PubMed · 4761344
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M R Tanga, A Bouchard, J B Ewing. 1973-08-01. Carcinoma developing in gall bladder remnants.. https://pubmed.ncbi.nlm.nih.gov/4761344/
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The G12 subfamily of heterotrimeric G proteins, comprised of the alpha-subunits Galpha12 and Galpha13, has been implicated as a signaling component in cellular processes ranging from cytoskeletal changes to cell growth and oncogenesis. In an attempt to elucidate specific roles of this subfamily in cell regulation, we sought to identify molecular targets of Galpha12. Here we show a specific interaction between the G12 subfamily and the cytoplasmic tails of several members of the cadherin family of cell-surface adhesion proteins. Galpha12 or Galpha13 binding causes dissociation of the transcriptional activator beta-catenin from cadherins. Furthermore, in cells lacking the adenomatous polyposis coli protein required for beta-catenin degradation, expression of mutationally activated Galpha12 or Galpha13 causes an increase in beta-catenin-mediated transcriptional activation. These findings provide a potential molecular mechanism for the previously reported cellular transforming ability of the G12 subfamily and reveal a link between heterotrimeric G proteins and cellular processes controlling growth and differentiation.
BACKGROUND: Synchronous bilateral breast carcinoma (SBBC) is an uncommon presentation, and the management of patients with this disease is not well established. METHODS: In order to evaluate whether patients with early-stage SBBC could be safely and effectively treated with bilateral breast-conserving therapy (BCT), the authors retrospectively reviewed the records of 24 patients with clinical Stage I-II SBBC treated during the period 1977-1989 with bilateral BCT. SBBC was defined as bilateral invasive carcinomas diagnosed no more than 1 month apart. The median age at diagnosis was 56 years (range, 32-85 years), and the median follow-up for surviving patients was 95 months (range, 68-157 months). Pathology slides were available for review in 19 cases. Cosmetic results and complications after BCT were scored. Outcome was compared with that of 1314 patients with unilateral Stage I or II breast carcinoma, within the same age range, treated during the same time period. RESULTS: There were no significant differences between the SBBC and unilateral groups in actuarial disease free survival (70% and 74%, respectively, at 5 years), overall survival (88% and 87%, respectively, at 5 years), or crude distribution of sites of first failure. Multivariate analysis of overall survival and disease free survival also did not show bilaterality to be a significant factor. The cosmetic results for the SBBC group were not significantly different from those for the unilateral group. Physician assessment of cosmetic outcome was excellent in 57% and good in 43% of SBBC patients evaluated 25-48 months after BCT. Long term complications were rare in both groups. CONCLUSIONS: Patients with early-stage SBBC can be safely treated with carefully planned, bilateral BCT, with outcome that appears to be comparable to that of patients with early-stage unilateral breast carcinoma.
BACKGROUND: Inactivation of the retinoblastoma (Rb) gene has been documented in various types of cancer, including lung cancer. Alterations of the p53 and ras genes are also common features in the molecular biology of lung carcinoma, and the authors of this article have reported previously on the prognostic significance of both of them. In the present study, the authors evaluated the prognostic significance of the loss of Rb protein expression alone, then performed a combined analysis of Rb protein and ras p21 status (Rb/ras) as well as an analysis of Rb and p53 protein status (Rb/p53) in patients with nonsmall cell lung cancer (NSCLC). METHODS: Ninety-one patients with NSCLC underwent potentially curative resection between 1977 and 1988, 65 of whom received postoperative combination chemotherapy. Tumor specimens were analyzed for Rb protein expression by immunohistochemistry. Univariate and multivariate analyses were performed to assess the association between Rb protein expression and survival. RESULTS: Nineteen (21%) of the 91 NSCLCs showed negative Rb protein expression. Positive or negative Rb protein expression (Rb+ or Rb-) as an individual factor was not statistically correlated with survival or prognosis in this cohort of NSCLC patients, although a tendency among Rb- patients to do worse was observed. The authors then combined the Rb protein status with previously studied results of ras p21 and p53 protein expression in the same tumor specimens, and compared the prognosis between the individuals with theoretically the best pattern of gene expression in their tumors and those with theoretically the worst pattern of expression, i.e., Rb+/ras- versus Rb-/ras+ and Rb+/p53- versus Rb-/p53+. In patients with adenocarcinoma, those with Rb-/ras+ tumors survived for a significantly shorter period after surgery (13% 5-year survival) than those with Rb+/ras- tumors (82% 5-year survival) (P = 0.01). Similarly, patients with Rb-/p53+ tumors survived for a significantly shorter period (20% 5-year survival) compared with those who had Rb+/p53- tumors (73% 5-year survival) (P = 0.008). Rb/ras status was a significant prognostic factor (P = 0.02 by univariate analysis, P = 0.048 by multivariate analysis), and Rb/p53 status tended to be significant as a prognostic factor (P = 0.04 by univariate analysis, P = 0.08 by multivariate analysis). In patients with squamous cell carcinoma, neither Rb/ras nor Rb/p53 status was a significant prognostic factor in this cohort. CONCLUSIONS: These results suggest that combined immunohistochemical analyses of Rb and ras p21 proteins and of Rb and p53 proteins may indicate their potentially synergistic effects on survival and prognosis. These analyses may also be useful for stratifying patients with adenocarcinoma of the lung into different prognostic groups and identifying populations with different risks of recurrence. Larger prospective studies with Stage I NSCLC patients are necessary to confirm the current findings.