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gemcitabine resistance

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https://www.readbyqxmd.com/read/28440469/clinical-significance-of-akt2-in-advanced-pancreatic-cancer-treated-with-erlotinib
#1
Eri Banno, Yosuke Togashi, Marco A de Velasco, Takuro Mizukami, Yu Nakamura, Masato Terashima, Kazuko Sakai, Yoshihiko Fujita, Ken Kamata, Masayuki Kitano, Masatoshi Kudo, Kazuto Nishio
Akt2 is an isoform of Akt, and an association between Akt2 and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been suggested in pancreatic cancer (PC) in vitro. In this study, we investigated the association between Akt2 expression as evaluated using immunohistochemistry and the outcome of patients with advanced PC who had received treatment with erlotinib (an EGFR-TKI). Although the difference was not significant, patients with high levels of Akt2 expression tended to have a poorer response and a shorter progression-free survival period after treatment with erlotinib plus gemcitabine than those with low expression levels (P=0...
April 18, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440428/inhibition-of-atr-potentiates-the-cytotoxic-effect-of-gemcitabine-on-pancreatic-cancer-cells-through-enhancement-of-dna-damage-and-abrogation-of-ribonucleotide-reductase-induction-by-gemcitabine
#2
Shuang Liu, Yubin Ge, Tingting Wang, Holly Edwards, Qihang Ren, Yiqun Jiang, Chengshi Quan, Guan Wang
Pancreatic cancer is a highly malignant disease with a dismal prognosis. Gemcitabine (GEM)-based chemotherapy is the first-line treatment for patients with advanced disease, although its efficacy is very limited, mainly due to drug resistance. Ataxia telangiectasia and Rad3-related (ATR) plays a critical role in the DNA damage response (DDR) which has been implicated in GEM resistance. Thus, targeting ATR represents a promising approach to enhance GEM antitumor activity. In the present study, we tested the antitumor activity of AZ20, a novel ATR-selective inhibitor, alone or combined with GEM in 5 pancreatic cancer cell lines...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28428074/melittin-inhibits-tumor-growth-and-decreases-resistance-to%C3%A2-gemcitabine-by-downregulating-cholesterol-pathway-gene%C3%A2-clu%C3%A2-in%C3%A2-pancreatic-ductal-adenocarcinoma
#3
Xinjing Wang, Jing Xie, Xiongxiong Lu, Hongzhe Li, Chenlei Wen, Zhen Huo, Junjie Xie, Minmin Shi, Xiaomei Tang, Hao Chen, Chenghong Peng, Yuan Fang, Xiaxing Deng, Baiyong Shen
Melittin is a Chinese traditional medicine for treating chronic inflammation, immunological diseases and cancers, however, the efficacy of melittin and its mechanism for treating pancreatic ductal adenocarcinoma (PDAC) are still unknown. Here we investigated the anti-cancer activity of melittin and its regulated mechanism(s) in the PDAC models. Melittin was found to suppress tumor growth by promoting cell apoptosis and cell-cycle arrest. Interestingly, the microarray analyses demonstrated that melittin significantly regulated cholesterol biosynthesis pathway during treatment...
April 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28418923/osu-a9-inhibits-pancreatic-cancer-cell-lines-by-modulating-p38-jak-stat3-signaling
#4
Wan-Chi Tsai, Li-Yuan Bai, Yi-Jin Chen, Po-Chen Chu, Ya-Wen Hsu, Aaron M Sargeant, Jing-Ru Weng
Pancreatic cancer is an aggressive malignancy that is the fourth leading cause of death worldwide. Since there is a dire need for novel and effective therapies to improve the poor survival rates of advanced pancreatic cancer patients, we analyzed the antitumor effects of OSU-A9, an indole-3-carbinol derivative, on pancreatic cancer cell lines in vitro and in vivo. OSU-A9 exhibited a stronger antitumor effect than gemcitabine on two pancreatic cancer cell lines, including gemcitabine-resistant PANC-1 cells. OSU-A9 treatment induced apoptosis, the down-regulation of Akt phosphorylation, up-regulation of p38 phosphorylation and decreased phosphorylation of JAK and STAT3...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416665/hippo-pathway-mediates-resistance-to-cytotoxic-drugs
#5
Taranjit S Gujral, Marc W Kirschner
Chemotherapy is widely used for cancer treatment, but its effectiveness is limited by drug resistance. Here, we report a mechanism by which cell density activates the Hippo pathway, which in turn inactivates YAP, leading to changes in the regulation of genes that control the intracellular concentrations of gemcitabine and several other US Food and Drug Administration (FDA)-approved oncology drugs. Hippo inactivation sensitizes a diverse panel of cell lines and human tumors to gemcitabine in 3D spheroid, mouse xenografts, and patient-derived xenograft models...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28407685/extra-pancreatic-invasion-induces-lipolytic-and-fibrotic-changes-in-the-adipose-microenvironment-with-released-fatty-acids-enhancing-the-invasiveness-of-pancreatic-cancer-cells
#6
Takashi Okumura, Kenoki Ohuchida, Masafumi Sada, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Chika Iwamoto, Daisuke Miura, Yusuke Mizuuchi, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura
Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404939/d-tocotrienol-a-natural-form-of-vitamin-e-inhibits-pancreatic-cancer-stem-like-cells-and-prevents-pancreatic-cancer-metastasis
#7
Kazim Husain, Barbara A Centeno, Domenico Coppola, Jose Trevino, Said M Sebti, Mokenge P Malafa
The growth, metastasis, and chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC) is characterized by the activation and growth of tumor-initiating cells in distant organs that have stem-like properties. Thus, inhibiting growth of these cells may prevent PDAC growth and metastases. We have demonstrated that δ-tocotrienol, a natural form of vitamin E (VEDT), is bioactive against cancer, delays progression, and prevents metastases in transgenic mouse models of PDAC. In this report, we provide the first evidence that VEDT selectively inhibits PDAC stem-like cells...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28365185/curcumin-and-its-cyclohexanone-analogue-inhibited-human-equilibrative-nucleoside-transporter-1-ent1-in-pancreatic-cancer-cells
#8
Jezrael L Revalde, Yan Li, Tharaka S Wijeratne, Piyush Bugde, Bill C Hawkins, Rhonda J Rosengren, James W Paxton
Our group investigated combining the phytochemical curcumin and gemcitabine in a liposome, to improve gemcitabine's activity against pancreatic tumours. While optimising the curcumin: gemcitabine ratio for co-encapsulation, we found that increasing curcumin concentrations relative to gemcitabine resulted in antagonistic interactions. As curcumin is a promiscuous transporter inhibitor; we suspected that increased resistance occurred via inhibition of Equilibrative nucleoside transporter 1 (ENT1)-mediated gemcitabine uptake...
May 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28356963/human-antigen-r-as-a-predictive-marker-for-response-to-gemcitabine-based-chemotherapy-in-advanced-cisplatin-resistant-urothelial-cancer
#9
Yasuyoshi Miyata, Kensuke Mitsunari, Asai Akihiro, Shin-Ichi Watanabe, Tomohiro Matsuo, Kojiro Ohba, Hideki Sakai
In patients with advanced urothelial cancer (UC), a combination of cisplatin (CDDP) and gemcitabine (GEM) is the most commonly used first-line systematic chemotherapy regimen. Although no standard regime for the treatment of CDDP-resistant UC has been established, GEM-based regimens are frequently used in these patients. In other types of cancer, human antigen R (HuR) status in cancer cells is closely associated with patient response to GEM. The aim of the present study was to establish the predictive potential of HuR expression for disease progression and survival in patients with UC who were treated with GEM-based regimens as a first or second-line chemotherapy...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28351036/hypoxia-induces-multidrug-resistance-via-enhancement-of-epidermal-growth-factor-like-domain-7-expression-in-non-small-lung-cancer-cells
#10
Xiaochun Shen, Qiaoming Zhi, Yunliang Wang, Zhi Li, Jin Zhou, Jianan Huang
Chemotherapy is widely used in non-small cell lung cancer (NSCLC) treatment, yet multidrug resistance (MDR) is a major chemotherapeutic obstacle in both resectable and advanced NSCLC. Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, is an endothelial cell-derived secreted factor that regulates vascular tube formulation. The aim of this study was to investigate the potential relationships between EGFL7 and MDR in NSCLC cells. We first obtained the CDDP-based MDR phenotype cell line A549/CDDP by repeated exposure to a proper concentration of CDDP (cisplatin) from original A549 cells...
2017: Chemotherapy
https://www.readbyqxmd.com/read/28325302/aptamer-drug-conjugates-of-active-metabolites-of-nucleoside-analogs-and-cytotoxic-agents-inhibit-pancreatic-tumor-cell-growth
#11
Sorah Yoon, Kai-Wen Huang, Vikash Reebye, Duncan Spalding, Teresa M Przytycka, Yijie Wang, Piotr Swiderski, Lin Li, Brian Armstrong, Isabella Reccia, Dimitris Zacharoulis, Konstantinos Dimas, Tomokazu Kusano, John Shively, Nagy Habib, John J Rossi
Aptamer-drug conjugates (ApDCs) have the potential to improve the therapeutic index of traditional chemotherapeutic agents due to their ability to deliver cytotoxic drugs specifically to cancer cells while sparing normal cells. This study reports on the conjugation of cytotoxic drugs to an aptamer previously described by our group, the pancreatic cancer RNA aptamer P19. To this end, P19 was incorporated with gemcitabine and 5-fluorouracil (5-FU), or conjugated to monomethyl auristatin E (MMAE) and derivative of maytansine 1 (DM1)...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325092/effectiveness-of-low-dose-oral-etoposide-treatment-in-patients-with-recurrent-and-platinum-resistant-epithelial-ovarian-cancer
#12
Yakup Bozkaya, Mutlu Doğan, Gökmen Umut Erdem, Gökhan Tulunay, Hikmet Uncu, Zafer Arık, Umut Demirci, Ozan Yazıcı, Nurullah Zengin
The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50 mg/day, days 1-14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment...
March 21, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28322141/lessons-learned-from-gemcitabine-impact-of-therapeutic-carrier-systems-and-gemcitabine-s-drug-conjugates-on-cancer-therapy
#13
REVIEW
Sathish Dyawanapelly, Animesh Kumar, Manish K Chourasia
Currently, drug delivery systems have a high impact in cancer therapy and are receiving more attention than conventional cancer treatment modalities. Compared with current cancer therapies, gemcitabine (2', 2'-difluoro-2'-deoxycytidine) has been proven to be an effective chemotherapeutic agent against pancreatic, colon, bladder, breast, ovarian, non-small-cell lung, and head and neck cancers in combination with other anticancer agents. To improve the safety and efficacy of cytotoxic drugs, several drug delivery systems have been explored...
2017: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/28302042/natural-anti-cancer-agents-implications-in-gemcitabine-resistant-pancreatic-cancer-treatment
#14
Bishal Marasini, Ravi P Sahu
Pancreatic cancer is one of the most lethal malignancy accounting for the fourth leading cause of cancer-related deaths in the United States. Among several explored anti-cancer agents, Gemcitabine, a nucleoside analogue remained a front line chemotherapeutic agent for the treatment of pancreatic cancer. However, gemcitabine exerts a low response rate with limited progression free survival in cancer patients due to cellular resistance of pancreatic tumors to this therapy. Several chemotherapeutic agents have been explored in combination with gemcitabine against pancreatic cancer with overall mixed responses and survival rates...
March 15, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28288630/overexpression-of-g-protein-coupled-receptor-gpr87-promotes-pancreatic-cancer-aggressiveness-and-activates-nf-%C3%AE%C2%BAb-signaling-pathway
#15
Li Wang, Wei Zhou, Yunfeng Zhong, Yongbao Huo, Ping Fan, Sudong Zhan, Jun Xiao, Xin Jin, Shanmiao Gou, Tao Yin, Heshui Wu, Tao Liu
BACKGROUND: Pancreatic cancer is a highly lethal disease and has the worst prognosis of any major malignancy. G protein-coupled receptor GPR87 is reported to be overexpressed in multiple cancers. The clinical significance and biological role of GPR87 in pancreatic cancer, however, remain to be established. METHODS: GPR87 expression in pancreatic cancer cell lines, paired patient tissues were determined using western blotting and Real-time PCR. Ninety-six human pancreatic cancer tissue samples were analyzed by immunochemistry (IHC) to investigate the association between GPR87 expression and the clinicopathological characteristics of pancreatic cancer...
March 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28270046/low-muc4-expression-is-associated-with-survival-benefit-in-patients-with-resectable-pancreatic-cancer-receiving-adjuvant-gemcitabine
#16
Carlos Urey, Bodil Andersson, Daniel Ansari, Agata Sasor, Katarzyna Said-Hilmersson, Johan Nilsson, Roland Andersson
BACKGROUND: Previous in vitro studies have shown that mucin 4 (MUC4) confers resistance toward gemcitabine in pancreatic cancer cells. To date, there are few clinical studies corroborating these findings. The aim of this study was to evaluate the predictive impact of MUC4 expression on survival in patients with resectable pancreatic cancer receiving adjuvant gemcitabine. MATERIALS AND METHODS: MUC4 expression was investigated by immunohistochemistry in 78 tissue sections from patients with pancreatic ductal adenocarcinoma undergoing Whipple resection...
May 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28264536/-a-case-of-papillary-renal-cell-carcinoma-40-years-after-radiation-therapy
#17
Kenta Onishi, Satoshi Anai, Yusuke Iemura, Yasushi Nakai, Makito Miyake, Yoshitomo Chihara, Nobumichi Tanaka, Kiyohide Fujimoto
Here, we report a case of papillary renal cell carcinoma in a 47-year-old woman. In 1970 (at 5 years old), she was diagnosed with Wilms tumor in her right kidney, and underwent surgery. However, nephrectomy was not possible. Consequently, she received radiation therapy (61. 5 Gy) at the former hospital. Thereafter, the patient regularly visited her physician and had no further problems. In 1998 (at 33 years old), blood was detected in her urine, and renal cell carcinoma was suspected. A computed tomography (CT)-guided biopsy was performed, but tissue collection was difficult due to calcification of the renal parenchyma after radiation treatment...
February 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28263231/appendix-derived-pseudomyxoma-peritonei-pmp-molecular-profiling-toward-treatment-of-a-rare-malignancy
#18
Elizabeth M Gleeson, Rebecca Feldman, Beth L Mapow, Lynn T Mackovick, Kristine M Ward, William F Morano, Rene R Rubin, Wilbur B Bowne
OBJECTIVES: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. METHODS: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization)...
March 3, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28259943/sclareolide-enhances-gemcitabine%C3%A2-induced-cell-death-through-mediating-the-nicd-and-gli1-pathways-in-gemcitabine%C3%A2-resistant-human-pancreatic-cancer
#19
Sheng Chen, Ye Wang, Wen-Long Zhang, Mao-Sheng Dong, Jian-Hua Zhang
Pancreatic cancer is a type of cancer, which rapidly develops resistance to chemotherapy. Gemcitabine is the treatment used clinically, however, gemcitabine resistance leads to limited efficacy and patient survival rates of only a few months following diagnosis. The aim of the present study was to investigate the mechanisms underlying gemcitabine resistance in pancreatic cancer and to select targeted agents combined with gemcitabine to promote the treatment of pancreatic cancer. Panc‑1 and ASPC‑1 human pancreatic cancer cells (HPCCs) were used to establish the experimental model, and HPCCs were exposed to gemcitabine of serially increased concentrations to generate gemcitabine‑resistant cells (GR‑HPCCs)...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28253715/microrna-1285-inhibits-malignant-biological-behaviors-of-human-pancreatic-cancer-cells-by-negative-regulation-of-yap1
#20
H Huang, G Xiong, P Shen, Z Cao, L Zheng, T Zhang, Y Zhao
Pancreatic ductal adenocarcinoma is a most deadly malignancy, with a 5-year survival rate of ~7%. Chemotherapy is the main treatment strategy of this disease. However, the high rate of resistance to chemotherapeutic agent contributes to poor prognosis. MicroRNAs are essential for the initiation, progression and chemoresistance of human malignancies. Previous studies have shown that miRNA-1285 participates in renal cell carcinoma and hepatocellular carcinoma. However, its roles in pancreatic ductal adenocarcinoma are poorly understood...
March 3, 2017: Neoplasma
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