Oral squamous cell carcinoma (OSCC) remains an under-studied and significant global cancer killer and dismal survival rates have not changed in decades. A better understanding of the molecular basis of OSCC progression and metastasis is needed to develop new approaches for treating this disease. The supportive network surrounding cancer tumor cells known as the tumor microenvironment (TME) has gained increasing interest lately since it performs essential pro-tumorigenic functions. Cancer-associated fibroblasts (CAFs) are one of the main cell types in the TME and are known to play a key role in influencing the biological behavior of tumors. CAFs present a heterogeneity both in phenotype as well as functions, leading to the suggestion of different CAF subtypes in several cancer forms. The task to subtype CAFs in OSCC has however just begun and there is today no united way of subtyping CAFs in this disease. This review aims to define the features of CAFs and to summarize CAF subtype research in OSCC including aspects as disease prognosis and therapeutic opportunities.

The risk of lung cancer continues to elevate for both smokers and never-smokers. With the increasing morbidities and mortalities related to lung cancer, there is much interest on establishing other confounding factors that lead to lung cancer, other than smoking which is the most common cause. Some of the environmental factors have been identified as potential lung cancer causes. Therefore, the aim of this systematic review is to assess the relationship of environmental factors and lung cancer incidences by investigating various carcinogenic risks exposures that predispose an individual to lung cancer. The objective of this systematic review is thus to assess the evidence of relationship between environmental carcinogens and lung cancer incidence by systematically reviewing relevant studies. A standard criterion for the review methodology was formulated to guide the review process and data extraction. Online databases like PubMed, MEDLINE, Scopus (EMBASE), Google Scholar, Web of Science, and CINAHL were systematically searched for articles published between 2000 and 2021 that explored potential environmental carcinogens that were believed to expose occupational workers and individuals within the environment with lung cancer risks. 25 studies were eligible based on the selection criteria, and were finally included in the systematic review among which four were case-control studies, seven were cohorts, five was prospective, four were previous systematic reviews and four were systematic analysis. Chemical exposures like pesticides were analyzed for their carcinogenesis. Air pollution was also discussed with particulate and coal being the core of evidence of association with lung cancer. Second hand smoke, Asbestos, metal compounds like copper, PVC dust particles and ionizing radiations also provided evidence of environmental carcinogenesis associating to lung cancer cases.

Cancer immunotherapy targeting immune checkpoints has exhibited promising clinical outcomes in many cancers, but it offers only limited benefits for pancreatic cancer (PC). Cancer stem cells (CSCs), a minor subpopulation of cancer cells, play important roles in tumor initiation, progression, and drug resistance. Accumulating evidence suggests that CSCs employ immunosuppressive effect to evade the immune recognition. However, clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD-L1) expression, and CSCs existence are poorly understood in PC. Immunostaining and quantitative analysis were performed to assess CD8+ T cells infiltration, PD-L1 expression, and their relationship with CD44+/CD133+ CSCs and disease progression in PC. CD8+ T cells infiltration was associated with better survival while PD-L1 expression was correlated with PC recurrence. Both the low CD8+ T cells infiltration/high PD-L1 expression group and the high CD8+ T cells infiltration/high PD-L1 expression group show high levels of CD44+/CD133+ CSCs, but patients with low CD8+ T cells infiltration/high PD-L1 expression had worse survival and higher recurrence risk than those with high CD8+ T cells infiltration/high PD-L1 expression. Moreover, CD8+ T cells infiltration could reduce unfavorable prognostic effect of high co-expression of PD-L1 and CD44/CD133. Our study highlights an interaction among CD8+ T cells infiltration, PD-L1 expression, and CD44+/CD133+ CSCs existence, which contributes to PC progression and immune evasion.

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.

Background: Oncology patients experience a large number of symptoms and, those referring to cognitive performance has an ever-increasing importance in clinical practice due to the increase in survival rates and interest in the patient's quality of life. The studies reviewed show that chemotherapy-related cognitive impairment may occur in 15 and 50% of oncology patients. The main objective of this research was to study the impact of chemotherapy on the cognitive function of patients with locoregional breast cancer.Method: Analytical, prospective, longitudinal study using three measures, unifactorial intrasubject design, non-probability and random selection sampling. The sample comprised women newly diagnosed with locoregional breast cancer in stages I, II, IIIA who received chemotherapy at the University Hospital of Salamanca (Complejo Asistencial Universitario de Salamanca) randomly selected for three years. Semi-structured interviews were conducted, and anxiety and depression (Hospital Anxiety and Depression scale, HAD); quality of life (QLQ-BR23 scale) and the following cognitive variables were assessed: processing speed, attention, memory and executive functions (subtests of the Wechsler Intelligence Scale and the Trail Making Test). Results: The final sample size included 151 participants; 23 were excluded. A decline in cognitive performance was observed in patients which was not completely recovered two months after chemotherapy had been completed. Also, worse cognitive performance was observed in patients with anxious or depressive symptoms. There is a negative impact on the quality of life. Conclusion: Chemotherapy has an impact on the cognitive performance of oncology patients in most of the cognitive domains studied.

(1) Background: This study aimed to investigate the effect of increased HER-2 expression on tumor-infiltrating lymphocytes (TILs) and determine its impact on the prognosis of colorectal cancer (CRC) patients; (2) Methods: HER-2, CD4, CD8, CD19, LY6G, CD56, CD68, CD11b, and EpCam expression in CRC tissues and adjacent paracancerous tissues were assessed using multiplex fluorescence immunohistochemical staining. The correlation between HER-2 expression and the number of TILs in CRC tissues was analyzed. Kaplan-Meier and Cox proportional hazards models were used to analyze survival outcomes; (3) Results: The expression of HER-2 in tumor tissues was higher than that in paracancerous tissues (1.31 ± 0.45 vs. 0.86 ± 0.20, P < 0.05). Additionally, there was an increase in the numbers of CD4+, CD8+, CD19+, and CD68+ cells in CRC tissues (14.11 ± 1.10 vs. 3.40 ± 0.18, P < 0.005; 0.16 ± 0.12 vs. 0.04 ± 0.04, P < 0.005; 0.71 ± 0.46 vs. 0.25 ± 0.13, P < 0.0005; 0.27 ± 0.24 vs. 0.03 ± 0.11, P < 0.05). The increase in HER-2 expression was positively correlated with an increase in CD4, CD8, and CD19 (p < 0.0001). In HER-2-positive CRC tissues, CD68 expression was increased (0.80 ± 0.55 vs. 0.25 ± 0.22, P < 0.05). In HER-2-upregulated CRC tissues, CD4, CD8, CD19, CD68, CD11b, Ly6G, and CD56 expressions were elevated (0.70 ± 0.37 vs. 0.32 ± 0.17, P = 0.03; 0.22 ± 0.13 vs. 0.09 ± 0.06, P = 0.03; 0.31 ± 0.19 vs. 0.12 ± 0.08, P = 0.02; 1.05 ± 0.62 vs. 0.43 ± 0.21, P < 0.01; 1.34 ± 0.81 vs. 0.53 ± 0.23, P < 0.01; 0.50 ± 0.31 vs. 0.19 ± 0.10, P < 0.01; 1.26 ± 0.74 vs. 0.52 ± 0.24, P < 0.01). Furthermore, increased HER-2 expression is an independent risk factor for recurrence-free survival (RFS) in patients (P < 0.01, HR = 3.421); (4) Conclusions: The increased expression of HER-2 and its relationship with immune cells will provide new insights for immunotherapy in CRC patients.

SETD7 is a member of the SET domain-containing lysine methyltransferase family and is a crucial component in the development and spread of a number of human cancers. However, the specific function of the SETD7 gene in ovarian cancer (OC) is still unclear. The purpose of this research was to elucidate the expression and role of SETD7 in OC. In comparison to normal controls, OC tissues (83%, 73/88) and cell lines exhibited higher protein levels of SETD7 (p < 0.001). High SETD7 protein levels were substantially correlated with M category (p = 0.019) and FIGO stage (p = 0.021). Furthermore, the high mRNA levels of SETD7 were correlated to poor progression-free survival (PFS) in all patients and serous patients with OC (p < 0.05). Importantly, the biological function experiments showed that SETD7 behaved as an oncogene in OC by dramatically facilitating the proliferation and migration of A2780 and SKOV3 cells. Additionally, SETD7 might promote cell migration via accelerating the EMT process in A2780 and SKOV3 cells. Our findings reveal that SETD7 may be a valuable molecular marker for identifying and anticipating the development of OC.

Pancreatic cancer is one of the most fatal common cancers affecting both men and women, representing about 3 percent of all new cancer cases in the United States. In this study, we aimed to investigate the association of pancreatic cancer risk with alcohol consumption as well as folate intake. We performed a case-control study of 384 patients diagnosed with pancreatic cancer from May 2004 to December 2009 and 983 primary care healthy controls. Our findings showed no significant association between risk of pancreatic cancer and either overall alcohol consumption or type of alcohol consumed (drinks/day). Our study showed dietary folate intake was modestly but significantly inversely associated with pancreatic cancer (OR=0.99, P <.0001). The current study supports the hypothesis that pancreatic cancer risk is reduced with higher food-based folate intake.

Chronic inflammation may have a detrimental impact on human health as it tends to result in cancer. In addition, it is often linked to different steps that participate in tumorigenesis, including cellular transformation, survival, promotion, invasion, proliferation, angiogenesis, and metastasis. Hence, inflammation predisposes cancer development and plays a vital role in promoting all tumorigenesis stages. Inflammation is caused by many factors, such as bacterial and viral infections, tobacco smoking, autoimmune diseases, obesity, asbestos exposure, and many others, increasing cancer risk. Moreover, cancer can be enhanced by mutations that proceed to cancer progression. Consequently, it leads to immunosuppression and provides a favorable background for tumor development. Although many studies address the question of relationships between inflammation and cancer development, little attention is paid to the link between inflammation and blood cancer. Therefore, the current study reviews the role of inflammation in cancer development, particularly in blood cancer. A meta-analysis research approach meets the research objective and answers the research question. The review results indicate that chronic inflammation directly relates to the development of many cancer types, blood cancer in particular.

The perspective suggests an unorthodox interpretation of cancer dynamics in terms of strange attractors and fluid turbulence. The relevance of strange attractors in tumor growth-invasion dynamics and chemical pattern formation are reviewed. Chemical turbulence, fractals and chaos are discussed as the principal characteristics of tumor ecosystems and their complex cybernetics. To conclude, cancers are presented as complex systems exhibiting chaotic gene expression dynamics.

Metastasis is a major cause factor for breast cancer (BC)-associated mortality. During the metastatic process, disseminated tumor cells (DTCs) detach from the primary sites, and enter the bloodstream and establish the secondary colonies. Recent studies have provided substantial evidence for the importance of Notch signaling in BC metastasis. Therefore, this review focuses on the mechanisms by which Notch contributes to the origin of BC DTCs, increases their motility, regulates their intravasation and extravasation, protects them from host surveillance, and finally facilitates colonization. Identification of the mechanisms underlying Notch-related BC metastasis will lead to the development of novel Notch-targeted therapeutic strategies to reduce metastasis and significantly improve outcomes.

Next Generation Sequencing based cancer risk screening with multigene panels has become the most successful method for programming cancer prevention strategies. ATM germ-line heterozygosity has been described as able to increase tumor susceptibility. In particular, families that carry heterozygous germ-line variants of ATM gene show a 5- to 9-fold risk of developing breast cancer. Recent studies identified ATM as the second most mutated gene after CHEK2 in BRCA-negative patients. Nowadays, more than 170 potential missense variants and several truncating mutations have been identified in ATM gene. Here we present the molecular characterization a new ATM deletion, identified thanks to the CNV algorithm implemented in the NGS analysis pipeline. An automated workflow implementing the SOPHiA Genetics’ Hereditary Cancer Solution (HCS) protocol was used to generate NGS libraries that were sequenced on Illumina MiSeq Platform. NGS data analysis allowed to identify a new inactivating deletion of exons 19-27 of ATM gene. DNA breakpoint was characterized both at DNA and RNA level

Podocalyxin (PODXL) overexpression is associated with poor clinical outcomes in various tumors. PODXL is involved in tumor malignant progression through the promotion of invasiveness and metastasis. Therefore, PODXL has been considered as a promising target of monoclonal antibody (mAb)-based therapy. However, PODXL also plays an essential role in normal cells such as vascular and lymphatic endothelial cells.Therefore, cancer-specificity or selectivity is required for the reduction of adverse effects on normal cells. Here, we developed an anti-PODXL cancer-specific mAb (CasMab), PcMab-6 (IgG₁, kappa), by immunizing mice with soluble PODXL ectodomain derived from a glioblastoma LN229 cell.PcMab-6 reacted with the PODXL-positive LN229 cells, but not with PODXL-knockout LN229 cells in flow cytometry. Importantly, PcMab-6 recognized pancreatic ductal adenocarcinoma (PDAC) cell lines (MIA PaCa-2, Capan-2, and PK-45H), but did not react with normal lymphatic endothelial cells (LECs). In contrast, one of the non-CasMabs, PcMab-47 showed high reactivity to both the PDAC cell lines and LECs. Next, we engineered PcMab-6 into a mouse IgG_2a type (PcMab-6-mG_2a) and a humanized IgG₁-type (humPcMab-6) mAbs, and further produced the core fucose-deficient types (PcMab-6-mG_2a-f and humPcMab-6-f, respectively) to potentiate the antibody-dependent cellular cytotoxicity (ADCC). Both PcMab-6-mG_2a-f and humPcMab-6-f exerted ADCC and complement-dependent cellular cytotoxicity in the presence of effector cells and complements, respectively. In the PDAC xenograft model, both PcMab-6-mG_2a-f and humPcMab-6-f exhibited potent antitumor effects. These results indicated that humPcMab-6-f could apply to antibody-based therapy against PODXL-expressing pancreatic cancers.

This document summarizes the evidence currently available about the effects of the anesthetic agents and techniques used in primary cancer surgery and long-term oncologic outcomes, and the biomolecular mechanisms involved in their interaction..

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.

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.

Background: We screened key genes involved in the dedifferentiation process of thyroid cancer by analyzing differentially expressed genes in anaplastic thyroid carcinoma (ATC) using Gene Expression Omnibus (GEO) database. Methods: We analyzed differentially expressed genes in ATC from GEO database and constructed a co-expression network using Weighted Gene Co-expression Network Analysis (WGCNA) . Cytoscape was used to calculate top ten key genes based on their gene scores. DEPDC1 was selected as interest gene for further validation, including examination of its prognostic relationship with thyroid cancer, correlation analysis with thyroid differentiation markers, immune cell infiltration, and tumor microenvironment. The impact of DEPDC1 on cancer cell migration, invasion, and proliferation was validated through downregulation and overexpression of DEPDC1 gene in thyroid cancer cell lines c643 and BCPAP. Results: We identified top 10 key genes in ATC: AURKA, TPX2, RACGAP1, MELK, DLGAP5, DEPDC1, KIF2C, NCAPG, CCNB1, and PBK. DEPDC1 showed a strong correlation with the prognosis of thyroid cancer. The odds ratio (OR) for overall survival was 3.5 (P=0.016) in individuals with high DEPDC1 expression, and the OR for disease-free survival was 2.6 (P=0.003). Additionally, the analysis revealed a significant negative correlation between the expression of DEPDC1 and thyroid differentiation markers. Gene Ontology enrichment analysis demonstrated that DEPDC1 co-expressed genes were enriched in cellular processes, cell cycle pathways, and dynamic protein groups. Matrix and immune scoring indicated tumor microenvironment and immune scores were associated with DEPDC1 expression. TIMER2.0 online analysis revealed a strong correlation between DEPDC1 expression and immune cell infiltration in papillary thyroid carcinoma. After downregulation of DEPDC1 expression, the invasion, migration, and proliferation abilities of tumor cells were significantly reduced. Conversely, overexpression of DEPDC1 exhibited the opposite effect. Conclusion: DEPDC1, a newly identified dedifferentiation gene in thyroid cancer, inversely correlated with the degree of differentiation. High expression of DEPDC1 promotes cancer progression and leads to poor prognosis in thyroid cancer.

Preferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen (CTA) that is selectively expressed in certain somatic tissues, predominantly in the testis and is overexpressed in various cancers. PRAME family proteins are leucine rich repeat proteins, that are localized in the nucleus and cytoplasm, with multifaceted roles in immunity, during gametogenesis and in the overall reproduction process. It is a widely studied CTA and has been associated with the prognosis and therapeutic outcome in patients with epithelial and non-epithelial tumors. PRAME has also been studied extensively as a therapeutic target. Moreover, it has been found to play a role in most of the well-known cancer hallmarks. Interestingly, the role of PRAME in tumorigenesis is paradoxical. Over the last decade, PRAME has garnered substantial interest as a target for immunotherapy. There are multiple clinical trials and pre-clinical studies targeting PRAME alone or in combination with other tumor antigens. This review article is an attempt to update our knowledge and understanding of the context-dependent oncogenic functions of PRAME in various carcinomas, and the current immunotherapeutic strategies, challenges, and perspectives on developing newer strategies to target PRAME for a better outcome.

Young women with breast cancer represent 15% of cancer cases in Latin America. Genomic studies have found that early-onset breast-cancer cases exhibit a higher genetic susceptibility and a specific genomic signature as compared to their older counterparts. The aim of this study was to describe clinically relevant germline mutations in a cohort of young women with breast cancer. To achieve this, we analyzed hereditary-cancer genes from whole-exome sequencing data in 108 unrelated women with an extreme phenotype of breast cancer (≤40 years of age), diagnosed and treated at the National Cancer Institute of Mexico; 11% of the patients carried a pathogenic variant. BRCA2 comprised 46% of the mutations, followed by BRCA1 with 23%; PALB2 with 15%; and TP53 and RAD51C with 8 % each. This article describes a novel pathogenic mutation in RAD51C c.519dupT. The median age at diagnosis was 35 years overall; however, it was six years younger in patients with mutations. Age at diagnosis (OR=0.82, CI 95% 0.71-0.94; P= 0.008) and first-degree family history of cancer (OR=8.26, CI95% 1.35-50; P= 0.022) were the only epidemiological variables associated with mutational status. We found no differences in disease-free survival (p=0.403) or overall survival (p=0.735) among mutational status subgroups.

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.

Comprehensive studies into the various causes of this ubiquitous disease have been prompted by the worldwide increase in cancer incidence. There are many potential causes of cancer, but environmental factors are of particular concern now. This abstract explores the complex link between environmental factors and the growing cancer epidemic, shedding light on the role that our immediate environment plays in the emergence of cancers. The environment can contain carcinogenic agents that gradually influence the course of cancer, including air pollutants, water contaminants, workplace exposures, and industrial activities. The ways through which environmental carcinogens may cause DNA damage and unchecked cell proliferation are discussed in this abstract. Environmental justice and the moral necessity to reduce inequities in exposure and health effects are highlighted to underline the disproportionate impact on vulnerable groups. The study presented here highlights the need for preemptive action to reduce environmental risks. Society can reduce the hidden threat posed by environmental carcinogens through strict legislation, sustainable practices, and community-driven initiatives. In order to lessen the cancer burden and secure a healthier future for all, the authors of this abstract argue that there must be a concerted effort to create surroundings that promote health and well-being.

Ferroptosis is a newly discovered iron-dependent form of regulated cell death driven by phospholipid peroxidation, associated with processes including iron overload, lipid peroxidation and dysfunction of cellular antioxidant systems. Ferroptosis is found closely related to many diseases including cancer, at its every stage. Epithelial-mesenchymal transition (EMT) in malignant tumors that originate from epithelia promotes cancer cell migration, invasion and metastasis by disrupting cell-cell and cell-martrix junctions, cell polarity, etc. Recent studies have shown that ferroptosis appears to share multiple initiators and overlapping pathways with EMT in cancers and identify ferroptosis as a potential predictor of various cancer grade and prognosis. Cancer metastasis involves multiple steps including local invasion of cancer cells, intravasation, survival in circulation, arrest at a distant organ site, extravasation and adaptation to foreign tissue microenvironments, angiogenesis and the formation of “premetastatic niche”. Numerous studies have revealed that ferroptosis is closely associated with cancer metastasis. From the cellular perspective, ferroptosis has been implicated in the regulation of cancer metastasis. From the molecular perspective, the signaling pathways activated during the two events interweave. This review briefly introduces the mechanisms of ferroptosis, and discusses how ferroptosis is involved in cancer progression including EMT, cancer angiogenesis, invasion and metastasis.

We previously described a model of deep intrinsic resistance of breast cancer wherein we used a function-based approach to selection of cancer cells that can survive a variety of challenges in prolonged but reversible quiescence. Our experimental results suggested that resistant cancer cells possess a variety of mechanisms, including modifications of the epigenome and transcriptome, for generating a high degree of cellular heterogeneity. In the present study, we evaluated JIB-04, a small-molecule epigenetic inhibitor initially discovered to inhibit cancer growth, to determine its ability to affect deep intrinsic resistance in our breast cancer model. We found that long pretreatment with JIB-04 sensitized resistant triple-negative inflammatory breast cancer cells and their parental cell line SUM149 to the chemotherapeutic drugs doxorubicin and paclitaxel. Resistant cancer cells derived from another inflammatory breast cancer cell line, FC-IBC02, were considerably more sensitive to JIB-04 than was the parental cell line. Investigating a mechanism of sensitization, we found that JIB-04 exposure increased the expression of PD-L1 in resistant cells, suggesting that JIB-04 may also sensitize resistant breast cancer cells to anti-PD-L1 immune therapy. Finally, these results support the usefulness of our experimental strategy for evaluating anticancer agents such as JIB-04 that may halt cancer evolution and prevent development of cancer resistance to currently used therapies.

S100A10, which is also known as p11 is located in the plasma membrane and forms a heterotetramer with annexin A2. The heterotetramer, comprising of 2 subunits of annexin A2 and S100A10, activates the plasminogen activation pathway which is involved in cellular repair of normal tissues. Increased expression of annexin A2 and S100A10 in cancer cells leads to increased levels of plasmin which promote degradation of the extracellular matrix, increased angiogenesis and invasion of the surrounding organs. Although many studies have investigated the functional role of annexin A2 in cancer cells including ovarian cancer, S100A10 has been less studied. We recently demonstrated that high stromal annexin A2 and high cytoplasmic S100A10 expression is associated with a 3.4 fold increased risk of progression and 7.9 fold risk of death in ovarian cancer patients. Other studies have linked S100A10 with multidrug resistance in ovarian cancer, however, no functional studies to date have been performed in ovarian cancer cells. This article reviews the current understanding on S100A10 function in cancer with a particular focus on ovarian cancer.

The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a pivotal role in cancer cells’ proliferation and metastatic spreading. Considering the high expression of the fibroblast activation protein (FAP) on cell membrane, CAFs emerged as appealing TME targets, namely for molecular imaging, leading to a pan-tumoral approach. Therefore, FAP inhibitors (FAPis) have been recently developed for PET imaging and radioligand therapy, exploring the clinical application in different tumor sub-types. The present review aimed to describe recent developments on radiolabeled FAP inhibitors and evaluate the possible translation of this pan-tumoral approach in clinical practice. At present, the application of FAPi-PET has been explored mainly in single-center studies, generally performed in small and heterogeneous cohorts of oncological patients. However, preliminary results were promising, in particular in low FDG-avid tumors such as primary liver and gastro-entero-pancreatic cancer, or in regions with unfavorable tumor-to-background ratio at FDG-PET/CT (i.e. brain), as well as in radiotherapy planning of head and neck tumors. Further promising results have been obtained in the detection of peritoneal carcinomatosis, especially in ovarian and gastric cancer. Data regarding the theranostics approach are still limited at presents, and definitive conclusion about its efficacy cannot be drawn at present. Nevertheless, the use of FAPi-based radio-ligand to treat the TME has been evaluated in first-in-human studies and appears feasible. Although the pan-tumoral approach in molecular imaging showed promising results, its real impact in day-to-day clinical practice has yet to be confirmed, and multi-center, prospective studies powered for efficacy are needed.

Background: Although previous studies have implicated a role for the stool microbiome in cancer cachexia, the fecal microbiome has not been previously characterized for patients with pancreatic ductal adenocarcinoma (PDAC) and cachexia treated with nutritional interventions such as enteral feeding. Methods: The PANCAX-1 (NCT02400398) prospective trial enrolled 31 cachectic advanced PDAC patients to receive jejunal tube peptide-based diet for 12 weeks who were planned for palliative chemotherapy. Out of 16 evaluable patients, 62.5% receiving enteral feeding met the primary endpoint of weight stability at 12 weeks. As part of an exploratory analysis of the PANCAX-1 trial, serial stool and blood samples were collected at 0 (C1D1), 6 (C2D1), and 12 (C3D1) weeks over the 12-week period of enteral feeding. Stool samples were analyzed using 16S v4 sequencing of the microbiome. Up to 219 plasma metabolites were analyzed by mass spectrometry and high-performance liquid chromatography. Results: A total of 29 stool samples were prospectively collected from 16 subjects with PDAC enrolled in PANCAX-1 who were evaluable for weight stability. Over 12 weeks of enteral feeding, statistically significant increases in the abundance of bacterial genera such as Veillonella (p=0.0150) and Actinomyces (p=0.0390) were observed, while there was a lower abundance of Bacteroides (p=0.0150) and Butyricicoccus (p=0.0390). Greater abundance of Veillonella and reduced Bifidobacterium at baseline were linked to greater weight stability. Plasma metabolomics in 10 subjects showed that weight unstable patients had significantly decreased levels of essential (L-histidine, L-phenylalanine) and non-essential amino acids (L-citrulline, L-tyrosine, all p<0.05) at the end of 12 weeks of enteral feeding. High stool Veillonella abundance was significantly associated with increases in the nucleotide 2-deoxycytidine 5-diphosphate and essential amino acid L-isoleucine but decreased TCA cycle metabolite alpha-ketoglutarate (all p<0.05). Conclusions: We are the first to demonstrate the feasibility of stool microbiome profiling and plasma metabolomics in paired stool and plasma samples from a prospective cohort of advanced PDAC patients on enteral feeding as their primary source of nutrition. Our findings are hypothesis-generating in that metabolites unique to weight stability and abundance of stool bacterial genera may inform future studies of anti-cachexia therapies involving enteral feeding or microbial modulation.

Background: Cancer has been one of the most critical health problems during the past decades which require serious consideration, especially in developing countries. Methods: 80 parents of the children with different types of cancers were studied via both questionnaire and person-to-person interview after announcing their informed consent. Results: The highest delay in patients' initial referral was due to the following factors: lack of attention or ignoring the first symptoms, delay in referring to the physician, low economic status and even lack of family support for the patient. In addition, visiting several doctors after the initial diagnosis, uncertainty about the first proposed method, and high cost of treatment can be mentioned as the main causes of delays in the start of treatment. Conclusion: Education plays an important role in identifying the signs of cancer. In addition, proper relationship and cooperation between the health system and physicians as well as provision of adequate information to patients could lead to the long-term cooperation of these patients in continuing their treatment.

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths, globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. This review examines the link of Reactive oxygen Species (ROS)-altered metabolic and signaling pathways in T2DM to cancer. These reprogrammed metabolic and signaling pathways are activated that contribute to diabetic complications, impact redox balance (Oxidative Stress), and have differential roles in early and late stages of cancer. If the respiratory chain is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevation. Amplification of ROS results in activation of PKC, an overarching signaling pathway that activates MAPK with subsequent regulation of several factors that result in pathophysiological manifestations of T2DM and cancer. Upregulation of PKC leads to deregulation of NF-kß that regulates the PKB/P13/Akt pathway that orchestrates cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in early and late stages of cancer make antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting formation of ROS early during the pre-diabetic stage whereas antioxidant therapy must be halted in later stages to retard metastasis.

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades, to over 80% as per today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is the cardiotoxicity. The chemotherapeutic agents that have been implicated as a cause of cardiotoxicity, are mostly anthracyclines and mitoxantrone, alkylating agents, proteasome inhibitors and to a lesser extent anti-microtubule agents, cisplatin, monoclonal antibodies, small molecular tyrosine kinase inhibitors, and nucleotide synthesis inhibitors. Routine diagnosis and monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite refinements in diagnostics still severe limitations exist, due to the increase of the above-mentioned biomarkers, only after significant cardiac damage has occurred. Lately, research has been expanded by introducing new technologies and finding new markers by omics approach. These new markers could be used not only for early detection, but also for early prevention of cardiotoxicity. The omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide understanding of mechanisms of cardiotoxicity, beyond traditional technologies. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents mainly involved in cardiotoxicity and the methods of early and preventive diagnosis, using omics technology.

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].

In this review, we will cover a general overview of the current panorama on lncRNAs with an actual or potential role as biological markers in cancer. We will discuss examples of multi-omics approaches that integrates information on somatic aberrations, gene expression and epigenomics, with the scope of providing a more comprehensive view of the functional impact of lncRNA profiles and how these paradigm can be exploited for the discovery and selection of lncRNAs with a functional role and their use as variables informing on progression and prognostic and help guiding the selection of therapeutic strategies for cancers. Finally, we propose a perspective for future evolution of the study of lncRNAs and the discovery of their functional and harnessing their potential to assist in clinical management of malignancies.

Laparoscopic partial nephrectomy (LPN) after hyperselective embolization of tumor vessels (HETV) in a hybrid operating room (HOR) that combines traditional surgical equipment with advanced imaging technology, is a non-clamping surgical approach to treat localized kidney tumors that have shown promising short-term results. The aim of this study was to evaluate the long-term oncological and functional outcomes of this procedure. All consecutive patients treated for a localized kidney tumor by LPN after HETV between May 2015 and October 2022 in a single academic institution were included in the study. Clinical, pathological and biological data were collected prospectively in the uroCCR database. We evaluated perioperative data, postoperative complications, surgical margin and modification of renal function after surgery. We included 245 patients. Median tumor size was 3.2 (2.5-4.4) cm. The R.E.N.A.L. complexity was low, medium and high for 104 (43.5%), 109 (45.6%) and 26 (10.9%) patients, respectively. Median LPN time was 75 (65 -100) min and median blood loss was 100 (50-300) mL. Surgical postoperative complications occurred in 56 (22.9%) patients with 17 (5.7%) major complications. The median preoperative Glomerular Function Rate (GFR) was 90.5 (77-101.8) mL/min and the median GFR variation at 6 months was -7.5 (-15- -2) mL/min. Malignant tumors were present in 211 (86.1%) patients and 12 (4.9%) patients had positive surgical margins. After a median follow-up of 27 (8-49) months, 20 (8.2%) patients had a tumor recurrence and 4 (1.6%) died from cancer. The use of a HOR to perform LPN after HETV is a safe and efficient non-clamping approach to treat localized kidney tumors.

Synucleins are a family of small, soluble proteins mainly expressed in neural tissue and in certain tumors. Since their discovery, tens of thousands of scientific reports have been published about this family of proteins as they are associated to severe human diseases. Although the physiological function of these proteins still elusive, their relation with neurodegeneration and cancer was clearly described over the years. In this review, we summarize data connecting synucleins and cancer, going from the structural description of these molecules, to their involvement in tumor-related processes, and discuss the putative use of this proteins as cancer molecular biomarkers.

Background: Opinions on the impact of cancer on patients with haemophilia literature are contradicting. There is a lack of data on the clinical presentation and management of cancer in patients with haemophilia (PWH). Methods: Papers were found following a comprehensive search in PubMed, Google Scholar, and Scopus using the terms “cancer” and “haemophilia” without time limits and using the English language as a filter. The references of all retrieved original articles and reviews were assessed for additional relevant articles. Results: Overall, 116 papers were collected. Managing cancer in patients with congenital bleeding disorders, such as haemophilia A and B, requires careful evaluation of bleeding risk and the effect of antitumor treatments on blood coagulation. Generally, patients with haemophilia do not have an increased risk of developing cancer compared to the general population; increased risk is found in the presence of HIV or hepatitis infection. However, if a patient with haemophilia develops cancer, the treatment must be managed to minimise the risk of bleeding. Bleeding and thrombotic complications are important causes of morbidity and mortality in critically ill patients with cancer; replacement therapy with factor VIII or IX or others should be maintained during antitumor treatment. Conclusion: Overall, managing cancer in patients with haemophilia requires careful evaluation and individualised planning involving a multidisciplinary team of physicians experienced in haematology, oncology, and surgery.

Nowadays, colon cancer prognosis still difficult to predict, especially in the early stages. Recurrences remain elevated, even in the early stages after curative surgery. Carcidiag Biotechnologies has developed an immunohistochemistry (IHC) kit called ColoSTEM Dx, based on a MIX of biotinylated plant lectins that specifically detects colon cancer stem cells (CSCs) through glycan patterns that they specifically (over)express. A retrospective clinical study was carried out on tumor tissues from 208 non-treated and 21 treated patients with colon cancer, that were stained by IHC with the MIX. Clinical performances of the kit were determined, and prognostic and predictive values were evaluated. With 78.3% and 70.6% of diagnostic sensitivity and specificity respectively, our kit shows great clinical performances. Moreover, patient prognosis is significantly poorer when the MIX staining is “High” compared to “Low”, especially at 5-years of overall survival and for early stages. The ColoSTEM Dx kit allows an earlier and a more precise determination of patients’ outcome. Thus, it affords an innovating clinical tool for predicting tumor aggressiveness earlier and determining prognosis value regarding therapeutic response in colon cancer patients.

Pancreatic cancer (PC) is the most lethal type of cancer, it has the lowest 5-year survival rate among all other types of cancers. More than half of PC cases are diagnosed at an advanced stage due to PC’s insidious and non-specific symptoms. Surgery remains the most efficacious treatment option currently available, but only 10-20% of PC cases are resectable upon diagnosis. As of now, the sole biomarker approved by the United States Food and Drug Administration (US-FDA) for PC is carbohydrate antigen 19-9 (CA19-9); however, its use is limited use for early diagnosis. An in-creasing number of studies have investigated a combination of biomarkers. Lately, there has been considerable interest in the application of a liquid biopsy, including the utilization of microRNAs (miRNAs), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs). Screening for PC is indicated for high-risk patients; studies on new diagnostic models combined with biomarkers for early detection have also shown promising results for the ability of these models and biomarkers to aid clinicians in deciding on whether to start screening. This review seeks to provide a concise overview of the advancements in existing biomarkers and explore novel strategies for the early detection of PC.

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

Discovery of novel variants from data derived from local population provides confident targets for developing biomarkers for personalized medicine. Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. We identified the need to generate high quality sequencing data from local population and understand the pattern of occurrence of variants in colorectal cancer patients. In this report, we used archived samples from Saudi Arabia and used Ampliseq Comprehensive Cancer panel to identify novel somatic variants. We report a comprehensive analysis of next generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in large intestine. APC, RET and EGFR genes were most frequently mutated. Higher number of variants were identified in left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population.

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase(QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p<0.05, AUC=0.89), when measured by multiple reaction monitoring(MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

There is a growing body of evidence supporting the significant role of bacterial biofilms in the pathogenesis of various human diseases including cancer. Biofilms are polymicrobial communities enclosed within an extracellular matrix composed of polysaccharides, proteins, extracellular DNA, and lipids. This complex matrix provides protection against antibiotics and host immune responses, enabling the microorganisms to establish persistent infections. Moreover, biofilms induce anti-inflammatory responses and metabolic changes in the host, further facilitating their survival. Many of these changes are comparable to those observed in cancer cells. This review will cover recent research on the role of bacterial biofilms in carcinogenesis, especially in colorectal (CRC) and gastric cancers, emphasizing the shared physical and chemical characteristics of biofilms and cancer. This review will also discuss the interactions between bacteria and the tumor microenvironment, which can facilitate oncogene expression and cancer progression. This information will provide insight into developing new therapies to identify and treat biofilm-associated cancers, such as utilizing bacteria as delivery vectors, using bacteria to upregulate immune function, or more selectively targeting biofilms and cancer for their shared traits.

Chemically modified forms of tetraiodothyroacetic acid (tetrac), an L-thyroxine derivative, have been shown to exert their anticancer activity at plasma membrane integrin αvβ3 of tumor cells. Via a specific hormone receptor on the integrin, tetrac-based therapeutic agents modulate expression of genes relevant to cancer cell proliferation, survival and energy metabolism. P-bi-TAT, a novel bivalent tetrac-containing synthetic compound has anticancer activity in vitro and in vivo against Glioblastoma Multiforme (GBM) and other types of human cancers. In the current study, microarray analysis was carried out on a primary culture of human GBM cells exposed to P-bi-TAT (10-6 tetrac equivalent) for 24 h. P-bi-TAT significantly affected expression of a large panel of genes implicated in cancer cell stemness, growth, survival, and angiogenesis. Recent interest elsewhere in ATP synthase as a target in GBM cells caused us to focus attention on expression of genes involved in energy metabolism. Significantly downregulated transcripts included multiple energy metabolism-related genes: electron transport chain genes ATP5A1 (ATP synthase 1), ATP51, ATP5G2, COX6B1 (cytochrome c oxidase subunit 6B1), NDUFA8 (NADH dehydrogenase [ubiquinone] FA8), NDUFV2I and other NDUF genes. The NDUF and ATP genes are also relevant to control of oxidative phosphorylation and transcription. Qualitatively similar actions of P-bi-TAT on expression of energy metabolism-linked genes were also detected in established human GBM and pancreatic cancer cell lines. In conclusion, acting at αvβ3 integrin, P-bi-TAT caused downregulation in human cancer cells of expression of a large number of genes involved in electron transport and oxidative phosphorylation. These observations suggest that cell surface thyroid hormone receptors on αvβ3 regulate expression of genes relevant to tumor cell stemness and energy metabolism.

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: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy. We determined the validity of a rare-cell detection platform and demonstrated the usefulness of a certain rare cell subset as a novel approach to characterize the breast cancer system. Methods: Linearity of the Rarmax® platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 non-cancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts and inflammation-associated cells, was performed using a phenotype and morphology-based classification system. Results: The platform performed linearly over a range of 5-950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 50% and 85.7%, respectively and the specificity was 100% and 96.6%, respectively. Conclusion: The present study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

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.

Introduction. Self-sampling has the potential to increase cervical cancer screening (CCS) among women living with HIV (WLWH) in low and middle-income countries (LMICs). However, our understanding of how HPV self-collection studies have been conducted in WLWH is limited. The purpose of this scoping review was to examine the extent to which the HPV self-sampling has been applied among WLWH in LMICs. Method: We conducted multiple searches in several databases for articles published between 2000 and January 2022. With the combination of keywords relating to HPV self-sampling, LMICs, and WLWH, we retrieved over 9,000 articles. We used pre-defined inclusion and exclusion criteria to select relevant studies for this review. Once a study met the inclusion criteria, we created a table to extract each study’s characteristics and classified them under common themes. We used a qualitative descriptive approach to summarize the scoping results. Results: A total of 12 articles were included in the final review. Overall, 3,178 women were enrolled in those studies and 2,105 (66%) of them were WLWH. The self-sampling participation rate was 92.6%. The findings of our study show that 43% of the WLWH in 8 of the studies reviewed tested positive for high-risk HPV (hr-HPV) genotypes, indicating 4 out of 10 WLWH in the studies are at risk of cervical cancer. The prevalence of the hr-HPV in WLWH was 18% higher than that of HIV-negative women. Most women in the study found the self-sampling experience acceptable, easy to use, convenient, and comfortable. Self-sampling performance in detecting hr HPV genotypes is comparable to clinician-performed sampling. However, limited access (i.e., affordability, availability, transportation), limited knowledge about self-screening, doubts about the credibility of self-sampling results, and stigma remain barriers to wide acceptance and implementation of self-sampling. In conclusion, the findings of this review highlight that (a) cervical cancer is a threat to every sexually active woman but for WLWH the threat increases, (b) self-sampling laboratory performance is similar to clinician performed sampling, (c) self-sampling is associated with an increase in cervical cancer screening uptake and (d) WLWH reported a positive experience with self-sampling. However, personal, environmental, and structural barriers challenge the application of self-sampling in LMICs, and these need to be addressed. Keywords: keyword 1; keyword 2; keyword 3 (List three to ten pertinent keywords specific to the article yet reasonably common within the subject discipline.)

Background: The management of penile cancer patients has some grey zones, one of them being the timing of prophylactic pelvic lymph node dissection. Here, we review the impact of timing of prophylactic inguinal and pelvic lymph node dissection on patients’ outcome. Methods: Relevant databases were searched according to recommendations by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Before the systematic review we present a narrative review on the indications for lymph node dissection and the impact of pathological anatomical considerations on the timing of prophylactic lymph node dissection and patients’ outcome. The primary research questions were disease-free and overall survival rate in patients who underwent early or late lymph node dissection after penile cancer diagnosis. Results: Four clinical trials were included in the systematic review. Conclusions: The survival rate of patients with penile cancer is strictly associated with the timing of prophylactic pelvic lymph node dissection. Even though there are no randomized controlled trials we conclude that there is evidence for a strong recommendation that lymph node dissection should be performed as soon as possible after diagnosis with3 months as a realistic cut-off time between early and late. According to the present evidence base, lymph node dissection should be offered the sooner the better to all patients at high risk of lymph node metastasis.

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.

Histone modifications, especially H3K27 and H3K36 methylations, are crucial for epigenetic regulation and are often dysregulated in cancer. In a comprehensive analysis of 11,194 patient samples across 32 cancer types, we identified significant genomic alterations in H3K27 and H3K36 modifiers, with the most common being in KDM6B, BRPF1, KDM6A, SETD2, and NSD1. Patients with these alterations also frequently exhibited mutations in genes like TP53 and PIK3CA. Moreover, the presence of these histone modifier alterations correlated with poorer overall survival, emphasizing their potential as both oncogenic drivers and prognostic markers in various cancers.

To examine the association of clinical, treatment, and dose parameters with late urinary toxicity after low-dose-rate brachytherapy (LDR-BT) for prostate cancer, we retrospectively studied patients with prostate cancer who underwent LDR-BT from January 2007 through December 2016. Urinary toxicity was assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder (OAB) Symptom Score (OABSS). Severe and moderate lower urinary tract symptoms (LUTS) were defined as IPSS ≥ 20 and ≥ 8, respectively; OAB was defined as a nocturnal frequency of ≥ 2 and a total OABSS of ≥ 3. In total, 203 patients (median age, 66 years) were included, with a mean follow-up of 8.4 years after treatment. The IPSS and OABSS worsened after 3 months of treatment; these scores improved to pretreatment levels after 18–36 months in most patients. Patients with a higher baseline IPSS and OABSS had a lower frequency of moderate and severe LUTS and OAB at 24 and 60 months, respectively. LUTS and OAB at 24 and 60 months were not correlated with the dosimetric factors of LDR-BT. Although the rate of long-term urinary toxicities assessed using IPSS and OABSS was low, the baseline scores were related to long-term function. Refining patient selection may further reduce long-term urinary toxicity.

There are four subtypes of adenosine receptors (ARs), named A1, A2A, A2B and A3, all of which are G protein-coupled receptors. The A2BAR, coupled to both Gαi and Gαq G proteins, is one of the several G-protein-coupled receptors that are expressed in a significantly higher level in some cancer tissues in comparison to adjacent normal tissues. There is growing evidence that the A2BAR plays an important role in tumor cell proliferation, angiogenesis, metastasis, and immune suppression. Thus, A2BAR antagonists are potentially novel attractive anticancer agents. Several antagonists targeting at the A2BAR are currently in clinical trials for various types of cancers. In this review, we first describe the signaling, agonists, and antagonists of the A2BAR. We further discuss the role of the A2BAR in the progression of various types cancers, and the rationale of using A2BAR antagonists in cancer therapy

BACKGROUND This study investigated the association of postprandial plasma glucose (PPG) with cancer mortality using a general cohort of US adults. METHODS This cohort study included 14,860 US adults who attended the third National Health and Nutrition Examination Survey from 1988 to 1994, with mortality being followed up to December 31, 2019. The experimental exposures were levels of plasma glucose, including PPG with a fasting time of 0-3.9 h (PPG_0-3.9h) and 4-7.9 h (PPG_4-7.9h), plasma glucose with a fasting time ≥ 8 h (PG_fasting), and plasma glucose at 2 h after oral glucose tolerance test (PG_2hOGTT). Plasma glucose-associated cancer mortality risk was assessed using Cox proportional hazards models. RESULTS A 1-natural-log-unit increase in PPG_4-7.9h was associated with a higher multivariate-adjusted risk for cancer mortality [hazard ratio (HR), 3.24; 95% confidence interval (CI), 1.50-7.00]. However, PPG_0-3.9h, PG_fasting, PG_2hOGTT, hemoglobin A_1c, and insulin were not significantly associated with cancer mortality. The positive association of PPG_4-7.9h with cancer mortality remained in those without a prior diagnosis of cancer. CONCLUSIONS High PPG_4-7.9h is associated with a higher cancer mortality risk in US adults. Lowering PPG_4-7.9h may reduce cancer mortality.

Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In last years the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality and survival rate for CRC.

Cancer stem cells (CSCs) are a tumor cell subpopulation that drives tumor progression and metastasis, leading to poor overall survival of patients. In colorectal cancer (CRC), hyper-activation of Wnt/β-catenin signaling by mutation of both Adenomatous polyposis coli (APC) and K-Ras increases the size of the CSC population. We previously showed that the CPD0857 inactivates Wnt/β-catenin signaling by promoting ubiquitin-dependent proteasomal degradation of β-catenin and Ras proteins, thereby decreasing proliferation and increasing apoptosis of CRC lines. CPD0857 also decreased growth and invasiveness of CRC cells harboring mutant K-Ras resistant to EGFR mAb therapy. Here, we show that CPD0857 treatment decreases proliferation and increases neuronal differentiation of neural progenitor cells (NPCs). CDP0857 effectively reduced expression of CSC markers and suppressed self-renewal capacity. CPD0857 treatment also inhibited proliferation and expression of CSC markers in D-K-Ras MT cells carrying K-Ras, APC and PI3K mutations, indicating inhibition of PI3K/AKT signaling. Moreover, CPD0857-treated xenograft mice showed regression of tumor growth and decreased numbers of CSCs in tumors. We conclude that CPD0857 could serve as the basis of a drug development strategy targeting CSCs activated through Wnt/β-catenin-Ras MAPK-PI3K/AKT signaling in CRCs.

Numerous studies have firmly established the role of ion channels in essentially all basic cellular functions. Apart from their role in ion transport, they can form macromolecular complexes with adhesion proteins, and signaling molecules. Ion channels are not only responsible for cellular electrogenesis and excitability, but they also regulate the necessary conditions for tissue homeostasis, such as differentiation, proliferation and apoptosis. Although cancer is not officially classified as a channelopathy, it has been increasingly recognized that ion channel aberrations play an important role in virtually all cancer types. Ion channels can exert pro-tumorigenic activities due to genetic or epigenetic alterations, or as a response to molecular signals, such as growth factors, hormones, etc. Prostate cancer is the second leading cause of cancer-related death in men in the United States. Increasing evidence suggests that ion channels and pumps play a critical role in the regulation of prostate cancer cell proliferation, apoptosis evasion, migration, epithelial-to-mesenchymal transition and angiogenesis. There is also evidence suggesting that ion channels might play a role in treatment failure in prostate cancer. Hence, they represent promising targets for diagnosis, staging and treatment. Here, the role of major types of ion channels involved in the development and progression of prostate cancer were reviewed. Identifying the underlying molecular mechanisms of the pro-tumorigenic effects of ion channels, may potentially inform the development of novel therapeutic strategies to counter this malignancy.

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques; whereas, in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy will be considered

The most important prognostic factors in curatively treated prostate cancer at the initial diagnosis are T and N stage, histological subtype, Gleason score, initial PSA, PSA density and percentage of core biopsy positivity. Newer, but non-standard prognostic factors are urine PCA3 and genetic markers of prostate cancer. A simple, but seemingly underestimated standard test is serum Calcium (Ca) level, which has been shown by a previous study group to be a good predictor of lethal prostate cancer, but there is scarce evidence regarding the prognostic value of calcium levels at diagnosis. We aimed to determine whether a Ca level in the upper part of normal values has a prognostic value in curatively treated prostate cancer. We have retrospectively included 84 consecutive patients with prostate cancer, who underwent curative radiotherapy (primary or adjuvant; external beam RT with or without brachytherapy). We have performed statistical analysis of available prognostic factors. Ca level at diagnosis was found to be a statistically significant predictor of disease-free survival.

Pain is frequently reported during cancer disease, and still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better control pain. Targeted treatments may cure cancer disease and significantly increase survival. Thereby, a novel population of patients (cancer survivors) has emerged, also enduring chronic pain (27.6% moderate to severe pain). The present review discuss the different options currently available to manage pain in (former) cancer patients in the light of progress made in the last decade. Major progress in the field are recent development of a chronic cancer pain taxonomy now included in International Classification of Diseases (ICD-11) and update of WHO analgesic ladder. Until recently, cancer pain management has mostly relied on pharmacotherapy, opioids being considered as mainstay. The opioids crisis has prompted the reassessment of opioids use, both in cancer patients and cancer survivors. The review focuses on the current utilization of opioids, on the neuropathic pain component often neglected and on techniques and non-pharmacological strategies available which help to personalize patient’s treatment. Cancer pain management is now closer to the management of chronic non-cancer pain i.e. “an integrative pain care” aiming to improve patient’s quality of life.

Evolutionary Cancer Cell Biology (ECCB) reveals that the majority of cancer hallmarks trace their origins back to the premetazoic era, approximately 2300 to 1750 million years ago. These cancer hallmarks share deep homology with the oxygen-sensitive non-gametogenic NG (Urgermline), which evolved from the common ancestor of Amoebozoan, Metazoan, and Fungi (AMF). The genes, gene modules, and gene regulatory networks of the premetazoic cell system are preserved in the ancestral genome compartment of metazoans and humans. The Urgermline serves as a blueprint for all germ and stem cell lineages, including parasitic amoebae. As observed in amoebae, DNA double-strand breaks (DSBs) manifest in the homologous recombination (HR) genes of NG germlines and stem cell lineages when exposed to specific hyperoxic conditions, referred to as AMF hyperoxia, characterized by an oxygen content exceeding 6.0%. The cells lose their stemness and differentiation potential but persist in proliferation as low-grade polyploids (4n) through defective symmetric cell division (DSCD phenotype). Genomic integrity can be restored through homotypic cell and nuclear fusion, resulting in the formation of high-grade polyploids known as multinuclear genome repair syncytia (MGRSs), or by inductive hyperpolyploidization of more than 64n, as observed in single-celled polyploid giant cancer cells (PGCCs). Interestingly, low-, middle-, and high-grade polyploidization are not exclusive to cancer. Therefore, we investigate (i) functional polyploidies that occur in healthy cells, including humans, mammals, and protists, (ii) dysfunctional polyploidies that occur in cells with impaired homologous recombination (HR) and irreparable DNA DSB defects, and (iii) the restoration of genome integrity through cyst-like and high-grade polyploidization events. Additionally, we explore dysfunction in aging stem cells, hepatocytes, and cardiomyocytes

Prostate cancer is the most common cancer among men in Poland. A significant proportion of prostate cancers can be cured, providing longer survival. Patients have the opportunity to undergo minimally invasive treatment methods like brachytherapy, while maintaining their previous quality of life. The disease itself, as well as treatment complications, primarily affect the functioning of the urinary and digestive systems and impact the sexual sphere. Aim: This study aims to assess the quality of life of patients after prostate brachytherapy. Methods: The research was conducted at the Lower Silesian Oncology Centre in Wroclaw. The study included fifty men aged between 51 and 85 years. The following questionnaires were used: EORTC QLQ-C30, QLQ-PR25. Scales: Katz, Mini-MAC, PSS-10. Moreover, the study used a self-designed survey covering socio-demographical factors. Results: Prostate brachytherapy has a significant impact on the degree of sexual dysfunction. Compared to sexually inactive individuals, sexually active individuals exhibit fewer negative psychological symptoms. Choosing a destructive coping strategy intensifies the occurrence of symptoms, lowers patients' level of independence, and negatively affects their quality of life. Conclusions: Brachytherapy contributes to worsening sexual function and temporarily affects urinary system function, which may lower the overall quality of life in patients.

Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be effected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention, and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment perform glycolysis to produce energy, i.e., ATP. Since the origin of CAFs is unidentified, it is not determined whether the intracellular metabolism transitions from oxidative phosphorylation (OXPHOS) to glycolysis when normal tissue fibroblasts differentiate into CAFs. In this study, we established an experimental system and induced the in vitro differentiation of mesenchymal stem cells (MSCs) to CAFs. Additionally, we performed metabolomic and RNA-sequencing analyses before and after differentiation to investigate changes in the intracellular metabolism. Consequently, we discovered that OXPHOS, which was the primary intracellular metabolism in MSCs, was reprogrammed to glycolysis. In addition, we identified CAF-specific metabolites that were expressed during this reprogramming and determined their presence in the pancreatic tumor tissues of mouse models. Thus, we conclude that normal tissue fibroblasts that differentiate into CAFs undergo a metabolic reprogramming from OXPHOS to glycolysis. Moreover, we identified the CAF-specific metabolites expressed during metabolic reprogramming as potential future biomarkers for pancreatic cancer.

Cancer stem cell (CSC) has paved the way to many fundamental and translational studies. Recent studies have highlighted differentiated breast cancer cells (non-CSCs) switching phenotype to CSCs in response to various stimuli, depicting the existence of cancer stem cell plasticity. Although strategies to reduce the phenotypic plasticity of non-CSCs into CSCs are likely to prevent treatment-resilient cancer cells driving recurrence, most phenotypic plasticity mechanisms involve Notch, Wnt or MAPK signaling pathways. In this study, breast cancer cells were irradiated to identify soluble reprogramming factors. Using conditioned medias, protein arrays analyses, flow cytometry and in cellulo/in vivo functional assays, we demonstrated, for the first time, that radiation-induced chemokine expression, especially CXCL1 and CCL5 and their receptors CXCR2, CCR1 and CCR5, stimulates reprogramming of breast non-CSCs into CSCs. Treatment of non-CSCs with recombinant CXCL1 and CCL5 is sufficient to induce cell reprogramming, while their inhibition can be used to prevent reprogramming and sensitize tumor to radiation. Moreover, analysis of gene expression profiles from 38 public merged databases demonstrated that combined over-expression of CXCL1/CXCR2, CCL5/CCR1 or CCL5/CCR5 has a poorer prognosis in patients treated with radiotherapy, suggesting a promising way for patient stratification, where individuals with elevated cytokine levels could benefit from radiotherapy in conjunction with cytokine inhibitors. Taken together, our findings provide a rationale to consider these axes as potential targets and predictive biomarkers in breast cancer patients.

Background: The patients with cancer, especially pancreas cancer, are frequently associated with thrombosis which is one of causes for poor outcome, and hypercoagulability exists in cancer patients. Hypercoagulability is considered to be caused by thrombin burst. Methods: Activated partial thromboplastin time (APTT), small amount of tissue factor induced FIX activation (sTF/FIXa) assays and thrombin time (TT) using clot waveform analysis (CWA) were performed in 138 patients with malignant neoplasm including pancreas cancer and 66 non-cancer patients. Results: Thrombosis was frequently associated in pancreas cancer and was observed in stage I. CWA-APTT showed that the peak times and heights were markedly long and heigh, respectively, in cancer patients, and the peak times were significantly longer in pancreas cancer patients than benign pancreas diseases, and the 1st DPH was significantly higher in pancreas cancers than other cancers or benign pancreas diseases. CWA-sTF/FIXa showed that the peak times and heights were longer and higher, respectively, in patients with cancer than those without cancers, and that the 1st DPH was significantly higher in pancreas cancers than in other cancers. CWA-TT showed that the peak times were significantly shorter in cancer patients than in healthy volunteers and that the peak heights were significantly higher in cancer than in benign pancreas diseases. Conclusions: Cancer patients including pancreas cancer were frequently associated with thrombosis due to hypercoagulability with thrombin burst detected by CWA.

Siam weed, scientifically known as Chromolaena odorata and belonging to the Asteraceae family, is a fast-growing plant with prolific seed production. Although it is a traditional medicinal plant, it has become an agricultural weed in Africa and Asia, posing a threat to biodiversity and causing environmental damage. Despite this, C. odorata is highly regarded as a medicinal herb in tropical Africa, with anticancer effects on breast, liver, and colorectal cancer. However, it is important to regulate the intake of the plant extract as it can have a hepatotoxic effect on liver cells at higher doses. Further research needs to be conducted on the plant extract, and proper orientation and knowledge of its oral daily administration are necessary. This review summarizes current scientific investigations using ethanolic and methanolic aqueous extracts of C. odorata leaves on various cancer cells, to uncover its potential as an anticancer agent. The investigations were sourced from online databases like Google Scholar, PubMed, and other online-based journals.

Introduction and objectives Obstructive sleep apnea (OSA) is defined as a cause of daytime sleepiness, as well as a clinical manifestation of sleep-disordered breathing. In the literature, there are numerous controversial studies regarding the etiology of this condition, but it is universally accepted that a significant role in its onset is played by the reduced activity of the upper airway muscles. Additionally, OSA has been associated with a series of comorbidities, such as type II diabetes, metabolic syndrome, cardiovascular and pulmonary conditions, as well as head and neck tumors, especially oropharyngeal and laryngeal tumors. The purpose of this review is to examine and demonstrate the prevalence of OSA in patients with associated pathologies, especially in patients with head and neck tumors, as well as the role of surgical and non-surgical therapeutic methods in improving the quality of life. Material and methods Taking into consideration the stated objective, a systematic analysis of the available literature was conducted, encompassing PubMed, Medline and Scopus databases. The evaluation was based on several keywords, including head and neck cancer, diabetes, diabetic, overlap syndrome, cardiovascular conditions, laryngeal neoplasm, radiotherapy, chemotherapy, as well as the concept of quality of life in laryngectomized patients and patients with OSA. Results Our results demonstrate the involvement of OSA in the presence of comorbidities and also, an increased incidence of OSA in patients with laryngeal cancer. It is important to note that surgical and post-surgical treatment can play a significant role in triggering OSA in these patients. Conclusions The clinician must recognize the increased prevalence of OSA in patients with head and neck cancer, as well as the coexistence of OSA with certain comorbidities. They should actively engage in early diagnosis and establish optimal treatment methods to improve the quality of life for patients with associated conditions such as head and neck tumors or cardiovascular pathology.

Cancer associated cachexia (CAC) is a critical contributor to pancreatic ductal adenocarcinoma (PDAC) mortality. Thus, there is an urgent need for new strategies to mitigate PDAC-associated cachexia; and the exploration of dietary interventions is a critical component. We previously observed that a ketogenic diet (KD) combined with gemcitabine enhances overall survival in the autochthonous LSL-KrasG12D/+; LSL-Trp53 R172H/+; Pdx1-Cre (KPC) mouse model. In this study, we investigated the effect and cellular mechanisms of a KD in combination with gemcitabine on the maintenance of skeletal muscle mass in KPC mice. For this purpose, male and female pancreatic tumor-bearing KPC mice were allocated to a control diet (CD), a KD, a CD + gemcitabine (CG), or a KD + gemcitabine (KG) group. We observed that a KD or a KG mitigated muscle strength decline over time and presented higher gastrocnemius weights compared CD-fed mice. Mechanistically, we observed sex-dependent effects of KG treatment, including the inhibition of autophagy, and increased phosphorylation levels of eIF2α in KG-treated KPC mice when compared to CG-treated mice. Our data suggests that a KG results in preservation of skeletal muscle mass. Additional research is warranted to explore whether this diet-treatment combination can be clinically effective in combating CAC in PDAC patients.

Pancreatic cancer is an intractable disease with the worst prognosis of all cancers. The currently used treatment regimens do not significantly impact patient survival, and therefore, effective treatment strategies are urgently needed. Drug repurposing, which identifies new indications for existing and approved drugs, has proven to be a promising approach to anti-cancer drug discovery. Indeed the antihelmintic drug, pyrvinium pamoate has shown promise as an anti-pancreatic cancer drug, but to date, the inhibition of mitochondrial function is the only mechanism of action described in pancreatic cancer. This study showed, using pancreatic cancer 2D cell cultures and 3D spheroids, that pyrvinium pamoate exhibited short- and long-term cytotoxicity, inhibited epithelial-to-mesenchymal transition and cell invasion and migration. Mechanistically, pyrvinium pamoate induced DNA damage, inhibited the PI3K/AKT cell survival pathway, and triggered cell cycle arrests, as well as apoptotic and autophagic cell death. Importantly, pyrvinium pamoate acted synergistically with the first-line drug, gemcitabine in 2D and 3D pancreatic cancer cell culture models. This study provided evidence that pyrvinium pamoate is effective as a single agent and in combination with gemcitabine for the treatment of pancreatic cancer.

Prostate cancer (PCa) is characterised by androgen-dependency. Unfortunately, under anti-androgen treatment pressure, castration-resistant prostate cancer (CRPC) emerges, characterised by heterogeneous cell populations that, over time, lead to the development of different androgen-dependent or -independent phenotypes. Despite important advances in therapeutic strategies, CRPC remains incurable. Context-specific essential genes represent valuable candidates for targeted anti-cancer therapies. Through the investigation of gene and protein annotations and the integration of several published transcriptomic data, we identified two consensus lists to stratify PCa patients' risk and discriminate CRPC phenotypes based on androgen receptor activity. ROC and Kaplan-Meier survival analyses were used for gene set validation in independent datasets. We further evaluated these genes for their association with cancer dependency. The deregulated expression of the PCa-related genes was associated with overall and disease-specific survival, metastasis and/or high recurrence risk, while the CRPC-related genes clearly discriminated between adeno and neuroendocrine phenotypes. Some of the genes showed context-specific essentiality. We further identified candidate drugs through a computational repositioning approach for targeting these genes and treating lethal variants of PCa. This work provides a proof-of-concept for the use of an integrative approach to identify candidate biomarkers involved in PCa progression and CRPC pathogenesis within the goal of precision medicine.

Cancer is the most feared disease, with more than 1.6 million cases each year. Cancer can start almost anywhere in the human body, from the uncontrollable growth and multiplication of damaged cells. Cancerous tumors can spread into the human body (a process called metastasis) as a solid form usually, but the cancers of blood generally do not. Cancer treatment includes chemotherapy, surgery and radiations. In this article we will address inorganic compounds as a source of treatment, diagnosis, carriers of active substances.

The PI3K-AKT-mTOR signal transduction pathway regulates a variety of biological processes including cell growth, cell cycle progression and proliferation, cellular metabolism and cytoskeleton reorganization. Fine-tuning of the PI3K pathway signaling output is essential for the maintenance of tissue homeostasis and uncontrolled activation of this cascade leads to a number of human pathologies including cancer. Inactivation of the tumour suppressor phosphatase PTEN and/or activating mutations in the proto-typical lipid kinase PI3K have emerged as some of the most frequent events associated with human cancer and as a result the PI3K pathway has become a highly sought-after target for cancer therapies. In this review we summarize the essential role of the PTEN-PI3K axis in controlling cellular behaviors by modulating activation of key proto-oncogenic molecular nodes and functional targets. Further, we highlight important functional redundancies and peculiarities of these two critical enzymes that over the last few decades have become a central part of the cancer research field and have instructed hundreds of pre-clinical and clinical trials to better cancer treatments.

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.

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.

This manuscript examines the role of artificial intelligence in cancer imaging. It throws light on how artificial intelligence (AI) can significantly cut the wait time of patients and their clinicians in getting cancer diagnoses and assist health care providers by highlighting areas of an image where the interpreter needs to focus more for better result analysis and quality output. It also provides details on how the rise of AI attempts to standardize imaging results across providers by eliminating inter- and intra-observer variations among health care providers. Finally, it exposes the numerous limitations associated with AI use in cancer imaging, such as the need to digitize pathology laboratories and workflows, as well as transform our century-old tissue processing methods to fit into modern technological standards. In the field of radiology, the challenge of curating the enormous amount of data generated through MRIs, CT scans, PET scans, etc., poses a significant challenge to the ability of researchers to train relevant AI models to high levels of accuracy and reliability. In addition, over-reliance on AI by clinicians can deprive them of a common-sense approach to the health care issues of their patients and negatively impact doctor-patient relationships and confidentiality.

Background: The identification of new cellular receptors has been increasing rapidly. A receptor is called “orphan” if an endogenous ligand has not been identified yet. Methods: Here we review receptors that contribute to prostate cancer and are considered orphan or partially orphan. This means that the full spectrum of their endogenous ligands remains unknown. Results: The orphan receptors are divided into two major families. The first group includes G protein-coupled receptors. Most are orphan olfactory receptors. OR51E1 inhibits cell proliferation and induces senescence in prostate cancer. OR51E2 inhibits prostate cancer growth, but promotes invasiveness and metastasis. GPR158, GPR110 and GPCR-X play significant roles in prostate cancer development and progression. However, GPR160 induces cell cycle arrest and apoptosis. The other major subset of orphan receptors are nuclear receptors. RORα inhibits tumor growth, but RORγ stimulates androgen receptor signaling. PXR contributes to metabolic deactivation of androgens and inhibits cell proliferation. TLX has pro-tumorigenic effects in prostate cancer, while its knockdown triggers cellular senescence and growth arrest. Estrogen-related receptor ERRγ can inhibit tumor growth but ERRα is pro-tumorigenic. Dax1 and Shp are also inhibitory in prostate cancer. Conclusion: There is a “zoo” of relatively underappreciated orphan receptors that play key roles in prostate cancer.

The benefit of adjuvant radiotherapy (RT) after radical hysterectomy in patients with cervical cancer remains controversial. The aim of this study was to determine the impact on survival of adjuvant RT according to the Sedlis criteria. Patients with early-stage cervical cancer who underwent radical hysterectomy between 2005 and 2022 at a single tertiary institution were included. A multivariate analysis was performed to determinate if RT was an independent prognostic factor for recurrence or death. We also analyzed whether there was a statistically significant difference in overall survival (OS) between patients who met only one or two Sedlis criteria, depending on whether they received adjuvant RT or not. In this retrospective study 121 patients were included of whom 48(39.7%) received adjuvant RT due to the presence of unfavorable pathological findings. In multivariate analysis, RT was not found to be a statistically significant prognostic factor for OS (p=0.584) or disease-free survival (DFS) (p=0.559). When comparing patients who met one or two Sedlis criteria, there were no statistically significant differences in OS between RT and no adjuvant treatment in either group. Since the selection of patients with cervical cancer eligible for surgery is becoming more accurate, adjuvant RT might not be necessary for patients with intermediate-risk factors.

Overexpression of BRF2, a selective subunit of RNA polymerase III, has been shown to be crucial in the development of several types of cancers, including breast cancer and lung squamous cell carcinoma . Predominately, BRF2 acts as a central redox-sensing transcription factor (TF) and is involved in rescuing oxidative stress (OS) -induced apoptosis. Here, we showed a novel link between BRF2 and DNA damage response. Due to the lack of BRF2 specific inhibitors, through virtual and molecular dynamics screening, we identified potential drug candidates that interfere with BRF2-TATA-binding Protein (TBP)-DNA complex interactions based on binding energy, intermolecular, and torsional energy parameters. We experimentally tested Bexarotene as a potential BRF2 inhibitor. We found that Bexarotene (Bex) treatment resulted in a dramatic decline in oxidative stress (Tert-butylhydroquinone (tBHQ))-induced levels of BRF2 and consequently, lead to a decrease in cellular proliferation of cancer cells which may in part be due to drug pretreatment induced reduction of ROS generated by the oxidizing agent. Our data thus, provide the first experimental evidence that BRF2 is a novel player in DNA damage response pathway and Bexarotene can be used as a potential inhibitor to treat cancers with the specific elevation of oxidative stress.

Recent evidence indicates that the risk of being diagnosed with cancer in a tissue is strongly correlated (0.80) with the number of stem cell divisions accumulated by the tissue. Since cell division can generate random mutations during DNA replication, this correlation has been used to propose that cancer is largely caused by the accumulation of unavoidable mutations in driver genes. However, no correlation between the number of gene mutations and cancer risk across tissues has been reported. Because many somatic mutations in cancers originate prior to tumor initiation and the number of cell divisions occurring during tumor growth is similar among tissues, here I use whole genome sequencing information from 22,086 cancer samples and incidence data from the largest cancer registry in each continent to study the relationship between the number of gene mutations and the risk of cancer across 33 tissue types. Results show a weak positive correlation (mean = 0.14) between these two parameters in each of the five cancer registries. The correlation became stronger (mean = 0.50) when gender-related cancers were excluded. Results also show that 1,003 samples from 29 cancer types have zero mutations in genes. These data suggest that cancer etiology can be better explained by the accumulation of stem cell divisions than by the accumulation of gene mutations. Possible mechanisms by which the accumulation of cell divisions in stem cells increases the risk of cancer are discussed.

Obesity, characterized by the excessive accumulation of body fat, contributes to a multitude of physiological dysfunctions. This paper explores the complex relationship between obesity and various risk factors and complications, shedding light on critical health implications. Obesity triggers alterations in insulin, leptin, adiponectin, cytokines, and insulin-like growth factors, fostering conditions conducive to cancer initiation. Aberrations in nutrient-dependent intracellular signaling pathways, driven by the excess nutrition characteristic of obesity, contribute to the neoplastic transformation of cells. The Body Mass Index (BMI) correlates directly with adiposity, underlining its significance in cancer risk. Furthermore, insulin and insulin-like growth factors, notably IGF-2, play pivotal roles in this relationship. The expression of IR-A receptors is elevated in cancer. Obesity and cardiovascular diseases share a strong association. Obesity elevates the risk of fatal events like myocardial infarction. High cholesterol levels contribute to atherosclerosis in the aorta and coronary arteries. The severity of coronary artery disease is influenced by plaque formation characterized by calcium deposits. Obesity is also linked to hypertension and increased ventricular mass, exacerbating cardiovascular risks. Hypercholesterolemia and hypertension correlate with a high Body Mass Index (BMI). Obesity is intricately connected to insulin resistance, particularly evident in childhood obesity. It entails a gradual decline in insulin sensitivity, leading to elevated insulin levels in the bloodstream. Insulin resistance is a central factor in the development of Type 2 Diabetes Mellitus. Obesity also results in elevated triglyceride levels and reduced high-density lipoproteins, contributing to atherogenic dyslipidemia and a heightened risk of atherosclerosis. Additionally, obesity is associated with various other disorders, including epilepsy, depression, and neuropsychological problems. Beyond its physiological impact, obesity is associated with significant psychosocial challenges. Studies indicate that individuals with obesity face a higher risk of depressive symptoms, often related to overeating and unhealthy dietary patterns. The social withdrawal tendencies of obese individuals exacerbate these symptoms, with higher rates of depression observed in this group. OSA, a sleep disorder characterized by intermittent breathing cessation during sleep, is strongly correlated with obesity. Approximately 58% of obese individuals experience OSA, with higher Body Mass Index (BMI) associated with an increased risk. Weight reduction has been found to mitigate the severity of OSA and related arrhythmias. Continuous positive airway pressure (CPAP) therapy demonstrates effectiveness in reducing visceral fat accumulation and leptin levels. This comprehensive review underscores the intricate web of health implications associated with obesity, emphasizing the critical need for preventive measures and intervention strategies to address the multifaceted challenges posed by this global health concern.

Pancreatic cancer stands out as one of the most lethal forms of malignancies, representing 2% of all cancer cases and contributing to 5% of cancer-related fatalities. Therefore, early detection of pancreatic cancer is crucial for enhancing treatment outcomes. Various hereditary cancer syndromes have been linked to an elevated risk of developing pancreatic cancer, suggesting potential benefits from surveillance strategies for individuals at risk. Presently, precision medicine employs PARP inhibitor therapy for pancreatic cancer patients carrying germline variants in Homologous Recombination Repair (HRR) genes. Our objective was to ascertain the occurrence of germline pathogenic/likely pathogenic variants in genes predisposing to cancer among pancreatic cancer patients. Methodologically, we analyzed 184 pancreatic cancer patients referred to our laboratory for genetic examination. Utilizing a Next-Generation Sequencing (NGS) approach, we scrutinized 52 genes implicated in hereditary cancer predisposition. Our findings revealed that 21% of the patients analyzed harbored germline pathogenic/likely pathogenic variants. Within this subset, 48% exhibited positive results in pancreatic cancer susceptibility genes, namely ATM (17%), BRCA1 (12%), BRCA2 (7%), CDKN2A (7%), and PALB2. Significantly, 64.3% of the pathogenic variants were associated with genes involved in the HRR pathway (ATM, BRCA1, BRCA2, BRIP1, CHEK2, FANCL, MRE11, PALB2, RAD50, RAD51B and RAD51C). In conclusion, our study underscores the significance of multigene genetic testing for pancreatic cancer patients, with 21% of individuals yielding findings linked to pancreatic or other cancer predisposition. Moreover, patients carried pathogenic/likely pathogenic variants in HRR genes, potentially benefiting from targeted therapies such as PARP inhibitors or platinum-based treatments.

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.

Most patients with pancreatic cancer at some point present with symptoms related to exocrine pancreatic insufficiency (EPI). These include diarrhea, abdominal bloating, indigestion, steatorrhea, weight loss, and anorexia. Even though up to 80% of pancreatic cancer patients eventually present with symptoms related to exocrine pancreatic insufficiency, only 21% are prescribed pancreatic enzyme replacement therapy. This treatment is profoundly underutilized in the palliative care of these patients. The objective of this review is to discuss the pharmacology, pharmacokinetics, side effects, available evidence of effectiveness of pancreatic enzyme use for patients with pancreatic cancer, and challenges along with proposed solutions regarding its use. Pancrelipase is an expensive drug, and it is inactive if not taken correctly. The impact of symptoms of EPI can lead to poorer overall well-being. Pharmacists play a crucial role in properly educating patients on the correct use of pancreatic enzyme replacement therapy. Pancreatic enzyme replacement therapy (PERT) is a key strategy in managing symptoms of EPI and can improve quality of life, which is a central focus in palliative care.

Lung cancer is known as lung carcinoma. It is a disease which is malignant tumor leading to the uncontrolled cell growth in the lung tissue. Lung Cancer disease is one of the most prominent cause of death in all over world. Early detection of this disease can assist medical care unit as well as physicians to provide counter measures to the patients. The objective of this paper is to approach an automated tool that takes influential causes of lung cancer as input and detect patients with higher probabilities of being affected by this disease. A neural network classifier accompanied by cross-validation technique is proposed in this paper as a predictive tool. Later, this proposed method is compared with another baseline classifier Gradient Boosting Classifier in order to justify the prediction performance.

Abstract: Cancer cells are originated by normal cells and with those share the need to be fed. Metabolic reprogramming in cancer cells is not yet fully understood although there is a vast literature suggesting that huge amounts of both energy and substrates are require for synthesis of components of new neoplastic cells so that any macronutrient may be efficiently utilized. Recently, in vitro data show that EAA supplementation promoted colon cancer cells apoptosis by enhanced autophagy. Therefore, in this study we tested in vivo the effects of matched macronutrients standard laboratory diet (control) versus EAA rich modified diet (EAArmd) in mice injected with colon cancer cells. Results of the first set of 12 animals, 6 controls and 6 EAArmd-fed, showed that controls mice develop cancer volume cancers 5 times larger and heavier than EAArmd-fed. If confirmed, these results would open new scenarios for the cancer integrate therapies.

Cancer cells are originated by normal cells and with those share the need to be fed. Metabolic reprogramming in cancer cells is not yet fully understood, and there is a vast literature suggesting that any macronutrient may be efficiently utilized by cancer for duplication purposes. Metabolic hyperactivity of cancer and continuous duplication requires huge amounts of both energy and substrates for syntheses of components of new cells, and the modifications of metabolism induced by cancer cells to survive and grow damaging lethally, the whole organism. In rodents, we have recently observed that by modifying diet in a way not existent in nature, changing radically the ratios among essential and non-essential amino acids (AA) (usually less than 0.9), largely increasing essential-AA (EAA) percentages, lifespans increased. In vitro, EAA supplementation promoted colon cancer cells (CT116) apoptosis by enhanced autophagy. Therefore, we tested in mice if injection of colon cancer cells would have been followed by unvaried development of cancer volumes in animals fed with standard laboratory diet (controls) versus EAA rich modified diets (EAAmd). Both diets perfectly matched the same total macronutrients and micronutrients contents; only quality of nitrogen was radically different. Results of the first set of 8 animals, 4 controls and 4 EAAmd-fed, showed that controls develop cancers near 5 times larger and heavier than EAAmd-fed (P&lt;0,002) on the same time. We discuss which epigenetic modifications would be involved and worth to be studied, and what kind of scenarios those preliminary findings, if confirmed, would open.

: 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.

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing in early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with different expressions using bioinformatics. A total of 108 microRNAs were significantly differentially expressed between normal breast and breast cancer tissues. Using clinicopathological information and microRNA sequencing data of 430 patients with breast cancer from The Cancer Genome Atlas (TCGA), the differences in candidate microRNAs between low- and high-grade cases were compared. Comparing the expression of the 108 microRNAs between low- and high-grade cases, 25 and 18 microRNAs were significantly upregulated and downregulated, respectively, in high-grade cases. Clustering analysis of the TCGA cohort using these 43 microRNAs identified two groups strongly predictive of histological grade. miR-3677 is a microRNA upregulated in high-grade breast cancer. The outcome analysis revealed that patients with high miR-3677 expression had a significantly worse prognosis than those with low miR-3677 expression. This study showed that microRNAs were associated with histological grade in early-stage invasive breast cancer. These findings contribute to the elucidation of a new mechanism of breast cancer growth regulated by specific microRNAs.

This comprehensive review delves into cancer's complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression and therapeutic strategies. This review covers cancer cell migration, invasion, and colonization of distant organs, emphasizing the significance of cell adhesion and the intricate metastasis process. Inhibition approaches targeting adhesion molecules, such as integrins and cadherins, are discussed. Overall, this review contributes significantly to advancing cancer research and developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising therapeutic targets to alleviate adhesion and metastasis of cancer cells. The effectiveness of integrin-blocking antibodies, small molecule inhibitors targeting FAK and the TGF-β pathway, and combination therapies underscores their potential to disrupt focal adhesions and control epithelial-mesenchymal transition processes. The identification of as FAK, Src, β-catenin and SMAD4 offers valuable starting points for further research and the development of targeted therapies. The complex interrelationships between adhesion and metastatic signaling networks will be relevant to the development of new treatment approaches.

The aim of the study was to compare the standard baseline imaging, with extended radiological staging. To assess our hypothesis, we performed a prospective, single-centre study which included 132 participants recruited between October 2015 and March 2020. Descriptive statistics, the Friedman and chi-squared tests were performed and p &lt; 0.05 was considered significant. Patients were grouped into two cohorts, CT scan cohort (n=87) and PET-CT cohort (n=43). In the first group the originally determined disease stage changed in 36.8 % of cases, in second group in 51.2 %. The consistency between assessment of axillary lymph nodes by imaging (cN) and the postoperative pathology report (pN) was evaluated. In most cases, clinical and pathological evaluation of involved nodes was consistent, for CT scan the result was χ2(1) = 18.98; p &lt; 0.001, for PET-CT the result was χ2(1) = 6.41; p = 0.03. Highly customized radiation therapy defined as dose boost within the involved lymph nodes, not covered by surgeon, was applied in nine patients.

The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.

Introduction: Novel robotic surgery systems (da Vinci Xi) are superior to classical open and laparoscopic techniques with its clear and three-dimensional view. We aimed to present the first case low anterior resection of rectal cancer and vaginal specimen extraction with Da Vinci Xi.Case: A 75-year-old female patient with rectum adenocarcinoma was undergone robotic-assisted low anterior resection (LAR) of the rectum, vaginal removal of the specimen, colorectal anastomosis and loop ileostomy. The operation time was 190 minutes. There were no postoperative complications. Pathological tumor stage was stage pT1N0 with negative proximal, distal and radial resection margins. The patient was discharged on the third postoperative day.Conclusion: Robot-assisted LAR, total mesorectal excision, vaginal removal of the specimen, colorectal anastomosis, and loop ileostomy can be performed easily and safely with Da Vinci Xi at early stage rectal cancer. And the vaginal extraction of the specimen avoids us from a traditional abdominal incision.

Currently, there are many studies on the application of nanotechnology in therapy. Metallic nanoparticles are promising nanomaterials in cancer therapy, however, functionalization of these nanoparticles with biomolecules has become relevant as their effect on cancer cells is con-siderably increased by photothermal and photodynamic therapy, drug nanocarriers, and speci-ficity by antibodies, resulting in new therapies that are more specific against different types of cancer. This review describes studies on the effect of functionalized palladium, gold, silver and platinum nanoparticles in the treatment of cancer.

Background: Music therapy (MT) is a non-pharmacological treatment increasingly used to reduce stress and anxiety in hospitalized children affected by cancers. The aim of this study was to eval-uate the impact of MT on quality of life of children with cancer. Methods: We have conducted a quasi-experimental study between April 1 and August 31, 2021 at Bechir Hamza children's Hos-pital in Tunis, including children treated for cancer. The child or the parent completed PedsQL Module Cancer french version 3.0 questionnaires before and after four weekly music therapy ses-sions. Child's respiratory and heart rate were measured before and after each session. Results: We included 20 children whose mean age was 7 ± 4.5 years [2-14]. The median value of the total questionnaire score increased from 57 [46; 70] to 72 [67; 85] (p < 10-3) with a significant reduction in pain (p = 0.02), nausea (p = 0.009), anxiety related to medical procedures (p = 0.009) and worry about the future (p = 0.005). We highlighted a significant decrease in respiratory and heart rate after MT (p<0,05). Conclusions: MT has positive impact of on quality of life of children with cancer.

Oncological changes in the prostate are a common cause of death among elderly men. Malignant cells are difficult to identify at early stages, which are asymptomatic. The patient often seeks medical assistance when the disease has already progressed, and the treatment is less effective. Early diagnosis of prostate cancer (PC) is thus one of the priority tasks of modern urology and healthcare in general. The aim of this study is the detection of microRNAs (miRNAs), which are known to be associated with PC. The detection of the target miRNAs in human plasma samples has been performed with a nanoribbon biosensor system, which was based on "silicon-on-insulator" structures (SOI-NR biosensor). In order to provide biospecific detection of the target miRNAs, the surface of individual nanoribbons has been modified with DNA oligonucleotide probes (oDNA probes), whose nucleotide sequences were complementary to those of the target miRNAs. The high detection sensitivity has been demonstrated with the use of model oDNAs, which are complementary to nanoribbon-immobilized oDNA probes, in buffer solutions. The sensitivity threshold was 1.1 × 10^-17 M. The successful detection of target miRNAs, isolated from real plasma samples of PC patients, has also been demonstrated. We believe that the development of highly sensitive nanotechnology-based biosensors for PC markers is a step towards personalized medicine.

There is no routine approach to identify patients with gynecologic malignancies at high risk for chemotherapy-resistance. Circulating tumor DNA (ctDNA) tumor fraction (TFx) represents a minimally-invasive approach to tumor profiling, with as yet limited data on utility in gynecologic malignancies. The objective was to investigate the use of ctDNA TFx in a cohort of patients with ovarian and endometrial cancer. Plasma samples from patients with biopsy-proven ovarian or endometrial cancer collected between 4/2018 and 4/2020 were subjected to shallow whole genome sequencing with determination of TFx via ichorCNA package. The association of TFx to continuous and categorical baseline clinicopathologic factors and progression-free survival was assessed. 210 plasma samples from 78 patients with gynecologic cancers were analyzed. Mean TFx for ovarian cancer was 5.5% and endometrial cancer 2.4% and there was no significant difference in TFx among histology either for endometrial or ovarian cancers. Grade was associated with significant difference in ‘sentinel’ TFx among ovarian cancers but not endometrial cancers. ctDNA TFx dynamics over time demonstrated rapid clearance of ctDNA in most patients with ovarian cancer, while endometrial cancer had consistently low TFx. ctDNA TFx is feasible in ovarian and endometrial cancers and may be a valuable important tool for prognostication.

Savolitinib is a highly selective small molecule inhibitor of the mesenchymal epithelial transition factor (MET) tyrosine kinase, primarily developed for the treatment of non-small cell lung cancer (NSCLC) with MET mutations. It is also being investigated as a treatment for breast, head and neck, colorectal, gastric, pancreatic, and other gastrointestinal cancers. In both preclinical and clinical studies, it has demonstrated efficacy in lung, kidney, and stomach cancers. Savolitinib is an oral anti-cancer medication taken as a 600 mg dose once daily. It can be used as a monotherapy in patients with non-small cell lung cancer with MET mutations, and in combination with epidermal growth factor receptor (EGFR) inhibitors for patients who have developed resistance to them. Furthermore, savolitinib has shown positive results in gastric cancer treatment, particularly in combination with docetaxel. As a result, this review aims to validate its efficacy in NSCLC and suggests its potential application in other gastrointestinal cancers, such as pancreatic cancer, based on related research in gastric and renal cancer.

Current therapeutic strategies targeting cancer cells within solid tumors have displayed limited success owing to the presence of non-cancer components referred to as the tumor stroma within the tumor microenvironment (TM). These stromal cells, extracellular matrix and blood vessels influence cancer cell response to therapy and play key roles in tumor relapse and resistance. Of the stromal cells present in the TM, a lot of attention has been given to cancer-associated fibroblasts (CAFs) as they are the most abundant and are important in cancer initiation, progression and therapy resistance. In this updated review I emphasize the role of CAFs in the regulation of tumor cell behaviour and reveal how CAF-derived factors and signaling influence tumor cell heterogeneity and development of novel strategies to combat cancer. To investigate the expression of CAF markers in tumor tissues versus normal tissues, transcriptomic data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases was used. Bioinformatic analysis reveals differential expression of CAF markers in several cancer types, underscoring the need for further multiomics and biochemical studies on CAFs, CAF subsets and markers. Differences in CAF markers’ expression could be due to different cellular origins as well as the effect of cancer-specific tumor microenvironmental effect on CAFs. Lastly, I present recent advances in therapeutic targeting of CAFs and the success of such endeavours or its lack thereof. It is recommended that for patients’ outcomes to improve, cancer treatment be combinatorial in nature, targeting both cancer cells and stromal cells and interactions.

The past decade has witnessed enormous progress, which has seen the noncoding RNAs (ncRNAs) turn from the so called dark matter RNA to critical functional molecules, influencing most physiological processes in development and disease contexts. Many ncRNAs interact with each other and are part of networks that influence the cell transcriptome and proteome and consequently the outcome of biological processes. The regulatory circuits controlled by ncRNAs have become increasingly more relevant in cancer. Further understanding of these complex network interactions and how ncRNAs are regulated, is paving the way for the identification of better therapeutic strategies in cancer.

It is estimated that pancreatic cancer will be the 2^nd leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options in this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are incompletely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, poor antigenicity, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored.

At present, the applications and efficacy of non-ionizing radiations (NIR) in oncotherapy are limited. In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, the development of more efficient heat nanomediators that may exhibit high specific absorption rates still is an unsolved problem. Our aim was to investigate if externally applied magnetic fields and a heat-inducing NIR affect tumor cell viability. To this end, under in vitro conditions, different human cancer cells (A2058 melanoma, AsPC1 pancreas carcinoma, MDA-MB-231 breast carcinoma) were treated with the combination of electromagnetic fields (EMFs, using solenoids) and hyperthermia (HT, using a thermostated bath). The effect of NIR was also studied in combination with standard chemotherapy and targeted therapy. An experimental device combining EMFs and high intensity focused ultrasounds (HIFU)-induced HT was tested in vivo. EMFs (25 T, 4h) or HT (52C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approx. 16%, 50%, and 21% of controls values in A2058, AsPC1, and MDA-MB-231 cells, respectively. Increased lysosomal permeability, release of cathepsins into the cytosol and mitochondria-dependent activation of cell death are the underlying mechanisms. Cancer cells could be completely eliminated combining EMFs, HT and standard chemotherapy or EMFs, HT and anti-Hsp70-targeted therapy. As a proof of concept, in vivo experiments performed in AsPC1 xenografts showed that combination of EMFs, HIFU-induced HT, standard chemotherapy and a lysosomal permeabilizer induces a complete cancer regression.