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J C Pector

Publications and source records attributed to J C Pector.

At least 19 recordsLinked to original sources
PubMed1992

Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis in portacaval shunted rats.

Hepatocarcinogenesis was initiated in rats with diethylnitrosamine (DEN) followed by a selection with 2-acetylamino-fluorene (2-AAF). Portacaval shunt was then performed in order to promote tumor development. Control rats were not submitted to the initiation--selection protocol and were sham-operated. In control rats, adenylate cyclase activity from crude liver membranes was stimulated 7- to 8-fold by maximal doses of glucagon (10(-6) M) or guanyl-5'-yl-imidophosphate [Gpp(NH)p] (10(-3) M), and 17-fold by a maximal (10(-5) M) dose of forskolin. Guanosine-5'-O-(2-thiodiphosphate) inhibited the response to forskolin (-38%) and to low doses of glucagon (-50%). The initiation--selection protocol increased the activity in basal conditions and in response to various stimuli. The portacaval shunt did not modify the activity of the enzyme with respect to basal activity or the response to glucagon. It significantly decreased the response to Gpp(NH)p (-45%) and to forskolin (-27%). The initiation--selection protocol increased the basal activity of the enzyme (+150%) and its response to Gpp(NH)p (+300%). When tumors developed, the activity of the cyclase further increased (+200%) and an inhibitory effect of GTP on the hormone-stimulated enzyme appeared (-40%). From these results, it is concluded that the promotion of hepatocarcinogenesis by portacaval shunt is coupled with modifications in the activity of adenylate cyclase in response to glucagon and guanylnucleotides.

2-Acetylaminofluorene↗
PubMed1991

Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis.

Crude plasma membranes were prepared from the liver of control rats or of rats submitted to an initiation by diethyl-nitrosamine and selection with 2-acetylaminofluorene and carbon tetrachloride (group IS) or of rats submitted to an initiation-selection protocol followed by a promotion with phenobarbital (group IS PB). In control rats, the diterpene forskolin and glucagon stimulated the activity of adenylate cyclase 6- to 7-fold. Guanosine-5'-O-(2-thiodiphosphate) (GDP beta S) inhibited the stimulation by both agents and the non-hydrolyzable GTP analog, guanyl-5'-yl-imidodiphosphate [Gpp(NH)p], potentiated the stimulatory effect of glucagon. In rats of the IS group, no modification of the activity of the liver cyclase was found, except for an increased response to forskolin and glucagon. In the IS PB group, for the rats without tumor, the only effect of adding phenobarbital was to increase the sensitivity of the cyclase to forskolin. In tumoral tissue, the response to Gpp(NH)p, glucagon and forskolin were increased when compared to the surrounding tissue. In contrast to the surrounding tissue, GDP beta S potentiated the stimulatory effect of forskolin. When the affinity of the glucagon receptors for the hormone was measured in binding experiments, no difference was observed among the rats of the various groups, except for a higher affinity in tumoral tissue. Similarly, GTP inhibited the binding of glucagon with the same potency in each group. It is concluded that during hepatocarcinogenesis, the sensitivity of the adenylate cyclase towards glucagon increases secondarily to a better binding of the hormone to its receptor and to an impairment of the inhibitory regulatory site.

Adenylyl Cyclases↗
PubMed1991

[Long-term venous access].

The authors summarize the technique of placement of long term venous access systems. The complications encountered are described. As an example, the experience of the Institut Jules Bordet in this field is presented.

Adult↗
PubMed1991

Hepatic artery ligation with and without portal infusion of 5-FU. A randomized study in patients with unresectable liver metastases from colorectal carcinoma. The E.O.R.T.C. Gastrointestinal Cancer Cooperative Group (G.I. Group).

The aim of this multicentric prospective randomized clinical trial was to study the efficacy of hepatic artery ligation (HAL) with and without portal infusion (PI) of 5-FU in patients with liver metastasis of colorectal origin. Seventy-four patients were randomized. Sixty-seven were fully evaluable. Thirty-five patients were eligible in the HAL + PI of 5-FU group and 32 in the HAL alone group. The 5-FU infusion had to be discontinued for technical reasons in 13 patients. Complications of HAL were relatively high, including four hepatic failures (WHO grading greater than 2). Side effects of chemotherapy were limited. Five patients out of 30 had a partial response (WHO criteria) and one patient had a complete response in the group treated by HAL and PI of 5-FU. Only one patient had a partial response in the HAL alone group. Median survival for both groups was 12 months. Median time to progression for both groups was 6 months. This study did not show any advantage of delivery using the portal route in addition to hepatic artery ligation in terms of progression nor in survival of patients.

Adenocarcinoma↗
PubMed1990

Characterization of human colorectal mucosa, polyps, and cancers by means of computerized morphonuclear image analyses.

Fifty-eight Feulgen-stained imprint smears from freshly resected colorectal tissue were analyzed by means of a SAMBA 200 cell image processor to establish a quantitative grading of their evolution from normal to malignant mucosa on the basis of 15 morphonuclear parameters relative to morphometry (nuclear size), densitometry (DNA content), and texture (chromatin pattern). The colorectal samples belonged to six groups: normal mucosa from patients without (Group 1) or with (Group 2) colorectal cancer, adenomas (Group 3), and cancers corresponding to the three stages of the Dukes' classification (Groups 4 to 6). Results indicated that analysis of the morphonuclear parameters computed on 250 to 300 nuclei/cases objectively and quantitatively showed the adenoma-cancer sequence. This need for only a small number of nuclei to assess a highly efficient analysis created a preoperative investigative tool using cytologic smears during endoscopy. The authors also made preliminary data banks for objective and reproducible grading of unknown cases by comparisons (discriminant analyses) with their contents. This approach must be validated prospectively on a large series of cases to furnish a system for colorectal malignancy diagnosis.

Cell Nucleus↗
PubMed1990

[Implanted venous access system in oncology. Review of 296 cases].

The authors present their experience of the use of a totally implanted vascular access system, at the Institut Jules Bordet. Between 1983 and 1988, 296 catheters were implanted in 289 patients. The average venous access period using this system was 232 days. The complication rate was only 0.36/1000 days of venous access. The totally implanted vascular system can provide a comfortable and reliable method of venous access in patients requiring prolonged intravenous chemotherapy.

Adolescent↗
PubMed1989

Adjuvant therapy of poor prognosis colon cancer with levamisole: results of an EORTC double-blind randomized clinical trial.

From 1978 to 1985, 297 patients were entered in a double-blind randomized trial comparing levamisole to placebo as adjuvant therapy of Dukes' C carcinoma of the colon. Therapy consisted of from two to five tablets of 50 mg levamisole (or placebo) twice a week, depending on bodyweight for 1 year. Levamisole was generally well tolerated, with only four reversible cases of agranulocytosis reported among 129 patients. The trial failed to show a benefit of levamisole on disease-free survival (P = 0.53) or on survival (P = 0.35). There was no difference between the two treatment groups in terms of number of disease relapses, sites of relapse, or time to relapse. The proportion of patients still alive at 5 years was 51 per cent (standard error, 5.5 per cent) in the levamisole group versus 39 per cent (standard error, 5.4 per cent) in the placebo group.

Adjuvants, Immunologic↗
PubMed1989

Local excision as conservative treatment for small rectal cancer.

Twenty patients with small rectal cancer, characterized by a well differentiated tumour localized within 10 cm of the anal margin, and by penetration limited to the submucosa or to the muscular layer, were treated by local excision. Four of them, who presented with a deep tumour invasion in the rectal wall, also received adjuvant radiation therapy. Our experience proves the reliability of the selection criteria for patients who may benefit from this procedure. They all stand a fair chance of cure and the quality of their lives will improve because local tumour excision avoids anal sphincter resection. Two patients had local recurrences and had to undergo further curative local excision. The two who died from their tumours and who had distant metastases were unsuitable for both local resection and other therapeutic procedure. Finally, there was no postoperative morbidity.

Adult↗
PubMed1989

Prolonged venous access in cancer patients.

One hundred and forty-eight Hickman-Broviac (HB) catheters and 299 Port-a-Cath R (PAC) were inserted over the past 5 years at the Institut Jules Bordet. The HB catheter was associated with a complication rate of 4.1/1000 days of access, of which infections were the most common, leading to catheter removal in 22% of patients. The average PAC remained in situ for 232.9 (range 1-1298) days; the complication rate was only 0.45/1000 days of access. The Hickman-Broviac catheter and the totally implanted port Port-a-Cath achieve safe and reliable venous access in cancer patients.

Adolescent↗
PubMed1989

Adjuvant radiotherapy and chemotherapy in resectable gastric cancer. A randomized trial of the gastro-intestinal tract cancer cooperative group of the EORTC.

One hundred and fifteen patients with curative and palliative surgery for gastric cancer were randomized to receive radiotherapy alone (1) or in combination with short-term (ST) 5-FU (2), long-term (LT) 5-FU (3), ST and LT 5-FU (4). The ST 5-FU was given at a daily dose of 575 mg/m2, every 4-6 h during the first 4 days of treatment before starting irradiation. The LT 5-FU was given at a dosage of 750 mg/m2 every 2 weeks for 18 months or until progression. The median survival times for treatment 1 to 4 was respectively 12, 10, 15 and 18 months. There was a statistically significant overall difference between the four treatments (P = 0.041). However, when the comparisons were adjusted for the most significant prognostic factors, the difference in survival disappeared. Moreover, no difference was found between treatments in terms of time progression. Nevertheless, among 22 patients with residual tumour, the three who were still alive without disease progression (with survivals of 19+, 49+ and 90+ months at the time of this analysis) had been treated with radiotherapy combined with ST and LT 5-FU.

Adenocarcinoma↗
PubMed1989

Controversies in the management of gastrointestinal non-Hodgkin's lymphomas.

Although more than a thousand GI non-Hodgkin's lymphomas have been reported, the literature does not indicate a clear optimal therapeutic approach. This is primarily due to histological confusion and to the absence of uniform staging procedures and therapeutic modalities. This overview attempts to summarize controversies in the multidisciplinary approach to GI non-Hodgkin's lymphomas and to introduce a European multicentric prospective randomized study for the treatment of this rare disease.

Combined Modality Therapy↗
PubMed1988

Intraperitoneal chemotherapy with cisplatin and melphalan.

Cisplatin and melphalan given ip exert a synergistic therapeutic effect against ascitic P388 leukemia in mice and have different dose-limiting toxic effects as well as favorable pharmacokinetic characteristics in ip phase I studies. We gave a total of 98 courses of cisplatin (escalated from 40 to 120 mg/m2) and melphalan (escalated from 12 to 30 mg/m2) to 30 patients with ip tumors, most of whom had residual ovarian cancer following iv cisplatin-containing regimens. Treatment was delivered in 2 L of 0.9% NaCl through a Tenckhoff catheter with or without a Port-a-Cath system every 28 days for one to nine cycles. Myelosuppression was dose-related and leukopenia was dose-limiting. The maximum tolerated dose was 120 mg of cisplatin/m2 and 20 mg of melphalan/m2. With the exception of treatment-induced nausea and vomiting, nonhematologic toxic effects were mild and no (or very little) local toxicity occurred. Pharmacokinetic analyses showed that the areas under the peritoneal concentration versus time curve averaged 16-fold and 17-fold more than the area under the plasma curve for cisplatin and melphalan, respectively. Objective responses were documented by third-look laparotomy in ovarian cancer patients with minimal (less than 2 cm) residual disease.

Adult↗
PubMed1988

Hepatic artery ligation or embolization and locoregional chemotherapy of liver metastases from colorectal cancer.

If liver metastases are diffuse and spread out in the two lobes of the liver, the question remains as to which treatment should be given. Experimental studies showed that when a tumor grows, its vascular pattern becomes mainly arterial. However, if the tumor is still increasing, its center becomes progressively necrotic. After hepatic artery ligation the blood flow of the liver metastases decreases by 90% in the tumor but depriving the arterial circulation of the tumor is not sufficient to achieve a complete cure since the portal blood supply always saves a rim of neoplastic cells around the necrotic area. On the other hand, local infusion of chemotherapy for liver metastases by the arterial route showed a response rate varying between 34 and 70% and the median survival varying between 8 and 17 months. When FUdR chemotherapy was administered using a totally implantable drug infusion pump no improvement in the survival was observed and moreover a high level of toxicity was described including hepatitis and biliary sclerosis. A combined therapy seems a rational approach to treat tumor cells in surviving to the arterial ligation by perfusing the liver with cytotoxic drugs via the portal vein. Taylor's study was very promising but a randomized phase III clinical trial led by the gastrointestinal cancer group of the EORTC with the aim to evaluate the effectiveness of hepatic artery ligation and portal infusion of 5-FU did not show any difference in the survival of the treated patients when compared with patients treated by hepatic artery ligation alone. 77 patients were registered. Data are now available for 55 patients, respectively 30 and 25 patients in the treated group and in the control group. In both groups the median time to progression was 6 months and the median survival time was 12 months. 20% of the patients treated by hepatic artery ligation and portal chemotherapy had a response, one of them with a complete response, 5 with partial response and 14 patients without significant change in the size of their metastases. On the contrary, in the group treated by hepatic artery ligation alone, only one patient had a partial response with 13 patients having no change in the size of their metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Enhanced hepatic adenylate cyclase activity in rats with portacaval shunt.

Male Wistar rats were submitted to a portacaval anastomosis (PCA). Control rats were sham operated and pair fed. After 20 days, PCA led to a decrease in liver weight (-40%) and fasting blood glucose (-35%) and to an increase in fasting glucagonemia (+65%). The in vitro response of adenylate cyclase in hepatic membranes to GTP, Gpp(NH)p, fluoride, and forskolin (in the absence of GTP), and to glucagon (in the presence of GTP) was greater in PCA rats than in controls (by 30-54%) whereas the response to L-isoproterenol (in the presence of GTP) was only slightly increased (by 8%) and that to vasoactive intestinal peptide (in the presence of GTP) was similar in both groups of rats. The binding of [125I]glucagon and [125I]VIP to liver membranes did not differ in both groups of animals. It is concluded that the hepatic adenylate cyclase system from PCA rats responded better to stimuli involving efficiently the guanyl nucleotide stimulatory site Ns. This implies that the fasting hypoglycemia observed in these animals, in spite of the hyperglucagonemia, was due to either the refractoriness of a step distal to adenylate cyclase activation or to limited glucose production by an atrophic liver.

Adenylyl Cyclases↗