A5061901964- Cancer Cells and Metastasis
- Estrogen and related hormone effects
- Cancer Research and Treatments
- Inflammatory mediators and NSAID effects
- Colorectal Cancer Treatments and Studies
- Digestive system and related health
- Cell Adhesion Molecules Research
- Pancreatic and Hepatic Oncology Research
- Genetic factors in colorectal cancer
- Adrenal Hormones and Disorders
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Wnt/β-catenin signaling in development and cancer
- RNA Interference and Gene Delivery
- Cellular Mechanics and Interactions
- Helicobacter pylori-related gastroenterology studies
- 3D Printing in Biomedical Research
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Pituitary Gland Disorders and Treatments
- Protein Degradation and Inhibitors
- Neuroblastoma Research and Treatments
- Enhanced Recovery After Surgery
- Diagnosis and Treatment of Venous Diseases
- TGF-β signaling in diseases
Novartis (Switzerland)
2017-2023
Novartis Institutes for BioMedical Research
2017-2021
Imperial College London
2001-2011
Vanderbilt University Medical Center
1997
Vanderbilt University
1997
Hammersmith Hospital
1985-1996
Molecular Oncology (United States)
1987
University of Cambridge
1987
Royal Marsden Hospital
1980
A considerable amount of evidence collected from several different experimental systems indicates that cyclooxygenase-2 (COX-2) may play a role in colorectal tumorigenesis. Large epidemiologic studies have shown 40-50% reduction mortality cancer persons taking aspirin or other nonsteroidal antiinflammatory drugs on regular basis. One property shared by all these is their ability to inhibit COX, key enzyme the conversion arachidonic acid prostaglandins. Two isoforms COX been characterized,...
Nonsteroidal antiinflammatory drugs reduce the risk of colon cancer, possibly via cyclooxygenase (COX) inhibition. The growth factor-inducible COX-2, which is overexpressed in neoplastic colonic tissue, an attractive target to mediate this effect. Herein we have exploited ability a human cancer cell line, HCA-7 Colony 29, polarize when cultured on Transwell (Costar) filters study COX-2 production and vectorial release prostaglandins (PGs). Administration type α transforming factor...
Human colorectal cancer is caused by mutations and thought to be maintained a population of stem cells. Further phenotypic changes occurring at the invasive edge suggest that colon cells are also regulated their microenvironment. Type I collagen, promoter malignant phenotype in pancreatic carcinoma cells, highly expressed front human cancer. This study investigates role type collagen specifying cell phenotype. The effect on morphology, localisation cell–cell adhesion proteins,...
Human colorectal epithelium is composed mainly of columnar, mucous and endocrine cells; origin these cell lineages from a multi-potential stem at the base crypt (the Unitarian hypothesis) has been proposed but not yet demonstrated. Gut cells have variously considered neural crest or endodermal origin, conclusive evidence, particularly in humans, lacking. It shown that mouse gastrointestinal tract, single progenitor gives rise to both columnar cells, it be demonstrated such can also give...
1 Three stable epithelial cell lines (HCA-7, HCA-7-Col and 3) all derived from the same human adenocarcinoma have been cultured on collagen-coated Millipore filters. These monolayers used to record short circuit current (SCC) in response a variety of secretagogues. Similar monolayers, but grown plastic dishes, were for measurements tissue cyclic AMP. 2 Lysylbradykinin, applied either side increased SCC HCA-7 cells had little effect other two lines. The responses showed rapid desensitization,...
Using epithelial monolayers of HCA-7 cells, derived from a primary human colonic adenocarcinoma and grown on pervious supports, it is shown that responses to lysylbradykinin can be elicited either side. It proposed kinin receptors are inserted into both apical basolateral membrane domains.
Abstract Resident adult epithelial stem cells maintain tissue homeostasis by balancing self-renewal and differentiation. The cell potential of human epidermal keratinocytes is retained in vitro but lost over time suggesting extrinsic intrinsic regulation. Transcription factor-controlled regulatory circuitries govern identity, are sufficient to induce pluripotency transdifferentiate cells. We investigate whether transcriptional circuitry also governs phenotypic changes within a given type...
The HCA-7 cell line was established from a moderately well differentiated mucinous adenocarcinoma of the colon, which showed histological heterogeneity. This reflected in morphological heterogeneity early passages but diminished as cells were passaged vitro. Nine subpopulations isolated passage cultures and maintained lines. Each subpopulation demonstrated unique set stable biological characteristics When vivo, there wide variation xenograft generation time. parent gave rise to six distinct...
The human colorectal epithelium is maintained by multipotent stem cells that give rise to absorptive, mucous, and endocrine lineages. Recent evidence suggests cancers are likewise a minority population of so-called cancer cells. We have previously established cell line with characteristics (HRA-19) developed serum-free medium induces endocrine, mucous absorptive lineage commitment HRA-19 in vitro. In this study, we investigate the role beta1 integrin family surface extracellular matrix...
Abstract A limited understanding of the pathology underlying chronic wounds has hindered development effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate molecular composition various common ulcer types facilitate drug discovery strategies. We conducted a comprehensive analysis leg ulcers (LUs), encompassing venous arterial ulcers, foot (FUs), pressure (PUs), compared them with surgical wound healing complications (WHCs). To explore pathophysiological...
Abstract Two monoclonal antibodies (MAbs) AUAI and HMFGI recognize antigens located on different membrane domains of polarized epithelial cells. We have assessed the accessibility these in multicellular tumour spheroids produced culture using a well‐polarized (HRA‐19) non‐polarized cell line (LoVo) human large‐bowel carcinoma origin. Multicellular HRA‐19 cells develop polarity, so that which is contact with medium (apical) becomes antigenically distinct from facing centre (basolateral). This...
ABSTRACT HRA-19a1.1. cells, derived from a primary human rectal adenocarcinoma, form polarized monolayers when grown on tissue-culture plastic. The apical membrane of the cells is in contact with culture medium while basolateral surface attached to plastic substratum. Cells cultured non-tissueculture floating colonies. within these colonies are orientated so that their faces centre colony. When embedded collagen gel organize glandular structures similar those observed xenografts this cell...
Abstract A human colonic carcinoma cell line (HCA‐7) isolated from a well differentiated mucoid adenocarcinoma of the colon has been maintained in vitro for 3 years. It spontaneously synthesizes HLA‐DR which is mainly intracytoplasmic. Stimulation with lymphocyte conditioned medium and recombinant γ‐interferon results enhanced synthesis appearance antigen on surface. dose response study showed that maximal stimulation culture was achieved 50 units/ml γ‐interferon. Staining uneven being...
Oral and intestinal mucositis is a debilitating side effect of radiation treatment. A mouse model radiation-induced leads to weight loss tissue damage, reflecting the human ailment as it responds keratinocyte growth factor (KGF), standard-of-care Cultured crypt organoids allowed development an assay monitoring treatments epithelium damage. This in vitro resembles KGF roof plate-specific spondin-1 (RSPO1) enhanced organoid recovery following radiation. Screening identified compounds that...
Cell culture is widely used to study gene or protein changes in response experimental conditions. The value of such experiments depends on stringent control and understanding the vitro environment. Despite well-documented evidence describing toxic effects clinical setting, antibiotics antimycotics are routinely cell without regard for their potential toxicity. We cultured MCF-7 breast cancer cells presence/absence (penicillin/streptomycin) and/or antimycotic amphotericin B. Differential...
BET bromodomain inhibitors hold promise as therapeutic agents in diverse indications, but their clinical progression has been challenging and none have received regulatory approval. Early trials cancer shown heterogeneous responses, development of resistance, adverse events. Increased understanding mechanism(s) action identification biomarkers are needed to identify appropriate indication(s) achieve efficacious dosing. Using genome-wide CRISPR-Cas9 screens at different concentrations, we...
The human large intestine is lined by a rapidly renewing epithelial monolayer where cell loss precisely balanced with production. continuous supply of new cells produced undifferentiated multipotent stem via coordinated program proliferation and differentiation yielding three lineages: absorptive, goblet enteroendocrine. Cell-matrix interactions have been suggested to be regulators the multilineage colorectal crypt but expression matrix proteins or their receptors does not appear subtlety...
The role of cell-matrix interactions in controlling phenotypic heterogeneity human colonic carcinoma sublines has been investigated. Four cell lines (colony 1, colony 3, 6 and 30) previously isolated from a single line, HCA-7, were grown 3-dimensional collagen gels. In collagen, the growth 4 ranged well-organised glandular structures to elongated branching 3). capability cells organise into correlated with degree differentiation observed their xenografts. Certain sublines, most notably able...