Breast and Cervical cancer are significant causes of morbidity and mortality among women worldwide. Usually, conventional therapies and early detection has shown success in metastasis and relapse rates and improved overall survival of the patients. The elimination of the efficacy of chemotherapies and target therapies because cancer stem cells create resistance against chemotherapy, metastasis, and relapse. Studies reveal that cancer stem cell markers are important for improving efficiencies of targeted therapies. Our study aims to analyze the stem cell markers and target the most significant stem cell marker by phytochemicals and their derivates. Through the analysis, it was observed that CXCR4 and SOX-2, mir-1, mir-125, and mir-429 may have a crucial role in stemness of breast and cervical cancer respectively, while BPMD & MD simulations revealed Di-valinoyl curcumin as a potential compound for CXCR4 targeting.

Self-employed individuals comprise around 15% of Canada’s workforce. For those with cancer, frequent functional loss and diminished work ability due to side effects of the disease and its treatment significantly impact their well-being and business vitality. Compared to salaried can-cer survivors, the self-employed experience greater reductions in work hours and up to 48% greater income loss, yet most research addresses the former population. To describe self-employed Canadian cancer survivors’ experiences continuing and returning to work, our quali-tative study examines their strategic efforts to continue working throughout the disease trajecto-ry or return to work post-recovery. Employing an interpretive description approach and an in-terview guide based on a vocational rehabilitation model for cancer survivors, we analyze data from 23 participants—both French- and English-speaking—from six Canadian provinces, with eight different job types and nine different cancer diagnoses. Our constant comparative analysis of the transcribed interviews reveals four major themes and twelve sub-themes: Impact of can-cer on the self-employed function (physical, cognitive, and psychological), on their ability to maintain their business, and financial well-being, and facilitating factors for working with can-cer. Cancer disclosure and non-disclosure were both deemed viable strategies, but ceasing work was not. We thus recommend professional support for self-employed cancer survivors in plan-ning any necessary business modifications to accommodate their condition and cancer treatment to lessen the negative impact of cancer on self and on their business well-being.

Ovarian cancer is a deadly disease attributed to late-stage detection as well as recurrence and development of chemoresistance. Ovarian cancer stem cells (OCSCs) are hypothesized to be largely responsible for emergence of chemoresistant tumors. Although chemotherapy may initially succeed at decreasing the size and number of tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that Aldehyde dehydrogenase 1A1 (ALDH1A1) is essential for the survival of OCSCs. We identified a novel ALDH1A1 inhibitor, compound 974, and used 974 as a tool to decipher the mechanism of stemness regulation by ALDH1A1. Treatment of OCSCs with 974 significantly inhibited ALDH activity, expression of stemness genes, spheroid, and colony formation. In vivo limiting dilution assay demonstrated that 974 significantly inhibited CSC frequency. Transcriptomic sequencing of cells treated with 974 revealed significant downregulation of genes related to stemness and chemoresistance as well as senescence and senescence associated secretory phenotype (SASP). We confirmed that 974 inhibited senescence and stemness induced by platinum-based chemotherapy in functional assays. Overall, these data establish that ALDH1A1 is essential for OCSCs survival and ALDH1A1 inhibition sup-presses chemotherapy induced senescence and stemness. Targeting ALDH1A1 using small molecule inhibitors in combination with chemotherapy therefore presents a promising strategy to pre-vent ovarian cancer recurrence and has potential for clinical translation.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44⁺/CD24^-) and epithelial (ALDH^high) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

In this study, we described the most critical risk factors for different malignancies including: breast, prostate, lung, and colorectal carcinoma among others, with an emphasis on modifiable risk factors. We revised the literature review about risk factors involved in the genesis of cancer in various databases, including articles indexed in PUBMED, SCOPUS, PMC, and Google Scholar. Awareness of risk factors enables conscious decisions to be made in an effort to combat malignancies. Knowing risk factors is a mode of fighting malignancy. Diet, lifestyle, practises, and laboratory/clinical interventions were among risk factors of diverse malignancy. Diet, lifestyle, laboratory/clinical interventions all contribute to the genesis and prognosis in a variety of malignancies. We concluded that abstaining from risk factors can prevent the development of many malignancies in a century where this conundrum is raising disproportionately. By informing the public about modifiable risk factors cancer mortality rates can be reduced. It is treated here is to make the public aware of the modifiable risks of cancers.

BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. BOLD-100 has been reported to inhibit the upregulation of the endoplasmic reticulum stress sensing protein GRP78. However, response to BOLD-100 varies in different cancer models and the precise mechanism of action in high-response versus low-response cancer cells remains unclear. In vitro studies have indicated that BOLD-100 induces cytostatic rather than cytotoxic effects as a monotherapy. To understand BOLD-100 mediated signaling mechanism in breast cancer cells, we used estrogen receptor positive (ER+) MCF7 breast cancer cells to obtain gene-metabolite integrated models. Particularly, BOLD-100 significantly reduced expression of genes involved in the DNA repair pathway. BOLD-100 also induced reactive oxygen species (ROS) and phosphorylation of histone H2AX, gH2AX (Ser139), suggesting disruption of proper DNA surveillance. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gH2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.

Tumor invasion, metastasis, and recrudesce remain a considerable challenge in the treatment of gastric cancer (GC). Herein, we first identified that RBFOX3 (RNA binding protein fox-1 homolog 3) was significantly up-regulated in GC tissues and negatively linked to the survival rate of GC patients. RBFOX3 promoted cell division and cell cycle progression in vitro as well as in vivo. Furthermore, RBFOX3 increased cell invasion and migration ability. Interestingly, both the suppression of GC cell multiplication and invasion moderated by the silencing of RBFOX3 was rescued by HTERT up-regulation. Additionally, RBFOX3 augmented the resistance of GC cells to 5-fluorouracil (5-Fu) by repressing RBFOX3. Mechanistically, exogenous up-regulation of RBFOX3 triggered promoter activity and HTERT expression thereby enhancing the division and development of GC cells. Importantly, our findings revealed that RBFOX3 interacted with AP-2β to modulate the HTERT expression as demonstrated by co-immunoprecipitation analysis. In conclusion, our study indicates that high expression of RBFOX3 promotes GC progression and development but predicts worse prognosis by stimulating HTERT signaling. Moreover, the results suggest that the RBFOX3/AP-2β/HTERT pathway is a novel target for the development of therapeutic agents for the prevention and treatment of GC reappearance and metastasis.

Modern research into carcinogenesis has undergone three phases. Surgeons and pathologists started the first phase and established autopsy and biopsy as routine pathology services, in turn establishing morphological traits for tumors and establishing immortality and autonomy as indispensable criteria for neoplasms. A century ago medical doctors and biologists initiated “experimental cancer research” as the second phase, in which they, with help from chemists, established many chemical-induced animal models of carcinogenesis. In this phase, the two-hit theory and stepwise carcinogenesis of “initiation-promotion” or “initiation-promotion-progression” were established, with an illustrious finding that outgrowths induced in animals depend on the inducers, and thus are not authentically neoplastic, until late stages. For the last 40 years, molecular biologists have gradually dominated the carcinogenesis research fraternity and have established numerous genetically-modified animal models of carcinogenesis. However, evidence has not been provided for immortality and autonomy of the lesions from most of these models. Probably, many peers had already collected the lesions from animals for analyses of “cancer” mechanisms before the lesions became autonomous. We herein review monumental work of many predecessors to reinforce that evidence for immortality and autonomy is essential for confirming a neoplastic nature. We extrapolate that immortality and autonomy are established early during sporadic human carcinogenesis, unlike the late establishment in all animal models. It is imperative to resume many forerunners’ work by determining the genetic bases for initiation, promotion and progression, the genetic bases for immortality and autonomy, and which animal models are, in fact, good for identifying such genetic bases.

Silencing of tumor suppressor genes (TSGs) by DNA promoter hypermethylation is an earlyevent in carcinogenesis; Hence TSGs may serve as early tumor biomarkers. We determinedthe promoter methylation levels of p16INK4a, RASSF1A, TIMP3 and PCQAP/MED15 TSGs in salivary DNA from oral cancer (OC), and oropharyngeal cancer (OPC) patients, using methylation specific PCR coupled with densitometry analysis. We assessed the association between DNA methylation of individual TSGs with OC and OPC risk factors. We evaluated the performance and the clinical validity of this quadruple methylation marker panel in discriminating OC and OPC patients from healthy controls using CombiROC web tool. Our study reported that RASSF1A, TIMP3 and PCQAP/MED15 TSGs were significantly hypermethylated in OC and OPC cases compared to healthy controls. We found that DNA methylation levels of TSGs were significantly augmented by smoking, alcohol use and betel quid chewing by indicating that the fact that frequent exposure to risk factors may drive oral and oropharyngeal carcinogenesis through TSG promoter hypermethylation. Also, this quadruple-methylation marker panel of p16INK4a, RASSF1A, TIMP3 and PCQAP/MED15 TSGs demonstrated excellent diagnostic accuracy in the early detection of OC at 91.7% sensitivity and 92.3% specificity, and OPC at 99.8% sensitivity and 92.1% specificity, from healthy controls.

Pyruvate kinase M2 (PKM2) is essential for aerobic glycolysis and is highly expressed in various cancer tissues. Although high PKM2 expression is observed in prostate cancer tissues, its functional role in cancer metabolism is unclear. Here, we investigated the role of PKM2 in regulating autophagy and its associated pathways in prostate cancer cells. PKM2 expression was silenced using various PKM2 small interfering RNAs (siRNAs) and then we measured PKM2-related cellular pathways associated with autophagy. PKM2 siRNA-transfected prostate cancer cells showed significantly reduced viability. Acridine orange staining and immunoblotting analysis showed that PKM2 downregulation markedly increased autophagic cell death. Results of western blotting analysis showed that PKM2 knockdown affected protein kinase B/mechanistic target of rapamycin 1 pathway, which consequently downregulated the expression of glycolytic enzymes lactate dehydrogenase A and glucose transporter 1. To the best of our knowledge, this is the first study to show that PKM2 inhibition alters cancer cell metabolism and induces autophagy. Thus, the present study provides a strategy for the development of PKM2-targeted novel anticancer drugs for the treatment of prostate cancer.

In our continuous search for selective anticancer treatments, we have screened 65 extracts from 45 plants collected in several areas of Western Andalusia (Spain) for cytotoxic activity against lung cancer cells and lung normal cells. Active extracts were also tested against 11 cell lines from other tissues. An extract from the leaves of Tetraclinis articulata (Vahl) Mast. (Cupressaceae) showed a marked cytotoxicity (IC₅₀ = 0.37 ± 0.03 µg/mL) and selectivity (selectivity index = 378.3) against the lung cancer cells; cisplatin, 5-fluorouracil and an extract from the leaves of Taxus baccata L. (Taxaceae) were less cytotoxic and selective.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play vital roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and potential therapeutic targets in this area.

Trace amines are a separate, independent group of biogenic amines, close in structure to classical monoamine neurotransmitters such as dopamine, serotonin and norepinephrine. G protein-coupled Trace Amine-Associated Receptors (TAAR) are mostly investigated for their involvement in the pathogenesis of neuropsychiatric disorders, but expression of TAAR family receptors is observed also in various populations of cells of the immune system. The review is focused on the basic information on the interaction of trace amines and their receptors with cells of the general immune system of humans and other mammals, as well as on data on TAARs role in the function of individual populations of myeloid and lymphoid cells. With further research on the regulatory role of the trace amine system in the pathogenesis of the immune response and determination of the biological mechanisms for their action it would be possible to develop new methods for treating diseases related to immune system dysfunctions.

Similarly to our healthy organs, tumor tissue also generates an ecosystem. This implies that stromal cells acquire an altered phenotype in tandem with tumor cells, thereby promoting tumor survival. Cancer cells are fueled by abnormal blood vessels, allowing them to develop and proliferate. Tumor-associated fibroblasts adapt their cytokine and chemokine production to the needs of tumor cells, alter the peritumoral stroma by generating more collagen, thereby stiffening the matrix, all promoting the epithelial-mesenchymal transition and tumor cell invasion. Chronic inflammation and the mobilization of pro-tumorigenic inflammatory cells further facilitate tumor expansion. All of these events can impede the effective administration of tumor treatment, so the successful inhibition of tumorous matrix remodeling could further enhance the success of tumor treatment. Numerous publications describe efforts to inhibit tumor matrix components, but the true breakthrough has yet to be achieved. If, on the other hand, we assume that tumorous blood vessels and inflammatory cells are residents of the tumorous stroma, then two steps forward have occurred.

Metachromatic leukodystrophy (MLD) is a hereditary neurodegenerative disease characterized by demye-lination and motor and cognitive impairment due to the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or the saposin B activator protein (SapB). Current treatments are limited; however, gene therapy using adeno-associated virus (AAV) vectors for ARSA delivery has shown promising results. The main challenges for MLD gene therapy include optimizing AAV dosage, selecting the most effective serotype, and determining the best route of administration for ARSA delivery into the central nervous system. This study aims to evaluate the safety and efficacy of AAV serotype 9 encoding ARSA (AAV9-ARSA) gene therapy when administered intrave-nously or intrathecally in minipigs, a large animal model with anatomical and physiological similarities to humans. By comparing these two administration methods, this study contributes to the understanding of how to improve the effectiveness of MLD gene therapy and offers valuable insights for future clinical applications.

Catheter-associated urinary tract infection (CAUTI) is one of the most common hospital-acquired infections (HAIs). Prolonged hospitalization, invasive devices such as catheters, and irrational use of antimicrobial agents are believed to be the major causes of high rates of HAIs. Infections such as pyelonephritis, urethritis, cystitis, and prostatitis are the main concern in catheterized ICU patients. In these cases, Gram-negative bacteria are the most common. The present study is undertaken to determine the frequency, antibiograms, disease pattern, and risk factors involved in providing an advocacy recommendation to prevent CAUTI. A total of 1078 patients were admitted to the hospital ICU, out of which healthcare-associated infection was reported in 316 patients. CAUTI was reported only in 70 patients. Klebsiella pneumoniae (20%) was the predominant isolate, with Serratia (3%) and Providencia (3%) species as the least common in this study. The present study provides CAUTI incidence rates in a tertiary care hospital in Hail, Saudi Arabia. Furthermore, information on risk factors of CAUTI common causative organism associated, and their antibiogram patterns are also presented. This study provides vital information that can be used to formulate an effective antibiotic stewardship program that can be implemented throughout the kingdom.

The X-linked FMR1 gene contains a non-coding trinucleotide repeat in its 5’ region that in normal, healthy individuals contains 20-44 copies. Large expansions of this region (>200 copies) cause fragile X syndrome (FXS), but expansions of 55-199 copies (referred to as premutation alleles) predispose carriers to a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). The cytopathological mechanisms underlying FXTAS are poorly understood, but abnormalities in mitochondrial function are believed to play a role. We previously reported that lymphoblastoid cell lines (LCLs, or lymphoblasts) of premutation carriers have elevated mitochondrial respiratory activities. In the carriers, especially those not clinically affected with FXTAS, AMPK activity was shown to be elevated. In the FXTAS patients, however, it was negatively correlated with brain white matter lesions, suggesting a protective role in the molecular mechanisms. Here we report an enlarged and extended study of mitochondrial function and associated cellular stress-signalling pathways in lymphoblasts isolated from male and female premutation carriers, regardless of their clinical status, and healthy controls. The results confirmed the elevation of AMPK and mitochondrial respiratory activities and reduction of reactive O2 species (ROS) levels in premutation cells and revealed for the first time that TORC1 activities are reduced. Extensive correlation, multiple regression and Principal Components analysis revealed the best fitting statistical explanations of these changes in terms of the other variables measured. These suggested which variables might be the most “proximal” regulators of the others in the extensive network of known causal interactions amongst the measured parameters of mitochondrial function and cellular stress signalling. In the resulting model, the premutation alleles activate AMPK and inhibit both TORC1 and ROS production, the reduced TORC1 activity contributes to activation of AMPK activation and of nonmitochondrial metabolism, and the higher AMPK activity results in elevated catabolic metabolism, mitochondrial respiration and ATP steady state levels. In addition the results suggest a separate CGG repeat number-dependent elevation of TORC1 activity that is insufficient to overcome the inhibition of TORC1 in premutation cells, but may presage the previously reported activation of TORC1 in FXS cells.

The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Therefore, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we will describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphoid cells.

Kaposi’s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the first in vivo model for a virally-induced lymphoma in zebrafish, whereby KSHV-infected PEL tumour cells engraft and proliferate in the yolk sac of zebrafish larvae. Using a PEL cell line engineered to produce the viral lytic switch protein RTA in the presence of doxycycline, we demonstrate drug-inducible reactivation from KSHV latency in vivo, which enabled real-time observation and evaluation of latent and lytic phases of KSHV infection. In addition, we developed a sensitive droplet digital PCR method to monitor latent and lytic viral gene expression and host cell gene expression in xenografts. The zebrafish yolk sac is not well-vascularized and using fluorogenic assays we confirmed that this site provides a hypoxic environment that may mimic the microenvironment of some human tumors. We found that PEL cell proliferation in xenografts was dependent on the host hypoxia-dependent translation initiation factor, eukaryotic initiation factor 4E2 (eIF4E2). This demonstrates that the zebrafish yolk sac is a functionally hypoxic environment and xenografted cells must switch to dedicated hypoxic gene expression machinery to survive and proliferate. The establishment of the PEL xenograft model enables future studies that exploit the innate advantages of the zebrafish as a model for genetic and pharmacologic screens.

Background: Tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). The dysfunctional TME promotes drug resistance, disease recurrence and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins and microRNAs. Results: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Co-culture of GAMs (and GAM derived exosomes) and GBM cell lines resulted in the increased GBM cells’ resistance against temozolomide (TMZ) by upregulating pro-survival gene, PDCD4 and stemness markers Sox2, STAT3, Nestin and miR-21-5p and increased M2 cytokines, IL-6 and TGF-β1 secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed markedly reduced ability to secret M2 cytokines and reduced miR-21 enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which tumor suppressor PDCD4 was targeted. We subsequently established a patient-derived xenograft models where mice bore patient GBM and GAMs. The treatment of pacritinib, and the combination of pacritinib/TMZ appeared to significantly reduce tumorigenesis of GBM/GAM PDX mice, overcome TMZ-resistance, and M2 polarization of GAMs. Conclusion: In summation, we showed that potential of pacritinib alone or in combination with TMZ for suppressing GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in the clinical settings.

Background: The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assesses circadian timing's impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. Aim: Evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes. Identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities related to social determinants of health (SDoH). Design: IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon. Survival analyses utilized Kaplan–Meier curves. Setting/Participants: Single-institution study involving patients receiving whole-brain radiotherapy. Collected demographic, disease, and socioeconomic parameters from electronic medical records. Results: Morning treatment (n=158) showed a trend towards improved overall survival vs. afternoon (n=79), median survival 158 vs. 79 days (p=0.20, HR=0.84, CI95% 0.84–0.91). Subgroup benefits for morning treatment in females (p=0.04) and trends in controlled primary disease (p=0.11) and breast cancer metastases (p=0.08). SDoH-based disparities observed, with Black and lower-income patients exhibiting diminished circadian influence. Conclusions: Emphasizes chronobiological factors' relevance in brain metastases radiation therapy. Morning treatment correlates with improved survival, particularly in specific subgroups. Identifies potential circadian influence disparities based on SDoH, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

Athletes living with and beyond cancer can continue to train and, in some cases, compete during treatment. Following cancer treatment, athletes can return to competitive sport but need to learn to adapt their physical strength and training to lingering effects of cancer. It is critical for oncology healthcare providers to use the principles of assess, refer and advise to exercise oncology programs that are appropriate for the individual. Managing side effects of treatment is key to being able to train during and immediately following cancer treatment. Keen attention to fatigue is important at any point in the cancer spectrum to avoid overtraining and optimize the effects of training.

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.

APE1 is an essential endodeoxyribonuclease of the base excision repair pathway that maintains genome stability. It was identified as a pivotal factor favoring tumor progression and chemo-resistance through the control of gene expression by a redox-based mechanism. APE1 is overex-pressed and serum-secreted in different cancers, representing a prognostic and predictive factor, and a promising non-invasive biomarker. Strategies directly targeting APE1 funtions led to the identification of inhibitors showing a potential therapeutic value, which some of them are cur-rently in clinical trials. Interestingly, evidence indicates novel roles of APE1 in RNA metabolism still not fully understood, including its activity in processing damaged RNA in chemoresistant phenotypes, regulating oncomiRs maturation, and oxidized-RNA decay. Recent data point out a control role of APE1 in the expression and sorting of oncomiRs, within secreted extracellular vesicles (EVs). This review is focused on giving a portrait of the pros and cons of the last two decades of research aiming at the identification of inhibitors of the redox or the DNA-repair functions of APE1 for the definition of novel targeted therapies for cancer. We will discuss the new perspectives in cancer therapy coming from the unexpected finding of the APE1 role in miRNA processing for personalized therapy.

Introduction: Cancer is a group of diseases caused by uncontrolled and abnormal cell growth caused by the accumulation of genetic and epigenetic changes. Based on data from Dr Kariadi Hospital in 2021, lung cancer, breast cancer, and cervical cancer were 1,259 cases, this incident increased significantly from 2020. Based on the data obtained, the sequence of lung cancer cases was 241, breast cancer 623 , and cervical cancer 395. Both cancer and its treatment can weaken the patient's immune system, this is what makes cancer sufferers have a risk of anxiety and depression. Objective: To find out the description of anxiety and depression in cancer patients at RSUP Dr. Kariadi Semarang. Methods: The design of this study was descriptive quantitative, with a population of 56 patients and calculated using a stratified random sampling formula so that a sample of 49 respondents was obtained. The instrument or measuring instrument in this study used the Hospital Anxiety and Depression Scale (HADS). Results: Most cancer patients experienced mild anxiety and did not experience depression or at normal levels, from the number of respondents as many as 49 respondents, 27 respondents experienced mild anxiety (55.1%) and did not experience depression or at normal levels as many as 22 respondents (44, 9%). Suggestion: It is hoped that it can provide input for nurses to provide counseling to patients as an effort to reduce the anxiety and depression felt by patients.

Pirin is an oxidative stress (OS) sensor belonging to the functionally diverse cupin superfamily of proteins. Pirin is a suggested quercetinase and transcriptional activator of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Its biological role in cancer development remains as a novel area of study. This review shows accumulating evidence on the contribution of Pirin in epithelial cancers, signaling pathways involved, and as a suggested therapeutic target. Finally, we propose a model in which Pirin is upregulated by physical, chemical or biological factors involved in OS and cancer development.

The study aimed to estimate the prevalence and associated factors of cervical and breast cancer screening among women in the general population in Jordan. Nationally representative cross-sectional data were analysed from 14,689 women (34 years median age, range 15-49) that took part in the “2017-18 Jordan Population and Family Health Survey”. Information about cancer screening uptake included Pap smear, clinical breast examination, and mammography. Results indicate that the prevalence of ever Pap smear cancer screening was 15.3%, clinical breast examination in the past 12 months 13.9% and ever mammography 8.7%. In adjusted logistic regression analysis, older age, higher wealth, greater media exposure and tobacco use were positively and being Syrian, and living in the southern region were negatively associated with ever Pap smear, clinical breast examination in the past 12 months, and ever mammography. In addition, high decision-making power was associated with the uptake of Pap smear and higher education was associated with ever mammography. The study showed a low cancer screening uptake, and several factors were identified that can assist in promoting cancer screening in Jordan.

Cancer, a disease of multicellular organisms, probably developed almost immediately following the transition from unicellular to metazoan life, about one billion years ago. Great efforts have been made to understand the carcinogenesis for many years. In this paper, We tried to explain the cancer based on “chaos”, “adaptation” and “information” with the context of new literature findings.

Cancer, a globally prevalent and often deadly disease, holds promise for improved treatment through the integration of innovative medical technologies and interdisciplinary collaborations. Despite advancements, current cancer therapies lack a specific focus on addressing recurrence and targeting cancer stem cells (CSCs), known contributors to relapse. In this study, we utilized three types of cancer cells and generated three types of CSCs derived from them to conduct proteomic analysis and identified shared cell surface biomarkers as potential targets for a comprehensive treatment strategy. The selected biomarkers underwent evaluation through shRNA treatment, revealing contrasting functions in cancer and CSCs. Knocking down the identified protein showed promising results in regulating epithelial-mesenchymal transition (EMT) and stemness via the ERK signaling pathway. This led to a reduction in resistance to anticancer agents, ultimately enhancing the overall anticancer effects. Additionally, the biomarker's significance in clinical patient outcomes was confirmed using bioinformatics. Our study suggests a novel cancer treatment strategy that addresses existing limitations in current anticancer therapies.

Introduction: Skin cancer is the 5th most common cancers in western countries with surge in the cases of occurrence with the passing time making it a global burden on health care system. In this present study, the cancer preventive activities of Argemone mexicana Linn (AM), which has been widely used by folklores to treat different ailments. Aim: The experiment advocates the cancer preventive activity of ethanolic extract of AM and to against DMBA/TPA induced skin cancer in mice model. Materials and Methods: Experimental animals were divided into doses group,100mg/kg B.W, 250mg/kg B.W, 500mg/kg B.W and 1000mg/kg B.W and subjected to toxic dose determination. The DMBA/TPA method was followed to induce the skin cancer in mice along with the feeding of non-toxic doses of 100mg/ kg, 250mg/kg, 500mg/kg mice were given as a pretreatment and 500mg/kg as a separate post treatment group as per body weight. The anti-cancerous activity was determined by different parameters on 0day, 30th day and 60th day including change in incidence of tumour induction, haematological parameters, histopathology and changes in pattern of TNF-α secretion and NF-kB (p65 subunit) signaling pathway in the blood serum. Results: The 1000 mg/kg BW was found to exhibit sub-acute toxicity. It was observed that the 500mg/kg BW pretreated group resisted and delayed the tumour formation for up to 8 weeks as compared to the Negative Control group where growth was seen in 4 weeks. The tumour burden was also found to be varying in a dose-dependent where on 60th day, Negative Control group and 100mg/kg BW was found to possess significantly high (p<0.001) tumour burden in comparison to the 500mg/kg BW group where tumour burden was not found till 60th day. The study was validated by body weight, blood parameters, histopathology and altered pattern in regulation of TNF-α and NF-kB signaling pathway which play an important role in cancer progression. The expression of TNF-α and p65 subunit of NF-kB signaling pathway was found to be reduced significantly in a dose dependent manner and found to be highly reduced in 500mg/kg BW group (p<0.001) as compared to Negative control. Conclusion: The 500mg/kg BW pretreated group was found to have significant results in comparison to 500mg/kg BW post treatment group. The study revealed effective cancer preventive activity of Argemone mexicana Linn leaves (AML) in the mice model and paved a pathway for molecular approaches which could be explored more in future studies.

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.

Current treatments in patients with pancreatic cancer offer limited benefits. In this report, we applied “alkalization therapy”, which was efficacious for other solid tumors at our clinic, to stage 4 pancreatic cancer patients, and investigated its effect on disease prognosis. Patients with metastatic pancreatic cancer who were treated at Karasuma Wada Clinic in Kyoto, Japan, between 2011 and 2022 were included in the study. All patients received alkalization therapy (combination of an alkaline diet, bicarbonate, and citric acid administration), alongside standard chemotherapy. Urine samples were collected to assess urine pH as a marker for whole-body alkalization. In the 98 patients analyzed, the median overall survival (OS) from the time of diagnosis was 13.2 months. Patients with a mean urine pH of 7.5 or greater had a median OS of 29.9 months, compared with 15.2 months for those with a mean urine pH of 6.5 to 7.5, and 8.0 months for those with a mean urine pH of less than 6.5, which suggests a trend of a longer OS in patients with a higher urine pH. Conclusions: Alkalization therapy may offer a viable approach to enhance the survival of stage 4 pancreatic cancer patients, who typically have an unfavorable prognosis.

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.

Prostate cancer (PCa) has become the most common tumor among males in Europe and the USA. Adoptive immunotherapy appears as a promising strategy to control the advanced stages of the disease by specific targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-γ in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy.

In the present study, we have followed the hydrothermal path for the synthesis of gold nanoparticles (Au NPs) from the biomaterial Elaeocarpus ganitrus seeds extract, which is a rapid, eco-friendly, non-chemical way. The prepared NPs were thoroughly analyzed by PXRD & HR-TEM studies and also tested for photocatalytic dye degradation and anticancer studies. Besides, antioxidant, antibacterial and anticancer properties of Au NPs were studied. In vitro studies revealed the dose-dependent cytotoxic effect of Au NPs. The prepared nanoparticles showed good cytotoxic impact against Prostate cancer (PC-3) cells line. The results of the present study could contribute to synthesize new and cost-effective drugs from Elaeocarpus ganitrus seeds extract by using bio approach.

Cachexia is a complex metabolic syndrome characterized by loss of skeletal muscle, leading to a significant weight loss that impacts patient morbidity and mortality. Given the complexity of gene regulatory networks that control gene expression, our objective was to perform an integrative mRNA and miRNA profiling to identify genetic programs that capture essential mechanistic details that promote muscle atrophy in cancer cachexia. Here, we used RNA sequencing to analyze miRNAs and mRNAs expression profiles in tibialis anterior (TA) muscles of the Lewis lung carcinoma model of cancer cachexia. In addition, we compared these findings with RNA-Seq data from C2C12 myotubes treated in vitro with the cachectic factors tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Extracellular matrix (ECM) alterations were validated by picrosirius staining, western blot, and fractal dimension analyses. We found 1,008 mRNAs and 18 miRNAs differentially expressed in cachectic mice. This set of genes was associated with the ECM, proteolysis, and inflammatory response. Enrichment analysis of transcriptional factor binding sites revealed activation of the atrophy-related transcriptional factors: NF-κB, Stat3, AP-1, and FoxO. Furthermore, the integration of mRNA and miRNA expression profiles identified post-transcriptional regulation by miRNAs of genes involved in ECM organization, cell migration, transcription factors binding, ion transport, and FoxO signaling pathway. C2C12 myotubes treated with TNF-α and IFN-γ similarly down-regulate subsets of ECM genes, including collagens. Our integrative analysis of miRNA-mRNA co-profiles comprehensive characterized regulatory relationships of molecular pathways and revealed miRNAs targeting ECM-associated genes in cancer cachexia. We also confirmed in C2C12 myotubes that changes in ECM-associated genes are dependent on inflammatory signaling of the cytokines TNF-α and IFN-γ.

Bladder cancer is one of the most common malignant diseases in the urinary system and a highly aggressive neoplasm. The prognosis is not favourable usually and its evolution for particular patients is very difficult to find out. In this paper we propose a dynamic mathematical model that describes the bladder tumor growth and the immune response evolution. This model is customized for a single patient, determining appropriate model parameter values via model calibration. Due to the uncertainty of the tumor evolution, using the calibrated model parameters, we predict the tumor size and the immune response evolution over the next few months assuming three different scenarios: favourable, neutral and unfavourable. In the former, the cancer disappears; in the second a 5mm tumor is expected around the middle of August 2018; in the worst scenario, a 5mm tumor is expected around the end of May 2018. The patient has been cited around June 15th, 2018, to check the tumor size, if it exists.

Purpose: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in present study. In DIACRT group, 25 patients had T2, 20 patients had T3. A total of 9 patients had T2 and 2 had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months respectively. The 5-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for DIACRT group, 60.6% and 63.6% for WIACRT group respectively. The LC rate and OS of DIACRT group were significantly higher than that of WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods both in two groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

Copper (Cu) is an essential micronutrient for the correct development of eukaryotic organisms. This metal plays a key role in many cellular and physiological activities, including enzymatic activity, oxygen transport, and cell signaling. Although the redox activity of Cu is crucial for enzymatic reactions, this property also makes it potentially toxic when found at high levels. Due to this dual action of Cu, highly regulated mechanisms are necessary to prevent both the deficiency and the accumulation of this metal since its dyshomeostasis may favor the development of multiple diseases, such as Menkes’ and Wilson’s diseases, neurodegenerative diseases, diabetes mellitus, and cancer. As the relationship between Cu and cancer has been the most studied, we analyze how this metal can affect three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis. Gynecological diseases are characterized by high prevalence, morbidity, and mortality, depending on the case, and mainly include benign and malignant tumors. The cellular processes that promote their progression are affected by Cu, and the mechanisms that occur may be similar. We analyze the crosstalk between Cu deregulation and gynecological diseases, focusing on therapeutic strategies derived from this metal.

One in eight women will be diagnosed with breast cancer (BC) in their lifetime, resulting in over 2 million cases annually. BC is the most common cancer among women. Unfortunately, the etiology of majority of cases remains unknown. Recently, evidence has shown that the human microbiota plays an important role in health and disease. Intriguingly, studies have revealed the presence of microorganisms in human breast tissue, which was previously presumed to be sterile. Next-generation sequencing technologies have paved way for the investigation of breast microbiota, uncovering bacterial signatures that are associated with BC. Some of the bacterial species were found to possess pro-carcinogenic and/or anti-carcinogenic properties, suggesting that the breast microbiota has potentially crucial roles in maintenance of breast health. In this review, we summarize the recent findings on breast tissue microbiota and its interplay with BC. Bacterial signatures identified via next-generation sequencing as well as their impact on breast carcinogenesis and cancer therapies are reviewed. Correlation of breast tissue microbiota and other factors, such as geographical and racial differences, in BC is discussed. Additionally, we discuss the future directions of research on breast microbiota as well as its potential role in prevention, diagnosis and treatment of BC.

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by swelling in at least one joint. Owing to an overactive immune response, extra-articular manifestations are observed in certain cases, with interstitial lung disease (ILD) being the most common. Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is characterized by chronic inflammation of the interstitial space, which causes fibrosis and the scarring of lung tissue. Controlling inflammation and pulmonary fibrosis in RA-ILD is important because they are associated with high morbidity and mortality. Pirfenidone and nintedanib are specific drugs against idiopathic pulmonary fibrosis and have shown efficacy against RA-ILD in several clinical trials. Immunosuppressants and disease-modifying antirheumatic drugs (DMARDs) with antifibrotic effects have also been used to treat RA-ILD. Immunosuppressants moderate the overexpression of cytokines and immune cells to reduce pulmonary damage and slow the progression of fibrosis. DMARDs with mild antifibrotic effects target specific fibrotic pathways to regulate fibrogenic cellular activity, extracellular matrix homeostasis, and oxidative stress levels. Therefore, specific medications are required to effectively treat RA-ILD. In this review, the commonly used RA-ILD treatments are discussed based on their molecular mechanisms and clinical trial results. In addition, a computational approach is proposed to develop specific drugs for RA-ILD.

Formal Calculation uses an auxiliary form to calculate various nested sums and provides results in three forms. In addition to computation, it is also a powerful tool for analysis, allowing one to study various numbers in a unified way. This article contains many results of two types of Stirling numbers, associated Stirling numbers, and Eulerian numbers, making a great generalization of Euler polynomials, Wilson's theorem, and Wolstenholme's theorem, showing that they are just special cases. Formal Calculation provides a novel method for obtaining combinatorial identities and analyzing q-binomial.This article has obtained a large number of results in q-analogues, including inversion formulas for q-binomial coefficients. This article also introduces a theorem on symmetry.

Tumor-associated macrophages (TAMs) play critical roles in the tumor microenvironment (TME), where they are recruited by signals released by cancer cells. Although they have great potential as therapeutic targets for cancer treatment, the dual roles of TAMs in promoting or inhibiting tumor growth, invasion, and metastasis make their function in cancer progression complex. In this review, we provide an overview of the current understanding of TAMs, including their phenotypic diversity, regulatory signaling pathways, and interactions with other cells in the TME. We also discuss the challenges related to the standard isolation protocols of TAMs, inconsistent research results, and translation of TAM knowledge into clinical applications. Additionally, we review the status of clinical trials involving TAMs and potential strategies to overcome the limitations. The future direction of TAM research should focus on developing more targeted therapies that specifically regulate TAM function and non-invasive methods for monitoring TAM activity in cancer patients. A comprehensive understanding of the complex role of TAMs in cancer may lead to the development of more effective treatments and improved outcomes for cancer patients.

Progressive supranuclear palsy (PSP) is a sporadic parkinsonism tauopathy characterised by the deposition of aggregations of abnormal, hyperphosphorylated four-repeat tau (4R-tau). A revised clinical diagnostic criterion for PSP allows early presentations for the full spectrum of clinical phenotypes to be recognised enabling doctors to make a more accurate diagnosis. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule-associated protein tau (MAPT). Research into the biochemical and pathological pathways of tau is vital to improve the chances of developing an effective diagnostic biomarker to monitor tau pathogenesis. Neuroimaging biomarkers, such as tau PET ligands, are proving the most successful tool in providing a differential diagnosis between neurodegenerative disorders. There are currently no effective treatments for PSP, however tau-directed therapies in the last five years have rapidly advanced. Latest tau therapies are proposed to have disease-modifying effects by reducing toxic aggregations of tau through manipulating tau gene expression. After encouraging results from long awaited trials, additional funding is being injected into this field and with new results expected, this proves an exciting area for scientific discovery. This paper reviews advances in pathophysiology, diagnosis, biomarkers and disease-modifying therapeutic treatments for PSP.

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

Auger electrons (AEs) represent an intriguing topic in the field of radionuclide therapy. They are emitted by several radionuclides commonly used in nuclear medicine (indium-111, iodine-123, iodine-125), allowing for highly localized energy deposition and thus exerting a radiotoxic effect on specific cellular and sub-cellular targets. However, due to their short range in matter, AEs have had limited use in therapeutic applications so far. In recent years, the synthesis of various radiopharmaceuticals capable of binding to the enzyme poly(ADP-ribose) polymerase 1 has reignited interest in this type of therapy, laying the groundwork for a theranostic approach based on radionuclides emitting AEs. The enzyme PARP-1 operates enzymatically in close proximity to DNA that represents the prime target of radionuclide therapies. Following this trend, several PARP-targeted radiopharmaceuticals for AE-based theranostics have been developed. We provide an updated overview of preclinical studies focused on the applications of this new theranostic approach in glioblastoma, breast, prostate and ovarian carcinoma, and pancreatic adenocarcinoma.

Abstract: Cervical cancer, which is the fourth most common malignancy and the fourth greatest cause of cancer-related deaths in women globally, continues to be a serious issue for global health. Despite advancements in treatment techniques, particularly the implementation of concomitant chemoradiation therapy, predicting the prognosis of locally advanced cervical cancer, especially for stage III, remains challenging. In recent years, neoadjuvant chemotherapy (NACT) has gained interest as a viable treatment strategy. The objective of this review paper is to scrutinize the clinical data and outcomes associated with NACT in the management of stage 3 cervical cancer. Electronic databases were used to perform a comprehensive literature search, and research up to 2023 were included. The findings suggest that NACT followed by irradiation may have advantages such as lowering tumor size, pelvic architectural distortion, and subclinical distant metastases, therefore enhancing radiation delivery. However, several studies have produced conflicting findings, raising questions regarding toxicity and finding no appreciable survival benefit over radiation alone. NACT followed by radical surgery has demonstrated more promising outcomes compared to surgery alone in terms of increasing rates of overall survival (OS) and progression-free survival (PFS). Additionally, NACT has been associated with decreased tumor growth, parametrial infiltration, nodal, metastases, and vascular space invasion. These findings suggest adjuvant radiation treatment. Although the overall survival rate has been markedly increased by concomitant chemoradiation treatment, metastatic disease continues to be a major factor in the death rate from cervical cancer. Therefore, improving outcomes in locally advanced cervical cancer requires investigating novel systemic treatments, such as NACT. The study also emphasizes how crucial it is to research factors like cisplatin dose-intensity and cycle lengths in order to maximize NACT's efficacy. To prevent the need for subsequent treatments and cumulative toxicity, more study should concentrate on patient selection for NACT followed by surgery.

Background: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was identification of serum biomarkers of early response to NAC. Methods: We conducted this prospective study in the MSCNRIO, in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers signed informed consent. Complete blood count, blood chemical tests, carcinoembryonic antigen (CEA) carcinoma antigen 125 (CA125), carcinoma an-tigen 19.9 (CA19.9), d-dimer, fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). Results: Of all the measured parameters, only IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in complete pathological re-sponse (pCR) vs non-pCR group (3.71 pg/mL vs 7.63 pg/mL, p=0,004). In all patients with IL-6 levels below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs ypN0 (7.69 pg/mL vs 2.89 pg/mL, p=0.022). Conclusions: The trial showed that elevated level of IL-6 prior to treatment and C2 might be a predictor of pathologic response to NAC.

The cancer burden is increasing worldwide with contrasting national patterns. Therefore, providing national estimations is necessary to understand and control this health issue. Herein, we comparatively describe incidence, mortality, and disability-adjusted lived years (DALYs) due to 29 groups of cancer in Mexico from 1990 to 2019 by sex and age. Using public data from the Global Burden of Disease Study 2019, we assessed the national burden of cancer using counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and their trends using the annual percentage of change from 1990 to 2019. In 2019, cancer caused 222,060 incident cases, 105,591 deaths, and 2,86,054 DALYs in the general population. Nonmelanoma skin cancer, prostate cancer, and breast cancer had the highest incidence, and six groups of cancer (lung, colorectal, stomach, prostate, breast, and pancreatic) caused 53% of the deaths in 2019. From 1990 to 2019, incidence and mortality showed an increasing trend that varied between 10% and 436% among the groups of cancer, whereas the crude and age-standardized rates showed cancer-specific sex disparities. Our results demonstrate a substantial growth of the national burden of cancer with sex-specific patterns of change. These results may guide national efforts toward reducing health loss due to cancer.

The genome sequencing technologies reveal the molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood. The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing (WGS) data. We analyzed sequencing data from 1076 unrelated individuals, released openly for academic and clinical research as The Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies. The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort (our study) was compared to the frequency estimated for the non-Finnish European population, obtained from the gnomAD database (gnomad.broadinstitute.org). Statistically significant variants included 23 genes. Even though the Polish population is genetically similar to other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as RET, CHECK2, BRCA1, SLC26A4 or TERT. Further studies are needed to identify genomic variants associated directly with DTC.

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.

Blood-based circulating cell free DNA(cfDNA) detection offers a non-invasive and easily accessible way for early cancer detection. Despite the extensive utility of cfDNA, there are still many challenges to develop the clinical biomarkers. For example, cfDNA with genetic alterations often compose a small portion of the DNA circulating in plasma, which can be confounded by cfDNA contributed by normal cells. Therefore, filtering out the potential false-positive cfDNA mutations from health population will be important for the cancer-based biomarkers. Additionally, many low-frequency genetic alterations are easily overlooked in small amount of cfDNA-based cancer test. We hypothesize that, the combination of diverse types of cancer studies on cfDNA can provide us a new insight to identify low-frequency genetic variant across cancer types for early clinical detection of cancers. By building a standardized computational pipeline for 1358 cfDNA samples across seven cancer types, we prioritize 129 shard genetic variants in the major cancer types. Further functional analysis of the 129 variants found that they are mainly enriched in ribosome pathways such as cotranslational protein targeting to membrane, some of which are tumor suppressor, oncogene and related to cancer initiation. In summary, our integrative analysis revealed the important roles of ribosome proteins as the common biomarkers in early cancer diagnosis.

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.

Transfer RNA fragments (tRFs) have gene silencing effects similarly to miRNAs, can be sorted into extracellular vesicles (EVs) and are emerging as potential circulating biomarkers for cancer diagnosis. We aimed at analyzing the expression of tRFs in gastric cancer (GC) and understanding their potential as biomarkers. We explored miRNA datasets from gastric tumors and normal adjacent tissues (NAT) from TCGA repository, and proprietary 3D-cultured GC cell lines and corresponding EVs, in order to identify differentially represented tRFs using MINTmap and R/Bioconductor packages. Selected tRFs were validated in patient-derived EVs. We found 613 Differentially Expressed (DE)-tRFs in the TCGA dataset, of which 19 were concomitantly upregulated in TCGA gastric tumors and present in 3D-cells and EVs, but barely expressed in NAT. Moreover, 20 tRFs were expressed in 3D-cells and EVs and downregulated in TCGA gastric tumors. Of these 39 DE-tRFs, 9 tRFs were also detected in patient-derived EVs. Interestingly, the targets of these 9 tRFs affect neutrophil activation and degranulation, cadherin binding, focal adhesion and cell-substrate junction, highlighting these pathways as major targets of EV-mediated crosstalk with the tumor microenvironment. Furthermore, as they are present in four distinct GC datasets and can be detected even in low quality patient-EV derived samples, they hold promise as GC biomarkers. By repurposing already available NGS data, we could identify and cross-validate a set of tRFs holding potential as GC diagnosis biomarkers.

Two related tumor suppressor genes, Brca1 and Brca2, attract a lot of attention from both fundamental and clinical points of view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset of breast and ovarian cancers. However, the molecular mechanisms that drive extensive mutagenesis in these genes are not known. In this review we hypothesize that one of the potential mechanisms behind this phenomenon can be mediated by Alu mobile genomic elements. Linking mutations in the BRCA1 and BRCA2 genes to the general mechanism(s) of genome stability and DNA repair is critical to ensure the rationalized choice of anti-cancer therapy. Accordingly, we review the literature available on mechanisms of DNA damage repair where these proteins are involved in and how the inactivating mutations in these genes (BRCAness) can be exploited in anti-cancer therapy. We also propose a hypothesis that explains why breast and ovarian epithelial tissues are preferentially susceptible to mutations in BRCA genes. Finally, we discuss perspectives of novel therapeutic approaches for treating BRCAness cancers.

Pancreatic cancer represents one of the difficult problems of contemporary medicine. The development illness evolves very slowly, takes place in special sake (stroma) and manifests clinically close to a final stage. Another feature of this pathology is a coexistence (symbiotic) effect between cancer cells and normal cells inside stroma. All these aspects make it difficult to understand the pathogenesis of pancreatic cancer and develop a proper therapy. The emergence of pancreatic pre-cancer and cancer cells represents a branching stochastic process engaging populations of 64 cells differing in the number of acquired mutations. In this study we formulate and calibrate the mathematical model of pancreatic cancer using the quasispecies framework. The mathematical model incorporates the mutation matrix, fineness landscape matrix and the death rates. Each element of the mutation matrix presents the probability of appearing a specific mutation in the branching sequence of cells representing the accumulation of mutations. The model incorporates the cancer cell elimination by effect CD8 T cells (CTL). The down-regulation of the effector function of CTLs and exhaustion are parameterized. The symbiotic effect of coexistence of normal and cancer cells is considered. The computational predictions obtained with the model are consistent with empirical data. The modelling approach can be used to investigate other types of cancers and examine various treatment procedures.

Cancer is the second leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. Although traditional molecular profiling techniques, i.e., bulk sequencing, can identify common mutations and gene expression patterns in cancer cells, they cannot detect tumour heterogeneity. However, single-cell technology has provided an ample opportunity to overcome this difficulty. Since this technology allows us to detect the heterogeneous properties of all cancer cells, this can further our knowledge of the signaling pathways in cancer cells. Indeed, single-cell transcriptomics technology has paved the road for identifying novel biomarkers and signaling pathways, which can serve as targets. This study aims to review the current knowledge about pathways involved in developing cancer cells and shed light on single-cell studies as promising therapeutic approaches.

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) of Minnesota, “Sage”, provides breast cancer screening to uninsured women. We introduce a novel mapping technique, spatially adaptive filters (SAFs), to estimate utilization of Sage screening in Minnesota. Sage screenings (N = 74,712) were geocoded. The eligible population was modeled with the RTI synthetic population dataset. Between 2011 and 2015, 36,979 women a year were Sage eligible. Utilization was highly variable across Minnesota (M = 37.2%, range 0% - 131%, SD = 18.7%). This replicable approach modeled utilization rates to the neighborhood-level, allowing Sage to prioritize locations and engage communities.

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.

Development of targeted therapies for triple-negative breast cancer (TNBC) is an unmet medical need. Cisplatin has demonstrated its promising potential for the treatment of TNBC in clinical trials; however, cisplatin treatment is associated with hypoxia that in turn promotes cancer stem cell (CSC) enrichment and drug resistance. Therapeutic approaches to attenuate this may lead to increased cisplatin efficacy in the clinic for the treatment of TNBC. In this report, we analyzed clinical dataset of TNBC and found that TNBC patients possessed higher levels of EGFR and hypoxia gene expression. A similar expression pattern was also observed in cisplatin-resistant ovarian cancer cells. We thus developed a new therapeutic approach to inhibit EGFR and hypoxia by combination of metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs. We demonstrated a similar inhibition efficacy on organotypic cultures of TNBC patient samples ex vivo. Since these drugs have already been used frequently in the clinic, this study illustrates a novel, clinically translatable therapeutic approach to treat patients with TNBC.

Submucosal invasion is a critical step in gastric cancer (GC) progression, which greatly enhances metastasis risk. Cancer stem cells are responsible for invasion, metastasis, and tumor growth. To identify stem cell-related markers associated with submucosal invasion in GCs, we investigated the expression of candidate cancer stem cell (CSC) markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs with submucosal invasion. Remarkably, expression of all ISC markers and CD133 was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer. The proportion of stem cell marker-positive cells substantially increased during submucosal invasion. Given that ISC markers are restricted to the crypt base of the normal intestinal mucosa, these findings suggest that many early GCs may retain hierarchical characteristics. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. RSPO2 from muscularis mucosa seem to be partly responsible for the increased expression of ISC markers in GC cells at the basal areas. We also found that ISC markers were correlated with CDX2 expression in GCs, indicating that ISC markers are involved in the intestinal differentiation in GCs. Interestingly, ISC markers (EPHB2 and OLFM4) and CD133 showed a positive impact on clinical outcomes. In particular, the prognostic value of EPHB2 was significant for intestinal-type GCs in a multivariate analysis. In summary, ISC markers and CD133 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs. EPHB2 was an independent prognostic marker in intestinal-type GCs.

Patient derived model systems are important tools for studying novel anti-cancer therapies. Patient derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient derived models for radiation research including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

Lung cancer remains the leading cancer killer worldwide. Early diagnosis can effectively increase the patient cure rate but existing diagnostic methods limit early lung cancer diagnosis. Therefore, development of a simple but efficient lung cancer screening method is important to improvement of both the diagnosis rate and the survival rate of lung cancer patients. In this study, ten photosensitive materials with high sensitivity and high specificity were screened accurately to construct a microarray sensor that can rapidly identify six types of lung cancer biomarkers in exhaled breath. Results from hierarchical cluster analysis (HCA), principal component analysis (PCA) and difference maps showed that the classification of the analytes agreed with structure similarity laws. The detection results from parallel experiments and structurally similar analytes, in turn, cluster into a group; the fingerprints of the different analytes have specific response regions. The well-screened sensor chip fabrication workload and cost were both reduced by approximately two thirds, while the microfluidic device sensitivity and stability increased by approximately 1.3 times their corresponding values before optimization. The dual-channel device also offers real-time contrast detection and synchronous parallel detection functions and has potential application prospects for use in extensive screening of high-risk populations for lung cancer.

BACKGROUND: Endoscopic placement of Self Expandable Metal Stents to relieve malignant colorectal obstruction has become a common therapeutic advancement in clinical practice. MATERIAL: In a 16 year period 167 patients had endoscopic placement of a Self Expandable Metal Stent in a center where gastroenterologists and surgeons cooperate in a daily basis, discussing indications. RESULTS: There was no operative mortality and no major complication in placement of the stent. Technical and clinical success was respectively 95.1% and 92.9%. Consultation among specialists changed the preoperative indication in 60 patients, during the same time period. CONCLUSIONS: Self expandable metal stents placement represents an important tool to treat patients with obstructing colorectal cancer and complications after colorectal resection . A proper training is required, and this training in operative endoscopy is not always available and possible. In this scenario, a close collaboration among specialists in selecting the most appropriate operative procedure is essential and brings to better results.

Coordinated sets of extremely numerous digital data, on a given social or economic event, are treated by Artificial Intelligence tools to obtain reasonably accurate, valuable predictions. The same approach, applied to biomedical issues, as how to choose the right drug to completely cure a given cancer patient, does not reach satisfactory results. It is the “organized biological complexity”, which requires a different systems approach, to integrate, in an Augmented Intelligence strategy, statistical computations of digital data, network construction of “omics” findings, well-designed mathematical models and new experiments in an iterative pathway to reconstruct the “logic” beneath the “organized complexity”, as shown here for Systems Metabolomics of cancer. On this basis new diagnostic approaches, able to identify precision drug treatments, as well as new discovery strategy for more effective anti-cancer drugs are described.

Mutations in the “guardian of the genome” TP53 predominate in solid tumors. In addition to loss of tumor suppressor activity, a specific subset of missense mutations confers additional oncogenic properties. These “gain-of-function” (GOF) mutations portend poor prognosis across cancer types regardless of treatment. Our objective in this study was to identify novel therapeutic opportunities to overcome the deleterious effects of GOF TP53 mutants. Using gynecologic cancer cell lines with known TP53 mutational status, we established that treatment with a proteasome inhibitor induced cell death in cells with two recurrent GOF TP53 mutations (R175H and R248Q), and addition of a histone deacetylase inhibitor (HDACi) enhanced this effect. By contrast, p53-null cancer cells were relatively resistant to the combination. Towards understanding the mechanism, we found that proteasome inhibition promotes apoptosis of cells with TP53 GOF mutations, potentially through induction of the unfolded protein response. In line with the reported hyperstabilization of GOF p53 protein, cells treated with HDACi exhibited reduced levels of p53 protein. Together, these data form the basis for future clinical studies examining therapeutic efficacy in a preselected patient population with GOF TP53 mutations.

In most industrialized countries, screening programs for cervical cancer have shifted from cytology (Pap smear or ThinPrep) alone on clinician-obtained samples to the addition of screening for human papillomavirus (HPV), its main causative agent. For HPV testing, self-sampling instead of clinician-sampling has proven to be equally accurate, in particular for assays that use nucleic acid amplification techniques. In addition, HPV testing of self-collected samples in combination with a follow-up Pap smear in case of a positive result is more effective in detecting precancerous lesions than a Pap smear alone. Self-sampling for HPV testing has already been adopted by some countries, while others have started trials to evaluate its incorporation into national cervical cancer screening programs. Self-sampling may result in more individuals willing to participate in cervical cancer screening, because it removes many of the barriers that prevent women, especially those in low socioeconomic and minority populations, from participating in regular screening programs. Several studies have shown that the majority of women who have been underscreened but who tested HPV-positive in a self-obtained sample, will visit a clinic for follow-up diagnosis and management. Additionally, a self-collected sample can also be used for vaginal microbiome analysis, which can provide additional information about HPV infection persistence as well as vaginal health in general.

Several evidences suggest that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometime inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between the intake of meat-related mutagens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: PhIP, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline: MeIQx, 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline: DiMeIQx, benzo(a) pyrene: (B(a)P) and “meat derived mutagenic activity”: MDM) and CRC/CRA risk. A random-effect model was used to calculate the risk association. Thirty-nine studies were included in the systematic review and meta-analysis. Polled CRA risk (15229 cases) was significantly increased by intake of PhIP (OR=1.20; 95%CI:1.13,1.28; p<0.001), MeIQx (OR=1.14; 95%CI:1.05,1.23; p=0.001), DiMeIQx (OR=1.13; 95%CI:1.05,1.21; p=0.001), B(a)P (OR=1.10; 95%CI:1.02,1.19; p=0.017) and MDM (OR=1.17; 95%CI:1.07,1.28; p=0.001). A linear and curvilinear trend was observed in dose-response meta-analisis between CRA risk in association with PhIP and MDM, MeIQx, respectively. CRC risk (21344 cases) was increased by uptake of MeIQx (OR=1.14; 95%CI:1.04,1.25; p=0.004), DiMeIQx (OR=1.12; 95%CI:1.02,1.22; p=0.014) and MDM (OR=1.12; 95%CI:1.06,1.19; p<0.001). No publication bias could be detected whereas heterogeneity was in some cases rather high. Mutagenic compounds formed during cooking of meat at high temperature may be responsible of its carcinogenicity.

BACKGROUND: Treatment failure in primary as well as metastatic cancer patients, caused by chemo and radio resistance, has truncated the research for the applicability of personalized medicine. The use of stem cells and cancer stem cells in such a treatment approach will be reviewed in this study. RESULTS: CRC stem cells prove to be a promising asset for CRC treatment optimization both by serving as biomarkers for the current therapy modalities by means of treatment personalization and patient/tumor stratification, as well as in the development of targeted therapies, selective for the stem cell population. Similar conclusions are drawn, regarding mesenchymal stromal cells and their effect in CRC therapy; while resident stromal cells of tumor microenvironment seem to promote the tumorigenic and metastatic processes in addition to conferring to the chemo- and radio resistance, under certain conditions they are able to improve the treatment outcome of CRC chemotherapy, e.g. by targeted enzyme/prodrug treatment of CRC cells. CONCLUSION: This review, truncates the dynamic potential of cancer stem cells and other stem cell types in CRC treatment personalization as well as, in the improvement of current treatment approaches opting to a higher therapeutic rate, improved prognosis, survival and quality of life for CRC patients.

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissoci-ated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9-days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular via-bility over time. Overall, this human-centered model offers a promising resource to study the cel-lular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics.

Transitions from seed to seedling represent a critical developmental step in the life cycle of higher plants, dramatically affecting plant ontogenesis and stress tolerance. The release from dormancy to acquiring the germination ability is defined by a balance of phytohormones, with a substantial contribution of abscisic acid (ABA), which inhibits germination. We studied the embryonic axes of Pisum sativum L. before and after radicle protrusion. Our previous work compared RNA sequencing-based transcriptomics in the embryonic axes isolated before and after radicle protrusion. The current study aims to analyze ABA-dependent gene regulation during the transition of embryonic axes from germination to post-germination stage. First, we determined the levels of abscisates (ABA, phaseic acid, dihydrophaseic acid, and neo-phaseic acid) using the ultra-high-performance liquid chromatography-tandem mass spectrometry. Second, we made a detailed annotation of ABA-associated genes using RNA sequencing-based transcriptome profiling. Finally, we analyzed the DNA methylation pattern in the promoters of the PsABI3, PsABI4, and PsABI5 genes. We showed that changes in the abscisate profile are characterized by the accumulation of ABA catabolites, and the ABA-related gene profile is accompanied by the upregulation of genes controlling the seedling development and the downregulation of genes controlling the water deprivation. The expression of ABI3, ABI4 and ABI5, which encode the crucial transcription factors during late maturation, was downregulated by more than 20-fold, and their promoters exhibited a high level of methylation already at the late germination stage. Thus, although ABA remains important, other regulators seems to be involved in the transition from seed to seedling.

Ambient vibration energy is widely being harnessed as a source of electrical energy to drive low-power devices. The vibration energy harvester (VEH) of interest employs an electromagnetic transduction mechanism, whereby ambient mechanical vibration is converted to electrical energy. The limitations affecting the performance of VEHs, with an electromagnetic transduction structure, include its operational bandwidth as well as the enclosure-size constraint. In this study, an analysis and design of a nonlinear VEH system is conducted, using the Output Frequency Response Function (OFRF) representations of the actual system model. However, the OFRF representations are determined from the Generalised Associated Linear Equation (GALE) decompositions of the system of interest. The effect of both nonlinear damping and stiffness characteristics, to respectively extend the average power and operational bandwidth of the VEH device, is demonstrated.

Introduction: Some of the practices in medicine are carried out of habit without proven benefits. This is the case of premature babies from 30 to 34 weeks of gestation who are always given parenteral fluids, even though this practice has been associated with an increase incidence of infection. At the end of 2017, we started a protocol of rationalization in the use of parenteral fluid. To administer nutrition/fluids, we used oral fluids by suction if this was possible or otherwise by oral/nasogastric tube at volumes of 70-80 mL/Kg/day divided every 3 hours, with 5 mL increments every 12-24 hours until 200 mL/K/day was achieved, always using breast milk when possible. Material and methods: The present study sought to compare results before and after this new policy. For this work, we review all premature babies between 30-34 weeks of gestation in two time periods, the first from 01/01/2010 to 12/31/2017 and the second from 01/01/2018 to 08/15/2022. The number of cases with and without parenteral fluids (PF), the incidence of infection, the weight at admission and discharge, and the change in the weight Z score between birth and discharge were compared. Both the anthropometric and outcome variables were compared using the different statistical methods according to each variable. Results: were found 920 cases with the described characteristics. The groups before and after the intervention did not show significant differences in their general demographic characteristics. We observed a decrease use of PF in the second period, from 425 cases (82.0%) before to 297 (26.2%) after implementation, p <0.0001 and fewer days of use (4.1 days/average before vs 1.3 after, p <0.0001) of PF. The weight at discharge and the change in weight Z-score were the same in both groups. Infections went from nine cases before to two cases after but it was not statistically significant. There were no complications due to less use of PF. Discussion: This study showed that the use of PF is not associated with significant changes in outcomes of interest, which reinforces that its use does not generate any benefit for the patient. Larger number of cases is required to detect differences in low incidence events such as infections.

Very little is known about laboratory confirmed blood stream infections (LCBIs) in neonatal intensive care units (NICUs) in resource-limited settings. The aim of this cohort study was to determine the incidence, risk factors, and causative agents of LCBIs in a level-2 NICU in India. The diagnosis of LCBIs was established using the Centre for Disease Control, USA criteria. A predesigned questionnaire containing risk factors associated with LCBIs was filled-in. A total of 150 neonates (43% preterm) were included in the study. The overall incidence of LCBIs was 31%. The independent risk factors for LCBIs were: preterm neonates (relative risk (RR) 2.23), duration of NICU stay more than 14 days (RR 1.75), chorioamnionitis in the mother (RR 3.18), premature rupture of membrane in mothers (RR 2.32), neonate born through meconium-stained amniotic fluid (RR 2.32), malpresentation (RR 3.05), endotracheal intubation (RR 3.41), umbilical catheterization (RR 4.18), and ventilator-associated pneumonia (RR 3.17). The initiation of minimal enteral nutrition was protective from LCBIs (RR 0.22). The predominant causative organisms were gram-negative pathogens (58%). The results of the present study can be used to design antibiotic interventions to reduce LCBIs in resource-limited settings.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

We present the case of a 35-year-old male with first degree family history of gastric cancer (father diagnosed at the age of 45), that was presumed to have gastric cancer himself when evaluating the features of his upper endoscopy performed after hematemesis. Surprisingly, no cancer cells were found in the biopsies. Thanks to a different diagnostic suspicion subsequent to performing a full clinical history, a more favorable diagnosis was reached: gastric syphilis.

Mesothelioma of the peritoneum is the second most prevalent type. The peritoneum, the membrane lining the abdomen and abdominal organs, is affected in this type of cancer. A common risk factor is exposure to asbestos. There isn’t a cure, but surgery, chemotherapy, and palliative care can improve your prognosis and quality of life. Here we present a case of a 47-year-old female with peritoneal mesothelioma.

Abstract The number of non-melanoma skin cancers (NMSC) removed from Australians is increasing every year. The number of deaths from NMSC is increasing but so is the population. However, the population has greatly changed with many people at low risk for skin cancer migrating to Australia. The death rate from NMSC for the entire population and susceptible populations since 1971 is examined in this article. Materials and methods Data on the Australian population was obtained from the Australian Bureau of Statistics (ABS). Every five years a census is held in Australia and detailed information of the population is provided. The ABS also provided yearly data on the causes of death in Australia. Results The total population increased from 12,755,638 in 1971 to 25,738,140 in 2021. However, the susceptible population increased by far less, from 12,493,780 to 19,773,783. The number of deaths from NMSC increased from 143 to 765. The crude death rate for the susceptible population increased for 1.1 per 100,000 to 3.9 per 100,000. The crude death rate in the susceptible population aged 65 or more increased from 9.4 to 18.2 per 100,000. Conclusion Deaths from NMSC are increasing despite public health campaigns to prevent skin cancer. On current trends, NMSC will cause more deaths than melanoma in Australia.

The Fractal Analysis of Medical Images is an investigation field in those that numerous results of important value have been obtained. This work describes the basic foundations of the Fractal Analysis and its application has more than enough medical images, leaning on in five scientific investigations.

N6-methyladenosine (m6A) is an RNA modification wherein N6-position of adenosine is methylated. It is one of the most prevalent internal modifications on RNA and regulates various aspects of RNA metabolism. M6A is deposited by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which modulate splicing, export, translation and stability of the modified mRNA. Recently evidence suggests that various classes of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), circular RNAs (circRNAs), and long con-coding RNAs (lncRNAs) are also targeted by this modification. Depending on the ncRNA species, m6A may affect processing, stability, or localization of these molecules. The m6A modified ncRNAs are implicated in a number of diseases including cancer. In this review, I summarize the role of m6A modification in the regulation and function of ncRNAs in tumor development. Moreover, the potential applications in cancer prognosis and therapeutics is discussed.

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.

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.

Background: The interruption of the activity of the population-based organized colorectal cancer (CRC) screening programs due to the COVID pandemic may have affected their results in terms of detection of preneoplastic lesions and CRC. We evaluated the impact of the COVID pandemic on the delays, participation, adherence to colonoscopies, lesions detected, and CRC stage at di-agnosis in a CRC screening program. Methods: We analyzed all the invitations between January 1, 2019, and December 31, 2021. We defined the pandemic period as the period after March 12, 2020. We calculated the delay intervals (successive and all rounds), the rates of participation, adherence to colonoscopy after a positive fecal immunochemical test (FIT), and the diagnostic yield of colonoscopy, specifically CRC and colorectal neoplasia (CRC and/or adenoma), as well as CRC stage at diagnosis. Results: In the period analyzed, 976,187 invitations were sent (61.0% pandemic), 439,687 FIT were returned (62.4% pandemic) and 23,092 colonoscopies were performed (59.1% pandemic). Colon-oscopies were normal in 7,378 subjects (32.4%) and a CRC was detected in 916 subjects (4.0%). In successive rounds, the delay increased significantly seven months during the pandemic period (p<0.001). In all the invitations, the delay from the invitation to the colonoscopy increased sig-nificantly by 8 days (p<0.001). Once adjusted for the confounding variables, participation in the screening program increased significantly (OR=1.1; 95% CI=1.09-1.11), with no changes in the adherence to colonoscopy (OR=0.9; 95% CI=0.8-1.0). We found no differences in the diagnostic yield of colonoscopy in terms of CRC (OR=0.90; 95% CI=0.78-1.02) or colorectal neoplasia (OR=0.98; 95% CI=0.92-1.03) detection. Finally, we found no differences in CRC stage at diagnosis (p=0.2). Conclusions: Although the interruption of the CRC screening program due to the COVID pan-demic increased the delays, it did not reduce participation, adherence to colonoscopy, or the di-agnostic yield of colonoscopy.

Abstract: Background and Objectives: A growing number of epidemiologic studies have found that diabetes mellitus may increase cancer risk and is implicated in numerous other metabolic and inflammatory disorders. The increase in pro-inflammatory cytokines plays a major role in insulin resistance and leads to hypoalbuminemia, and micro- and macrovascular diabetes complications, including kidney disease and anemia. This study aimed to investigate the utility of CEA, CRP, serum albumin level, hemoglobin, and LDH as biomarkers for cancer risk and the biological implications of diabetes on the evolution and prognosis of oncological patients. Material and methods: We conducted a retrospective, longitudinal, observational study, on a total group of 434 patients, 217 diagnosed with a form of cancer and with type 2 diabetes as a comorbidity, and the other 217 – control group, without diabetes. These patients were admitted to the oncology clinic. In subgroups, the same number of patients was considered, depending on the location of the oncological pathology. Anemia, hypoalbuminemia, elevated lactate dehydrogenase, glycated hemoglobin, and C-reactive protein levels are more pronounced in subjects with type 2 diabetes and cancer. Conclusions: The presence of diabetes negatively affects the clinical and biological prognosis of cancer patients.

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug. Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. Additionally, the interplay between hereditary variations and acquired mutations in the EGFR pathway remains unknown. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic effectiveness, considering their interaction with the EGFR pathway mutations. In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1 and MTHFR polymorphisms are independent indicators of a poor prognostic, irrespective of EGFR pathway mutations. BRAF V600E wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYD rs1801265, ABCB1 rs1045642 and MTHFR rs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of EGFR pathway mutations.

Backgound: Exosomes are extracellular nanovesicles, carriers of different biomolecules such as lipids, proteins, nucleic acids. Their composition and the fact that their release dramatically increases in case of tumorigenesis, opens different scenarios on the possible application in the research for new biomarkers.Methods: The most widely applied methodologies include ultracentrifugation techniques, size-based techniques, immunoaffinity capture-based techniques (mainly ELISA) and precipitation. To optimize the acquisition of exosomes from the reference sample, more techniques can be applied in sequence for a single extraction, determining an increase in labor time and costs. Results: The analysis of PSA-expressing exosomes provides an incredibly accurate way to discriminate between healthy patients and those with prostate disease. Specifically, IC-ELISA alone method achieved 98.57% sensitivity and 80.28% specificity in discriminating prostate cancer (PC) from benign prostatic hyperplasia (BPH).An immunocapture-based ELISA assay was performed to quantify and characterize carbonic anhydrase (CA) IX expression in exosomes. The results revealed that CA IX positive exosomes were 25-fold higher in plasma samples from PC patients than in those from healthy control. Conclusions: The analysis of PC-linked exosomes represents a promising diagnostic model that can effectively distinguish patients with PC from those with non-malignant prostatic disease, However, the use of exosome analysis in clinical practice is currently limited by several issues, including a lack of standardization in the analytical process and high costs, which are still too high for a large-scale use.

Topoisomerases, common targets for anti-tumor therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effect of thiosemicarbazones (TSC) and metal-TSC complexes has been demonstrated by targeting several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition. The processes by which metal-TSCs or TSCs inhibit topoisomerases are still being studied. In this brief review, we summarize the TSCs and metal-TSCs that inhibit various types of human topoisomerases.

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.

Transglutaminase 2 (TG2) is a critical cancer cell survival factor that activates several signaling pathways to foster drug resistance, cancer stem cell survival, metastasis, inflammation, epithelial mesenchymal transition, and angiogenesis. All-trans retinoic acid (ATRA) and chemotherapy have been the standard treatments for acute promyelocytic leukemia (APL), but clinical studies have shown that arsenic trioxide (ATO), alone or in combination with ATRA, can improve outcomes. ATO exerts cytotoxic effects in a variety of ways by inducing oxidative stress, genotoxicity, altered signal transduction, and/or epigenetic modification. In the present study, we showed that ATO increased ROS production and apoptosis ratios in ATRA-differentiated NB4 leukemia cells and that these responses were enhanced when TG2 was deleted. The combined ATRA+ATO treatment also increased the amount of nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor, an adaptive regulator of cellular oxidative stress response, and proteolytic activity of calpain, resulting in TG2 degradation and reduced survival of WT leukemia cells. We further showed that upon ATO treatment, the induced TG2 protein expression was degraded in the MCF-7 epithelial cell line, and primary peripheral blood mononuclear cells, thereby sensitizing these cell types to apoptotic signals.

Selectins are responsible for the early stages of cell migration as they control cell adhesion. They make the microenvironment permissive for metastatic events by promoting the activation of other cell adhesion molecules (CAMs). We employed several robust bioinformatics tools to evaluate gene sequence; single nucleotide polymorphisms (SNPs) in intronic and UTR regions; and missense SNPs with amino acid change in L-selectin (SELL), E-selectin (SELE), P-selectin (SELP) and PSGL-1 (SELPLG). We demonstrated that gene polymorphisms rs2229569, rs1131498, rs4987360, rs4987301 and rs2205849; polymorphisms rs3917777, rs2205894 and rs2205893 of SELP gene; rs7138370, rs7300972 and rs2228315 variants of SELPLG gene; and rs1534904 and rs5368 polymorphisms of SELE gene may produce important alterations in the DNA structure and consequent alterations in the morphology and function of the corresponding proteins. These Selectin polymorphic variants deserve further investigation in cancer patients, as they may become useful clinical markers for risk determination, diagnostic and prognostic biomarkers or even targets for targeted therapies.

Background: Metformin is a drug used to treat patients with type 2 diabetes, especially those who suffer from obesity. It is also used in the treatment of women with polycystic ovary syndrome (PCOS). This disease has been shown to be related to insulin resistance and multiplied blood sugar ranges. Further, it has been found that the use of metformin improves the menstrual cycles and ovulation rates of these women. Methods: A structured questionnaire will be conducted to determine the prevalence of breast cancer among women using metformin in the Ha’il region. Result: Incidence of breast cancer among women using metformin in the Ha’il region is very low. Conclusions: According to previous findings, metformin has been linked to lower breast cancer risk in women with type 2 diabetes. Furthermore, the findings of this study have corroborated the literature for the same by indicating that there is a substantial connection between metformin use and a lower risk of breast cancer in women with type 2 diabetes

Regardless of the advances in our ability to detect early and treat breast cancer, it is still one of the common types of malignancy worldwide, with the majority of patients decease upon metastatic disease. Nevertheless, due to these advances, we have extensively characterized the drivers and molecular profiling of breast cancer and further dividing it into subtypes. These subgroups are based on immunohistological markers (Estrogen Receptor-ER, Progesterone Receptor-PR and Human Epidermal Growth Factor Receptor 2-HER-2) and transcriptomic signatures, with distinct therapeutic approaches and regiments. These therapeutic approaches include targeted therapy (HER-2+), endocrine therapy (HR+) or chemotherapy (TNBC) with optional combination radiotherapy, depending on clinical stage. Technological and scientific advances in the identification of molecular pathways that contribute to therapy-resistance and establishment of metastatic disease, have provided the rationale for revolutionary targeted approaches against Cyclin-Dependent Kinases 4/6 (CDK4/6), PI3 Kinase (PI3K), Poly ADP Ribose Polymerase (PARP) and Programmed Death-Ligand 1 (PD-L1), among others. In this review, we focus on the comprehensive overview of epidemiology and current standard of care treatment of metastatic breast cancer, along with ongoing clinical trials. Towards this goal, we utilized available literature from PubMed and ongoing clinical trial information from clinicaltrials.gov to reflect the up to date and future treatment options for metastatic breast cancer.

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.

Background: ethical issues that arise during the care of a pregnant woman with cancer are challenging to physicians, policymakers, lawyers, and the bioethics community. This article is restricted to a discussion of ethical dilemmas and controversial case reports, mainly focused before the third trimester of pregnancy, when a conflict could exist between cancer and pregnancy outcomes.Methods: published literature was retrieved through searches in PubMed or Medline, CINAHL, the Cochrane and Google Academic in April 2020, using appropriate controlled keywords (cancer, neoplasm, pregnancy, ethics). Results were restricted to review articles, ethical perspectives, clinical practice guidelines and case-based teaching guides.Discussion: when a conflict arises in the maternal-foetus dyad, like the one related with cancer treatment and the risk of foetal demise, a range of ethical frameworks might be useful to consider in the decision-making process. Pragmatic theoretical approaches include case-based analysis, ethics of care, feminist theory, and traditional ethical principlism using the framework of autonomy, beneficence, non-maleficence, and justice. Also, societal and practitioner values could add value and an ethics consultation may be helpful to mediate conflict resolution. The physician must balance autonomy and beneficence-based obligations to the pregnant woman with cancer, along with beneficence-based obligations to the foetus.Conclusions: ethical challenges have received less attention in the literature, particularly before the third trimester of pregnancy. Best, unbiased and balanced information must be granted both to the patient and to the family, regarding the benefits and harms for the woman herself as well as for the foetal outcome.

PDEF is expressed in luminal epithelial cells of the prostate gland and associates with luminal phenotype. Hippo pathway regulates cell growth/proliferation, cellular homeostasis, and organ development by modulating phosphorylation of its downstream effectors. In previous studies, we observed decreased levels of PDEF during prostate cancer progression. In the present studies, we evaluated the effects of PDEF on total and phospho (Ser-127)YAP1 protein(a downstream effector of the Hippo pathway) levels in PC3 cells, a line of castrate resistant prostate cancer. We observed that the expression of PDEF in PC3 cells resulted in increased increased phospho(Ser127) -YAP1 protein levels. Our immunofluorescence analysis for YAP1 revealed an increased cytoplasmic/nuclear ratio of YAP1 in PDEF-PC3 cells as compared to VC-PC3 cells, suggesting PDEF may play a critical role in modulating YAP1 phosphorylation, and by extension in the regulation of the Hippo pathway. We also observed a decrease in YAP1 protein levels in prostate cancer tissues as compared to normal prostate tissues. Our analysis of multiple publicly available clinical cohorts revealed a gradual decrease in YAP1 mRNA expression during prostate cancer progression and metastasis. This decrease was similar to the decrease in PDEF levels which we reported earlier. In addition we observed further decreased in PDEF and YAP1 expression in Neuro-Endocrine Prostate Cancer (NEPC), and a direct correlation between PDEF and YAP1 expression. To the best of our knowledge, these results provide the first demonstration of modulation of YAP1 by PDEF in any system and suggest a cross-talk between PDEF and the Hippo pathway.

With the continuous progress in modern medicine, the early detection rate of gastric cancer has increased, and the mortality rate has decreased. However, gastric cancer remains the third leading cause of cancer-related death worldwide, with a high recurrence rate. Metastasis is the leading cause of death and recurrence of gastric cancer, which greatly hinders treatment success. Cancer development is a complex process involving multiple sequential steps. In the metastatic cascade, local invasion may be considered an initial, crucial step in the development of a malignant tumor, which leads to distant metastasis. Epithelial-mesenchymal transformation (EMT) is one of the most important developmental processes that occur during tumor invasion. EMT confers certain basic abilities to cancer cells, such as migration, invasion and anti-apoptotic ability, thus initiating and increasing metastasis. However, little is known about the molecular mechanisms that promote EMT and gastric cancer cell metastasis. A number of recent studies have found that circular RNAs（circRNAs）are associated with gastric cancer EMT, regulating the EMT process and promoting the occurrence and development of tumors. Because of their unique continuous circular structure, circRNAs have relatively high stability in plasma and cells, making them more suitable as diagnostic biomarkers in malignant tumors. Therefore, understanding the mechanism of circRNAs in EMT in gastric cancer is an important research direction to actively prevent tumor metastasis and improve the therapeutic effect on advanced malignant tumors.

Background: Peroxiredoxins (Prxs) comprise antioxidant factors that are widely found in prokaryotes and eukaryotes. Abnormal expression of Prxs is closely related to tumorigenesis. Methods: This study examined the prognostic value and expression of Prxs in lung cancer by Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier Plotter, cBioPortal and Functional Enrichment Analysis Tool (FunRich) databases. Results: We found that Prx1/2/3/4/5 were overexpressed in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) relative to normal lung cells. However, the expression level of Prx6 was lower in LUAD and higher in LUSC than normal lung cells. The level of Prx3 and Prx6 were associated with pathological stage. Prognostic analysis showed that elevated Prx1 and Prx2 expression were correlated with low Overall Survival (OS), whereas high Prx5 and Prx6 expression level predicted high OS. Conclusions: Our results effectively revealed the level of Prxs in lung cancer and its influence on the prognosis of lung carcinoma, contributing to the study of the role of Prxs in tumorigenesis.

With the advancement of next generation sequencing in past several years, a rising number of non-coding RNAs have been found as new actors to regulate gene expression. Non-coding RNAs not only play important roles in carcinogenesis, but also affect the clinical treatment strategies. They have been proved to be deeply correlated with chemoresistance in several cancers. Ovarian cancer is the leading cause of death in gynecological malignancy, with low 5-year survival rate. Most patients are identified when they have late-stage disease. This review mainly makes a compilation of the most relevant research literature in this field with the purpose of shedding light on the relation between ncRNAs and chemoresistance in ovarian cancer.