ABSTRACT
Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF−, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1β, IL-6, IFN-γ, LT-α, and TNF-α were significantly increased in CCA patients compared with non-CCA (APF− and APF+) cases. Polymorphisms in genes encoding IL-1β-511C/T, IL-6-174G/C, IFN-γ +874T/A, LT-α +252A/G, and TNF-α−308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-α +252A/G and TNF-α−308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-γ +874T/A were significantly higher than the variants in CCA cases. IFN-γ +874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6 −174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.
Subject(s)
Humans , Alleles , Asian People , Cholangiocarcinoma , Cytokines , Fasciola hepatica , Fibrosis , Inflammation , Interleukin-6 , Liver , Opisthorchis , Pathology , UltrasonographyABSTRACT
Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo.
Subject(s)
Animals , Cricetinae , Male , Allografts , Antineoplastic Agents/isolation & purification , Berberine/therapeutic use , Cell Culture Techniques , Cell Line, Tumor , Cell Transplantation/methods , Cholangiocarcinoma/drug therapy , Culture Media/chemistry , Disease Models, Animal , Drug Evaluation, Preclinical/methods , MesocricetusABSTRACT
Two cases of massive upper gastrointestinal haemorrhage that had short histories and were unresponsive to conservative treatment are presented. Both cases underwent emergency operations to stop bleeding and were found to be non epithelial gastric tumours. The surgical pathology and surgical decisions are discussed in this report
ABSTRACT
A retrospective study was done on 50 children with tuberculosis diagnosed at Srinagarind hospital from 1980 – 1984. The most common forms of disease were pulmonary tuberculosis (38%), military tuberculosis (26%) and tuberculous meningitis (16%). History of contact was elicited in 63.3%. Forty percent of patients had BCG scar. Abnormalitities in chest x-rays were found in 70% of cases. Laboratory findings included positive smear and culture from sputum and gastric wash in 15.4%, positive tuberculin test in in 47.7%. Patients who gave negative results to tuberculin test, 61.9% were in second and third degree malnutrition. Patients with active severe disease and young patients under 2 years of age yielded few positive results to tuberculin test.
ABSTRACT
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