GENETIC DELETION OF DETOXIFIC ENZYME GSTM1 AND GSTTI AS A HOST SUSCEPTIBLE FACTOR FOR NASOPHARYNGEAL CARCINOMA

Objective: To study the gene polymorphisms of GSTT1 and GSTM1 in nasopharyngeal carcinoma (NPC) patients and controls in an incidental area to evaluate the relationship between specific genotype and genotype combinations of these polymorphisms with the risk of NPC. Methods: Cases and controls all came from the Southwestern Guangxi. DNAs were extracted from their WBC. PCR technique was used to calculate the deletion rate of the two detoxific enzyme genes. Results: In this high risk area of NPC, the residents had high level deletion rates of 47.4% (64/135) Ml and T1 40.7% (55/135). The deletion rates were even higher in NPC patients, 61.5% (56/91) for Ml and 59.3% (54/91) for T1 respectively. There were statistical significances compared with control,P<0.05 andP<0.01 for Ml and T1 respectively. The difference was more significant in terms of combined Ml and T1 deletion between patients and controlsx ²=12.533,P=0.002. Conclusion: The combined deletion of detoxific enzyme genes GSTM1 and GSTT1 may be an important genetic susceptible factor for NPC in Guangxi. Biography: DENG Zhuo-lin (1929-), male, professor of pathology, Guangxi Medical University, majors in tumor pathology. E-mail :zhuolin@hotmail.com     

A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer.

PURPOSE: Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease. PATIENTS AND METHODS: Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX). The primary end point was time to progression, with secondary end points of response rate, survival time, and toxicity. RESULTS: A total of 795 patients were randomly assigned between May 1999 and April 2001. A median time to progression of 8.7 months, response rate of 45%, and median survival time of 19.5 months were observed for FOLFOX. These results were significantly superior to those observed for IFL for all end points (6.9 months, 31%, and 15.0 months, respectively) or for IROX (6.5 months, 35%, and 17.4 months, respectively) for time to progression and response. The FOLFOX regimen had significantly lower rates of severe nausea, vomiting, diarrhea, febrile neutropenia, and dehydration. Sensory neuropathy and neutropenia were more common with the regimens containing oxaliplatin. CONCLUSION: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe. It should be considered as a standard therapy for patients with advanced colorectal cancer.     

Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 given as a 1-hour intravenous infusion in patients with advanced solid tumors.

PURPOSE: BMS-214662 is a nonsedating benzodiazepine derivative that exhibits broad spectrum cytotoxicity against human solid tumor cell lines and potently inhibits farnesylation of the H-ras and K-ras oncogenic proteins. This report describes the initial Phase I clinical trial of the compound. The main objective of the study was to determine the dose-limiting toxicities and the maximum tolerated dose of BMS-214662 when administered as a single dose i.v. over 1 h every 21 days to patients with advanced solid tumors. EXPERIMENTAL DESIGN: Patients with advanced solid tumors and adequate organ function were eligible for the study. The dose was escalated according to a modified Fibonacci schedule after evaluating groups of at least three patients for toxicity during the first cycle of therapy at each dose level. Pharmacokinetic and pharmacodynamic studies were performed after administration of the two initial doses. RESULTS: The dose of BMS-214662 was escalated from 36 to 225 mg/m(2) through 5 intermediate dose levels in a total of 44 patients. Dose-limiting toxicities occurred in 3 of the 13 (23%) patients during the first cycle of treatment with 225 mg/m(2), consisting of grade 3 nausea/vomiting in 2 patients and grade 3 diarrhea in another patient. In addition, four of these patients experienced reversible grade 3 transaminitis, which was not considered to be dose-limiting. At the recommended dose for Phase II studies, 200 mg/m(2), the most common side effects were reversible transaminitis, nausea, and vomiting. Although there were no objective responses, one patient with pancreatic cancer continues to receive treatment more than 3.5 years after entering the study. BMS-214662 exhibited linear pharmacokinetics and had a mean biological half-life of 1.55 +/- 0.27 h and a total body clearance of 21.8 +/- 10.8 liters/h/m(2), with a low apparent volume of distribution at steady state (31.5 +/- 12.9 liters/m(2)). In patients treated with the recommended Phase II dose, the mean maximum plasma concentration of the drug was 6.57 +/- 2.94 microg/ml, and farnesyltransferase activity in peripheral blood mononuclear cells decreased to a nadir of 10.5 +/- 6.4% of baseline at the end of the infusion but fully recovered within 24 h. CONCLUSIONS: BMS-214662 can be delivered safely as a single 1-h i.v. infusion at a dose that results in pronounced inhibition of farnesyltransferase activity in peripheral blood mononuclear cells. However, the duration of enzyme inhibition was transient, recovering in parallel with the decline in plasma concentrations of this rapidly eliminated drug. Because indications of anticancer activity were observed in several patients, further optimization of the administration schedule for this promising new compound is warranted.     

Lanzoprazole promotes gastric carcinogenesis in rats with duodenogastric reflux

Background Duodenogastric reflux is known to cause an increased frequency of cancer in the glandular portion of the stomach in rats. Furthermore, it is debated whether inhibition of gastric acid secretion may promote gastric carcinogenesis. In the present study we examined the combined effect of gastroduodenal reflux and acid inhibition with respect to the development of gastric carcinoma in the rat.Methods Following the construction of a gastrojejunostomy in male Wistar rats, half of them were given the proton pump inhibitor lanzoprazole for 1 year. The rats were then killed and the pH in the stomach and gastrin in blood were measured. The stomach was examined macroscopically as well as histologically.Results Gastrin levels at autopsy were significantly increased in treated rats compared to the control group, confirming an effect of lanzoprazole on gastric acid secretion. Body weight was significantly reduced in the treated rats. Thirty of 79 rats developed gastric cancer, and they were all adenocarcinomas of the Lauren intestinal type. Gastric cancers occurred significantly more often in lanzoprazole-treated rats (50%) compared with controls (27%).Conclusion Lanzoprazole given orally enhances the carcinogenic effect of duodenogastric reflux in rats.     

The endoscopic evaluation of gastritis,gastric remnant residue,and the incidence of secondary cancer after pylorus-preserving and transverse gastrectomies

Background Pylorus-preserving gastrectomy (PPG) and transverse gastrectomy (TrG) have been accepted as function-preserving procedures for node-negative early gastric cancer. It is believed that a better quality of life is guaranteed after PPG or TrG compared to that after distal subtotal gastrectomy (DSG) with Billroth type-I reconstruction. However, objective evaluations of the gastric remnant following gastrectomy have not been widely reported, and the real advantages and disadvantages of PPG or TrG over DSG remain unclear. Moreover, the risk of secondary cancer after PPG or TrG is uncertain.Methods Between 1991 and 2000, 834 DSGs were carried out in our institute for preoperatively diagnosed patients with early gastric cancer. The degree of residual gastritis and the amount of diet residue in the gastric remnant were evaluated by annual gastrointestinal endoscopic investigations prospectively for 72 patients after PPG, 95 patients after TrG, and 60 patients after DSG. These analyses were performed using the RGB classification (residue, gastritis, bile). The incidence of disease greater than or equal to grade 2 was calculated, and the time trends of the incidence for each procedure were also studied for 3 years after gastrectomy. In addition, secondary cancer cases in the gastric remnant mucosa were checked for each procedure during this period, and the incidence of secondary cancer after each operation was calculated.Results The incidence of gastritis, of grade 2 or more, found in the gastric remnant was significantly lower after PPG (1.4%) and TrG (2.1%) than after DSG (43.3%). However, the incidence of moderate or greater residue in the gastric remnant, grade 2 or more, was significantly higher after PPG (45.8%) and TrG (40.0%) than after DSG (11.7%). The analysis of time trends of gastritis and diet residue reflected the significant advantage or disadvantage for each procedure 1 year after surgery. The analysis also included these factors without consideration of elapsed time following surgery. Two patients after PPG (2.8%) and three patients after TrG (3.2%) developed secondary cancer in the gastric remnant. No DSG-treated patient showed new cancer genesis in the remaining stomach.Conclusion PPG and TrG have the advantage over DSG in preventing postoperative gastritis in the gastric remnant. On the other hand, moderate or greater diet residue in the gastric remnant is more common after PPG or TrG than after DSG. For the risk of carcinogenesis in the remnant gastric mucosa, we could not conclude that there was any apparent difference between these range-limited gastrectomies and conventional DSG. Further study is necessary to determine the significant advantages and disadvantages of using PPG or TrG.     

Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer

Background Despite curative resection, 50%–90% of gastric cancer patients die of disease relapse. Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities, more recent studies have not been able to define the standard treatment for advanced gastric cancer. The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG (bacille Calmette-Guérin) and FAM (5-fluorouracil, adriamycin, mitomycin C) chemotherapy on the survival of patients with locally advanced resectable gastric cancer.Methods A total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were randomly assigned to three treatment groups: BCG + FAM (immunochemotherapy), FAM (chemotherapy), and control (surgery only). Treatment was continued for 2 years or until death. Further postsurgical follow up was carried on for up to 10 years.Results Overall 10-year survival was 47.1% for the immunochemotherapy group (P < 0.037 vs FAM and P < 0.0006 vs control), 30% for the chemotherapy group (vs control, NS), and 15.2% for the control group. In patients with pT2/T3 primary tumors, 10-year survival was 55.3% for BCG + FAM vs 28.2% for FAM (P < 0.01) and 14.6% for the control group (P < 0.00018). BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer. Immunochemotherapy was well tolerated.Conclusion This study, based on a limited number of patients, indicates that adjuvant immunochemotherapy (BCG + FAM) may prolong the survival of gastric cancer patients after curative gastrectomy; in particular, in patients with pT2/T3 tumors and intestinal-type primary tumors. There was no survival benefit from FAM adjuvant chemotherapy.     

Prostatosis treated with acupuncture and herbal medicine

According to differentiation of symptoms and signs, prostatosis was divided into pattern of dampness and heat in the lower energizer, pattern of qi stagnation and blood stasis, pattern of deficiency and cold in the lower abdomen, and pattern of qi deficiency and kidney deficiency. Prostatosis were treated mainly by acupuncture, plus moxibustion and Chinese medicine, and the effect was good. Author: Zhao Chang-quan (1949-), male, junior consultant doctor Translator: Huang Guo-qi     

Acupuncture treatment of 32 cases of lumbar intervertebral disc protrusion

Yaoyangguan (GV 3), Shiqizhui (Ex-B 8) and Yanglingquan (GB 34) were selected as main points and a three-part needle insertion technique was used to treat 32 cases of lumbar intervertebral disc protrusion. The curative rate was 96.9%. Deep puncture is the key to the treatment. Author: Chen Feng(1962-), male, junior consultant doctor Translator: Wang Si-you     

Kneading manipulation

In the performance of rubbing manipulation, because of the fingers comparatively light vertical pressure and large-range circular movement, the palm and fingers cannot adhere to the patient's skin, and the relative friction movement.