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https://www.readbyqxmd.com/read/28817206/loureirin-b-promotes-insulin-secretion-through-inhibition-of-katp-channel-and-influx-of-intracellular-calcium
#1
Yijie Sha, Yuelin Zhang, Jing Cao, Kai Qian, Bing Niu, Qin Chen
The development of new diabetes drugs continues to be explored. Loureirin B, a flavonoid, extracted from Dracaena cochinchinensis, has been confirmed to increase insulin secretion and decrease blood glucose levels. For searching the promotion of insulin secretion with the treatment of loureirin B, experiments were employed based on cell experiments and computational methods. Firstly, promotion of insulin secretion was dependent on extracellular glucose concentration. At the genetic level, loureirin B enhanced the relative mRNA level of Pdx-1 and MafA...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28810913/selinexor-kpt-330-demonstrates-anti-tumor-efficacy-in-preclinical-models-of-triple-negative-breast-cancer
#2
Natalia Paez Arango, Erkan Yuca, Ming Zhao, Kurt W Evans, Stephen Scott, Charissa Kim, Ana Maria Gonzalez-Angulo, Filip Janku, Naoto T Ueno, Debu Tripathy, Argun Akcakanat, Aung Naing, Funda Meric-Bernstam
BACKGROUND: Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo. METHODS: Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC50) and to test the effects in combination with chemotherapy...
August 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28808038/the-phosphatidylinositol-3-kinase-pathway-as-a-potential-therapeutic-target-in-bladder-cancer
#3
Shuxiong Zeng, Yanjun Zhu, Ai-Hong Ma, Weimin Yu, Hongyong Zhang, Tzu-Yin Lin, Wei Shi, Clifford G Tepper, Paul T Henderson, Susan Airhart, Jianming Guo, Chuanliang Xu, Ralph de Vere White, Chong-Xian Pan
PURPOSE: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action and resistant mechanisms of drugs targeting the PI3K pathway. EXPERIMENTAL DESIGN: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine...
August 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28806950/precision-medicine-approaches-to-lung-adenocarcinoma-with-concomitant-met-and-her2-amplification
#4
Doo-Yi Oh, Kyungsoo Jung, Ji-Young Song, Seokhwi Kim, Sang Shin, Yong-Jun Kwon, Ensel Oh, Woong-Yang Park, Sang Yong Song, Yoon-La Choi
BACKGROUND: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models. METHODS: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28804556/anti-tumor-efficacy-evaluation-of-a-novel-monoclonal-antibody-targeting-neutral-amino-acid-transporter-asct2-using-patient-derived-xenograft-mouse-models-of-gastric-cancer
#5
Noriyuki Kasai, Aya Sasakawa, Kenta Hosomi, Tze Wei Poh, Bernadette Lynn Chua, Wei Peng Yong, Jimmy So, Shing Leng Chan, Richie Soong, Koji Kono, Toshihiko Ishii, Kazuya Yamano
ASC amino acid transporter 2 (ASCT2), also known as solute linked carrier family 1 member A5 (SLC1A5) is a Na+-dependent glutamine/neutral amino acid transporter. ASCT2 acts as a high-affinity transporter of L-glutamine (Gln) and has been reported to be up-regulated in a variety of cancerous tissues including stomach, liver, and kidney. In this study, we evaluated anti-tumor efficacy of a novel anti-ASCT2 humanized monoclonal antibody, KM8094, which has a neutralizing activity against glutamine uptake, as a therapeutic antibody against gastric cancer and explored clinical predictive biomarker candidates by utilizing patient-derived xenograft (PDX) mouse models...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28801594/deficiency-in-catechol-o-methyltransferase-is-linked-to-a-disruption-of-glucose-homeostasis-in-mice
#6
Megumi Kanasaki, Swayam Prakash Srivastava, Fan Yang, Ling Xu, Sumiyo Kudoh, Munehiro Kitada, Norikazu Ueki, Hyoh Kim, Jinpeng Li, Satoru Takeda, Keizo Kanasaki, Daisuke Koya
2-methoxyestradiol (2-ME), an estrogen metabolite generated via catechol-o-methyltransferase (COMT), is multifunctional methoxy-catechol. Here, we report that COMT deficiency leads to glucose intolerance and 2-ME rescues COMT-deficient-associated metabolic defects. Liver COMT protein was suppressed in high fat diet (HFD)-fed or in pregnant mice. COMT suppression, by Ro41-0960 or siRNA, in HFD fed mice or in pregnant mice exacerbated glucose intolerance; 2-ME intervention ameliorated these defects. 2-ME effects on glucose tolerance were associated with AMPK phosphorylation in the liver and in islet cells...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790197/breast-tumors-educate-the-proteome-of-stromal-tissue-in-an-individualized-but-coordinated-manner
#7
Xuya Wang, Arshag D Mooradian, Petra Erdmann-Gilmore, Qiang Zhang, Rosa Viner, Sherri R Davies, Kuan-Lin Huang, Ryan Bomgarden, Brian A Van Tine, Jieya Shao, Li Ding, Shunqiang Li, Matthew J Ellis, John C Rogers, R Reid Townsend, David Fenyö, Jason M Held
Cancer forms specialized microenvironmental niches that promote local invasion and colonization. Engrafted patient-derived xenografts (PDXs) locally invade and colonize naïve stroma in mice while enabling unambiguous molecular discrimination of human proteins in the tumor from mouse proteins in the microenvironment. To characterize how patient breast tumors form a niche and educate naïve stroma, subcutaneous breast cancer PDXs were globally profiled by species-specific quantitative proteomics. Regulation of PDX stromal proteins by breast tumors was extensive, with 35% of the stromal proteome altered by tumors consistently across different animals and passages...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28783167/toosendanin-demonstrates-promising-antitumor-efficacy-in-osteosarcoma-by-targeting-stat3
#8
T Zhang, J Li, F Yin, B Lin, Z Wang, J Xu, H Wang, D Zuo, G Wang, Y Hua, Z Cai
Signal transducer and activator of transcription 3(STAT3) is an emerging target for cancer therapy. In this study, we identify Toosendanin (TSN) is an effective inhibitor of STAT3, leading to the impediment of various oncogenic processes in osteosarcoma. TSN selectively inactivates phospho-STAT3 (Tyr-705); subsequent molecular docking and in vitro SPR analysis uncover TSN directly binds to the SH2 domain of STAT3. Consequently, TSN blocks STAT3 dimerization and impairs the complex formation of STAT3 and epidermal growth factor receptor (EGFR)...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28778085/investigation-of-factors-affecting-the-efficacy-of-3c23k-a-human-monoclonal-antibody-targeting-misiir
#9
Sarah E Gill, Qing Zhang, Gary L Keeney, William A Cliby, S John Weroha
MISIIR is a potential target for ovarian cancer (OC) therapy due to its tissue-specific pattern of expression. 3C23K is a novel therapeutic monoclonal anti-MISIIR antibody designed to recruit effector cells and promote cell death through ADCC (antibody dependent cell-mediated cytotoxicity). Our objective was to determine the tolerability and efficacy of 3C23K in OC patient-derived xenografts (PDX) and to identify factors affecting efficacy. Quantitative RT-PCR, immunohistochemistry (IHC), and flow cytometry were used to categorize MISIIR expression in established PDX models derived from primary OC patients...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28776175/synthesis-and-identification-of-acedoxypc-a-protectin-containing-structured-phospholipid-using-liquid-chromatography-mass-spectrometry
#10
Amanda Lo Van, Baptiste Fourmaux, Madeleine Picq, Michel Guichardant, Michel Lagarde, Nathalie Bernoud-Hubac
Fatty acids have many health benefits in a great variety of diseases ranging from cardiovascular to cerebral diseases. For instance, docosahexaenoic acid (DHA), which is highly enriched in brain phospholipids, plays a major role in anti-inflammatory or neuroprotective pathways. Its effects are thought to be due, in part, to its conversion into derived mediators such as protectins. 1-Lyso,2-docosahexaenoyl-glycerophosphocholine (LysoPtdCho-DHA) is one of the physiological carrier of DHA to the brain. We previously synthesized a structured phosphatidylcholine to mimic 1-lyso,2-docosahexaenoyl-glycerophosphocholine, named AceDoPC(®) (1-acetyl,2-docosahexaenoyl-glycerophosphocholine), that is considered as a stabilized form of the physiological LysoPtdCho-DHA and that is neuroprotective in experimental ischemic stroke...
August 3, 2017: Lipids
https://www.readbyqxmd.com/read/28774890/mir-338-controls-bpa-triggered-pancreatic-islets-insulin-secretory-dysfunction-from-compensation-to-decompensation-by-targeting-pdx-1
#11
Jie Wei, Dongxiao Ding, Tao Wang, Qiong Liu, Yi Lin
Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet function; however, the mechanisms behind these effects are poorly understood. Male mice (4 wk old) were treated with BPA (50 or 500 μg/kg/day) for 8 wk. Whole-body glucose homeostasis, pancreatic islet morphology and function, and miR-338-mediated molecular signal transduction analyses were examined. We showed that BPA treatment led to a disruption of glucose tolerance and a compensatory increase of pancreatic islets insulin secretion and pancreatic and duodenal homeobox 1 (Pdx1) expression in mice...
August 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28765154/gemcitabine-induced-timp1-attenuates-therapy-response-and-promotes-tumor-growth-and-liver-metastasis-in-pancreatic-cancer
#12
Zenobia D'Costa, Keaton Jones, Abul Azad, Ruud van Stiphout, Su Y Lim, Ana L Gomes, Paul Kinchesh, Sean C Smart, W Gillies McKenna, Francesca M Buffa, Owen J Sansom, Ruth J Muschel, Eric O'Neill, Emmanouil Fokas
Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in pre-clinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both in vitro techniques and animal models...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28754817/multifaceted-role-of-btla-in-the-control-of-cd8-t-cell-fate-after-antigen-encounter
#13
Krit Ritthipichai, Cara Haymaker, Melisa Martinez-Paniagua, Andrew Aschenbrenner, Xiaohui Yi, Minying Zhang, Charuta Kale, Yared Hailemichael, Willem W Overwijk, Luis Vence, Jason Roszik, Navin Varadarajan, Roza Nurieva, Laszlo G Radvanyi, Patrick Hwu, Chantale Bernatchez
Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown an overall clinical response rate 40-50% in metastatic melanoma patients. BTLA (B-and-T lymphocyte attenuator) expression on transferred CD8(+) TIL was associated with better clinical outcome. The suppressive function of the ITIM and ITSM motifs of BTLA is well described. Here, we sought to determine the functional characteristics of the CD8(+)BTLA(+)TIL subset and define the contribution of the Grb2 motif of BTLA in T cell co-stimulation...
July 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28751627/local-blockage-of-self-sustainable-erythropoietin-signaling-suppresses-tumor-progression-in-non-small-cell-lung-cancer
#14
Lei He, Shouzhen Wu, Qiang Hao, Elhadji M Dioum, Kuo Zhang, Cun Zhang, Weina Li, Wei Zhang, Yingqi Zhang, Jiming Zhou, Zhijun Pang, Lijuan Zhao, Xiaowen Ma, Meng Li, Qiuyang Zhang
Functional significance of co-expressed erythropoietin (EPO) and its receptor (EPOR) in non-small cell lung cancer (NSCLC) had been under debate. In this study, co-overexpression of EPO/EPOR was confirmed to be positively associated with poor survival in NSCLC. The serum EPO in 14 of 35 enrolled NSCLC patients were found elevated significantly and decreased to normal level after tumor resection. With primary tumor cell culture and patient-derived tumor xenograft (PDX) mouse model, the EPO secretion from the tumors of these 14 patients was verified...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751462/selective-met-kinase-inhibition-in-met-dependent-glioma-models-alters-gene-expression-and-induces-tumor-plasticity
#15
Corina N A M van den Heuvel, Anna C Navis, Tessa de Bitter, Houshang Amiri, Kiek Verrijp, Arend Heerschap, Karen Rex, Isabelle Dussault, Sean Caenepeel, Angela Coxon, Paul N Span, Pieter Wesseling, Wiljan J Hendriks, William P J Leenders
The receptor tyrosine kinase (RTK) MET represents a promising tumor target in a subset of glioblastomas. Most RTK inhibitors available in the clinic today, including those inhibiting MET, affect multiple targets simultaneously. Previously it was demonstrated that treatment with cabozantinib (MET/VEGFR2/RET inhibitor) prolonged survival of mice carrying orthotopic patient derived xenografts (PDX) of the MET-addicted glioblastoma model E98, yet did not prevent development of recurrent and cabozantinib-resistant tumors...
July 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28747710/a-high-content-image-analysis-approach-for-quantitative-measurements-of-chemosensitivity-in-patient-derived-tumor-microtissues
#16
Ilmari Ahonen, Malin Åkerfelt, Mervi Toriseva, Eva Oswald, Julia Schüler, Matthias Nees
Organotypic, three-dimensional (3D) cancer models have enabled investigations of complex microtissues in increasingly realistic conditions. However, a drawback of these advanced models remains the poor biological relevance of cancer cell lines, while higher clinical significance would be obtainable with patient-derived cell cultures. Here, we describe the generation and data analysis of 3D microtissue models from patient-derived xenografts (PDX) of non-small cell lung carcinoma (NSCLC). Standard of care anti-cancer drugs were applied and the altered multicellular morphologies were captured by confocal microscopy, followed by automated image analyses to quantitatively measure phenotypic features for high-content chemosensitivity tests...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747628/the-anti-cancer-effects-of-itraconazole-in-epithelial-ovarian-cancer
#17
Chel Hun Choi, Ji-Yoon Ryu, Young-Jae Cho, Hye-Kyung Jeon, Jung-Joo Choi, Kris Ylaya, Yoo-Young Lee, Tae-Joong Kim, Joon-Yong Chung, Stephen M Hewitt, Byoung-Gie Kim, Duk-Soo Bae, Jeong-Won Lee
We assessed the anti-proliferative activity of itraconazole using an EOC cell line (SKOV3ip1) and endothelial cell lines (HUVEC & SVEC4-10). We also examined angiogenesis (VEGFR2, p-ERK, p-PLCr1/2), hedgehog (Gli1, Ptch1, SMO), and mTOR (pS6K1) signaling pathways to determine the mechanism of action of itraconazole. Furthermore, we evaluated the synergistic effects of itraconazole and paclitaxel using orthotopic mouse models with established EOC cells (SKOV3ip1 or HeyA8) as well as patient-derived xenografts (PDXs)...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746017/tumor-evolution-heterogeneity-and-therapy-for-our-patients-with-advanced-cancer-how-far-have-we-come
#18
Wafik S El-Deiry, Barry Taylor, Joel W Neal
The clinical and molecular heterogeneity of various cancer types is well documented. In the era of precision oncology whereby molecular profiling of tumors is incorporated into clinical care, both intra- and intertumoral molecular and genetic heterogeneity have been described. Together, they impact patient treatment and outcomes. Host genetics and the tumor microenvironment impact on tumor evolution and heterogeneity through variations in immune cell infiltration, stromal variations, and selection pressures from hypoxia or nutrient stress, among others...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28741929/putidaredoxin-binds-to-the-same-site-on-cytochrome-p450cam-in-the-open-and-closed-conformation
#19
Shu-Hao Liou, William K Myers, Jason D Oswald, R David Britt, David B Goodin
Cytochrome P450 CYP101A1 (P450cam) hydroxylates camphor by receiving two distinct electrons from its unique reductase, putidaredoxin (Pdx). Upon binding ferric P450cam, Pdx is now known to trigger a conformational change in the enzyme. This Pdx-induced conversion may provide the trigger to coordinate enzyme turnover and protect the enzyme from oxidative damage, so the interactions responsible for this conversion are of significant current interest. This proposed role for Pdx requires that its interactions with P450cam are different for the open and closed conformations...
July 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28730707/establishment-and-characterization-of-a-novel-murine-model-of-pancreatic-cancer-cachexia
#20
Katherine A Michaelis, Xinxia Zhu, Kevin G Burfeind, Stephanie M Krasnow, Peter R Levasseur, Terry K Morgan, Daniel L Marks
BACKGROUND: Cachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC-associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRAS(G12D) P53(R172H) Pdx-Cre(+/+) (KPC) mouse...
July 20, 2017: Journal of Cachexia, Sarcopenia and Muscle
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