neoplasms for which no effective therapies exist. Glyoxalases are enzymes that catalyzes the glutathione-dependent metabolism of cytotoxic methylglyoxal (MG), thus protecting against cellular damage and apoptosis. They are generally overexpressed in numerous cancers as a survival strategy by providing a safeguard through enhancement of MG detoxification. Increasing evidence suggest that glyoxalases, especially Glo1, would act as oncogenes in urological malignancies and be central to their initiation, growth and progression. In this review, we highlight the critical role of glyoxalases as regulators of tumorigenesis in the prostate through modulation of various critical signaling pathways, and provide an overview of the current knowledge on glyoxalases in bladder, kidney and testis cancers. We also discuss the promise and challenges for Glo1 inhibitors as future anti-PCa therapeutics and the potential of glyoxalases as biomarkers for PCa diagnosis.

Gastroesophageal (GE) junction adenocarcinoma is an aggressive malignancy of growing incidence and is associated with public health issues such as obesity and GERD. Management has evolved over the last 2 decades to incorporate a multidisciplinary approach including endoscopic intervention, and neoadjuvant chemotherapy/ chemoradiation and minimally invasive or more limited surgical approaches. Surgical approaches include esophagectomy, total gastrectomy, and more recently proximal gastrectomy. This review analyzes the evidence for and applicability of these varied approaches in management as well areas of continued controversy and investigation.

ABSTRACT: Background: Virtual Reality (VR) emerges as a promising non-pharmacological intervention for managing symptoms and providing distraction during chemotherapy. This study aims to assess VR's effectiveness on cancer-related symptoms, vital signs, and patients' perception of the chemotherapy in lung cancer patients. Methods: A quasi-experimental study was conducted on 100 patients. Participants were allocated into an intervention group (n = 55), which experienced immersive VR, and a comparison group (n = 45), which received usual care. Data were collected through questionnaires and checklists, including feedback on the VR experience, pain, vital signs, and common cancer symptoms, assessed through the Edmonton Symptom Assessment Scale. Results: VR had a significant impact on reducing the perception of the chemotherapy length. Patients reported high levels of satisfaction and tolerability. No adverse events were observed. VR did not have significant influence on pain intensity and vital signs. The only exceptions were oxygen saturation, where a significant difference (p = 0.02) was reported, and perception of chemotherapy duration. Conclusions: As a non-pharmacological intervention, VR proves beneficial in minimizing the perceived length of chemotherapy session for lung cancer patients, enhancing their overall treatment experience. The intervention showed to be a safe, feasible, and well-accepted distraction technique. Future research should explore VR's potential effects on a wider range of symptoms and evaluate its impact on long-term outcomes.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Blood cancers, including leukemia, lymphoma, and myeloma, pose significant diagnostic challenges due to their diverse and complex nature. Detecting these cancers early and accurately is crucial for timely intervention and improved patient outcomes. This review explores current and emerging detection methods for human blood cancers, focusing on their principles, advantages, limitations, and potential clinical applications.

Epidemiological studies on micronutrient consumption have reported protective associations in the incidence and/or progression of various cancer types. Supplementation with some of these micronutrients has been analyzed, showing chemoprotection, low toxicity, antiproliferation, and the ability to modify epigenetic signatures in various cancer models. The following review inves-tigates the reported effects of micronutrient intake or supplementation in breast cancer progres-sion. A PubMed search was conducted with the keywords “micronutrients breast cancer progres-sion,” and the results were analyzed. The selected micronutrients were: Vitamins (A, C, D, and E), Folic Acid, metals (Cu, Fe, Se, and Zn), fatty acids, polyphenols, and iodine. The majority of in vitro models showed antiproliferative, cell cycle arrest, and antimetastatic effects for almost all the micronutrients analyzed, but these effects do not reflect animal or human studies. Only one clinical trial with Vitamin D and one pilot study with molecular iodine showed favorable overall survival and disease-free interval.

: Cancer metastasis is the lethal developmental step in cancer, responsible for the majority of cancer deaths. To metastasize, cancer cells must acquire the ability to disseminate systemically and to escape an activated immune response. Here, we endeavoured to investigate if metastatic dissemination reflects acquisition of genomic traits that are selected for. We acquired mutation and copy number data from 8,332 tumours representing 19 cancer types acquired from The Cancer Genome Atlas and the Hartwig Medical Foundation. A total of 827,344 non-synonymous mutations across 8,332 tumour samples representing 19 cancer types were timed as early or late relative to copy number alterations, and potential driver events were annotated. We found that metastatic cancers had significantly higher proportion of clonal mutations and a general enrichment of early mutations in p53 and RTK/KRAS pathways. However, while individual pathways demonstrated a clear time-separated preference for specific events, the relative timing did not vary between primary and metastatic cancers. These results indicate that the selective pressure that drives cancer development does not change dramatically between primary and metastatic cancer on a genomic level, and is mainly focused on alterations that increase proliferation.

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neo-plasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched Pubmed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors, and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further pre-clinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

Cancer risk is known to increase tremendously when the immune system is suppressed, e.g., as observed in young organ-transplant recipients and AIDS patients. Based on such data, it may be hypothesized that the main reason for the development of clinical cancer is the weakening or suppression of the immune system, and that uncontrolled multiplication of cancer cells occurs when some aspects of the immune system fall below certain critical levels. Therefore, cancer may be prevented and treated by boosting these critical aspects of the immune system so that they are maintained above the critical levels. If multiple immune system boosting interventions are utilized, more aspects of the immune system would be boosted, increasing the likelihood of enhancing the critical aspects of the immune system and generating a cancer preventive and/or therapeutic effect. Clinical trials are needed to validate this approach for cancer prevention and treatment. If validated, the proposed approach could result in a major reduction of the death and suffering caused by cancer in the world.

Background: Cancer stem cells (CSC) are small subpopulation of cancer cells that has the potential to self-renew and has the strong proliferative capacity that sustain tumorigenesis capability. This ability of the CSCs to escape immune responses make the CSCs a primary source of functionally altered, immune-resistant, chemo-resistant aggressive tumor cells. Mentioned characteristic determines the potential advantage of targeting CSCs for the treatment of solid tumor. Method: We downloaded different gene expression datasets of CSCs from the NCBI-GEO database and identified common gens by using suitable Venn tool. Then explored the prognostic significance of the particular genes in particular cancer along with analysis of expression of these genes at protein level in human carcinomas by using different webserver. Finally, using toxicogenomic database we selected several important drugs or chemicals. Result: In this study, we identified common targets between three types of solid tumor and the prognostic significance of the identified genes. The identified drugs capable of targeting the expression or signaling network of designated genes of CSC that may contribute in CSC targeted cancer therapy. Conclusion: We identified several CSC associated genes in human breast, lung and ovarian carcinomas and several drugs that can target the function of these genes. Our study also suggests that there is need for more experimental investigations to find out the actual functional activity and the mechanism of action of the genes of CSC.

Epidemiological data highlight prostate cancer as a significant global health issue, with high incidence and substantial impact on patients' quality of life. The prevalence of this disease is associated with various factors, including age, heredity, and race. Recent research in prostate cancer genetics has identified several genetic variants that may be associated with an increased risk of developing the disease. However, despite the significance of these findings, genetic markers for prostate cancer are not currently utilized in clinical practice as reliable indicators of the disease. In addition to genetics, epigenetic alterations also play a crucial role in prostate cancer development. Aberrant DNA methylation, changes in chromatin structure, and microRNA (miRNA) expression are major epigenetic events that influence oncogenesis. Existing markers for prostate cancer, such as prostate-specific antigen (PSA), have limitations in terms of sensitivity and specificity. The cost of testing, follow-up procedures, and treatment for false-positive results and overdiagnosis contributes to the overall healthcare expenditure. Improving the effectiveness of prostate cancer diagnosis and prognosis requires either narrowing the risk group by identifying new genetic factors or enhancing the sensitivity and specificity of existing markers. Immunological biomarkers (both circulating and intra-tumoral), including markers of immune response and immune dysfunction, represent a potentially useful area of research for enhancing the diagnosis and prognosis of prostate cancer. Our review emphasizes the need for developing novel immunological biomarkers to improve the diagnosis, prognosis, and management of prostate cancer. We highlight the most recent achievements in the identification of biomarkers provided by circulating monocytes and tumor-associated macrophages (TAMs). We highlight that monocytes-derived and TAMs-derived biomarkers can enable to establish the missing links between genetic predisposition, hormonal metabolism and immune responses in prostate cancer.

Introduction: Identifying the complexity of palliative care needs is a key aspect of referral to specialised multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains, developed in 2018 and validated in 2023, to identify the level of complexity in patients with advanced cancer. Objectives: The main objective of this study was to determine the degree of instability (likelihood of level change or death), health resource consumption and survival of patients according to the level of palliative complexity assigned at the baseline visit during a 6-month follow-up. Method: An observational, prospective, multicentre study was conducted using pooled data from the development and validation cohort of the PALCOM scale. The main outcome variables were: a) instability ratio (IR), defined as the probability of level change or death; b) emergency department visits; c) days of hospitalisation; d) hospital death; e) survival. All variables were analysed monthly according to the level of complexity assigned at the baseline visit. Results: A total of 607 patients with advanced cancer were enrolled. According to the PALCOM scale, 20% of patients were classified as low complexity, 50% as medium and 30% as high complexity. The overall IR was 45% in the low complexity group, 68% in the medium complexity group and 78% in the high complexity group (p

Purpose: This study aimed to investigate useful preoperative clinical and hematologic variables in predicting malignancy in patients with the atypia of undetermined significance (AUS) nodules, and to suggest a machine learning-based prediction model. Methods: We enrolled 280 patients who underwent surgery for the AUS nodules at Wonju Severance Christian Hospital between 2018 and 2022. We evaluated preoperative hematologic indices, including Delta Neutrophil Index (DNI), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR), as well as preoperatively identifiable clinical variables such as age and sex at diagnosis, history of radiation exposure, familial history of thyroid cancer, primary tumor size, and the 2016 Korean Thyroid Imaging Reporting and Data System (K-TIRADS) classification. Results: A total of 116 patients (41.4%) were finally diagnosed with various types of thyroid malignancy, excluding 32 patients (11.4%) with thyroid cancer incidentally identified. Age at diagnosis (p = 0.012), primary tumor size (p = 0.048), and the K-TIRADS classification (p = 0.003) were independent risk factors to predict the diagnosis of malignancy in patients with AUS nodules younger than 55 years, not in those aged of 55 years or older. Adding the NLR to these risk factors significantly improved the predictability for malignancy in the same patient group (p < 0.001). Conclusions: The inclusion of NLR in the ma-lignancy prediction model enhances the predictive accuracy for malignancy in younger patients with AUS nodules. This finding suggests that incorporating NLR into preoperative assessment could refine management strategies and improve decision-making for surgical interventions.

In the era of nanotechnology, researchers are implementing point to care service to cancer patients to detect malignancy beforehand and to reduce the mortality rate of cancers. Cancer is known to be the most fatal disease among all other diseases and the survivability from cancer is quite impossible if the stage of the cancer is an advanced level. Though the early detection of cancer can increase the chances of survival with a double fold. Biosensor is a part of nanotechnology which is capable to provide point to care service in the field of medicine. With the rising number of cancer occurrences being identified around the world and the increasing number of deaths because of the identification of advanced cancer, biosensors can play a significant part in the early detection of cancer. New molecular methods, including as genomic and proteomic approaches, are increasingly being used to study patient molecular profiles. When such diagnosis method is paired with bioinformatics tools, they generate new data that can be used to discover new disease biomarkers. Finding precise and sensitive indicators that are corelated to a specific disease, as with many other diseases, can be challenging. Furthermore, the concentration of biomarkers in biological fluids varies according to illness states and phases. Peptides, proteins, up or down regulated expression of gene markers, and gene alternation are all examples of molecular markers that are commonly used to diagnose cancer. In this article, we have highlighted six different deadliest cancers such as Ovarian, Breast, Prostrate, Lung, Colorectal and Liver cancer. The article contains distinct types of biomarkers which are normally found in these kinds of cancer and generally used as a potential diagnostic target in the medicine field. The article mainly summarized the application of different types of biosensors devices in the detection of the mostly found biomarkers in the above cancer types.

Gambogic acid, a common traditional Chinese medicine and widely distributed throughout South China, Vietnam, Cambodia, and Thailand. It is prenylated xanthone which is the significant bioactive compound of gamboge. Gambogic acid is known as a strong apoptotic inducer in cancer cells. It has been found as strong anticancer agent against various types of cancer cells lines such as breast cancer, pancreatic, and cervical cancer. It induces apoptosis, down regulates the anti-apoptotic proteins (survivin and BCL2,) and down regulates the activities of P-glycoprotein in drug sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. Similarly, it also exerts alteration in P13K, AKT, p21, MMP-2 &-9, and phosphorylated-AKT expressions. The current review highlights the anticancer and chemo-preventive perspectives of gambogic acid and its mechanistic role against human and animal cancers.

Objective: To provide mechanistic evidence for the epidemiological link between long-term use of alcohol containing mouthwashes and oral cancer.Methods: Human epithelial keratinocytes were exposed for 30 seconds to concentrations of ethanol commonly present in mouthwashes. After a recovery period, cell viability was assessed with the MTT assay.Results: A marked cytotoxic effect was observed for ethanol concentrations of 20% and above. Conclusions: The cytotoxicity of ethanol can explain the epidemiological association between mouthwash use and oral cancer. Recent findings indicate that the risk of developing cancer in a tissue is strongly determined by the number of stem cell divisions accumulated by the tissue during a person's lifetime; cell division is a major source of mutations and other cancer-promoting errors. Since cell death activates the division of stem cells, the cytotoxicity of ethanol on the cells lining the oral mucosa will promote the division of the stem cells located in deeper layers to produce new cells to regenerate the damaged epithelium. If we regularly use mouthwashes containing cytotoxic concentrations of ethanol, we will force the stem cells of the oral cavity to divide more often than usual and our risk of developing oral cancer will probably increase.Clinical significance: Many mouthwashes contain percentages of ethanol above 20%. Because ethanol is not crucial to prevent and reduce gingivitis and plaque, members of the dental team should consider the potential risk of oral cancer associated with frequent use of alcohol containing mouthwashes when advising their patients.

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration-resistance is often developed during the course of treatment, though its influences require further understanding. This study explores the human microbiome for its implications in castration-resistance and metastasis in prostate cancer. RNA sequencing data was downloaded for bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These sequences were mapped to bacterial sequences to yield species-level abundance approximations. Numerous species were found to correlate to the expression of known markers of castration-resistance, including AR, PI3K, and AKT. Castration-resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for relation to these species. EGFR and SLC3A2 were widely downregulated with greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration-resistance and stemness in prostate cancer. By considering the microbiome’s importance in these factors, we may better understand the highly aggressive and highly invasive nature of prostate cancer, allowing for needed improvement in the treatment of this disease.

The cancer stem cell hypothesis suggests that neoplastic cells with stem characteristics hierarchically regulate tumor generation and its high cellular heterogeneity. These cells have been detected in all cancer types, and specific signaling pathways give the regulation of self-renewal and differentiation. In prostate cancer, androgen receptor signaling has been extensively studied, and in non-stem cells, it promotes cell proliferation and tumor progression, but in the cancer stem cell population, it negatively regulates processes such as self-renewal. However, in other types of cancer, such as breast and glioblastoma, the androgen receptor seems to favor the maintenance of cancer stem cells, suggesting that androgen signaling has different effects depending on the tumor context. This review discusses the role of androgen receptor in maintaining cancer stem cells by regulating proliferation, self-renewal, and differentiation, as well as the possible signaling pathways involved in these processes.

Despite the recognized benefits of fecal occult blood test (FOBT) and mammography screenings, participation in breast (BC) and colorectal cancer (CRC) screening programs is still suboptimal. This study investigates municipal characteristics associated with their BC/CRC screening uptake profiles among women aged 55–69 years. Using data from 308 municipalities of Flanders from 2014 to 2017, a profile for each municipality based on its BC/CRC screening uptake compared with the median screening uptake was created. Logistic regression with generalized estimating equations was used to assess the associations between municipal characteristics and BC/CRC screening uptake profiles. The overall median uptake of cancer screening was higher for CRC (57.4%) than for BC (54.6%). The following municipal characteristics were associated with worse performance in terms of only CRC, only BC, or both CRC and BC screening uptake, respectively: foreign nationality, self-employment rate, (early) retirement rate, diabetes, disabilities; (early) retirement rate; age group 65–69, foreign nationality, self-employment rate, (early) retirement rate, wage-earners, diabetes. The following municipal characteristics were associated with better performance in terms of only CRC, only BC, or both CRC and BC screening uptake respectively: residential stability, having a partner, having children, jobseeker rate, GP visits, preventive dental visits; having children, GP visits; age group 55–59, residential stability, having a partner, having children, jobseeker rate, higher education, GP visits, preventive dental visits. This study’s results regarding the interrelation between the BC and CRC screening could be used to tailor interventions to improve the participation of the target population in both programs.

Several infectious agents are ascertained causes of cancer, but the burden of cancer mortality attributable to carcinogenic infections in Italy was still unknown. To tackle this issue, we calculated the rate and regional distribution of cancer deaths due to infections sustained by seven pathogens ranked as group-1 carcinogenic agents in humans by IARC. Population attributable fractions related to these agents were applied to annual statistics of cancer deaths coded according to 10th International Classification of Diseases. The estimated burden of cancer mortality attributable to carcinogenic infections in Italy during the period 2011-2015 was on average 8.7% of all cancer deaths registered yearly. Approximately 60% of deaths occurred in men and almost the whole burden was due to four infectious agents (Helicobacter pylori, HCV, HPV, and HBV). The analysis of regional distribution showed a higher number of infection-related cancer deaths in the northern regions, where the estimates reached 30 (Liguria) and 28 (Friuli Venezia Giulia) deaths per 100,000 inhabitants in 2015. Since one-twelfth of cancer deaths were attributable to these modifiable risk factors, the implementation of appropriate prevention and treatment interventions may help to reduce the impact of these infections on cancer mortality.

Inherited mutations in BRCA1 and BRCA2 genes increase risks for breast, ovarian, and other cancers. Both genes encode proteins for accurately repairing chromosome breaks. If mutations inactivate this function, chromosome fragments may not be restored correctly. Resulting chromosome rearrangements can become critical breast cancer drivers. Because I had data from thousands of cancer structural alterations that matched viral infections, I wondered whether infections contribute to chromosome breaks and rearrangements in hereditary breast cancers. There are currently no interventions to prevent chromosome breaks because they are thought to be unavoidable. However, if chromosome breaks come from infections, they can be treated or prevented. I used bioinformatic analyses to test publicly available breast cancer sequence data around chromosome breaks for DNA similarity to all known viruses. Human DNA flanking breakpoints usually had the strongest matches to Epstein-Barr virus (EBV) tumor variants HKHD40 and HKNPC60. Many breakpoints were near sites that anchor EBV genomes, human EBV tumor-like sequences, EBV-associated epigenetic marks, and fragile sites. On chromosome 2, sequences near EBV genome anchor sites accounted for 90% of breakpoints (p<0.0001). On chromosome 4, 51/52 inter-chromosomal breakpoints were close to EBV-like sequences. Five EBV genome anchor sites were near breast cancer breakpoints at precisely defined, disparate gene or LINE locations. Breakpoint flanking regions resembled known EBV-cancers. Twenty-five breakpoints in breast cancers were within 1.25% of EBV cancer breakpoints. In addition to BRCA1 or BRCA2 mutations, all the breast cancers had mutated genes essential for immune responses. Because of this immune compromise, herpes viruses can activate and produce nucleases that break chromosomes. Alternatively, anchored viral episomes can obstruct break repairs, whatever the cause. The results, therefore, imply proactive treatment and prevention of herpes viral infections may prevent some chromosome breaks and benefit BRCA mutation carriers.

There is a rich history of cancer treatments which provides a number of important lessons for present and future cancer therapies. We outline this history by looking in the past, reviewing the current landscape of cancer treatments, and by glancing at the potential future cancer therapies.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we evaluated the anticancer activity of 17 artificial diets in a challenging animal model of renal cell carcinoma. The model was stablished by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential of this simple and inexpensive anticancer strategy.

Background and Objectives: The new molecular classification of endometrial cancer continuously changes the management of the disease in every day clinical practice. Lately, FIGO released a new staging system for endometrial cancer, which incorporates molecular sub-stages and subdivides further early-stage disease. The aim of this study is to investigate the differences between the two FIGO staging systems and evaluate the prognostic precision of the new one. Materials and Methods: We retrospectively analyzed the records of patients with endometrial cancer that were fully treated in the 1st Department of Obstetrics-Gynecology, 2012-2023. Patient characteristics, oncological outcome and follow-up information were collected. The primary outcomes were the stage shifts and the survival data. Results: 67 (15.5%) patients had a stage shift and the majority of them concerned early-stage disease and specifically up-shift from 2009 stages IA and IB to 2023 stage IIC. Concerning, survival a better median and 5-year PFS was present in Stage II disease and when compering the prognostic precision of the two FIGO staging systems no significant difference was present. Conclusions: The new 2023 FIGO staging system better distinguishes early-stage endometrial cancer into its prognostic groups and seems to be as precise as the old 2009 FIGO staging system.

This review explores the challenges and emerging trends in pancreatic cancer therapy. In particular, we focus on the tumor microenvironment and the potential of immunotherapy in pancreatic cancer. We discuss novel strategies targeting the desmoplastic barrier and immunosuppressive cells to enhance immune cell infiltration and activation. Recent clinical trials, particularly those involving novel immunotherapeutic agents and tumor vaccines, are examined to understand their efficacy and limitations. This review aims to highlight the ongoing efforts to refine immunotherapy approaches for better patient outcomes.

The causes of pediatric cancers often remain unknown; however, due to the development of medicine and technology, genetic disorders may play a crucial role in the genesis of neoplasms. Over time, the number of cancer predisposition syndromes (CPS) and awareness of them are increasing, providing the possibility of cancer prevention and early detection. In this study, we presented data concerning the number and type of oncological cases and their correlation with CPS occurrence in a cohort of Central and Eastern European pediatric population. The data were collected between 2000 and 2019 at the Karol Jonscher Clinical Hospital of Poznan University of Medical Sciences, resulting in a cohort of 2,190 cases in total, of which 193 children (8.81%) were confirmed to have CPS. CPS occurred most frequently in infancy (22.90% of all children suffering from any diagnosed cancer during the first year of life, p &lt; 0.0001), accounting for more than a quarter of all CPS cases in our cohort. CPS were least likely to be observed in patients aged 14 and 15 years (2.17% and 2.44% of children diagnosed with any of the listed cancers at the exact age, respectively, p &lt; 0.05). Among CPS, the most common were neurofibromatosis type I (NF1), Li-Fraumeni syndrome (LFS), and Down syndrome (DS). To conclude, it is important to emphasize the need for personalized treatment for each patient affected by both CPS and subsequent cancer in order to reduce the toxicity of therapy and improve quality of life by reducing the risk of side effect.

Breast cancer (BC) is a prevalent malignancy with various subtypes, each presenting unique diagnostic and therapeutic challenges. Triple-negative breast cancer (TNBC), which comprises 12-17% of breast cancers, is particularly aggressive due to its lack of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. This case report details the management of a 64-year-old woman with TNBC. Initially presenting with a left breast nodule, she underwent a biopsy that confirmed triple-negative infiltrating ductal carcinoma. Despite negative BRCA genetic testing, her significant family history of cancer and a newly detected right breast lesion led to a bilateral mastectomy. Post-surgery imaging revealed multiple hypodense nodules and a spiculated pulmonary nodule, prompting further investigation. An endoscopic lung biopsy identified a primary pulmonary carcinoma with histological features similar to the breast cancer, indicating the lung as the primary source. This case underscores the complexity of TNBC, the importance of comprehensive diagnostic evaluations, and the need for considering extramammary origins in metastatic cases. The findings emphasize the role of multidisciplinary teams in managing such rare and challenging cases and highlight the necessity for thorough and repeated evaluations in atypical BC presentations.

Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in regulation of both apoptosis and mitosis. Survivin has emerged as an attractive target for cancer therapy because its overexpression has been found in most human cancers and is frequently associated with chemotherapy resistance, recurrence, and poor survival rate in cancer patients. In this review, we discuss our current understanding of how survivin mediates various aspects of malignant transformation and drug resistance, as well as efforts that have been made to develop therapeutics targeting survivin for the treatment of cancer.

Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.

Tobacco use, most people would say. Smoking tobacco increases the risk of developing many types of cancer and is responsible for approximately one-third of all cancer deaths. The association between tobacco use and lung cancer is well known; lung cancer occurs about 20 times more often in heavy smokers than in nonsmokers [1]. However, many lung cancers are diagnosed in never smokers [2], and most smokers do not develop lung cancer [3,4].

Background: So far, vaccination has been considered the most crucial defense against viral infection, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncology patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. Objective: This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. Material and methods: 1,668 people were observed. Over two years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in three groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. Results: The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, and colon cancer, although the response varies significantly depending on the type of cancer. Summary: The size of the humoral response and the presence of specific antibodies directed against the SARS-CoV-2, IgM, and IgG, in response to the supply of the vaccine antigen or assessed after COVID-19, is an indicator of adequate immune protection against reinfection. This study highlights for the first time the phenomenon of increased humoral response in response to a viral infection in patients with certain types of cancer that are assumed to be sensitive to oncological therapy, the initiation of which, according to generally accepted principles, was blocked by infection with the SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also seems to explain the asymptomatic course of SARS-CoV-2 infection in some of the above patients. It remains an open question to what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients.

The mechanisms involved in immune responses to cancer have been extensively studied for several decades and, considerable attention has been paid to harnessing the immune system's therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell-cancer therapy and immune test therapy have gained prominence through immunotherapy. However, it remains to be accomplished the full potential of cancer immunotherapy. In spite of having startling aspects, the cancer immunotherapies have some difficulties including the inability to effectively targeting the cancer antigens and the abnormalities in patient response. With the advancement of technology, this system has changed the genome-based immunotherapy process in the human body including generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome-editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR-T cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR-T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against the cancer. In this review, we have broadly focused on the use of CRISPR-Cas9 technology for the modification of the T-cell, which can specifically recognize cancer cells and be used as immune therapeutics against cancer. We have also demonstrated the other potential strategies for the treatment of cancer.

Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.

Cancer-derived extracellular exosomes (EXs) promote tumor metastasis. This study investigates novel EXs influencing tumor aggressiveness and metastasis in gynecologic cancer. Data from ES2-derived EXs on aggressive ES2 cells and ascites-derived mesenchymal-type ovarian carcinoma stromal progenitor cells (MSC-OCSPCs) were analyzed using LC-MS/MS and integrated with TCGA survival analysis. Two novel EXs, UBE2NL and HIST2H3PS2, were identified in more aggressive ES2-derivatives and MSC-OCSPCs cells, but not in less aggressive SKOV3 cells. High UBE2NL and HIST2H3PS2 expression in EOC tissues was associated with advanced-stage carcinoma (p&lt;0.01) and shorter overall survival (p&lt;0.01). Besides, high HIST2H3PS2 expression in endometrial cancer (EC) tissues was also associated with shorter overall survival (p&lt;0.001) in all stages and advanced stages (p&lt;0.0001). In vitro, SKOV3 cells overexpressing UBE2NL or HIST2H3PS2 exhibited significantly greater invasion ability than controls (p&lt;0.001), further enhanced by their respective EXs (p&lt;0.001). In contrast, ES2 knockdown UBE2NL reduced invasion ability than ES2 cells (p&lt;0.001). In vivo, mice injected with ES2/shUBE2NL cells had a higher survival rate (p&lt;0.001) and fewer disseminated tumors (p&lt;0.05); in contrast, those injected with SKOV3/HIST2H3PS2 cells showed greater tumor dissemination (p&lt;0.01) and more severe ascites (p&lt;0.05) than controls. Tumor dissemination increased in mice receiving SKOV3/HIST2H3PS2 cells with EXs than those controls (p&lt;0.05). These findings suggest that UBE2NL and HIST2H3PS2 expression and EXs contribute to tumor aggressiveness and metastasis in gynecologic cancer.

This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year [the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting]. Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecologic malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future.

Breast cancer develops from cells lining the milk ducts and slowly grows into a lump or a tumour. Breast cancer may be invasive or non-invasive. Invasive cancer spreads from the milk duct or lobule to other tissues in the breast, whereas, non-invasive ones lack the ability to invade other breast tissues. Non-invasive breast cancer is called in situ and may remain inactive for entire lifetime. Due to heterogeneity nature of breast, density as well as masses is variable in size and shape. A dataset of 18056 patients are collected from 20 Government Hospitals and 50 Private Hospitals in West Bengal before COVID-19 and after COVID-19. The classification of patients are made on three classes- Normal, Sign of Abnormality and Abnormality. The reports of MRIs of patients in January 2020 and February 2020 are collected from different hospitals. It is treated as dataset before COVID-19 . MRIS of patients in April 2020 and May 2020 are dataset during COVID-19. The entire datasets are accumulated for testing of any change in patients MRIS after the official announcement of new virus COVID-19 in March 2020. The aim of the paper is to make a comparison of any change in size and shape of masses of MRIs of patients before and after COVId-19. All collected MRIs reports are diagnosed by radiologists of hospitals.

Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

Background: Colorectal Cancer screening programs are effective in reducing incidence and mor-tality. In Europe, every FIT+ patient is referred to colonoscopy. Available data shows that ~75.0% of these patients are negative. It is desirable to select patients at greater risk of having a positive colonoscopy. Methods: 711 subjects, aged 50-74, attending the screening program of ASL-NA-3-SUD (Na-ples, Italy), were enrolled in a cross-sectional study to evaluate the performance of QuantiDNA™ test and non-inferiority of an alternative approach (AAP). This evaluation is based on FIT+ and QuantiDNA™+ patients referred to colonoscopy, compared to Standard of Care (SOC), colon-oscopy following a FIT+ test alone. A non-inferiority margin for Colorectal Neoplasia (CN) and Advanced Adenomas (AA) was set at -10% and at -3.8% for CRC. Results: The odds ratio was 1.76 (p-value= 0.009). The detection rate of AAP was 15.9% for colorectal neoplasia (CN), 13.0% for advanced adenoma (AA), and 3.0% for CRC. The risk dif-ference between AAP and SOC was -5.07% (95% C.I -9.23, -0.90) for CN, -4.02% (95% C.I. -7.89, -0.16) for AA, and -1.04% (95% C.I. -3.16, 1.07) for CRC. This data suggests that AAP is non-inferior to SOC for detecting CN, AA, and CRC. The expected decrease in colonoscopies is 33.4%. Conclusions: The QuantiDNA™ test is straightforward, non-invasive, and well-tolerated. Data from this study indicates it is effective in the reduction of the need for colonoscopy examina-tions (-33.4%) and is non-inferior to SOC in the detection of significant colorectal lesions.

Background/Objectives: Chemerin, which is a multifunctional cytokine and adipokine, has been implicated in inflammatory and metabolic processes and might play a role in upper gastrointes-tinal (GI) malignancies, particularly gastric and esophageal cancer. The aim of this review is to explore the role of chemerin in the pathophysiology of upper GI cancers, as well as its potential as a biomarker for early detection and as a therapeutic target. Methods: A comprehensive review of recent studies about chemerin's biochemical properties and interaction with its receptors, as well as its effects on inflammatory responses, immune regulation and metabolic processes was con-ducted. Clinical implications of chemerin on gastric and esophageal cancer were analyzed, whereas the potential therapeutic strategies targeting chemerin were discussed. Results: Elevated chemerin levels are associated with poor prognosis in gastric cancer and promote invasiveness and metastasis in esophageal cancer. Chemerin receptor antagonists show promising results in inhibiting cancer cell migration, invasion and progression. Conclusions: Chemerin could repre-sent a valuable prognostic biomarker and therapeutic target for upper GI cancers. Future observa-tional studies should validate its clinical applications and investigate the efficacy of chemerin in-hibitors as potential therapeutic targets.

Cancer, notably breast cancer, is a significant health concern globally, with a substantial burden in Asia, particularly in Pakistan. Late diagnosis exacerbates mortality rates, emphasizing the importance of robust screening programs. This article examines the effectiveness of breast cancer screening initiatives and intervention four years after initial pilot study that spanned 2015-2019, using data from the Islamabad Federal Breast Screening Centre, to assess readiness for national guideline implementation in Pakistan and beyond. Methods: This retrospective cross-sectional study, conducted at the Federal Breast Screening Center (FBSC), involved 5,580 patients undergoing mammography screening over an four-year period from 2015 to 2023. The study examined patients' data, including Breast Imaging Reporting and Data System (BIRADS) categories through double reading mammography and complementary ultrasound (USG) findings. Demographic information, including age, ethnicity, education status, socio-economic factors, breastfeeding history, breast density, and family history, was recorded to analyze its correlation with breast cancer diagnosis and subsequent management. Data analysis was performed using SPSS 2021. Results: The study included a total of 5580 patients who visited the Federal Breast Screening Centre from 2020 to 2023. The mean age of patients attending screenings from 2020 to 2023 was 48.50 ± 9.55 years, with the most common age group being 41-45 years 1,364 (24.4%), followed by 46-50 years 1,008 (18.1%). The ethnicity with the highest frequency was Punjabi 4,647 (83.3%). The distribution of patients across BI-RADS categories was as follows: BI-RADS 0 (n=175, 3.10%), BI-RADS I (n=1,933, 34.60%), BI-RADS II (n=1,691, 30.30%), BI-RADS III (n=642, 11.50%), BI-RADS IV (n=612, 11.00%), BI-RADS V (n=389, 7.00%), and BI-RADS VI (n=138, 2.50%). The prevalence rate of invasive breast cancer during these four years was 10.4%. Conclusion:In conclusion, breast cancer poses an escalating challenge associated with increasing mortality rates. Pakistan, alongside its South Asian counterparts, is witnessing a surge in cases, emphasizing the urgency for comprehensive interventions. Research endeavors such as this provide valuable insights into demographic profiles, aiding in the formulation of tailored guidelines. Moreover, the establishment of additional federal centers for screening is imperative to enhance patient access and mitigate the issue of delayed diagnoses, aligning Pakistan's healthcare infrastructure with that of developed nations.

(1) Background: The interplay between coronavirus disease 2019 (COVID-19) and laryngeal cancer represents a substantial challenge for both patients and healthcare. To garner information on recent mortality data for laryngeal cancer, including during the COVID-19 pandemic, we analyzed real-world data from the US Centers for Disease Control and Prevention (CDC). (2) Methods: We searched the CDC WONDER on-line database 2018-2022 using with the ICD-10 code for laryngeal cancer (C32; malignant neoplasm of larynx). We also performed a sub-analysis between genders, and across ten-year age groups. Data were analyzed with one-way analysis of variance (ANOVA) and Tukey post-hoc test. (3) Results: The trend of age-adjusted mortality ×100,000 did not change significantly between 2018-2022 (p=0.553). Males had higher age-adjusted mortality rates (M/F ratios between 4.6 and 5.0), but no significant variation was found in both genders (males: p=0.676; females: p=0.596). Although the mortality rate remained unchanged in people aged 35-84 years, the variation reached statistical significance in those aged 85 or older (p=0.004), displaying significant increase in 2021 compared to 2018 (p=0.006) and 2019 (p=0.039). (4) Conclusions: The impact of the COVID-19 pandemic on mortality for laryngeal cancer seemed to be relatively modest in the general US population. Nevertheless, closer attention must be paid to older people, in whom the unfavorable consequences of misdiagnosis or mistreating can be exacerbated.

Metformin, a widely used anti-diabetic drug, has garnered attention for its potential in cancer management, particularly in breast and colorectal cancer. It is established that metformin reduces mitochondrial respiration, but its specific molecular targets within mitochondria vary. Proposed mechanisms include inhibiting mitochondrial respiratory chain Complex I and/or Complex IV, and mitochondrial glycerophosphate dehydrogenase, among others. These actions lead to cellular energy deficits, redox state changes, and several molecular changes that reduce hyperglycemia in type 2 diabetic patients. Clinical evidence supports metformin’s role in cancer prevention in type 2 diabetes mellitus patients. Moreover, in these patients with breast and colorectal cancer, metformin consumption leads to an improvement of survival outcomes and prognosis. The synergistic effects of metformin with chemotherapy and immunotherapy highlights its potential as an adjunctive therapy for breast and colorectal cancer. However, nuanced findings underscore the need for further research and stratification by molecular subtype, particularly for breast cancer. This comprehensive review integrates metformin-related findings from epidemiological, clinical, and preclinical studies in breast and colorectal cancer. Here, we discuss current research addressed to define metformin's bioavailability and efficacy, exploring novel metformin-based compounds and drug delivery systems, including derivatives targeting mitochondria, combination therapies, and novel nanoformulations, showing enhanced anticancer effects.

In recent years, cancer therapy has witnessed significant advancements, with a focus on personalized and targeted treatment strategies. One promising approach involves the use of stimuli-responsive biomaterials for site-specific drug release. Among these biomaterials, pH, and redox-triggered polymer-nano composites have gained immense attention due to their ability to respond to the specific tumor microenvironment, enhancing therapeutic efficacy while reducing off-target effects. Cancer cells often exhibit anomalous biochemical properties, attributed to lower cytosolic pH (acidic) and elevated redox potential through the epitomized upregulation of undesired genes. Such biological process substantially imbalance the level ions (protons) and biological thiols glutathione (GHS) in the cytoplasm as well as in the subcellular organelles. Superfluous accumulation of ions and redox imbalance is associated with proliferation, invasion, and growth of tumor. Because of high surface area, deep tissue penetration capability, higher hydrophilicity, hydrophobic interior for drug/gene efficient loading, biocompatibility and site-specific targeting efficiency, functionalized polymer nanocomposites are superior to conventional small molecular materials. Paradoxically conventional methods of drug delivery aided therapeutics accompanied with inherent drug/genes are encapsulated in biocompatible carrier or suitable transfecting agents generally suffered with low bioavailability, uncontrolled drug release, low cellular penetration, cellular internalization, toxicity, and poor drug loading efficiency. To overcome these issues, recently various multifunctional nanomaterials were developed, based on synergistic stimuli responsive aided drug release in a specified cellular or subcellular system. High therapeutic efficacy, of nanoparticles (NPs) mainly associated with surface functionalization through biocompatible polymeric materials, site-specific targeting units accompanied with stimuli responsive components. Followed by therapeutically important drug or genetic materials were loaded into NPs either in covalent or non-covalent approach. Intriguingly, combined pH and redox dual stimuli based functional materials specially based on polymeric nanocomposites for cancer therapeutics scarcely reported. This article provides the recent progress in pH and redox-responsive polymer-nano composites for site-specific drug delivery in cancer therapy. It explores design principles, fabrication methods, mechanism of action, and prospects of these dual-stimuli responsive biomaterials.

Breast cancer is the most prevalent malignancy among women globally. Early diagnosis and treatment improvements are leading to a growing population of survivors. This has increased the risk of developing contralateral breast cancer (CBC), a distinct occurrence in the opposite breast of a previously diagnosed patient. The treatment options for breast cancer are often mas-tectomy or lumpectomy. Patients with lumpectomy frequently undergo a contralateral reduc-tion procedure to achieve more symmetry after the primary breast cancer surgery. The reduc-tion specimen is usually routinely examined by pathology to check for malignancies. The exci-sion in pieces and the absence of specific markers or ink make an examination of tumor size and margin status more challenging, impacting treatment decisions. A new protocol introduced in July 2022 seeks to improve diagnostic precision and treatment planning by excision in toto, marking, and inking excised reduction tissue to examine and treat potential CBC more effectively.

Prostate cancer is a highly heterogeneous disease, and mortality is mainly due to metastases, but the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM) from 43 patients enrolled in clinical trial. We present evidence that while there are some cases of clonally independent primary tumor foci, 87% of primary tumor foci and metastases are descended from a common ancestor. We demonstrate that genes related to oxidative phosphorylation are upregulated in LNM and in African-American patients relative to White patients. We further show that mutations in TP53, FLT4, EYA1, NCOR2, CSMD3, and PCDH15 are enriched in prostate cancer metastases. These findings were validated in a meta-analysis of 3,929 primary tumors and 2,721 metastases and reveal a pattern of molecular alterations underlying the pathology of metastatic prostate cancer. We show that LNM contain multiple subclones that are already present in primary tumor foci. We observed enrichment of mutations in several genes including understudied genes such as EYA1, CSMD3, FLT4, NCOR2, and PCDH15 and find that mutations in EYA1 and CSMD3 are associated with poor outcome in prostate cancer.

Cancer is a catchall term that refers to a collection of more than one chronic disease that can adversely affect the body, including the organs of the body. These diseases can be grouped together under the umbrella term "cancer." Cancer is a catch-all term that is used to refer to a number of different diseases. During the process of looking for new chemical entities, it was found that certain compounds with a basic nucleus of benzoic acid (BA) exhibit a remarkable anticancer potential. This was discovered while the researchers were looking for new chemical entities. In the sixteenth century, the aromatic chemical known as BA, which is also known as an aromatic carboxylic acid, was discovered. BA is also referred to as an aromatic carboxylic acid. When it comes to the chemical synthesis of a wide range of different active molecules, the utilization of a sizeable quantity of BA as a raw material is absolutely necessary. In addition to being present in a variety of other naturally occurring compounds, the BA moiety is the component that is responsible for the activity of the naturally occurring compounds vanillin, gallic acid, and syringic acid. In the synthesis of a wide variety of synthetic bioactive molecules, the BA scaffold is utilized as a building block. The drugs furosemide, bumetanide, benzocaine, tetracaine, and bexarotene are all examples of molecules that fall into this category. The scope of this review article allows for the discussion of a number of noteworthy and recent achievements of BA derivatives in terms of their effectiveness against cancer.

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, 68Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of 68Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: 68Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those 2/17 had NePC. Semiquantitative analysis with standardized uptake values (SUV) (e.g. SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. 68Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastic lesion with identifiable 68Ga-DOTATATE uptake. Marked 68Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. 3 patients had mild 68Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after 68Ga-DOTATATE imaging. Conclusions: 68Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with 68Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.

One of the most notable changes in the Esophageal Cancer (EC) epidemiology is the rising incidence and prevalence of esophageal adenocarcinoma (EAC) in developed countries, likely due to lifestyle and/or environmental factors that may play an important role in EAC onset. The aim of this systematic review was to collect and summarize all the available evidence regarding lifestyle, diet and EAC risk. We searched the PubMed and Scopus databases in January 2021 for studies providing information about lifestyle, diet, WCRF/AICR recommendations and EAC risk. A total of 106 publications met the inclusion criteria. Body mass index (BMI) and waist circumference (WC) are associated with increased EAC risk. Physical activity does not appear to have a significant direct role in EAC risk. A diet rich in fruit, vegetables, and whole grains appeared to be more protective than a diet rich in animal fat, red meat, and processed meat. Alcohol does not seem to be related to EAC whereas smokers, particularly heavy smokers, have an increased risk of EAC. Primary prevention remains the best option to avert EAC. BMI and WC, along with low consumption of red and processed meat, high consumption of plant food, and the avoidance of smoking are pivotal for EAC prevention.

Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that "breaks through" a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) is a subtype of BTcP that occurs in the absence of any specific activity. Since NP-BTcP has an important clinical impact, this analysis is aimed at characterizing the NP-BTcP phenomenon through a multidimensional statistical technique. This is a secondary analysis based on the Italian Oncologic Pain multiSetting - Multicentric Survey (IOPS-MS) . A correlation analysis was performed to characterize NP-BTcP profile about its intensity, number of episodes per day, and type. The Multidimensional Correspondence Analysis (MCA) determined the identification of 4 groups (Phenotypes). A univariate analysis was performed to assess differences between the 4 Phenotypes and selected covariates. The four phenotypes represent the hierarchical classification according to the status of NP-BTcP: from the best (Phenotype 1) to the worst (Phenotype 4). The univariate analysis found a significant association between the onset time &gt;10 min in the Phenotype 1 (37.3%) vs. the onset ≤ 10 min in Phenotype 4 (74.2%) (p&lt;0.001). The Phenotype 1 was characterized by gastrointestinal type of cancer (26.4%) respect to Phenotype 4 where the most frequent cancer affected the lung (28.8%) (p&lt;0.001). Phenotype 4 was mainly managed with rapid onset opioids, while in Phenotype 1 many patients were treated with oral, subcutaneous, or intravenous morphine (56.4% and 44.4%, respectively; p=0.008). The ability to characterize NP-BTcP can offer enormous benefits for the management of this serious aspect of cancer pain. This strategy can provide many indications for identifying the diagnostic and therapeutic gaps on NP-BTcP management.

Ongoing concerns regarding the morbidity and mortality from cancer-associated thrombosis led the European Cancer Patient Coalition (ECPC), the voice of cancer patients across Europe, to create a pan-European cancer-associated awareness patient survey to assess CAT knowledge among a large population of patients with cancer. The ECPC survey represents the largest of its kind amongst patients/caregivers with CAT and identified significant gaps in patient awareness and knowledge of CAT. It also identified a need for educational CAT-related discussions and interventions between healthcare professionals and patients with cancer and their caregivers. The aim of this paper is to highlight these gaps and to provide healthcare professionals with awareness of what information should be shared with patients/caregivers as well as how and when that information should be provided. Notably, the importance of providing information on CAT risk and risk factors, how to reduce their risk of CAT, the role of anticoagulant prophylaxis and treatment (short- and long-term) including possible side-effects, and finally how to early identify CAT symptoms. Here we outline what type of information should be provided, as well as when and how to best discuss CAT with our oncology patients and their caregivers along the cancer care continuum, to reduce the risk of CAT and associated complications with a goal of improving patient outcomes.

Despite advances in the understanding of its molecular pathophysiology, prostate cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate specific membrane antigen (PSMA), a glycoprotein that is overexpressed in prostate cancer, which expression involves neovasculature of several tumor entities, thus envisaging an additional antiangiogenic effect. To optimize the CAR design, we compared two CARs with signaling domains containing one or two T cell costimulatory elements, in addition to CD3ζ. Conversely, what has been described for other CARs, a third-generation CAR (containing CD28 and 41BB co-signaling domains) induced a potent antitumor effect similar to a second-generation CAR (containing CD28 co-signaling domain), though we observed a detrimental effect of the additional costimulatory domain that was attributed to increased activation-induced cell death (AICD). This “super-stimulation” resulted in exhaustion of cells, higher frequencies of cell death and, more importantly, the impossibility of sufficiently expanding the CAR cells to obtain the minimum number of cells requested for in vivo therapies. While the superiority of 2nd and 3rd generation over 1st generation CAR T cells has been clearly shown in both preclinical and clinical studies, the optimal combination of costimulatory domains for 3rd generation CAR-T cells must still be defined and should be evaluated case-by-case in order to fine-tune immunotherapy approaches.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute - Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and ran exome sequencing. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

The central reason behind emergence of clinically-detectable tumors is evasion from immune surveillance due to lack of cancer cells surface membrane expression of tumor-specific peptides in association with MHC class I molecules, concealment of natural killer cells-activating molecules, and absence of inflammation resulting from inefficient stimulation of innate immunity receptors and co-stimulatory molecules. The tumor microenvironment (TME) also contributes to tumor initiation, progression and resistance to therapeutic interventions because of its dense, fibrogenic, barrier-like composition, aberrant vasculature, and production of cytokines and chemokines responsible for recruitment of immune suppressive cells, notably myeloid-derived suppressor cells, M2 macrophages, regulatory T cells, extracellular trap-forming neutrophils, and cancer-associated fibroblasts. We herein show that the relentless efforts and strategies to overcome the TME elusive tumor-promoting impact produced contrasting, opposed, controversial effects, characterized by limited efficacy and proven adversity, and most importantly deterred from attempts to discover and counteract the fundamental inherent mechanisms initiating, and not consequent to, carcinogenesis.

Background: Extensive-stage SCLC (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to 21-question web-based survey about the ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses, the majority were radiation oncologists (89%) with more than 10 years of experience (51%). Preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy before starting immunotherapy (37%), with three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in case of both intrathoracic and extrathoracic response with a RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients.

Background: Colorectal cancer (CRC) is prevalent globally, constituting 11.9% of cases in Mexico. Lymph node metastases are established prognostic indicators, with extracapsular lymph node extension (ENE) playing a crucial role in modifying prognosis. While ENE is associated with adverse factors, certain aspects, like lymph node conglomerates, are underexplored. Matted nodes, clusters of lymph nodes infiltrated by cancer cells, are recognized as an independent prognostic factor in other cancers. This study investigates the prognostic implications of lymph node conglomerates, particularly matted nodes, in colon cancer. Methods: A retrospective analy-sis of 502 colon cancer cases (2005–2018) identified 255 with lymph node metastasis. Cases were categorized into two groups: 1) lymph node metastasis alone (n=208), and 2) lymph node metas-tasis with matted nodes (n=47). A comparative survival analysis was performed. Results: Of the 255 patients, 38% had lymph node metastasis. Patients with matted nodes (18.4%) showed an association with higher pN stage and lymphovascular invasion. The 5-year survival rate for pa-tients with matted nodes was 47.7%, compared to 60% without; however, this association demonstrated only a statistical tendency. Multivariate analysis identified clinical stage and ad-juvant chemotherapy use as independent factors contributing to survival. Conclusion: This study underscores matted nodes as potential prognostic indicators in colon cancer, emphasizing their association with higher pN stage and reduced survival. Further research is essential for validat-ing these findings and integrating matted nodes into the broader context of colorectal cancer management.

Cancer theragnostics is a novel approach that combines diagnostic imaging and radionuclide therapy. It is based on the use of a pair of radiopharmaceuticals, one optimized for positron emission tomography imaging, through linkage to a proper radionuclide, and the other bearing a beta-emitter isotope that can induce significant damage to cancer cells. In recent years, the use of theragnostics in nuclear medicine clinical practice has increased considerably, and thus investigation has focused on the identification of novel radionuclides that can bind to molecular targets which are typically dysregulated in different cancers. The major advantages of the theragnostic approach include elimination of multi-step procedures, reduced adverse effects to normal tissues, early diagnosis, better predicting responses and personalized patient care. This review aims to discuss emerging theragnostic molecules that have been investigated in a series of human malignancies, including gliomas, thyroid cancer, neuroendocrine tumors, cholangiocarcinoma and prostate cancer, as well as potent and recently introduced molecular targets, like cell-surface receptors, kinases, and cell adhesion proteins. Furthermore, special reference has been made to copper radionuclides as theragnostic agents, and their radiopharmaceutical applications since they present promising alternatives to the well-studied gallium-68 and lutetium-177.

Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and better treatment options for cancer, novel and alternative modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are well able to penetrate cancer stem cell niche, simultaneously killing cancer cells and eradicate drug-resistant cancer stem cells, yielding therapeutic efficiency up to 100 fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be considered when using Nano-mediated therapy as the effects of extended exposure to biological environments are still to be determined.

Background: The endocannabinoid system (ECS) is a very heterogeneous array consisting of many proteins like ligands, enzymes and receptors synthetized in various tissues and immunity cells. The main endogenous ligands are unsaturated fatty acid derivatives like anandamide(AEA), 2-arachidonoylglycerol(2-AG), but many others are under study. Endocannabinoids are involved in both physiological and pathological conditions. ECS plays an important role in the regulation of main processes which lead to cancer and also in sex steroid hormone-related cancers. Methods: With focus on gynaecological cancers, main papers and review articles, up to April 2018, on the role of the ECS, were acquired by PubMed searches using the search terms: ‘cancer’, ‘cannabinoid’, ‘endocannabinoid’, ‘gynaecology’ and ‘malignancy’. Results: The review of recent literature data showed the involvement of the endocannabinoid system in numerous physiological and pathological conditions of the female genital tract up to the development of gynaecological malignancy as cervical, endometrial and ovarian cancer. Conclusions: The endocannabinoid system has an important role in antitumor actions involving different signalling receptor and receptor-independent pathways. It represents an exciting challenge to researchers for its potential use in diagnosis and treatment of all gynaecological malignancies

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

This thesis presents a comprehensive review of cancer, with a particular focus on its physical and biochemical basis. Cancer, a leading cause of mortality worldwide, is characterized by the uncontrolled growth and spread of abnormal cells. Understanding the fundamental differences between cancerous and normal cells is essential for developing effective diagnostic tools and therapeutic strategies. The review begins by exploring the physical anomalies of cancer cells, including their irregular shape, size, and structural organization. These cells often exhibit altered cell membranes, disrupted cytoskeletal architecture, and irregularities in cell adhesion and communication, which contribute to their invasive and metastatic potential. The biochemical basis of cancer is examined in detail, with an emphasis on the dysregulation of key metabolic pathways. Cancer cells undergo profound metabolic reprogramming, often referred to as the Warburg effect, where they preferentially utilize glycolysis over oxidative phosphorylation, even in the presence of oxygen. This metabolic shift supports the rapid proliferation of cancer cells and their survival in hypoxic conditions. Additionally, cancer cells produce abnormal proteins that contribute to tumor progression, such as mutant p53, and fail to produce critical tumor suppressor proteins like RB1, leading to unchecked cell division and evasion of apoptosis. Furthermore, the thesis reviews the role of oncogenes and tumor suppressor genes in cancer development, highlighting how mutations and epigenetic alterations drive the transformation of normal cells into malignant ones. The complex interplay between these genetic changes and the tumor microenvironment is also discussed, emphasizing the importance of signaling pathways, immune evasion, and angiogenesis in cancer progression. This detailed review synthesizes current research and insights from authoritative sources, including peer-reviewed journals and foundational medical texts, to provide a thorough understanding of the physical and biochemical underpinnings of cancer. The findings underscore the importance of continued research in these areas to advance the diagnosis, treatment, and prevention of cancer.

The integration of artificial intelligence, particularly Large Language Models (LLMs), has the potential to significantly enhance therapeutic decision-making in clinical oncology. Initial studies across various disciplines have demonstrated that LLM based treatment recommendations can rival those of multidisciplinary tumor boards (MTBs); however, such data are currently lacking for urological cancers. This study provides the methodological foundation for the prospective CONCORDIA trial, which will generate this data for the first time. In this preliminary work, we evaluated the proposed measurement tool for the CONCORDIA study -the System-Causability-Scale (SCS) and its modified version (mSCS) - based on recommendations from ChatGPT-4 and an MTB for 40 urological cancer-scenarios. Both scales demonstrated strong validity, reliability (all aggregated Cohen’s K &gt; 0.74), and internal consistency (all Cronbach’s Alpha &gt; 0.9), with the mSCS showing superior reliability, internal consistency, and clinical applicability (p&lt;0.01). Two Delphi processes were used to define the LLMs to be tested in the CONCORDIA study (ChatGPT-4 and Claude 3.5 Sonnet) and to establish the acceptable non-inferiority margin for LLM recommendations compared to MTB recommendations. The forthcoming ethics-approved and registered CONCORDIA non-inferiority trial will require 110 urological cancer scenarios, with an mSCS difference threshold of 0.15, a Bonferroni corrected alpha of 0.025, and a beta of 0.1. Blinded mSCS assessments of MTB recommendations will then be compared to those of the LLMs. In summary, this work establishes the necessary prerequisites prior to initiating the CONCORDIA study and validates a modified score with high applicability and reliability for this and future trials.

The immune system attempts to eliminate foreign substances, such as pathogens and viruses, that invade the body. As normal cells transform into cancerous cells, the immune system can eliminate these cells and suppress cancer onset. The immune system is regulated so that it does not become overactive or attack normal cells. When cancer cells transform from normal cells, they acquire various characteristics, and some cancer cells influence the regulatory function of the immune system to suppress it and escape immune attack. Therefore, treatments have been developed to eliminate the suppression of the immune system by cancer cells and to restore the immune system's ability to eliminate cancer cells. Immunotherapies include immune checkpoint inhibitors, cytokines, cancer vaccines, and effector cell therapies. Cytokine therapy activates the immune system by injecting substances produced by immune cells (such as interleukin 2 and interferon alpha) into the body, thereby increasing the ability of the immune system to attack cancer cells. Cancer vaccine therapy enhances the attack on cancer cells by injecting substances (antigens) that serve as markers for cancer cells into the body to make it easier for immune cells to detect the cancer. Depending on the type of antigen, cancer peptides, tumor cells, and dendritic cell vaccines are available. Effector cell therapy is a treatment method in which immune cells that directly attack cancer cells (CD8+ T cells, NK cells, etc.) are taken from the patient's body, expanded outside the body, activated, and returned to the body to attack cancer cells. To develop these treatments, it is essential to understand the cells and molecules related to immunity as well as the local tumor environment. In this article, we consider the factors related to antitumor immunity.