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gemcitabine resistance

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https://www.readbyqxmd.com/read/29163710/combination-of-histoculture-drug-response-assay-and-qpcr-as-an-effective-method-to-screen-biomarkers-for-personalized-chemotherapy-in-esophageal-cancer
#1
Bin Wei, Jiru Wang, Xiaohui Zhang, Zhaoye Qian, Jingjing Wu, Yuan Sun, Qin Han, Li Wan, Jing Zhu, Yong Gao, Xiaofei Chen
Personalized chemotherapy with the use of biomarkers helps to maximize clinical efficiency. Therefore, the present study aimed to identify a potential method for identifying biomarkers in esophageal cancer. A total of 49 freshly resected tumor tissues and 72 paraffin-embedded specimens from patients with esophageal cancer were obtained. mRNA expression levels of ERCC1, BRCA1, TUBB3, FBW7, RRM1, MDM2, TS and TOP1 were measured quantitative reverse transcription polymerase chain reaction (RT-qPCR). In vitro chemosensitivity to cisplatin, docetaxel, gemcitabine, etoposide, fluorouracil and irinotecan were tested using histoculture drug response assay (HDRA)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29158911/a-retrospective-evaluation-of-activity-of-gemcitabine-platinum-regimens-in-the-treatment-of-recurrent-ovarian-cancer
#2
Tran N Le, Rachel E Harvey, Christine K Kim, Jubilee Brown, Robert L Coleman, Judith A Smith
Background: While many of these agents have been compared in prospective clinical trials, the gemcitabine/platinumbased regimens have not been compared in a prospective, randomized clinical trial. While bothgemcitabine/carboplatin and gemcitabine/cisplatin have a similar ORR in separate clinical trials, the tworegimens have never been directly been compared. With overlapping dose-limiting toxicity of thrombocytopenia, the gemcitabine/carboplatin regimen has been challenging to employ in the clinical setting in previously treated ovarian cancer patients and is often associated with treatment delays and/or dose reductions...
2017: Gynecologic Oncology Research and Practice
https://www.readbyqxmd.com/read/29156697/exploring-brusatol-as-a-new-anti-pancreatic-cancer-adjuvant-biological-evaluation-and-mechanistic-studies
#3
Zheng Lu, Zheng-Quan Lai, Albert W N Leung, Po Sing Leung, Zhao-Shen Li, Zhi-Xiu Lin
Pancreatic cancer is highly resistant to chemotherapeutic agents and is known to have a poor prognosis. The development of new therapeutic entities is badly needed for this deadly malignancy. In this study, we demonstrated for the first time that brusatol, a natural quassinoid isolated from a Chinese herbal medicine named Bruceae Fructus, possessed potent cytotoxic effect against different pancreatic adenocarcinoma cell lines. Its anti-pancreatic cancer effect was comparable to that of the first-line chemotherapeutic agents such as gemcitabine and 5-fluorouracil, with a more favorable safety profile...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29144412/pancreatic-cancer-chemoresistance-to-gemcitabine
#4
REVIEW
Manoj Amrutkar, Ivar P Gladhaug
Pancreatic ductal adenocarcinoma (PDAC), commonly referred to as pancreatic cancer, ranks among the leading causes of cancer-related deaths in the Western world due to disease presentation at an advanced stage, early metastasis and generally a very limited response to chemotherapy or radiotherapy. Gemcitabine remains a cornerstone of PDAC treatment in all stages of the disease despite suboptimal clinical effects primarily caused by molecular mechanisms limiting its cellular uptake and activation and overall efficacy, as well as the development of chemoresistance within weeks of treatment initiation...
November 16, 2017: Cancers
https://www.readbyqxmd.com/read/29143983/growth-of-doxorubicin-resistant-undifferentiated-spindle-cell-sarcoma-pdox-is-arrested-by-metabolic-targeting-with-recombinant-methioninase
#5
Kentaro Igarashi, Shukuan Li, Qinghong Han, Yuying Tan, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Yunfeng Li, Scott D Nelson, Sarah M Dry, Arun S Singh, Irmina A Elliott, Tara A Russell, Mark A Eckardt, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Undifferentiated spindle-cell sarcoma (USCS) is a recalcitrant -cancer in need of individualized therapy. A high-grade USCS from a striated muscle of a patient was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. In a previous study, we evaluated the efficacy of standard first-line chemotherapy of doxorubicin (DOX), gemcitabine (GEM) combined with docetaxel (DOC), compared to pazopanib (PAZ), a multi-targeting tyrosine-kinase inhibitor, in an USCS PDOX model...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29137060/a-case-report-of-mixed-acinar-endocrine-carcinoma-of-the-pancreas-treated-with-s-1-chemotherapy-does-it-work-or-induce-endocrine-differentiation
#6
Masataka Yokode, Ryosuke Itai, Yukimasa Yamashita, Yoh Zen
RATIONALE: Acinar cell carcinomas (ACCs) and mixed acinar-endocrine carcinomas (MAECs) of the pancreas are rare, accounting for only 1% of pancreatic tumors. Although both typically present at an advanced stage, chemotherapeutic regimes have not yet been standardized. PATIENT CONCERNS: A 65-year-old man presented with a large mass in the pancreatic tail with multiple liver metastases. DIAGNOSIS, INTERVENTIONS, OUTCOMES: He was initially treated with gemcitabine for suspected ductal carcinoma of the pancreas, but no response was observed...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29127277/dual-protein-kinase-and-nucleoside-kinase-modulators-for-rationally-designed-polypharmacology
#7
Kahina Hammam, Magali Saez-Ayala, Etienne Rebuffet, Laurent Gros, Sophie Lopez, Berengere Hajem, Martine Humbert, Emilie Baudelet, Stephane Audebert, Stephane Betzi, Adrien Lugari, Sebastien Combes, Sebastien Letard, Nathalie Casteran, Colin Mansfield, Alain Moussy, Paulo De Sepulveda, Xavier Morelli, Patrice Dubreuil
Masitinib, a highly selective protein kinase inhibitor, can sensitise gemcitabine-refractory cancer cell lines when used in combination with gemcitabine. Here we report a reverse proteomic approach that identifies the target responsible for this sensitisation: the deoxycytidine kinase (dCK). Masitinib, as well as other protein kinase inhibitors, such as imatinib, interact with dCK and provoke an unforeseen conformational-dependent activation of this nucleoside kinase, modulating phosphorylation of nucleoside analogue drugs...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29123259/tumour-infiltrating-inflammatory-and-immune-cells-in-patients-with-extrahepatic-cholangiocarcinoma
#8
Yuki Kitano, Hirohisa Okabe, Yo-Ichi Yamashita, Shigeki Nakagawa, Yoichi Saito, Naoki Umezaki, Masayo Tsukamoto, Takanobu Yamao, Kensuke Yamamura, Kota Arima, Takayoshi Kaida, Tatsunori Miyata, Kosuke Mima, Katsunori Imai, Daisuke Hashimoto, Yoshihiro Komohara, Akira Chikamoto, Takatoshi Ishiko, Hideo Baba
BACKGROUND: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC). METHODS: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b(+) neutrophils (TANs; tumour associated neutrophils), CD163(+) M2 macrophages (TAMs; tumour associated macrophages), CD8(+) T cells, and FOXP3(+) regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated...
November 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29121415/efficacy-and-safety-of-trametinib-in-japanese-patients-with-advanced-biliary-tract-cancers-refractory-to-gemcitabine
#9
Masafumi Ikeda, Tatsuya Ioka, Akira Fukutomi, Chigusa Morizane, Akiyoshi Kasuga, Hideaki Takahashi, Akiko Todaka, Takuji Okusaka, Caretha L Creasy, Shelby Gorman, Daniel J Felitsky, Mikiro Kobayashi, Fanghong Zhang, Junji Furuse
Gemcitabine-based therapy remains the mainstay of treatment for patients with biliary tract cancers (BTCs) with no second-line treatment(s) established yet. Aberrant activation of MAPK pathway in patients with BTC indicates its importance in BTC. Trametinib is a potent, highly selective, allosteric non-competitive inhibitor of MEK1/MEK2. In this Phase IIa open-label, single-arm study, we investigated efficacy and safety of trametinib in Japanese patients with advanced BTC refractory to gemcitabine-based therapy...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29120411/alternative-polyadenylation-of-zeb1-promotes-its-translation-during-genotoxic-stress-in-pancreatic-cancer-cells
#10
Ilaria Passacantilli, Valentina Panzeri, Pamela Bielli, Donatella Farini, Emanuela Pilozzi, Gianfranco Delle Fave, Gabriele Capurso, Claudio Sette
Pancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis. The standard chemotherapeutic drug, gemcitabine, does not offer significant improvements for PDAC management due to the rapid acquisition of drug resistance by patients. Recent evidence indicates that epithelial-to-mesenchymal transition (EMT) of PDAC cells is strictly associated to early metastasization and resistance to chemotherapy. However, it is not exactly clear how EMT is related to drug resistance or how chemotherapy influences EMT...
November 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29118324/suppression-of-the-fa-pathway-combined-with-chk1-inhibitor-hypersensitize-lung-cancer-cells-to-gemcitabine
#11
Chun-Hua Dai, Yi Wang, Ping Chen, Qian Jiang, Ting Lan, Mei-Yu Li, Jin-Yu Su, Yan Wu, Jian Li
The combination of platinum and gemcitabine is one of the standard regimens in the treatment of advanced lung squamous carcinoma (LSC). Resistance to gemcitabine is main barrier to the successful treatment of LSC. In this study, we showed that suppression of the Fanconi anemia (FA) pathway increased the sensitivity of two LSC cell lines SK-MES-1 and KLN205 to gemcitabine. Moreover, we found that the CHK1 pathway and the FA pathway are functionally compensatory in the repair of DNA damage in the LSC cell lines...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29113279/hmgb1-mediated-autophagy-confers-resistance-to-gemcitabine-in-hormone-independent-prostate-cancer-cells
#12
Yi-Xiang Zhang, Ye-Qing Yuan, Xue-Qi Zhang, Dong-Long Huang, Yu-Ying Wei, Jiang-Gen Yang
As a main treatment of prostate cancer, castration therapy has been widely applied in the clinic. However, the therapeutic strategy for hormone-independent prostate cancer (HIPC) was not satisfied. Gemcitabine is an important chemotherapeutic agent that has been approved for the treatment of numerous human solid tumors, including HIPC, whereas the gemcitabine resistance has become a serious problem in clinical chemotherapy. In the present study, the mechanisms of resistance to gemcitabine were investigated in HIPC cell lines...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113179/blocking-integrin-%C3%AE-1-decreases-adhesion-in-chemoresistant-urothelial-cancer-cell-lines
#13
Stefan Vallo, Jochen Rutz, Miriam Kautsch, Ria Winkelmann, Martin Michaelis, Felix Wezel, Georg Bartsch, Axel Haferkamp, Florian Rothweiler, Roman A Blaheta, Jindrich Cinatl Jr
Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first-line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabine- and four cisplatin-resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC-SUP, HT1376, T24, and 5637) were used...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29107110/nimbolide-reduces-cd44-positive-cell-population-and-induces-mitochondrial-apoptosis-in-pancreatic-cancer-cells
#14
Sandeep Kumar, Joseph R Inigo, Rahul Kumar, Ajay K Chaudhary, Jordan O'Malley, Srimmitha Balachandar, Jianmin Wang, Kristopher Attwood, Neelu Yadav, Steven Hochwald, Xinjiang Wang, Dhyan Chandra
Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive disease and current treatment regimens fail to effectively cure PDAC. Development of resistance to current therapy is one of the key reasons for this outcome. Nimbolide (NL), a triterpenoid obtained from Azadirachta indica, exhibits anticancer properties in various cancer including PDAC cells. However, the underlying mechanism of this anticancer agent in PDAC cells remains undefined. We show that NL exerts a higher level of apoptotic cell death compared to the first-line agent gemcitabine for PDAC, as well as other anticancer agents including sorafenib and curcumin...
October 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29100320/suppression-of-pancreatic-adenocarcinoma-upregulated-factor-pauf-increases-the-sensitivity-of-pancreatic-cancer-to-gemcitabine-and-5fu-and-inhibits-the-formation-of-pancreatic-cancer-stem-like-cells
#15
Jae Hee Cho, Sun A Kim, Soo Been Park, Hee Man Kim, Si Young Song
Pancreatic cancer stem cells (CSCs) play a crucial role in tumorigenesis and chemoresistance of pancreatic ductal adenocarcinoma. Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel secretory protein, has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the associations between the functional role of PAUF and pancreatic CSCs. Pancreatic cancer sphere cultured from the CFPAC-1 cells showed elevated expression of PAUF and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2), and the mRNA of PAUF were increased in CD44(+)CD24(+)ESA(+) pancreatic CSCs...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098031/astaxanthin-inhibits-gemcitabine-resistant-human-pancreatic-cancer-progression-through-emt-inhibition-and-gemcitabine-resensitization
#16
Tao Yan, Hai-Ying Li, Jian-Song Wu, Qiang Niu, Wei-Hong Duan, Qing-Zeng Han, Wang-Ming Ji, Tao Zhang, Wei Lv
Pancreatic cancer rapidly acquires resistance to chemotherapy resulting in its being difficult to treat. Gemcitabine is the current clinical chemotherapy strategy; however, owing to gemcitabine resistance, it is only able to prolong the life of patients with pancreatic cancer for a limited number of months. Understanding the underlying molecular mechanisms of gemcitabine resistance and selecting a suitable combination of agents for the treatment of pancreatic cancer is required. Astaxanthin (ASX) is able to resensitize gemcitabine-resistant human pancreatic cancer cells (GR-HPCCs) to gemcitabine...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29096687/synergistic-effects-of-combining-proteasome-inhibitors-with-chemotherapeutic-drugs-in-lung-cancer-cells
#17
Linda Sooman, Joachim Gullbo, Michael Bergqvist, Stefan Bergström, Johan Lennartsson, Simon Ekman
BACKGROUND: The prognosis for patients with disseminated lung cancer is poor and current treatments have limited survival benefit as resistance often occurs, and is often associated with significant toxicity. A possible strategy to improve treatment and evade chemoresistance may be to find new combinations of drugs. The aim of this study was to analyze the potential of combining proteasome inhibitors (PIs) with chemotherapeutic drugs used in the routine treatment for lung cancer patients...
November 2, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29095283/experience-of-weekly-cisplatin-concurrent-with-intensity-modulated-radiotherapy-for-locally-advanced-nasopharyngeal-carcinoma-patients-with-resistance-to-neoadjuvant-chemotherapy
#18
Chuanben Chen, Taojun Chen, Chaoxiong Huang, Jing Wang, Zhaodong Fei
Nasopharyngeal carcinoma (NPC) is highly sensitive to radiotherapy. Locally advanced NPC has a relatively poor prognosis if treated with radiotherapy alone. Several studies have demonstrated that chemoradiotherapy confers survival benefit in locally advanced NPC. However, a small proportion of patients are resistant to chemotherapy based on cisplatin. So, it is important to make a valuable and inexpensive schedule for these patients. After 2 cycles of neoadjuvant chemotherapy that consisted of gemcitabine and cisplatin (80 mg/m, every 3 weeks) or paclitaxel and cisplatin (80 mg/m, every 3 weeks), magnetic resonance imaging (MRI) was used to evaluate efficacy...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29092062/gemcitabine-based-chemotherapy-in-adrenocortical-carcinoma-a-multicenter-study-of-efficacy-and-predictive-factors
#19
Judith E K Henning, Timo Deutschbein, Barbara Altieri, Sonja Steinhauer, Stefan Kircher, Silviu Sbiera, Vanessa Wild, Wiebke Schlötelburg, Matthias Kroiss, Paola Perotti, Andreas Rosenwald, Alfredo Berruti, Martin Fassnacht, Cristina L Ronchi
Context: Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29080971/combination-chemotherapy-with-irinotecan-and-gemcitabine-for-taxane-platinum-resistant-refractory-ovarian-and-primary-peritoneal-cancer-a-multicenter-phase-i-ii-trial-gogo-ov-6
#20
Kiyoshi Yoshino, Shoji Kamiura, Takeshi Yokoi, Ruriko Nakae, Masami Fujita, Masahiko Takemura, Kazushige Adachi, Akinori Wakimoto, Takamichi Nishizaki, Yasuhiko Shiki, Tateki Tsutsui, Yuki Kanda, Eiji Kobayashi, Kae Hashimoto, Seiji Mabuchi, Yutaka Ueda, Kenjiro Sawada, Takuji Tomimatsu, Tadashi Kimura
PURPOSE: To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy. METHODS: Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m(2), respectively; level 2: 100 and 1000 mg/m(2)) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity...
October 28, 2017: Cancer Chemotherapy and Pharmacology
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