Chun-Jean Lee

Genetic polymorphisms of XRCC1 and risk of the esophageal cancer.

A variety of environmental factors were identified to be associated with the risk of esophageal cancer. The variation in capacity of DNA repair might influence environmental chemical‐associated carcinogenesis. We hypothesized that the polymorphic XRCC1 genes might modify cancer susceptibility of the esophagus. To investigate the effect of XRCC1 genetic polymorphisms on codons 194, 280 and 399, we evaluated data from 105 patients of esophageal squamous cell carcinoma and 264 healthy controls, matching with age (±3 years), gender and ethnicity. The distribution of the 3 genotypes were not significantly different among patients and controls. However, among alcohol drinkers, the XRCC1399 Arg/Arg genotype was more frequently found in patients with esophageal cancer. After adjustment with other environmental confounders, the OR for the genotype of XRCC1399 Arg/Arg was 2.78 (95% CI =1.15–6.67) as compared with the XRCC1399 Arg/Gln and XRCC1399 Gln/Gln genotypes in the alcohol drinkers. Similar trends were observed among cigarette smokers and areca chewers. However, they did not reach a statistical significance. Our findings suggest that the polymorphic XRCC1 genes might modify the risk of alcohol‐associated esophageal cancers.

Genetic polymorphisms of p53 and GSTP1,but not NAT2,are associated with susceptibility to squamous-cell carcinoma of the esophagus.

The interaction of genetic and environmental factors can determine an individuals susceptibility to various cancers. We present a hospital‐based case‐control study, which included 90 patients of esophageal squamous‐cell carcinoma (ESCC) and 254 healthy people in Taiwan, to investigate the effects of genetic polymorphisms of p53, GSTP1 and NAT2 on the risk of ESCC. Polymorphisms of p53, NAT2 and GSTP1 were determined by PCR‐RFLP. The codon 72 p53 Pro allele was more frequently found in ESCC patients [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.04–3.35 for Arg/Pro genotype and OR 2.56, 95% CI 1.29–5.08 for Pro/Pro genotype]. In cigarette smokers, the frequency of GSTP1 Ile/Ile genotype was higher in ESCC patients (OR 2.8, 95% CI 1.4–5.7). Among alcohol drinkers, borderline significance was also found for GSTP1 Ile/Ile genotype (OR 2.0, 95% CI 0.9–4.4). Results were not similar for the NAT2 genetic polymorphism. Using logistic analyses, we found that individuals with p53 Pro/Pro genotype had a significantly higher risk of developing ESCC than those with Arg/Arg genotype (OR 2.3, 95% CI 1.1–5.1), after adjusting for other significant environmental risk factors. This result remained similar (OR 2.2, 95% CI 1.0–4.8 for p53 Pro/Pro vs. Arg/Arg), even after further adjustment for NAT2 and GSTP1 polymorphisms. The codon 72 p53 Pro/Pro genotype in the general population and GSTP1 Ile/Ile in cigarette smokers may predict a higher risk of developing ESCC. Int. J. Cancer 89:458–464, 2000.

Association of GSTP1 Polymorphism and Survival for Esophageal Cancer

Purpose: Activity of glutathione S-transferase (GST) is associated with detoxification of xenobiotics and the maintenance of cell viability. Genetically variant GSTs produce different enzymatic activities. The clinical significance of this variation is still puzzling. We investigated whether genetic polymorphisms of GST including GSTP1, GSTM1, and GSTT1 affect survival among esophageal cancer patients. Experimental Design: From 1996 to 2002, 233 patients with pathologically proven esophageal cancer were recruited from the Department of Surgery, National Taiwan University Hospital. GST genotypes, including GSTT1, GSTM1, and GSTP1, were determined by PCR or PCR-RFLP. The influence of the genetic polymorphisms on patient survival was estimated using the method of Kaplan-Meier survival function and Cox proportional hazards models. Results: The mean survival times (months) of the GSTP1 Ile/Ile, Ile/Val, and Val/Val were 11, 10, and 7, respectively (P < 0.05). The more the patients carried GSTP1 variant Val alleles, the poorer the survival rate (adjusted hazard ratio, 1.36; 95% confidence interval, 1.01-1.84; Ptrend = 0.045). In contrast, no association of GSTT1 or GSTM1 genotypes with survival rate was noted. Conclusion: The presence of the GSTP1 variant allele (Val) is associated with a poorer prognosis of esophageal cancer.

Adjuvant immunotherapy with intrapleural Streptococcus pyogenes (OK-432) in lung cancer patients after resection

A prospective randomized study to evaluate the effect of adjuvant intrapleural OK-432 immunotherapy after resection of lung tumor was conducted in 93 patients with primary lung cancer. Among them, 46 patients had had intrapleural OK-432 injection, 47 had not. In the meantime, serial measurements of serum immunosuppressive acidic protein, of serum interleukin-2 receptor and of the sub-population of the peripheral blood cells and lymphocytes were performed in all these patients. Patient characteristics in these two groups (sex, age, histological type, pathological stage, type of operation, and performance status) were compatible. The results showed that adjuvant intrapleural OK-432 injection after resection had no beneficial effect on a patients survival time. Patients who received intrapleural OK-432, had an increase in blood leukocytes, granulocytes and monocytes and serum immunosuppressive acidic protein level. But the cell numbers of total T cells, suppressor/cytoxic cells, helper/inducer cells and natural killer cells of peripheral blood were decreased in the OK-432 positive group. Over half of the patients had transient 1- or 2-day febrile reactions after intrapleural OK-432 injection. It was concluded that neither clinical observation nor immunological monitoring of peripheral blood could demonstrate a beneficial effect from intrapleural OK-432 immunotherapy after complete resection of the tumor.

Rapid detection of human HLA transgenes in pigs by fluorescence in situ hybridization (FISH) for adjuvant study of human xenotransplantation

Abstract:  Objectives:  We have recently generated several lines of transgenic pigs for HLA‐DP and ‐DQ to elucidate the role of HLA‐II antigens in the modulation of cell‐mediated rejection of xenotransplantation. Using fluorescence in situ hybridization (FISH) analysis, the aim of this study was to determine integration sites and to test zygosity of these transgenes in the piglets after cross mating.

Enduring effects of thoracoscopic Heller myotomy for treating achalasia.

Minimal invasive surgery using a laparoscopic or thoracoscopic approach for cardiomyotomy (Heller myotomy) has become a widely accepted procedure to treat achalasia of the esophagus. In this study, we evaluated the long-term results of Heller myotomy achieved by performing video-assisted thoracic surgery (VATS). We recruited patients with achalasia who had undergone VATS for Heller myotomy from 1991 to 2000 at the National Taiwan University Hospital. The myotomy was performed 6 cm above and 1 cm below the gastroesophageal junction. No fundoplication was performed during the procedure. The symptom score, which included dysphagia, regurgitation, and chest pain, was evaluated before and after surgery. Body weight was also recorded before and after surgery. The cases of 14 patients (4 men, 10 women) were studied. The mean patient age was 41.8 ± 4.9 years. No postoperative mortality or morbidity was found in these patients. The follow-up duration was 56 ± 7.17 months. The dysphasia score improved from 3.0 preoperatively to 0.79 ± 0.30 postoperatively (p = 0.001). The reflux score improved from 2.64 ± 0.17 preoperatively to 0.50 ± 0.20 postoperatively (p = 0.001). All the improvements were still in place at the time of the most recent follow-up examinations. Heller myotomy to treat achalasia using a thoracoscopic approach can provide satisfactory long-term results.

Comparison of Histidine-Tryptophan-Ketoglutarate and Euro-Collins Solutions for Lung preservation Using the Minipig In Situ Warm Ischemia Model

BACKGROUND AND PURPOSE Reperfusion injury remains a common problem in lung transplantation. This study compared the effect of lung preservation with histidine-tryptophan-ketoglutarate (HTK), a relatively low potassium solution, and Euro-Collins (EC) solution by using a minipig in situ model of warm ischemia. METHODS The left lungs of 5 minipigs were selectively flushed with EC solution. HTK was used for flush perfusion in 6 other minipigs. After 60 minutes of warm ischemia, the left lungs were reperfused. Hemodynamics, aerodynamics, and arterial blood gas were measured after the blood flow and ventilation of the contralateral lungs were temporally blocked. Bronchoalveolar lavage fluid (BALF) analysis, lung wet-to-dry weight ratio (W/D ratio) and histological analysis were done before perfusion (right lung) and 2 hours after reperfusion (left lung). RESULTS This in situ model of warm ischemia induced significantly increased pulmonary arterial pressure, pulmonary vascular resistance, BALF albumin contents and neutrophil counts, histological injury score, lung W/D ratio and tissue myeloperoxidase assay. The HTK perfusion group had a significantly lower degree of lung injury than the EC perfusion group. CONCLUSIONS Lung preservation with HTK solution resulted in better lung function after reperfusion than preservation by EC solution in this minipig model.

The Association of GSTT1 Genetic Polymorphism with the Risk of Esophageal Cancer-Interactive with Environmental Exposure

In this study, we investigated the association of the genetic polymorphisms of CYPlAl, CYP2E1, GSTMl and GSTTl with the risk of esophageal cancer in Taiwan. We recruited 105 cases of esophageal squamous cell carcinoma and 266 persons of healthy controls during 1996-1999. The genotypes of the xenobiotic metabolizing enzymes were determined by PCR or PCR-RFLP. There was no significant difference in distribution of these genotypes between the patients and controls. However, among the cigarette smokers, GSTTl null genotype was found to associate a higher risk of esophageal cancer, after adjustment with other environmental confounders (OR: 2.44;95% CI:1.17-5.08). Our results revealed that the GSTTl genetic polymorphism might interact with cigarette smoke to modulate the risk of esophageal cancer in Taiwan.