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Your search keyword '"Clarke, Cassie J."' showing total 3 results
Start Over Author "Clarke, Cassie J." Topic cancer research
3 results on '"Clarke, Cassie J."'

1. Preclinical approaches in chronic myeloid leukemia: from cells to systems

Author

Clarke, Cassie J. and Holyoake, Tessa L.

Subjects
Cancer Research, Cell Transplantation, Drug Evaluation, Preclinical, Cell Biology, Hematology, Review, In Vitro Techniques, Xenograft Model Antitumor Assays, Animals, Genetically Modified, Disease Models, Animal, Transduction, Genetic, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Genetics, Tumor Cells, Cultured, Animals, Humans, Transgenes, Molecular Biology, Cell Line, Transformed
Abstract

Advances in the design of targeted therapies for the treatment of chronic myeloid leukemia (CML) have transformed the prognosis for patients diagnosed with this disease. However, leukemic stem cell persistence, drug intolerance, drug resistance, and advanced-phase disease represent unmet clinical needs demanding the attention of CML investigators worldwide. The availability of appropriate preclinical models is essential to efficiently translate findings from the bench to the clinic. Here we review the current approaches taken to preclinical work in the CML field, including examples of commonly used in vivo models and recent successes from systems biology-based methodologies., Highlights • CML is a hematopoietic stem cell disorder caused by a chromosomal translocation. • TKIs have transformed CML treatment but do not eradicate LSC which maintain disease. • The current preclinical approaches applied in CML research are reviewed. • Successfully combining approaches to deliver preclinical packages is discussed.

Published
2017

2. Correction: CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy

Author

Kinstrie, Ross, Horne, Gillian A., Morrison, Heather, Irvine, David, Munje, Chinmay, Castañeda, Eduardo Gómez, Moka, Hothri A., Dunn, Karen, Cassels, Jennifer E., Parry, Narissa, Clarke, Cassie J., Scott, Mary T., Clark, Richard E., Holyoake, Tessa L., Wheadon, Helen, and Copland, Mhairi

Subjects
Cancer Research, Membrane Glycoproteins, Neoplasm, Residual, Cancer stem cells, Correction, Hematology, Receptors, Complement, Mice, Oncology, Drug Resistance, Neoplasm, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Biomarkers, Tumor, Neoplastic Stem Cells, Animals, Heterografts, Humans, Protein Kinase Inhibitors, Chronic myeloid leukaemia
Abstract

The introduction of BCR-ABL tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia (CML). A major clinical aim remains the identification and elimination of low-level disease persistence, termed "minimal residual disease". The phenomenon of disease persistence suggests that despite targeted therapeutic approaches, BCR-ABL-independent mechanisms exist which sustain the survival of leukemic stem cells (LSCs). Although other markers of a primitive CML LSC population have been identified in the preclinical setting, only CD26 appears to offer clinical utility. Here we demonstrate consistent and selective expression of CD93 on a lin

Published
2020

3. The Initiator Methionine tRNA Drives Secretion of Type II Collagen from Stromal Fibroblasts to Promote Tumor Growth and Angiogenesis.

Author

Clarke, Cassie J., Berg, Tracy J., Birch, Joanna, Ennis, Darren, Mitchell, Louise, Cloix, Catherine, Campbell, Andrew, Sumpton, David, Nixon, Colin, Campbell, Kirsteen, Bridgeman, Victoria L., Vermeulen, Peter B., Foo, Shane, Kostaras, Eleftherios, Jones, J. Louise, Haywood, Linda, Pulleine, Ellie, Yin, Huabing, Strathdee, Douglas, and Sansom, Owen

Subjects
*TRANSFER RNA, *METHIONINE, *CANCER research, *CANCER invasiveness, *ENDOTHELIAL cells
Abstract

Summary Expression of the initiator methionine tRNA (tRNA i Met ) is deregulated in cancer. Despite this fact, it is not currently known how tRNA i Met expression levels influence tumor progression. We have found that tRNA i Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNA i Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNA i Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNA i Met gene (2+tRNA i Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNA i Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNA i Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNA i Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNA i Met -overexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl-3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNA i Met -driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNA i Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNA i Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis. [ABSTRACT FROM AUTHOR]

Published
2016
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