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renal cancer model

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https://www.readbyqxmd.com/read/28314474/sulforaphane-as-an-adjunctive-to-everolimus-counteracts-everolimus-resistance-in-renal-cancer-cell-lines
#1
Eva Juengel, Stephanie Euler, Sebastian Maxeiner, Jochen Rutz, Saira Justin, Frederik Roos, Wael Khoder, Karen Nelson, Wolf O Bechstein, Roman A Blaheta
BACKGROUND: The mechanistic target of rapamycin (mTOR) inhibitors, everolimus and temsirolimus, have widened therapeutic options to treat renal cell carcinoma (RCC). However, chronic treatment with these inhibitors often induces resistance, leading to therapeutic failure. PURPOSE: The natural compound, sulforaphane (SFN), was added to an everolimus based regime in vitro in the hopes of preventing resistance development. METHODS: A panel of RCC cell lines (A498, Caki-1, KTCTL-26) was treated with everolimus or SFN or with an everolimus-SFN-combination, either short- (24h) or long-term (8 weeks), and cell growth, proliferation, apoptosis, and cell cycle phases were measured...
April 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28301684/economic-evaluation-of-nivolumab-as-a-second-line-treatment-for-advanced-renal-cell-carcinoma-from-us-and-chinese-perspectives
#2
Xiao Min Wan, Liu Bao Peng, Jin An Ma, Yuan Jian Li
BACKGROUND: Nivolumab is a new standard of care for patients with metastatic renal cell carcinoma (mRCC) and provides an overall survival benefit of 5.40 months in comparison with everolimus. This study evaluated the cost-effectiveness of nivolumab for the second-line treatment of mRCC from the perspective of US payers and identified the range of drug costs for which the addition of nivolumab to standard therapy could be considered cost-effective from a Chinese perspective. METHODS: A partitioned survival model was constructed to estimate lifetime costs, life-years, and quality-adjusted life-years (QALYs)...
March 16, 2017: Cancer
https://www.readbyqxmd.com/read/28299963/cost-effectiveness-analysis-on-the-use-of-fidaxomicin-and-vancomycin-to-treat-clostridium-difficile-infection-in-france
#3
Maureen Watt, Aurélien Dinh, Alban Le Monnier, Patrick Tilleul
BACKGROUND: Fidaxomicin is a macrocyclic antibiotic with proven efficacy against Clostridium difficile infection (CDI) in adults. It was licensed in France in 2012, but, due to higher acquisition costs compared with existing treatments, healthcare providers require information on its cost/benefit profile. OBJECTIVE: To compare healthcare costs and health outcomes of fidaxomicin and vancomycin, as reference treatment for CDI. METHODS: A Markov model was used to simulate the treatment pathway, over 1 year, of adult patients with CDI receiving fidaxomicin or vancomycin...
March 16, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28296193/investigating-transporter-mediated-drug-drug-interactions-using-a-physiologically-based-pharmacokinetic-model-of-rosuvastatin
#4
Q Wang, M Zheng, T Leil
Rosuvastatin is a frequently used probe in transporter-mediated drug-drug interaction (DDI) studies. This report describes the development of a physiologically based pharmacokinetic (PBPK) model of rosuvastatin for prediction of pharmacokinetic (PK) DDIs. The rosuvastatin model predicted the observed single (i.v. and oral) and multiple dose PK profiles, as well as the impact of coadministration with transporter inhibitors. The predicted effects of rifampin and cyclosporine (6.58-fold and 5.07-fold increase in rosuvastatin area under the curve (AUC), respectively) were mediated primarily via inhibition of hepatic organic anion-transporting polypeptide (OATP)1B1 (Inhibition constant (Ki ) ∼1...
March 13, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28296030/comprehensive-assessment-of-renal-tumor-complexity-in-a-large-percutaneous-cryoablation-cohort
#5
Bimal Bhindi, R Houston Thompson, Ross J Mason, Mustafa M Haddad, Jennifer R Geske, A Nicholas Kurup, James D Hannon, Stephen A Boorjian, Bradley C Leibovich, Thomas D Atwell, Grant D Schmit
OBJECTIVE: To evaluate the association between renal tumor complexity and outcomes in a large cohort of patients undergoing percutaneous cryoablation (PCA). PATIENTS AND METHODS: Patients with renal tumors treated with PCA were identified using our prospectively-maintained ablation registry (2003-2015). Salvage procedures and inherited tumor syndromes were excluded. The associations between R.E.N.A.L. Nephrometry Score (NS) and risk of complications, renal function impairment, local failure, and cancer-specific mortality (CSM) were evaluated using univariate and multivariable logistic, linear and Cox regression models...
March 13, 2017: BJU International
https://www.readbyqxmd.com/read/28295960/interactions-of-renal-clearable-gold-nanoparticles-with-tumor-microenvironments-vasculature-and-acidity-effects
#6
Mengxiao Yu, Chen Zhou, Li Liu, Shanrong Zhang, Shasha Sun, Julia D Hankins, Xiankai Sun, Jie Zheng
The success of nanomedicines in the clinic depends on our comprehensive understanding of nano-bio interactions in tumor microenvironments, which are characterized by dense leaky microvasculature and acidic extracellular pH (pHe ) values. Herein, we investigated the accumulation of ultrasmall renal-clearable gold NPs (AuNPs) with and without acidity targeting in xenograft mouse models of two prostate cancer types, PC-3 and LNCaP, with distinct microenvironments. Our results show that both sets of AuNPs could easily penetrate into the tumors but their uptake and retention were mainly dictated by the tumor microvasculature and the enhanced permeability and retention effect over the entire targeting process...
March 13, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28292893/small-molecule-selectively-suppresses-myc-transcription-in-cancer-cells
#7
Claire Bouvard, Sang Min Lim, John Ludka, Nahid Yazdani, Ashley K Woods, Arnab K Chatterjee, Peter G Schultz, Shoutian Zhu
Stauprimide is a staurosporine analog that promotes embryonic stem cell (ESC) differentiation by inhibiting nuclear localization of the MYC transcription factor NME2, which in turn results in down-regulation of MYC transcription. Given the critical role the oncogene MYC plays in tumor initiation and maintenance, we explored the potential of stauprimide as an anticancer agent. Here we report that stauprimide suppresses MYC transcription in cancer cell lines derived from distinct tissues. Using renal cancer cells, we confirmed that stauprimide inhibits NME2 nuclear localization...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28285387/development-and-external-validation-of-preoperative-risk-models-for-operative-morbidities-after-total-gastrectomy-using-a-japanese-web-based-nationwide-registry
#8
Hirotoshi Kikuchi, Hiroaki Miyata, Hiroyuki Konno, Kinji Kamiya, Ai Tomotaki, Mitsukazu Gotoh, Go Wakabayashi, Masaki Mori
BACKGROUND: Total gastrectomy is a relatively difficult and invasive procedure among gastrointestinal surgeries, and major morbidities following total gastrectomy can be serious and fatal. This study aimed to develop and validate preoperative risk models of morbidities associated with total gastrectomy using a Japanese web-based nationwide registry. METHODS: The national clinical database was used to retrieve the records of 39,253 patients who underwent total gastrectomy in 1,841 hospitals between January 1, 2011 and December 31, 2012...
March 11, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28284894/can-partial-nephrectomy-provide-equal-oncological-efficiency-and-safety-compared-with-radical-nephrectomy-in-patients-with-renal-cell-carcinoma-%C3%A2-4cm-a-propensity-score-matched-study
#9
Hakmin Lee, Jong Jin Oh, Seok Soo Byun, Chang Wook Jeong, Cheol Kwak, Byong Chang Jeong, Seong Soo Jeon, Hyun Moo Lee, Han-Yong Choi, Seong Il Seo
OBJECTIVE: Although partial nephrectomy (PN) is the standard treatment for localized clinical T1a renal cell carcinoma (RCC), treatment of larger renal tumors is controversial. We evaluated the oncological outcomes and perioperative complications after radical and PN for RCC ≥4cm. PATIENTS AND METHODS: We retrospectively analyzed the data of 2,373 patients surgically treated for nonmetastatic RCC with clinical T1b or T2 (≥4cm). The propensity scores for surgery type were calculated, and the partial group was matched to the radical group in a 1:3 ratio...
March 8, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28280347/high-expression-of-aldolase-a-predicts-poor-survival-in-patients-with-clear-cell-renal-cell-carcinoma
#10
Ning Na, Heng Li, Chengfang Xu, Bin Miao, Liangqing Hong, Zhengyu Huang, Qiu Jiang
BACKGROUND: Aldolase A (ALDOA) is a glycolytic enzyme that drives the glycolytic metabolic pathway in mammalian cells. The overexpression of ALDOA was observed in a variety of cancers including clear-cell renal cell carcinoma (ccRCC). However, little was known about the clinicopathological significance and prognostic value of ALDOA in ccRCC patients. METHODS: The expression of ALDOA was detected using immunohistochemical staining in 162 formalin-fixed, paraffin-embedded ccRCC sections...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28273641/betulinic-acid-attenuates-renal-fibrosis-in-rat-chronic-kidney-disease-model
#11
Anshuk Sharma, Richa Thakur, Madhu C Lingaraju, Dhirendra Kumar, Karikalan Mathesh, Avinash G Telang, Thakur Uttam Singh, Dinesh Kumar
BACKGROUND: Most chronic kidney diseases (CKDs), regardless of the nature of the initial injury, progress to end-stage renal disease (ESRD) characterized by fibrosis with irreversible loss of tissue and function. Thus, improved and more effective therapies are critical. Betulinic acid (BA), a pentacyclic triterpene is a compound in the pipeline of anti-cancer drug development. It has been shown to a possess variety of beneficial effects in many disease conditions. However, its efficacy against CKD is yet to be explored...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28270950/trends-of-partial-and-radical-nephrectomy-in-managing-small-renal-masses
#12
Ibrahim Khalid Al Saidi, Kholoud Saleh Alqasem, Saeda Turki Gharaibeh, Naim Z N Qamhia, Ibrahim Abukhiran, Ali Ahmad Al-Daghmin
OBJECTIVE: Use of partial nephrectomy (PN) for renal tumors appears to have relatively lower incidence rates in Jordan. We sought to characterize its trend at King Hussein Cancer Center for the last 10 years. MATERIAL AND METHODS: A retrospective review of our renal cell cancer data was performed. We identified 169 patients who had undergone surgery for renal tumors measuring ≤7 cm between 2005 and 2015. We characterized tumor size, pathology, type of surgery and clinical outcomes...
March 2017: Turkish Journal of Urology
https://www.readbyqxmd.com/read/28270699/fty720-attenuates-angiotensin-ii-induced-podocyte-damage-via-inhibiting-inflammatory-cytokines
#13
Ke Su, Ping Zeng, Wei Liang, Zhengyu Luo, Yiman Wang, Xifeng Lv, Qi Han, Miao Yan, Cheng Chen
FTY720, a new chemical substance derived from the ascomycete Isaria sinclairii, is used for treating multiple sclerosis, renal cancer, and asthma. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite and exists in red blood cells. FTY720 is a synthetic S1P analog which can block S1P evoking physiological effects. Recently studies show that S1P was participating in activated inflammation cells induced renal injury. The objective of this study was to assess the protective effect of FTY720 on kidney damage and the potential mechanism of FTY720 which alleviate podocyte injury in chronic kidney disease...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28270206/meis1-inhibits-clear-cell-renal-cell-carcinoma-cells-proliferation-and-in-vitro-invasion-or-migration
#14
Jie Zhu, Liang Cui, Axiang Xu, Xiaotao Yin, Fanglong Li, Jiangping Gao
BACKGROUND: Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. METHODS: MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells...
March 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28267958/comparison-of-multivariate-risk-estimation-models-to-predict-prognosis-in-patients-with-implantable-cardioverter-defibrillators-with-or-without-cardiac-resynchronization-therapy
#15
Salima Akoudad, Lara Dabiri Abkenari, Beat A Schaer, Christian Sticherling, Wayne C Levy, Luc Jordaens, Dominic A M J Theuns
Several multivariate risk score models were developed to predict prognosis of patients with heart failure (HF). We compared 3 models with regard to prediction of mortality in patients with HF who received an implantable defibrillator (ICD) or a cardiac resynchronization therapy defibrillator (CRT-D), as primary prevention of sudden death. The study cohort consisted of 823 patients (ICD = 410; CRT-D = 413). The evaluated models were the Seattle Heart Failure Model (SHFM), the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) score, and an adjusted Charlson Comorbidity Index (aCCI)...
February 10, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28262413/checkmate-025-randomized-phase-3-study-outcomes-by-key-baseline-factors-and-prior-therapy-for-nivolumab-versus-everolimus-in-advanced-renal-cell-carcinoma
#16
Bernard Escudier, Padmanee Sharma, David F McDermott, Saby George, Hans J Hammers, Sandhya Srinivas, Scott S Tykodi, Jeffrey A Sosman, Giuseppe Procopio, Elizabeth R Plimack, Daniel Castellano, Howard Gurney, Frede Donskov, Katriina Peltola, John Wagstaff, Thomas C Gauler, Takeshi Ueda, Huanyu Zhao, Ian M Waxman, Robert J Motzer
BACKGROUND: The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). OBJECTIVE: To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. DESIGN, SETTING, AND PARTICIPANTS: Subgroup OS analyses were performed using Kaplan-Meier methodology...
March 2, 2017: European Urology
https://www.readbyqxmd.com/read/28259840/quinazoline-derivatives-as-selective-cyp1b1-inhibitors
#17
Mohd Usman Mohd Siddique, Glen J P McCann, Vinay R Sonawane, Neill Horley, Linda Gatchie, Prashant Joshi, Sandip B Bharate, Venkatesan Jayaprakash, Barij N Sinha, Bhabatosh Chaudhuri
CYP1B1 is implicated to have a role in the development of breast, ovarian, renal, skin and lung carcinomas. It has been suggested that identification of potent and specific CYP1B1 inhibitors can lead to a novel treatment of cancer. Flavonoids have a compact rigid skeleton which fit precisely within the binding cavity of CYP1B1. Systematic isosteric replacement of flavonoid 'O' atom with 'N' atom led to the prediction that a 'quinazoline' scaffold could be the basis for designing potential CYP1B1 inhibitors...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28259474/excisional-precision-matters-understanding-the-influence-of-excisional-volume-loss-on-renal-function-after-partial-nephrectomy
#18
Julien Dagenais, Matthew J Maurice, Pascal Mouracade, Onder Kara, Ercan Malkoc, Jihad H Kaouk
Renal function after partial nephrectomy (PN) may depend on modifiable factors including ischemia time, excision of healthy parenchyma (excisional volume loss, EVL), and reconstructive methods. We retrospectively reviewed our institutional robotic PN database to identify the predictors of glomerular filtration rate (GFR) preservation (GFR-P) at 3-12 mo postoperatively, during which GFR decline plateaus. Baseline clinical, sociodemographic, and radiologic characteristics were captured. Univariate and multivariate (MV) linear regression analyses were performed and marginal effects were employed to examine the relative effect of EVL on renal function...
March 1, 2017: European Urology
https://www.readbyqxmd.com/read/28258697/tim-3-and-its-role-in-regulating-anti-tumor-immunity
#19
REVIEW
Madhumita Das, Chen Zhu, Vijay K Kuchroo
Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28258630/everolimus-suppresses-invasion-and-migration-of-renal-cell-carcinoma-by-inhibiting-fak-activity-and-reversing-epithelial-to-mesenchymal-transition-in-vitro-and-in-vivo
#20
Sheng-Wen Wu, Pei-Ni Chen, Chin-Yin Lin, Yih-Shou Hsieh, Horng-Rong Chang
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and the major cause of mortality in urological cancer. Most patients with RCC are asymptomatic until the disease is advanced and unresectable. In this situation, systemic therapy with immunotherapy or molecularly targeted therapy agents play an important role in therapeutic strategy. Everolimus (EVE), an m-TOR inhibitor, has the potential to inhibit tumor progression at multiple levels and is indicated for the treatment of advanced RCC in patients whose disease has metastasis...
March 4, 2017: Environmental Toxicology
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