Kidney Cancer最新文献_第7页

miR-22 Regulates Invasion, Gene Expression and Predicts Overall Survival in Patients with Clear Cell Renal Cell Carcinoma miR-22调节透明细胞肾细胞癌患者的侵袭、基因表达并预测总生存率

IF 1.2

Kidney Cancer Pub Date : 2019-05-07 DOI: 10.3233/KCA-190051

Xue Gong, Hongjuan Zhao, M. Saar, D. Peehl, J. Brooks

{"title":"miR-22 Regulates Invasion, Gene Expression and Predicts Overall Survival in Patients with Clear Cell Renal Cell Carcinoma","authors":"Xue Gong, Hongjuan Zhao, M. Saar, D. Peehl, J. Brooks","doi":"10.3233/KCA-190051","DOIUrl":"https://doi.org/10.3233/KCA-190051","url":null,"abstract":"Background: Clear cell renal cell carcinoma (ccRCC) is molecularly diverse and distinct molecular subtypes show different clinical outcomes. MicroRNAs (miRNAs) are essential components of gene regulatory networks and play a crucial role in progression of many cancer types including ccRCC. Objective: Identify prognostic miRNAs and determine the role of miR-22 in ccRCC. Methods: Hierarchical clustering was done in R using gene expression profiles of over 450 ccRCC cases in The Cancer Genome Atlas (TCGA). Kaplan-Meier analysis was performed to identify prognostic miRNAs in the TCGA dataset. RNA-Seq was performed to identify miR-22 target genes in primary ccRCC cells and Matrigel invasion assay was performed to assess the effects of miR-22 overexpression on cell invasion. Results: Hierarchical clustering analysis using 2,621 prognostic genes previously identified by our group demonstrated that ccRCC patients with longer overall survival expressed lower levels of genes promoting proliferation or immune responses, while better maintaining gene expression associated with cortical differentiation and cell adhesion. Targets of 26 miRNAs were significantly enriched in the 2,621 prognostic genes and these miRNAs were prognostic by themselves. MiR-22 was associated with poor overall survival in the TCGA dataset. Overexpression of miR-22 promoted invasion of primary ccRCC cells in vitro and modulated transcriptional programs implicated in cancer progression including DNA repair, cell proliferation and invasion. Conclusions: Our results suggest that ccRCCs with differential clinical outcomes have distinct transcriptomes for which miRNAs could serve as master regulators. MiR-22, as a master regulator, promotes ccRCC progression at least in part by enhancing cell invasion.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"3 1","pages":"119 - 132"},"PeriodicalIF":1.2,"publicationDate":"2019-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43761464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Everolimus Exposure as a Predictor of Toxicity in Renal Cell Cancer Patients in the Adjuvant Setting: Results of a Pharmacokinetic Analysis for SWOG S0931 (EVEREST), a Phase III Study (NCT01120249) 依维莫司暴露作为辅助治疗肾细胞癌患者毒性的预测因子:SWOG S0931 (EVEREST)的药代动力学分析结果，一项III期研究(NCT01120249)

IF 1.2

Kidney Cancer Pub Date : 2019-04-05 DOI: 10.3233/KCA-180049

T. Synold, M. Plets, C. Tangen, E. Heath, G. Palapattu, P. Mack, M. Stein, M. Meng, P. Lara, N. Vogelzang, I. Thompson, C. Ryan

{"title":"Everolimus Exposure as a Predictor of Toxicity in Renal Cell Cancer Patients in the Adjuvant Setting: Results of a Pharmacokinetic Analysis for SWOG S0931 (EVEREST), a Phase III Study (NCT01120249)","authors":"T. Synold, M. Plets, C. Tangen, E. Heath, G. Palapattu, P. Mack, M. Stein, M. Meng, P. Lara, N. Vogelzang, I. Thompson, C. Ryan","doi":"10.3233/KCA-180049","DOIUrl":"https://doi.org/10.3233/KCA-180049","url":null,"abstract":"Background: S0931 is assessing recurrence-free survival in renal cell carcinoma (RCC) patients randomized to receive everolimus (EVE) versus placebo for one year following nephrectomy. Due to a higher than expected dropout rate, we assessed EVE trough levels in the adjuvant setting to evaluate the relationship between EVE exposure and probability of toxicity. Methods: Patients received 10 mg daily EVE for nine 6-week cycles. Pre-dose whole blood samples were collected pre-cycle 2 and pre-cycle 3 and analyzed for EVE. Patients with pre-cycle 2 and/or pre-cycle 3 EVE results were used in the analysis. Patients were segregated into quartiles (Q) based on EVE levels and logistic regression was used to model the most common adverse event outcomes using EVE trough as a predictor. Hazard and odds ratios were adjusted for age, BMI and performance status. Results: A total of 467 patients were included in this analysis. Quartiles normalized to an EVE dose of 10 mg/day were < 9.0, 9.0–12.9, 12.9–22.8, and > 22.8 ng/mL, respectively. EVE trough levels increased with increasing age (p < 0.001). Furthermore, EVE trough levels were higher in men than women (19.4 versus 15.4 ng/mL, p = 0.01). Risk of grade 2 + triglycerides was increased in Q2 and Q3 vs Q1 (OR = 2.08; p = 0.02 and OR = 2.63; p = 0.002). Risk of grade 2 + rash was increased in Q2 and Q4 vs Q1 (OR = 2.99; p = 0.01 and OR = 2.90; p = 0.02). There was also an increased risk of any grade 3 + tox in Q2 vs Q1 (OR = 1.71; p = 0.05). Conclusions: We identified significant gender and age-related differences in EVE trough levels in patients receiving adjuvant treatment for RCC. Furthermore, our analysis identified significant associations between EVE exposure and probability of toxicity.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"3 1","pages":"111 - 118"},"PeriodicalIF":1.2,"publicationDate":"2019-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47744097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Abstracts from the Seventeenth International Kidney Cancer Symposium, 2nd-3rd November 2018, Miami, Florida 第十七届国际肾癌研讨会摘要，2018年11月2日至3日，佛罗里达州迈阿密

IF 1.2

Kidney Cancer Pub Date : 2019-02-19 DOI: 10.3233/kca-189005

引用次数: 0

Radiation Therapy for Renal Cell Carcinoma 放射治疗肾细胞癌

IF 1.2

Kidney Cancer Pub Date : 2019-02-05 DOI: 10.3233/KCA-180040

R. Choi, James B. Yu

引用次数: 1

Double Immune Checkpoint Blockade in Renal Cell Carcinoma 双免疫检查点阻断在肾细胞癌中的作用

IF 1.2

Kidney Cancer Pub Date : 2019-01-01 DOI: 10.3233/KCA-190054

M. Luyo, L. Carril-Ajuria, F. Schutz, D. Castellano, G. Velasco

{"title":"Double Immune Checkpoint Blockade in Renal Cell Carcinoma","authors":"M. Luyo, L. Carril-Ajuria, F. Schutz, D. Castellano, G. Velasco","doi":"10.3233/KCA-190054","DOIUrl":"https://doi.org/10.3233/KCA-190054","url":null,"abstract":"Long considered an immunogenic tumour, immunotherapy has been the cornerstone of systemic treatment in renal cell carcinoma (RCC) for decades. Since the introduction of interleukin 2 and interferon-alfa in the 80s to the more recently approved nivolumab (anti-PD-1) in second line setting. Moreover, on the basis that anti-CTLA-4 and anti-PD-1/PDL1 intrinsic mechanisms are different, double checkpoint inhibition was proposed to further improve anti-tumor immune response. The first trial to assess double checkpoint inhibition was the Checkmate 016 (nivolumab and ipilimumab), showing acceptable safety and promising antitumor activity that led to the first phase III trial with combination immunotherapy in RCC, the Checkmate 214. This trial showed superior overall survival and response rate of the combination immunotherapy (nivolumab and ipilimumab) versus sunitinib in intermediateand poorrisk advanced RCC, leading to its approval in this setting. Despite these advances, there is still room for improvement. In this sense, cytokines and T-cell costimulatory molecules are currently under investigation. This review summarizes the principles of immunotherapy and its role in RCC, provides an update on double checkpoint blockade and finally discusses the major challenges with double checkpoint blockade. 7","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

The Emerging Role of Combination Angiogenesis Inhibitors and Immune Checkpoint Inhibitors in the Treatment of Metastatic Renal Cell Cancer 血管生成抑制剂和免疫检查点抑制剂联合治疗转移性肾细胞癌的新作用

IF 1.2

Kidney Cancer Pub Date : 2019-01-01 DOI: 10.3233/KCA-190050

A. Nizam, L. Rhea, Brinda Gupta, J. Aragon-Ching

{"title":"The Emerging Role of Combination Angiogenesis Inhibitors and Immune Checkpoint Inhibitors in the Treatment of Metastatic Renal Cell Cancer","authors":"A. Nizam, L. Rhea, Brinda Gupta, J. Aragon-Ching","doi":"10.3233/KCA-190050","DOIUrl":"https://doi.org/10.3233/KCA-190050","url":null,"abstract":"The advent of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs) a decade ago revolutionized the treatment paradigm in advanced metastatic clear cell renal cell carcinoma (RCC) with improved survival rates compared to the pre-TKI era. Monotherapy with VEGF TKIs has remained first-line. However, sequencing of different TKIs, mammalian target of rapamycin (mTOR) inhibitors, or immune checkpoint inhibitors (ICIs) has been the subject of controversy in the treatment landscape of metastatic RCC. First-line treatment further evolved with the approval of nivolumab plus ipilimumab in intermediateand poor-risk patients based on an overall survival (OS) benefit demonstrated in the CheckMate214 trial as well as a progression-free survival (PFS) benefit of cabozantinib in the CABOSUN trial. Optimal sequencing, patient selection, and understanding resistance pathways continue to be prominent concerns. Efforts to bypass resistance mechanisms have led to the study of combination therapies. Given enhancement of immune checkpoint inhibitor (ICI) T-cell mediated effects by VEGF-mediated immunosuppression, the combination of VEGF inhibitors and ICIs in treatment-naı̈ve locally advanced and metastatic RCC has shown promise. Available results of phase III trials utilizing these combinations are discussed herein.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Cell-free Circulating Tumor DNA (ctDNA) in Metastatic Renal Cell Carcinoma (mRCC): Current Knowledge and Potential Uses 转移性肾细胞癌(mRCC)中无细胞循环肿瘤DNA (ctDNA):目前的知识和潜在的应用

IF 1.2

Kidney Cancer Pub Date : 2019-01-01 DOI: 10.3233/KCA-180048

A. Hahn, R. Nussenzveig, B. Maughan, N. Agarwal

引用次数: 5

Metastasectomy in Advanced Renal Cell Carcinoma: A Systematic Review 晚期肾细胞癌的转移性切除术:一项系统综述

IF 1.2

Kidney Cancer Pub Date : 2019-01-01 DOI: 10.3233/KCA-180042

Tala Achkar, J. Maranchie, L. Appleman

引用次数: 4

Current Trends in Partial Nephrectomy After Guideline Release: Health Disparity for Small Renal Mass 指南发布后部分肾切除术的当前趋势:小肾肿块的健康差异

IF 1.2

Kidney Cancer Pub Date : 2019-01-01 DOI: 10.3233/kca-190066

A. May, Anirudh Guduru, J.P. Fernelius, S. Raza, F. Davaro, S. Siddiqui, Z. Hamilton

{"title":"Current Trends in Partial Nephrectomy After Guideline Release: Health Disparity for Small Renal Mass","authors":"A. May, Anirudh Guduru, J.P. Fernelius, S. Raza, F. Davaro, S. Siddiqui, Z. Hamilton","doi":"10.3233/kca-190066","DOIUrl":"https://doi.org/10.3233/kca-190066","url":null,"abstract":"Background: Renal masses can be surgically treated by partial nephrectomy (PN) or radical nephrectomy (RN); however, in 2009 guidelines recommended PN as the standard of care for cT1a renal masses. Objective: To evaluate national trends of surgically appropriate patients using the National Cancer Database (NCDB) for utilization of PN focusing on guideline release, evaluating underlying health disparity. Methods: We identified 99,035 patients from 2004–2015 that underwent surgical resection of cT1a renal masses. We evaluated treatment proportions over time of patients treated with PN or RN. Logistic regression was utilized for multivariable analysis. Results: PN increased from 40.2% in 2004 to 71.3% in 2015 (p < 0.001). Older patients were more likely to be treated with RN (OR 1.018, p < 0.001), as were those with Charlson score 2 or 3+ (OR 1.288 and 2.074, p < 0.001). Patients with lower income were more likely to be treated with RN (OR 1.186, p < 0.001) as were uninsured patients (OR 1.108, p = 0.018) and low volume centers (OR 1.063, p < 0.001). Females were more likely to undergo RN (OR 1.123, p < 0.001) as were black patients (OR 1.339, p < 0.001). While these demographic trends persisted after the release of the guidelines, all associations decreased except for Charlson score and race. Black patients became more likely to undergo RN (pre-guideline OR 1.248 vs post-guideline OR 1.474, p < 0.001). Patients treated with RN had worsened mortality (17.4% vs. 7.3%, p < 0.001). Conclusions: Although use of PN in surgically appropriate patients for cT1a renal masses has increased over time, 30% of patients underwent RN in 2015. Socioeconomic disparities affect treatment decisions and require additional research.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-190066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Sunitinib Dose Escalation in Metastatic Renal Cell Carcinoma 舒尼替尼剂量递增在转移性肾细胞癌中的应用

IF 1.2

Kidney Cancer Pub Date : 2019-01-01 DOI: 10.3233/KCA-190055

A. Bruchbacher, Sebastian Nachbargauer, H. Fajkovic, M. Schmidinger

{"title":"Sunitinib Dose Escalation in Metastatic Renal Cell Carcinoma","authors":"A. Bruchbacher, Sebastian Nachbargauer, H. Fajkovic, M. Schmidinger","doi":"10.3233/KCA-190055","DOIUrl":"https://doi.org/10.3233/KCA-190055","url":null,"abstract":"Background and objective: Sunitinib has been a standard treatment for patients with metastatic renal cell carcinoma (mRCC) since 2006. However, almost all patients will eventually progress. Besides well described mechanisms of primary or secondary resistance, insufficient drug exposure may lead to disease progression. The aim of this study was to identify patients in whom sunitinib dose escalation was performed and to analyse safety and efficacy of this strategy in clinical practice. Methods: A single-centre retrospective study on dose escalation in mRCC patients who were treated with sunitinib at the Medical University of Vienna between January 2011 and May 2016. Dose escalation was studied in patients who had either progressed (cohort 1: PD) or had stable disease with minor progression (cohort 2: SD). The primary endpoints were response rate before and after dose escalation, global progression free survival and overall survival. Secondary endpoints were treatment duration before and after dose escalation and toxicity. Results: Dose escalation up to 75 mg was offered in 21 out of 265 patients. Response rates before and after dose escalation were 42,8% and 23.8%, respectively. The median global PFS and OS were 15.60 and 32.95 months, respectively. The median treatment duration before and after dose escalation was 6.1 months (1.3–29.3 months) and 6.6 months (2.5–16.6 months). No new toxicities emerged under escalated dose and no grade 4 adverse events occurred. Conclusion: Sunitinib dose escalation may be a strategy in patients with few toxicities at the time point of progression.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1