•Umbrella review of various cancer risks related to red and processed meat intake.•100 g/d increment of red meat could increase by 11–51% risk of multiple cancer.•50 g/d increment of processed meat ...could increase by 8–72% risk of multiple cancer.•Red and processed meat consumption seems to be not related to any benefit of cancer.
The purpose of this umbrella review was to evaluate the quality of evidence, validity and biases of the associations between red and processed meat consumption and multiple cancer outcomes according to existing systematic reviews and meta-analyses. The umbrella review identified 72 meta-analyses with 20 unique outcomes for red meat and 19 unique outcomes for processed meat. Red meat consumption was associated with increased risk of overall cancer mortality, non-Hodgkin lymphoma (NHL), bladder, breast, colorectal, endometrial, esophageal, gastric, lung and nasopharyngeal cancer. Processed meat consumption might increase the risk of overall cancer mortality, NHL, bladder, breast, colorectal, esophageal, gastric, nasopharyngeal, oral cavity and oropharynx and prostate cancer. Dose-response analyses revealed that 100 g/d increment of red meat and 50 g/d increment of processed meat consumption were associated with 11%-51% and 8%-72% higher risk of multiple cancer outcomes, respectively, and seemed to be not correlated with any benefit.
Systemic immune-inflammation index (SII) has recently emerged as a biomarker for the prognosis of a variety of malignant tumors. However, the role of SII in bladder cancer (BC) remains unclear. To ...this end, we performed a pooled analysis to investigate the prognostic value of preoperative SII in patients with BC.
A comprehensive search of electronic databases (PubMed/Medline, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials) was conducted to determine the eligible studies that were published until January 2022. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between preoperative SII and the prognosis and clinicopathological characteristics of BC.
Ten studies with 7,087 patients were included in this analysis. SII was observed to be correlated with inferior overall survival (HR = 1.22, 95% CI 1.04-1.44, p = 0.013), cancer-specific survival (HR = 1.68, 95% CI 1.14-2.47,
= 0.009), and recurrence-free survival (HR = 1.29, 95% CI 1.03-1.61,
= 0.027). An increased preoperative SII was also associated with poor tumor differentiation, higher tumor stage, presence of lymph node involvement, and tumor size ≥3 cm (all
< 0.05).
An elevated preoperative SII is significantly associated with worse survival outcomes and adverse pathological features in patients with BC. Hence, SII may serve as a strong independent prognostic predictor for patients with BC after surgery.
The mechanisms resulting in resistance to next-generation antiandrogens in castration-resistant prostate cancer are incompletely understood. Numerous studies have determined that constitutively ...active androgen receptor (AR) signaling or full-length AR bypass mechanisms may contribute to the resistance. Previous studies established that AKR1C3 and AR-V7 play important roles in enzalutamide and abiraterone resistance. In the present study, we found that AKR1C3 increases AR-V7 expression in resistant prostate cancer cells through enhancing protein stability via activation of the ubiquitin-mediated proteasome pathway. AKR1C3 reprograms AR signaling in enzalutamide-resistant prostate cancer cells. In addition, bioinformatical analysis of indomethacin-treated resistant cells revealed that indomethacin significantly activates the unfolded protein response, p53, and apoptosis pathways, and suppresses cell-cycle, Myc, and AR/ARV7 pathways. Targeting AKR1C3 with indomethacin significantly decreases AR/AR-V7 protein expression
and
through activation of the ubiquitin-mediated proteasome pathway. Our results suggest that the AKR1C3/AR-V7 complex collaboratively confers resistance to AR-targeted therapies in advanced prostate cancer.
Protein homeostasis (proteostasis) is a potential mechanism that contributes to cancer cell survival and drug resistance. Constitutively active androgen receptor (AR) variants confer anti-androgen ...resistance in advanced prostate cancer. However, the role of proteostasis involved in next generation anti-androgen resistance and the mechanisms of AR variant regulation are poorly defined. Here we show that the ubiquitin-proteasome-system (UPS) is suppressed in enzalutamide/abiraterone resistant prostate cancer. AR/AR-V7 proteostasis requires the interaction of E3 ubiquitin ligase STUB1 and HSP70 complex. STUB1 disassociates AR/AR-V7 from HSP70, leading to AR/AR-V7 ubiquitination and degradation. Inhibition of HSP70 significantly inhibits prostate tumor growth and improves enzalutamide/abiraterone treatments through AR/AR-V7 suppression. Clinically, HSP70 expression is upregulated and correlated with AR/AR-V7 levels in high Gleason score prostate tumors. Our results reveal a novel mechanism of anti-androgen resistance via UPS alteration which could be targeted through inhibition of HSP70 to reduce AR-V7 expression and overcome resistance to AR-targeted therapies.
The tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor‐associated macrophages (TAMs) are ...considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2β1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2β1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.
We determined that tumor‐associated macrophages regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin inhibitor showed intensive anticancer effects, revealing an innovative approach to clinical bladder cancer treatment.
To investigate the practical value of the transrectal two-dimensional shear-wave elastography (SWE) in benign prostatic hyperplasia (BPH).OBJECTIVETo investigate the practical value of the ...transrectal two-dimensional shear-wave elastography (SWE) in benign prostatic hyperplasia (BPH).Consecutive male participants with and without BPH constituted the BPH and control group respectively were enrolled prospectively between March and December 2022. Transrectal conventional ultrasound and SWE examinations for the prostate were performed on these participants. Data of quantitative stiffness of the transitional zone (TZ) and peripheral zone (PZ) of prostate, volume of prostate (VP) and volume of TZ (VTZ) and prostate specific androgen (PSA), etc., were collected. Linear regression analyses were used to investigate the associations between quantitative stiffness data and other clinical parameters.METHODSConsecutive male participants with and without BPH constituted the BPH and control group respectively were enrolled prospectively between March and December 2022. Transrectal conventional ultrasound and SWE examinations for the prostate were performed on these participants. Data of quantitative stiffness of the transitional zone (TZ) and peripheral zone (PZ) of prostate, volume of prostate (VP) and volume of TZ (VTZ) and prostate specific androgen (PSA), etc., were collected. Linear regression analyses were used to investigate the associations between quantitative stiffness data and other clinical parameters.There were 200 participants evaluated, including 100 healthy participants and 100 BPH patients. For every one-year increment in age, it was correlated with 0.50 kPa increasement of TZ stiffness. VP and VTZ were correlated with TZ stiffness. Higher TZ stiffness was associated with higher free prostate specific antigen (PSA) and total PSA.RESULTSThere were 200 participants evaluated, including 100 healthy participants and 100 BPH patients. For every one-year increment in age, it was correlated with 0.50 kPa increasement of TZ stiffness. VP and VTZ were correlated with TZ stiffness. Higher TZ stiffness was associated with higher free prostate specific antigen (PSA) and total PSA.The prostate is stiffer and larger in BPH group compared to control group. Quantitative stiffness of the TZ was related with age, VP, VTZ and PSA.CONCLUSIONSThe prostate is stiffer and larger in BPH group compared to control group. Quantitative stiffness of the TZ was related with age, VP, VTZ and PSA.
The purpose of this study was to evaluate the efficacy and safety of the Amplatz dilation (AD), metal telescopic dilation (MTD), balloon dilation (BD), and one-shot dilation (OSD) methods for tract ...dilation during percutaneous nephrolithotomy (PCNL). Relevant eligible studies were identified using three electronic databases (Medline, EMBASE, and Cochrane CENTRAL). Database acquisition and quality evaluation were independently performed by two reviewers. Efficacy (stone-free rate, surgical duration, and tract dilatation fluoroscopy time) and safety (transfusion rate and hemoglobin decrease) were evaluated using Review Manager 5.2. Four randomized controlled trials and eight clinical controlled trials involving 6,820 patients met the inclusion criteria. The pooled result from a meta-analysis showed statistically significant differences in tract dilatation fluoroscopy time and hemoglobin decrease between the OSD and MTD groups, which showed comparable stone-free and transfusion rates. Significant differences in transfusion rate were found between the BD and MTD groups. Among patients without previous open renal surgery, those who underwent BD exhibited a lower blood transfusion rate and a shorter surgical duration compared with those who underwent AD. The OSD technique is safer and more efficient than the MTD technique for tract dilation during PCNL, particularly in patients with previous open renal surgery, resulting in a shorter tract dilatation fluoroscopy time and a lesser decrease in hemoglobin. The efficacy and safety of BD are better than AD in patients without previous open renal surgery. The OSD technique should be considered for most patients who undergo PCNL therapy.
To evaluate the efficacy and safety of percutaneous nephrolithotomy (PCNL) for patients in the supine position vs prone position.
Eligible studies were identified from electronic databases (Cochrane ...CENTRAL, Medline and EMBASE). The database search, quality assessment, and data extraction were independently performed by two reviewers. Efficacy (stone-free rate, operative time) and safety (complication, such as fever and transfusion rate) were explored by using Review Manager 5.0. Sensitivity analysis was performed to explore the influence of low-quality studies.
Two randomized controlled trials and two case-control studies including 389 patients met the inclusion criteria. Meta-analysis of extractable data showed that PCNL in the supine position was associated with a significantly shorter operative time than PCNL in the prone position (mean difference: -24.84; 95% confidence interval CI: -34.45 to -15.23; P < 0.00001). There was no difference between the positions with regard to success rate (odds ratio OR: 1.16; 95% CI: 0.68-1.48; P = 0.59), complication (OR: 1.09; 95% CI: 0.67-1.80; P = 0.72), transfusion rate (OR: 2.19; 95% CI: 0.93-5.13; P = 0.07), and fever rate (OR: 0.39; 95% CI: 0.13-1.16; P = 0.09).
PCNL in the supine position took a shorter operative time than the prone position, but both positions appeared to be equivalent with regard to the stone-free rate and complication rate, transfusion rate, and fever rate. In brief, PCNL in the supine position is as effective and safe as PCNL in the prone position and was an alternate option for removal of renal calculi in PCNL.
Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function ...as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.
The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.
Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.
The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
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