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patient derived xenograft metastasis

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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
#1
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
#2
Paulina Marona, Judyta Górka, Zofia Mazurek, Waclaw Wilk, Janusz Rys, Marcin Majka, Jolanta Jura, Katarzyna Miekus
<p>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 IL-6, IL-1 and IL-12. 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
#3
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
https://www.readbyqxmd.com/read/28692661/the-extracellular-matrix-and-focal-adhesion-kinase-signaling-regulate-cancer-stem-cell-function-in-pancreatic-ductal-adenocarcinoma
#4
Asma Begum, Theodore Ewachiw, Clinton Jung, Ally Huang, K Jessica Norberg, Luigi Marchionni, Ross McMillan, Vesselin Penchev, N V Rajeshkumar, Anirban Maitra, Laura Wood, Chenguang Wang, Christopher Wolfgang, Ana DeJesus-Acosta, Daniel Laheru, Irina M Shapiro, Mahesh Padval, Jonathan A Pachter, David T Weaver, Zeshaan A Rasheed, William Matsui
Cancer stem cells (CSCs) play an important role in the clonogenic growth and metastasis of pancreatic ductal adenocarcinoma (PDAC). A hallmark of PDAC is the desmoplastic reaction, but the impact of the tumor microenvironment (TME) on CSCs is unknown. In order to better understand the mechanisms, we examined the impact of extracellular matrix (ECM) proteins on PDAC CSCs. We quantified the effect of ECM proteins, β1-integrin, and focal adhesion kinase (FAK) on clonogenic PDAC growth and migration in vitro and tumor initiation, growth, and metastasis in vivo in nude mice using shRNA and overexpression constructs as well as small molecule FAK inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28679654/neoadjuvant-chemotherapy-induces-breast-cancer-metastasis-through-a-tmem-mediated-mechanism
#5
George S Karagiannis, Jessica M Pastoriza, Yarong Wang, Allison S Harney, David Entenberg, Jeanine Pignatelli, Ved P Sharma, Emily A Xue, Esther Cheng, Timothy M D'Alfonso, Joan G Jones, Jesus Anampa, Thomas E Rohan, Joseph A Sparano, John S Condeelis, Maja H Oktay
Breast cancer cells disseminate through TIE2/MENA(Calc)/MENA(INV)-dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we show that chemotherapy increases the density and activity of TMEM sites and Mena expression and promotes distant metastasis. Moreover, in the residual breast cancers of patients treated with neoadjuvant paclitaxel after doxorubicin plus cyclophosphamide, TMEM score and its mechanistically connected MENA(INV) isoform expression pattern were both increased, suggesting that chemotherapy, despite decreasing tumor size, increases the risk of metastatic dissemination...
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28668848/a-novel-small-molecule-wnt-inhibitor-ic-2-has-the-potential-to-suppress-liver-cancer-stem-cells
#6
Kenzo Seto, Tomohiko Sakabe, Noriko Itaba, Junya Azumi, Hiroyuki Oka, Minoru Morimoto, Yoshihisa Umekita, Goshi Shiota
BACKGROUND/AIM: The presence of cancer stem cells (CSCs) contributes to metastasis, recurrence, and resistance to chemo/radiotherapy in hepatocellular carcinoma (HCC). The WNT signaling pathway is reportedly linked to the maintenance of stemness of CSCs. In the present study, in order to eliminate liver CSCs and improve the prognosis of patients with HCC, we explored whether small-molecule compounds targeting WNT signaling pathway suppress liver CSCs. MATERIALS AND METHODS: The screening was performed using cell proliferation assay and reporter assay...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666098/anti-rhoj-antibody-functionalized-au-i-nanoparticles-as-ct-guided-tumor-vessel-targeting-radiosensitizers-in-patient-derived-tumor-xenograft-model
#7
Sen Liu, Hui Li, Luyao Xia, Peipei Xu, Yin Ding, Da Huo, Yong Hu
The clinical success of radiotherapy is greatly hampered due to its intolerable off-target cytotoxicity induced by the high dose of radiation. Meanwhile, low dose of irradiation greatly potentiates the intratumoral angiogenesis, which promotes the local relapse and metastasis of tumor. Therefore, it is essential to reduce the irradiation dosage while inhibiting the tumor angiogenesis during radiotherapy. In this work, tumor vessel specific ultrafine Au@I nanoparticles (AIRA NPs) are fabricated and used as targeted radiosensitizers...
June 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/28650393/orthotopic-patient-derived-pancreatic-cancer-xenografts-engraft-into-the-pancreatic-parenchyma-metastasize-and-induce-muscle-wasting-to-recapitulate-the-human-disease
#8
Kristina L Go, Daniel Delitto, Sarah M Judge, Michael H Gerber, Thomas J George, Kevin E Behrns, Steven J Hughes, Andrew R Judge, Jose G Trevino
OBJECTIVE: Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer (PC). In an effort to develop more reliable preclinical models, we have recently established a subcutaneous patient-derived xenograft (PDX) model. However, critical aspects of PC responsible for its highly lethal nature, such as the development of distant metastasis and cancer cachexia, remain underrepresented in the flank PDX model...
June 22, 2017: Pancreas
https://www.readbyqxmd.com/read/28645290/establishment-of-an-orthotopic-patient-derived-xenograft-mouse-model-using-uveal-melanoma-hepatic-metastasis
#9
Ken Kageyama, Masahiro Ohara, Kengo Saito, Shinji Ozaki, Mizue Terai, Michael J Mastrangelo, Paolo Fortina, Andrew E Aplin, Takami Sato
BACKGROUND: Metastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment...
June 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28625518/histone-chaperone-asf1a-predicts-poor-outcomes-for-patients-with-gastrointestinal-cancer-and-drives-cancer-progression-by-stimulating-transcription-of-%C3%AE-catenin-target-genes
#10
Xiuming Liang, Xiaotian Yuan, Jingya Yu, Yujiao Wu, Kailin Li, Chao Sun, Shuyan Li, Li Shen, Feng Kong, Jihui Jia, Magnus Björkholm, Dawei Xu
Epigenetic mechanisms play a key role in gastrointestinal cancer (GIC) development and progression, and most studies have been focused on aberrant DNA methylation and histone modifying enzymes. However, the histone H3-H4 chaperone ASF1A is an important factor regulating chromatin assembling and gene transcription, while it is currently unclear whether ASF1A is involved in cancer pathogenesis. The present study is thus designed to address this issue. Here we showed that ASF1A expression was widespread in GIC-derived cell lines and up-regulated in primary GIC...
July 2017: EBioMedicine
https://www.readbyqxmd.com/read/28624783/malignant-pericytes-expressing-gt198-give-rise-to-tumor-cells-through-angiogenesis
#11
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...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609371/orthotopic-patient-derived-pancreatic-cancer-xenografts-engraft-into-the-pancreatic-parenchyma-metastasize-and-induce-muscle-wasting-to-recapitulate-the-human-disease
#12
Kristina L Go, Daniel Delitto, Sarah M Judge, Michael H Gerber, Thomas J George, Kevin E Behrns, Steven J Hughes, Andrew R Judge, Jose G Trevino
OBJECTIVE: Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer (PC). In an effort to develop more reliable preclinical models, we have recently established a subcutaneous patient-derived xenograft (PDX) model. However, critical aspects of PC responsible for its highly lethal nature, such as the development of distant metastasis and cancer cachexia, remain underrepresented in the flank PDX model...
July 2017: Pancreas
https://www.readbyqxmd.com/read/28588211/transcription-factor-networks-derived-from-breast-cancer-stem-cells-control-the-immune-response-in-the-basal-subtype
#13
W A da Silveira, P V B Palma, R D Sicchieri, R A R Villacis, L R M Mandarano, T M G Oliveira, H M R Antonio, J M Andrade, V F Muglia, S R Rogatto, C Theillet, S du Manoir, D G Tiezzi
Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586644/endothelial-to-osteoblast-conversion-generates-osteoblastic-metastasis-of-prostate-cancer
#14
Song-Chang Lin, Yu-Chen Lee, Guoyu Yu, Chien-Jui Cheng, Xin Zhou, Khoi Chu, Monzur Murshed, Nhat-Tu Le, Laura Baseler, Jun-Ichi Abe, Keigi Fujiwara, Benoit deCrombrugghe, Christopher J Logothetis, Gary E Gallick, Li-Yuan Yu-Lee, Sankar N Maity, Sue-Hwa Lin
Prostate cancer (PCa) bone metastasis is frequently associated with bone-forming lesions, but the source of the osteoblastic lesions remains unclear. We show that the tumor-induced bone derives partly from tumor-associated endothelial cells that have undergone endothelial-to-osteoblast (EC-to-OSB) conversion. The tumor-associated osteoblasts in PCa bone metastasis specimens and patient-derived xenografts (PDXs) were found to co-express endothelial marker Tie-2. BMP4, identified in PDX-conditioned medium, promoted EC-to-OSB conversion of 2H11 endothelial cells...
June 5, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28581516/pancreatic-cancer-heterogeneity-and-response-to-mek-inhibition
#15
K Pedersen, F Bilal, C Bernadó Morales, M T Salcedo, T Macarulla, D Massó-Vallés, V Mohan, A Vivancos, M-J Carreras, X Serres, M Abu-Suboh, J Balsells, E Allende, I Sagi, L Soucek, J Tabernero, J Arribas
Our increasing knowledge of the mechanisms behind the progression of pancreatic cancer (PC) has not yet translated into effective treatments. Many promising drugs have failed in the clinic, highlighting the need for better preclinical models to assess drug efficacy and characterize mechanisms of resistance. Using different experimental models, including patient-derived xenografts (PDXs), we gauged the efficacy of therapies aimed at two hallmark lesions of PCs: activation of signaling pathways by oncogenic KRAS and inactivation of tumor-suppressor genes...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28522590/notch-inhibitor-pf-03084014-inhibits-hepatocellular-carcinoma-growth-and-metastasis-via-suppression-of-cancer-stemness-due-to-reduced-activation-of-notch1-stat3
#16
Chuan Xing Wu, Aimin Xu, Cathy C Zhang, Peter Olson, Lin Chen, Terence K Lee, Tan To Cheung, Chung Mau Lo, Xiao Qi Wang
Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma (HCC), indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in HCC. HCC spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28499452/current-status-and-perspectives-of-patient-derived-xenograft-models-in-cancer-research
#17
REVIEW
Yunxin Lai, Xinru Wei, Shouheng Lin, Le Qin, Lin Cheng, Peng Li
Cancers remain a major public health problem worldwide, which still require profound research in both the basic and preclinical fields. Patient-derived xenograft (PDX) models are created when cancerous cells or tissues from patients' primary tumors are implanted into immunodeficient mice to simulate human tumor biology in vivo, which have been extensively used in cancer research. The routes of implantation appeared to affect the outcome of PDX research, and there has been increasing applications of patient-derived orthotopic xenograft (PDOX) models...
May 12, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28494180/intra-arterial-administration-of-tumor-targeting-salmonella-typhimurium-a1-r-regresses-a-cisplatin-resistant-relapsed-osteosarcoma-in-a-patient-derived-orthotopic-xenograft-pdox-mouse-model
#18
Kentaro Igarashi, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jane Yanagawa, Tara A Russell, Arun S Singh, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Previously, a patient-derived orthotopic xenograft (PDOX) model was established with a lung metastasis from an osteosarcoma patient which developed after adjuvant cisplatinum (CDDP) treatment. In this model, we previously demonstrated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared with CDDP. In the present report, osteosarcoma tissue was implanted orthotopically in the distal femur of mice which were randomized into the following groups when tumor volume reached approximately 100 mm(3); On day 14 after initiation of treatment, all but CDDP significantly inhibited tumor volume growth compared with untreated controls...
June 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28472820/clinical-value-of-r-spondins-in-triple-negative-and-metaplastic-breast-cancers
#19
F Coussy, F Lallemand, S Vacher, A Schnitzler, W Chemlali, M Caly, A Nicolas, S Richon, D Meseure, R El Botty, L De-Plater, L Fuhrmann, T Dubois, S Roman-Roman, V Dangles-Marie, E Marangoni, I Bièche
BACKGROUND: RSPO ligands, activators of the Wnt/β-catenin pathway, are overexpressed in different cancers. The objective of this study was to investigate the role of RSPOs in breast cancer (BC). METHODS: Expression of RSPO and markers of various cancer pathways were measured in breast tumours and cell lines by qRT-PCR. The effect of RSPO on the Wnt/β-catenin pathway activity was determined by luciferase assay, western blotting, and qRT-PCR. The effect of RSPO2 inhibition on proliferation was determined by using RSPO2 siRNAs...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28467965/intratumoral-acidosis-fosters-cancer-induced-bone-pain-through-the-activation-of-the-mesenchymal-tumor-associated-stroma-in-bone-metastasis-from-breast-carcinoma
#20
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)...
April 13, 2017: Oncotarget
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