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patient derived xenograft metastasis

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https://www.readbyqxmd.com/read/28077676/a-ptk7-targeted-antibody-drug-conjugate-reduces-tumor-initiating-cells-and-induces-sustained-tumor-regressions
#1
Marc Damelin, Alexander Bankovich, Jeffrey Bernstein, Justin Lucas, Liang Chen, Samuel Williams, Albert Park, Jorge Aguilar, Elana Ernstoff, Manoj Charati, Russell Dushin, Monette Aujay, Christina Lee, Hanna Ramoth, Milly Milton, Johannes Hampl, Sasha Lazetic, Virginia Pulito, Edward Rosfjord, Yongliang Sun, Lindsay King, Frank Barletta, Alison Betts, Magali Guffroy, Hadi Falahatpisheh, Christopher J O'Donnell, Robert Stull, Marybeth Pysz, Paul Escarpe, David Liu, Orit Foord, Hans Peter Gerber, Puja Sapra, Scott J Dylla
Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28065789/choline-kinase-alpha-mediates-interactions-between-the-epidermal-growth-factor-receptor-and-mtorc2-in-hepatocellular-carcinoma-cells-to-promote-drug-resistance-and-xenograft-tumor-progression
#2
Xi-Meng Lin, Liang Hu, Jin Gu, Ruo-Yu Wang, Liang Li, Jing Tang, Bao-Hua Zhang, Xing-Zhou Yan, Yan-Jing Zhu, Cong-Li Hu, Wei-Ping Zhou, Shao Li, Jing-Feng Liu, Frank J Gonzalez, Meng-Chao Wu, Hong-Yang Wang, Lei Chen
BACKGROUND & AIMS: Choline kinase alpha (CHKA) catalyzes conversion of choline to phosphocholine and can contribute to carcinogenesis. Little is known about the role of CHKA in the pathogenesis of hepatocellular carcinoma (HCC). METHODS: We performed whole-exome and transcriptome sequence analyses of 9 paired HCC and non-tumor adjacent tissues. We performed tissue chip analyses of 120 primary HCC and non-tumor adjacent tissues from patients who received surgery in Shanghai, China from January 2006 through December 2009; 48 sets of specimens (HCC and non-tumor adjacent tissues) were also analyzed...
January 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28060954/activation-of-the-mtor-pathway-by-oxaliplatin-in-the-treatment-of-colorectal-cancer-liver-metastasis
#3
Min Lu, Amelia S Zessin, Wayne Glover, David S Hsu
BACKGROUND: Standard of care treatment for colorectal cancer liver metastasis consists of a cytotoxic chemotherapy in combination with a targeted agent. Clinical trials have guided the use of these combinatory therapies, but it remains unclear what the optimal combinations of cytotoxic chemotherapy with a targeted agent are. METHODS: Using a genomic based approach, gene expression profiling was obtained from tumor samples of patient with colorectal cancer liver metastasis who received an oxaliplatin based therapy...
2017: PloS One
https://www.readbyqxmd.com/read/28018977/heterogeneous-perivascular-cell-coverage-affects-breast-cancer-metastasis-and-response-to-chemotherapy
#4
Jiha Kim, Pedro Correa de Sampaio, Donna Marie Lundy, Qian Peng, Kurt W Evans, Hikaru Sugimoto, Mihai Gagea, Yvonne Kienast, Nayra Soares do Amaral, Rafael Malagoli Rocha, Hans Petter Eikesdal, Per Eystein Lønning, Funda Meric-Bernstam, Valerie S LeBleu
Angiogenesis and co-optive vascular remodeling are prerequisites of solid tumor growth. Vascular heterogeneity, notably perivascular composition, may play a critical role in determining the rate of cancer progression. The contribution of vascular pericyte heterogeneity to cancer progression and therapy response is unknown. Here, we show that angiopoietin-2 (Ang2) orchestrates pericyte heterogeneity in breast cancer with an effect on metastatic disease and response to chemotherapy. Using multispectral imaging of human breast tumor specimens, we report that perivascular composition, as defined by the ratio of PDGFRβ(-) and desmin(+) pericytes, provides information about the response to epirubicin but not paclitaxel...
December 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/28008721/therapy-of-primary-and-metastatic-liver-cancer-by-human-ips-cell-derived-myeloid-cells-producing-interferon-%C3%AE
#5
Masataka Sakisaka, Miwa Haruta, Yoshihiro Komohara, Satoshi Umemoto, Keiko Matsumura, Tokunori Ikeda, Motohiro Takeya, Yukihiro Inomata, Yasuharu Nishimura, Satoru Senju
BACKGROUND: iPS-ML are myeloid lineage cells with a proliferative capacity derived from induced pluripotent stem (iPS) cells. This study aimed to examine therapeutic effect of iPS-ML producing interferon-β (iPS-ML/IFN-β) towards primary and metastatic liver cancer and investigate the mechanism of that effect. METHODS: We established a xenograft model of liver metastasis by injecting the spleen of SCID mice with MKN-45 human gastric cancer cells and also a primary liver cancer model by injecting SK-HEP-1 human hepatocellular carcinoma cells into the liver...
December 23, 2016: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/28003307/pi3k-inhibition-reduces-mammary-tumor-growth-and-facilitates-anti-tumor-immunity-and-anti-pd1-responses
#6
Jiqing Sai, Philip Owens, Sergey V Novitiskiy, Oriana E Hawkins, Anna E Vilgelm, Jinming Yang, Tammy Sobolik-Delmaire, Nicole Lavender, Andrew C Johnson, Colt McClain, Gregory D Ayers, Mark C Kelley, Melinda Sanders, Ingrid A Mayer, Harold L Moses, Mark Boothby, Ann Richmond
PURPOSE: Metastatic breast cancers continue to elude current therapeutic strategies, including those utilizing PI3K inhibitors. Given the prominent role of PI3Kα,β in tumor growth and PI3Kγ,δ in immune cell function, we sought to determine whether PI3K inhibition altered anti-tumor immunity. EXPERIMENTAL DESIGN: The effect of PI3K inhibition on tumor growth, metastasis, and anti-tumor immune response was characterized in mouse models utilizing orthotopic implants of 4T1 or PyMT mammary tumors into syngeneic or PI3Kγ null mice, and patient-derived breast cancer xenografts in humanized mice...
December 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27998973/nectin-4-a-new-prognostic-biomarker-for-efficient-therapeutic-targeting-of-primary-and-metastatic-triple-negative-breast-cancer
#7
REVIEW
M M-Rabet, O Cabaud, E Josselin, P Finetti, R Castellano, A Farina, E Agavnian-Couquiaud, G Saviane, Y Collette, P Viens, A Gonçalves, C Ginestier, E Charafe-Jauffret, D Birnbaum, D Olive, F Bertucci, M Lopez
BACKGROUND: Triple-negative breast cancers (TNBCs) are associated with a poor prognosis. In contrast to other molecular subtypes, they have no identified specific target and chemotherapy remains the only available systemic treatment. The adhesion molecule nectin-4 represents a new potential therapeutic target in different cancer models. Here, we have tested the prognostic value of nectin-4 expression and assessed the therapeutic efficiency of an anti-nectin 4 antibody drug conjugate (ADC) on localised and metastatic TNBC in vitro and in vivo MATERIAL AND METHODS: : We analysed nectin-4/PVRL4 mRNA expression in 5,673 invasive breast cancers and searched for correlations with clinicopathological features including metastasis-free survival (MFS)...
December 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27929464/labeling-of-breast-cancer-patient-derived-xenografts-with-traceable-reporters-for-tumor-growth-and-metastasis-studies
#8
Colton Hanna, Letty Kwok, Jessica Finlay-Schultz, Carol A Sartorius, Diana M Cittelly
The use of preclinical models to study tumor biology and response to treatment is central to cancer research. Long-established human cell lines, and many transgenic mouse models, often fail to recapitulate the key aspects of human malignancies. Thus, alternative models that better represent the heterogeneity of patients' tumors and their metastases are being developed. Patient-derived xenograft (PDX) models in which surgically resected tumor samples are engrafted into immunocompromised mice have become an attractive alternative as they can be transplanted through multiple generations,and more efficiently reflect tumor heterogeneity than xenografts derived from human cancer cell lines...
November 30, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27923843/therapeutic-activity-of-anti-axl-antibody-against-triple-negative-breast-cancer-patient-derived-xenografts-and-metastasis
#9
Wilhem Leconet, Myriam Chentouf, Stanislas Du Manoir, Clément Chevalier, Audrey Sirevnt, Imade Aït-Arsa, Muriel Busson, Marta Jarlier, Nina Radosevic-Robin, Charles G Theillet, Dany Chalbos, Jean-Max Pasquet, André Pèlegrin, Christel Larbouret, Bruno Robert
PURPOSE: AXL receptor tyrosine kinase has been described as a relevant molecular marker and a key player in invasiveness, especially in triple negative breast cancer (TNBC). EXPERIMENTAL DESIGN: We evaluate the anti-tumor efficacy of the anti-AXL monoclonal antibody 20G7-D9 in several TNBC cell xenografts or patient-derived xenograft (PDX) models and decipher the underlying mechanisms. In a dataset of 254 basal-like breast cancer samples, genes correlated with AXL expression are enriched in EMT, migration and invasion signaling pathways...
December 6, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27913947/preclinical-evaluation-of-cathepsin-based-fluorescent-imaging-system-for-cytoreductive-surgery
#10
Carlos H F Chan, Lukas F Liesenfeld, Isabel Ferreiro-Neira, James C Cusack
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal surface malignancies. The ability to detect microscopic foci of peritoneal metastasis intraoperatively may ensure the completeness of cytoreduction. In this study, we evaluated the suitability of a hand-held cathepsin-based fluorescent imaging system for intraoperative detection of appendiceal and colorectal peritoneal metastasis. METHODS: Peritoneal tumors and normal peritoneal tissues were collected from patients with appendiceal and colorectal peritoneal metastasis...
December 2, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27907907/expression-analysis-and-clinical-significance-of-eif4e-vegf-c-e-cadherin-and-mmp-2-in-colorectal-adenocarcinoma
#11
Minna Gao, Xiong Zhang, Dan Li, Ping He, Wenguang Tian, Bo Zeng
The underlying mechanisms of colorectal carcinoma (CRC) metastasis remain to be elucidated. The aim of this study is to investigate clinical significance and the expression of eIF4E, VEGF-C, MMP-2, and E-cadherin in the CRC metastasis. We investigated their expressions in 108 patients, analyzed the relationships between their expressions in CRC and evaluated the relationships between their expressions and clinical pathogenic parameters. Furthermore, their roles in patient survival and in CRC metastasis were also investigated...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27875522/hedgehog-inhibition-enhances-efficacy-of-radiation-and-cisplatin-in-orthotopic-cervical-cancer-xenografts
#12
Naz Chaudary, Melania Pintilie, David Hedley, Richard P Hill, Michael Milosevic, Helen Mackay
BACKGROUND: The Hedgehog (Hh) pathway is upregulated in cervical cancer and associated with poor outcome. We explored the effects of Hh pathway inhibition in combination with RTCT in a patient derived orthotopic cervical cancer xenograft model (OCICx). METHODS: 5E1, a monoclonal antibody for SHH, or Sonidegib (LDE225), a clinical SMO inhibitor (Novartis) were added to RTCT. We investigated tumour growth delay, metastasis and GI toxicity using orthotopic cervical cancer xenografts models...
January 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27874835/heterotypic-mouse-models-of-canine-osteosarcoma-recapitulate-tumor-heterogeneity-and-biological-behavior
#13
Milcah C Scott, Hirotaka Tomiyasu, John R Garbe, Ingrid Cornax, Clarissa Amaya, M Gerard O'Sullivan, Subbaya Subramanian, Brad A Bryan, Jaime F Modiano
Osteosarcoma (OS) is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed...
December 1, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27870570/activating-notch1-mutations-define-a-distinct-subgroup-of-patients-with-adenoid-cystic-carcinoma-who-have-poor-prognosis-propensity-to-bone-and-liver-metastasis-and-potential-responsiveness-to-notch1-inhibitors
#14
Renata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N William, Bonnie S Glisson, Michael J Wick, Ann M Kapoun, Amita Patnaik, Gail Eckhardt, Pamela Munster, Leonardo Faoro, Jakob Dupont, J Jack Lee, Andrew Futreal, Adel K El-Naggar, John V Heymach
Purpose Adenoid cystic carcinomas (ACCs) represent a heterogeneous group of chemotherapy refractory tumors, with a subset demonstrating an aggressive phenotype. We investigated the molecular underpinnings of this phenotype and assessed the Notch1 pathway as a potential therapeutic target. Methods We genotyped 102 ACCs that had available pathologic and clinical data. Notch1 activation was assessed by immunohistochemistry for Notch1 intracellular domain. Luciferase reporter assays were used to confirm Notch1 target gene expression in vitro...
November 21, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27867497/murine-models-of-breast-cancer-bone-metastasis
#15
Laura E Wright, Penelope D Ottewell, Nadia Rucci, Olivier Peyruchaud, Gabriel M Pagnotti, Antonella Chiechi, Jeroen T Buijs, Julie A Sterling
Bone metastases cause significant morbidity and mortality in late-stage breast cancer patients and are currently considered incurable. Investigators rely on translational models to better understand the pathogenesis of skeletal complications of malignancy in order to identify therapeutic targets that may ultimately prevent and treat solid tumor metastasis to bone. Many experimental models of breast cancer bone metastases are in use today, each with its own caveats. In this methods review, we characterize the bone phenotype of commonly utilized human- and murine-derived breast cell lines that elicit osteoblastic and/or osteolytic destruction of bone in mice and report methods for optimizing tumor-take in murine models of bone metastasis...
2016: BoneKEy Reports
https://www.readbyqxmd.com/read/27835901/mutational-activation-of-braf-confers-sensitivity-to-transforming-growth-factor-beta-inhibitors-in-human-cancer-cells
#16
Lindsay C Spender, G John Ferguson, Sijia Liu, Chao Cui, Maria Romina Girotti, Gary Sibbet, Ellen B Higgs, Morven K Shuttleworth, Tom Hamilton, Paul Lorigan, Michael Weller, David F Vincent, Owen J Sansom, Margaret Frame, Peter Ten Dijke, Richard Marais, Gareth J Inman
Recent data implicate elevated transforming growth factor-β (TGFβ) signalling in BRAF inhibitor drug-resistance mechanisms, but the potential for targeting TGFβ signalling in cases of advanced melanoma has not been investigated. We show that mutant BRAFV600E confers an intrinsic dependence on TGFβ/TGFβ receptor 1 (TGFBR1) signalling for clonogenicity of murine melanocytes. Pharmacological inhibition of the TGFBR1 blocked the clonogenicity of human mutant BRAF melanoma cells through SMAD4-independent inhibition of mitosis, and also inhibited metastasis in xenografted zebrafish...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835884/combination-of-cox-2-expression-and-pik3ca-mutation-as-prognostic-and-predictive-markers-for-celecoxib-treatment-in-breast-cancer
#17
Sandrine Tury, Véronique Becette, Franck Assayag, Sophie Vacher, Camille Benoist, Maud Kamal, Elisabetta Marangoni, Ivan Bièche, Florence Lerebours, Céline Callens
COX-2 expression level and prognostic value are still a matter of debate in breast cancer (BC). We addressed these points in the context of PIK3CA mutational status. Based on an interesting study of aspirin efficacy in colorectal cancer, we hypothesized that celecoxib antitumoral activity may be restricted to PIK3CA mutated BC.COX-2 mRNA expression was analyzed in 446 BC samples and in 61 BC patient-derived xenografts (PDX) using quantitative RT-PCR. The prognostic impact of COX-2 expression level was assessed independently and according to PIK3CA mutational status in our cohort and in a validation set of 817 BC...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27827359/vasculogenic-mimicry-in-small-cell-lung-cancer
#18
Stuart C Williamson, Robert L Metcalf, Francesca Trapani, Sumitra Mohan, Jenny Antonello, Benjamin Abbott, Hui Sun Leong, Christopher P E Chester, Nicole Simms, Radoslaw Polanski, Daisuke Nonaka, Lynsey Priest, Alberto Fusi, Fredrika Carlsson, Anders Carlsson, Mary J C Hendrix, Richard E B Seftor, Elisabeth A Seftor, Dominic G Rothwell, Andrew Hughes, James Hicks, Crispin Miller, Peter Kuhn, Ged Brady, Kathryn L Simpson, Fiona H Blackhall, Caroline Dive
Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form 'endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (P<0...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27815673/erratum-to-patient-derived-mammosphere-and-xenograft-tumour-initiation-correlates-with-progression-to-metastasis
#19
Rachel Eyre, Denis G Alférez, Kath Spence, Mohamed Kamal, Frances L Shaw, Bruno M Simões, Angélica Santiago-Gómez, Aida Sarmiento-Castro, Maria Bramley, Mohammed Absar, Zahida Saad, Sumohan Chatterjee, Cliona Kirwan, Ashu Gandhi, Anne C Armstrong, Andrew M Wardley, Ciara S O'Brien, Gillian Farnie, Sacha J Howell, Robert B Clarke
No abstract text is available yet for this article.
December 2016: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/27811013/characteristics-of-a-thyroid-carcinoma-cell-line-derived-from-spinal-metastasis
#20
Zhenhua Zhou, Yan Li, Xu Yan, Xudong Wang, Su Chen, Jianru Xiao
A thyroid carcinoma cell line named THY28 was established through primary culture of the surgical specimens, which were derived from a Chinese patient with spinal metastasis. The cell morphology, growth kinetics, cell cycle, chromosome number, cell capability of migration, tumorigenicity and cytogenetic features of the cell line were investigated. THY28 cells were subcultured in vitro for more than 50 passages with a human karyotype. The modal number of its chromosomes was mainly from 67 to 85. The doubling time of THY28 cells was 56 hours...
December 2016: Bioscience Reports
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