Although recent evidence has suggested that a high-fat diet (HFD) plays an important role in prostate carcinogenesis, the underlying mechanisms have largely remained unknown. This review thus summarizes previous preclinical studies that have used prostate cancer cells and animal models to assess the impact of dietary fat on prostate cancer development and progression. Large variations in the previous studies were found during the selection of preclinical models and types of dietary intervention. Subcutaneous human prostate cancer cell xenografts, such as LNCaP, LAPC-4, and PC-3 and genetic engineered mouse models, such as TRAMP and Pten knockout, were frequently used. The dietary interventions had not been standardized, and distinct variations in the phenotype were observed in different studies using distinct HFD components. The use of different dietary components in the research models is reported to influence the effect of diet-induced metabolic disorders. The proposed underlying mechanisms for HFD-induced prostate cancer were divided into (1) growth factor signaling, (2) lipid metabolism, (3) inflammation, (4) hormonal modulation, and others. A number of preclinical studies proposed that dietary fat and/or obesity enhanced prostate cancer development and progression. However, the relationship still remains controversial, and care should be taken when interpreting the results in a human context. Future studies using more sophisticated preclinical models are imperative in order to explore deeper understanding regarding the impact of dietary fat on the development and progression of prostate cancer.
Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this “obesity paradox” is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin. Overweight and obese patients had significantly lower grade cancers than normal patients in all patients and in those without metastasis (p = 0.003 and p = 0.027, respectively). Cancer-specific survival was significantly longer in overweight and obese patients than in normal patients in all patients (p = 0.035). There was a weak inverse correlation between sAd level and BMI in RCC patients (r = −0.344, p = 0.002). Tumor size was slightly correlated with sAd level, and high sAd was significantly associated with poor overall survival rates in patients with non-metastatic RCC (p = 0.035). Adiponectin levels in perinephric adipose tissue and intratumoral AdipoR1/R2 expression were not correlated with RCC aggressiveness or survival. Proliferation significantly increased in 786-O and Caki-2 cells exposed to exogenous adiponectin, whereas cell invasion and migration were unaffected. In addition, exogenous adiponectin significantly inhibited starvation- and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels. In summary, low BMI and high adiponectin levels are associated with aggressive cell behaviors and poor survival in surgically-treated RCC patients. The effects of adiponectin on proliferation and apoptosis might underlie the “obesity paradox” of RCC.
Robot-assisted radical prostatectomy may potentially achieve the lowest positive surgical margin rate among three surgical approaches. The bladder neck was the most common location of positive surgical margin in robot-assisted radical prostatectomy and apex in open radical prostatectomy and laparoscopic radical prostatectomy. Although robot-assisted radical prostatectomy may contribute to the reduction of positive surgical margin, dissection of the bladder neck requires careful attention to avoid positive surgical margins.
Recent evidence suggests that a high-fat diet (HFD) plays an important role in prostate carcinogenesis; however, underlying mechanisms largely remain unknown. Here, we investigated microRNA (miRNA) expression changes in murine prostate cancer (PCa) xenografts using two different diets: HFD and control diet. We then assessed the roles and targets of altered miRNAs in HFD-induced PCa progression. We identified 38 up- and 21 downregulated miRNAs in xenografts under HFD conditions using the miRCURY LNA™ microRNA array. The differences in 10 candidate miRNAs were validated using quantitative RT-PCR. We focused on miR-130a because the expression levels were significantly lower in the three PCa cell lines in comparison with benign prostate PINT1B cells. PCa cells cultured in a medium containing HFD mouse serum were associated with significantly higher cell proliferation rates and lower miR-130a expression levels. Further, miR-130a modulated MET expression in PCa cells, and MET was overexpressed in in vitro and in vivo HFD-induced PCa progression models. Moreover, ectopic miR-130a downregulated AR in LNCaP cells and DICER1 in PC-3 and DU145 cells, respectively. In human tissues, as elucidated using laser capture microdissection, the mean miR-130a expression level in cancer epithelium was significantly lower than that in normal epithelium. Furthermore, cytoplasmic MET in PCa tissues was overexpressed in patients with higher body mass index. In conclusion, a substantial number of miRNAs was altered in HFD-induced PCa growth. Specifically, miR-130a was attenuated in HFD-induced PCa progression with MET overexpression. miRNAs thus have implications in the mechanism, prevention and treatment of HFD-induced PCa progression.
To evaluate the efficacy and safety of anti-PD1 therapy (nivolumab) in advanced renal cell carcinoma (RCC) in a clinical setting. Between March 2013 and January 2018, 33 patients with RCC (27 men and 6 women) were treated with nivolumab. Before anti-PD1 treatment, 12, 9 and 12 patients received one, two, and three or more therapies, respectively. Objective response, survival rate, and clinical adverse events were evaluated by the revised RECIST criteria (version 1.1). The median patient age was 68 years (range: 37-79). In total, 14 (42%) patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 while 17 (52%) and two (6%) had an ECOG PS of 1 and 2 or higher, respectively. One (3%), 24 (73%) and eight (24%) were classified as having favorable, intermediate, and poor risk, respectively. The median follow-up duration after nivolumab initiation was 26 months (range: 1-131). The median progression-free and overall survival were 10.3 months and 45.9 months, respectively. Nivolumab was associated with a disease control rate of 58%, with an objective response of 24% (complete response, 1; partial response, 7; stable disease, 11; progressive disease, 10; not assessed, 4). A total of 15 (46%) patients experienced adverse events, of which six were severe (grade 3 or more) and 10 were immunotherapy-related. This study examined the initial experience of nivolumab administration in Japanese patients with advanced RCC. Our results suggest that nivolumab can achieve acceptable outcomes in a real clinical setting, with outcomes that are comparable to those of clinical trials. Patients and methods Eligibility criteria. The present study included patients who were diagnosed with advanced RCC and treated with nivolumab from two institutes between March 2013 and January 2018. All patients with histologically-proven mRCC, regardless of Eastern Cooperative Oncology Group (ECOG) performance status (PS), were eligible for inclusion. All patients received at least two cycles of nivolumab and were assessed for treatment efficacy and toxicity. This study was approved by both institutional review boards, The Research
Background: This study assessed the incidence and impact of acute kidney injury (AKI) on renal prognosis in patients who underwent robot-assisted laparoscopic radical prostatectomy (RARP). Methods: Medical records of 305 patients treated with RARP were retrospectively reviewed. The patients with postoperative AKIs were dichotomized into early AKI (immediately after surgery) and late AKI (1-7 days after surgery). The impact of AKIs and their risk factors were statistically assessed. Results: Early and late AKI were observed in 143 (46.9%) and 12 (3.9%) patients, respectively. Hypertension and console time were independent risk factors for early AKI. Among the patients with preoperative eGFR ≥60 mL/min, the eGFR decline 12 months after surgery was significantly greater in patients with early AKI than that without early AKI (−6.8 vs −3.2 mL/min, P = .02). Conclusions: Approximately half of patients developed early AKI after RARP. The patients with early AKI had reduced renal function 12 months after surgery. K E Y W O R D S acute kidney injury, prostate cancer, robot-assisted laparoscopic radical prostatectomy 1 | INTRODUCTION Prostate cancer is the second leading cause of cancer-related death in men worldwide. 1 Radical prostatectomy is one of the standard modalities for localized prostate cancer. 2 Robotic surgery has been accepted to improve surgical quality 3 in urological surgery, and robot-assisted laparoscopic radical prostatectomy (RARP) has become one of the most widely used procedures due to its minimal invasiveness and comparable outcomes with conventional procedures. 4,5 Therefore, it is important to achieve satisfactory surgical outcomes of RARP without peri-and postoperative complications. Acute kidney injury (AKI) is a postoperative complication of prostatectomy that is associated with chronic kidney disease (CKD) and death. 6,7 There are several potential causes of postoperative AKI, including patient and surgical factors. 7 RARP can impair renal function due to high pneumoperitoneum pressure and an extremely steep head-down position of the patient. 8,9 Several studies report the incidence of AKI after RARP compared with that after conventional open surgery. 7,10 However, the frequency and clinical significance of AKI after RARP remains unclear. In this study, we assessed the incidence, risk factors and impact on renal prognosis of AKI observed during the very early period after surgery in patients with prostate cancer who underwent RARP. 2 | PATIENTS AND METHODS 2.1 | Patients and study design We retrospectively reviewed the medical records of 305 consecutive patients with localized prostate cancer patients who underwent
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