Diagnostic role of serum interleukin-18 in gastric cancer patients

AIM: To determine the current status in various aspects of gastric cancer patients and to find out the clinical correlation with prognostic role of serum interleukins in Thai patients. METHODS: Sixty-eight patients were enrolled in this study at King Chulalongkorn Memorial Hospital during April 2003 to May 2005. Gastric cancer was histologically proven in 51 patients and gastric ulcer in 17 patients. Serum IL-6, IL-10, IL-12, and IL-18 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were 26 males (55.32%) and 21 females (44.68%) with their age ranging from 33 to 85 years (mean age 64.49±13.83 years). The common presentations were weight loss (41.2%), dyspepsia (39.2%), and upper gastrointestinal bleeding (15.7%). A total of 35.3% gastric cancer patients and 6.3% of gastric ulcer patients were smokers (P = 0.029). Moreover, 32.4% of gastric cancer patients and 6.3% of gastric ulcer patients were alcoholic drinkers (P = 0.044). Lesion location was pyloric-antrum in 39.4%, gastric body in 39.4%, upper stomach in 12.2% and entire stomach in 6.1% of the patients. H pylori infection was detected in 44.4%. The poorly-differentiated adenocarcinoma was the most common pathologic finding (60.7%). Surgical treatment was performed in 44.1% patients (total gastrectomy in 5.9%, subtotal gastrectomy in 32.4% and palliative bypass surgery in 5.9%). Systemic chemotherapy was given as an adjuvant therapy in 8.8% patients. Carcinomatosis peritoneii were found in 18.8% patients. The mean survival time was 13.03±9.75 mo. The IL-18 level in gastric cancer patient group (58.54±43.96 pg/mL) was significantly higher than that in gastric ulcer patient group (30.84±11.18 pg/mL) (P = 0.0001) (95% CI was 42.20, 13.19). The cut point of IL-18 for diagnosis of gastric cancer was 40 pg/mL, the positive predictive value was 92.31%. The IL-6 level in gastric cancer patients with distant metastasis (20.21±9.37 pg/mL) was significantly higher than that in those with no metastasis (10.13±7.83 pg/mL) (P = 0.037) (95% CI was 19.51, 0.65). The role of IL-10 and IL-12 levels in gastric cancer patients was to provide data with no significant difference. CONCLUSION: These findings demonstrate that serum IL-6 and IL-18, but not IL-10 and IL-12 levels may be the useful biological markers of clinical correlation and prognostic factor in patients with gastric cancer. Moreover, IL-18 could serve as a diagnostic marker for gastric cancer with a high positive predictive value.     

SEN virus infection in patients with chronic liver disease and hepatocellular carcinoma in Thailand

Background: SEN virus (SENV) has been recently identified as a candidate agent of non-A-E hepatitis virus. However, the exact role of this novel virus in the pathogenesis of chronic liver disease, including chronic hepatitis and cirrhosis, and the development of hepatocellular carcinoma (HCC) remains to be established. Methods: Using seminested polymerase chain reaction (PCR) amplification to detect SENV-D and SENV-H strains in serum, we investigated SENV infection in voluntary blood donors and in patients with chronic liver disease and HCC. Results: SENV was detected in 5 of 100 blood donors (5%), in 15 of 60 patients with chronic liver disease (25%), and in 25 of 60 patients with HCC (42%). The prevalence of SENV in patients with HCC was higher than that in patients with chronic liver disease (P = 0.05) and in blood donors (P < 0.001). An age-specific prevalence of SENV was found at high levels among individuals aged 21–40 years, but was not detected among individuals in the lower age group. No differences between SENV-infected and non-infected patients were demonstrated with respect to demographic data, assumed source of infection, biochemical abnormalities, and severity of chronic liver disease and HCC. Moreover, SENV infection had no apparent effect on the survival of patients with HCC. Conclusions: Our data suggest that SENV infection is frequent among patients with chronic liver disease and HCC. However, pathogenic effects associated with SENV infection in chronic liver disease and HCC need further investigation. Received: April 4, 2002 / Accepted: July 26, 2002 Acknowledgments. We would like to express our gratitude to the entire staff of the Viral Hepatitis Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, for their tireless effort in this research project. We also would like to thank the Center of Excellence Fund, Rachadaphisek Somphot Endowment, Chulalongkorn University, and the Thailand Research Fund, Senior Research Scholar, for supporting this research. Reprint requests to: Y. Poovorawan     

A case–control study on sequence variations in the enhancer II/core promoter/precore and X genes of hepatitis B virus in patients with hepatocellular carcinoma

Purpose  

To evaluate the sequence variations in the enhancer II (EnhII)/basal core promotor (BCP)/precore (PC) and X genes of hepatitis B virus (HBV) in Thai patients with hepatocellular carcinoma (HCC) by conducting a cross-sectional case–control study.     

Seroprevalence of Antibodies to Measles, Mumps, and Rubella among Thai Population: Evaluation of Measles/MMR Immunization Programme

Stored serum specimens, from four regions of Thailand, of healthy children attending well baby clinics and of healthy people with acute illnesses visiting outpatient clinics were randomly sampled and tested for IgG antibody to measles, mumps, and rubella (MMR). The immunity patterns of rubella and mumps fitted well with the history of rubella and MMR vaccination, seroprotective rates being over 85% among those aged over seven years. A high proportion of younger children acquired the infection before the age of vaccination. MMR vaccination should preferably be given to children at an earlier age. For measles, 73% seroprotective rates among children, aged 8-14 years, who should have received two doses of measles/MMR vaccine, were lower than expected. This finding was consistent with the age-group reported in outbreaks of measles in Thailand. The apparent ineffectiveness (in relation to measles) of MMR immunization of 1^st grade students warrants further studies.Key words: Antibodies, Immunization, Measles, Measles vaccine, Mumps, MMR vaccine, Rubella, Seroepidemiologic studies, Seroprevalence, Vaccination, Thailand     

Detection of influenza virus types A and B and type A subtypes (H1, H3, and H5) by multiplex polymerase chain reaction

Infections with influenza virus type A and B present serious public health problems on a global scale. However, only influenza A virus has been reported to cause fatal pandemic in many species. To provide suitable clinical management and prevent further virus transmission, efficient and effective clinical diagnosis is essential. Therefore, we developed multiplex PCR assays for detecting influenza types A and B and the subtypes of influenza A virus (H1, H3 and H5). Upon performing multiplex PCR assays with type-specific primer sets, the clearly distinguishable products representing influenza A and B virus were separated by agarose gel electrophoresis. In addition, the subtypes of influenza A virus (H1, H3 and H5), which are most common in humans, can be readily distinguished by PCR with subtype-specific primer sets, yielding PCR products of different sizes depending on which subtype has been amplified. This method was tested on 46 influenza virus positive specimens of avian and mammalian (dog and human) origins collected between 2006 and 2008. The sensitivity of this method, tested against known concentrations of each type and subtype specific plasmid, was established to detect 10(3) copies/microl. The method's specificity was determined by testing against other subtypes of influenza A virus (H2, H4 and H6-H15) and respiratory pathogens commonly found in humans. None of them could be amplified, thus excluding cross reactivity. In conclusion, the multiplex PCR assays developed are advantageous as to rapidity, specificity, and cost effectiveness.     

Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects

OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IkappaB/NFkappaB via TLR4 and whether FFAs increase TLR4 expression/content in muscle. RESULTS- Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IkappaBalpha content, an indication of elevated IkappaB/NFkappaB signaling. The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IkappaB/NFkappaB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IkappaB/NFkappaB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.     

Role of serum interleukin-18 as a prognostic factor in patients with hepatocellular carcinoma

AIM To determine whether serum interleukin-18 (IL-18)levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC).METHODS Serum IL-18, IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls.RESULTS Serum IL-18, IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (≥ 105 pg/mL) had a poorer survival than those with low serum IL-18 levels (＜ 105 pg/mL)(4 and 11 mo, respectively, P = 0.015). Multivariate analyses showed that serum IL-18 level, but not IL-6 and IL-12 levels, was a significant and independent prognostic factor of survival.CONCLUSION These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patien ts with HCC. Thus, the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.