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Biomedical subjects

H Perrin

Publications and source records attributed to H Perrin.

12 recordsLinked to original sources
PubMed1998

Are hepatomas a good target for suicide gene therapy? An experimental study in rats using retroviral-mediated transfer of thymidine kinase gene.

BACKGROUND: Suicide gene transfer into tumor cells has been proposed for the treatment of various tumors. The most common suicide gene is coded for the herpes simplex type I thymidine kinase (HSV1-TK), which converts nontoxic nucleoside analogs such as ganciclovir into toxic triphosphated compounds. This study evaluated the potential of this treatment for gene therapy of liver tumors. METHODS: The sensitivity of different colon carcinoma and hepatoma cell lines to infection by recombinant retroviruses was evaluated. Next, HSV1-TK-expressing derivatives of these cells were generated to analyze their sensitivity to ganciclovir. Finally, these cells were used to generate experimental hepatomas in rats after injection under the liver capsule, and the efficacy and safety of a ganciclovir treatment on tumor growth and survival were evaluated. RESULTS: All the different cell lines analyzed were sensitive to retroviral-mediated gene transfer, although the susceptibility of individual cell lines to this transfer varied significantly. HSV1-TK derivatives were about 1000-fold more sensitive to the toxic effects of ganciclovir than parental cells. Tumors with HSV1-TK expressing MCA-RH8994 hepatoma cells were then generated. Intraperitoneal injection of 75 mg/kg ganciclovir twice daily for 5 days dramatically reduced the size of HSV1-TK-positive tumors compared with tumor size in untreated control rats (0.4 mm3 versus 65 mm3, p < 0.02). A long-term study demonstrated that this reduction of tumor volume was associated with a significant increase in survival (p < 0.01). Pathologic examination 26 days after the end of ganciclovir injections showed that complete tumor regression was observed in two of five rats. Most important, there was no toxicity associated with these tumors. CONCLUSIONS: In a clinical perspective the good tolerance to treatment and the significant clinical effect observed were encouraging. Gene transfer methods should be established to allow efficient targeting of the tumor cells in vivo.

3T3 Cells↗
PubMed1997

A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumors together with a distant transduced tumor.

Antitumor gene therapy using herpes simplex type 1 thymidine kinase (TKh) and ganciclovir (GCV) treatment has revealed an important intratumoral bystander effect. A whole tumor can be eliminated when only a fraction of its tumor cells express TKh. We now report that the bystander effect not only acts within a tumor, but also between distant tumors. One TKh+ tumor was generated simultaneously with one or multiple TKh- tumors in different rat liver lobes such that there was no contact between the resulting tumors. Both the TKh+ and the TKh- tumors regressed after GCV treatment and showed infiltration with macrophages and T lymphocytes. This distant bystander effect, which is likely immune mediated, should be of major importance for gene therapy of disseminated tumors.

3T3 Cells↗
PubMed1997

Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis.

OBJECTIVE: To investigate the impact of preoperative transarterial lipiodol chemoembolization (TACE) in the management of patients undergoing liver resection or liver transplantation for hepatocellular carcinoma. PATIENTS AND METHODS: TACE was performed before surgery in 49 of 76 patients undergoing resection and in 54 of 111 patients undergoing liver transplantation. Results were retrospectively analyzed with regard to the response to treatment, the type of procedure performed, the incidence of complications, the incidence and pattern of recurrence, and survival. RESULTS: In liver resection, downstaging of the tumor by TACE (21 of 49 patients [42%]) and total necrosis (24 of 49 patients [50%]) were associated with a better disease-free survival than either no response to TACE or no TACE (downstaging, 29% vs. 10% and 11 % at 5 years, p = 0.08 and 0.10; necrosis, 22% vs. 13% and 11% at 5 years, p = 0.1 and 0.3). Five patients (10%) with previously unresectable tumors could be resected after downstaging. In liver transplantation, downstaging of tumors >3 cm (19 of 35 patients [54%]) and total necrosis (15 of 54 patients [28%]) were associated with better disease-free survival than either incomplete response to TACE or no TACE (downstaging, 71 % vs. 29% and 49% at 5 years, p = 0.01 and 0.09; necrosis, 87% vs. 47% and 60% at 5 years, p = 0.03 and 0.14). Multivariate analysis of the factors associated with response to TACE showed that downstaging occurred more frequently for tumors >5 cm. CONCLUSIONS: Downstaging or total necrosis of the tumor induced by TACE occurred in 62% of the cases and was associated with improved disease-free survival both after liver resection and transplantation. In liver resection, TACE was also useful to improve the resectability of primarily unresectable tumors. In liver transplantation, downstaging in patients with tumors >3 cm was associated with survival similar to that in patients with less extensive disease.

Aged↗
PubMed1996

Coloanal anastomosis for benign lesions: long term functional results in 11 patients.

OBJECTIVE: To assess the indications, morbidity, and long-term functional results of rectal resection and coloanal anastomosis for benign rectal lesions. DESIGN: Retrospective study. SETTING: Teaching hospital, France. SUBJECTS AND INTERVENTIONS: Eleven patients were operated on for villous adenoma (n = 5), radiation proctitis (n = 2), solitary rectal ulcer (n = 2), rectal stenosis (n = 1) and rectovaginal fistula (n = 1). MAIN OUTCOMES MEASURES: Morbidity, mortality, and long-term results. RESULTS: There were no postoperative deaths. 2 patients (18%) developed major postoperative complications: one pelvic abscess was treated conservatively and one anastomotic fistula required a diverting colostomy. The mean (SD) follow-up period was 89 (35) months. Functional results were judged as perfect (n = 4), good (n = 1), or acceptable (n = 2) (mean stool frequency: 1.4), including the five with villous adenoma, one with radiation proctitis, and the one with a rectovaginal fistula. By the end of the follow-up period, 4 patients (36%) had permanent colostomies (including the two patients with solitary rectal ulcers). Two of them were required soon after operation, and two following failure 5 and 2 years later, respectively, after initially good functional results. CONCLUSION: Rectal resection with coloanal anastomosis can safely be proposed for selected patients with benign rectal lesions including diffuse villous adenoma, rectovaginal fistula, and radiation proctitis without deterioration of the anal sphincter. The poor results in the 2 cases of solitary rectal ulcer suggest that for this condition coloanal anastomosis should be done only after the failure of previous surgical treatment.

Adenoma, Villous↗
PubMed1993

Utilization of medical services by drug abusers in detoxification.

To establish the extent of health services, including inpatient, emergency room, and outpatient care utilized by illicit drug users during the previous year, we surveyed 77 drug abusers, who were not known to be HIV-positive, entering a detoxification unit and a comparison group of 70 drug nonusers. Over the previous year, drug abusers had a greater number of visits to their usual source of care, to emergency rooms, and to other sites than drug nonusers. Drug abusers were significantly more likely to have been hospitalized during the past year. Using a logistic model including sociodemographic factors, drug abusers were 2.3 times as likely to use an emergency room and 6.7 times as likely to be hospitalized as drug nonusers. We conclude that drug abusers are heavy users of health services compared to a group of drug nonusers.

Ambulatory Care↗