LDHA-mediated M2-type macrophage polarization via tumor-derived exosomal EPHA2 promotes renal cell carcinoma progression.

Lactate dehydrogenase A (LDHA) is known to promote the growth and invasion of various types of tumors, affects tumor resistance, and is associated with tumor immune escape. But how LDHA reshapes the tumor microenvironment and promotes the progression of renal cell carcinoma (RCC) remains unclear. In this study, we found that LDHA was highly expressed in clear cell RCC (ccRCC), and this high expression was associated with macrophage infiltration, while macrophages were highly infiltrated in ccRCC, affecting patient prognosis via M2-type polarization. Our in vivo and in vitro experiments demonstrated that LDHA and M2-type macrophages could enhance the proliferation, invasion, and migration abilities of ccRCC cells. Mechanistically, high expression of LDHA in ccRCC cells upregulated the expression of EPHA2 in exosomes derived from renal cancer. Exosomal EPHA2 promoted M2-type polarization of macrophages by promoting activation of the PI3K/AKT/mTOR pathway in macrophages, thereby promoting the progression of ccRCC. All these findings suggest that EPHA2 may prove to be a potential therapeutic target for advanced RCC.

Intravesical Therapy for Upper Urinary Tract Urothelial Carcinoma: A Comprehensive Review.

Upper tract urothelial carcinoma (UTUC) poses unique challenges in diagnosis and treatment. This comprehensive review focuses on prophylactic intravesical therapy for UTUC, summarizing key aspects of intravesical therapy in various clinical scenarios, including concurrent with or following radical nephroureterectomy, kidney-sparing surgery, ureteroscopy-guided biopsy. The incidence of intravesical recurrence in UTUC after surgical treatment is significant, necessitating effective preventive measures. Intravesical therapy plays a vital role in reducing the risk of bladder recurrence following UTUC surgery. Tailoring timing, drug selection, dosage, and frequency is vital in optimizing treatment outcomes and reducing intravesical recurrence risk in UTUC. This review provides a comprehensive summary of the history, clinical trials, guideline recommendations, and clinical applications of intravesical therapy for UTUC. It also discusses the future directions based on current clinical needs and ongoing trials. Future directions entail optimizing dosage, treatment duration, and drug selection, as well as exploring novel agents and combination therapies. Intravesical therapy holds tremendous potential in improving outcomes for UTUC patients and reducing the risk of bladder recurrence. Although advancements have been made in UTUC treatment research, further refinements are necessary to enhance efficacy and safety.

Laparoendoscopic single-site radical nephrectomy for localized renal cancer: a descriptive research study with at least a 10-year follow-up.

Background: Laparoendoscopic single-site (LESS) surgery is performed to further narrow the incisions and reduce tissue injury. It has been more than10 years since the surgery was first described. However, there is still no report on the results of 10-year follow-up. This study evaluated the use of long-term oncology and the renal outcomes of LESS radical nephrectomy (LESS-RN) in the treatment of localized renal cancer. Methods: We retrospectively analyzed the clinical data of patients treated with LESS-RN at Changhai Hospital from 2009 to 2012. Patients with localized kidney cancer who were followed-up for at least 10 years were included in the study. The baseline data and major perioperative outcome variables were analyzed. Overall survival (OS) and cancer-specific survival (CSS) were calculated using the Kaplan-Meier method. Results: A total of 48 patients were included in the study, which had a median follow-up of 11 years (interquartile range, 10.7-11.8 years). The 10-year OS and CSS rates were 87.5% [42/48; 95% confidence interval (CI): 0.778-0.972] and 97.9% (47/48; 95% CI: 0.937-1.021), respectively. At the most recent follow-up, there were 5 patients with a chronic kidney disease stage ≥3. Among these 5 patients, 3 developed uremia and required continuous dialysis. Conclusions: For localized renal cancer, LESS-RN is safe and effective with excellent long-term oncology controllability and good functional outcomes. Prospective studies with large sample sizes need to be conducted to validate our results.

A novel thinking: DDR axis refines the classification of ccRCC with distinctive prognosis, multi omics landscape and management strategy.

Background: DNA damage response and repair (DDR) related signatures play an important role in maintaining genome stability and other biological processes. It also affects the occurrence, development, and treatment of cancer. However, in renal cell carcinoma (RCC), especially clear cell renal carcinoma (ccRCC), the potential association between DDR-related signatures and tumor heterogeneity and tumor microenvironment (TME) remains unclear. Methods: Utilizing unsupervised clustering algorithm, we divided RCC into two subgroups, DCS1 and DCS2, according to the differences in DDR gene expression, and compared the characteristics of the two subgroups through multiple dimensions. Results: Compared with DCS1, DCS2 patients have higher clinical stage/grade and worse prognosis, which may be related to active metabolic status and immunosuppression status. At the same time, the high mutation rate in DCS2 may also be an important reason for the prognosis. We also analyzed the sensitivity of the two subgroups to different therapeutic agents and established a subtypes' biomarkers-based prognostic system with good validation results to provide ideas for clinical diagnosis and treatment. Finally, we identified a pivotal role for DDX1 in the DDR gene set, which may serve as a future therapeutic target. Conclusion: This study showed that DDR has an important impact on the development and treatment of RCC. DCS2 subtypes have a poor prognosis, and more personalized treatment and follow-up programs may be needed. The assessment of DDR gene mutations in patients may be helpful for clinical decision-making. DDX1 may be one of the effective targets for RCC treatment in the future.

Photocatalytic Material-Microorganism Hybrid System and Its Application-A Review.

The photocatalytic material-microorganism hybrid system is an interdisciplinary research field. It has the potential to synthesize various biocompounds by using solar energy, which brings new hope for sustainable green energy development. Many valuable reviews have been published in this field. However, few reviews have comprehensively summarized the combination methods of various photocatalytic materials and microorganisms. In this critical review, we classified the biohybrid designs of photocatalytic materials and microorganisms, and we summarized the advantages and disadvantages of various photocatalytic material/microorganism combination systems. Moreover, we introduced their possible applications, future challenges, and an outlook for future developments.

A Prospective Study Comparing Cancer Detection Rates of Transperineal Prostate Biopsies Performed by Junior Urologists versus a Senior Consultant in a Real-World Setting.

INTRODUCTION: Prostate biopsy (PB) is a typical daily practice method for the diagnosis of prostate cancer (PCa). This study aimed to compare the PCa detection rates and peri- and postoperative complications of PB among 3 residents and a consultant. PATIENTS AND METHODS: A total of 343 patients who underwent PB between August 2018 and July 2019 were involved in this study. Residents were systematically trained for 2 weeks by a consultant for performing systematic biopsy (SB) and targeted biopsy (TB). And then, 3 residents and the consultant performed PB independently every quarter due to routine rotation in daily practice. The peri- and postoperative data were collected from a prospectively maintained database (www.pc-follow.cn). The primary outcome and secondary outcome were to compare the PCa detection rates and complications between the residents and consultant, respectively. RESULTS: There was no significant difference between the residents and consultant in terms of overall PCa detection rates of SB and TB or further stratified by prostate-specific antigen value and prostate imaging reporting and data system (PI-RADS) scores. We found the consultant had more TB cores (175 cores vs. 86-114 cores, p = 0.043) and shorter procedural time (mean 16 min vs. 19.7-20.1 min, p < 0.001) versus the residents. The complication rate for the consultant was 6.7% and 5%-8.2% for the residents, respectively (p = 0.875). CONCLUSIONS: The residents could get similar PCa detection and complication rates compared with that of the consultant after a 2-week training. However, the residents still need more cases to shorten the time of the biopsy procedure.

A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay.

Cell culture is important for the rapid screening of anti-cancer drug candidates, attracting intense interest. Traditional 2D cell culture has been widely utilized in cancer biological research. However, 3D cellular spheroids are able to recapitulate the in vivo microenvironment of tissues or tumors. Thus far, several 3D cell culture methods have been developed, for instance, the hanging drop method, spinner flasks and micropatterned plates. Nevertheless, these methods have been reported to have some disadvantages, for example, medium replacement is inconvenient or causes cellular damage. Here, we report on an easy-to-operate and useful micro-hole culture chip (SimpleDrop) for 3D cellular spheroid formation and culture and drug analysis, which has advantages over the traditional method in terms of its ease of operation, lack of shear force and environmentally friendliness. On this chip, we observed the formation of a 3D spheroid clearly. Three drugs (paclitaxel, cisplatin and methotrexate) were tested by both cell viability assay and drug-induced apoptotic assay. The results show that the three drugs present a similar conclusion: cell viability decreased over time and concentration. Moreover, the apoptotic experiment showed a similar trend to the live/dead cell assay, in that the fraction of the apoptotic and necrotic cells correlated with the concentration and time. All these results prove that our SimpleDrop method is a useful and easy method for the formation of 3D cellular spheroids, which shows its potential for both cell-cell interaction research, tissue engineering and anticancer drug screening.