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Cholelithiasis↗
Biomedical subjects
T Christopher Windham
Publications and source records attributed to T Christopher Windham.
Activated SRC protein tyrosine kinase is overexpressed in late-stage human ovarian cancers.
OBJECTIVE: The objective of this study was to determine if the Src tyrosine kinase is overexpressed and activated in late-stage human ovarian cancers. METHODS: Western analysis and immune complex kinase assays were performed on a panel of human ovarian cancer cell lines and normal ovarian epithelial cell cultures, and immunohistochemical analysis for Src and activated Src were performed on a panel of late-stage human ovarian tumors. RESULTS AND CONCLUSIONS: Src is overexpressed and activated in a majority of late-stage ovarian tumors as well as in a panel of cultured malignant human ovarian epithelium grown in vitro, but not in normal ovarian epithelium (NOE) or immortalized NOE. Src overexpression was found to be frequently, but not always, associated with HER-2/neu overexpression, but no statistical association between Src and Her-2/neu overexpression could be demonstrated.
Enzyme Activation↗
Src activation regulates anoikis in human colon tumor cell lines.
Src is a non-receptor protein tyrosine kinase, the expression and activity of which is increased in >80% of human colon cancers with respect to normal colonic epithelium. Previous studies from this and other laboratories have demonstrated that Src activity contributes to tumorigenicity of established colon adenocarcinoma cell lines. Src participates in the regulation of many signal transduction pathways, among which are those leading to cellular survival. In this study, we addressed the potential role of Src activation to a specific aspect of tumor cell survival, resistance to detachment-induced apoptosis (anoikis). Using five colon tumor cell lines with different biologic properties and genetic alterations, we demonstrate that expression and activity of Src corresponds with resistance to anoikis. Enforced expression of activated Src in subclones of SW480 cells (of low intrinsic Src expression and activity) increases resistance to anoikis; whereas decreased Src expression in HT29 cells (of high Src expression and activity) by transfection with anti-sense Src expression vectors increases susceptibility to anoikis. In contrast, increasing or decreasing Src expression had no effect on susceptibility to staurosporine-induced apoptosis in attached cells. PD173955, a Src family-specific tyrosine kinase inhibitor, increases the susceptibility of HT29 cells to anoikis in a dose- and time-dependent manner. Increasing Src expression and activity led to increased phosphorylation of Akt, a mediator of cellular survival pathways, whereas decreasing Src activity led to decreased Akt phosphorylation. In colon tumor cells with high Src activity, the PI3 kinase inhibitor LY 294002 sensitized cells to anoikis. These results suggest that Src activation may contribute to colon tumor progression and metastasis in part by activating Akt-mediated survival pathways that decrease sensitivity of detached cells to anoikis.
Adenocarcinoma↗
Adenocarcinoma of the stomach in patients age 35 years and younger: no impact of early diagnosis on survival outcome.
BACKGROUND AND OBJECTIVES: Patients aged 35 years and younger with gastric adenocarcinoma constitute a group of patients who have been observed to have low survival rates as compared with older gastric adenocarcinoma patients. A low index of suspicion for gastric cancer in this age group has been suspected to result in a delay in diagnosis. The use of computed tomography (CT) scanning and endoscopy has become much more common during the past 15 years. We hypothesized that early diagnosis would result in improved survival for these patients. METHODS: We performed a retrospective study of 127 patients aged 35 years and younger with gastric (median follow-up, 9 months). RESULTS: High proportions of female patients and Hispanic patients were observed. Overall survival of this group of patients was poor, with a median survival of only 8 months. Comparison of patients diagnosed within 2 months of the onset of symptoms with those diagnosed later revealed no survival advantage to early diagnosis. Similarly, diagnosis within 2 months of presentation to a physician conferred no survival advantage. CONCLUSIONS: Long-term survival is rare, with a short overall median survival. Early diagnosis conferred no survival advantage. This group of patients should be considered for protocol based multi-modality therapy, even with potentially resectable disease.
Adenocarcinoma↗
Retroperitoneal sarcomas.
BACKGROUND: The evaluation and treatment of retroperitoneal sarcomas are challenging because the tumors are relatively rare and frequently present with advanced disease in an anatomically complex location. METHODS: We reviewed the literature on experience in the management of retroperitoneal sarcomas, and we present our own experience in the treatment of these tumors. RESULTS: The identification of prognostic factors other than the adequacy of resection has been inconsistent. Due to a lack of associated symptoms, retroperitoneal sarcomas smaller than 5 cm are rare. Computed tomography is the most useful tool in the evaluation of retroperitoneal tumors. Surgery, radiation therapy, and chemotherapy are treatment options, but the most important factor in the treatment of primary tumors is complete surgical resection. The role of neoadjuvant and adjuvant therapies is not defined and should be considered within the context of clinical trials. CONCLUSIONS: Early referral of patients with retroperitoneal soft tissue tumors will help to ensure that they will receive the benefits of multidisciplinary evaluation and treatment of their disease and ready access to clinical trials.
Antineoplastic Agents↗