ABSTRACT
Thunbergia laurifolia Linn (Rang Chuet) possesses antioxidant and anti-inflammatory properties as well as anticancer activities. The aim of the present study was to evaluate the efficacy of T. laurifolia in reducing inflammation from pathological changes in Syrian hamsters infected with the human liver fluke Opisthorchis viverrini. Hamster groups were also administered N-nitrosodimethylamine (NDMA) and treated with T. laurifolia. Light microscopic observation of histopathological changes, liver function tests for alanine transaminase (ALT) and alkaline phosphatase (ALP) and kidney function tests for blood urea nitrogen (BUN) and creatinine were performed. Antioxidant effects of both fresh and dried Rang Chuet solutions were observed. Analysis of the histopathological changes showed anti-inflammatory properties, both in the case of O. viverrini infection or with NDMA administration, by reducing the aggregation of inflammatory cells surrounding the hepatic bile ducts as indicated by normal serum ALT, ALP, BUN and creatinine levels in treated Syrian hamsters. The present study found that fresh and dried Rang Chuet solutions clearly reduced the inflammatory cells in both O. viverrini-infected and NDMA-administered groups and was correlated with the total antioxidant capacity. These findings suggest that T. laurifolia possesses antioxidant and anti-inflammatory properties and that its application may be useful for prevention of the inflammatory process, one of the risk factors of O. viverrini-associated cholangiocarcinoma (CCA).
Subject(s)
Acanthaceae/chemistry , Anthelmintics/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Antioxidants/administration & dosage , Opisthorchiasis/drug therapy , Plant Extracts/administration & dosage , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Anthelmintics/isolation & purification , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Creatinine/blood , Cricetinae , Disease Models, Animal , Histocytochemistry , Liver/pathology , Mesocricetus , Microscopy , Opisthorchiasis/parasitology , Opisthorchiasis/pathology , Plant Extracts/isolation & purification , Treatment Outcome , Urea/bloodABSTRACT
Cholangiocarcinoma is a crucial health problem in northeast Thailand. Although rare, it is a highly fatal disease and the prognosis of CCA patients is very poor. To determine if expression of specific genes is useful for diagnosis and prognosis for CCA. We examined the expression of HSP70, HSP90, RB1, cyclin D1, and HDAC6 in 50 resections of human CCA tissues by quantitative real-time PCR. The expression of HSP70, RB1, and HDAC6 was "dominant down-regulation," while the expression of cyclin D1 and HSP90 was "dominant up-regulation." There were no correlations between RB1, cyclin D1, HSP90, and clinicopathological parameters such as status, histology type, histological grading, stage of CCA, and metastasis. A significant association was found between HDAC6 and CCA staging (p = 0.000), CCA gross type and HSP70 (p = 0.046) as well as RB1 expression (p = 0.046). Patients with down-regulation of HSP70 had significantly poorer prognosis than those in the up-regulation group (p = 0.002). Expression of HSP70 may be useful as a new prognostic marker for CCA.
Subject(s)
Bile Duct Neoplasms/genetics , Bile Ducts, Intrahepatic/metabolism , Cholangiocarcinoma/genetics , HSP70 Heat-Shock Proteins/genetics , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/pathology , Cyclin D1/genetics , Cyclin D1/metabolism , Down-Regulation , Female , HSP70 Heat-Shock Proteins/metabolism , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/metabolism , Histone Deacetylase 6 , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Humans , Male , Middle Aged , Neoplasm Metastasis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Retinoblastoma Protein/genetics , Retinoblastoma Protein/metabolismABSTRACT
Cholangiocarcinoma (CCA) is a crucial health problem in northeastern part of Thailand, which is caused by a combination of Opisthorchis viverrini infection and nitrosamine. A better understanding of its molecular mechanism is an important step to discover and develop the new diagnostics and therapies for CCA. To reveal the involvement of potential genes in the development of CCA, the present study investigated the expression kinetics of platelet-derived growth factor alpha (Pdgfa) and its receptor (Pdgfra) during the tumorigenesis of CCA induced by O. viverrini infection with quantitative RT-PCR, and confirmed the expression with immunohistological staining. The results showed that in the hamster model of opisthorchiasis-associated CCA, the expression of Pdgfa was increased after infection plus N-nitrosodimethylamine (NDMA) administration, reached its peak at 2 months post infection, and remained at the high level until 6 months. Similarly, the expression of Pdgfra was increased time-dependently. The positive immunostaining for PDGFA proteins was observed in the cytoplasm of epithelial tumor cells of hamster CCA. Moreover, the analysis of the expression of these genes in 10 cases of human opisthorchiasis-associated CCA showed that Pdgfa was overexpressed in 80%, and Pdgfra was overexpressed in 40% cases (>3.0 folds, compared with the expressions of adjacent normal tissues). This result suggests that PDGFA is likely involved in the tumorigenesis of opisthorchiasis-associated CCA, and may be a promising candidate biomarker for diagnosis and treatment strategies of CCA.
