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gemcitabine resistance

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https://www.readbyqxmd.com/read/28325302/aptamer-drug-conjugates-of-active-metabolites-of-nucleoside-analogs-and-cytotoxic-agents-inhibit-pancreatic-tumor-cell-growth
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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)...
February 8, 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
#10
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
https://www.readbyqxmd.com/read/28244691/up-regulation-of-glycolysis-promotes-the-stemness-and-emt-phenotypes-in-gemcitabine-resistant-pancreatic-cancer-cells
#11
Hengqiang Zhao, Qingke Duan, Zhengle Zhang, Hehe Li, Heshui Wu, Qiang Shen, Chunyou Wang, Tao Yin
Cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT)-type cells are considered as underlying causes of chemoresistance, tumour recurrence and metastasis in pancreatic cancer. We aimed to describe the mechanisms - particularly glycolysis - involved in the regulation of the CSC and EMT phenotypes. We used a gemcitabine-resistant (GR) Patu8988 cell line, which exhibited clear CSC and EMT phenotypes and showed reliance on glycolysis. Inhibition of glycolysis using 2-deoxy-D-glucose (2-DG) significantly enhanced the cytotoxicity of gemcitabine and inhibited the CSC and EMT phenotypes in GR cells both in vitro and in vivo...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28243729/expression-of-rab5a-correlates-with-tumor-progression-in-pancreatic-carcinoma
#12
Yuandong Li, Xiaofang Sun, Donghui Ji, Xiangshun Kong, Dengxiang Liu, Zhenya Zhao, Jingbo Yan, Shubo Chen
Rab family protein Rab5a has been implicated in cancer progression. To date, its expression pattern in human pancreatic cancer has not been investigated. This study aims to examine clinical significance, biological role, and potential mechanism of action of mRab5a in human pancreatic cancer. We analyzed Rab5a protein in cancer tissue of 111 cases of pancreatic cancer using immunohistochemistry. The results show that Rab5a overexpression correlates with high T stage, positive nodal status, and advanced TNM stage...
February 27, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28223335/cooperation-of-musashi-2-numb-mdm2-and-p53-in-drug-resistance-and-malignant-biology-of-pancreatic-cancer
#13
Weiwei Sheng, Ming Dong, Chuanping Chen, Zixin Wang, Yunwei Li, Kewei Wang, Yuji Li, Jianping Zhou
Our earlier work showed that Musashi (MSI)-2 promoted the development of pancreatic cancer (PC) by down-regulating Numb, which prevented murine double-minute (MDM)-2-mediated p53 ubiquitin degradation. Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC in vitro and invivo, an association that has not been reported to our knowledge. MSI2 had no relationship with mutant p53 (mtp53) and wild-type p53 (wtp53) in normal PC cells. However, in response to gemcitabine or cisplatin treatment, MSI2 silencing simultaneously down-regulated MDM2 and up-regulated Numb and wtp53 protein levels...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28215943/all-trans-retinoic-acid-enhances-gemcitabine-cytotoxicity-in-human-pancreatic-cancer-cell-line-aspc-1-by-up-regulating-protein-expression-of-deoxycytidine-kinase
#14
Hiroki Kuroda, Masanori Tachikawa, Yasuo Uchida, Koetsu Inoue, Hideo Ohtsuka, Sumio Ohtsuki, Michiaki Unno, Tetsuya Terasaki
We previously showed that gemcitabine resistance in pancreatic cancer chemotherapy correlates with suppressed expression of deoxycytidine kinase (dCK), which catalyzes the rate-limiting step of gemcitabine activation. The purpose of the present study was to find a drug that might be useful to enhance the cytotoxicity of gemcitabine by increasing dCK expression in gemcitabine-resistant human pancreatic cancer cell line AsPC-1. Screening of 40 prescription drugs identified 35 with no intrinsic cytotoxicity towards AsPC-1 cells...
February 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28210844/elevated-interferon-induced-protein-with-tetratricopeptide-repeats-3-ifit3-is-a-poor-prognostic-marker-in-pancreatic-ductal-adenocarcinoma
#15
Yue Zhao, Annelore Altendorf-Hofmann, Ioannis Pozios, Peter Camaj, Therese Däberitz, Xiaoyan Wang, Hanno Niess, Hendrik Seeliger, Felix Popp, Christopher Betzler, Utz Settmacher, Karl-Walter Jauch, Christiane Bruns, Thomas Knösel
PURPOSE: Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients. METHODS: The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3...
February 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28209616/octn1-is-a-high-affinity-carrier-of-nucleoside-analogs
#16
Christina Drenberg, Alice A Gibson, Stanley Pounds, Lei Shi, Dena Rhinehart, Lie Li, Shuiying Hu, Guoqing Du, Anne T Nies, Matthias Schwab, Navjotsingh Pabla, William Blum, Tanja A Gruber, Sharyn D Baker, Alex Sparreboom
Resistance to xenobiotic nucleosides used to treat acute myeloid leukemia (AML) and other cancers remains a major obstacle to clinical management. One process suggested to participate in resistance is reduced uptake into tumor cells via nucleoside transporters, although precise mechanisms are not understood. Through transcriptomic profiling, we determined that low expression of the ergothioneine transporter OCTN1 (SLC22A4; ETT) strongly predicts poor event-free survival and overall survival in multiple cohorts of AML patients receiving treatment with the cytidine nucleoside analog cytarabine...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209496/uterine-leiomyosarcoma-epidemiology-contemporary-treatment-strategies-and-the-impact-of-uterine-morcellation
#17
REVIEW
Stephanie Ricci, Rebecca L Stone, Amanda N Fader
Leiomyosarcoma, a rare tumor subtype, accounts for 1% of all uterine malignancies, but contributes to a significant proportion of uterine cancer deaths. Surgery is considered the mainstay of treatment for all soft tissue sarcomas, including uterine variants. However, uterine leiomyosarcoma is challenging to diagnose preoperatively and can mimic the appearance of benign uterine leiomyomas. Recently, concerns have grown in this regard, as surgeons have utilized uterine morcellation and myomectomy procedures unknowingly in the setting of occult uterine sarcoma...
February 13, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28198398/microrna-155-controls-exosome-synthesis-and-promotes-gemcitabine-resistance-in-pancreatic-ductal-adenocarcinoma
#18
Manabu Mikamori, Daisaku Yamada, Hidetoshi Eguchi, Shinichiro Hasegawa, Tomoya Kishimoto, Yoshito Tomimaru, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Koichi Kawamoto, Kunihito Gotoh, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki
The cancer drug gemcitabine (GEM) is a key drug for treating pancreatic ductal adenocarcinoma (PDAC), but PDAC cells develop chemoresistance after long-term administration. Since the tolerance was immediately spread to every PDAC tissue in a patient, it is assumed that some certain efficient mechanisms underlay in the development of chemoresistance. Changes in the levels of particular microRNAs or alterations in intercellular communication play a dominant role in chemoresistance development, and recent data also suggest that exosomes play an important role in this process...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196872/muc16-regulates-tspyl5-for-lung-cancer-cell-growth-and-chemoresistance-by-suppressing-p53
#19
Imayavaramban Lakshmanan, Shireen Salfity, Parthasarathy Seshacharyulu, Satyanarayana Rachagani, Abigail Thomas, Srustidhar Das, Prabin D Majhi, Rama Krishna Nimmakayala, Raghupathy Vengoji, Subodh M Lele, Moorthy P Ponnusamy, Surinder K Batra, Apar Kishor Ganti
PURPOSE: MUC16, a tumor biomarker and cell surface associated mucin, is overexpressed in various cancers; however, its role in lung cancer pathogenesis is unknown. Here, we have explored the mechanistic role of MUC16 in lung cancer. EXPERIMENTAL DESIGN: To identify the functional role of MUC16, stable knockdown was carried in lung cancer cells with two different shRNAs. Clinical significance of MUC16 was evaluated in lung cancer patient's tissues using IHC. We have generated genetically engineered mouse model (KrasG12D; AdCre) to evaluate the preclinical significance of MUC16...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28192521/acquired-resistance-to-oxaliplatin-is-not-directly-associated-with-increased-resistance-to-dna-damage-in-sk-n-asroxali4000-a-newly-established-oxaliplatin-resistant-sub-line-of-the-neuroblastoma-cell-line-sk-n-as
#20
Emily Saintas, Liam Abrahams, Gulshan T Ahmad, Anu-Oluwa M Ajakaiye, Abdulaziz S H A M AlHumaidi, Candice Ashmore-Harris, Iain Clark, Usha K Dura, Carine N Fixmer, Chinedu Ike-Morris, Mireia Mato Prado, Danielle Mccullough, Shishir Mishra, Katia M U Schöler, Husne Timur, Maxwell D C Williamson, Markella Alatsatianos, Basma Bahsoun, Edith Blackburn, Catherine E Hogwood, Pamela E Lithgow, Michelle Rowe, Lyto Yiangou, Florian Rothweiler, Jindrich Cinatl, Richard Zehner, Anthony J Baines, Michelle D Garrett, Campbell W Gourlay, Darren K Griffin, William J Gullick, Emma Hargreaves, Mark J Howard, Daniel R Lloyd, Jeremy S Rossman, C Mark Smales, Anastasios D Tsaousis, Tobias von der Haar, Mark N Wass, Martin Michaelis
The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin...
2017: PloS One
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