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patient derived xenograft metastasis

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https://www.readbyqxmd.com/read/28930697/overexpression-of-muc1-and-genomic-alterations-in-its-network-associate-with-prostate-cancer-progression
#1
Xiaozeng Lin, Yan Gu, Anil Kapoor, Fengxiang Wei, Tariq Aziz, Diane Ojo, Yanzhi Jiang, Michael Bonert, Bobby Shayegan, Huixiang Yang, Khalid Al-Nedawi, Pierre Major, Damu Tang
We investigate the association of MUC1 with castration-resistant prostate cancer (CRPC), bone metastasis, and PC recurrence. MUC1 expression was studied in patient-derived bone metastasis and CRPCs produced by prostate-specific PTEN(-/-) mice and LNCaP xenografts. Elevations in MUC1 expression occur in CRPC. Among nine patients with hormone-naïve bone metastasis, eight express MUC1 in 61% to 100% of PC cells. Utilizing cBioPortal PC genomic data, we organized a training (n=300), testing (n=185), and validation (n=194) cohort...
September 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28903357/intratumoral-acidosis-fosters-cancer-induced-bone-pain-through-the-activation-of-the-mesenchymal-tumor-associated-stroma-in-bone-metastasis-from-breast-carcinoma
#2
Gemma Di Pompo, Silvia Lemma, Lorenzo Canti, Nadia Rucci, Marco Ponzetti, Costantino Errani, Davide Maria Donati, Shonagh Russell, Robert Gillies, Tokuhiro Chano, Nicola Baldini, Sofia Avnet
Cancer-induced bone pain (CIBP) is common in patients with bone metastases (BM), significantly impairing quality of life. The current treatments for CIBP are limited since they are often ineffective. Local acidosis derived from glycolytic carcinoma and tumor-induced osteolysis is only barely explored cause of pain. We found that breast carcinoma cells that prefer bone as a metastatic site have very high extracellular proton efflux and expression of pumps/ion transporters associated with acid-base balance (MCT4, CA9, and V-ATPase)...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28886423/molecular-imaging-of-colorectal-tumors-by-targeting-colon-cancer-secreted-protein-2-ccsp-2
#3
Jaeil Kim, Eun-Ju Do, Helen Moinova, Sang Mun Bae, Ja Young Kang, Seung-Mo Hong, Stephen P Fink, Jinmyoung Joo, Young-Ah Suh, Se Jin Jang, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Jaewon Choe, Suk-Kyun Yang, Sanford D Markowitz, Sang-Yeob Kim, Seung-Jae Myung
A versatile biomarker for detecting colonic adenoma and colon cancer has yet to be developed. Colon cancer secreted protein-2 (CCSP-2) is a protein specifically expressed and secreted in colon adenomas and cancers. We developed a fluorescent imaging method based on CCSP-2 targeting for a more sensitive and specific detection of colorectal tumors. CCSP-2 expression was evaluated in human colon adenoma and colorectal specimens. Anti-CCSP-2 antibody was labeled with a near-infrared fluorescent dye, FPR-675, and molecular imaging of surgical human colorectal tumors was performed...
September 4, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28882943/tissue-directed-implantation-using-ultrasound-visualization-for-development-of-biologically-relevant-metastatic-tumor-xenografts
#4
Raelene A VAN Noord, Tina Thomas, Melanie Krook, Sahiti Chukkapalli, Mark J Hoenerhoff, Jonathan R Dillman, Elizabeth R Lawlor, Valerie P Opipari, Erika A Newman
BACKGROUND: Advances in cancer therapeutics depend on reliable in vivo model systems. To develop biologically relevant xenografts, ultrasound was utilized for tissue-directed implantation of neuroblastoma (NB) cell line and patient-derived tumors in the adrenal gland, and for renal subcapsular engraftment of Ewing's sarcoma (ES). MATERIALS AND METHODS: NB xenografts were established by direct adrenal injection of luciferase-transfected NB cell lines (IMR32, SH-SY5Y, SK-N-BE2) or NB patient-derived tumor cells (UMNBL001, UMNBL002)...
September 2017: In Vivo
https://www.readbyqxmd.com/read/28881671/malignant-pericytes-expressing-gt198-give-rise-to-tumor-cells-through-angiogenesis
#5
Liyong Zhang, Yan Wang, Mohammad H Rashid, Min Liu, Kartik Angara, Nahid F Mivechi, Nita J Maihle, Ali S Arbab, Lan Ko
Angiogenesis promotes tumor development. Understanding the crucial factors regulating tumor angiogenesis may reveal new therapeutic targets. Human GT198 (PSMC3IP or Hop2) is an oncoprotein encoded by a DNA repair gene that is overexpressed in tumor stromal vasculature to stimulate the expression of angiogenic factors. Here we show that pericytes expressing GT198 give rise to tumor cells through angiogenesis. GT198(+) pericytes and perivascular cells are commonly present in the stromal compartment of various human solid tumors and rodent xenograft tumor models...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880889/loss-of-kaiso-expression-in-breast-cancer-cells-prevents-intra-vascular-invasion-in-the-lung-and-secondary-metastasis
#6
Jacek M Kwiecien, Blessing I Bassey-Archibong, Wojciech Dabrowski, Lyndsay G Rayner, Alexandra R Lucas, Juliet M Daniel
The metastatic activity of breast carcinomas results from complex genetic changes in epithelial tumor cells and accounts for 90% of deaths in affected patients. Although the invasion of the local lymphatic vessels and veins by malignant breast tumor cells and their subsequent metastasis to the lung, has been recognized, the mechanisms behind the metastatic activity of breast tumor cells to other distal organs and the pathogenesis of metastatic cancer are not well understood. In this study, we utilized derivatives of the well-established and highly metastatic triple negative breast cancer (TNBC) cell line MDA-MB-231 (MDA-231) to study breast tumor metastasis in a mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28874669/phenotype-driven-precision-oncology-as-a-guide-for-clinical-decisions-one-patient-at-a-time
#7
Shumei Chia, Joo-Leng Low, Xiaoqian Zhang, Xue-Lin Kwang, Fui-Teen Chong, Ankur Sharma, Denis Bertrand, Shen Yon Toh, Hui-Sun Leong, Matan T Thangavelu, Jacqueline S G Hwang, Kok-Hing Lim, Thakshayeni Skanthakumar, Hiang-Khoon Tan, Yan Su, Siang Hui Choo, Hannes Hentze, Iain B H Tan, Alexander Lezhava, Patrick Tan, Daniel S W Tan, Giridharan Periyasamy, Judice L Y Koh, N Gopalakrishna Iyer, Ramanuj DasGupta
Genomics-driven cancer therapeutics has gained prominence in personalized cancer treatment. However, its utility in indications lacking biomarker-driven treatment strategies remains limited. Here we present a "phenotype-driven precision-oncology" approach, based on the notion that biological response to perturbations, chemical or genetic, in ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic response in the clinic. We generated a library of "screenable" patient-derived primary cultures (PDCs) for head and neck squamous cell carcinomas that reproducibly predicted treatment response in matched patient-derived-xenograft models...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28854237/tumor-engraftment-in-patient-derived-xenografts-of-pancreatic-ductal-adenocarcinoma-is-associated-with-adverse-clinicopathological-features-and-poor-survival
#8
Ilaria Pergolini, Vicente Morales-Oyarvide, Mari Mino-Kenudson, Kim C Honselmann, Matthew W Rosenbaum, Sabikun Nahar, Marina Kem, Cristina R Ferrone, Keith D Lillemoe, Nabeel Bardeesy, David P Ryan, Sarah P Thayer, Andrew L Warshaw, Carlos Fernández-Del Castillo, Andrew S Liss
Patient-derived xenograft (PDX) tumors are powerful tools to study cancer biology. However, the ability of PDX tumors to model the biological and histological diversity of pancreatic ductal adenocarcinoma (PDAC) is not well known. In this study, we subcutaneously implanted 133 primary and metastatic PDAC tumors into immunodeficient mice. Fifty-seven tumors were successfully engrafted and even after extensive passaging, the histology of poorly-, moderately-, and well-differentiated tumors was maintained in the PDX models...
2017: PloS One
https://www.readbyqxmd.com/read/28841829/hypoxic-exosomes-facilitate-bladder-tumor-growth-and-development-through-transferring-long-non-coding-rna-uca1
#9
Mei Xue, Wei Chen, An Xiang, Ruiqi Wang, He Chen, Jingjing Pan, Huan Pang, Hongli An, Xiang Wang, Huilian Hou, Xu Li
BACKGROUND: To overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells...
August 25, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28835536/single-cell-functional-and-chemosensitive-profiling-of-combinatorial-colorectal-therapy-in-zebrafish-xenografts
#10
Rita Fior, Vanda Póvoa, Raquel V Mendes, Tânia Carvalho, António Gomes, Nuno Figueiredo, Miguel Godinho Ferreira
Cancer is as unique as the person fighting it. With the exception of a few biomarker-driven therapies, patients go through rounds of trial-and-error approaches to find the best treatment. Using patient-derived cell lines, we show that zebrafish larvae xenotransplants constitute a fast and highly sensitive in vivo model for differential therapy response, with resolution to reveal intratumor functional cancer heterogeneity. We screened international colorectal cancer therapeutic guidelines and determined distinct functional tumor behaviors (proliferation, metastasis, and angiogenesis) and differential sensitivities to standard therapy...
August 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28783171/the-pdgfr%C3%AE-laminin-b1-keratin-19-cascade-drives-tumor-progression-at-the-invasive-front-of-human-hepatocellular-carcinoma
#11
O Govaere, M Petz, J Wouters, Y-P Vandewynckel, E J Scott, B Topal, F Nevens, C Verslype, Q M Anstee, H Van Vlierberghe, W Mikulits, T Roskams
Human hepatocellular carcinomas (HCCs) expressing the biliary/hepatic progenitor cell marker keratin 19 (K19) have been linked with a poor prognosis and exhibit an increase in platelet-derived growth factor receptor α (PDGFRα) and laminin beta 1 (LAMB1) expression. PDGFRα has been reported to induce de novo synthesis of LAMB1 protein in a Sjogren syndrome antigen B (La/SSB)-dependent manner in a murine metastasis model. However, the role of this cascade in human HCC remains unclear. This study focused on the functional role of the PDGFRα-La/SSB-LAMB1 pathway and its molecular link to K19 expression in human HCC...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28783167/toosendanin-demonstrates-promising-antitumor-efficacy-in-osteosarcoma-by-targeting-stat3
#12
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/28782139/low-doses-of-curcuma-longa-modulates-cell-migration-and-cell-cell-adhesion
#13
Paloma Santos de Campos, Bibiana Franzen Matte, Leonardo Francisco Diel, Luciano Henrique Jesus, Lisiane Bernardi, Alessandro Menna Alves, Pantelis Varvaki Rados, Marcelo Lazzaron Lamers
Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell-cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC...
August 7, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28778066/inhibition-of-lsd1-epigenetically-attenuates-oral-cancer-growth-and-metastasis
#14
Saqer F Alsaqer, Mustafa M Tashkandi, Vinay K Kartha, Ya-Ting Yang, Yazeed Alkheriji, Andrew Salama, Xaralabos Varelas, Maria Kukuruzinska, Stefano Monti, Manish V Bais
Lysine-specific demethylase 1 (LSD1) is a nuclear histone demethylase and a member of the amine oxidase (AO) family. LSD1 is a flavin-containing AO that specifically catalyzes the demethylation of mono- and di-methylated histone H3 lysine 4 through an FAD-dependent oxidative reaction. LSD1 is inappropriately upregulated in lung, liver, brain and esophageal cancers, where it promotes cancer initiation, progression, and metastasis. However, unlike other lysine-specific demethylases, the role and specific targets of LSD1 in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765324/glesatinib-exhibits-antitumor-activity-in-lung-cancer-models-and-patients-harboring-met-exon-14-mutations-and-overcomes-mutation-mediated-resistance-to-type-i-met-inhibitors-in-nonclinical-models
#15
Lars Engstrom, Ruth Aranda, Matthew Lee, Elizabeth A Tovar, Curt Essenburg, Zachary B Madaj, Harrah Chiang, David Briere, Jill Hallin, Pedro P Lopez-Casas, Natalia Banos, Camino Menéndez, Manuel Hidalgo, Vanessa Tassell, Richard Chao, Darya I Chudova, Richard B Lanman, Peter Olson, Lyudmila Bazhenova, Sandip P Patel, Carrie R Graveel, Mizuki Nishino, Geoffrey I Shapiro, Nir Peled, Mark M Awad, Pasi A Janne, James G Christensen
MET exon 14 deletion (METex14 del) mutations represent a novel class of non-small cell lung cancer (NSCLC) driver mutations.  We evaluated glesatinib, a spectrum-selective MET inhibitor exhibiting a type II binding mode, in METex14 del-positive nonclinical models and NSCLC patients and assessed its ability to overcome resistance to type I MET Inhibitors.<br /><br />Experimental Design: As most MET inhibitors in clinical development bind the active site with a type I binding mode, we investigated mechanisms of acquired resistance to each MET inhibitor class utilizing in vitro and in vivo models and in glesatinib clinical trials...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28754458/terfenadine-combined-with-epirubicin-impedes-the-chemo-resistant-human-non-small-cell-lung-cancer-both-in-vitro-and-in-vivo-through-emt-and-notch-reversal
#16
Li An, Dan-Dan Li, Hai-Xiao Chu, Qiao Zhang, Chang-Li Wang, Yan-Hua Fan, Qi Song, Hong-Da Ma, Fan Feng, Qing-Chun Zhao
The acquired resistance of non-small cell lung cancer (NSCLC) to taxanes eventually leads to the recurrence and metastasis of tumours. Thus, the development of therapeutic strategies based on the mechanisms by which cells acquire resistance to prolong their survival rate in chemotherapy drug treatment failure patients are warranted. In this study, we found that the resistant cells acquired increased migratory and invasive capabilities, and this transformation was correlated with epithelial-mesenchymal transition (EMT) and Notch pathway deregulation in the resistant cells...
July 25, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28753202/targeting-the-cxcr4-cxcl12-axis-in-treating-epithelial-ovarian-cancer
#17
T L Mao, K F Fan, C L Liu
Ovarian carcinoma is the most crucial and difficult target for available therapeutic treatments among gynecological malignancies, and great efforts are required to find an effective solution. Molecular studies showed that the chemokine stromal cell-derived factor (SDF)-1 (also known as CXCL12) and its receptor, CXCR4, are key determinants of tumor initiation, progression, and metastasis in ovarian carcinomas. Hence, it is generally believed that blocking the CXCR4/CXCL12 pathway could serve as a potential therapy for patients with ovarian cancer...
July 28, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28723652/a-patient-derived-orthotopic-xenograft-pdox-mouse-model-of-a-cisplatinum-resistant-osteosarcoma-lung-metastasis-that-was-sensitive-to-temozolomide-and-trabectedin-implications-for-precision-oncology
#18
Kentaro Igarashi, Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Yong Zhang, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jane Yanagawa, Tara A Russell, Arun S Singh, Hiroyuki Tsuchiya, Irmina Elliott, Fritz C Eilber, Robert M Hoffman
In the present study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to cisplatinum (CDDP) on a patient-derived orthotopic xenogrraft (PDOX) of a lung-metastasis from an osteosarcoma of a patient who failed CDDP therapy. Osteosarcoma resected from the patient was implanted orthotopically in the distal femur of mice to establish PDOX models which were randomized into the following groups when tumor volume reached approximately 100 mm3: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28716897/mcpip1-downregulation-in-clear-cell-renal-cell-carcinoma-promotes-vascularization-and-metastatic-progression
#19
Paulina Marona, Judyta Górka, Zofia Mazurek, Waclaw Wilk, Janusz Rys, Marcin Majka, Jolanta Jura, Katarzyna Miekus
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28708595/angptl4-promotes-the-progression-of-cutaneous-melanoma-to-brain-metastasis
#20
Sivan Izraely, Shlomit Ben-Menachem, Orit Sagi-Assif, Tsipi Meshel, Diego M Marzese, Shuichi Ohe, Inna Zubrilov, Metsada Pasmanik-Chor, Dave S B Hoon, Isaac P Witz
In an ongoing effort to identify molecular determinants regulating melanoma brain metastasis, we previously identified Angiopoietin-like 4 (ANGPTL4) as a component of the molecular signature of such metastases.The aim of this study was to determine the functional significance of ANGPTL4 in the shaping of melanoma malignancy phenotype, especially in the establishment of brain metastasis.We confirmed that ANGPTL4 expression is significantly higher in cells metastasizing to the brain than in cells from the cutaneous (local) tumor from the same melanoma in a nude mouse xenograft model, and also in paired clinical specimens of melanoma metastases than in primary melanomas from the same patients...
July 5, 2017: Oncotarget
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