Research Topics
| A F ChambersSummaryAffiliation: London Regional Cancer Centre Country: Canada Publications
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Detail Information
Publications
The metastatic process: basic research and clinical implicationsA F Chambers
London Regional Cancer Centre, and Department of Oncology, University of Western Ontario, London, Canada
Oncol Res 11:161-8. 1999....
Molecular biology of breast cancer metastasis. Clinical implications of experimental studies on metastatic inefficiencyA F Chambers
London Regional Cancer Centre, London, Ontario, Canada
Breast Cancer Res 2:400-7. 2000..This understanding will be of use in guiding clinical studies to assess the significance of isolated tumour cells and micrometastases in cancer patients...
Dissemination and growth of cancer cells in metastatic sitesAnn F Chambers
London Regional Cancer Centre, London, Ontario N6A 4L6, Canada
Nat Rev Cancer 2:563-72. 2002..Inhibition of the growth of metastases in secondary sites offers a promising approach for cancer therapy...
Clinical targets for anti-metastasis therapyA F Chambers
Department of Oncology, University of Western Ontario, Canada
Adv Cancer Res 79:91-121. 2000..A variety of therapeutic approaches to target this phase are under active development, including inhibition of angiogenesis or signal transduction pathways needed to support the growth of metastatic cells...
Preclinical assessment of anti-cancer therapeutic strategies using in vivo videomicroscopyA F Chambers
Department of Oncology, University of Western Ontario, London, Canada
Cancer Metastasis Rev 17:263-9. 1998....
Osteopontin(OPN)-induced increase in human mammary epithelial cell invasiveness is urokinase (uPA)-dependentA B Tuck
Department of Pathology, University of Western Ontario, London, Canada
Breast Cancer Res Treat 70:197-204. 2001..These data thus provide direct evidence that OPN-induced invasion and migration of these cells requires uPA...
Osteopontin-induced, integrin-dependent migration of human mammary epithelial cells involves activation of the hepatocyte growth factor receptor (Met)A B Tuck
Department of Pathology, University of Western Ontario, London, Canada
J Cell Biochem 78:465-75. 2000..OPN-induced cell migration is thus mediated by different cell surface integrins in MEC lines representing different stages of progression, and involves activation of the HGF receptor, Met...
Tumour metastasis to the liver, and the roles of proteinases and adhesion molecules: new concepts from in vivo videomicroscopyA C Groom
Department of Medical Biophysics, University of Western Ontario, London
Can J Gastroenterol 13:733-43. 1999..Key targets against which future therapeutic strategies should be directed include the initiation and maintenance of growth of micrometastases, and the activation of dormant solitary cells...
Comparative analysis of two alternative first exons reported for the mouse osteopontin geneE I Behrend
London Regional Cancer Centre, Ontario, Canada
J Biol Chem 268:11172-5. 1993..is present in murine genomic DNA but is not found in cytoplasmic message. Our results also show that OPN RNA molecules from mouse fibroblasts and macrophages do not differ significantly in the regions tested...
Identification of a serum-inducible messenger RNA (5B10) as the mouse homologue of calcyclin: tissue distribution and expression in metastatic, ras-transformed NIH 3T3 cellsX J Guo
Cancer Research Laboratory, University of Western Ontario, London, Canada
Cell Growth Differ 1:333-8. 1990..In addition, high 5B10 mRNA levels were associated with metastatic ability in a series of ras-transformed cells, in proportion to levels of ras p21 expressed by the cells, implicating 5B10 even more deeply in carcinogenesis...
The functional and clinical roles of osteopontin in cancer and metastasisK A Furger
London Regional Cancer Centre, Ontario, Canada
Curr Mol Med 1:621-32. 2001..We also will discuss recent clinical evidence that suggests that OPN is not only associated with several tumor types, but that levels of OPN in cancer patients' blood or tumors may provide prognostic information...
Solitary cancer cells as a possible source of tumour dormancy?G N Naumov
Medical Biophysics Department, University of Western Ontario, London, Ontario, Canada N6A 5C1
Semin Cancer Biol 11:271-6. 2001..Here we review these in vivo techniques and findings. We also discuss the potential clinical implications if dormant solitary cells exist in appreciable numbers in cancer patients...
Critical steps in hematogenous metastasis: an overviewA F Chambers
London Regional Cancer Centre, London, Ontario, Canada
Surg Oncol Clin N Am 10:243-55, vii. 2001....
Site-directed mutagenesis of the arginine-glycine-aspartic acid sequence in osteopontin destroys cell adhesion and migration functionsJ W Xuan
London Regional Cancer Centre, Ontario, Canada
J Cell Biochem 57:680-90. 1995..Together these results suggest that the conserved RGD sequence in OPN is required for the majority of the protein's cell attachment and migration-stimulating functions...
A human promyelocyte mRNA transiently induced by TPA is homologous to yeast IPP isomeraseJ W Xuan
Cancer Research Laboratory, University of Western Ontario, London, Canada
Genomics 20:129-31. 1994..Sequence analysis revealed that this cDNA was likely a human homolog of yeast isopentenyl diphosphate:dimethylallyl diphosphate isomerase, an enzyme important for isoprenoid synthesis and the prenylation of proteins such as ras p21...
The role of osteopontin in breast cancer: clinical and experimental studiesA B Tuck
Department of Oncology, University of Western Ontario, London, Canada
J Mammary Gland Biol Neoplasia 6:419-29. 2001..g. uPA). We also summarize clinical studies that show that OPN levels in tumors and blood are elevated in women with metastatic breast cancer and may offer promise as prognostic markers in breast cancer...
Osteopontin expression in a group of lymph node negative breast cancer patientsA B Tuck
London Regional Cancer Centre, London Health Sciences Centre, Department of Pathology, University of Western Ontario, Canada
Int J Cancer 79:502-8. 1998..The results of this pilot study thus suggest that the ability of breast cancer cells to either synthesize OPN or to bind and sequester OPN from the microenvironment may be associated with tumor aggressiveness and poor prognosis...
Changing views of the role of matrix metalloproteinases in metastasisA F Chambers
Department of Oncology, University of Western Ontario, and London Regional Cancer Centre, Canada
J Natl Cancer Inst 89:1260-70. 1997..Further clarification of the mechanisms by which MMPs regulate growth of primary and metastatic tumors will be important in the development of novel therapeutic strategies against metastases...
Alternative splicing of PSP94 (prostatic secretory protein of 94 amino acids) mRNA in prostate tissueJ W Xuan
Department of Surgery, University of Western Ontario, London, Canada
Oncogene 11:1041-7. 1995..Our results suggest the possible existence of a novel PSP protein that originates from alternative splicing of PSP94 mRNA in urogenital tissues...
Volume measurement variability in three-dimensional high-frequency ultrasound images of murine liver metastasesL A Wirtzfeld
Biomedical Engineering Graduate Program, University of Western Ontario, London, Ontario, N6A 5B9, Canada
Phys Med Biol 51:2367-81. 2006..These results enable design of more efficient imaging studies by using the measured variability to estimate the time required to observe a significant change in tumour volume...
Osteopontin expression in salivary gland tumoursM R Darling
Department of Pathology, University of Western Ontario, 1151 Richmond Street, Room 4015 DSB, London, Ontario, Canada N6A 5C1
Oral Oncol 42:363-9. 2006..The results of this study indicate that OPN expression is present in normal salivary gland tissue, and is increased in certain salivary gland tumours, but further investigation is necessary to clarify its role...
Therapeutic targets for antimetastatic therapyBenjamin D Hedley
Department of Medical Biophysics, University of Western Ontario, London Regional Cancer Program, London Health Sciences Centre, Ontario, N6A 4L6, Canada
Expert Opin Ther Targets 8:527-36. 2004..This review discusses potential biological targets, as defined by the steps in the metastatic process, for antimetastatic therapies and provides examples of clinical strategies for preventing or treating successful metastasis...
Dormancy of solitary metastatic cellsJason L Townson
Department of Medical Biophysics, University of Western Ontario and the London Regional Cancer Program, London, Ontario, Canada
Cell Cycle 5:1744-50. 2006....
New clinical and experimental approaches for studying tumor dormancy: does tumor dormancy offer a therapeutic target?Paul Goss
Massachusetts General Hospital Cancer Center, and Department of Medicine, Harvard Medical School, Boston, MA, USA
APMIS 116:552-68. 2008..A better understanding of mechanisms responsible for tumor dormancy and recurrence will be important for improving care of patients at risk for late-developing metastases...
In vivo videomicroscopy reveals differential effects of the vascular-targeting agent ZD6126 and the anti-angiogenic agent ZD6474 on vascular function in a liver metastasis modelHemanth J Varghese
Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada
Angiogenesis 7:157-64. 2004..Understanding differences in the modes of action of VTAs and anti-angiogenic agents will be important in optimizing their clinical application and in developing appropriate combination strategies...
Breast cancer metastasis progression as revealed by intravital videomicroscopyIan C MacDonald
Department of Medical Biophysics, University of Western Ontario, 1151 Richmond Street, London, ON, N6A 5C1, Canada
Expert Rev Anticancer Ther 6:1271-9. 2006....
Osteopontin knockdown suppresses tumorigenicity of human metastatic breast carcinoma, MDA-MB-435Lalita A Shevde
University of South Alabama Mitchell Cancer Institute, Mobile, AL 36688 0002, USA
Clin Exp Metastasis 23:123-33. 2006..Thus, in addition to the widely reported roles of OPN in late stages of tumor progression, these results provide functional evidence that OPN contributes to breast tumor growth as well...
Osteopontin induction of hyaluronan synthase 2 expression promotes breast cancer malignancyAmy C Cook
Department of Pathology, University of Western Ontario, London, Ontario N6A 5C1, Canada
J Biol Chem 281:24381-9. 2006....
Tumor dormancy and the role of metastasis suppressor genes in regulating ectopic growthBenjamin D Hedley
University of Western Ontario, Schulich School of Medicine and Dentistry, London Regional Cancer Program, Department of Oncology, London, Ontario, Canada
Future Oncol 2:627-41. 2006....
In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brainChris Heyn
Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada
Magn Reson Med 56:1001-10. 2006....
In vivo inhibition of growth of human tumor lines by flavonoid fractions from cranberry extractPeter J Ferguson
London Regional Cancer Program, Health Sciences Centre, 790 Commissioners Road East, London, Ontario, Canada
Nutr Cancer 56:86-94. 2006..05) and also induce cell death within 24 to 48 h of exposure (P < 0.05). These results indicate the presence of a potential anticancer constituent in the flavonoid-containing fractions from cranberry extracts...
Distinct karyotypes in three breast cancer cell lines --21PTCi, 21NTCi, and 21MT-1 --derived from the same patient and representing different stages of tumor progressionJie Xu
Cytogenetics Laboratory, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada
Cancer Genet Cytogenet 186:33-40. 2008..These three cell lines, with their different karyotypes and biologic characteristics, provide a vital tool for further study of the genetic and epigenetic events involved in transitions between premalignant and malignant phenotypes...
Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeletonDalit Barkan
Laboratory of Cell Biology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Cancer Res 68:6241-50. 2008..Targeting this process may provide therapeutic strategies for inhibition of the dormant-to-proliferative metastatic switch...
Downregulation of osteopontin contributes to metastasis suppression by breast cancer metastasis suppressor 1Benjamin D Hedley
London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
Int J Cancer 123:526-34. 2008..These studies clarify one mechanism by which BRMS1 can suppress metastasis...
Experimental metastasis assays in the chick embryoSylvia M Wilson
London Regional Cancer Centre, London, Ontario, Canada
Curr Protoc Cell Biol . 2004..These assays provide a cost-effective, readily accessible, and rapid approach for studying the process of cancer metastasis...
Brain metastases of breast cancerDiane Palmieri
Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
Breast Dis 26:139-47. 2006..New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells...
Tumor dormancy and cancer stem cells: implications for the biology and treatment of breast cancer metastasisAlison L Allan
London Regional Cancer Program, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
Breast Dis 26:87-98. 2006....
The biology of metastasis to a sanctuary siteDiane Palmieri
Women s Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
Clin Cancer Res 13:1656-62. 2007..Specific, new approaches to combat brain metastatic disease are needed...
Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-kappaB activationRajeev S Samant
Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA
Mol Cancer 6:6. 2007..BRMS1 is a member of mSin3-HDAC transcription co-repressor complex and has been shown to suppress the metastasis of breast cancer and melanoma cells in animal models. Hence we hypothesized that BRMS1 regulates OPN expression...
Molecular mechanisms of metastasisDave S B Hoon
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA 90404, USA
Cancer Metastasis Rev 25:203-20. 2006..The hope is that further unraveling of the direct and indirect molecular events of lymphatic metastasis will lead to new approaches in developing effective therapeutics...
Enhanced cell surface CD44 variant (v6, v9) expression by osteopontin in breast cancer epithelial cells facilitates tumor cell migration: novel post-transcriptional, post-translational regulationSubarna A Khan
Department of Cell Biology and Neuroscience, Nelson Laboratories, Rutgers University, 604 Allison Road, Piscataway, NJ 08854, USA
Clin Exp Metastasis 22:663-73. 2005..Our data provide evidence that in 21NT cells OPN enhances CD44s mRNA expression, increases cell surface expression of CD44 variant forms without a change in mRNA levels, and stimulates cell migration...
Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancyGeorge N Naumov
Department of Medical Biophysics, University of Western Ontario, London, Ontario, N6A 5C1 Canada
Cancer Res 62:2162-8. 2002..If such cells are present in patients, they could contribute to tumor recurrence and would not be susceptible to current therapeutic strategies targeting proliferating cells...
Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profilingDeepak Agrawal
Department of Cell Biology, Interdisciplinary Oncology, H. Lee Moffitt Cancer Center, University of South Florida, Tampa 33612, USA
J Natl Cancer Inst 94:513-21. 2002..We identified osteopontin as a clinically useful marker of tumor progression by use of gene expression profiling on pooled samples...
Plasma osteopontin: associations with survival and metastasis to bone in men with hormone-refractory prostate carcinomaSebastien J Hotte
Department of Oncology, University of Western Ontario, London Regional Cancer Center, 790 Commmissioners Road East, London, Ontario, Canada N6A 4L6
Cancer 95:506-12. 2002....
Cancer spread and micrometastasis development: quantitative approaches for in vivo modelsIan C MacDonald
Department of Medical Biophysics, University of Western Ontario, London, Canada
Bioessays 24:885-93. 2002..Furthermore, solitary tumor cells may remain dormant for long periods of time in secondary sites. These findings suggest that metastatic growth and angiogenesis are prime targets for anti-metastatic therapy...
Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transduction pathwaysAlan B Tuck
Department of Pathology, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada
Oncogene 22:1198-205. 2003..A number of potential targets are thus provided for strategies aimed at blocking the malignancy-promoting effects of OPN...
Transcriptional regulation of osteopontin and the metastatic phenotype: evidence for a Ras-activated enhancer in the human OPN promoterDavid T Denhardt
Nelson Laboratories, Rutgers University, Piscataway, New Jersey 88854, USA
Clin Exp Metastasis 20:77-84. 2003..In this communication we address two issues: (1) How does OPN facilitate the metastatic phenotype? (2) What mechanisms are responsible for the increase in OPN transcription in metastatic cells?..
The role of apoptosis in tumor progression and metastasisJason L Townson
Department of Medical Biophysics, University of Western Ontario, London, Canada N6A 4L6
Curr Mol Med 3:631-42. 2003....
Evaluating the role of serine protease inhibition in the management of tumor micrometastasesJoe B Putnam
University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA
Oncology (Williston Park) 17:9-30; quiz 31-2. 2003
Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastasesGeorge N Naumov
Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada
Breast Cancer Res Treat 82:199-206. 2003..This study has important clinical implications for patients being treated with cytotoxic chemotherapy...
Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologiesDomenico Coppola
Department of Pathology, University of South Florida College of Medicine, Tampa, Florida, USA
Clin Cancer Res 10:184-90. 2004..The strong correlation between pathological stage and OPN across multiple tumor types suggests a role for OPN in tumor progression...
Osteopontin identified as colon cancer tumor progression markerDeepak Agrawal
Department of Cell Biology, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL, USA
C R Biol 326:1041-3. 2003..Osteopontin is a secreted glycoprotein known to bind integrins and CD44. Its actual molecular function remains elusive but its increased expression correlates strongly with tumor progression...
A flavonoid fraction from cranberry extract inhibits proliferation of human tumor cell linesPeter J Ferguson
Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
J Nutr 134:1529-35. 2004..05) and induce cells to undergo apoptosis (P < 0.05) in a dose-dependent manner. Fr6 is potentially a source of a novel anticancer agent...
Detection and quantification of circulating tumor cells in mouse models of human breast cancer using immunomagnetic enrichment and multiparameter flow cytometryAlison L Allan
London Regional Cancer Program, London, Ontario, Canada
Cytometry A 65:4-14. 2005..CONCLUSIONS: This technique has the potential to be a valuable and sensitive tool for investigating the biological relevance of CTCs in experimental mouse models of breast cancer...
Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer modelSharon A Vantyghem
Department of Pathology, University of Western Ontario, Canada
Cancer Res 65:3396-403. 2005..The availability of well-characterized, clinically relevant animal models for studying factors that regulate metastatic outgrowth postsurgery will provide an important tool for developing new systemic adjuvant therapies...
Osteopontin induces multiple changes in gene expression that reflect the six "hallmarks of cancer" in a model of breast cancer progressionAmy C Cook
Department of Pathology, The University of Western Ontario, London, Ontario, Canada
Mol Carcinog 43:225-36. 2005..This study provides the first evidence that OPN can lead to numerous gene expression changes that influence multiple aspects of tumor progression and malignant growth...
Activated ras regulates the proliferation/apoptosis balance and early survival of developing micrometastasesHemanth J Varghese
Department of Medical Biophysics, University of Western Ontario, London, Ontario, N6A 5C1 Canada
Cancer Res 62:887-91. 2002....
