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Bladder cancer (BC) is the most common malignant tumor of the genitourinary system. The age of individuals diagnosed with BC tends to decrease in recent years. A variety of standard therapeutic options are available for the clinical management of BC, but limitations exist. It is difficult to surgically eliminate small lesions, while radiation and chemotherapy damage normal tissues, leading to severe side effects. Therefore, new approaches are required to improve the efficacy and specificity of BC treatment. Synthetic biology is a field emerging in the last decade that refers to biological elements, devices, and materials that are artificially synthesized according to users' needs. In this review, we discuss how to utilize genetic elements to regulate BC-related gene expression periodically and quantitatively to inhibit the initiation and progression of BC. In addition, the design and construction of gene circuits to distinguish cancer cells from normal cells to kill the former but spare the latter are elaborated. Then, we introduce the development of genetically modified T cells for targeted attacks on BC. Finally, synthetic nanomaterials specializing in detecting and killing BC cells are detailed. This review aims to describe the innovative details of the clinical diagnosis and treatment of BC from the perspective of synthetic biology.

Introduction : Recently increasing evidence has suggested that obesity is associated with the development and prognosis of renal cell carcinoma. The aim of the study was to investigate the association between different obesity measurements and overall survival in patients with surgically treated clear cell renal cell carcinoma. Patients and Methods : The data of 342 consecutive patients who underwent radical or partial nephrectomy at Peking University People's Hospital from January 2009 to November 2014 were retrospectively reviewed. Median follow-up was 82 months. The association between different obesity measurements and overall survival was evaluated using the Kaplan-Meier method and Cox regression models. Results : In univariate Cox regression analyses, perirenal fat accumulation was significantly associated with overall survival (HR: 2.271; 95%CI: 1.311-3.935; p=0.003), as well as age, sex, clinical manifestation, surgical option, tumor size and grade. The other obesity measurements, including body mass index, waist circumference, total adipose tissue, visceral adipose tissue and percentage of visceral adipose tissue, were not assessed as prognostic indicators of overall survival in this study (p>0.05). After adjusting for age, sex, clinical manifestation, surgical option, tumor size, T stage and tumor grade, perirenal fat accumulation was still identified as an independent predictor of overall survival (HR: 2.264; 95%CI: 1.305-3.926; p=0.004). The results of Kaplan-Meier model also revealing that patients with higher percentage of perirenal fat showed poorer overall survival (p=0.003). Conclusion : Higher percentage of perirenal adipose tissue is independently associated with increased mortality risk in surgically treated clear cell renal cell carcinoma. MicroAbstract : The association between obesity and the prognosis of ccRCC patients is conflicting. Herein we conducted this study to examine the association between different obesity measurements and overall survival in patients with surgically treated ccRCC. In total, 342 patients with ccRCC were enrolled. The results indicate that the percentage of perirenal adipose tissue is superior to both BMI and percentage of visceral fat surface area for predicting overall survival.

Background Regional anesthesia appears to reduce cancer recurrence, but the optimal anesthesia modality for non-muscle invasive bladder cancer (NMIBC) were still under debate. Therefore, we sought to assess the effect of regional and GA only upon the recurrence and long-term prognosis of NMIBC through this meta-analysis. Methods We performed an extensive literature search of PubMed, Embase, Web of Science, the Cochrane Library and China National Knowledge Infrastructure (up to October 30, 2022) to identify eligible articles on the possible impact of different anesthetic modalities for the recurrence rate of NMIBC. Results Eight studies comprising 3764 participants, including 2117 subjects with RA and 1647 with GA, were finally enrolled. Cancer recurrence rate was significantly lower in subjects with RA than those with GA. (RR 0.84, 95%CI 0.72–0.98, P = 0.031). Significant differences were not detected between GA and RA in the time of recurrence (SMD 2.07, 95% CI -0.49-4.64, P = 0.113) and cancer progression (RR 1.14, 95%CI 0.71–1.84, P = 0.589). Results from subgroup analysis demonstrated that spinal anesthesia could significantly decrease the incidence of cancer recurrence in comparison with general anesthesia (RR 0.80, 95%CI 0.72–0.88, P

To explore factors associated with decision regret after cystectomy among Chinese bladder cancer patients.This cross-sectional study involved 112 patients, who had received radical bladder cancer resection. Participants were recruited from August 2021 until January 2022. The decision regret scale (DRS), decision conflict scale (DCS), and the Functional Assessment of Cancer Therapy-Bladder cancer (FACT-BL) form were used to measure decision regret, decision conflict, and quality of life. Investigator-designed items further explored perceptions involved in decision-making participation and outcomes.The average score for decision regret was 26.21 (SD 15.886), while decision conflict was 20.27 (SD 13.375) and quality of life was 94.74 (SD 20.873). 57.1% of our participants had a little knowledge about the quality of life of patients who chose an alternate urinary diversion method; however, only 13.4% reported having a clear understanding. In addition, 8.9%, 26.8%, and 36.6% thought that quality of life related to alternate decisions was poor, average, or good, respectively. Multiple regression analysis suggested that decision regret is associated with decision conflict, quality of life, and the perceptions that others (who took alternate urinary diversion decisions) had a better quality of life.Decision regret is common among Chinese bladder cancer patients, after cystectomy. The prevalence of regret appears to be much higher in Chinese bladder cancer patients compared to similar studies from other regions. Decisions in mainland China are often made by the treating physician or by family members which may cause more profound regret. However, education and economic status are positively related to higher levels of regret which creates questions around knowing, participation, and expectations, which must be explored.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Even with complete tumor resection and adjuvant therapies, the prognosis of patients with ACC remains unsatisfactory. In the microtumor environment, the impact of a disordered immune system and abnormal immune responses is enormous. To improve treatment, novel prognostic predictors and treatment targets for ACC need to be identified. Hence, credible prognostic biomarkers of immune-associated genes (IRGs) should be explored and developed.We downloaded RNA-sequencing data and clinical data from The Cancer Genome Atlas (TCGA) data set, Genotype-Tissue Expression data set, and Gene Expression Omnibus data set. Gene set enrichment analysis (GSEA) was applied to reveal the potential functions of differentially expressed genes.GSEA indicated an association between ACC and immune-related functions. We obtained 332 IRGs and constructed a prognostic signature on the strength of 3 IRGs (INHBA, HELLS, and HDAC4) in the training cohort. The high-risk group had significantly poorer overall survival than the low-risk group (p .001). Multivariate Cox regression was performed with the signature as an independent prognostic indicator for ACC. The testing cohort and the entire TCGA ACC cohort were utilized to validate these findings. Moreover, external validation was conducted in the GSE10927 and GSE19750 cohorts. The tumor-infiltrating immune cells analysis indicated that the quantity of T cells, natural killer cells, macrophage cells, myeloid dendritic cells, and mast cells in the immune microenvironment differed between the low-risk and high-risk groups.Our three-IRG prognostic signature and the three IRGs can be used as prognostic indicators and potential immunotherapeutic targets for ACC. Inhibitors of the three novel IRGs might activate immune cells and play a synergistic role in combination therapy with immunotherapy for ACC in the future.

Background Immune checkpoint blockade (ICB) therapy has become a first-line treatment option for metastatic urothelial carcinoma (mUC) patients who do not meet the criteria of cisplatin. Still, only a few people can benefit from it, so useful predictive markers are needed. Methods Download the ICB-based mUC and chemotherapy-based bladder cancer cohorts, and extract the expression data of pyroptosis-related genes (PRG). The LASSO algorithm was used to construct the PRG prognostic index (PRGPI) in the mUC cohort, and we verified the prognostic ability of PRGPI in two mUC and two bladder cancer cohorts. Results Most of the PRG in the mUC cohort were immune-activated genes, and a few were immunosuppressive genes. The PRGPI composed of GZMB, IRF1, and TP63 can stratify the risk of mUC. In IMvigor210 and GSE176307 cohorts, the P-values of Kaplan Meier analysis was

Background Intratumoral fibrosis was positively correlated with histological grade of renal clear cell carcinoma (ccRCC) and intratumoral inflammation. However, the association of intratumoral fibrosis with the immune infiltration of ccRCC was few evaluated. Methods We used the second harmonic generation (SHG)-based imaging technology and evaluated the intratumoral fibrosis in ccRCC, and then divided the patients into the high fibrosis group (HF) and the low fibrosis group (LF). Meanwhile, the Kaplan–Meier survival curve analysis was performed to analyze the relationship between intratumoral fibrosis and the disease-free survival rate. Antibody arrays were used for seeking difference in cytokines and immune infiltration between the HF group (N = 11) and LF group (N = 11). The selected immune infiltration marker was then verified by immunohistochemistry (IHC) staining in 45 ccRCC samples. Results Out of 640 cytokines and immune infiltration markers, we identified 115 proteins that were significantly different in quantity between ccRCC and adjacent normal tissues. In addition, the Venn diagram indicated that six proteins, including Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), were significantly associated with intratumoral fibrosis (p p Conclusions The study indicated that the intratumoral fibrosis level was negatively correlated with the expression of CTLA4 in the tumor immune microenvironment of the ccRCC, which posed the potential value of targeting the stroma of the tumor, a supplement to immunotherapy. However, the specific mechanism of this association is still unclear and needs further investigation.

To identify key biomarkers in gemcitabine (GEM)-resistant bladder cancer (BCa) and investigate their associations with tumor-infiltrating immune cells in a tumor immune microenvironment, we performed the present study on the basis of large-scale sequencing data. Expression profiles from the Gene Expression Omnibus GSE77883 dataset and The Cancer Genome Atlas BLCA dataset were analyzed. Both BCa development and GEM-resistance were identified to be immune-related through evaluating tumor-infiltrating immune cells. Eighty-two DEGs were obtained to be related to GEM-resistance. Functional enrichment analysis demonstrated they were related to regulation of immune cells proliferation. Protein–protein interaction network selected six key genes (CAV1, COL6A2, FABP4, FBLN1, PCOLCE, and CSPG4). Immunohistochemistry confirmed the down-regulation of the six key genes in BCa. Survival analyses revealed the six key genes were significantly associated with BCa overall survival. Correlation analyses revealed the six key genes had high infiltration of most immune cells. Gene set enrichment analysis further detected the key genes might regulate GEM-resistance through immune response and drug metabolism of cytochrome P450. Next, microRNA-gene regulatory network identified three key microRNAs (hsa-miR-124-3p, hsa-miR-26b-5p, and hsa-miR-192-5p) involved in GEM-resistant BCa. Connectivity Map analysis identified histone deacetylase inhibitors might circumvent GEM-resistance. In conclusion, CAV1, COL6A2, FABP4, FBLN1, PCOLCE, and CSPG4 were identified to be critical biomarkers through regulating the immune cell infiltration in an immune microenvironment of GEM-resistance and could act as promising treatment targets for GEM-resistant muscle-invasive BCa.

Background During ureteroscopy, severe ureter straightness or contortion may occur before the stone is passed. Purpose To identify clinical factors associated with distal ureteral status below the ureteral calculi in patients before surgery. Material and Methods From October 2016 to March 2017, 101 patients with ureteral calculi who underwent ureteroscopic lithotripsy were reviewed. Patients who lacked clinical data and underwent preoperative indwelling ureteral stent placement were excluded. Univariate and multivariate analyses were performed to determine the clinical factors associated with intraoperative findings. Results A total of 101 patients were enrolled in the study (mean age = 54 years; mean stone size = 7.9 ± 4.5 mm). Overall, 25 of the 101 patients (24.7%) were diagnosed with poor distal ureteral status defined as intraoperative ureterostenosis or contortion resulting in a ureteroscope being unable to pass during the initial attempt. Univariate analysis showed significant differences in renal parenchyma thickness, ureteral wall thickening on imaging, and stone location (all, P Conclusion In conclusion, renal parenchyma thickness and ureteral wall thickening on imaging were associated with poor distal ureteral status. Therefore, patients with these predictive factors should undergo more intensive preparation before surgery.

Background The expression of Siglec-15, as a critical immune suppressor, in renal clear cell carcinoma (ccRCC) was few evaluated and remains unclear, especially in protein level. As previous studies reported, tumor fibrosis plays an essential role in assessing the prognosis of ccRCC, but the exact mechanism is not precise. This study evaluated the expression of Siglec-15, its role in prognosis, and the association with tumor fibrosis in ccRCC.Methods: Immunohistochemistry was used to analyze the Siglec-15 expression in one tissue microarray (cohort A, tumor: n=134, adjacent normal tissues: n=29). Subsequently, the mRNA expression of Siglec-15 and its clinical significance in ccRCC were analyzed using The Cancer Genome Atlas database (TCGA, cohort B, n = 534) and samples. Spearman correlation coefficients were calculated for correlation analysis of correlated expression genes of Siglec-15, and then functional annotation analysis was obtained with correlated expression genes. We detected the tumor fibrosis grade in cohort C (n=32) via second harmonic generation/two-photon excitation fluorescence. Results: Siglec-15 was overexpressed in tumor tissues compared with adjacent normal tissues in both cohort A (n=29, p0.05). Moreover, over-expression of Siglec-15 is associated with higher Fuhrman grade in cohort A＆C (n=166, p=0.001, OR=3.132, 1.563-6.275), cohort B (n=534, p=0.008, OR=1.606, 1.138-2.267). Univariate Kaplan-Meir survival analysis showed that patients with high Siglec-15 mRNA expression had shorter survival periods without significance in cohort B (p=0.073). Multivariate analysis employing the Siglec-15 regression model revealed that AJCC and Fuhrman grade was the only significant independent prognostic indicators. Besides, an inverse correlation was found between Siglec-15 protein expression and the tumor's fibrosis level (p = 0.02).Conclusions: Siglec-15 expression increases in ccRCC compared with adjacent normal tissues. Siglec-15 was frequently expressed and positively associated with pathology grade in ccRCC. This study indicated a significant role of Siglec-15 in the prognosis and immunotherapy target of ccRCC. This study also found an inverse correlation between Siglec-15 protein expression and the fibrosis level of the tumor.

Background Although androgen deprivation therapy (ADT) is the initial treatment strategy for prostate cancer (PCa), recurrent castration-resistant prostate cancer (CRPC) eventually ensues. In this study, cancer-derived immunoglobulin G (CIgG) is found to be induced after ADT, identifying CIgG as a potential CRPC driver gene. Methods The expression of CIgG and its clinical significance in PCa tissue was analyzed by The Cancer Genome Atlas database and immunohistochemistry. Subsequently, the sequence features of prostate cell line VHDJH rearrangements were analyzed. We also assessed the effect of CIgG on the migratory, invasive and proliferative abilities of PCa cells in vitro and vivo. Suspended microsphere, colony formation and drug-resistant assays were performed using PC3 cells with high CIgG expression (CIgGhigh ) and low CIgG expression (CIgG-/low ), and A nonobese diabetic/severe combined immunodeficiency mouse tumor xenograft model was developed for the study of the tumorigenic effects of the different cell populations. The SOX2-CIgG signaling pathway was validated by immunohistochemistry, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, Western blot, luciferase, and chromatin immunoprecipitation assays and bioinformatics analyses. Finally, we investigated the effect of RP215 inhibition on the progression of PCa in vivo using a Babl/c nude mouse xenograft model. Results CIgG is frequently expressed in PCa and associated with clinicopathological characteristics, moreover, CIgG transcripts with unique patterns of VHDJH rearrangements are found in PCa cells. Functional analyses identified that CIgG was induced by ADT and upregulated by SOX2 (SRY (sex determining region Y)-box 2) in PCa, promoting the development of PCa. In addition, our findings underscore a novel role of CIgG signaling in the maintenance of stemness and the progression of cancer through mitogen activated protein kinase/extracellular-signal-regulated kinase and AKT in PCa. In vivo experiments further demonstrated that depleting CIgG significantly suppressed the growth of PCa cell xenografts. Furthermore, a CIgG monoclonal antibody named RP215 exhibits tumor inhibitory effect as well. Conclusion Our data suggests that CIgG could be a driver of PCa development, and that targeting the SOX2-CIgG axis may therefore inhibit PCa development after ADT.

Sex determining region Y (SRY)-box 18 (SOX18) gene encodes transcription factors that have been recently confirmed to be overexpressed in various human types of cancer and maintain the malignant behavior of cancer cells. However, the role and its potential function in prostate cancer (PCa) has not been demonstrated and the mechanisms of SOX18 involved in tumor progression remain largely unclear. In the present study, the expression of SOX18 was analyzed in 98 PCa and 81 adjacent non-tumor tissues using immunohistochemistry. The data showed that SOX18 was overexpressed in 72 of 98 (73.5%) PCa tissues compared with that in 28 of 81 (34.6%) non-tumor tissues. In addition, the expression of SOX18 was related with the clinical features of patients with PCa. To explore the potential role of SOX18 in PCa cells, Cell Counting Kit-8 (CCK-8), migration, invasion and xenograft assays were performed. Our data showed that knockdown of SOX18 decreased the proliferation, migration and invasion of PCa cells in vitro, in addition to the tumor growth in vivo. Markedly, SOX18 knockdown caused the decreased expression of TCF1, c-Myc, cyclin D1 and MMP-7. In conclusion, SOX18 was overexpressed in PCa and may regulate the malignant capacity of cells via the upregulation of TCF1, c-Myc, cyclin D1 and MMP-7.

Analysis of tissue and cell lipidomics by LC/MS/MS. (DOCX 16 kb)

An increased risk of renal cell carcinoma (RCC) has been linked with obesity and metabolic syndrome. However, the mechanisms by which lipid metabolic disorders affect the development of RCC remain unclear and highly controversial. Integrin-linked kinase (ILK) is a serine/threonine protein kinase involved in the regulation of tumor cell growth and angiogenesis. In the present study, the effect of free fatty acids in the promotion of RCC progression was investigated by upregulating ILK. Results of the MTT assay indicated that treatment of 786-O cells with oleic acid induced a concentration-dependent increase in cell viability. Flow cytometry analysis revealed that the effect of oleic acid on cell apoptosis was not significant. Following treatment with oleic acid, the expression of ILK, phospho-Akt and G protein-coupled receptor 40 (GPR40) was increased in 786-O cells. These effects were reversed when the expression of ILK was downregulated using specific small interfering RNA. These results indicate that free fatty acids are associated with the development of renal cell carcinoma via activation of the GPR40/ILK/Akt pathway, revealing a novel mechanism for the correlation between metabolic disturbance and renal carcinoma.

To elucidate the glycoprotein non-metastatic melanoma protein B(Gpnmb) expression in clear-cell renal cell carcinoma (ccRCC) and to determine its potential prognostic relevance.A total of 12 pairs of ccRCC tissue specimens were collected from patients undergoing surgery in our hospital from March 2009 to March 2012. Gpnmb expression were determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for another 43 evaluable patients.The expression level of Gpnmb was significantly higher in metastatic ccRCCs than that in matched primary samples ((6.36±4.01) vs (3.14±2.38) scores, P=0.036). The high expression of Gpnmb was not affected by age, gender, clinical stage and pathological grade (all P0.05). Kaplan-Meier analysis disclosed significant differences in overall survival for patients with higher and lower average Gpnmb expression levels (P=0.020). Cox regression analysis revealed that a high Gpnmb protein expression level in the tumor cell could be identified as an independent poor prognostic marker of overall survival in ccRCC patients (P=0.049).Over expression of Gpnmb in tumour cell predicts a poor prognosis of patients with ccRCC.

It is widely accepted that immunoglobulin (Ig), the classical immune molecule, is extensively expressed in many cell types other than B-cells (non-B-IgG), including some malignant cells. The expression of Ig in malignant cells has been associated with a poor prognosis. In the present study, immunohistochemical analysis detected strong positive staining of IgG in three bladder cancer cell lines, the cancer cells in 77 bladder cancer patient samples and the cells in 3 cystitis glandularis tissue samples, while negative staining was observed in 4 specimens of normal transitional epithelial tissues. Importantly, functional transcripts of IgG with unique VHDJH rearrangement patterns were also found in bladder cancer cells. The knockdown of IgG in bladder cancer cell lines using small interfering RNA significantly inhibited the proliferation, migration and invasion of the cells. Notably, high IgG expression, as determined by immunostaining, was significantly correlated with a high histological grade and recurrence. The results of the present study suggested that IgG expression is involved in the malignant biological behavior and poor prognosis of bladder cancer. Therefore, IgG may serve as a novel target for bladder cancer therapy.

Glycoprotein nonmetastatic melanoma protein B is a type 1 transmembrane protein that has been recently found to play a role in cancer cell proliferation, angiogenesis, and invasion. Due to its potential responsibility in cancer aggressiveness, the main objective of this work was to investigate its expression in bladder cancer and the biological functions in bladder cancer cells. Using immunohistochemistry, western blot, and reverse transcription polymerase chain reaction, we analyzed the expression of glycoprotein nonmetastatic melanoma protein B in bladder cancer tissues and bladder cancer cell lines. The effects of glycoprotein nonmetastatic melanoma protein B on proliferation, migration, and invasion were tested after knocking down the glycoprotein nonmetastatic melanoma protein B in bladder cancer cells with small interfering RNAs by CCK-8, Transwell, and Matrigel assays. Our results showed that glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer tissues and cell lines. Downregulating glycoprotein nonmetastatic melanoma protein B could suppress the proliferation, migration, and invasion in bladder cancer cells. Glycoprotein nonmetastatic melanoma protein B expression was related to the poor differentiation and recurrence by immunohistochemistry analysis. The survival analysis also showed that glycoprotein nonmetastatic melanoma protein B was related to the patient prognosis. In conclusion, Glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer, which was related to the poor prognosis in bladder cancer patients. Glycoprotein nonmetastatic melanoma protein B promoted the proliferation, migration, and invasion in bladder cancer cells.

Current cancer therapies are largely reliant upon drugs and radiation that kill dividing cells or inhibit cell division in the primary tumor after radical surgery, whereas metastatic tumors should be more commonly the focus of targeted molecular therapies. Glycoprotein non‑metastatic melanoma protein B (Gpnmb) is expressed in various types of cancer, and promotes the migration, invasion and metastasis of tumor cells. Thus, it was hypothesized that a unique clear‑cell renal carcinoma (ccRCC) subclone expressing a high level of Gpnmb may metastasize more easily and thus be associated with poor prognosis. In the present study, the expression of Gpnmb was analyzed in primary and metastatic ccRCC samples, and the expression levels of Gpnmb were significantly higher in metastatic ccRCCs than in matched primary samples (P=0.036). Receiver operating characteristic (ROC) curve analysis was then performed to determine a cutoff score for Gpnmb expression in another 43 primary ccRCCs. For validation, the ROC‑derived cutoff score was subjected to an analysis of the association between Gpnmb expression and patient outcome/clinical characteristics. Kaplan‑Meier analysis demonstrated that elevated Gpnmb expression predicted a poorer overall survival (OS) in 43 cases of primary ccRCC. In addition, multivariate analyses revealed that Gpnmb expression served as an independent risk factor for ccRCC. Thus, the overexpression of Gpnmb identified patients at high risk and Gpnmb is a potential therapeutic molecular target for this type of tumor.

Integrin-linked kinase (ILK) localizes at focal adhesion sites, plays an important role in cell-matrix interactions and is involved in the regulation of tumor cell growth and migration. The aim of the present study was to clarify the functional characterization of ILK in prostate cancer (PCa) cells. ILK was shown to be overexpressed in 57.1% (36/63) of PCa samples and 18.2% (2/11) of benign prostatic hyperplasia (BPH) samples using immunohistochemical analysis. DU145 PCa cells knocked down for ILK were examined using western blot analysis, proliferation assay, flow cytometry and wound healing assay. Depletion of ILK significantly impaired cell growth and motility, induced apoptosis in vitro, and delayed xenograft tumor proliferation in nude mice, which were important for oncogenesis and tumor progression. Western blot analysis showed that Akt activity was attenuated in ILK‑depleted cells compared with the control cells. These results indicate that ILK knockdown attenuates the biological behavior of PCa cells by decreasing Akt activity, demonstrating that ILK is involved in the development and progression of PCa. Thus, ILK is suggested to serve as a potential therapeutic target for PCa.