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gemcitabine resistance

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https://www.readbyqxmd.com/read/28210844/elevated-interferon-induced-protein-with-tetratricopeptide-repeats-3-ifit3-is-a-poor-prognostic-marker-in-pancreatic-ductal-adenocarcinoma
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28182192/dabigatran-potentiates-gemcitabine-induced-growth-inhibition-of-pancreatic-cancer-in-mice
#7
Kun Shi, Helene Damhofer, Joost Daalhuisen, Marieke Ten Brink, Dick J Richel, C Arnold Spek
Pancreatic cancer is one of the most lethal solid malignancies with little treatment options. We have recently shown that expression of protease activated receptor (PAR)-1 in the tumor microenvironment drives progression and induces chemoresistance of pancreatic cancer. As thrombin is the prototypical PAR-1 agonist, here we addressed the effect of the direct thrombin inhibitor dabigatran on pancreatic cancer growth and drug resistance in an orthotropic pancreatic cancer model. We show that dabigatran treatment did not affect primary tumor growth whereas it significantly increased tumor dissemination throughout the peritoneal cavity...
February 6, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28176634/targeting-the-akt-pi3k-signaling-pathway-as-a-potential-therapeutic-strategy-for-the-treatment-of-pancreatic-cancer
#8
Safieh Ebrahimi, Mina Hosseini, Soodabeh Shahidsales, Mina Maftouh, Gordon A Ferns, Majid Ghayour-Mobarhan, Seyed Mahdi Hassanian, Amir Avan
The phosphoinositide 3 kinase AKT mammalian target of rapamycin (PI3K-AKT-mTOR) signaling pathway is an important signaling pathway in pancreatic cancer (PC). It is frequently activated in PC and is associated with worse outcome. Aberrant activation of this pathway is involved in cell metabolism and survival, cell cycle progression, regulation of apoptosis, protein synthesis, and genomic instability. Several agents have been developed to target Akt/PI3K pathways, including PI3K inhibitors, (e.g. LY294002, Wortmannin), PI3K/mTOR inhibitors (e...
February 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28176365/high-efficacy-of-pazopanib-on-an-undifferentiated-spindle-cell-sarcoma-resistant-to-first-line-therapy-is-identified-with-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#9
Kentaro Igarashi, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Arun S Singh, Scott D Nelson, Sarah Dry, Yunfeng Li, 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. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). In the present study, we evaluated the efficacy of standard first-line chemistry of doxorubicin (DOX), gemcitabine (GEM) combined with docetaxel (DOC), compared to pazopanib (PAZ), a multi-targeting tyrosine-kinase inhibitor, in an USCS PDOX model. A high-grade USCS from a striated muscle of the patients was grown orthotopically in the right biceps femoris muscle of nude mice to establish the PDOX model...
February 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28166242/combination-of-anti-l1-cell-adhesion-molecule-antibody-and-gemcitabine-or-cisplatin-improves-the-therapeutic-response-of-intrahepatic-cholangiocarcinoma
#10
Seulki Cho, Tae Sup Lee, In Ho Song, A-Ram Kim, Yoon-Jin Lee, Haejung Kim, Haein Hwang, Mun Sik Jeong, Seung Goo Kang, Hyo Jeong Hong
Cholangiocarcinoma has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Improving survival of patients with advanced cholangiocarcinoma urgently requires the development of new effective targeted therapies in combination with chemotherapy. We previously developed a human monoclonal antibody (mAb) Ab417 that binds to both the human and mouse L1 cell adhesion molecule (L1CAM) with high affinities. In the present study, we observed that Ab417 exhibited tumor targeting ability in biodistribution studies and dose-dependent tumor growth inhibition in an intrahepatic cholangiocarcinoma (Choi-CK) xenograft mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28165150/everolimus-inhibits-growth-of-gemcitabine-resistant-pancreatic-cancer-cells-via-induction-of-caspase-dependent-apoptosis-and-g2-m-arrest
#11
Tao Peng, Q Ping Dou
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. While Gemcitabine-based chemotherapy is the first-line treatment for locally advanced pancreatic cancer, its resistance is a large obstacle in the field. Understanding the molecular basis of gemcitabine resistance is therefore critical for increasing the efficacy of gemcitabine-based chemotherapy and improving the survival rate of the cancer patients. Here, we investigated the sensitivity of a pair of established human pancreatic cancer cell lines, MIAPaCa-E (relatively sensitive to gemcitabine, called GS) and MIAPaCa-M (highly resistant to gemcitabine, called GR) to various inhibitors of EGFR or PI3K/AKT/mTOR pathways...
February 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28161480/multifunctionalized-iron-oxide-nanoparticles-for-selective-targeting-of-pancreatic-cancer-cells
#12
Sara Trabulo, Antonio Aires, Alexandra Aicher, Christopher Heeschen, Aitziber L Cortajarena
Nanomedicine nowadays offers novel solutions in cancer therapy by introducing multimodal treatments in one single formulation. In addition, nanoparticles act as nanocarriers changing the solubility, biodistribution and efficiency of the therapeutic molecules, thus generating more efficient treatments and reducing their side effects. To apply these novel therapeutic approaches, efforts are focused on the multi-functionalization of the nanoparticles and will open up new avenues to advanced combinational therapies...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28155658/knockdown-of-pola2-increases-gemcitabine-resistance-in-lung-cancer-cells
#13
Vivien Koh, Hsueh Yin Kwan, Woei Loon Tan, Tzia Liang Mah, Wei Peng Yong
BACKGROUND: Gemcitabine is used as a standard drug treatment for non-small cell lung cancer (NSCLC), but treatment responses vary among patients. Our previous studies demonstrated that POLA2 + 1747 GG/GA single nucleotide polymorphism (SNP) improves differential survivability and mortality in NSCLC patients. Here, we determined the association between POLA2 and gemcitabine treatment in human lung cancer cells. RESULTS: Human PC9, H1299 and H1650 lung cancer cell lines were treated with 0...
December 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28153717/ku70-inhibits-gemcitabine-induced-dna-damage-and-pancreatic-cancer-cell-apoptosis
#14
Jiali Ma, Pingping Hui, Wenying Meng, Na Wang, Shihao Xiang
The current study focused on the role of Ku70, a DNA-dependent protein kinase (DNA-PK) complex protein, in pancreatic cancer cell resistance to gemcitabine. In both established cell lines (Mia-PaCa-2 and PANC-1) and primary human pancreatic cancer cells, shRNA/siRNA-mediated knockdown of Ku70 significantly sensitized gemcitabine-induced cell death and proliferation inhibition. Meanwhile, gemcitabine-induced DNA damage and subsequent pancreatic cancer cell apoptosis were also potentiated with Ku70 knockdown...
January 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28144610/pediatric-hepatocellular-carcinoma-challenges-and-solutions
#15
REVIEW
Irene Schmid, Dietrich von Schweinitz
Hepatocellular carcinoma (HCC) is a very rare entity in children, making it nearly impossible to orchestrate Phase II/III studies even as multinational cooperative trials. In contrast to adults, nearly 50% of the children have a response (α-fetoprotein decline and/or tumor shrinkage) to chemotherapeutic agents such as cisplatin and doxorubicin (PLADO), demonstrating that HCC in childhood can be chemotherapy sensitive. As a result, the main treatment options in pediatric HCC focus on systemic drug therapies and resection as the central therapy...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/28143426/the-marine-triterpene-glycoside-frondoside-a-induces-p53-independent-apoptosis-and-inhibits-autophagy-in-urothelial-carcinoma-cells
#16
Sergey A Dyshlovoy, Ramin Madanchi, Jessica Hauschild, Katharina Otte, Winfried H Alsdorf, Udo Schumacher, Vladimir I Kalinin, Alexandra S Silchenko, Sergey A Avilov, Friedemann Honecker, Valentin A Stonik, Carsten Bokemeyer, Gunhild von Amsberg
BACKGROUND: Advanced urothelial carcinomas represent a considerable clinical challenge as they are difficult to treat. Platinum-based combination regimens obtain response rates ranging from 40 to 70% in first-line therapy of advanced urothelial carcinoma. In the majority of cases, however, the duration of these responses is limited, and when progression occurs, the outcome is generally poor. Therefore, novel therapeutic strategies are urgently needed. The purpose of the current research is to investigate the anticancer effects and the mode of action of the marine triterpene glycoside frondoside A in p53-wild type and p53-deficient human urothelial carcinoma cells...
February 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28142120/nanotechnology-for-delivery-of-gemcitabine-to-treat-pancreatic-cancer
#17
REVIEW
Gebremariam Birhanu, Hamid Akbari Javar, Ehsan Seyedjafari, Ali Zandi-Karimi
Pancreatic cancer (PC) is one of the most deadly and quickly fatal human cancers with a 5-year mortality rate close to 100%. Its prognosis is very poor, mainly because of its hostile biological behavior and late onset of symptoms for clinical diagnosis; these bring limitations on therapeutic interventions. Factors contributing for the difficulties in treating PC include: high rate of drug resistance, fast metastasis to different organs, poor prognosis and relapse of the tumor after therapy. After being approved by US FDA 1997, Gemcitabine (Gem) is the first line and the gold standard drug for all stages of advanced PC till now...
January 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28134290/a-novel-hdac-inhibitor-cg200745-inhibits-pancreatic-cancer-cell-growth-and-overcomes-gemcitabine-resistance
#18
Hee Seung Lee, Soo Been Park, Sun A Kim, Sool Ki Kwon, Hyunju Cha, Do Young Lee, Seonggu Ro, Joong Myung Cho, Si Young Song
Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28133097/-a-study-of-gemctabine-plus-nab-paclitaxel-therapy-for-advanced-local-progressive-pancreatic-cancer
#19
Yutaka Itoh, Hiroyuki Saito, Shunsuke Yamagishi, Yuki Suematsu, Miyuki Takahashi, Mao Nakayama, Michiko Fukabori, Akihiko Morita, Kazuhiko Wakabayashi
We studied the significance of gemcitabine plus nab-paclitaxel(GnP)therapy for locally progressive pancreatic cancer. We enrolled 10 patients with local progression without distant metastasis. We used GnP therapy for the ablative borderline resectable(BR)and unresectable(UR)cases based on images that followed NCCN pancreatic cancer treatment guidelines. In 1 case of resectable(R)pancreatic cancer, the tumor was located in the pancreas body but we determined that surgery was impossible because of the underlying disease detected on imaging analysis...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133073/-antitumor-effects-of-a-combined-treatment-with-bortezomib-and-gemcitabine-in-bile-duct-cancer-cell-lines
#20
Kazunori Sugimura, Tsutomu Namikawa, Yuka Takezaki, Hiroyuki Kitagwa, Masaya Munekage, Kazuhiro Hanazaki
Several studies have reported that activation of nuclear factor-kappa B(NF-kB)leads to resistance to chemotherapy and radiotherapy, whereas inhibition of NF-kB activity decreases malignant manifestations and enhances sensitivity to anticancer drugs. In the present study, we used bile duct cancer(BDC)cell lines HuH28 and HuCCT1 to examine if bortezomib, an inhibitor of NF-kB activity, enhances the sensitivity to the currently used chemotherapy drug gemcitabine. We carried out experiments in the following 4 treatment groups: control, 100 nM gemcitabine, 80 nM bortezomib, and a combination of 80 nM bortezomib and 100 nM gemcitabine...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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