Evaluation of the management of Urachal carcinoma: single center experience over 13 years.

INTRODUCTION: Urachal carcinoma is characterized by high malignancy, poor prognosis, and late stage of diagnosis. There is a lack of unanimous clinical treatment guidelines. We summarize the characteristics, treatment and outcomes of urachal carcinoma from our center, hoping to provide a reference for diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data of 21 patients with urachal carcinoma who were treated at our center from January 2010 to August 2022, and all patients were followed up. RESULTS: The average survival time was 67.1 ± 9.1 (ranging from 49.3 to 84.9) months. The average relapse free survival was 48.8 ± 9.9 (ranging from 29.5 to 68.2) months. Six patients received adjuvant therapy, mainly chemotherapy. Five patients died during follow-up. CONCLUSIONS: Early physical examination may be helpful for early detection of Urachal carcinoma. Surgical treatment is still preferred for localized urachal carcinoma. Lymph node dissection may facilitate accurate staging, and positive margin usually results in a worse prognosis. Adjuvant therapy, mainly chemotherapy, may help to improve the prognosis. The application of radiotherapy, targeted therapy and immunotherapy still needs further exploration.

Feasibility study of ADCs targeting TROP-2, HER2, and CD46 in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

BACKGROUND: Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions. PATIENTS AND METHODS: We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues. RESULTS: Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively). CONCLUSIONS: Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.

Lanthanum doping and surface Li3BO3 passivating layer enabling 4.8 V nickel-rich layered oxide cathodes toward high energy lithium-ion batteries.

Single crystalline Ni-rich layered oxide cathodes show high energy density and low cost, have been regarded as one of the most promising candidates for next generation lithium-ion batteries (LIBs). Extending the cycling voltage window will significantly improve the energy density, however, suffers from bulk structural and interfacial chemistry degradation, leading to rapidly cycle performance deterioration. Here, we propose a dual-modification strategy to synthesize La doping and Li3BO3 (LBO) coating layers modified LiNi0.8Co0.1Mn0.1O2 (NCM811) by a facile one-step heating treatment processing. In-situ EIS and XRD, ex-situ XPS techniques are applied to demonstrate that the La diffused amorphous domains and Li3BO3 passivating layers dampen the lattice distortion, enhance the interfacial chemistry behavior as well as lithium ion transportation kinetics. Specifically, surface La doping amorphous domains successfully suppress the intense lattice stress and volume changes induced by the phase transitions during lithiation/delithiation, thus avoiding the intergranular crack and enhancing the mechanical stability of the material. Moreover, the LBO layer formed by the consumption of residual lithium prevents successive parasitic reactions at the interface as well as provides rapid Li-ion diffusion channels. Furthermore, the coating layer also diminishes the residual lithium compounds, increasing the atmosphere stability and safety of LIBs. Consequently, the La doping and LBO coating NCM811 exhibits an exceptional initial specific capacity (230.6 mAh/g) at 0.5C under a high cutoff voltage of 4.8 V, and a 73.8 % capacity retention following 100 cycles. In addition, a superior specific capacity of 133.8 mAh/g is provided even at a high current density (4C). Our work paves a promising road to tackle the integral structure deterioration and interfacial instability of Ni-rich cathodes.

A single-arm, multicenter, phase 2 clinical study of recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate (MRG002) in HER2-positive unresectable locally advanced or metastatic urothelial carcinoma.

BACKGROUND: MRG002 is a novel HER2-targeted antibody-drug conjugate being investigated in the MRG002-006 trial to evaluate the efficacy and safety in HER2-positive urothelial carcinoma patients. METHODS: This is an open-label, single-arm, multicenter phase II study. Eligibility criteria included: histologically confirmed HER2 IHC 2 + or 3 + UC, prior received ≥ 1 standard treatment. Patients in this study received MRG002 every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was confirmed ORR per RECIST 1.1. RESULTS: As of February 24, 2023, a total of 43 patients were enrolled. The median age was 60. 9 patients were dosed at 2.6 mg/kg and 34 patients were dosed at 2.2 mg/kg. At baseline, most patients (29/43) received ≥ 2 lines of treatment and 35 (81.4%) patients had prior ICI therapy. FISH test was performed in 41 patients and 9 (22.0%) were positive. By the cut-off date, 41 patients were evaluable and the ORR was 53% (95%CI：38.9%-67.5%), with 6.9% CR, and the DCR was 83.7% (95%CI：70.0%-91.9%). The median PFS and OS for the 43 patients were 7.0 months (95%CI：5.4-NE) and 14.9 months (95%CI：11.9-NE), respectively. The ORR was 77.8% in 9 patients with positive HER2 FISH results. Most common treatment-related AEs were anemia (51.2%), alopecia (44.2%) and neutropenia (39.5%); most were grade 1 or 2. CONCLUSION: Preliminary results of MRG002 demonstrated a clinically meaningful response in pretreated HER-2 positive unresectable locally advanced or metastatic UC patients. MRG002 at 2.2 mg/kg was well tolerated with a manageable toxicity.

Wood-inspired anisotropic hydrogel electrolyte with large modulus and low tortuosity realizing durable dendrite-free zinc-ion batteries.

While aqueous zinc-ion batteries exhibit great potential, their performance is impeded by zinc dendrites. Existing literature has proposed the use of hydrogel electrolytes to ameliorate this issue. Nevertheless, the mechanical attributes of hydrogel electrolytes, particularly their modulus, are suboptimal, primarily ascribed to the substantial water content. This drawback would severely restrict the dendrite-inhibiting efficacy, especially under large mass loadings of active materials. Inspired by the structural characteristics of wood, this study endeavors to fabricate the anisotropic carboxymethyl cellulose hydrogel electrolyte through directional freezing, salting-out effect, and compression reinforcement, aiming to maximize the modulus along the direction perpendicular to the electrode surface. The heightened modulus concurrently serves to suppress the vertical deposition of the intermediate product at the cathode. Meanwhile, the oriented channels with low tortuosity enabled by the anisotropic structure are beneficial to the ionic transport between the anode and cathode. Comparative analysis with an isotropic hydrogel sample reveals a marked enhancement in both modulus and ionic conductivity in the anisotropic hydrogel. This enhancement contributes to significantly improved zinc stripping/plating reversibility and mitigated electrochemical polarization. Additionally, a durable quasi-solid-state Zn//MnO2 battery with noteworthy volumetric energy density is realized. This study offers unique perspectives for designing hydrogel electrolytes and augmenting battery performance.

Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

[Retracted] microRNA­195 inhibits cell proliferation in bladder cancer via inhibition of cell division control protein 42 homolog/signal transducer and activator of transcription­3 signaling.

[This retracts the article DOI: 10.3892/etm.2015.2633.].

Androgen-repressed lncRNA LINC01126 drives castration-resistant prostate cancer by regulating the switch between O-GlcNAcylation and phosphorylation of androgen receptor.

BACKGROUND: Prostate cancer (PCa) initially shows satisfactory response to therapies targeting the androgen receptor (AR). However, progression to a castration-resistant stage indicates poor prognosis in PCa patients. AR signalling still plays a central role in most castration-resistant prostate cancers (CRPC). Therefore, unveiling the mechanisms of AR reactivation under androgen-deprived conditions is imperative to discover novel therapeutic targets for CRPC. METHODS: Using an integrative analysis of the transcriptomics of three independent PCa cohorts and a published landscape of AR-regulated long non-coding RNA (lncRNA), lncRNA LINC01126 was selected as a candidate gene that could drive CRPC progression for further study. Quantitative reverse transcription polymerase chain reaction, in situ hybridisation (ISH) and fluorescent ISH were performed to detect LINC01126 in PCa tissues and cells. The functional role and mechanism of LINC01126 were further investigated using in vitro and in vivo gain and loss of function assays. RESULTS: LINC01126, identified as an AR-repressed lncRNA, was significantly upregulated after AR-targeted therapies. In addition, we found that LINC01126 was upregulated in CRPC and was associated with poor prognosis. We also proved that LINC01126 stabilised AR protein and enhanced AR nuclear translocation and transactivation by promoting the transition from O-GlcNAcylation at threonine 80 to phosphorylation at serine 81 (S81) within the AR protein. Mechanism analysis revealed that LINC01126 facilitates the interaction of CDK9 with AR and impedes the binding of O-linked N-acetylglucosamine (O-GlcNAc) transferase to AR. Consequently, LINC01126 expression was sufficient to activate AR signalling without androgen. LINC01126 overexpression increased, whereas LINC01126 knockdown decreased castration resistance traits in PCa cells in vitro and in vivo. Furthermore, our data showed that LINC01126-targeting antisense oligonucleotides (ASO) substantially inhibited CRPC cells in vitro. CONCLUSIONS: Our research expands the functions of AR-regulated lncRNA in sustaining androgen-independent AR activity and promoting CRPC progression and reveals that LINC01126 may be a new therapeutic target for PCa.

Suppressing Rampant and Vertical Deposition of Cathode Intermediate Product via PH Regulation Toward Large-Capacity and High-Durability Zn//MnO2 Batteries.

Despite great prospects, Zn//MnO2 batteries suffer from rampant and vertical deposition of zinc sulfate hydroxide (ZSH) at the cathode surface, which leads to a significant impact on their electrochemical performance. This phenomenon is primarily due to the drastic increase in the electrolyte pH value upon discharging, which is closely associated with the electrodissolution of Mn-based active materials. Herein, the pH value change is effectively inhibited by employing an electrolyte additive with excellent pH buffering capability. As such, the formation of ZSH at the cathode is postponed, resulting in the deposition of ZSH in a horizontal arrangement. This strategy can significantly enhance the utilization efficiency of cathode active material, while also enabling a solid electrolyte interphase layer at the Zn anode to address low Zn stripping/plating reversibility. With the optimal electrolyte, the Zn//MnO2 battery realizes a 25.6% increase in the specific capacity at 0.2 A g-1 compared to that with the baseline electrolyte, great rate capability (161.6 mAh g-1 at 5 A g-1 ), and superior capacity retention (90.2% over 5,000 cycles). In addition, the pH buffering strategy is highly applicable in hydrogel electrolytes. This work underscores the importance of pH regulation for Zn//MnO2 batteries and provides enlightening insights.

Scalable fabrication of free-standing and integrated electrodes with commercial level of areal capacity for aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (AZIBs) present a highly promising avenue for the deployment of grid-scale energy storage systems. However, the electrodes fabricated through conventional methodologies not only suffer from insufficient mass loadings, but also are susceptible to exfoliation under deformations. Herein, a scalable and cost-effective freezing-thawing method is developed to construct free-standing and integrated electrode, comprising H11Al2V6O23.2, carboxymethyl cellulose, and carbon nanotubes. Benefiting from the synergistic effect of these components, the resultant electrode exhibits superior flexibility and robustness, large tensile strength, exceptional electrical conductivity, and favorable electrolyte wettability. Under a large mass loading of 8 mg cm-2 (corresponding to a negative/positive electrode capacity ratio of 2.09), the electrode achieves remarkable capacity of 345.2 mAh/g (2.76 mAh cm-2) at 0.2 A/g and maintains 235.2 mAh/g (1.88 mAh cm-2) at 4 A/g, while sustaining an impressive capacity retention of 97.7 % over 5000 cycles. These considerably outperform conventional electrodes employing traditional binders. Even at an elevated mass loading of 14 mg cm-2 or when operated at a low temperature of - 30 °C, the electrode continues to deliver excellent electrochemical performance (e.g., extraordinary areal capacity of 4.32 mAh cm-2). In addition, the electrode owns outstanding tolerance to external forces. This research contributes to our understanding of the pivotal challenges within the realm of AZIB technology.

Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway.

Osteosarcoma (OS) patients, particularly those with distant metastasis, experience rapid progression and derive poor survival benefits from traditional therapies. Currently, effective drugs for treating patients with metastatic OS remain scarce. Here, we found that the cyclic hexadepsipeptide beauvericin (BEA) functioned as a new selective TGFBR2 inhibitor with potent antiproliferative and antimetastatic activities against OS cells. Functionally, BEA inhibited TGF-ß signaling-mediated proliferation, invasiveness, mesenchymal phenotype, and extracellular matrix remodeling of OS cells, and suppressed tumor growth and reduced pulmonary metastasis in vivo. Mechanistic investigation revealed that BEA selectively and directly bound to Asn 332 of TGFBR2 and inhibited its kinase activity, thereby suppressing the aggressive progression of OS cells. Together, our study identifies an innovative and natural selective TGFBR2 inhibitor with effective antineoplastic activity against metastatic OS and demonstrates that targeting TGFBR2 could be a potential therapeutic strategy for metastatic OS.

Clinical outcomes of immune checkpoint inhibitor plus nab-paclitaxel in metastatic upper tract urothelial carcinoma.

Background: Metastatic upper tract urothelial carcinoma (mUTUC) is a malignant cancer associated with poor prognosis. Few studies have investigated the clinical outcome of a recently developed combination regimen of programmed cell death 1 (PD-1) inhibitor plus nab-paclitaxel in mUTUC. Methods: We retrospectively retrieved data from the electronic medical records of cisplatin-ineligible or cisplatin-refractory mUTUC patients from five participating Chinese centers, who received treatment of PD-1 inhibitor plus nab-paclitaxel between April 2018 and January 2022. Clinical response was assessed according to Response Evaluation Criteria in Solid Tumors criteria version 1.1 (RECIST 1.1). Duration of response (DOR), overall survival (OS), and progression-free survival (PFS) were evaluated by the Kaplan-Meier method. Results: The confirmed overall response rate (ORR) was 14/34 (41.2%), and the disease control rate (DCR) was 24/34 (70.6%). Complete response (CR) was achieved in one case, partial response (PR) in 13 cases (38.2%), stable disease (SD) in 10 cases (29.4%), and progressive disease (PD) occurred in 10 cases (29.4%). After a median follow-up period of 16.0 months [95% confidence interval (CI): 9.9-22.1], 14 deaths were reported, with a median OS of 15.0 months (95% CI: 9.9-20.1); 22 progressions were reported, with a median PFS of 6.0 months (95% CI: 2.4-9.6). Patients with visceral metastasis had a similar PFS [hazard ratio (HR): 1.28, 95% CI: 0.53-3.09, P=0.574) and OS (HR: 1.94, 95% CI: 0.64-5.83, P=0.279] to patients with lymph node metastasis only. Conclusions: This real-world study suggests that PD-1 inhibitor plus nab-paclitaxel is effective in cisplatin-ineligible and cisplatin-refractory mUTUC patients with acceptable toxicity, especially for patients with visceral metastasis.

Modified Tubeless Ureterocutaneostomy in High-Risk Patients After Radical Cystectomy and its Long-Term Clinical Outcomes.

OBJECTIVES: This work aimed to prevent stoma stenosis and achieve tubeless cutaneous ureterostomy in elderly and high-risk patients with our modified cutaneous ureterostomy. METHODS: We retrospectively analyzed 40 and 49 patients (176 renal units) who underwent Toyoda (group 1) and modified cutaneous ureterostomy (group 2) between 2012 and 2021. The average follow-up period was 44 months. The primary results of our study were the catheter-free rate and clinical outcomes, especially renal function and urinary diversion-related complications. Significant differences in catheter-free rate and urinary diversion-related complications were found between our modified method and the Toyoda technique. RESULTS: A total of 56 (71.8%) of 78 renal units in group 1 and 89 (90.8%) of 98 renal units in group 2 remained catheter free. Compared with group 1, group 2 had a higher catheter-free rate (P = .001). Multivariate analysis indicated that the surgical procedure (HR = 0.268; P = .001) and body mass index (HR = 3.127; P = .002) were the predictors independently associated with catheter insertion. During follow-up, renal deterioration was observed in 32 (36.0%) patients. Patients with catheter insertion were more likely to suffer from renal deterioration (P < .001), postoperative pyelonephritis (P < .001), and urolithiasis (P < .001) than their counterparts. CONCLUSION: Our modified cutaneous ureterostomy method may provide an effective and simple approach to tubeless cutaneous ureterostomy in elderly and high-risk patients.

ENO2-derived phosphoenolpyruvate functions as an endogenous inhibitor of HDAC1 and confers resistance to antiangiogenic therapy.

Metabolic reprogramming is associated with resistance to antiangiogenic therapy in cancer. However, its molecular mechanisms have not been clearly elucidated. Here, we identify the glycolytic enzyme enolase 2 (ENO2) as a driver of resistance to antiangiogenic therapy in colorectal cancer (CRC) mouse models and human participants. ENO2 overexpression induces neuroendocrine differentiation, promotes malignant behaviour in CRC and desensitizes CRC to antiangiogenic drugs. Mechanistically, the ENO2-derived metabolite phosphoenolpyruvate (PEP) selectively inhibits histone deacetylase 1 (HDAC1) activity, which increases the acetylation of ß-catenin and activates the ß-catenin pathway in CRC. Inhibition of ENO2 with enolase inhibitors AP-III-a4 or POMHEX synergizes the efficacy of antiangiogenic drugs in vitro and in mice bearing drug-resistant CRC xenograft tumours. Together, our findings reveal that ENO2 constitutes a useful predictive biomarker and therapeutic target for resistance to antiangiogenic therapy in CRC, and uncover a previously undefined and metabolism-independent role of PEP in regulating resistance to antiangiogenic therapy by functioning as an endogenous HDAC1 inhibitor.

Salting-Out Effect Realizing High-Strength and Dendrite-Inhibiting Cellulose Hydrogel Electrolyte for Durable Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries are limited by poor Zn stripping/plating reversibility. Not only can hydrogel electrolytes address this issue, but also they are suitable for constructing flexible batteries. However, there exists a contradiction between the mechanical strength and the ionic conductivity for hydrogel electrolytes. Herein, high-concentration kosmotropic ions are introduced into the cellulose hydrogel electrolyte to take advantage of the salting-out effect. This can significantly improve both the mechanical strength and ionic conductivity. Additionally, the obtained cellulose hydrogel electrolyte (denoted as Con-CMC) has strong adhesion, a wide electrochemical stability window, and good water retaining ability. The Con-CMC is also found to accelerate the desolvation process, improve Zn deposition kinetics, promote Zn deposition along the (002) plane, and suppress parasitic reactions. Accordingly, the Zn/Zn cell with Con-CMC demonstrates dendrite-free behavior with prolonged lifespan and can endure extremely large areal capacity of 25 mAh cm-2. The Con-CMC also enables a large average Coulombic efficiency of 99.54% over 500 cycles for the Zn/Cu cell. Furthermore, the assembled pouch-type Zn/polyaniline full battery provides great rate capability, superior cyclability (even with limited Zn anode excess), a slow self-discharge rate, and outstanding affordability to external forces. Overall, this work extends our knowledge of the rational design of hydrogel electrolytes.

TCAF2 in Pericytes Promotes Colorectal Cancer Liver Metastasis via Inhibiting Cold-Sensing TRPM8 Channel.

Hematogenous metastasis is the main approach for colorectal cancer liver metastasis (CRCLM). However, as the gatekeepers in the tumor vessels, the role of TPCs in hematogenous metastasis remains largely unknown, which may be attributed to the lack of specific biomarkers for TPC isolation. Here, microdissection combined with a pericyte medium-based approach is developed to obtain TPCs from CRC patients. Proteomic analysis reveals that TRP channel-associated factor 2 (TCAF2), a partner protein of the transient receptor potential cation channel subfamily M member 8 (TRPM8), is overexpressed in TPCs from patients with CRCLM. TCAF2 in TPCs is correlated with liver metastasis, short overall survival, and disease-free survival in CRC patients. Gain- and loss-of-function experiments validate that TCAF2 in TPCs promotes tumor cell motility, epithelial-mesenchymal transition (EMT), and CRCLM, which is attenuated in pericyte-conditional Tcaf2-knockout mice. Mechanistically, TCAF2 inhibits the expression and activity of TRPM8, leading to Wnt5a secretion in TPCs, which facilitates EMT via the activation of the STAT3 signaling pathway in tumor cells. Menthol, a TRPM8 agonist, significantly suppresses Wnt5a secretion in TPCs and CRCLM. This study reveals the previously unidentified pro-metastatic effects of TPCs from the perspective of cold-sensory receptors, providing a promising diagnostic biomarker and therapeutic target for CRCLM.

Comparative analysis of salvage partial nephrectomy versus radical nephrectomy after the failure of initial partial nephrectomy.

OBJECTIVES: To compare the oncologic outcomes and renal function discrepancy of salvage partial nephrectomy (sPN) and salvage radical nephrectomy (sRN) after an initial failed PN. MATERIALS AND METHODS: Retrospective data from multiple centers between 2008 and 2022 were analyzed in this study. Patients who received sPN or sRN after an initial failed PN were identified. Comparative analysis and propensity score matching (PSM) was performed and the RENAL score, tumor size, and pathological T stage at salvage surgery were used to match the 2 groups. Local recurrence-free survival (LRFS) and recurrence-free survival (RFS) were assessed using the Cox proportional hazards model and log-rank tests. Renal function after salvage surgery was assessed using the Wilcoxon rank sum test. RESULTS: A total of 140 patients who underwent salvage surgery were evaluated, of whom 60 were considered for PSM analysis after matching. At a median follow-up of 27.0 months, LRFS and RFS showed no significant difference between sPN and sRN, either before (LRFS, HR = 0.673 [95% CI: 0.171-2.644], P = 0.610; RFS, HR = 0.744 [95% CI: 0.271-1.344], P = 0.595) or after matching (LRFS, HR = 1.080 [95% CI: 0.067-17.30], P = 0.957; RFS, HR = 1.199 [95% CI: 0.241-5.983], P = 0.822). During long-term follow-up, sPN preserved renal function (after matching, eGFR, 71.4 vs. 54.0, P < 0.001) and prevented eGFR loss (after matching: 6.6% vs. 25.6%, P < 0.001). CONCLUSION: Salvage partial nephrectomy offers a better alternative than sRN for recurrence after initial PN, as sPN preserves renal function better while maintaining parallel tumor control and acceptable complication rates.

Key Molecules in Bladder Cancer Affect Patient Prognosis and Immunotherapy Efficacy: Further Exploration for CNTN1 and EMP1.

PURPOSE: Immunotherapy has been widely used in bladder cancer (BCa) in recent years and has significantly improved the prognosis of patients with BCa. However, further identification of immunotherapy-sensitive individuals to improve the efficacy of immunotherapy remains an important unmet need. MATERIALS AND METHODS: The key genes were screened and identified from Gene Expression Omnibus database and The Cancer Genome Atlas database to construct the risk prediction function (risk scores). Real-time polymerase chain reaction, immunohistochemistry, and IMvigor210 data sets were used to verify the roles of key molecules and efficacy of risk scores. The biologic function of CNTN1 and EMP1 was further explored through cell proliferation experiments. RESULTS: Five key genes, CNTN1, MAP1A, EMP1, MFAP5, and PTGIS, which were significantly related to the prognosis and immune checkpoint molecules of patients, were screened out. CNTN1 and EMP1 were further experimentally confirmed for their significant tumor-promoting effects. Besides, the constructed risk scores on the basis of these five key genes can accurately predict the prognosis and immunotherapy efficacy of patients with BCa. Interestingly, the high-risk patients identified by the risk scores have significantly worse prognosis and immunotherapy effects than low-risk patients. CONCLUSION: The key genes we screened can affect the prognosis of BCa, tumor microenvironment immune infiltration, and the efficacy of immunotherapy. The risk scores tool we constructed will contribute to the development of individualized treatment for BCa.

MIR663AHG as a competitive endogenous RNA regulating TGF-ß-induced epithelial proliferation and epithelial-mesenchymal transition in benign prostate hyperplasia.

Benign prostate hyperplasia (BPH) is the most commonly seen disease among aging males. Transforming growth factor(TGF)-ß-mediated epithelial-mesenchymal transition (EMT) and epithelial overproliferation might be central events in BPH etiology and pathophysiology. In the present study, long noncoding RNA MIR663AHG, miR-765, and FOXK1 formed a competing endogenous RNAs network, modulating TGF-ß-mediated EMT and epithelial overproliferation in BPH-1 cells. miR-765 expression was downregulated in TGF-ß-stimulated BPH-1 cells; miR-765 overexpression ameliorated TGF-ß-mediated EMT and epithelial overproliferation in BPH-1 cells. MIR663AHG directly targeted miR-765 and negatively regulated miR-765; MIR663AHG knockdown also attenuated TGF-ß-induced EMT and epithelial overproliferation in BPH-1 cells, whereas miR-765 inhibition attenuated MIR663AHG knockdown effects on TGF-ß-stimulated BPH-1 cells. miR-765 directly targeted FOXK1 and negatively regulated FOXK1. FOXK1 knockdown attenuated TGF-ß-induced EMT and epithelial overproliferation and promoted autophagy in BPH-1 cells, and partially attenuated miR-765 inhibition effects on TGF-ß-stimulated BPH-1 cells. In conclusion, this study provides a MIR663AHG/miR-765/FOXK1 axis modulating TGF-ß-induced epithelial proliferation and EMT, which might exert an underlying effect on BPH development and act as therapeutic targets for BPH treatment regimens.

S100A5 Attenuates Efficiency of Anti-PD-L1/PD-1 Immunotherapy by Inhibiting CD8+ T Cell-Mediated Anti-Cancer Immunity in Bladder Carcinoma.

Although immune checkpoint blockade (ICB) therapies have been approved for bladder cancer (BLCA), only a minority of patients respond to these therapies, and there is an urgent need to explore combined therapies. Systematic multi-omics analysis identified S100A5 as a novel immunosuppressive target for BLCA. The expression of S100A5 in malignant cells inhibited CD8+ T cell recruitment by decreasing pro-inflammatory chemokine secretion. Furthermore, S100A5 attenuated effector T cell killing of cancer cells by inhibiting CD8+ T cell proliferation and cytotoxicity. In addition, S100A5 acted as an oncogene, thereby promoting tumor proliferation and invasion. Targeting S100A5 synergized with the efficacy of anti-PD-1 treatment by enhancing infiltration and cytotoxicity of CD8+ T cells in vivo. Clinically, there was a spatially exclusive relationship between S100A5+ tumor cells and CD8+ T cells in tissue microarrays. Moreover, S100A5 negatively correlated with immunotherapy efficacy in our real-world and several public immunotherapy cohorts. In summary, S100A5 shapes a non-inflamed tumor microenvironment in BLCA by inhibiting the secretion of pro-inflammatory chemokines and the recruitment and cytotoxicity of CD8+ T cells. Targeting S100A5 converts cold tumors into hot tumors, thus enhancing the efficacy of ICB therapy in BLCA.