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https://www.readbyqxmd.com/read/29227282/hypoxia-induced-upregulation-of-bmx-kinase-mediates-therapeutic-resistance-in-acute-myeloid-leukemia
#1
Jolieke G van Oosterwijk, Daelynn R Buelow, Christina D Drenberg, Aksana Vasilyeva, Lie Li, Lei Shi, Yong-Dong Wang, David Finkelstein, Sheila A Shurtleff, Laura J Janke, Stanley Pounds, Jeffrey E Rubnitz, Hiroto Inaba, Navjotsingh Pabla, Sharyn D Baker
Oncogenic addiction to the Fms-like tyrosine kinase 3 (FLT3) is a hallmark of acute myeloid leukemia (AML) that harbors the FLT3-internal tandem duplication (FLT3-ITD) mutation. While FLT3 inhibitors like sorafenib show initial therapeutic efficacy, resistance rapidly develops through mechanisms that are incompletely understood. Here, we used RNA-Seq-based analysis of patient leukemic cells and found that upregulation of the Tec family kinase BMX occurs during sorafenib resistance. This upregulation was recapitulated in an in vivo murine FLT3-ITD-positive (FLT3-ITD+) model of sorafenib resistance...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29225833/longer-recurrence-free-survival-in-a-patient-with-metastatic-renal-cell-carcinoma-treated-with-temsirolimus
#2
Tendo Satoh, Takuya Koie, Hirotaka Horiguchi, Noriko Tokui, Satoshi Narita, Chikara Ohyama
Temsirolimus did not demonstrate an efficacy advantage compared with sorafenib as second-line therapy in patients with metastatic renal cell carcinoma (mRCC). Only a few patients achieved complete responses, and the median progression-free survival rate remains short. We report one patient with mRCC who had a continuing response to temsirolimus.
December 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/29223619/differential-effects-of-hepatic-cirrhosis-on-the-intrinsic-clearances-of-sorafenib-and-imatinib-by-cyps-in-human-liver
#3
Michael Murray, Tina B Gillani, Sussan Ghassabian, Robert J Edwards, Tristan Rawling
The tyrosine kinase inhibitors sorafenib and imatinib are important in the treatment of a range of cancers but adverse effects in some patients necessitate dosage modifications. CYP3A4 has a major role in the oxidation of sorafenib to its N-oxide and N-hydroxymethyl metabolites and also acts in concert with CYP2C8 to mediate imatinib N-demethylation. CYP3A4 expression and function are impaired in patients with advanced liver disease, whereas the functions of CYP2C enzymes are relatively preserved. We evaluated the biotransformation of sorafenib and imatinib in well-characterized microsomal fractions from 17 control subjects and 19 individuals with hepatic cirrhosis of varying severity...
December 6, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29221172/the-prognostic-value-of-inflammation-based-scores-in-advanced-hepatocellular-carcinoma-patients-prior-to-treatment-with-sorafenib
#4
Guillaume Conroy, Julia Salleron, Arthur Belle, Mouni Bensenane, Abdelbasset Nani, Ahmet Ayav, Didier Peiffert, Anthony Lopez, Cédric Baumann, Hélène Barraud, Jean-Pierre Bronowicki
Background and Aims: The multikinase inhibitor sorafenib is the only currently approved drug for the indication of advanced hepatocellular carcinoma (HCC). It provides a limited gain in survival time but is frequently associated with adverse events. We currently lack simple prognostic factors in sorafenib-treated HCC patients. Various inflammation-based scores (IBSs) have been evaluated as predictors of tumor recurrence and survival in various malignancies (including HCC). The objective of the present study was to determine the prognostic value of IBSs for overall survival (OS) in advanced HCC patients prior to the initiation of sorafenib therapy...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220734/high-throughput-routine-determination-of-17-tyrosine-kinase-inhibitors-by-lc-ms-ms
#5
Camille Merienne, Marine Rousset, Dominique Ducint, Nadège Castaing, Karine Titier, Mathieu Molimard, Stéphane Bouchet
Several studies have shown that therapeutic drug monitoring of tyrosine kinase inhibitors (TKI) can improve their benefit in cancer. An analytical tool has been developed in order to quantify 17 tyrosine kinase inhibitors and 2 metabolites in human plasma (afatinib, axitinib, bosutinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, regorafenib, regorafenib M2, regorafenib M5, ruxolitinib, sorafenib, sunitinib, vandetanib). Drugs were arranged in four groups, according to their plasma concentration range: 0...
November 28, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29211397/efficacy-of-targeted-therapy-for-advanced-renal-cell-carcinoma-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#6
Chao Wei, Shen Wang, Zhangqun Ye, Zhiqiang Chen
We conducted a systematic review and meta-analysis of the literature on the efficacy of the targeted therapies in the treatment of advanced RCC and, via an indirect comparison, to provide an optimal treatment among these agents. A systematic search of Medline, Scopus, Cochrane Library and Clinical Trials unpublished was performed up to Jan 1, 2015 to identify eligible randomized trials. Outcomes of interest assessing a targeted agent included progression free survival (PFS), overall survival (OS) and objective response rate (ORR)...
December 7, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/29209641/the-folate-cycle-is-a-new-metabolic-weakness-of-cancer
#7
Derek Lee, Carmen Chak-Lui Wong
Cancer cells harness nutrients to support its rapid proliferation through metabolic reprogramming. Our report identified folate cycle as a metabolic target in hepatocellular carcinoma. Folate cycle stagnation via inhibition of its mitochondrial folate enzyme methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) greatly induced oxidative stress improving HCC cells' response to sorafenib.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29209273/updates-on-the-management-of-advanced-metastatic-and-radioiodine-refractory-differentiated-thyroid-cancer
#8
REVIEW
Dario Tumino, Francesco Frasca, Kate Newbold
Differentiated thyroid cancer (DTC) accounts for 95% of all thyroid cancers and is generally an indolent tumor, treated effectively with surgery, radioactive iodine, and thyroid-stimulating hormone suppressive therapy. However, 5-10% of patients have advanced disease, with aerodigestive tract invasion, distant metastases, or radioiodine refractory disease, with poor prognosis. This review focuses on the approaches for treating advanced DTC, including management of gross extra-thyroidal extension, recurrent loco-regional or distant metastatic disease, the role of external beam radiation therapy and systemic treatment...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29209114/combined-endovascular-brachytherapy-sorafenib-and-transarterial-chemobolization-therapy-for-hepatocellular-carcinoma-patients-with-portal-vein-tumor-thrombus
#9
Zi-Han Zhang, Qing-Xin Liu, Wen Zhang, Jing-Qin Ma, Jian-Hua Wang, Jian-Jun Luo, Ling-Xiao Liu, Zhi-Ping Yan
AIM: To evaluate the safety and efficacy of combined endovascular brachytherapy (EVBT), transarterial chemoembolization (TACE), and sorafenib to treat hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT). METHODS: This single-center retrospective study involved 68 patients with unresectable HCC or those who were unfit for liver transplantation and percutaneous frequency ablation according to the BCLC classification. All patients had Child-Pugh classification grade A or B, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and MPVTT...
November 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29207653/melatonin-enhances-sorafenib-actions-in-human-hepatocarcinoma-cells-by-inhibiting-mtorc1-p70s6k-hif-1%C3%AE-and-hypoxia-mediated-mitophagy
#10
Néstor Prieto-Domínguez, Carolina Méndez-Blanco, Sara Carbajo-Pescador, Flavia Fondevila, Andrés García-Palomo, Javier González-Gallego, José L Mauriz
The antiangiogenic effects of sustained sorafenib treatment in hepatocellular carcinoma (HCC) lead to the occurrence of hypoxia-mediated drug resistance resulting in low therapy efficiency and negative outcomes. Combined treatments with coadjuvant compounds to target the hypoxia-inducible factor-1α (HIF-1α) represent a promising therapeutic approach through which sorafenib efficiency may be improved. Melatonin is a well-documented oncostatic agent against different cancer types. Here, we evaluated whether melatonin could enhance sorafenib cytotoxicity and overcome the hypoxia-mediated resistance mechanisms in HCC...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207150/inhibition-of-autophagy-enhances-the-targeted-therapeutic-effect-of-sorafenib-in-thyroid-cancer
#11
Heqing Yi, Ting Ye, Minghua Ge, Mengdi Yang, Lijun Zhang, Shui Jin, Xuemei Ye, Bin Long, Linfa Li
The multi-target kinase inhibitor sorafenib has been approved for the treatment of patients with advanced differentiated thyroid cancer. However, different sensitivities to sorafenib have been observed, and few patients have benefited from sorafenib treatment in the long term. In the event of acquired resistance to sorafenib it is not beneficial to continue treatment in most patients. Autophagy can be induced in a variety of cancer treatments and plays an important role in cancer treatment. The role of autophagy in sorafenib treatment of thyroid cancer has not been fully demonstrated...
November 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29205034/augmentation-of-anticancer-drug-efficacy-in-murine-hepatocellular-carcinoma-cells-by-a-peripherally-acting-competitive-n-methyl-d-aspartate-nmda-receptor-antagonist
#12
Mikko Gynther, Ilaria Proietti Silvestri, Jacob C Hansen, Kasper B Hansen, Tarja Malm, Yevheniia Ishchenko, Younes Larsen, Liwei Han, Silke Kayser, Seppo Auriola, Aleksanteri Petsalo, Birgitte Nielsen, Darryl S Pickering, Lennart Bunch
The most common solid tumors show intrinsic multidrug resistance (MDR) or inevitably acquire such when treated with anticancer drugs. In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA receptor antagonist 1l by a structure-activity study of the broad-acting ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma cells. The underlying biological mechanism was shown to be interference with the lipid signaling pathway, leading to reduced expression of MDR transporters and thereby an increased accumulation of sorafenib in the cancer cells...
December 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29204178/biological-evaluation-docking-and-molecular-dynamic-simulation-of-some-novel-diaryl-urea-derivatives-bearing-quinoxalindione-moiety
#13
Sedighe Sadeghian-Rizi, Ghadamali Ali Khodarahmi, Amirhossein Sakhteman, Ali Jahanian-Najafabadi, Mahboubeh Rostami, Mahmoud Mirzaei, Farshid Hassanzadeh
In this study a series of diarylurea derivatives containing quinoxalindione group were biologically evaluated for their cytotoxic activities using MTT assay against MCF-7 and HepG2 cell lines. Antibacterial activities of these compounds were also evaluated by Microplate Alamar Blue Assay (MABA) against three Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi), three Gram-positive (Staphylococcus aureus, Bacillus subtilis and Listeria monocitogenes) and one yeast-like fungus (Candida albicans) strain...
December 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29201061/selective-and-irreversible-induction-of-necroptotic-cell-death-in-lung-tumorspheres-by-short-term-exposure-to-verapamil-in-combination-with-sorafenib
#14
Juan Sebastian Yakisich, Yogesh Kulkarni, Neelam Azad, Anand Krishnan V Iyer
The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1) adherent cells growing under prolonged periods of serum starvation (PPSS) and (2) cells growing as floating tumorspheres (FTs) to evaluate the effect of Verapamil (VP) in combination with Sorafenib (SF). Compared to cells growing under routine culture conditions (RCCs), PPPS cells or FTs were highly sensitive to short-term exposure (24 h) to VP 100 μM + SF 5 μM (VP100 + SF5)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29200680/poor-risk-advanced-renal-cell-carcinoma-outcomes-from-a-registry-in-a-tertiary-cancer-center
#15
Anant Ramaswamy, Amit Joshi, Vanita Noronha, Vijay Patil, Arvind Sahu, Deepan R Manickam, Rushabh Kothari, Nilesh Sable, Archi Agrawal, Santosh Menon, Kumar Prabhash
Background: Poor-risk advanced Renal cell carcinoma (RCC) are an under-evaluated and difficult to treat subset of patients with poor prognosis. While Temsirolimus is the approved first line therapy for this category, Tyrosine kinase inhibitors (TKIs) are also commonly uses as initial treatment. We present an analysis of poor-risk advanced RCC treated in our institute. Materials and Methods: Patients diagnosed as poor-risk (as per Heng criteria) advanced RCC from June 2008 to December 2015 were analysed for baseline demographics, treatment received, toxicity (primarily Grade 3 and Grade 4), response rates (RR) and survival...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29199677/effect-of-tyrosine-kinase-inhibitors-on-the-glucose-levels-in-diabetic-and-nondiabetic-patients
#16
E Y Romero-Ventosa, L Otero-Millán, S González-Costas, P Vilasoa-Boo, A Silva-López, C Arroyo-Conde, G Piñeiro-Corrales
CONTEXT: Tyrosine kinase inhibitors (TKIs) are used in different types of cancers due to their good profile of adverse reactions and their convenience in the oral administration. Some studies describe that certain TKIs are associated with changes in the glycemic profile of the patients. AIMS: This study aims to determine if treatment with ITK affects to serum glucose levels in clinical practice. SETTINGS AND DESIGN: A retrospective study was carried out in 136 episodes (112 patients treated with sorafenib, sunitinib, imatinib, dasatinib, or nilotinib)...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29199553/apoptotic-effect-of-taiwanofungus-salmoneus-agaricomycetes-mycelia-and-solid-state-fermented-products-on-cancer-cells
#17
Rao-Chi Chien, Yu-Chieh Lin, Jeng-Leun Mau
Because of the high incidence of and high mortality rates associated with cancer, effective therapy for cancer is currently an imperative issue. Taiwanofungus salmoneus, a medicinal mushroom indigenous to Taiwan, has been demonstrated to exhibit various physiological activities and harmless effects. The bioactive compounds and anticancer abilities of T. salmoneus mycelia and fermented products were evaluated in this study. Total phenols, flavonoids, and ergothioneine were detected in mycelia and fermented products, and the amount of ergothioneine was evaluated in buckwheat (56...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/29198946/prognostic-factors-for-survival-after-transarterial-chemoembolization-combined-with-sorafenib-in-the-treatment-of-bclc-stage-b-and-c-hepatocellular-carcinomas
#18
Jia-Yan Ni, Jian Kong, Hong-Liang Sun, Yao-Ting Chen, Jiang-Hong Luo, Wei-Dong Wang, Dong Chen, Xiong-Ying Jiang, Lin-Feng Xu
RATIONALE AND OBJECTIVE: The objective of this study was to analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with sorafenib for hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stages B and C. MATERIALS AND METHODS: Clinical data of 198 patients with BCLC stage B and C HCCs who underwent TACE combined with sorafenib between June 2012 and January 2017 were retrospectively collected and analyzed. Survival curves were detected using log-rank test...
November 29, 2017: Academic Radiology
https://www.readbyqxmd.com/read/29198329/examining-the-bleeding-incidences-associated-with-targeted-therapies-used-in-metastatic-renal-cell-carcinoma
#19
REVIEW
MacKenzie Crist, Elizabeth Hansen, Lipika Chablani, Elizabeth Guancial
A systematic review was conducted to illustrate the bleeding risks associated with targeted therapies used in the treatment of metastatic renal cell carcinoma (mRCC). Eligible studies included phase II, III, or IV clinical trials using pazopanib, sunitinib, cabozantinib, lenvatinib, everolimus, temsirolimus, bevacizumab, axitinib, and/or sorafenib in the setting of mRCC. Types of bleeding event(s), bleeding event frequency, and incidence of thrombocytopenia were collected from the relevant articles. ClinicalTrials...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29196964/the-earlier-the-better-the-effects-of-different-administration-timepoints-of-sorafenib-in-suppressing-the-carcinogenesis-of-vegf-in-rats
#20
Nan Li, Bin Chen, Run Lin, Ni Liu, Hai-Tao Dai, Ke-Yu Tang, Jian-Yong Yang, Yong-Hui Huang
PURPOSE: To investigate the optimal starting time point of sorafenib therapy in suppressing the tumor-promoting effects of VEGF up-regulation, which is frequently found after local therapy in clinical practice. METHODS: VEGF was intravenously injected to imitate the evaluated expression after local tumor therapy, such as TACE. A total of 40 SD rats bearing hepatic tumors were randomly divided into four groups and sorafenib was administered at different timepoints: (A) control group: VEGF injection only; (B) initiating sorafenib 72 h prior to VEGF injection; (C) initiating sorafenib simultaneously with VEGF injection; (D) initiating sorafenib 72 h post-VEGF injection...
December 1, 2017: Cancer Chemotherapy and Pharmacology
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