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https://www.readbyqxmd.com/read/28096934/first-line-treatment-options-in-metastatic-renal-cell-cancer
#1
REVIEW
Anil Kapoor
The introduction of targeted therapy a decade ago revolutionized the treatment of metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Currently recommended first-line treatments in Canada include sunitinib, pazopanib, and temsirolimus. With the heterogeneity of mRCC disease, the choice of treatment is driven largely by prognostic factors...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28077238/patterns-of-care-and-clinical-outcomes-in-patients-with-metastatic-renal-cell-carcinoma-results-from-a-tertiary-cancer-center-in-india
#2
Anant Ramaswamy, Amit Joshi, Vanita Noronha, Vijay M Patil, Rushabh Kothari, Arvind Sahu, Ram Abhinav Kannan, Nilesh Sable, Palak Popat, Santosh Menon, Kumar Prabhash
INTRODUCTION: The current treatment of metastatic renal cell carcinoma (mRCC) revolves around targeted agents, which have resulted in a median overall survival of 22 to 26 months in registration trials. However, the outcomes in a non-trial, real-world Indian population have not yet been evaluated. MATERIALS AND METHODS: The present study was a part of a prospective Clinical Trials Registry-India-registered study, the Kidney Cancer Registry, a prospectively maintained kidney cancer registry...
October 19, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28061764/biological-toxicities-as-surrogate-markers-of-efficacy-in-patients-treated-with-mtor-inhibitors-for-metastatic-renal-cell-carcinoma
#3
M Jebali, R Elaidi, M Brizard, J Fouque, C Takouchop, B Sabatier, S Oudard, J Medioni
BACKGROUND: Metabolic toxicities of mTOR inhibitors (mTORi) are well characterized. The purpose of the study was to investigate the relationship between these metabolic toxicities and mTORi efficacy. METHODS: From 2007 to 2011, metabolic toxicities were retrospectively collected in patients treated with an mTORi (everolimus, temsirolimus) for a metastatic renal cell carcinoma (mRCC) in a single institution. Patients were eligible if they have received an mTORi for at least 28 days...
January 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28039705/safety-profile-of-temsirolimus-in-patients-with-metastatic-renal-cell-carcinoma
#4
Ivan Levakov, Sasa Vojinov, Goran Marusic, Milan Popov, Olivera Levakov, Mladen Popov, Dimitrije Jeremic
PURPOSE: Various targeted disease-specific therapeutics are currently approved, demonstrating a survival benefit over therapy with interferon-alpha (IFN-α) in patients with metastatic renal cell carcinoma (mRCC). Temsirolimus, a highly specific inhibitor of the mammalian target of rapamycin (mTOR), improves the overall and progression-free survival of high-risk patients with mRCC. The purpose of this study was to estimate the effects of temsirolimus on several laboratory parameters and to report the potential adverse events (AEs) in patients with mRCC...
November 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28035748/a-phase-i-study-of-perifosine-with-temsirolimus-for-recurrent-pediatric-solid-tumors
#5
Oren J Becher, Stephen W Gilheeney, Yasmin Khakoo, David C Lyden, Sofia Haque, Kevin C De Braganca, Jill M Kolesar, Jason T Huse, Shakeel Modak, Leonard H Wexler, Kim Kramer, Ivan Spasojevic, Ira J Dunkel
BACKGROUND: The PI3K/AKT/mTOR pathway is aberrantly activated in many pediatric solid tumors including gliomas and medulloblastomas. Preclinical data in a pediatric glioma model demonstrated that the combination of perifosine (AKT inhibitor) and temsirolimus (mTOR inhibitor) is more potent at inhibiting the axis than either agent alone. We conducted this study to assess pharmacokinetics and identify the maximum tolerated dose for the combination. PROCEDURE: We performed a standard 3+3 phase I, open-label, dose-escalation study in patients with recurrent/refractory pediatric solid tumors...
December 30, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28004284/a-phase-i-study-of-tivantinib-in-combination-with-temsirolimus-in-patients-with-advanced-solid-tumors
#6
Christos E Kyriakopoulos, Amy M Braden, Jill M Kolesar, Jens C Eickhoff, Howard H Bailey, Jennifer Heideman, Glenn Liu, Kari B Wisinski
Background A wide variety of human cancers exhibit dysregulated c-Met activity that has implications in oncogenesis. Phosphorylation of c-Met results in activation of the PI3K/AKT/mTOR pathway. Combined blockade of c-Met and mTOR pathways has shown efficacy in preclinical studies. Tivantinib is a c-Met inhibitor and temsirolimus is a selective mTOR inhibitor. We aimed to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D), dose-limiting toxicities (DLT), adverse events (AEs), clinical activity and pharmacokinetic (PK) parameters of the combination...
December 21, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/28000286/population-pharmacokinetics-of-temsirolimus-and-sirolimus-in-children-with-recurrent-solid-tumours-a-report-from-the-children-s-oncology-group
#7
Tomoyuki Mizuno, Tsuyoshi Fukuda, Uwe Christians, John P Perentesis, Maryam Fouladi, Alexander A Vinks
AIMS: Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR). Pharmacokinetic (PK) characterization of temsirolimus in children is limited and there is no paediatric temsirolimus population PK model available. The objective of this study was to simultaneously characterize the PK of temsirolimus and its metabolite sirolimus in paediatric patients with recurrent solid or central nervous system tumours and to develop a population PK model. METHODS: The PK data for temsirolimus and sirolimus were collected as a part of a Children's Oncology Group phase I clinical trial in paediatric patients with recurrent solid tumours...
November 7, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27995456/current-treatment-strategies-in-relapsed-refractory-mantle-cell-lymphoma-where-are-we-now
#8
REVIEW
Erden Atilla, Pinar Ataca Atilla, Taner Demirer
The management of relapsed/refractory mantle cell lymphoma remains challenging. Patients with relapsed mantle cell lymphoma have been treated with multi-agent salvage chemotherapies; however, outcomes are poor. Although there have been studies in the relapse/refractory setting, current data indicate that autologous hematopoietic stem cell transplantation may be an especially useful approach in the front line setting in patients in first complete or partial remission following induction chemotherapy. Allogeneic hematopoietic stem cell transplantation is the only curative option, although reduced intensity conditioning in chemo-sensitive relapse or refractory mantle cell lymphoma provides better survival rates...
December 19, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27979728/temsirolimus-induced-structural-transition-of-cancerous-renal-cystatin-to-normal-form-in-rats-in-vitro-mechanistic-approach-underlying-renal-cancer-prevention
#9
Anas Shamsi, Azaj Ahmed, Bilqees Bano
Globally, renal cell carcinomas (RCCs) represent a major portion of patients suffering from cancer. Temsirolimus is an anti-renal cancer drug that has already been approved in poor-risk metastatic RCC (mRCC) patients. In our present study, we have evaluated the in vitro effect of varying concentrations of temsirolimus on cancerous rat kidney cystatin; renal cancer was induced in rats making use of dimethylnitrosamine (DMN). It has already been reported that cancerous rat kidney cystatin performs its activity in an efficacious manner as compared to normal rat kidney cystatin, so here an attempt was made to see the effect of temsirolimus on this increased activity of cystatin in renal cancers...
December 12, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27931828/targeting-mtor-pathway-in-gynecological-malignancies-biological-rationale-and-systematic-review-of-published-data
#10
REVIEW
Loay Kassem, Omar Abdel-Rahman
BACKGROUND: mTOR inhibitors are widely used in different malignancies with several trials testing their efficacy and safety in gynecological malignancies. We aimed to review the current evidence that support the expansion of using such drugs in the treatment of advanced gynecological cancers. METHODS: A comprehensive systematic review of literature has been conducted to include prospective trials that used everolimus, temsirolimus or ridaforolimus in the management of gynecological cancers and have available efficacy and toxicity results...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27893038/targeting-the-pi3k-akt-mtor-pathway-for-the-treatment-of-mesenchymal-triple-negative-breast-cancer-evidence-from-a-phase-1-trial-of-mtor-inhibition-in-combination-with-liposomal-doxorubicin-and-bevacizumab
#11
Reva K Basho, Michael Gilcrease, Rashmi K Murthy, Thorunn Helgason, Daniel D Karp, Funda Meric-Bernstam, Kenneth R Hess, Shelley M Herbrich, Vicente Valero, Constance Albarracin, Jennifer K Litton, Mariana Chavez-MacGregor, Nuhad K Ibrahim, James L Murray, Kimberly B Koenig, David Hong, Vivek Subbiah, Razelle Kurzrock, Filip Janku, Stacy L Moulder
Importance: Triple-negative breast cancer (TNBC) classified by transcriptional profiling as the mesenchymal subtype frequently harbors aberrations in the phosphoinositide 3-kinase (PI3K) pathway, raising the possibility of targeting this pathway to enhance chemotherapy response. Up to 30% of mesenchymal TNBC can be classified histologically as metaplastic breast cancer, a chemorefractory group of tumors with a mixture of epithelial and mesenchymal components identifiable by light microscopy...
November 23, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27863926/combination-of-temsirolimus-and-adriamycin-exhibits-an-enhanced-antitumor-effect-in-hepatocellular-carcinoma
#12
Hong-Gang Kang, Bao-Zhong Wang, Jing Zhang, Mei-Rong Liu, Ying-Xue Li
OBJECTIVE: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in hepatocellular carcinoma (HCC). The aim of this study is to investigate the anti-HCC effect of combination of temsirolimus, an mTOR inhibitor, and adriamycin, a routinely used drug for treating HCC. METHODS AND MATERIALS: Proliferation of HCC cells exposure to temsirolimus, adriamycin, and their combination was determined using MTT assay in vitro as well as in a nude mice model in vivo. Cell apoptosis was examined using flow cytometry...
November 15, 2016: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/27799065/a-case-study-of-an-integrative-genomic-and-experimental-therapeutic-approach-for-rare-tumors-identification-of-vulnerabilities-in-a-pediatric-poorly-differentiated-carcinoma
#13
Filemon S Dela Cruz, Daniel Diolaiti, Andrew T Turk, Allison R Rainey, Alberto Ambesi-Impiombato, Stuart J Andrews, Mahesh M Mansukhani, Peter L Nagy, Mariano J Alvarez, Andrea Califano, Farhad Forouhar, Beata Modzelewski, Chelsey M Mitchell, Darrell J Yamashiro, Lianna J Marks, Julia L Glade Bender, Andrew L Kung
BACKGROUND: Precision medicine approaches are ideally suited for rare tumors where comprehensive characterization may have diagnostic, prognostic, and therapeutic value. We describe the clinical case and molecular characterization of an adolescent with metastatic poorly differentiated carcinoma (PDC). Given the rarity and poor prognosis associated with PDC in children, we utilized genomic analysis and preclinical models to validate oncogenic drivers and identify molecular vulnerabilities...
October 31, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27793908/co-treatment-of-ly294002-or-mk-2206-with-azd5363-attenuates-azd5363-induced-increase-in-the-level-of-phosphorylated-akt
#14
Ae-Ran Choi, Ju-Hwa Kim, Yeon Hwa Woo, Ji Hyun Cheon, Hyung Sik Kim, Sungpil Yoon
Clinical trials are in progress on AZD5363, an inhibitor of protein kinase B (AKT), to assess its effects on the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Cells treated with AKT inhibitors have been reported to activate alternative pathways in order to escape growth inhibition. AZD5363-sensitized Hs578T breast cancer cells displayed reduced levels of phosphorylated glycogen synthase kinase 3 beta (pGSK3β). Interestingly, in AZD5363-treated cells, the level of phosphorylated (activated) AKT (pAKT) increased...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27791402/attributable-risk-of-infection-to-mtor-inhibitors-everolimus-and-temsirolimus-in-the-treatment-of-cancer
#15
Christine A Garcia, Shenhong Wu
The risk of infection attributable to mTOR inhibitors has not been determined. Databases from PubMed and abstracts presented at the American Society of Clinical Oncology meetings were searched. Eligible studies included randomized controlled trials, in which everolimus or temsirolimus was compared with placebo. A total of 12 trials were included. The attributable incidences of all-grade and high-grade infections to mTOR inhibitors were 9.3% (95% confidence interval (CI): 5.8-14.6%) and 2.3% (95% CI: 1.2-4.4%) respectively...
November 25, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27741505/wide-spetcrum-mutational-analysis-of-metastatic-renal-cell-cancer-a-retrospective-next-generation-sequencing-approach
#16
Michelangelo Fiorentino, Elisa Gruppioni, Francesco Massari, Francesca Giunchi, Annalisa Altimari, Chiara Ciccarese, Davide Bimbatti, Aldo Scarpa, Roberto Iacovelli, Camillo Porta, Sarhadi Virinder, Giampaolo Tortora, Walter Artibani, Riccardo Schiavina, Andrea Ardizzoni, Matteo Brunelli, Sakari Knuutila, Guido Martignoni
Renal cell cancer (RCC) is characterized by histological and molecular heterogeneity that may account for variable response to targeted therapies. We evaluated retrospectively with a next generation sequencing (NGS) approach using a pre-designed cancer panel the mutation burden of 32 lesions from 22 metastatic RCC patients treated with at least one tyrosine kinase or mTOR inhibitor. We identified mutations in the VHL, PTEN, JAK3, MET, ERBB4, APC, CDKN2A, FGFR3, EGFR, RB1, TP53 genes. Somatic alterations were correlated with response to therapy...
October 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27737762/cb1-cannabinoid-receptors-mediate-cognitive-deficits-and-structural-plasticity-changes-during-nicotine-withdrawal
#17
Rocio Saravia, África Flores, Ainhoa Plaza-Zabala, Arnau Busquets-Garcia, Antoni Pastor, Rafael de la Torre, Vincenzo Di Marzo, Giovanni Marsicano, Andrés Ozaita, Rafael Maldonado, Fernando Berrendero
BACKGROUND: Tobacco withdrawal is associated with deficits in cognitive function, including attention, working memory, and episodic memory. Understanding the neurobiological mechanisms involved in these effects is crucial because cognitive deficits during nicotine withdrawal may predict relapse in humans. METHODS: We investigated in mice the role of CB1 cannabinoid receptors (CB1Rs) in memory impairment and spine density changes induced by nicotine withdrawal precipitated by the nicotinic antagonist mecamylamine...
July 16, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27721266/a-comparison-of-drug-resistances-of-targeted-drugs-for-advanced-renal-cell-cancer-approved-by-the-food-and-drug-administration-a-meta-analysis-of-randomized-clinical-trials
#18
Ming Guo, Yunsong Cao, Jingzhe Yang, Jingfeng Zhang
PURPOSE: The purpose of this study was to conduct network meta-analysis to assess drug resistances of the Food and Drug Administration-approved drugs for advanced renal cell carcinoma. MATERIALS AND METHODS: Database searches were conducted to identify randomized controlled trials reporting results for eligible treatments. After searching for PubMed, MEDLINE, EMBASE, and ISI Web of Science, 22 studies (n = 7854 patients) were included for the comparison of drug resistance in the present meta-analysis...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/27714772/mammalian-target-of-rapamycin-inhibition-with-temsirolimus-in-myelodysplastic-syndromes-mds-patients-is-associated-with-considerable-toxicity-results-of-the-temsirolimus-pilot-trial-by-the-german-mds-study-group-d-mds
#19
Martin Wermke, Claudia Schuster, Florian Nolte, Haifa-Kathrin Al-Ali, Philipp Kiewe, Claudia Schönefeldt, Christiane Jakob, Malte von Bonin, Leopold Hentschel, Ina-Maria Klut, Gerhard Ehninger, Martin Bornhäuser, Gustavo Baretton, Ulrich Germing, Regina Herbst, Detelef Haase, Wolf K Hofmann, Uwe Platzbecker
The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively...
October 7, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27664394/improvement-in-survival-end-points-of-patients-with-metastatic-renal-cell-carcinoma-through-sequential-targeted-therapy
#20
REVIEW
Emiliano Calvo, Manuela Schmidinger, Daniel Y C Heng, Viktor Grünwald, Bernard Escudier
Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab...
November 2016: Cancer Treatment Reviews
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