PubMed · 5404336
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J Robert, B Benyahia, O Cherkaoui. 1969. [Problems posed by the cold thyroid nodule].. https://pubmed.ncbi.nlm.nih.gov/5404336/
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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.
PURPOSE: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer. METHODS AND MATERIALS: From May 1989 until September 1995, 66 patients with primary, solitary muscle invasive bladder cancer were treated with TUR, EBRT, and IRT, aiming at bladder preservation. According to the protocol, in three patients low-dose EBRT was applied, whereas 63 patients received high-dose EBRT. Immediately prior to IRT, 42 patients underwent a lymphnode dissection, and in 16 cases a partial cystectomy was performed. For IRT, two to five catheters were used and IRT was started within 24 h after surgery. The majority of patients received 30 Gy of IRT, with a mean dose rate of .58 Gy/h. In three patients, additional EBRT was applied following IRT. Follow-up consisted of regular cystoscopies, mostly done during joint clinics of urologist and radiation oncologist, with urine cytology routinely performed. The median follow-up period was 26 months. The Kaplan-Meier method was used for the determination of survival rates. RESULTS: In seven patients, a bladder relapse developed. The probability of remaining bladder relapse free at 5 years was 88%. The bladder was preserved in 98% of the surviving patients. Metastases developed in 16 patients, and the probability of remaining metastasis free at 5 years was 66%. The cumulative 5-year overall and bladder and distant relapse free survival were 48% and 69%, respectively. Acute toxicity was not serious in the majority of cases; surgical correction of a persisting vesicocutaneous fistula was necessary in two patients, whereas a wound toilet had to be performed in another patient. Serious late toxicity (bladder, RTOG Grade 3) was experienced by only one patient. CONCLUSIONS: Interstitial radiation preceded by TUR and EBRT, in a selected group of patients with muscle invasive bladder cancer, yields an excellent bladder tumor control rate with a high probability of bladder preservation. Survival was mainly dependent on the development of distant metastases. Serious acute and late toxicity was rare.
PURPOSE: To describe the results of a series of 63 Western patients presenting with gastric adenocarcinoma and treated with surgery and intraoperative radiation therapy (IORT) over a 8-year period and to discuss the role of IORT when combined with limited lymph node dissection. METHODS AND MATERIALS: From 1986 to 1993, 63 patients with gastric adenocarcinoma have been operated in the department of radiation oncology of the Hospices Civils de Lyon. The stage was: I in 17, II in 11, IIIA in 9, IIIB in 20, and IV in 6. The lymph node dissection was considered to be limited in 56 patients and extended in 7. The IORT dose ranged from 12 to 23 Gy (median: 15). Thirty patients also underwent a postoperative external beam irradiation with a standard dose of 44-46 Gy. RESULTS: The postoperative mortality rate was 4.8%. The 5-year overall survival in the entire series was 47% and was 82, 55, 78, 20, and 0% in Stages I, II, IIIA, IIIB, and IV, respectively. Loco-regional relapse occurred in 15 of 63 patients and metastases in 15 of 63. CONCLUSION: In Western patients treated by gastrectomy for adenocarcinoma of the stomach, IORT combined with limited lymph node dissection may provide overall survival similar to that observed after gastrectomy with extended lymph node dissection but with less postoperative mortality.