The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways.

Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within the tumor microenvironment (TME) have deepened our understanding of the mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug resistance suggesting that targeting the TME could be a viable strategy to combat this issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, and angiogenesis, contribute to drug resistance could be a viable strategy to combat this issue. Overexpression of STAT3 is commonly associated with drug-resistant cancer cells or stromal cells. Current research often generalizes the impact of stromal cells on resistance, lacking specificity and statistical robustness. Thus, future research should take notice of this issue and aim to provide high-quality evidence. Despite the existing limitations, targeting the TME to overcome therapy resistance hold promising and valuable potential.

Relationship between clonal evolution and drug resistance in bladder cancer: A genomic research review.

Bladder cancer stands as a prevalent global malignancy, exhibiting notable sex-based variations in both incidence and prognosis. Despite substantial strides in therapeutic approaches, the formidable challenge of drug resistance persists. The genomic landscape of bladder cancer, characterized by intricate clonal heterogeneity, emerges as a pivotal determinant in fostering this resistance. Clonal evolution, encapsulating the dynamic transformations within subpopulations of tumor cells over time, is implicated in the emergence of drug-resistant traits. Within this review, we illuminate contemporary insights into the role of clonal evolution in bladder cancer, elucidating its influence as a driver in tumor initiation, disease progression, and the formidable obstacle of therapy resistance.

Preoperative blood-based nutritional biomarkers as significant prognostic factors after intravesical BCG therapy in patients with non-muscle-invasive bladder cancer.

The aim of this study was to investigate the prognostic role of blood-based nutritional biomarkers, including red blood cell (RBC count), hemoglobin (Hb), total protein (TP), albumin, the serum albumin to globulin ratio (AGR) and the prognostic nutritional index (PNI) in patients who underwent intravesical treatment for non-muscle invasive bladder cancer (NMIBC). A total of 501 NMIBC patients who received intravesical Bacillus Calmette-Guerin (BCG) treatment following transurethral resection of bladder tumor (TURBT) were included. The optimal cutoff values for these nutrition-based indicators were determined using receiver operating characteristic curve analysis. We observed a significantly higher recurrence-free survival (RFS) rate in patients with elevated levels of RBC count, Hb, TP, and albumin. Cox univariate and multivariate Cox regression analyses demonstrated that serum albumin (P = 0.002, HR = 0.51, 95%CI: 0.33-0.78), RBC count (P = 0.002, HR = 0.50, 95%CI: 0.32-0.77), TP (P = 0.028, HR = 0.62, 95%CI: 0.41-0.95), Hb (P = 0.004, HR = 0.53, 95%CI: 0.33-0.84), AGR (P = 0.003, HR = 0.46, 95%CI: 0.27-0.76) and PNI (P = 0.019, HR = 0.56, 95%CI: 0.35-0.91) were significant independent factors predicting RFS. These cost-effective and convenient blood-based nutritional biomarkers have the potential to serve as valuable prognostic indicators for predicting recurrence in NMIBC patients undergoing BCG-immunotherapy.

Unraveling links between aging, circadian rhythm and cancer: Insights from evidence-based analysis.

Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.

Focal ablation therapy presents promising results for selectively localized prostate cancer patients.

Due to its lower risk of consequences when compared to a radical approach, focal treatment is a viable and minimally invasive option for treating specific localized prostate cancer. Although several recent good non-randomized trials have suggested that focused therapy may be an alternative choice for some patients, additional high-quality evidence is needed before it can be made widely available as a conventional treatment. As a result, we have summarized the most recent findings from the 38th Annual European Association of Urology Congress, one of the most renowned annual conferences in the area of urology, regarding focal ablation therapy for patients with localized prostate cancer. Additionally, we also provided clinical trials in progress for researchers to better understand the current research status of this field.

Efficiency of transurethral en-bloc resection vs. conventional transurethral resection for non-muscle-invasive bladder cancer: An umbrella review.

BACKGROUND: En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist regarding the comparisons between ERBT and conventional transurethral resection of bladder tumor (cTURBT). METHODS: We conducted a comprehensive search in PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and performed manual searches of reference lists to collect and extract data. Data evaluation was carried out using Review Manager 5.4.0, Rx64 4.1.3, and relevant packages. RESULTS: There were nine eligible meta-analyses and nine eligible RCTs in our study. NMIBC patients undergoing ERBT were significant associated with a lower rate of bladder perforation and obturator nerve reflex compared to those receiving cTURBT. Our pooled result indicated that ERBT and cTURBT required similar operation time. Regarding postoperative outcomes, ERBT demonstrated superior performance compared to cTURBT in terms of detrusor muscle presence, catheterization time, and residual tumor. ERBT exhibited a higher rate of three-month recurrence-free survival (RFS) compared to those receiving cTURBT (p < 0.05; I2 = 0%). In bipolar subgroup, ERBT had a significant better 12-month RFS than cTURBT (p < 0.05; I2 = 0%). Simultaneously, the exclusion of Hybrid Knife data revealed a significant improvement in 12-month RFS associated with ERBT (p < 0.05; I2 = 50%). CONCLUSION: Using a combination of umbrella review and meta-analysis, we demonstrated that ERBT had better or comparable perioperative outcome and improved 3 and 12 month RFS than cTURBT. We suggest that ERBT maybe a better surgical method for patients with NMIBC compared with cTURBT.

Efficiency of bladder-sparing strategies for bladder cancer: an umbrella review.

Bladder preservation (BP) has emerged as a clinical alternative to radical cystectomy (RC) for alleviating the substantial physical and psychological burden imposed on localized bladder cancer patients. Nevertheless, disparities persist in the comparative evaluations of BP and RC. We aimed to address the disparities between BP and RC. An umbrella review and meta-analysis were conducted to explore these disparities. We extracted data from meta-analyses and randomized controlled trials (RCTs) selected after searching PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Review Manager 5.4.0 and R x64 4.1.3 were used to evaluate the collected data. Our study included 11 meta-analyses and 3 RCTs. In terms of progression-free survival, all the meta-analyses reported that patients with localized bladder cancer who underwent BP exhibited outcomes comparable to those who underwent RC. Meta-analyses regarding the outcomes of cancer-specific survival (CSS) and overall survival (OS) are controversial. To solve these issues, we conducted a pooled analysis of CSS data, which supported the similarity of CSS between BP and RC with no significant heterogeneity [odds ratio (OR): 1.2; 95% confidence interval (CI): 0.71-2.02; I2 = 26%]. Similarly, the pooled OS results extracted from three RCTs indicated the comparability of OS between BP and RC with no significant heterogeneity (OR: 1.12; 95% CI: 0.41-3.07; I2 = 33%). A combination of umbrella review and meta-analysis results suggested that BP had survival rates comparable to those of RC. We suggest that BP may be a more eligible therapy than RC for patients with localized muscle-invasive bladder cancer. This conclusion warrants further validation through randomized controlled trials.

A Prognostic Index Derived From LASSO-Selected Preoperative Inflammation and Nutritional Markers for Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: There is an urgent need to identify a robust predictor for BCG response in patients with non-muscle-invasive bladder cancer (NMIBC). We aimed to employ the Lasso regression model for the selection and construction of an index (BCGI) utilizing inflammation and nutrition indicators to predict the response to BCG therapy. METHODS: After acquiring the ethics approval, we searched the electric medical records in our institution and performed data screening. Then, we developed the BCGI using a Lasso regression model and subsequently evaluated its performance in both the train and internal test datasets through Kaplan-Meier survival curves and Cox regression analysis. Then, we also evaluated the prognostic value of BCGI alongside the EAU2021 model. RESULTS: The training dataset and internal test dataset contained 295 and 196 patients, respectively. Referring to the Lasso results, BCGI consisted of hemoglobin, albumin, and platelet count, which could significantly predict the recurrence of NMIBC patients who accepted BCG in train (P = .012) and test (P = .004) datasets. The BCGI also exhibited statistically prognostic value in no smoking history, World Health Organization high grade, and T1 subgroups, both in train and test datasets. In multivariable analysis, BCGI exhibited independent prognostic value in train (P = .012) and test (P = .012) datasets. Finally, we constructed a nomogram that consisted of smoking history, T stage, World Health Organization grade, tumor size, and BCGI. Then, BCGI demonstrated significant independent prognostic value in NMIBC patients treated with BCG, a result not observed with the EAU2021 score or classification. CONCLUSION: Based on the results, we reasonably suggest that BCGI may be a useful predictor for NMIBC patients who accepted BCG. Furthermore, we have demonstrated the efficacy of constructing a prognostic index using clinical factors and a Lasso regression model, a versatile approach applicable to various medical conditions.

A pan-cancer analysis of the oncogenic and immunological roles of transglutaminase 1 (TGM1) in human cancer.

BACKGROUND: There is currently a limited number of studies on transglutaminase type 1 (TGM1) in tumors. The objective of this study is to perform a comprehensive analysis across various types of cancer to determine the prognostic significance of TGM1 in tumors and investigate its role in the immune environment. METHOD: Pan-cancer and mutational data were retrieved from the TCGA database and analyzed using R (version 3.6.4) and its associated software package. The expression difference and prognosis of TGM1 were examined, along with its correlation with tumor heterogeneity, stemness, mutation landscape, and RNA modification. Additionally, the relationship between TGM1 expression and tumor immunity was investigated using the TIMER method. RESULTS: TGM1 is expressed differently in various tumors and normal samples and is associated with the overall survival and progression-free time of KIRC, ACC, SKCM, LIHC, and STES. In LICH, we found a negative correlation between TGM1 expression and 6 indicators of tumor stemness. The mutation frequencies of BLCA, LIHC, and KIRC were 1.7%, 0.3%, and 0.3% respectively. In BLCA and BRCA, there was a significant correlation between TGM1 expression and the infiltration of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells. CONCLUSION: TGM1 has the potential to serve as both a prognostic marker and a drug target.

An endothelial-related prognostic index for bladder cancer patients.

BACKGROUND: Within the tumor microenvironment, endothelial cells hold substantial sway over bladder cancer (BC) prognosis. Herein, we aim to elucidate the impact of endothelial cells on BC patient outcomes by employing an integration of single-cell and bulk RNA sequencing data. METHODS: All data utilized in this study were procured from online databases. R version 3.6.3 and relevant packages were harnessed for the development and validation of an endothelial-associated prognostic index (EPI). RESULTS: EPI was formulated, incorporating six genes (CYTL1, FAM43A, GSN, HSPG2, RBP7, and SLC2A3). EPI demonstrated significant prognostic value in both The Cancer Genome Atlas (TCGA) and externally validated dataset. Functional results revealed a profound association between EPI and endothelial cell functionality, as well as immune-related processes. Our findings suggest that patients with low-risk EPI scores are more likely to respond positively to immunotherapy, as indicated by immune checkpoint activity, immune infiltration, tumor mutational burden, stemness index, TIDE, and IMvigor210 analyses. Conversely, individuals with high-risk EPI scores exhibited heightened sensitivity to cisplatin, docetaxel, and gemcitabine treatment regimens. CONCLUSION: We have effectively discerned pivotal genes from the endothelial cell perspective and constructed an EPI for BC patients, thereby offering promising prospects for precision medicine.

Biological clock regulation by the PER gene family: a new perspective on tumor development.

The Period (PER) gene family is one of the core components of the circadian clock, with substantial correlations between the PER genes and cancers identified in extensive researches. Abnormal mutations in PER genes can influence cell function, metabolic activity, immunity, and therapy responses, thereby promoting the initiation and development of cancers. This ultimately results in unequal cancers progression and prognosis in patients. This leads to variable cancer progression and prognosis among patients. In-depth studies on the interactions between the PER genes and cancers can reveal novel strategies for cancer detection and treatment. In this review, we aim to provide a comprehensive overview of the latest research on the role of the PER gene family in cancer.

Natural products and derivatives in renal, urothelial and testicular cancers: Targeting signaling pathways and therapeutic potential.

BACKGROUND: Natural products have demonstrated significant potential in cancer drug discovery, particularly in renal cancer (RCa), urothelial carcinoma (UC), and testicular cancer (TC). PURPOSE: This review aims to examine the effects of natural products on RCa, UC and TC. STUDY DESIGN: systematic review METHODS: PubMed and Web of Science databases were retrieved to search studies about the effects of natural products and derivatives on these cancers. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: This review highlighted their diverse impacts on key aspects such as cell growth, apoptosis, metastasis, therapy response, and the immune microenvironment. Natural products not only hold promise for novel drug development but also enhance the efficacy of existing chemotherapy and immunotherapy. Importantly, we exert their effects through modulation of critical pathways and target genes, including the PI3K/AKT pathway, NF-κB pathway, STAT pathway and MAPK pathway, among others in RCa, UC, and TC. CONCLUSION: These mechanistic insights provide valuable guidance for researchers, facilitating the selection of promising natural products for cancer management and offering potential avenues for further gene regulation studies in the context of cancer treatment.

Establishment of novel ferroptosis-related prognostic subtypes correlating with immune dysfunction in prostate cancer patients.

Background: We aimed to identify two new prognostic subtypes and create a predictive index for prostate cancer (PCa) patients based on ferroptosis database. Methods: The nonnegative matrix factorization approach was used to identify molecular subtypes. We investigate the differences between cluster 1 and cluster 2 in terms of clinical features, functional pathways, tumour stemness, tumour heterogeneity, gene mutation and tumour immune microenvironment score after identifying the two molecular subtypes. Colony formation assay and flow cytometry assay were performed. Results: The stratification of two clusters was closely connected to BCR-free survival using the nonnegative matrix factorization method, which was validated in the other three datasets. Furthermore, multivariate Cox regression analysis revealed that this classification was an independent risk factor for patients with PCa. Ribosome, aminoacyl tRNA production, oxidative phosphorylation, and Parkinson's disease-related pathways were shown to be highly enriched in cluster 1. In comparison to cluster 2, patients in cluster 1 exhibited significantly reduced CD4+ T cells, CD8+ T cells, neutrophils, dendritic cells and tumor immune microenvironment scores. Only HHLA2 was more abundant in cluster 1. Moreover, we found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of C4-2B and DU145 cell lines. Conclusions: We discovered two new prognostic subtypes associated with immunological dysfunction in PCa patients based on ferroptosis-related genes and found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of PCa cell lines.

Identification of circadian clock-related immunological prognostic index and molecular subtypes in prostate cancer.

BACKGROUND: Evidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). METHODS: PCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis. RESULTS: TOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients. CONCLUSIONS: In this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice.

SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications - review article.

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore, which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, the authors comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis, and narrative summary. The authors also provided the top 10 predicted drugs targeting SKA3. The authors proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients.

Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF).

The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pan-cancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention.

Chronobiology of the Tumor Microenvironment: Implications for Therapeutic Strategies and Circadian-Based Interventions.

Numerous research works have emphasized the critical role that circadian rhythm plays in the tumor microenvironment (TME). The goal of clarifying chrono-pharmacological strategies for improving cancer treatment in clinical settings is a continuous endeavor. Consequently, to enhance the use of time-based pharmaceutical therapies in oncology, combining existing knowledge on circadian rhythms' roles within the TME is essential. This perspective elucidates the functions of circadian rhythms in the TME across various stages of cancer development, progression, and metastasis. Specifically, aging, angiogenesis, and inflammation are implicated in modulating circadian rhythm within the TME. Furthermore, circadian rhythm exerts a profound influence on current cancer treatments and thereby generates chronotheray to manage tumors. From a TME perspective, circadian rhythm offers promising opportunities for cancer prevention and treatment; nevertheless, further study is needed to address unanswered scientific problems.

Exploring the role of ADAMTSL2 across multiple cancer types: A pan-cancer analysis and validated in colorectal cancer.

BACKGROUND: Recent studies have established a correlation between ADAMTSL2 (ADAMTS-like 2) and the development of various cancers. This study aims to conduct a comprehensive pan-cancer analysis in 37 cancer types and investigate its potential role in colon and rectal adenocarcinoma (COADREAD). METHOD: Pan-cancer and mutation data were sourced from The Cancer Genome Atlas (TCGA) database and analyzed using Sangerbox analysis platform. We explored the expression patterns and prognostic implications of ADAMTSL2, and investigated its relationships with tumor heterogeneity, stemness, immune checkpoint genes, immune cell infiltration, RNA modifications, and mutational profiles across different cancers. Additionally, with Ethics Committee approval, we conducted immunohistochemical (IHC) analysis on 120 COADEAD samples to evaluate ADAMTSL2 expression and its association with clinicopathological parameters. RESULTS: ADAMTSL2 expression was positively correlated with the hazard ratio of OS, DSS, DFI and PFI for ESCA and COADREAD. A negative correlation was observed between ADAMTSL2 expression and NEO levels in COAD. Gene alterations in ADAMTSL2 were observed, with a mutation frequency of 5.0% in COAD. There is a significant correlation between ADAMTSL2 expression and immune cell infiltration in a variety of cancers. The expression level of ADAMTSL2 protein was associated with T stage, N stage, M stage (p < 0.05). Kaplan‒Meier survival curves demonstrated that the high ADAMTSL2 group had a shorter OS time (p = 0.047) and progression free survival time (p = 0.026) than the low ADAMTSL2 group. CONCLUSION: In summary, we conducted a comprehensive pan-cancer analysis of ADAMTSL2 and we demonstrated that ADAMTSL2 may serve as a novel prognostic biomarker and immunotherapy target in COADREAD.

Telemedicine-medical "snack community"-PHS ecosystem: Insights into the double-edged sword role of telemedicine in clinical practice and medical education during the COVID-19 pandemic and beyond.

Telemedicine has gained tremendous development during the COVID-19 pandemic. With deblocking and opening, telemedicine accelerates the evolvution of the medical "snack community" and undermines the perception of medical students and staff, which promotes the incidence of psychosocial-related disorders. Moreover, the inconsistent telemedicine adaptability between medical workers and patients aggravates the doctor-patient conflict due to the aging population and COVID-19 squeal. Telemedicine is colliding with the national healthcare system, whose synchronization with conventional medical service is crucial to coordinate the relationship among medical payment, patient privacy and qualifications of clinicians. This study puts more emphasis on the double-edged sword role of telemedicine in clinical practice and medical education during the COVID-19 pandemic and beyond. Overall, while telemedicine has demonstrated its utility in health care throughout the COVID pandemic, it is pretty critical to continue evaluating the efficacy and limitations of telemedicine in order to maintain equal access to medical service and high-quality medical education. A new concept as telemedicine-medical "snack community"-PHS ecosystem, where the psychological health education system and partners healthcare system with enough bandwidth, especially 5G technology, could optimize the effect of telemedicine on medical practice and education, is proposed.