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https://www.readbyqxmd.com/read/29330297/characterization-and-evidence-of-the-mir-888-cluster-as-a-novel-cancer-network-in-prostate
#1
Tsuyoshi Hasegawa, Garrison Glavich, Mary Pahuski, Aleena M Short, Oliver John Semmes, Lifang Yang, Vitold Galkin, Richard R Drake, Aurora Esquela-Kerscher
Prostate cancer afflicts 1 in 7 men and is the second leading cause of male cancer-related deaths in the United States. MicroRNAs (miRNAs), an extensive class of ~22 nucleotide non-coding RNAs, are often aberrantly expressed in tissues and fluids from prostate cancer patients but the mechanism of how specific miRNAs regulate prostate tumorigenesis and metastasis are poorly understood. Here, miR-888 was identified as a novel prostate factor that promotes proliferation and migration. miR-888 resides within a genomic cluster of 7 miRNA genes (mir-892c, mir-890, mir-888, mir-892a, mir-892b, mir-891b, mir-891a) on human chromosome Xq27...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29312549/the-akt-inhibitor-triciribine-in-combination-with-paclitaxel-has-order-specific-efficacy-against-zfp217-induced-breast-cancer-chemoresistance
#2
Christopher D Suarez, Junmin Wu, Sunil S Badve, Joseph A Sparano, William Kaliney, Laurie E Littlepage
We previously identified the transcription factor ZNF217 (human) / Zfp217 (mouse) as an oncogene and prognostic indicator of reduced survival, increased metastasis, and reduced response to therapy in breast cancer patients. Here we investigated the role of Zfp217 in chemotherapy resistance. Preclinical animal models of Zfp217 overexpression were treated with a combination therapy of the microtubule inhibitor epothilone B, doxorubicin (Adriamycin), and cyclophosphamide (EAC). Tumors overexpressing Zfp217 increased their tumor burden compared to control tumors after treatment and accumulated a mammary gland progenitor cell population (K8+K14+)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290975/gper-is-involved-in-the-regulation-of-the-estrogen-metabolizing-cyp1b1-enzyme-in-breast-cancer
#3
Francesca Cirillo, Michele Pellegrino, Rocco Malivindi, Vittoria Rago, Silvia Avino, Luigina Muto, Vincenza Dolce, Adele Vivacqua, Damiano Cosimo Rigiracciolo, Paola De Marco, Anna Sebastiani, Sergio Abonante, Miki Nakajima, Rosamaria Lappano, Marcello Maggiolini
The cytochrome P450 1B1 (CYP1B1) is a heme-thiolate monooxygenase involved in both estrogen biosynthesis and metabolism. For instance, CYP1B1 catalyzes the hydroxylation of E2 leading to the production of 4-hydroxyestradiol that may act as a potent carcinogenic agent. In addition, CYP1B1 is overexpressed in different tumors including breast cancer. In this scenario, it is worth mentioning that CYP1B1 expression is triggered by estrogens through the estrogen receptor (ER)α in breast cancer cells. In the present study, we evaluated whether the G protein estrogen receptor namely GPER may provide an alternate route toward the expression and function of CYP1B1 in ER-negative breast cancer cells, in main players of the tumor microenvironment as cancer associated fibroblasts (CAFs) that were obtained from breast cancer patients, in CAFs derived from a cutaneous metastasis of an invasive mammary ductal carcinoma and in breast tumor xenografts...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29259971/alk1fc-suppresses-the-human-prostate-cancer-growth-in-in-vitro-and-in-vivo-preclinical-models
#4
Letizia Astrologo, Eugenio Zoni, Sofia Karkampouna, Peter C Gray, Irena Klima, Joël Grosjean, Marie J Goumans, Lukas J A C Hawinkels, Gabri van der Pluijm, Martin Spahn, George N Thalmann, Peter Ten Dijke, Marianna Kruithof-de Julio
Prostate cancer is the second most common cancer in men and lethality is normally associated with the consequences of metastasis rather than the primary tumor. Therefore, targeting the molecular pathways that underlie dissemination of primary tumor cells and the formation of metastases has a great clinical value. Bone morphogenetic proteins (BMPs) play a critical role in tumor progression and this study focuses on the role of BMP9- Activin receptor-Like Kinase 1 and 2 (ALK1 and ALK2) axis in prostate cancer...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29249655/the-plag1-gdh1-axis-promotes-anoikis-resistance-and-tumor-metastasis-through-camkk2-ampk-signaling-in-lkb1-deficient-lung-cancer
#5
Lingtao Jin, Jaemoo Chun, Chaoyun Pan, Avi Kumar, Guojing Zhang, Youna Ha, Dan Li, Gina N Alesi, Yibin Kang, Lu Zhou, Wen-Mei Yu, Kelly R Magliocca, Fadlo R Khuri, Cheng-Kui Qu, Christian Metallo, Taofeek K Owonikoko, Sumin Kang
Loss of LKB1 is associated with increased metastasis and poor prognosis in lung cancer, but the development of targeted agents is in its infancy. Here we report that a glutaminolytic enzyme, glutamate dehydrogenase 1 (GDH1), upregulated upon detachment via pleomorphic adenoma gene 1 (PLAG1), provides anti-anoikis and pro-metastatic signals in LKB1-deficient lung cancer. Mechanistically, the GDH1 product α-KG activates CamKK2 by enhancing its substrate AMPK binding, which contributes to energy production that confers anoikis resistance...
December 12, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29242606/murine-stroma-adopts-a-human-like-metabolic-phenotype-in-the-pdx-model-of-colorectal-cancer-and-liver-metastases
#6
Arnaud Blomme, Gaetan Van Simaeys, Gilles Doumont, Brunella Costanza, Justine Bellier, Yukihiro Otaka, Félicie Sherer, Pierre Lovinfosse, Sébastien Boutry, Ana Perez Palacios, Edwin De Pauw, Touko Hirano, Takehiko Yokobori, Roland Hustinx, Akeila Bellahcène, Philippe Delvenne, Olivier Detry, Serge Goldman, Masahiko Nishiyama, Vincent Castronovo, Andrei Turtoi
Cancer research is increasingly dependent of patient-derived xenograft model (PDX). However, a major point of concern regarding the PDX model remains the replacement of the human stroma with murine counterpart. In the present work we aimed at clarifying the significance of the human-to-murine stromal replacement for the fidelity of colorectal cancer (CRC) and liver metastasis (CRC-LM) PDX model. We have conducted a comparative metabolic analysis between 6 patient tumors and corresponding PDX across 4 generations...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29237805/preclinical-evaluation-of-scc244-glumetinib-a-novel-potent-and-highly-selective-inhibitor-of-c-met-in-met-dependent-cancer-models
#7
Jing Ai, Yi Chen, Xia Peng, Yinchun Ji, Yong Xi, Yanyan Shen, Xinying Yang, Yi Su, Yi-Ming Sun, Yinglei Gao, Yuchi Ma, Bing Xiong, Jingkang Shen, Jian Ding, Meiyu Geng
Because the receptor tyrosine kinase c-Met plays a critical role in tumor growth, metastasis, tumor angiogenesis and drug resistance, the c-Met axis represents an attractive therapeutic target. Herein, we report the first preclinical characterization of SCC244, a novel, potent and highly selective inhibitor of c-Met kinase. SCC244 showed subnanomolar potency against c-Met kinase activity and high selectivity versus 312 other tested protein kinases, making it one of the most selective c-Met inhibitors described to date...
December 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29228593/proteasome-inhibitor-bortezomib-enhances-the-effect-of-standard-chemotherapy-in-small-cell-lung-cancer
#8
Sanaz Taromi, Florentine Lewens, Ruza Arsenic, Dagmar Sedding, Jörg Sänger, Almut Kunze, Markus Möbs, Joana Benecke, Helma Freitag, Friederike Christen, Daniel Kaemmerer, Amelie Lupp, Mareike Heilmann, Hedwig Lammert, Claus-Peter Schneider, Karen Richter, Michael Hummel, Britta Siegmund, Meike Burger, Franziska Briest, Patricia Grabowski
Small cell lung cancer (SCLC) is an aggressive cancer showing a very poor prognosis because of metastasis formation at an early stage and acquisition of chemoresistance. One key driver of chemoresistance is the transcription factor Forkhead box protein M1 (FOXM1) that regulates cell cycle proliferation, maintenance of genomic stability, DNA damage response, and cell differentiation in numerous tumor entities. In this study we investigated the role of FOXM1 in SCLC progression and analyzed the effect of FOXM1 inhibition using two proteasome inhibitors, bortezomib and siomycin A...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29208672/cd271-confers-an-invasive-and-metastatic-phenotype-of-head-and-neck-squamous-cell-carcinoma-through-the-upregulation-of-slug
#9
Man Ki Chung, Young Ho Jung, Joon Kyoo Lee, Soo Youn Cho, Oihana J Murillo-Sauca, Ravindra Uppaluri, June Ho Shin, John B Sunwoo
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is comprised of heterogeneous populations of cells, and CD271 (NGFR; p75NTR) has been associated with a tumor-initiating cell subpopulation. This study assessed the role of CD271 in modulating metastatic behavior in HNSCC. EXPERIMENTAL DESIGN: CD271 was overexpressed in murine and human oral squamous cell carcinoma cells to assess the impact of CD271 activation on the invasive and metastatic phenotype of these cells, using in vitro and orthotopic in vivo modeling...
December 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29187559/reprograming-of-glucose-metabolism-by-zerumbone-suppresses-hepatocarcinogenesis
#10
Nissar Wani, Bo Zhang, Kun-Yu Teng, Juan Barajas, Tasneem Motiwala, Peng Hu, Lianbo Yu, Rafael Brüschweiler, Kalpana Ghoshal, Samson T Jacob
Hepatocellular carcinoma (HCC) is the most prevalent and a highly aggressive liver malignancy with limited therapeutic options. Here, the therapeutic potential of zerumbone, a sesquiterpene derived from the ginger plant Zingiber zerumbet, against HCC was explored. Zerumbone inhibited proliferation and clonogenic survival of HCC cells in a dose-dependent manner by arresting cell at the G2/M phase, and inducing apoptosis. To elucidate the underlying molecular mechanism, a phosphokinase array was performed that showed significant inhibition of the PI3K/AKT/mTOR and STAT3 signaling pathways in zerumbone treated HCC cells...
November 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29179470/constitutive-activated-stat3-is-an-essential-regulator-and-therapeutic-target-in-esophageal-squamous-cell-carcinoma
#11
Fang Tian, Xiawen Yang, Ying Liu, Xiao Yuan, Tianli Fan, Fanmiao Zhang, Jimin Zhao, Jing Lu, Yanan Jiang, Ziming Dong, Yili Yang
Esophageal carcinoma is among the most common cancers worldwide and a leading cause of cancer death [1]. Large numbers of studies indicated that chronic inflammation is closely associated with its development [21, 25]. Furthermore, the JAK/STAT pathway, which plays a critical role in inflammation and immunity, has been implied in a number of malignancies [11]. It has been shown that targeting the pathway affected the growth, apoptosis, and metastasis of cultured esophageal squamous cell carcinoma cells [26]...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29174804/organoids-an-intermediate-modeling-platform-in-precision-oncology
#12
Ming-Zhu Jin, Run-Run Han, Guan-Zhong Qiu, Xiang-Chun Ju, Ge Lou, Wei-Lin Jin
Cancer harbors variable heterogeneity and plasticity. Thus far, our comprehension is greatly based on cell lines, organoids, and patient-derived tumor xenografts (PDTXs). Organoids are a three-dimensional in vitro culture platform constructed from self-organizing stem cells. They can almost accurately recapitulate tumor heterogeneity and microenvironment "in a dish," which surpass established cell lines and are not as expensive and time-consuming as PDTXs. As an intermediate model, tumor organoids are also used to study the fundamental issues of tumorigenesis and metastasis...
November 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29171033/actin-cytoskeleton-remodeling-drives-epithelial-mesenchymal-transition-for-hepatoma-invasion-and-metastasis
#13
Jei-Ming Peng, Rabindranath Bera, Chih-Yung Chiou, Ming-Chin Yu, Tse-Chin Chen, Chia-Wei Chen, Tsung-Rui Wang, Wan-Ling Chiang, Yongkun Wei, Huamin Wang, Mien-Chie Hung, Sen-Yung Hsieh
High invasiveness is a hallmark of human hepatocellular carcinoma (HCC). Large tumors predict invasion and metastasis. Epithelial-mesenchymal transition (EMT) is crucial for cancer invasion and metastasis. However, the mechanisms whereby large tumors tend to undergo EMT remain unclear. We conducted a subgenome-wide screen and identified KLHL23 as an HCC invasion suppressor via inhibiting EMT. KLHL23 binds to actin and suppresses actin polymerization. KLHL23 silencing induced filopodium and lamellipodium formation...
November 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29164052/development-of-novel-patient-derived-xenografts-from-breast-cancer-brain-metastases
#14
María J Contreras-Zárate, D Ryan Ormond, Austin E Gillen, Colton Hanna, Nicole L Day, Natalie J Serkova, Britta M Jacobsen, Susan M Edgerton, Ann D Thor, Virginia F Borges, Kevin O Lillehei, Michael W Graner, Peter Kabos, Diana M Cittelly
Brain metastases are an increasing burden among breast cancer patients, particularly for those with HER2(+) and triple negative (TN) subtypes. Mechanistic insight into the pathophysiology of brain metastases and preclinical validation of therapies has relied almost exclusively on intracardiac injection of brain-homing cells derived from highly aggressive TN MDA-MB-231 and HER2(+) BT474 breast cancer cell lines. Yet, these well characterized models are far from representing the tumor heterogeneity observed clinically and, due to their fast progression in vivo, their suitability to validate therapies for established brain metastasis remains limited...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29162812/role-of-epithelial-to-mesenchymal-transition-associated-genes-in-mammary-gland-regeneration-and-breast-tumorigenesis
#15
Shaheen S Sikandar, Angera H Kuo, Tomer Kalisky, Shang Cai, Maider Zabala, Robert W Hsieh, Neethan A Lobo, Ferenc A Scheeren, Sopheak Sim, Dalong Qian, Frederick M Dirbas, George Somlo, Stephen R Quake, Michael F Clarke
Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts we demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of EMT-associated genes...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158255/nitro-fatty-acid-inhibition-of-triple-negative-breast-cancer-cell-viability-migration-invasion-and-tumor-growth
#16
Chen-Shan Chen Woodcock, Yi Huang, Steven R Woodcock, Sonia R Salvatore, Bhupinder Singh, Franca Golin-Bisello, Nancy E Davidson, Carola Neumann, Bruce A Freeman, Stacy G Wendell
Triple negative breast cancer (TNBC) comprises ~20% of all breast cancers and is the most aggressive mammary cancer subtype. Devoid of the estrogen and progesterone receptors, along with the receptor tyrosine kinase ERB2 (HER2) that define most mammary cancers, there are no targeted therapies for patients with TNBC. This, combined with a high metastatic rate and a lower 5-year survival rate than for other breast cancer phenotypes, means there is significant unmet need for new therapeutic strategies. Herein, the anti-neoplastic effects of the electrophilic fatty acid nitroalkene derivative, 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA), were investigated in multiple preclinical models of TNBC...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29141225/a-comprehensive-patient-derived-xenograft-collection-representing-the-heterogeneity-of-melanoma
#17
Clemens Krepler, Katrin Sproesser, Patricia Brafford, Marilda Beqiri, Bradley Garman, Min Xiao, Batool Shannan, Andrea Watters, Michela Perego, Gao Zhang, Adina Vultur, Xiangfan Yin, Qin Liu, Ioannis N Anastopoulos, Bradley Wubbenhorst, Melissa A Wilson, Wei Xu, Giorgos Karakousis, Michael Feldman, Xiaowei Xu, Ravi Amaravadi, Tara C Gangadhar, David E Elder, Lauren E Haydu, Jennifer A Wargo, Michael A Davies, Yiling Lu, Gordon B Mills, Dennie T Frederick, Michal Barzily-Rokni, Keith T Flaherty, Dave S Hoon, Michael Guarino, Joseph J Bennett, Randall W Ryan, Nicholas J Petrelli, Carol L Shields, Mizue Terai, Takami Sato, Andrew E Aplin, Alexander Roesch, David Darr, Steve Angus, Rakesh Kumar, Ensar Halilovic, Giordano Caponigro, Sebastien Jeay, Jens Wuerthner, Annette Walter, Matthias Ocker, Matthew B Boxer, Lynn Schuchter, Katherine L Nathanson, Meenhard Herlyn
Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29137305/mir-93-3p-inhibition-suppresses-clear-cell-renal-cell-carcinoma-proliferation-metastasis-and-invasion
#18
Lu Wang, Guang Yang, Xiangwei Zhu, Ziqi Wang, Hongzhi Wang, Yang Bai, Pengcheng Sun, Li Peng, Wei Wei, Guang Chen, Guangbin Li, Andrey A Zamyatnin, Peter V Glybochko, Wanhai Xu
miRNA dysregulation is associated with many human diseases, including cancer. This study explored the effects of miR-93-3p on clear cell renal cell carcinoma (ccRCC). We found that miR-93-3p is upregulated an average of 38-fold in 138 ccRCC specimens compared to matched normal kidney tissues, which correlated with poor patient outcome. miR-93-3p inhibition reduced ccRCC cell growth, invasion, and migration in vitro and in a mouse xenograft model. A search of the TargetScan, miRanda, and PicTar databases revealed that miR-93-3p is predicted to regulate pigment epithelium-derived factor (PEDF)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29115601/ginsenoside-rg3-targets-cancer-stem-cells-and-tumor-angiogenesis-to-inhibit-colorectal-cancer-progression-in-vivo
#19
Yu-Chen Tang, Yan Zhang, Jin Zhou, Qiaoming Zhi, Meng-Yao Wu, Fei-Ran Gong, Meng Shen, Lu Liu, Min Tao, Bairong Shen, Dong-Mei Gu, Jie Yu, Meng-Dan Xu, Yuan Gao, Wei Li
Anti-angiogenic therapy has been successfully applied to treat colorectal cancer (CRC). Ginsenoside Rg3, derived from the Chinese herb ginseng, has anti-vascularization effects and can inhibit tumor growth and metastasis, and can sensitize cancer cells to chemotherapy. Therefore, in the present study, we investigated whether Rg3 could be appropriate for CRC treatment. Growth of CRC cells was assessed by an MTT (methyl thiazolyl tetrazolium) assay in vitro and using orthotopic xenograft models in vivo. mRNA expression was evaluated using real-time PCR...
November 1, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29109980/the-abundance-of-metabolites-related-to-protein-methylation-correlates-with-the-metastatic-capacity-of-human-melanoma-xenografts
#20
Xiaolei Shi, Alpaslan Tasdogan, Fang Huang, Zeping Hu, Sean J Morrison, Ralph J DeBerardinis
Metabolic reprogramming is a major factor in transformation, and particular metabolic phenotypes correlate with oncogenotype, tumor progression, and metastasis. By profiling metabolites in 17 patient-derived xenograft melanoma models, we identified durable metabolomic signatures that correlate with biological features of the tumors. BRAF mutant tumors had metabolomic and metabolic flux features of enhanced glycolysis compared to BRAF wild-type tumors. Tumors that metastasized efficiently from their primary sites had elevated levels of metabolites related to protein methylation, including trimethyllysine (TML)...
November 2017: Science Advances
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