RC48-Antibody-Drug Conjugate in Metastatic Urothelial Carcinoma: A Multicenter Real-World Study in China.

OBJECTIVES: RC48 is an antibody-drug conjugate (ADC) that targets HER2. In China, RC48 is approved for patients with HER-2-positive metastatic urothelial carcinoma (mUC) who have failed at least platinum-based chemotherapy. This study aimed to evaluate RC48 for mUC in a cohort of real-world patients. MATERIALS AND METHODS: We retrospectively collected data from 103 mUC patients from 12 centers between July 2021 and August 2023 in China. RC48 alone or with immunotherapy was administered until disease progression, intolerable toxicity, death, or other reasons. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of treatment-related adverse events (TRAEs) were evaluated. RESULTS: The median age of the patients was 68 years, and 68.0% were men. Twenty-nine (28.2%) patients received RC48 alone; 73 (70.9%) received RC48 combination therapy. The response rates were as follows: complete response in 2 (1.9%) patients, partial response in 50 (48.5%) patients, stable disease in 30 (29.1%) patients. The ORR was 50.5%. In patients with ≥80 years, Eastern Cooperative Oncology Group (ECOG) performance status ≥2 and creatinine clearance rate (CCr) <30 mL/min, the ORR was 75%, 48.6%, and 40.0%, respectively. The median PFS was 6 (3.9-8.1) months, and the median OS was not reached. The most reported TRAEs were peripheral sensory neuropathy (53.4%), alopecia (42.7%), asthenia (38.8%), decreased appetite (35.9%) and weight loss (35.9%) and TRAE did not increase in patients with poor condition or impaired renal function. CONCLUSION: Administration of RC48 for real-world patients is both effective and safe. mUC patients can benefit from RC48-based therapy, regardless of their poor condition or impaired renal function.

Association between family income to poverty ratio and nocturia in adults aged 20 years and older: A study from NHANES 2005-2010.

BACKGROUND: Nocturia, the most common lower urinary tract symptom (LUTS), significantly impacts socioeconomic factors and individuals' quality of life and is closely related to many diseases. This study utilized data from NHANES 2005-2010 to explore the relationship between family income to poverty ratio (PIR) and the presence of nocturia symptoms in adults aged 20 or older in the United States. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) in 2005-2010, including 6,662 adults aged 20 or older, were utilized for this cross-sectional study. The baseline data was used to display the distribution of each characteristic visually. Multiple linear regression and smooth curve fitting were used to study the linear and non-linear correlations between PIR and nocturia. Subgroup analysis and interaction tests were conducted to examine the stability of intergroup relationships. RESULTS: Out of the 6,662 adult participants aged 20 or older, 1,300 households were categorized as living in poverty, 3,671 households had a moderate income, and 1,691 households were classified as affluent. Among these participants, 3,139 individuals experienced nocturia, representing 47.12% of the total, while 3,523 individuals were nocturia-free, constituting 52.88% of the total population. After adjusting for all other covariates, it was found that PIR was significantly negatively correlated with nocturia (OR: 0.875, 95%CI: 0.836-0.916 P<0.0001). This trend persisted when PIR was divided into three groups (PIR <1, PIR 1-4, PIR > 4) or quartiles. There was a non-linear negative correlation between PIR and nocturia. CONCLUSION: Our findings indicated that lower PlR was associated with a higher risk of nocturia in adults aged 20 or older in the United States. These findings highlight the importance of considering socioeconomic factors in preventing and managing nocturia. Nonetheless, further exploration of the causal nexus between these factors was precluded due to the constraints of a cross-sectional design.

Low ACADM expression predicts poor prognosis and suppressive tumor microenvironment in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) represents a highly frequent renal cancer subtype. However, medium-chain acyl-CoA dehydrogenase (ACADM) encodes an important enzyme responsible for fatty acid ß-oxidation (FAO) and its association with prognosis and immunity in cancers has rarely been reported. Therefore, the present work focused on exploring ACADM's expression and role among ccRCC cases. We used multiple public databases and showed the hypo levels of ACADM protein and mRNA within ccRCC. Additionally, we found that ACADM down-regulation showed a remarkable relation to the advanced stage, high histological grade, as well as dismal prognostic outcome. As suggested by Kaplan-Meier curve analysis, cases showing low ACADM levels displayed shorter overall survival (OS) as well as disease-free survival (DFS). Moreover, according to univariate/multivariate Cox regression, ACADM-mRNA independently predicted the prognosis of ccRCC. In addition, this work conducted immunohistochemistry for validating ACADM protein expression and its prognostic role in ccRCC samples. KEGG and GO analyses revealed significantly enriched genes related to ACADM expression during fatty acid metabolism. The low-ACADM group with more regulatory T-cell infiltration showed higher expression of immune negative regulation genes and higher TIDE scores, which might contribute to poor response to immunotherapies. In conclusion, our results confirmed that downregulated ACADM predicted a poor prognosis for ccRCC and a poor response to immunotherapy. Our results provide important data for developing immunotherapy for ccRCC.

A risk model based on pyroptosis subtypes predicts tumor immune microenvironment and guides chemotherapy and immunotherapy in bladder cancer.

Although immunotherapy has revolutionized bladder cancer (BLCA) therapy, only few patients demonstrate durable clinical benefits due to the heterogeneity. Emerging evidence has linked pyroptosis to shaping tumor microenvironment (TME) and predicting therapy response. However, the relationship between pyroptosis and immunotherapy response in BLCA remains elusive. In this study, we performed a comprehensive bioinformatic analysis to dissect the role of pyroptosis in BLCA. Differentially expressed pyroptosis-related genes (DEPRGs) between tumor and normal tissues were identified using publicly available datasets. Kaplan-Meier analysis was performed to screen for DEPRGs associated with survival. Consensus clustering was used for BLCA subtyping. TME characteristics were evaluated by CIBERSORT, ESTIMATE and immune checkpoint genes (ICGs). Following univariate COX regression and LASSO analyses with pyroptosis-related DEGs, the risk model and nomogram were constructed with TCGA dataset and validated in the GEO dataset. Furthermore, therapeutic responses in high- and low-risk groups were compared using TIDE and GDSC databases. Two pyroptosis-related subtypes (Cluster 1 and 2) were identified based on expression patterns of GSDMA and CHMP4C. Bioinformatic analyses showed that cluster 1 had poor survival, more M0/M1/M2 macrophages, higher immune/stromal/ESTIMATE scores, and higher expression levels of ICGs. A 15-gene signature for predicting prognosis could classify patients into high- and low-risk groups. Furthermore, the correlation of risk scores with TIDE score and IC50 showed that patients in low-risk group were more sensitive to immunotherapy, whereas patients in high-risk group could better benefit from chemotherapy. Our study identified two novel pyroptosis-related subtypes and constructed a risk model, which can predict the prognosis, improve our understanding the role of PRGs in BLCA, and guide chemotherapy and immunotherapy.

Computational construction of TME-related lncRNAs signature for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma.

BACKGROUND: The tumor microenvironment (TME) is closely related to clear cell renal cell carcinoma (ccRCC) prognosis, and immunotherapy response. In current study, comprehensive bio-informative analysis was adopted to construct a TME-related lncRNA signature for immune checkpoint inhibitors (ICIs) and targeted drug responses in ccRCC patients. METHODS: The TME mRNAs were screened following the immune and stromal scores with the data from GSE15641, GSE29609, GSE36895, GSE46699, GSE53757, and The Cancer Genome Atlas (TCGA)-kidney renal clear cell carcinoma (KIRC). And the TME-related lncRNAs were recognized using correlation analysis. The TME-related lncRNAs prognostic model was constructed using the training dataset. Kaplan-Meier analysis, principal-component analysis, and time-dependent receiver operating characteristic were used to evaluate the risk model. The immune cell infiltration in TME was evaluated using the single-sample gene set enrichment analysis (ssGSEA), ESTIMATE, and microenvironment cell populations counter algorithm. The immunophenoscore (IPS) was used to assess the response to immunotherapy with the constructed model. RESULTS: In the current study, 364 TME-related lncRNAs were selected based on the integrated bioinformatical analysis. Six TME-related lncRNAs (LINC00460, LINC01094, AC008870.2, AC068792.1, and AC007637.1) were identified as the prognostic signature in the training dataset and subsequently verified in the testing and entire datasets. Patients in the high-risk group exhibited poor overall survival and disease-free survival than those in the low-risk group. The 1-, 3-, and 5-year areas under the curves of the prognostic signature in the entire dataset were 0.704, 0.683, and 0.750, respectively. The risk score independently predicted ccRCC survival based on univariate and multivariate Cox regression. GSEA analysis suggested that the high-risk group was concentrated on immune-related pathways. The high-risk group were characterized by high immune cell infiltration, high TMB and somatic mutation counters, high IPS-PD-1 + CTLA4 scores, and immune checkpoints expression upregulation, reflecting the higher ICIs response. The half inhibitory concentrations of sunitinib, temsirolimus, and rapamycin were low in the high-risk group. CONCLUSION: The TME-related lncRNAs signature constructed could reliably predict the prognosis and immunotherapy response and targeted ccRCC patients' therapy.

Novel immune-related signature based on immune cells for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney and is characterized by poor prognosis. We sought to build an immune-related prognostic signature and investigate its relationship with immunotherapy response in ccRCC. METHODS: Immune-related genes were identified by ssGSEA and WGCNA. The prognostic signature was conducted via univariate, least absolute shrinkage and selection operator, and multivariable Cox regression analyses. Kaplan-Meier analysis, PCA, t-SNE, and ROC were used to evaluate the risk model. RESULTS: A total of 119 immune-related genes associated with prognosis were screened out. Six immune-related genes (CSF1, CD5L, AIM2, TIMP3, IRF6, and HHLA2) were applied to construct a prognostic signature for KIRC. Kaplan-Meier analysis showed that patients in high-risk group had a poorer survival outcome than in low-risk group. The 1-, 3- and 5-year AUC of the prognostic signature was 0.754, 0.715, and 0.739, respectively. Univariate and multivariate Cox regression models demonstrated that the risk signature was an independent prognostic factor for KIRC survival. GSEA analysis suggested that the high-risk group was concentrated on immune-related pathways. The high-risk group with more regulatory T-cell infiltration showed a higher expression of immune negative regulation genes. The risk score had positively relationship with TIDE score and negatively with the response of immunotherapy. The IC50 values of axitinib, sunitinib, sorafenib, and temsirolimus were lower in the high-risk group. CONCLUSION: Our study defined a robust signature that may be promising for predicting clinical outcomes and immunotherapy and targeted therapy response in ccRCC patients.

Constructing an immune- and ferroptosis-related lncRNA signature to predict the immune landscape of human bladder cancer.

BACKGROUND: LncRNAs play a variety of roles in the tumor microenvironment and cancer immune responses. Determining the significance of bladder cancer (BLCA)-related genes to predict the prognostic and therapeutic response of BLCA is important. METHODS: IrlncRNA/ frlncRNA pairs were determined using univariate analysis. The signature was constructed based on this pairs. Finally, analysis and internal validation were performed from several aspects. RESULTS: We identified 60 immune- and ferroptosis-related lncRNA pairs, among which 12 were included in the Cox proportional hazards model. Patients in low-risk group survived for significantly longer. Survival and riskScore analyses showed that the low-risk group had a significantly better clinical outcome. ROC curve analysis showed that AUC of OS values were more than 0.75 in the training set and the whole cohort. As assessed using Cox analysis, the riskScore was an independent prognostic predictor in the training, testing set and the whole cohort. The areas under the multi-index ROC in the training set, the testing set, and the whole cohort were 0.777, 0.692, and 0.748, respectively. High-risk group was positively associated with most of tumor-infiltrating immune cells. High-risk Scores correlated positively with high expression of CD274, but not with PD-1. Low riskScores correlated positively with high expression levels of the genes ERBB2 and nectin-4. High-risk Score was associated with a lower IC50 value for Docetaxel, cisplatin, and Pazopanib, while there was an opposite result for metformin. CONCLUSIONS: The signature constructed by pairing irlncRNAs and frlncRNAs showed a notable clinical predictive value.

A multicenter retrospective study of transurethral prostate split for benign prostate hyperplasia.

Background: Transurethral split of the prostate (TUSP) is effective in treating benign prostatic hyperplasia (BPH). However, there is still a lack of research focusing on the optimal target population for TUSP. This study aimed to compare the efficacy of TUSP in patients with different prostate volumes or ages. Methods: The study was a multicenter retrospective study. The outcomes of TUSP in BPH patients with different prostate volumes or different ages were compared. A total of 439 patients were included in the study. Patients were divided into two groups according to prostate volume, with a cut-off value of 50 mL. Similarly, the cut-off value for the age groups was 70 years. Baseline patient characteristics and perioperative outcomes were recorded. Follow-up was performed at 1, 6, and 12 months after surgery. Results: The mean age of the patients was 73.4 years, and the mean prostate volume was 51.2 mL. At 12-month follow-up after TUSP treatment, the patients' International Prostate Symptom Scores (IPSS), quality of life (QoL) scores, and postvoid residual (PVR) volumes decreased significantly, while peak urinary flow rate (Qmax) increased significantly. Intraoperative hemoglobin (Hb) reduction was significantly lower in the small volume group than in the large volume group. The incidence of postoperative urinary urgency and transient incontinence was lower in the small volume group. IPSS score, PVR, and Qmax in the small volume group showed more remarkable changes at several time points compared to the preoperative period. Postoperative pain scores were higher in the small volume group than in the large volume group. There were no differences between the two groups in terms of long-term complications. The younger group showed greater variation in PVR and Qmax at some time points but less variation in QoL than the older group. Conclusions: TUSP is overall safe and effective in treating BPH. This study showed differences in the outcomes of TUSP in treating different prostate volumes or ages of BPH patients. The optimal surgical approach for BPH patients might be selected clinically based on a combination of prostate volume or patient age.

The oxidative degradation of Caffeine in UV/Fe(II)/persulfate system-Reaction kinetics and decay pathways.

In this study, the degradation of caffeine was investigated by UV/Fe2+ /persulfate (PS) process. Caffeine (CAF) degradation in sole-UV, UV/Fe2+ , UV/PS, and Fe2+ /PS systems was also conducted to examine the contribution of isolated processes to CAF degradation. The effects of pH levels, the concentration of Fe2+ and PS, inorganic anions, and initial concentration of CAF on the performance of UV/Fe2+ /PS process were evaluated. Radical competitive reactions indicated both hydroxyl radicals and sulfate radicals played important roles in CAF degradation in UV/Fe2+ /PS system. Nine intermediates, among which three were detected for the first time, were identified by ultra-performance liquid chromatography/electrospray-time-of-flight mass spectrometry (UPLC/ESI-TOF-MS) and SPME (solid-phase microextraction)/GC/MS. The possible degradation pathways of CAF were proposed, among which demethylation, hydroxylation, the oxidation of olefinic double bond, and the cleavage of pyrimidine ring and imidazole ring were involved in the degradation of CAF in UV/Fe2+ /PS system. PRACTITIONER POINTS: Caffeine degradation by UV/Fe2+ /PS process was investigated. Caffeine degradation did not follow a simple pseudo-first order kinetics Chloride ions promoted CAF degradation. The anions NO3 - , SO4 2- , and H2 PO4 - exerted a negative influence on caffeine degradation. Nine intermediates were detected, and decay pathways were proposed.

Diagnostic and prognostic value of CEP55 in clear cell renal cell carcinoma as determined by bioinformatics analysis.

Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant adult kidney tumor. Tumor recurrence and metastasis is the primary cause of cancer­associated mortality in patients with ccRCC. Therefore, identification of efficient diagnostic and prognostic molecular markers may improve survival times. The GSE46699, GSE36895, GSE53000 and GSE53757 gene datasets were downloaded from the Gene Expression Omnibus database and contained 196 ccRCC samples and 164 adjacent normal kidney samples. Bioinformatics analysis was used to integrate the four microarray datasets to identify and analyze differentially expressed genes. Functional analysis revealed that there were 12 genes associated with cancer, based on the tumor­associated gene database. Erb­B2 receptor tyrosine kinase 4, centrosomal protein 55 (CEP55) and vascular endothelial growth factor A are oncogenes, all of which were associated with tumor stage, whereas only CEP55 was significantly associated with survival time as determined by Gene Expression Profiling Interactive Analysis. The mRNA expression levels of CEP55 in ccRCC samples were significantly higher than those observed in adjacent normal kidney tissues based on The Cancer Genome Atlas data and reverse transcription­polymerase chain reaction results. The receiver operating characteristic curve analysis revealed that CEP55 may be considered a diagnostic biomarker for ccRCC with an area under the curve of >0.85 in the training and validation sets. High CEP55 expression was strongly associated with sex, histological grade, stage, T classification, N classification and M classification. Univariate and multivariate Cox proportional hazards analyses demonstrated that CEP55 expression was an independent risk factor for poor prognosis. In addition, gene set enrichment analysis indicated that high CEP55 expression was associated with immunization, cell adhesion, inflammation, the Janus kinase/signal transducer and activator of transcription signaling pathway and cell proliferation. In conclusion, CEP55 was increased in ccRCC samples, and may be considered a potential diagnostic and prognostic biomarker for ccRCC.

[Effects of RNA interference upon EGFR and its intracellular effective proteins in prostate cancer].

OBJECTIVE: To investigate the growth of prostate cancer in vitro or in vivo by inhibiting the expression of EGFR and its intracellular effective proteins with small RNA interference ( SiRNA). METHODS: The hormone independence prostate cancer (HIPC) cell line PC-3 was transfected by EGFR SiRNA synthesized and cloned into a recombinant lentivirus vector. The growth rate of transfected PC-3 cell was measured by MTT. The expression of EGFR and the expression and phosphorylation of its intracellular proteins, such as Akt and MAPK, were detected by fluorescent Real-Time PCR and Western blot respectively. Meanwhile nude mice were transplanted with PC-3 cell to establish the tumor model and the tumor growth was observed. RESULTS: The transfection efficiency was stable over 75% in PC-3 cell transfected with the recombinant lentivirus vector carrying EGFR SiRNA and the survival rate of PC-3 cell was only 40%-50%. Such depressant effects might be obtained by inhibiting the expression of EGFR mRNA and protein to only 10% as compared with their untreated levels (P < 0.01); meanwhile, the expression level and phosphorylation of Akt and MAPK also obviously decreased to 76.49% and 47.15% respectively (P < 0.05). Compared with the control group, the proliferation activity of tumors in nude mice was inhibited significantly by 34.83% (P < 0.05). CONCLUSION: Lentivirus-mediated EGFR SiRNA can inhibit the growth of HIPC in vivo and in vitro by effectively suppressing the expression of EGFR and its intracellular proteins. The latter may be a potential candidate for future targeted therapy.

[Comparative study on transperitoneal retroperitoneal laparoscopic adrenalectomy and open adrenalectomy for adrenal tumours].

OBJECTIVE: To compare and evaluate the clinical value among transperitoneal, retroperitoneal laparoscopic adrenalectomy and open adrenalectomy for the treatment of adrenal tumours. METHODS: From January 1996 to June 2002, transperitoneal laparoscopic adrenalectomy (TLA) was performed for 19 cases, 17 cases were successful (Group A), retroperitoneal laparoscopic adrenalectomy (RLA) for 21 cases, 19 cases were successful (Group B), during the same period 41 patients with adrenal tumours under 6 cm in diameter underwent open adrenalectomy (Group C). The procedure was evaluated and compared in the respects of tumors weight, operation time, blood loss, recovery time of GI function, hospital stay, complications transferable rate and indications among three groups. RESULTS: Average tumors weight was (13.86) g in group A, (15.66) g in group B and (18.03) g in group C; mean operating time: group A was 17.21 min longer than group B, group A. B was 48.53 min longer and 31.32 min longer han group C respectively, mean blood loss in group A. B was less diminished by 121.55 ml and 137.05 ml than group C, and the blood loss in group B was less diminished by 15.50 ml than group A; mean recovery of Gl function, group A and B was 1.87 day and 2.17 day earlier than group C respectively, group B was 0.3 day earlier than group A, mean hospital stay was 2.60 day and 3.87 day shorter than group C, group B was 1.27 day shorter, than group A; transferable rate of operation was 10.5% (group A) and 9.5% (group B). Postoperative complication rate was 10.5%, 14.3% and 9.7% in group A. B and C respectively. CONCLUSIONS: TLA and RLA were better than open method. On the hand of approach to adrenal gland disturbs to abdominal organ and postoperative recovery on RLA have some slight advantage.