• Parasites, Hosts and Diseases
• /
• v.51 no.6
• /
• pp.711-717
• /
• 2013

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.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.14
• /
• pp.5873-5878
• /
• 2014

Hypoxia and autophagy are known to facilitate tumor progression. We here aimed to investigate the role of hypoxia-associated autophagy in cholangiocarcinoma (CCA) survival and metastasis. Immunostaining of hypoxic-responsive proteins (HIF-$1{\alpha}$ and BNIP3) and a key regulator of autophagy (PI3KC3) were examined in CCA tissues and their expression levels were compared with clinicopathological parameters. A hypoxia mimicking condition ($CoCl_2$ treatment) was also tested regarding CCA cell functions. Our results showed that HIF-$1{\alpha}$ (66%), BNIP3 (44%) and PI3KC3 (46%) showed strong staining in human CCA tissues. Positive expression of HIF-$1{\alpha}$ (p=0.033), BNIP3 (p=0.040) and PI3KC3 (p=0.037) was significantly correlated with lymph node metastasis. HIF-$1{\alpha}$ was well associated with BNIP3 (r=0.3, p<0.01) and PI3KC3 (r=0.2, p<0.01). The survival rates of patients who were positive with HIF-$1{\alpha}$ (p=0.047) or co-expressed HIF-$1{\alpha}$ and BNIP3 (p=0.032) or HIF-$1{\alpha}$ and PI3KC3 (p=0.043) were significantly greater than in the negative groups. CCA cells treated with $CoCl_2$ showed an increase in HIF-$1{\alpha}$, BNIP3, PI3KC3 and LC3-II, with increased cell migration and pFAK levels. These data suggest that hypoxia associated autophagy enhances CCA metastasis, resulting in a poor prognosis of CCA.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.16
• /
• pp.7231-7235
• /
• 2015

This study was conducted to determine whether advancing age is an independent predictor of increased risk of high-grade pathologies among women referred for colposcopy after abnormal cervical cytology. Medical records were reviewed for women with abnormal cervical cytology who underwent colposcopy at Khon Kaen University Hospital. Logistic regression was used to determine the independent impact of age on the risk of high-grade pathologies. Mean age of the women was 42.8 years. Of 482 women, 97 (20.1%) were postmenopausal, and 92 (19.1%) were nulliparous. The rate of high-grade pathologies included cervical intraepithelial neoplasia 2-3, 99 (20.5%), adenocarcinoma in situ, 4 (0.8%), cervical cancer, 30 (6.2%), and endometrial cancer, 1 (0.2%). The prevalence of significant lesions was 26.9% (95% CI, 23.1%-31.2%). In total, 31 women had cancers (6.4%; 95% CI, 4.4%-9.0%). When controlling for smear types and parity, age was noted to be a significant independent predictor of high-grade histopathology. Women older than 35-40 years were approximately 2 times as likely to have severe histopathology as the younger women. This study illustrates the substantial risk of underlying significant lesions especially invasive cancer in Thai women with abnormal cervical cytology. Age was a significant independent factor predicting the risk of high-grade pathologies.

• Parasites, Hosts and Diseases
• /
• v.51 no.6
• /
• pp.755-757
• /
• 2013

Gnathostoma spinigerum can cause subarachnoid hemorrhage (SAH). The detection of specific antibodies in serum against G. spinigerum antigen is helpful for diagnosis of neurognathostomiasis. There is limited data on the frequency of G. spinigerum infection in non-traumatic SAH. A series of patients diagnosed as non-traumatic SAH at the Srinagarind Hospital, Khon Kaen University, Thailand between January 2011 and January 2013 were studied. CT or MR imaging of the brain was used for diagnosis of SAH. Patients were categorized as aneurysmal subarachnoid hemorrhage (A-SAH) or non-aneurysmal subarachnoid hemorrhage (NA-SAH) according to the results of cerebral angiograms. The presence of specific antibodies in serum against 21- or 24-kDa G. spinigerum antigen was determined using the immunoblot technique. The detection rate of antibodies was compared between the 2 groups. Of the 118 non-traumatic SAH patients for whom cerebral angiogram and immunoblot data were available, 80 (67.8%) patients had A-SAH, whereas 38 (32.2%) had NASAH. Overall, 23.7% were positive for specific antibodies against 21- and /or 24-kDa G. spinigerum antigen. No significant differences were found in the positive rate of specific antibodies against G. spinigerum in both groups (P-value=0.350).

• Parasites, Hosts and Diseases
• /
• v.51 no.6
• /
• pp.747-749
• /
• 2013

The 2 principal species of hookworms infecting humans are Necator americanus and Ancylostoma duodenale. Case studies on zoonotic hookworm infections with Ancylostoma ceylanicum and/or Ancylostoma caninum are known mainly from Asian countries. Of these 2 zoonotic species, only A. ceylanicum can develop to adulthood in humans. In the present study, we report a molecular-based survey of human hookworm infections present in southern and northeastern Thailand. Thirty larval hookworm samples were obtained from fecal agar plate cultures of 10 patients in northeastren Thailand and 20 in southern Thailand. Partial ITS1, 5.8S, and ITS2 regions of the ribosomal DNA genes were amplified using PCR. The amplicons were sequenced, aligned, and compared with other hookworm sequences in GenBank database. The results showed that, in Thailand, N. americanus is more prevalent than Ancylostoma spp. and is found in both study areas. Sporadic cases of A. ceylanicum and A. duodenale infection were seen in northeastern Thailand.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.2
• /
• pp.767-770
• /
• 2016

Background: The proportion of aged Thais (${\geq}65$ years old) is expected to be 30% by 2030, leading to an increased number of elderly cancer cases. Older individuals have distinct patterns of cancer and treatment needs. We therefore conducted the present study of new cancer cases and trends to get a perspective on the elderly cancer situation in Northeast Thailand. Materials and Methods: All new elderly cancer cases (${\geq}65$ years) registered in the hospital-based cancer registry at the Faculty of Medicine, Srinagarind Hospital, Khon Kaen University during 1993-2012 were included in the study. Results: Elderly patients accounted for 31.6% of all cancer patients and new cancer cases in the older age group increased 46% from the first to second decades. The absolute number of oldest old (80+ years) doubled. The top three cancers in males were liver and bile duct, lung, and colorectal. In females, the three most common cancers were liver and bile duct, oral cavity, and cervix. Cancers with the highest percentages of increase were thyroid, prostate, and colorectal. Conclusions: Elderly cancer cases are increasing. Treatment modalities and palliative care for older populations are urgently needed.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.23
• /
• pp.10463-10468
• /
• 2015

Opisthorchis viverrini (Ov) infection is the major etiological factor for cholangiocarcinoma (CCA), especially in northeast Thailand. We have previously reported significant involvement of PI3K/AKT/PTEN and $Wnt/{\beta}$-catenin in human CCA tissues. The present study, therefore, examined the expression and activation of PI3K/AKT/PTEN and $Wnt/{\beta}$-catenin signaling components during Ov-induced cholangiocarcinogenesis in a hamster animal model. Hamsters were divided into two groups; non-treated and Ov plus NDMA treated. The results of immunohistochemical staining showed an upregulation of PI3K/AKT signaling as determined by elevated expression of the $p85{\alpha}$-regulatory and $p110{\alpha}$-catalytic subunits of PI3K as well as increased expression and activation of AKT during cholangiocarcinogenesis. Interestingly, the staining intensity of activated AKT (p-AKT) increased in the apical regions of the bile ducts and strong staining was detected where the liver fluke resides. Moreover, PTEN, a negative regulator of PI3K/AKT, was suppressed by decreased expression and increased phosphorylation during cholangiocarcinogenesis. We also detected upregulation of $Wnt/{\beta}$-catenin signaling as determined by increased positive staining of Wnt3, Wnt3a, Wnt5a, Wnt7b and ${\beta}$-catenin, corresponded with the period of cholangiocarcinogenesis. Furthermore, nuclear staining of ${\beta}$-catenin was observed in CCA tissues. Our results suggest the liver fluke infection causes chronic inflammatory conditions which lead to upregulation of the PI3K/AKT and $Wnt/{\beta}$-catenin signaling pathways which may drive CCA carcinogenesis. These results provide useful information for drug development, prevention and treatment of CCA.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.7
• /
• pp.3043-3050
• /
• 2015

The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$, FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.9
• /
• pp.3931-3936
• /
• 2015

Fatty liver disease (FLD) can be a precondition for other liver pathology including cholangiocarcinoma (CCA). Diabetes mellitus (DM) has been suggested in some studies to be a risk factor for FLD as well as cancers, including cholangiocellular carcinoma; however, there are currently very few studies on FLD in DM subjects, although the rate of FLD continues to increase annually. To determine the association between DM and FLD ultrasonographic data were analyzed from the Cholangiocarcinoma Screening and Care Program (CASCAP), in northeast Thailand. DM was reported by the subjects based on the CASCAP health questionnaire. Factors that were associated with FLD were determined by prevalence, odds ratio (ORs) and its 95% confidence intervals (CIs) using multiple logistic regression. There were 45,263 subjects with a mean age of 53.46 (${\pm}9.25$) years. FLD was found in 36.3% of DM subjects but only in 20.7% of non-DM subjects. The association between DM and FLD was adjusted for all other factors including gender, age, education level, relatives diagnosed with CCA, smoking, alcohol consumption, and hepatitis B and C. The risk of DM in subjects having FLD was highly significant compared with the non-DM subjects (OR 2.13; 95%CI: 1.92 to 2.35; p-value < 0.001). Thus DM is significantly associated with FLD which in turn may facilitate the development of several diseases including CCA. DM should be taken into consideration in future ultrasonic investigations of FLD and CCA.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.17
• /
• pp.7765-7768
• /
• 2015

This study was conducted to determine the incidence of wound complications after laparotomy for endometrial cancer and significant predictors of risks. Medical records of patients with endometrial cancer undergoing laparotomy for surgical staging at Srinagarind Hospital, Khon Kaen University between January 2007 and December 2013 were reviewed. Intravenous antibiotic prophylaxis was routinely given 30 minutes before surgery. The primary endpoint was wound complications (including seroma, hematoma, separation, or infection) requiring additional medical and/or surgical management within 4 weeks of laparotomy. During the study period, 357 patients with complete medical records were reviewed. The mean age was 56.9 years. Wound complications were observed in 28 patients (7.84%, 95% CI, 5.27% to 11.14%). Body mass index (BMI) ${\geq}30kg/m^2$, diabetes mellitus (DM), and prior abdominal surgery were observed as significant independent factors predicting an increased risk of wound complications with adjusted odds ratios (95% CIs) of 2.96 (1.23-7.16), 2.43 (1.06-5.54), and 3.05 (1.03-8.98), respectively. In conclusion, the incidence of wound complications after laparotomy for endometrial cancer was 7.8%. Significant independent predictors of risk included BMI, DM and prior abdominal surgery.