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Gemcitabine

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https://www.readbyqxmd.com/read/29792309/metabolic-and-physiologic-imaging-biomarkers-of-the-tumor-microenvironment-predict-treatment-outcome-with-radiation-or-a-hypoxia-activated-prodrug-in-mice
#1
Shingo Matsumoto, Shun Kishimoto, Keita Saito, Yoichi Takakusagi, Jeeva P Munasinghe, Nallathamby Devasahayam, Charles Hart, Robert J Gillies, James B Mitchell, Murali C Krishna
Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxic niches that lead to treatment resistance. Therefore, studies of tumor oxygenation and metabolic profiling should contribute to improved treatment strategies. Here we define two imaging biomarkers that predict differences in tumor response to therapy: 1) partial oxygen pressure (pO2), measured by EPR imaging; and 2) [1-13C] pyruvate metabolism rate, measured by hyperpolarized 13C MRI. Three human PDAC xenografts with varying treatment sensitivity (Hs766t, MiaPaCa-2, and Su...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29791286/metastatic-pancreatic-cancer-asco-clinical-practice-guideline-update
#2
Davendra P S Sohal, Erin B Kennedy, Alok Khorana, Mehmet S Copur, Christopher H Crane, Ignacio Garrido-Laguna, Smitha Krishnamurthi, Cassadie Moravek, Eileen M O'Reilly, Philip A Philip, Ramesh K Ramanathan, Joseph T Ruggiero, Manish A Shah, Susan Urba, Hope E Uronis, Michelle W Lau, Daniel Laheru
Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018...
May 23, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29790676/gemcitabine-and-cisplatin-regimen-facilitates-prognosis-of-advanced-nasopharyngeal-carcinoma
#3
Qiongxuan Li, Zhi Yin, Tingting Wang, Lizhang Chen, Zhanzhan Li
This study was conducted to assess the efficacy and adverse effects of GP (gemcitabine + cisplatin) regimen and FP (fluouracil + cisplatin) regimen in treatment of advanced nasopharyngeal carcinoma. Systematic online searches were performed in PubMed, Web of Sciences, China Knowledge Infrastructure and Weipu from the inception to November 15, 2017. Potential studies were assessed using the Cochrane risk of bias scale. Statistical analyses were performed on Stata 14.0 and RevMan 5.3. Finally, twelve studies entered final qualitative synthesis and quantitative analysis...
May 23, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29789314/inhibition-of-atr-acutely-sensitizes-acute-myeloid-leukemia-cells-to-nucleoside-analogs-that-target-ribonucleotide-reductase
#4
Sarah E Fordham, Helen J Blair, Claire J Elstob, Ruth Plummer, Yvette Drew, Nicola J Curtin, Olaf Heidenreich, Deepali Pal, David Jamieson, Catherine Park, John Pollard, Scott Fields, Paul Milne, Graham H Jackson, Helen J Marr, Tobias Menne, Gail L Jones, James M Allan
The ataxia telangiectasia and Rad3-related (ATR) protein kinase promotes cancer cell survival by signaling stalled replication forks generated by replication stress, a common feature of many cancers including acute myeloid leukemia (AML). Here we show that the antileukemic activity of the chemotherapeutic nucleoside analogs hydroxyurea and gemcitabine was significantly potentiated by ATR inhibition via a mechanism involving ribonucleotide reductase (RNR) abrogation and inhibition of replication fork progression...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29788155/phase-i-study-of-the-checkpoint-kinase-1-inhibitor-gdc-0575-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#5
A Italiano, J R Infante, G I Shapiro, K N Moore, P M LoRusso, E Hamilton, S Cousin, M Toulmonde, S Postel-Vinay, S Tolaney, E M Blackwood, S Mahrus, F V Peale, X Lu, A Moein, J Epler, K DuPree, M Tagen, E R Murray, J L Schutzman, J O Lauchle, A Hollebecque, J-C Soria
Background: Checkpoint kinase 1 (Chk1) inhibition following chemotherapy-elicited DNA damage overrides cell cycle arrest and induces mitotic catastrophe and cell death. GDC-0575 is a highly-selective oral small-molecule Chk1 inhibitor that results in tumor shrinkage and growth delay in xenograft models. We evaluated the safety, tolerability, and pharmacokinetic properties of GDC-0575 alone and in combination with gemcitabine. Antitumor activity and Chk1 pathway modulation were assessed...
February 23, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29787943/venous-thromboembolism-with-egfr-monoclonal-antibody-necitumumab-in-stage-iv-non-small-cell-lung-cancer-a-retrospective-cohort-analysis
#6
Kelvin Young, Luis Paz-Ares, Nick Thatcher, David R Spigel, Javad Shahidi, Victoria Soldatenkova, Gerrit Grau, Raffael Kurek, Frances A Shepherd
INTRODUCTION: Metastatic non-small cell lung cancer (NSCLC) is a recognized risk factor for VTE. Some systemic treatments may increase this risk further. Here, we present the risk of VTE and its prognostic significance for patients treated with chemotherapy (chemo) and the EGFR monoclonal antibody necitumumab (neci) for metastatic NSCLC. METHODS: Four trials of 1st-line treatment for Stage IV NSCLC were analyzed: two randomized phase 3 studies of cisplatin/gemcitabine ±neci in squamous NSCLC (SQUIRE: N = 1079) and cisplatin/pemetrexed ±neci in non-squamous NSCLC (INSPIRE: N = 616); JFCL (N = 161), a randomized phase 2 trial of carboplatin/paclitaxel ±neci in squamous NSCLC; and JFCK (N = 61), a single arm phase 2 trial of cisplatin/gemcitabine +neci in squamous NSCLC...
May 7, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29785621/comparison-of-efficacy-and-toxicity-of-second-line-combination-chemotherapy-regimens-in-patients-with-advanced-urothelial-carcinoma
#7
Yuji Takeyama, Minoru Kato, Chikako Nishihara, Takeshi Yamasaki, Taro Iguchi, Satoshi Tamada, Katsuyuki Kuratsukuri, Tatsuya Nakatani
BACKGROUND: The aim of this study was to evaluate the efficacy and toxicities of second-line chemotherapy regimens with docetaxel and gemcitabine (GD), or paclitaxel and gemcitabine (GP) for advanced or metastatic urothelial carcinoma (UC) that did not respond to first-line platinum-based chemotherapy. METHODS: From 2002 to 2017, 78 patients with metastatic UCs that progressed after platinum-based chemotherapy were treated with either GD (n = 41) or GP (n = 37)...
May 21, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29783721/azd1775-increases-sensitivity-to-olaparib-and-gemcitabine-in-cancer-cells-with-p53-mutations
#8
Xiangbing Meng, Jianling Bi, Yujun Li, Shujie Yang, Yuping Zhang, Mary Li, Haitao Liu, Yiyang Li, Megan E Mcdonald, Kristina W Thiel, Kuo-Kuang Wen, Xinhao Wang, Meng Wu, Kimberly K Leslie
Tumor suppressor p53 is responsible for enforcing cell cycle checkpoints at G1/S and G2/M in response to DNA damage, thereby allowing both normal and tumor cells to repair DNA before entering S and M. However, tumor cells with absent or mutated p53 are able to activate alternative signaling pathways that maintain the G2/M checkpoint, which becomes uniquely critical for the survival of such tumor cells. We hypothesized that abrogation of the G2 checkpoint might preferentially sensitize p53-defective tumor cells to DNA-damaging agents and spare normal cells with intact p53 function...
May 19, 2018: Cancers
https://www.readbyqxmd.com/read/29782821/licoricidin-enhances-gemcitabine-induced-cytotoxicity-in-osteosarcoma-cells-by-suppressing-the-akt-and-nf-%C3%AE%C2%BAb-signal-pathways
#9
Yifei Wang, Shengli Wang, Jianhua Liu, Yanxiao Lu, Donghui Li
Osteosarcoma (OS) is the most common bone malignancy in children and adolescents. Combined treatments of anti-cancer drugs can remarkably improve chemotherapeutic outcomes. Gemcitabine and licoricidin both have potential anti-tumor activity in several cancers. However, the combined therapeutic efficiency of gemcitabine and licoricidin for OS has not been explored. Here, we found that licoricidin or gemcitabine inhibited OS cell viability in a dose-dependent manner. Cotreatment with licoricidin and gemcitabine enhanced gemcitabine-induced cytotoxicity in OS cells...
May 18, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29781056/phase-ib-study-of-pevonedistat-a-nedd8-activating-enzyme-inhibitor-in-combination-with-docetaxel-carboplatin-and-paclitaxel-or-gemcitabine-in-patients-with-advanced-solid-tumors
#10
A Craig Lockhart, Todd M Bauer, Charu Aggarwal, Carrie B Lee, R Donald Harvey, Roger B Cohen, Farhad Sedarati, Tsz Keung Nip, Hélène Faessel, Ajeeta B Dash, Bruce J Dezube, Douglas V Faller, Afshin Dowlati
Purpose This phase Ib study (NCT01862328) evaluated the maximum tolerated dose (MTD), safety, and efficacy of pevonedistat in combination with standard-of-care chemotherapies in patients with solid tumors. Methods Patients received pevonedistat with docetaxel (arm 1, n = 22), carboplatin plus paclitaxel (arm 2, n = 26), or gemcitabine (arm 3, n = 10) in 21-days (arms 1 and 2) or 28-days (arm 3) cycles. A lead-in cohort (arm 2a, n = 6) determined the arm 2 carboplatin dose. Dose escalation proceeded via continual modified reassessment...
May 21, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29781034/specific-inhibitor-of-notch%C3%A2-3-enhances-the-sensitivity-of-nsclc-cells-to-gemcitabine
#11
Bi-Dan Hu, Jia Guo, Yuan-Zi Ye, Ting Du, Chun-Song Cheng, Qian Jiang, Ruo-Nan Liu, Yan-Bei Zhang
Notch‑3 is a receptor of the Notch signaling pathway and plays an important role in regulating self‑renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch‑3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non‑small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3)...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29781033/microarray-analysis-of-circular-rna-expression-profiles-associated-with-gemcitabine-resistance-in-pancreatic-cancer-cells
#12
Chao Xu, Yue Yu, Fei Ding
Pancreatic cancer (PC) is one of the most malignant tumors of the digestive system due to its rapid progression, metastasis and resistance to chemotherapy. Gemcitabine (GEM) chemotherapy is the first‑choice treatment for advanced PC. However, the effect of GEM‑based chemotherapy on PC is limited due to the development of chemoresistance, and the molecular mechanisms underlying this resistance have yet to be investigated. Circular RNAs (circRNAs), which can function as microRNA sponges, have been found to be involved in the development of several types of cancer...
May 17, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29775835/analysis-of-the-cytotoxic-effects-of-combined-ultrasound-microbubble-and-nucleoside-analog-combinations-on-pancreatic-cells-in-vitro
#13
Julia Mariglia, Shadab Momin, Imogen R Coe, Raffi Karshafian
Ultrasonically-stimulated microbubbles enhance the therapeutic effects of various chemotherapy drugs. However, the application of ultrasound and microbubbles (USMB) for enhancing the therapeutic effect of nucleoside analogs, which are used as front-line treatments in a range of cancers, and its underlying mechanism is not well understood. This study investigated the effect of gemcitabine, a nucleoside analog drug, in combination with USMB in increasing cell cytotoxicity relative to either treatment alone in BxPC3 pancreatic cancer cells...
May 5, 2018: Ultrasonics
https://www.readbyqxmd.com/read/29775284/multifunctional-tumor-targeting-cathepsin-b-sensitive-gemcitabine-prodrug-covalently-targets-albumin-in-situ-and-improves-cancer-therapy
#14
Huicong Zhang, Zhisu Sun, Kuanglei Wang, Na Li, Hongxiang Chen, Xiao Tan, Lingxiao Li, Zhonggui He, Jin Sun
We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting and site-specific drug release are achieved and such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.
May 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29772747/involvement-of-cyp4f2-in-the-metabolism-of-a-novel-monophosphate-ester-prodrug-of-gemcitabine-and-its-interaction-potential-in-vitro
#15
Yedong Wang, Yuan Li, Jia Lu, Huixin Qi, Isabel Cheng, Hongjian Zhang
Compound- 3 is an oral monophosphate prodrug of gemcitabine. Previous data showed that Compound- 3 was more potent than gemcitabine and it was orally active in a tumor xenograft model. In the present study, the metabolism of Compound- 3 was investigated in several well-known in vitro matrices. While relatively stable in human and rat plasma, Compound- 3 demonstrated noticeable metabolism in liver and intestinal microsomes in the presence of NADPH and human hepatocytes. Compound- 3 could also be hydrolyzed by alkaline phosphatase, leading to gemcitabine formation...
May 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29772221/mir-301a-plays-a-pivotal-role-in-hypoxia-induced-gemcitabine-resistance-in-pancreatic-cancer
#16
Guangtao Luo, Xiang Xia, Xiaofeng Wang, Kundong Zhang, Jun Cao, Tao Jiang, Qian Zhao, Zhengjun Qiu
Hypoxia is a hallmark of pancreatic cancer (PC) and is associated with gemcitabine resistance. However, the mechanisms underlying hypoxia-induced gemcitabine resistance in PC remain greatly unknown. Our previous work showed that miR-301a, a hypoxia-sensitive miRNA, is involved in PC metastasis under hypoxia via regulation of its target gene P63. Here, we showed that miR-301a was upregulated in a NF-κB independent manner under hypoxia and promoted gemcitabine resistance under hypoxic conditions in vitro. In addition, TAp63, a member of the P63 family, reversed hypoxia-induced gemcitabine resistance by promoting degradation of HIF-1α...
May 14, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29770997/gemcitabine-nab-paclitaxel-for-pediatric-relapsed-refractory-sarcomas
#17
Jonathan L Metts, Adina L Alazraki, Dana Clark, Ernest K Amankwah, Karen J Wasilewski-Masker, Bradley A George, Thomas A Olson, Thomas Cash
BACKGROUND: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. PROCEDURE: We reviewed the records of fifteen relapsed/refractory patients and one treatment-naïve patient who received gemcitabine/nab-paclitaxel at our institution...
May 17, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29768050/getting-up-to-date-in-the-management-of-soft-tissue-sarcoma
#18
Jean-Yves Blay
Surgery (+ radiation therapy in selected cases) is standard treatment for adult-type localized soft tissue sarcoma (STS). Accumulating randomized clinical evidence also supports adjuvant chemotherapy as a treatment option, although this remains contentious. Doxorubicin (± ifosfamide) is the standard first-line systemic treatment for advanced STS; however, newer chemotherapeutic agents may improve outcomes achieved with single-agent doxorubicin. In a Phase II study, adding olaratumab to doxorubicin markedly improved overall survival...
May 2018: Future Oncology
https://www.readbyqxmd.com/read/29768008/striking-a-balance-between-carbonate-carbamate-linkage-bond-and-reduction-sensitive-disulfide-bond-bearing-linker-for-tailored-controlled-release-in-situ-covalently-albumin-binding-gemcitabine-prodrugs-promote-bioavailability-and-tumor-accumulation
#19
Huicong Zhang, Kuanglei Wang, Kexin Na, Dan Li, Zhenbao Li, Dongyang Zhao, Lu Zhong, Menglin Wang, Longfa Kou, Cong Luo, Haotian Zhang, Qiming Kan, Huaiwei Ding, Zhonggui He, Jin Sun
To address the challenge of rapid enzyme inactivation, poor tumor targeting, acquired drug resistance in gemcitabine (GEM) application, we report two groups of maleimide-functionalised GEM prodrugs conjugating covalently in situ with cys-34 of blood-circulating albumin, resulting in macromolecular prodrugs after intravenous administration. Specially, tailored and accurate controlled release was achieved through different combinations of linkage bonds relatively stable and labile (carbamate and carbonate, respectively) and linkers with or without insertion of a disulfide bond...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29767464/platinum-resistant-recurrent-ovarian-cancer-with-long-survival-on-bevacizumab-and-gemcitabine
#20
Shinichi Komiyama, Tsuyoki Kugimiya, Chiaki Takeya, Rena Takahashi, Kaneyuki Kubushiro
Platinum-resistant recurrent ovarian cancer has a poor prognosis, but combined therapy with bevacizumab and anticancer agents may be useful. We report a patient with long-term disease control by the combination of bevacizumab and gemcitabine (BEV + GEM). The patient was a 77-year-old woman with high-grade Stage IIIC serous ovarian carcinoma. In 2012, a complete response (CR) was obtained by neoadjuvant and adjuvant chemotherapy using paclitaxel plus carboplatin and tumor debulking surgery. After recurrence in 2013, CR was achieved again with gemcitabine plus carboplatin...
May 16, 2018: Journal of Obstetrics and Gynaecology Research
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