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https://www.readbyqxmd.com/read/29141225/a-comprehensive-patient-derived-xenograft-collection-representing-the-heterogeneity-of-melanoma
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/29100268/angptl4-promotes-the-progression-of-cutaneous-melanoma-to-brain-metastasis
#5
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...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29094026/establishing-a-colorectal-cancer-liver-metastasis-patient-derived-tumor-xenograft-model-for-the-evaluation-of-personalized-chemotherapy
#6
Joohee Jung, Jisup Kim, Hyun Kyung Lim, Kyoung Mee Kim, Yun Sun Lee, Joon Seong Park, Dong Sup Yoon
Purpose: In order to suggest optimal anticancer drugs for patient-tailored chemotherapy, we developed a colorectal cancer (CRC)-liver metastasis patient-derived tumor xenograft (PDTX) model. Methods: Tissue obtained from a patient with CRC-liver metastasis (F0) was transplanted in a nonobese female mouse with diabetic/severe combined immune deficiency (F1) and the tumor tissue was retransplanted into nude mice (F2). When tumor volumes reached ~500 mm(3), the F2 mice were randomly divided into 4 groups (n = 4/group) of doxorubicin, cisplatin, docetaxel, and nontreated control groups...
October 2017: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/29050333/characterization-of-cadd522-a-small-molecule-that-inhibits-runx2-dna-binding-and-exhibits-antitumor-activity
#7
Myoung Sook Kim, Ramkishore Gernapudi, Eun Yong Choi, Rena G Lapidus, Antonino Passaniti
The RUNX2 transcription factor promotes breast cancer growth and metastasis through interactions with a variety of cofactors that activate or repress target genes. Using a direct drug discovery approach we identified CADD522 as a small molecule that inhibits the DNA binding of the runt box domain protein, RUNX2. The current study defines the effect of CADD522 on breast cancer growth and metastasis, and addresses the mechanisms by which it exerts its anti-tumor activity. CADD522 treatment resulted in significant growth inhibition, clonogenic survival, tumorsphere formation, and invasion of breast cancer cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046702/in-vivo-validation-of-metastasis-regulating-microrna-766-in-human-triple-negative-breast-cancer-cells
#8
Keunhee Oh, Dong-Sup Lee
Breast cancer is the second most common cancer and the most frequent cancer in women worldwide. Recent improvements in early detection and effective adjuvant chemotherapies have improved the survival of breast cancer patients. Even with initial disease remission, one-third of all breast cancer patients will relapse with distant metastasis. Breast cancer metastasis is largely an incurable disease and the main cause of death among breast cancer patients. Cancer metastasis is comprised of complex processes that are usually not controllable by intervention of a single molecular target...
September 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28993429/tgf-%C3%AE-1-secreted-by-tregs-in-lymph-nodes-promotes-breast-cancer-malignancy-via-up-regulation-of-il-17rb
#9
Shih-Chia Huang, Pei-Chi Wei, Wendy W Hwang-Verslues, Wen-Hung Kuo, Yung-Ming Jeng, Chun-Mei Hu, Jin-Yuh Shew, Chiun-Sheng Huang, King-Jen Chang, Eva Y-Hp Lee, Wen-Hwa Lee
Lymph node (LN) metastasis is commonly associated with systemic distant organ metastasis in human breast cancer and is an important prognostic predictor for survival of breast cancer patients. However, whether tumor-draining LNs (TDLNs) play a significant role in modulating the malignancy of cancer cells for distant metastasis remains controversial. Using a syngeneic mouse mammary tumor model, we found that breast tumor cells derived from TDLN have higher malignancy and removal of TDLNs significantly reduced distant metastasis...
October 9, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28981962/the-bmp-antagonist-noggin-is-produced-by-osteoblasts-in-response-to-the-presence-of-prostate-cancer-cells
#10
Huda F AlShaibi, Farid Ahmed, Clive Buckle, Ann Cm Fowles, Jalaluddin Awlia, Marco G Cecchini, Colby L Eaton
BACKGROUND: Bone metastasis is a key event responsible for morbidity in prostate cancer patients. Interactions between prostate cancer cells and the bone microenvironment facilitate survival of tumour cells and alter bone turnover, a process that is thought to enhance the growth of metastases in this site. This study aimed to test the hypothesis that the presence of tumours cells increases TGFβ signaling in bone and that this regulates the proliferation and differentiation of osteoblastic lineage cells in metastatic sites...
October 5, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28977930/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
#11
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 mm(3): G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966935/brain-derived-neutrophic-factor-bdnf-coordinates-lympho-vascular-metastasis-through-a-fibroblast-governed-paracrine-axis-in-the-tumor-microenvironment
#12
Tilahun Jiffar, Turker Yilmaz, Junegoo Lee, Yair Miller, Lei Feng, Adel El-Naggar, Michael E Kupferman
It has long been known that the tumor microenvironment contributes to the proliferation and survival of neoplasms through the constant interaction with the stromal and immune compartments. In this investigation, we explored the role of cancer-associated fibroblasts (CAFs) in the regulation of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) though a complex intercellular BDNF-TrkB signaling system. Our studies show that conditioned media derived from patient-derived CAFs promoted HNSCC cell proliferation, in vitro cell migration, cell invasion and chemotherapy resistance, compared to normal fibroblasts...
2017: Cancer Cell & Microenvironment
https://www.readbyqxmd.com/read/28961841/dual-met-and-erbb-inhibition-overcomes-intratumor-plasticity-in-osimertinib-resistant-advanced-non-small-cell-lung-cancer-nsclc
#13
A Martinez-Marti, E Felip, J Matito, E Mereu, A Navarro, S Cedrés, N Pardo, A Martinez de Castro, J Remon, J M Miquel, A Guillaumet-Adkins, E Nadal, G Rodriguez-Esteban, O Arqués, R Fasani, P Nuciforo, H Heyn, A Villanueva, H G Palmer, A Vivancos
Background: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib are the last line of targeted treatment of metastatic non-small-cell lung cancer (NSCLC) EGFR-mutant harboring T790M. Different mechanisms of acquired resistance to third-generation EGFR-TKIs have been proposed. It is therefore crucial to identify new and effective strategies to overcome successive acquired mechanisms of resistance. Methods: For Amplicon-seq analysis, samples from the index patient (primary and metastasis lesions at different timepoints) as well as the patient-derived orthotopic xenograft tumors corresponding to the different treatment arms were used...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28930697/overexpression-of-muc1-and-genomic-alterations-in-its-network-associate-with-prostate-cancer-progression
#14
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...
November 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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