PubMed · 4502004
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N Arimizu, S Inoue, T Murata, T Saegusa. 1972. [Bone tumors].. https://pubmed.ncbi.nlm.nih.gov/4502004/
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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: This study was conducted to assess the prognostic significance of adjunctive radiation in the surgical management of rectal carcinoma patients with tumor fixation. METHODS: Two hundred and ninety-seven patients with a histologic diagnosis of adenocarcinoma of the rectum were treated with high dose preoperative radiation ( > or = 45 Gray [Gy]) followed by surgical resection of the tumor (Group A). One hundred and seventy-four patients underwent initial curative surgery (Group B) followed by selective postoperative radiation (45-50 Gy) for those with pathologic T3, T4, or N+ (B2, C) cancers (N = 143). The two patient groups were compared by presenting clinical stage of the disease to assess the prognostic significance of tumor fixation on results of adjunctive therapy. Follow-up ranged from 24 months to 180 months. RESULTS: The 5-year actuarial survival of Groups A and B was similar, 69% and 61% respectively. Survival was significantly better for Group A patients with fixed cancer (57% vs. 33%, P = 0.003). Survival was also better for patients in Group A with tumors located in the distal rectum (70% vs. 56%, P = 0.02). The local recurrence rate for patients with tumors located in the distal rectum was 17% for Group A and 19% for Group B (P = 0.74). The local recurrence rate for fixed cancers was 23% and 50% for Group A and Group B respectively (P = 0.0009). The incidence of small bowel complications (Grade 3 or 4) was lower for patients undergoing preoperative radiation compared with patients treated with postoperative radiation, (4% vs. 13%, P < 0.05). CONCLUSIONS: When special considerations of sphincter-preserving surgery are not an issue, mobile rectal carcinoma may be effectively treated with surgery and selective postoperative radiation. However, fixed tumors, especially those located in the distal rectum, are better treated with high dose preoperative radiation.
BACKGROUND: The measurement of estrogen receptors (ER) in breast cancer specimens has traditionally been assessed with a dextran-coated charcoal assay (DCCA). More recently the immunohistochemical staining (IHC) method has gained increasing popularity because of its ability to use fixed tissue, assess needle biopsies, and reduce cost. Controversy exists over the accuracy of IHC compared with that of DCCA in determining ER. We compared these two techniques using tumor tissue obtained from a large group of females with lymph node positive breast carcinoma with long term follow-up. METHODS: Breast carcinoma tissue was obtained from a large group of females with node positive breast carcinoma participating in two adjuvant chemotherapy trials. ER was determined by the traditional DCCA method and by IHC using the ER1D5 antibody. Disease free survival (DFS) and overall survival (OS) were assessed by each of these methods. RESULTS: ER status was determined by DCCA and IHC in tumor tissue obtained from 316 females. A concordance of 79% was observed for the determination of ER-positive tumors. Of the discordant results, the majority of DCCA-negative, IHC-positive tumors could be explained by a low level of DCCA positivity (< 10 fmol) or IHC staining of nonmalignant cells. A much higher rate of discordant results was observed in premenopausal females. Of the DCCA-negative, IHC-positive patients 97% were premenopausal and of the DCCA-positive, IHC-negative patients 79% were premenopausal. ER by DCC appears to perform better than ER by IHC as a prognostic factor in terms of DFS and OS. CONCLUSIONS: When compared with DCCA, IHC with monoclonal antibody ER1D5 appears to be a reasonable substitute for the determination of ER. Although DCCA appeared to perform better as a determinant of prognosis, ER detection is used primarily for deciding on hormonal therapy. Review of discordant cases indicates IHC may more accurately reflect the ER status of malignant cells in some patients. Attention must be paid to quality control considerations in performance of IHC staining.