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https://www.readbyqxmd.com/read/28932277/a-retrospective-review-of-the-multidisciplinary-management-of-medullary-thyroid-cancer-eligibility-for-systemic-therapy
#1
Georgia Geller, Janessa Laskin, Winson Y Cheung, Cheryl Ho
BACKGROUND: Medullary thyroid carcinoma (MTC) accounts for 1-2% of all thyroid cancers. The clinical course of metastatic disease can be indolent. Our aim was to characterize the natural history of disease to evaluate the true proportion of patients who would be eligible for the currently available systemic therapies. METHODS: The British Columbia Cancer Agency (BCCA) provides cancer care to a population of 4.6 million. A retrospective chart review was conducted of all patients with MTC referred to the BCCA from 1991 to 2013...
2017: Thyroid Research
https://www.readbyqxmd.com/read/28926611/activation-of-the-unfolded-protein-response-in-sarcoma-cells-treated-with-rapamycin-or-temsirolimus
#2
Joseph W Briggs, Ling Ren, Kristi R Chakrabarti, Yien Che Tsai, Allan M Weissman, Ryan J Hansen, Daniel L Gustafson, Yousuf A Khan, Jonathan D Dinman, Chand Khanna
Activation of the unfolded protein response (UPR) in eukaryotic cells represents an evolutionarily conserved response to physiological stress. Here, we report that the mTOR inhibitors rapamycin (sirolimus) and structurally related temsirolimus are capable of inducing UPR in sarcoma cells. However, this effect appears to be distinct from the classical role for these drugs as mTOR inhibitors. Instead, we detected these compounds to be associated with ribosomes isolated from treated cells. Specifically, temsirolimus treatment resulted in protection from chemical modification of several rRNA residues previously shown to bind rapamycin in prokaryotic cells...
2017: PloS One
https://www.readbyqxmd.com/read/28901501/mtor-inhibition-reduces-growth-and-adhesion-of-hepatocellular-carcinoma-cells-in%C3%A2-vitro
#3
Tobias Engl, Jochen Rutz, Sebastian Maxeiner, Eva Juengel, Frederik Roos, Wael Khoder, Wolf O Bechstein, Karen Nelson, Igor Tsaur, Axel Haferkamp, Roman A Blaheta
Mechanistic target of rapamycin (mTOR) signaling is typically increased in hepatocellular carcinoma (HCC). A panel of HCC cell lines (HepG2, Hep3B and HuH6) was exposed to various concentrations of the mTOR inhibitors, everolimus and temsirolimus, in order to investigate their effects on cell growth, clonal formation, cell cycle progression, and adhesion and chemotactic migration using MTT and clonal cell growth assays, fluorometric detection of cell cycle phases and a Boyden chamber assay. In addition, integrin α and β adhesion receptors were analyzed by flow cytometry and blocking studies using function blocking monoclonal antibodies were conducted to explore functional relevance...
August 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28840097/a-case-of-delayed-exacerbation-of-interstitial-lung-disease-after-discontinuation-of-temsirolimus
#4
Rei Matsuki, Kenichi Okuda, Akihisa Mitani, Yasuhiro Yamauchi, Goh Tanaka, Haruki Kume, Yukio Homma, Munetoshi Hinata, Akimasa Hayashi, Junji Shibahara, Masashi Fukayama, Takahide Nagase
Temsirolimus is an inhibitor of mammalian target of rapamycin and interstitial lung disease (ILD) is known to be one of the adverse events associated with temsirolimus, which usually improves rapidly after discontinuation of the drug and rarely worsens thereafter. Herein, we report a case of delayed exacerbation of ILD after discontinuation of temsirolimus for metastatic renal cell carcinoma in an 86-year-old male with chronic ILD. The patient developed gradually worsening dyspnea five weeks after an initiation of temsirolimus and was admitted to our facility...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28821555/p53-non-genotoxic-activation-and-mtorc1-inhibition-lead-to-effective-combination-for-neuroblastoma-therapy
#5
Myrthala Moreno-Smith, Anna Lakoma, Zaowen Chen, Ling Tao, Kathleen A Scorsone, Linda Schild, Kevin Aviles-Padilla, Rana Nikzad, Yankai Zhang, Rikhia Chakraborty, Jan J Molenaar, Sanjeev Vasudevan, Vivien Sheehan, Eugene S Kim, Silke Paust, Jason M Shohet, Eveline Barbieri
mTORC1 inhibitors are promising agents for neuroblastoma therapy, however they have shown limited clinical activity as monotherapy, thus rational drug combinations need to be explored to improve efficacy. Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR signaling. <br /><br />Experimental Design: Using an orthotopic xenograft model and modulating p53 levels, we investigated the anti-tumor effects of the mTORC1 inhibitor temsirolimus in neuroblastoma expressing normal, decreased, or mutant p53, both as single agent and in combination with first and second generation MDM2 inhibitors to reactivate p53...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28811872/current-and-emerging-treatment-options-for-mantle-cell-lymphoma
#6
REVIEW
Bita Fakhri, Brad Kahl
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy...
August 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28793293/triggering-of-eryptosis-the-suicidal-erythrocyte-death-by-mammalian-target-of-rapamycin-mtor-inhibitor-temsirolimus
#7
Abdulla Al Mamun Bhuyan, Hang Cao, Florian Lang
BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is utilized for the treatment of malignancy. Temsirolimus is at least in part effective by triggering suicidal tumor cell death. The most common side effect of temsirolimus treatment is anemia. At least in theory, the anemia following temsirolimus treatment could result from stimulation of eryptosis, the suicidal erythrocyte death. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28777104/mood-stabilizing-effects-of-rapamycin-and-its-analog-temsirolimus-relevance-to-autophagy
#8
Nirit Z Kara, Shlomit Flaisher-Grinberg, Grant W Anderson, Galila Agam, Haim Einat
Accumulated data support a relationship between mood disorders and cellular plasticity and resilience, some suggesting relevance to autophagy. Our previous data show that pharmacological enhancement of autophagy results in antidepressant-like effects in mice. The current study was designed to further examine the effects of autophagy enhancement on mood by testing the effects of subchronic treatment with the mammalian target of rapamycin inhibitors and autophagy enhancers rapamycin and temsirolimus in a model for mania and in a model for antidepressant action, respectively...
August 2, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28772211/autophagy-as-a-potential-therapeutic-target-during-epithelial-to-mesenchymal-transition-in-renal-cell-carcinoma-an-in-vitro-study
#9
Mamta Singla, Shalmoli Bhattacharyya
Cancer progression toward invasive and metastatic disease is aided by reactivation of epithelial-mesenchymal transition (EMT), involving transdifferentiation of epithelial cells into mesenchymal phenotype. This leads to increased migratory and stem cell-like features in the cells. These EMT cells are more resistant to chemotherapy and it is hypothesized that the phenomenon of autophagy induces resistance, providing a survival strategy for cells. In the present study, we induced EMT-like phenotype in renal carcinoma cells and identified corresponding higher autophagy flux in these cells...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28768446/comparison-of-two-doses-of-intravenous-temsirolimus-in-patients-with-relapsed-refractory-mantle-cell-lymphoma
#10
Wojciech Jurczak, Sundra Ramanathan, Pratyush Giri, Alessandra Romano, Heidi Mocikova, Jill Clancy, Mariajose Lechuga, Michelle Casey, Joseph Boni, Agnieszka Giza, Georg Hess
Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly intravenously dosed (175/75 mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75 mg without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n = 47) or 75 mg (n = 42). Treatment continued until objective disease progression...
August 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28761748/new-treatment-options-for-metastatic-renal-cell-carcinoma
#11
REVIEW
Alejo Rodriguez-Vida, Thomas E Hutson, Joaquim Bellmunt, Michiel H Strijbos
During the last decade, the treatment of advanced or metastatic renal cell carcinoma (RCC) was revolutionised with the advent of antiangiogenic drugs and tyrosine-kinase inhibitors. Several agents targeting the vascular endothelial growth factor (VEGF) pathway (sunitinib, bevacizumab, pazopanib, axitinib) or the mammalian target of rapamycin pathway (temsirolimus, everolimus) were since then progressively approved for first-line or later-line use in the treatment of patients with advanced RCC and became the new standard of care...
2017: ESMO Open
https://www.readbyqxmd.com/read/28759157/mtor-notch3-signaling-mediates-pulmonary-hypertension-in-hypoxia-exposed-neonatal-rats-independent-of-changes-in-autophagy
#12
Julijana Ivanovska, Sparsh Shah, Mathew J Wong, Crystal Kantores, Amish Jain, Martin Post, Behzad Yeganeh, Robert P Jankov
BACKGROUND/AIM: Mammalian target of rapamycin (mTOR) is a pivotal regulator of cell proliferation, survival, and autophagy. Autophagy is increased in adult experimental chronic pulmonary hypertension (PHT), but its contributory role to pulmonary vascular disease remains uncertain and has yet to be explored in the neonatal animal. Notch is a major pro-proliferative pathway activated by mTOR. A direct relationship between autophagy and Notch signaling has not been previously explored. Our aim was to examine changes in mTOR-, Notch-, and autophagy-related pathways and the therapeutic effects of autophagy modulators in experimental chronic neonatal PHT secondary to chronic hypoxia...
July 31, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28759045/tumor-microenvironment-confers-mtor-inhibitor-resistance-in-invasive-intestinal-adenocarcinoma
#13
T Fujishita, Y Kojima, R Kajino-Sakamoto, M M Taketo, M Aoki
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is frequently activated in cancers and can be counteracted with the clinical mTORC1 inhibitors everolimus and temsirolimus. Although mTORC1 and dual mTORC1/2 inhibitors are currently under development to treat various malignancies, the emergence of drug resistance has proven to be a major complication. Using the cis-Apc/Smad4 mouse model of locally invasive intestinal adenocarcinoma, we show that administration of everolimus or the dual mTORC1/2 inhibitor AZD8055 significantly reduces the growth of intestinal tumors...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28723497/pharmacogenomic-markers-of-targeted-therapy-toxicity-in-patients-with-metastatic-renal-cell-carcinoma
#14
Guillermo de Velasco, Kathryn P Gray, Lana Hamieh, Yuksel Urun, Hallie A Carol, Andre P Fay, Sabina Signoretti, David J Kwiatkowski, David F McDermott, Matthew Freedman, Mark M Pomerantz, Toni K Choueiri
BACKGROUND: Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity. OBJECTIVE: To investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs)...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28714357/pharmaceutical-assistance-programs-for-cancer-patients-in-the-era-of-orally-administered-chemotherapeutics
#15
Aaron Mitchell, Benyam Muluneh, Rachana Patel, Ethan Basch
Introduction The rising cost of cancer drugs may make treatment unaffordable for some patients. Patients often rely on drug manufacturer-administered Pharmaceutical Assistance Programs (PAPs) to obtain drugs and reduced or no cost. The overall usage of PAPs within cancer care delivery is unknown. Methods We included all cancer patients across an academically affiliated, integrated health system in North Carolina during 2014 ( N = 8591). We identified the subset of patients receiving PAP assistance to afford one or more cancer drugs, in order to calculate the proportion of patients receiving PAP assistance, and the retail value of the assistance...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28694417/-a-case-report-metastatic-carcinoma-of-the-collecting-ducts-of-bellini-in-a-hemodialysis-patient-treated-with-temsirolimus
#16
Mizuho Akahane, Masakazu Nakashima, Hiromasa Sakamoto, Teruyoshi Aoyama, Jun Kawai
Carcinoma of the collecting ductsof Bellini isa rare histological subtype of renal cell carcinoma and mostly has unfavorable prognosis. Radical nephrectomy is generally chosen for the 1st line treatment but therapeutic approaches for the metastasis/recurrence have not been established. We report a case of carcinoma of collecting ducts of Bellini in a patient receiving hemodialysis treated with temsirolimus. A 62- year-old man receiving hemodialysis was admitted to our hospital with drug-resistant anemia and high-grade cyclic fever...
June 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28693022/temsirolimus-sensitive-stimulation-of-platelet-activity-apoptosis-and-aggregation-by-collagen-related-peptide
#17
Hang Cao, Rosi Bissinger, Anja T Umbach, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus stimulates apoptosis of tumor cells and is thus therapeutically used for the treatment of diverse malignancies. On the other hand, temsirolimus has been shown to protect against apoptosis of hippocampal neurons. Similar to nucleated cells, blood platelets may enter suicidal death characterized by cell shrinkage and cell membrane scrambling. Platelet apoptosis is frequently preceded by Ca2+ entry, degranulation, integrin activation and stimulation of caspases...
July 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28676972/erratum-to-a-phase-i-dose-escalation-study-of-selumetinib-in-combination-with-erlotinib-or-temsirolimus-in-patients-with-advanced-solid-tumors
#18
Jeffrey R Infante, Roger B Cohen, Kevin B Kim, Howard A Burris, Gregory Curt, Ugochi Emeribe, Delyth Clemett, Helen K Tomkinson, Patricia M LoRusso
No abstract text is available yet for this article.
July 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28676933/association-of-nr1i2-cyp3a5-and-abcb1-genetic-polymorphisms-with-variability-of-temsirolimus-pharmacokinetics-and-toxicity-in-patients-with-metastatic-bladder-cancer
#19
Litaty C Mbatchi, Matthieu Gassiot, Philippe Pourquier, Alejando Goberna, Hakim Mahammedi, Loic Mourey, Florence Joly, Serge Lumbroso, Alexandre Evrard, Nadine Houede
PURPOSE: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor that exhibits antitumor activity in renal cell carcinoma and mantle cell lymphoma. The metabolism of temsirolimus and its active metabolite sirolimus mainly depends on cytochrome P450 3A4/5 (CYP3A4/A5) and the ABCB1 transporter. Differently from sirolimus, no pharmacogenetic study on temsirolimus has been conducted. Therefore, the aim of this pilot study was to identify genetic determinants of the inter-individual variability in temsirolimus pharmacokinetics and toxicity...
July 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28662274/phase-2-study-evaluating-the-combination-of-sorafenib-and-temsirolimus-in-the-treatment-of-radioactive-iodine-refractory-thyroid-cancer
#20
Eric J Sherman, Lara A Dunn, Alan L Ho, Shrujal S Baxi, Ronald A Ghossein, Matthew G Fury, Sofia Haque, Cami S Sima, Grace Cullen, James A Fagin, David G Pfister
BACKGROUND: Patients with recurrent and/or metastatic, radioactive iodine-refractory thyroid carcinoma have limited treatment options. Sorafenib, an oral kinase inhibitor, is approved by the US Food and Drug Administration for the treatment of radioactive iodine-refractory thyroid carcinoma, although it demonstrated low response rates (12.2%) as a single agent in the first-line setting. The objective of the current study was to determine whether adding the mammalian target of rapamycin inhibitor temsirolimus to sorafenib could improve on these results...
June 29, 2017: Cancer
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