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Biomedical subjects

Robert J S Thomas

Publications and source records attributed to Robert J S Thomas.

7 recordsLinked to original sources
PubMed2006

Identification of candidate murine esophageal stem cells using a combination of cell kinetic studies and cell surface markers.

The identification and characterization of esophageal stem cells are critical to our understanding of the biology of the esophageal epithelium in health and disease. However, the proliferative compartment within the mouse esophageal epithelium remains poorly characterized. Here, we report that the basal cells of the mouse esophagus can be separated into three phenotypically and functionally distinct subpopulations based on the expression of alpha(6) integrin and transferrin receptor (CD71). Cells that express high levels of alpha(6) integrin and low levels of CD71, termed alpha(6)(bri)CD71(dim), are a minor subpopulation of small and undifferentiated cells that are enriched for label-retaining cells and thus represent a putative esophageal stem cell population. Conversely, cells expressing high levels of both alpha(6) integrin and CD71 (alpha(6)(bri)CD71(bri)), the majority of basal esophageal cells, are enriched for actively cycling cells and therefore represent a transit-amplifying population. Kinetic analyses revealed that a third cell population, which is alpha(6) integrin-dim and CD71-bright (alpha(6)(dim)), is destined to leave the basal layer and differentiate.

Animals↗
PubMed2006

Mutation analysis of PIK3CA and PIK3CB in esophageal cancer and Barrett's esophagus.

Mutation of PIK3CA, the gene coding for the p110alpha catalytic subunit of phosphoinositide 3-kinase (PI3K), has been reported in a limited range of human tumors. We now report that PIK3CA is also mutated in esophageal tumors. Single-strand conformational polymorphism (SSCP) and denaturing high-performance liquid chromatography (DHPLC) were used to screen all 20 exons of PIK3CA in 101 samples from 95 individuals with esophageal cancer and/or Barrett's esophagus. Somatic mutation of PIK3CA was detected in 4 of 35 (11.8%) of esophageal squamous cell carcinomas (SCC) and 3 of 50 (6%) adenocarcinomas. No mutations were detected in any of 17 samples of Barrett's esophagus. For PIK3CB, we screened exons 11 and 22, which code for the regions corresponding to the exon 9 and 20 mutational 'hotspots' of PIK3CA. No somatic changes were detected in PIK3CB This study extends previous observations in other tumor types by demonstrating the presence of somatic PIK3CA mutations in both SCC and adenocarcinoma of the esophagus, thus implicating the PI3K pathway in the initiation and/or progression of esophageal cancers.

Adenocarcinoma↗
PubMed2006

FDG-PET status following chemoradiotherapy provides high management impact and powerful prognostic stratification in oesophageal cancer.

PURPOSE: The purpose of this study was to evaluate the impact of FDG-PET following chemoradiotherapy (CRT) on treatment planning and survival in patients with oesophageal cancer (OC). METHODS: Fifty-three consecutive OC patients had a post-treatment PET scan to evaluate tumour response to CRT prior to possible surgery. Baseline pre-CRT PET was performed in 33 patients. Prospectively recorded post-CRT management plans were compared with post-PET treatment. High impact was defined as a change in treatment intent or modality. Survival was analysed using the Kaplan-Meier product limit method and Cox proportional hazards regression model. RESULTS: After completion of CRT, 23/53 patients (43%) achieved complete metabolic response (CMR), as compared with only four (8%) with complete response on computed tomography. High PET impact was observed in 19 patients (36%). CMR was strongly predictive of survival (p<0.008) on multivariate analysis. CMR patients in whom resection was not performed had comparable survival to those (CMR and non-CMR) who underwent resection. CONCLUSION: The use of post-treatment FDG-PET for assessment of tumour response after CRT changed the clinical management of more than one-third of OC patients. CMR status as assessed by PET powerfully stratified prognosis. Even in the absence of a baseline study, normalisation of uptake at all sites of known tumoral involvement carries a good medium-term prognosis.

Adult↗
PubMed2006

Significant clinical impact and prognostic stratification provided by FDG-PET in the staging of oesophageal cancer.

PURPOSE: To evaluate the clinical impact of FDG-PET in staging oesophageal cancer and whether this information improves prognostic stratification. METHODS: Impact was based on comparison of a prospectively recorded pre-PET plan with post-PET treatment in 68 consecutive patients undergoing primary staging. Survival was analysed using the Kaplan-Meier product limit method and the Cox proportional hazards regression model. RESULTS: FDG-PET findings impacted on the management of 27/68 patients (40%): in 12 therapy was changed from curative to palliative and in three from palliative to curative, while in 12 other patients there was a change in the treatment modality or delivery but not in the treatment intent. The median survival was 21 months, with post-PET stage and treatment intent both strongly associated with survival (p<0.001). Conventional stage was not able to clearly stratify this population. CONCLUSION: The use of FDG-PET for primary staging of oesophageal cancer changed the clinical management of more than one-third of patients and provided superior prognostic stratification compared with conventional investigations.

Adult↗
PubMed2005

Frizzled-7 receptor ectodomain expression in a colon cancer cell line induces morphological change and attenuates tumor growth.

Frizzled (FZD) receptors have a conserved N-terminal extracellular cysteine-rich domain that interacts with Wnts and co-expression of the receptor ectodomain can antagonize FZD-mediated signalling. Using the ectodomain as an antagonist we have modulated endogenous FZD7 signalling in the moderately differentiated colon adenocarcinoma cell line, SK-CO-1. Unlike the parental cell line, which grows as tightly associated adherent cell clusters, the FZD7 ectodomain expressing cells display a spread out morphology and grow as a monolayer in tissue culture. This transition in morphology was associated with decreased levels of plasma membrane-associated E-cadherin and beta-catenin, localized increased levels of vimentin and redistribution of alpha6 integrin to cellular processes in the FZD7 ectodomain expressing cells. The morphological and phenotype changes induced by FZD7 ectodomain expression in SK-CO-1 cells is thus consistent with the cells undergoing an epithelial-to-mesenchymal-like transition. Furthermore, initiation of tumor formation in a xenograft tumor growth assay was attenuated in the FZD7 ectodomain expressing cells. Our results indicate a pivotal role for endogenous FZD7 in morphology transitions that are associated with colon tumor initiation and progression.

Adenocarcinoma↗
PubMed2002

Rectal cancer in Victoria in 1994: patterns of reported management.

BACKGROUND: A retrospective survey of medical practitioners was conducted to describe the management of patients newly diagnosed with rectal cancer in 1994, prior to the publication of best practice guidelines. METHODS: A sample of 908 patients with rectal cancer diagnosed between 1 January and 31 December 1994 was identified from the Victorian Cancer Registry. Questionnaires were then sent to the treating doctor(s) for completion. The topics covered by the questionnaires included: reported management by method of diagnosis; staging investigations; and treatment by surgery, chemotherapy and radiotherapy. RESULTS: Seven hundred and twenty-six (80%) of 908 eligible patients were surveyed. Surgery was the primary treatment in 681 (93.8%) with curative intent in 483 (70.9%) of these cases. One- third (163; 33.7%) of curative cases were pathologically staged as Dukes' C. Almost all patients (96%) were symptomatic, and three-quarters were referred by general practitioners to 166 surgeons. One-third (221; 32.5%) underwent liver computed tomography or ultrasound, and only three cases had transrectal ultrasound. Restorative anterior resection was the most common surgical procedure (431; 63.3%) with 160 (23.5%) and 34 (5.0%) patients being managed with abdominoperineal resections and local excision, respectively. Chemotherapy and radiotherapy were administered as part of the initial management to 216 (31.7%) and 171 (25.1%) patients, respectively. In five of the 171 cases, radiotherapy was given preoperatively. CONCLUSIONS: There was considerable variation in preoperative assessment. Staging was less complete than expected by today's standards. The diversity of surgical techniques observed may reflect both the lack of clinical trials and disparity in surgical training and experience. Referral to stomal therapists, and medical and radiation oncologists was lower than would now be expected, as was the use and timing of adjuvant therapies. These findings will be useful as a baseline for comparison with subsequent surveys conducted since the introduction of evidence-based guidelines.

Antineoplastic Combined Chemotherapy Protocols↗