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https://www.readbyqxmd.com/read/27923774/mechanistic-insights-into-selective-killing-of-oxphos-dependent-cancer-cells-by-arctigenin
#1
Karin Brecht, Virginie Riebel, Philippe Couttet, Franziska Paech, Armin Wolf, Salah-Dine Chibout, Francois Pognan, Stephan Krähenbühl, Marianne Uteng
Arctigenin has previously been identified as a potential anti-tumor treatment for advanced pancreatic cancer. However, the mechanism of how arctigenin kills cancer cells is not fully understood. In the present work we studied arctigenin's mechanism of toxicity in the human pancreatic cell line, Panc-1, with special emphasis on the mitochondria. A comparison of Panc-1 cells cultured in glucose versus galactose medium was applied, allowing assessments of effects in glycolytic versus oxidative phosphorylation (OXPHOS)-dependent Panc-1 cells...
December 3, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27919126/-a-case-of-renal-cell-carcinoma-with-malignant-pleural-effusion-showing-marked-response-to-axitinib
#2
Yu Ishizuya, Takuya Okusa, Koji Hatano, Yasutomo Nakai, Masashi Nakayama, Ken-Ichi Kakimoto, Kazuo Nishimura
A 36-year-old woman had undergone left radical nephrectomy followed by interferon-α and sunitinib for the treatment of renal cell carcinoma with para-aortic lymph node and lung involvements (papillary renal cell carcinoma, G3, cT3aN1M1) in the previous hospital. She was referred to our hospital for further treatment and received serial molecular targeted agents (everolimus, sorafenib, sunitinib) and radiation therapy for right ischial and femoral bone metastases. Then she was found to have multiple metastatic lesions in the lungs and carcinomatous pleural effusion associated with dyspnea...
October 2016: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/27917085/sorafenib-in-combination-with-transarterial-chemoembolization-for-the-treatment-of-hepatocellular-carcinoma
#3
Jean-Francois H Geschwind, Julius Chapiro
No abstract text is available yet for this article.
August 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27916938/comprehensive-analysis-of-mirnome-alterations-in-response-to-sorafenib-treatment-in-colorectal-cancer-cells
#4
Anna-Maria Pehserl, Anna Lena Ress, Stefanie Stanzer, Margit Resel, Michael Karbiener, Elke Stadelmeyer, Verena Stiegelbauer, Armin Gerger, Christian Mayr, Marcel Scheideler, Georg C Hutterer, Thomas Bauernhofer, Tobias Kiesslich, Martin Pichler
MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib...
December 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916795/first-and-second-line-targeted-systemic-therapy-in-hepatocellular-carcinoma-an-update-on-patient-selection-and-response-evaluation
#5
REVIEW
Johann von Felden, Kornelius Schulze, Ines Gil-Ibanez, Tobias Werner, Henning Wege
Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy...
November 28, 2016: Diagnostics
https://www.readbyqxmd.com/read/27916773/a-case-of-unresectable-combined-hepatocellular-cholangiocarcinoma-showing-favorable-response-to-lfp-therapy
#6
Sayuri Kato, Yasuto Takeuchi, Nozomu Wada, Yuuki Morimoto, Kenji Kuwaki, Hideki Ohnishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada
A woman in her 50s was admitted to our hospital because of multiple tumors detected in her liver. She was diagnosed with combined hepatocellular cholangiocarcinoma using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biopsy of the liver tumors. We judged the tumors to be unresectable because they were found in both lobes of the liver, with a tumor thrombus being found in the main left portal vein. The pathological findings showed that the tumors exhibited characteristics of hepatocellular carcinoma...
2016: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/27914862/neurotensin-regulation-induces-overexpression-and-activation-of-egfr-in-hcc-and-restores-response-to-erlotinib-and-sorafenib
#7
Zherui Wu, Antoine Galmiche, Jin Liu, Nicolas Stadler, Dominique Wendum, Evelyne Segal-Bendirdjian, Valerie Paradis, Patricia Forgez
Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer due to the combination of late diagnosis and a lack of curative treatments. The identification of factors which promote tumor aggressiveness, and those that predict treatment responses, are a means to optimize the management of HCC patients. The complex of Neurotensin (NTS) and its high affinity receptor (NTSR1) has been shown to induce tumor growth and metastasis process in various cancers. In this paper, we propose that NTS and NTSR1 can assist in the management of HCC...
November 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27913861/cxcl12-expression-and-pd-l1-expression-serve-as-prognostic-biomarkers-in-hcc-and-are-induced-by-hypoxia
#8
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors...
December 2, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27911268/texture-analysis-of-intermediate-advanced-hepatocellular-carcinoma-prognosis-and-patients-selection-of-transcatheter-arterial-chemoembolization-and-sorafenib
#9
Sirui Fu, Shuting Chen, Changhong Liang, Zaiyi Liu, Yanjie Zhu, Yong Li, Ligong Lu
Transcatheter arterial chemoembolization (TACE) and sorafenib combination treatment for unselected hepatocellular carcinoma (HCC) is controversial. We explored the potential of texture analysis for appropriate patient selection. There were 261 HCCs included (TACE group: n = 197; TACE plus sorafenib (TACE+Sorafenib) group n = 64). We applied a Gabor filter and wavelet transform with 3 band-width responses (filter 0, 1.0, and 1.5) to portal-phase computed tomography (CT) images of the TACE group. Twenty-one textural parameters per filter were extracted from the region of interests delineated around tumor outline...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27909950/hatt-a-phase-iv-single-arm-open-label-study-of-sorafenib-in-taiwanese-patients-with-advanced-hepatocellular-carcinoma
#10
Shi-Ming Lin, Sheng-Nan Lu, Ping-Tsung Chen, Long-Bin Jeng, Shinn-Cherng Chen, Chi-Tan Hu, Sien-Sing Yang, Marie-Aude Le Berre, Xuan Liu, David Y Mitchell, Klaas Prins, Joachim Grevel, Carol A E Peña, Gerold Meinhardt
BACKGROUND: Sorafenib significantly improves survival in patients with advanced hepatocellular carcinoma (HCC). This phase IV study assessed sorafenib efficacy/safety in Taiwanese patients with advanced HCC and Child-Pugh A status. METHODS: All patients received 400 mg sorafenib BID. Safety, efficacy, sorafenib pharmacokinetics, and Child-Pugh progression were evaluated. A hand-foot skin reaction (HFSR) prevention substudy assessed HFSR incidence and grade/severity and time to HFSR in 29 and 34 patients randomized to corticosteroid and noncorticosteroid ointments, respectively, and in 88 nonrandomized patients...
December 1, 2016: Hepatology International
https://www.readbyqxmd.com/read/27908881/pre-clinical-studies-of-gilteritinib-a-next-generation-flt3-inhibitor
#11
Lauren Y Lee, Daniela Hernandez, Trivikram Rajkhowa, Samuel C Smith, Jayant Ranganathan Raman, Bao Nguyen, Donald Small, Mark Levis
Activating mutations in the receptor tyrosine kinase FLT3 comprise approximately one-third of genetic lesions in acute myeloid leukemia (AML) and are associated with a poor prognosis. Internal tandem duplication (FLT3-ITD) mutations in particular are associated with a high relapse rate. Although FLT3 tyrosine kinase inhibitors (TKIs) appear to improve clinical outcomes for patients with FLT3-ITD AML, the development of early-generation FLT3 TKIs has been impeded by several obstacles such as low potency and selectivity, myelosuppression, and the emergence of resistance-conferring point mutations...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27906677/the-implication-of-flt3-amplification-for-flt-targeted-therapeutics-in-solid-tumors
#12
Sung Hee Lim, Sun-Young Kim, Kyung Kim, Hyojin Jang, Soomin Ahn, Kyoung-Mee Kim, Nayoung K D Kim, Woongyang Park, Su Jin Lee, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Young Suk Park, Se-Hoon Lee, Ho Yeong Lim, Keunchil Park, Won Ki Kang, Jeeyun Lee
We investigated the patients with solid cancers harboring Fms-like tyrosine kinase 3 (FLT3) amplification using targeted sequencing of tumor tissue specimen and FISH assay. Simultaneously, FLT3-amplified patient-derived cells (PDCs) were generated to evaluate the sensitivity to FLT3 inhibition. A patient with metastatic colon cancer who was previously treated with more than 3rd line cytotoxic chemotherapy was found to have FLT3 amplification and then received regorafenib showing partial response. In two PDC cell lines with FLT3 amplification, FLT3 mRNA expression was increased, however, the growth of tumor cells was not significantly inhibited by either regorafenib or sorafenib which is known to block the activity FLT3...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27905019/multi-disciplinary-concurrent-management-of-recurrent-hepatocellular-therapy-is-superior-to-sequential-therapy
#13
Tyler D Fields, Prejesh Philips, Charles R Scoggins, Cliff Tatum, Lawrence Kelly, Kelly M McMasters, Robert C G Martin
BACKGROUND: Recurrent hepatocellular carcinoma after a patient's initial therapy, whether it is transplantation, resection, or ablation, remains a challenging clinical problem. Since recurrence occurs in 70% of all initially treated disease within 5 years, optimal management to treat this recurrence is needed. Currently, a bias exists toward mono-therapy (i.e., ablation alone, hepatic arterial therapy alone, or sorafenib therapy alone) instead of concurrent sequential therapy-as is common in other primary and metastatic disease to the liver...
November 30, 2016: World Journal of Surgery
https://www.readbyqxmd.com/read/27896243/profile-of-tivantinib-and-its-potential-in-the-treatment-of-hepatocellular-carcinoma-the-evidence-to-date
#14
REVIEW
Daniel Pievsky, Nikolaos Pyrsopoulos
Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related death in the United States and carries a very poor prognosis, with a median survival time of <50% at 1 year for advanced disease. To date, sorafenib is the only therapy approved by the Food and Drug Administration for the treatment of advanced HCC. Tivantinib (ARQ-197), a non-ATP competitive inhibitor of cellular mesenchymal-epithelial transcription factor (c-MET), has shown a survival benefit in patients with advanced HCC who have failed or are intolerant to sorafenib in Phase I and II trials...
2016: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/27895433/complete-response-with-sorafenib-and-transcatheter-arterial-chemoembolization-in-unresectable-hepatocellular-carcinoma
#15
Michitoshi Takano, Takashi Kokudo, Yoshihiro Miyazaki, Yumiko Kageyama, Amane Takahashi, Katsumi Amikura, Hirohiko Sakamoto
Patients with advanced hepatocellular carcinoma (HCC) showing portal vein tumor thrombosis (PVTT) have an extremely poor prognosis. According to treatment guidelines, the only option for HCC patients with PVTT is sorafenib chemotherapy. However, in Asia, various treatments have been attempted and possible prolongation of overall survival has been repeatedly reported. We herein report the first case of a patient with an initially unresectable advanced HCC with PVTT who underwent curative hepatectomy after sorafenib and transcatheter arterial chemoembolization (TACE) showing complete histological response...
November 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27894955/blocking-preferential-glucose-uptake-sensitizes-liver-tumor-initiating-cells-to-glucose-restriction-and-sorafenib-treatment
#16
Hui-Lu Zhang, Ming-Da Wang, Xu Zhou, Chen-Jie Qin, Gong-Bo Fu, Liang Tang, Han Wu, Shuai Huang, Ling-Hao Zhao, Min Zeng, Jiao Liu, Dan Cao, Lin-Na Guo, Hong-Yang Wang, He-Xin Yan, Jie Liu
Cancer cells display altered metabolic phenotypes characterized by a high level of glycolysis, even under normoxic conditions. Because of a high rate of glycolytic flux and inadequate vascularization, tumor cells often suffer from nutrient deficiency and require metabolic adaptations to address such stresses. Although tumor-initiating cells (T-ICs) have been identified in various malignancies, the cells' metabolic phenotypes remain elusive. In this study, we observed that liver T-ICs preferentially survived under restricted glucose treatment...
November 26, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27893163/sorafenib-and-azacitidine-as-salvage-therapy-for-relapse-of-flt3-itd-mutated-aml-after-allo-sct
#17
Christina Rautenberg, Kathrin Nachtkamp, Ariane Dienst, Pia Verena Schmidt, Claudia Heyn, Mustafa Kondakci, Ulrich Germing, Rainer Haas, Guido Kobbe, Thomas Schroeder
OBJECTIVE: Patients with acute myeloid leukemia (AML) carrying FLT3-ITD mutations (FLT3-ITD+) who relapse after allogeneic 3transplantation (allo-SCT) have a very dismal prognosis with the currently available treatment options. METHODS: We treated 8 patients with FLT3-ITD+ AML who had relapsed in median 91 days (range, 28 - 249) following allo-SCT with a combination of the multikinase inhibitor Sorafenib and the DNA methyltransferase inhibitor Azacitidine (Aza)...
November 28, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27890855/linker-stability-influences-the-anti-tumor-activity-of-acetazolamide-drug-conjugates-for-the-therapy-of-renal-cell-carcinoma
#18
Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Small molecule-drug conjugates (SMDCs) are increasingly being considered as an alternative to antibody-drug conjugates (ADCs) for the selective delivery of anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of renal cell carcinomas and which can be efficiently targeted in vivo, using charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here, we show that SMDC products, obtained by the coupling of acetazolamide with monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti-tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27887628/implications-of-vessel-co-option-in-sorafenib-resistant-hepatocellular-carcinoma
#19
Elizabeth A Kuczynski, Robert S Kerbel
The reason why tumors generally have a modest or transient response to antiangiogenic therapy is not well understood. This poses a major challenge for sorafenib treatment of advanced hepatocellular carcinoma (HCC) where alternate therapies are lacking. We recently published a paper entitled "Co-option of liver vessels and not sprouting angiogenesis drives acquired sorafenib resistance in hepatocellular carcinoma" in the Journal of the National Cancer Institute, providing a potential explanation for this limited benefit...
November 25, 2016: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/27884331/inhibition-of-acquired-resistance-hepatocellular-carcinoma-cell-growth-by-combining-sorafenib-with-phosphoinositide-3-kinase-and-rat-sarcoma-inhibitor
#20
Chang-Hao Wu, Xiang Wu, Hong-Wei Zhang
BACKGROUND: To provide support for combined usage of phosphoinositide 3-kinase (PI3K) inhibitors or mitogen-activated protein kinase pathway inhibitors together with sorafenib in treatment of sorafenib-resistant hepatocellular carcinoma. MATERIALS AND METHODS: The sorafenib-resistant cell lines were established to evaluate the effects of MK-2206 2HCL, a dual PI3K/mammalian target of rapamycin (mTOR) inhibitor, and PD0325901, an rat sarcoma (RAS) and/or extracellular signal-regulated kinase (ERK) inhibitor, on cell proliferation and apoptosis, as both single and combined treatments with sorafenib...
December 2016: Journal of Surgical Research
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