Metastatic renal cell carcinoma (mRCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKIs), the novel targeted agents have been used for the treatment of mRCC and have shown efficacy. Interferon (IFN)-α is also one of the most frequently used agents in immunotherapy. However, drug resistance needs to be overcome to achieve a sufficiently positive effect. Interleukin-6 (IL-6), which induce suppressor of cytokine signaling-3 (SOCS3) expression, is one of the factors associated with poor prognosis of patients with renal cell carcinoma (RCC). To analyze the influence of IL-6 in drug resistance of RCC, anti-IL-6 receptor antibody was used in combination with IFN or TKIs. The SOCS3 mRNA expression level was significantly increased by IFNα stimulation in 786-O RCC cells which were resistant to IFN, but not in ACHN cells that were sensitive to IFN. The overexpression of SOCS3 by gene transfection in ACHN significantly inhibited the growthinhibitory effect of IFNα. An in vivo study demonstrated that coadministration of SOCS3-targeted siRNA promoted INFαinduced cell death and growth suppression in 786-O cell xenograft. SOCS3 could be a key component in the resistance to interferon treatment of renal cell carcinoma. Because SOCS3 is rapidly upregulated by IL-6 and a negative regulator of cytokine signaling, IL-6 expression on RCC cells was also analyzed and the 786-O cells showed the high level of IL-6 mRNA expression under the condition of interferon stimulation. IL-6R antibody, tocilizumab, significantly suppressed cell proliferation in 786-O cells by interferon stimulation accompanied with phosphorylation of STAT1 and inhibited SOCS3 expression. The in vivo effects of combination therapy with tocilizumab and interferon showed significant suppression of 786-O tumor growth in a xenograft model. We also hypothesized that TKI resistance and IL-6 secretion are causally connected. And we found that 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFκB, HIF-2α and VEGF expression. Tocilizumab neutralizes the AKT-mTOR pathway activation and results in reduced proliferation. A combination therapy with tocilizumab and TKI suppresses 786-O tumor growth and inhibits angiogenesis in vivo more efficient than TKI alone. Our findings suggest that IL-6 could induce drug resistance on RCC, and combination therapy of IL-6R inhibitors and IFN/TKIs may represent a novel therapeutic approach for RCC treatment.
PurposeWe investigated that preoperative membranous urethral length (MUL) would be associated with the recovery of urinary continence after robot-assisted laparoscopic prostatectomy (RALP).Patients and methodsWe studied 204 patients who underwent RALP between May 2013 and March 2016. All patients underwent pelvic magnetic resonance imaging (MRI) preoperatively to measure MUL. Urinary continence was defined as the use of one pad or less (safety pad). The 204 patients were divided into two groups: continence group, those who achieved recovery of continence at 3, 6, and 12 months after RALP, and incontinence group, those who did not. We retrospectively analyzed the patients in terms of preoperative clinical factors including age, body mass index (BMI), estimated prostate volume, neurovascular bundle salvage, history of preoperative hormonal therapy, and MUL.ResultsThe safety pad use rate was 69.6%, 86.9%, and 91.1% at 3, 6, and 12 months, respectively. On univariate and multivariate analyses, MUL were significant factors in every term of recovery of urinary continence in both groups. According to the receiver operating characteristic (ROC) curve analysis, the preoperative MUL that could best predict early recovery of urinary continence at 3 months after RALP was 12 mm.ConclusionsWe suggest that preoperative MUL > 12 mm would be a predictor of early recovery of urinary continence after RALP.
Squamous cell carcinoma of the prostate is a rare tumor. It has been typically described as an aggressive cancer, with a median survival time of 14 months. We present a case of locally advanced squamous cell carcinoma of the prostate with a regional lymph node metastasis. The patient received a novel combination chemotherapy regimen, docetaxel, cisplatin, and 5-fluorouracil, with radiotherapy to the whole pelvis and prostate. He was subsequently treated with seven courses of docetaxel, cisplatin, and 5-fluorouracil chemotherapy without any severe adverse events. We identified a 60.1 % reduction in the prostatic tumor, and the lymph node metastasis was shrunk after chemotherapy. A needle biopsy of the prostate after chemotherapy revealed no malignancy. No recurrence has been observed for 24 months. A combination of docetaxel, cisplatin, and 5-fluorouracil chemotherapy and radiotherapy might be an effective therapy for squamous cell carcinoma of the prostate.
Indoxyl sulfate (IS) is related to the development of cardiovascular disease and total mortality in dialysis patients. High‐performance liquid chromatography (HPLC) is the conventional measurement approach. However, the HPLC method is difficult to perform in real time. Recently, the IS Assay Kit “NIPRO”, which enables the measuring of total IS by the enzyme method, was developed. This new reagent allows the easy and quick measurement of many samples using the automatic biochemical analyzer. Moreover, it was reported that it demonstrated satisfactory analytical performance. If this enzyme method is useful for measuring IS in hemodialysis, we can expect that the mechanism in which the IS effects adversely on a body as uremic toxins will be clarified. However, the enzyme method is more easily influenced by other coexisting substances. In this study, we have assessed on how the uremic toxins and anticoagulation effect on this new reagent and evaluate whether it can be put into practice effectively for hemodialysis patients. For the enzyme method, accuracy, simultaneous repeatability, linearity, limit of detection, influence of coexisting materials, and correlation with the HPLC method were examined. Accuracy and simultaneous repeatability were satisfactory, and linearity was good. The limit of detection was acceptable, and there was no influence of coexisting materials. With regard to the correlation, the regression equation was y = 0.947X + 7.987 and the correlation coefficient (r) was 0.972. This new reagent showed sufficient fundamental performance and had a good correlation with the conventional HPLC method for assessing the plasma of dialysis patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.