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https://www.readbyqxmd.com/read/27913947/preclinical-evaluation-of-cathepsin-based-fluorescent-imaging-system-for-cytoreductive-surgery
#1
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
#2
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
#3
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...
November 22, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27874835/heterotypic-models-of-osteosarcoma-recapitulate-tumor-heterogeneity-and-biological-behavior
#4
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, as 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...
November 3, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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.
November 4, 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
#11
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, 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...
November 3, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27791181/targeted-molecular-genetic-imaging-and-ligand-directed-therapy-in-aggressive-variant-prostate-cancer
#12
Fortunato Ferrara, Daniela I Staquicini, Wouter H P Driessen, Sara D'Angelo, Andrey S Dobroff, Marc Barry, Lesley C Lomo, Fernanda I Staquicini, Marina Cardó-Vila, Suren Soghomonyan, Mian M Alauddin, Leo G Flores, Marco A Arap, Richard C Lauer, Paul Mathew, Eleni Efstathiou, Ana M Aparicio, Patricia Troncoso, Nora M Navone, Christopher J Logothetis, Serena Marchiò, Juri G Gelovani, Richard L Sidman, Renata Pasqualini, Wadih Arap
Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients...
October 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27779717/mir-148a-inhibits-self-renewal-of-thyroid-cancer-stem-cells-via-repressing-ino80-expression
#13
Weizhong Sheng, Yusheng Chen, Yuda Gong, Tiangeng Dong, Bo Zhang, Weidong Gao
Anaplastic thyroid carcinoma (ATC) is aggressive and lethal with extrathyroidal invasion, distant metastasis, and resistance to conventional therapies. Cancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in ATC. MicroRNAs (miRNAs) have recently been found as an important class of cellular regulators of ATC carcinogenesis. Identification of CSC-related miRNAs and targets is therefore a priority for the development of new therapeutic paradigms. Patient-derived ATC cells were cultured in conditional media on poly-hema-treated dish...
October 25, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27768028/development-and-maintenance-of-a-preclinical-patient-derived-tumor-xenograft-model-for-the-investigation-of-novel-anti-cancer-therapies
#14
Stacey Bagby, Wells A Messersmith, Todd M Pitts, Anna Capasso, Marileila Varella-Garcia, Peter J Klauck, Jihye Kim, Aik-Choon Tan, S Gail Eckhardt, John J Tentler, John Arcaroli
Patient derived tumor xenograft (PDTX) models provide a necessary platform in facilitating anti-cancer drug development prior to human trials. Human tumor pieces are injected subcutaneously into athymic nude mice (immunocompromised, T cell deficient) to create a bank of tumors and subsequently are passaged into different generations of mice in order to maintain these tumors from patients. Importantly, cellular heterogeneity of the original tumor is closely emulated in this model, which provides a more clinically relevant model for evaluation of drug efficacy studies (single agent and combination), biomarker analysis, resistant pathways and cancer stem cell biology...
September 30, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27756881/targeting-the-cancer-associated-fibroblasts-as-a-treatment-in-triple-negative-breast-cancer
#15
Ken Takai, Annie Le, Valerie M Weaver, Zena Werb
Increased collagen expression in tumors is associated with increased risk of metastasis, and triple-negative breast cancer (TNBC) has the highest propensity to develop distant metastases when there is evidence of central fibrosis. Transforming growth factor-β (TGF-β) ligands regulated by cancer-associated fibroblasts (CAFs) promote accumulation of fibrosis and cancer progression. In the present study, we have evaluated TNBC tumors with enhanced collagen to determine whether we can reduce metastasis by targeting the CAFs with Pirfenidone (PFD), an anti-fibrotic agent as well as a TGF-β antagonist...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27752996/pi3k-and-mapk-pathways-mediate-the-bdnf-trkb-increased-metastasis-in-neuroblastoma
#16
Zhongyan Hua, Xiao Gu, Yudi Dong, Fei Tan, Zhihui Liu, Carol J Thiele, Zhijie Li
Brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB have been reported to be associated with poor prognosis in neuroblastoma (NB) patients. Our previous studies indicated that BDNF activation of TrkB induces chemo-resistance through activation of phosphoinositide-3-kinase (PI3K)/Akt pathway. In this study, we investigated the role of BDNF/TrkB on metastasis in NB. A tetracycline-regulated TrkB-expressing NB cell line (TB3) was used. Scratch wound healing assay, Boyden chamber migration, and invasion assays were performed to study the migration and invasion of TB3 cells...
October 17, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27735939/natural-product-pectolinarigenin-inhibits-osteosarcoma-growth-and-metastasis-via-shp-1-mediated-stat3-signaling-inhibition
#17
Tao Zhang, Suoyuan Li, Jingjie Li, Fei Yin, Yingqi Hua, Zhouying Wang, Binhui Lin, Hongsheng Wang, Dongqing Zou, Zifei Zhou, Jing Xu, Chengqing Yi, Zhengdong Cai
Signal transducer and activator of transcription 3 (STAT3) has important roles in cancer aggressiveness and has been confirmed as an attractive target for cancer therapy. In this study, we used a dual-luciferase assay to identify that pectolinarigenin inhibited STAT3 activity. Further studies showed pectolinarigenin inhibited constitutive and interleukin-6-induced STAT3 signaling, diminished the accumulation of STAT3 in the nucleus and blocked STAT3 DNA-binding activity in osteosarcoma cells. Mechanism investigations indicated that pectolinarigenin disturbed the STAT3/DNA methyltransferase 1/HDAC1 histone deacetylase 1 complex formation in the promoter region of SHP-1, which reversely mediates STAT3 signaling, leading to the upregulation of SHP-1 expression in osteosarcoma...
October 13, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27718126/suppression-of-cd26-inhibits-growth-and-metastasis-of-pancreatic-cancer
#18
Chunxiang Ye, Xiuyun Tian, Guanjun Yue, Liang Yan, Xiaoya Guan, Shan Wang, Chunyi Hao
CD26/DPPIV is a glycosylated transmembrane type II protein and has a multitude of biological functions, while its impact on the malignant phenotypes of cancer cells has not been fully understood. This study aimed to investigate the effect of CD26 on growth and metastasis of pancreatic cancer cells in vitro and in vivo. We found in this study that CD26 expression was higher in cell lines that derived from the metastatic sites than those from the primary tumor sites. In specimens of pancreatic cancer patients, CD26 expression was higher in cancerous tissues than in paired normal tissues...
October 7, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27715452/cabozantinib-inhibits-tumor-growth-and-metastasis-of-a-patient-derived-xenograft-model-of-papillary-renal-cell-carcinoma-with-met-mutation
#19
Hongjuan Zhao, Rosalie Nolley, Andy M W Chan, Erinn B Rankin, Donna M Peehl
MET plays an important role in the development and progression of papillary renal cell carcinoma (pRCC). Evaluation of efficacy of MET inhibitors against pRCC has been hampered by limited preclinical models depicting MET abnormalities. We established a new patient-derived xenograft (PDX) model of pRCC carrying an activating mutation of MET and tested the ability of cabozantinib, an inhibitor of receptor tyrosine kinases including MET, to inhibit tumor growth and metastasis. Precision-cut, thin tissue slices from a pRCC specimen obtained by nephrectomy were implanted under the renal capsule of RAG2(-/-)γC(-/-) mice to establish first generation TSG-RCC-030...
August 11, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27680982/patient-derived-mammosphere-and-xenograft-tumour-initiation-correlates-with-progression-to-metastasis
#20
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
Breast cancer specific mortality results from tumour cell dissemination and metastatic colonisation. Identification of the cells and processes responsible for metastasis will enable better prevention and control of metastatic disease, thus reducing relapse and mortality. To better understand these processes, we prospectively collected 307 patient-derived breast cancer samples (n = 195 early breast cancers (EBC) and n = 112 metastatic samples (MBC)). We assessed colony-forming activity in vitro by growing isolated cells in both primary (formation) and secondary (self-renewal) mammosphere culture, and tumour initiating activity in vivo through subcutaneous transplantation of fragments or cells into mice...
September 28, 2016: Journal of Mammary Gland Biology and Neoplasia
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