• Journal of Life Science
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• v.21 no.11
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• pp.1518-1525
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• 2011

Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5203-5209
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• 2016

Objective: To explore the prevalence of malignant tumors in the adult population through 2003-2014 in parts of the Aral Sea region: a zone of ecological disaster, a zone of ecological crisis and a zone of precritical conditions. Methods: The long-time average annual levels of cancer morbidity stratified by zones of the Aral Sea region and trends of long-time average annual incidence indicators of malignant tumors were identified. Leading cancer localizations in the adult population was established and associations between cancer incidence and environmental pollution were analyzed. In addition, associations between individual risk factors and cancer incidence in the adult population was established. Correlations between a hazard index and the cancer incidence in the adult population were calculated. Results: In all three Aral Sea regions, as well as in Zhanaarkinskii district, leading cancer in adult population was esophageal, stomach, tracheal, lung, hepatobiliary, and breast. Long-time average annual levels of cancer morbidity in adult population living in the Aral sea region is 1.5 times higher comparing to the control region. In particular, long-time average annual levels of cancer morbidity in adult population living in the zone of ecological disaster was 57.2% higher, in the zone of ecological crisis - 61.9% higher, and in the zone of precritical condition - 16.8% higher. Long-time average annual levels in the adult population of the Aral Sea region significantly exceeded control levels for brain and central nervous system cancer, cancer of bone and articular cartilage, and thyroid cancer. Conclusion: It has was established that the total cancer morbidity depended on the total hazard index associated with the inhalation of nickel and the combined cadmium intake (r=0.8).

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6321-6326
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• 2013

Introduction: Lung cancer is extremely harmful to human health and has one of the highest worldwide incidences of all malignant tumors. Approximately 80% of lung cancers are classified as non-small cell lung cancers (NSCLCs). Cisplatin-based multidrug chemotherapy regimen is standard for such lesions, but drug resistance is an increasing problem. F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-box protein family that regulates cell cycle progression, and cell growth and differentiation. FBW7 also functions as a tumor suppressor. Methods: We used cell viability assays, Western blotting, and immunofluorescence combined with siRNA interference or plasmid transfection to investigate the underlying mechanism of cisplatin resistance in NSCLC cells. Results: We found that FBW7 upregulation significantly increased cisplatin chemosensitivity and that cells expressing low levels of FBW7, such as NCI-H1299 cells, have a mesenchymal phenotype. Furthermore, siRNA-mediated silencing or plasmid-mediated upregulation of FBW7 resulted in altered epithelial-mesenchymal transition (EMT) patterns in NSCLC cells. These data support a role for FBW7 in regulating the EMT in NSCLC cells. Conclusion: FBW7 is a potential drug target for combating drug resistance and regulating the EMT in NSCLC cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2711-2715
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• 2013

Background: Cancer of the gallbladder is a relatively rare neoplasm with a poor prognosis. The exact mechanisms of its genesis are not known and very little information is available on molecular events leading to labeling this as an orphan cancer. Materials and Methods: In this prospective case control study we evaluated the expression of p16, pRb and cyclin D1 by immunohistochemistry to study the G1-S cell-cycle check point and its possible role in gallbladder carcinogenesis. A total of 25 patients with gallbladder carcinoma (group I), 25 with cholelithiasis (group II) and 10 normal controls. were enrolled Results: Cyclin D1 expression was seen in 10 (40%) patients each with carcinoma and cholelithiasis while only in 2 (20%) of the normal gallbladders but differences were not statistically significant (p value=0.488). p16 was expressed in 12% patients of carcinoma of the gallbladder and 28% of cholelithiasis, however this difference was not statistically significant (p value=0.095). Retinoblastoma protein was found to be expressed in 50% of normal gallbladders and 6 (24%) of carcinoma and 8 (32%) of gallstones. The present study failed to demonstrate any conclusive role of cyclin D1/RB/ p16 pathway in carcinoma of the gallbladder. Conclusions: The positive relation observed between tumor metastasis and cyclinD1 expression and p16 with nodal metastasis suggested that higher cyclin D1/p16 expression may act as a predictive biomarker for aggressive behavior of gallbladder malignancies.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.225-229
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• 2012

Background: Males have a higher prevalence of hepatocellular carcinoma (HCC) than females in general, but the reasons for the sex disparity are still obscure. DNA copy number alteration (CNA) is a major feature of solid tumors including HCC, but whether CNA plays a role in sex-related differences in HCC development has never been evaluated. Methods: High-resolution array comparative genomic hybridization (CGH) was used to examine 17 female and 46 male HCC patients with chronic hepatitis B virus (HBV) infection in Shanghai, China. Two-tailed Fisher's exact or ${\chi}^2$ tests was used to compare CNAs between females and males. Results: The overall frequencies and patterns of CNAs in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to those in males on 1q21.3-q22 (76.5% vs. 37.0%, P = 0.009), 11q11 (35.3% vs. 0.0%, P = 0.0002) and 19q13.31-q13.32 (23.5% vs. 0.0%, P = 0.004), and loss on 16p11.2 (35.3% vs. 6.5%, P = 0.009). Relative to females, male cases had greater copy number loss on 11q11 (63.0% vs. 17.6%, P = 0.002). Further analyses showed that 11q11 gain correlated with 19q13.31-q13.32 gain (P = 0.042), 11q11 loss (P = 0.011) and 16p11.2 loss (P = 0.033), while 1q21.3-q22 gain correlated with 19q13.31-q13.32 gain (P = 0.046). Conclusions: These findings suggest that CNAs may play a role in sex-related differences in HBVassociated HCC development.

• Journal of Hospice and Palliative Care
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• v.23 no.1
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• pp.5-10
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• 2020

Purpose: The aim of this study was to investigate celiac plexus neurolysis (CPN) for the treatment of cancerous upper abdominal pain in a tertiary university hospital in Korea. Methods: At the tertiary university hospital in Korea, electronic medical records of cancer patients who underwent CPN and died in the hospital from November 2009 to June 2018 were retrospectively analyzed. Results: The total number of subjects was 51. The 17 patients were from the Department of Gastroenterology (33.0%), followed by 11 patients from the Department of Hemato-oncology (21.6%), 11 patients from the Department of Anesthesia and Pain Medicine (21.6%), 9 patients from the Department of General Surgery (17.6%). The diagnosis was pancreatic cancer in 15 patients (29.4%), stomach cancer in 8 patients (15.7%), hepatobiliary cancer in 20 patients (39.2%), colon cancer in 1 patient (2.0%), esophageal cancer in 2 patient (3.9%) and intra-abdominal metastasis in 5 patients (9.8%). The mean survival time after the surgery was 66.4±55.0 days. The pain intensity before and 1 week after the procedure significantly decreased, but the amounts of opioids consumed before and 1 week after the procedure were not statistically significant. Side effects occurred after the procedure including temporary localized pain in 24 patients (47.0%), hypotension in 12 (23.5%), and diarrhea in 6 (11.8%). Conclusion: CPN is an effective and safe procedure for reducing upper abdominal pain caused by cancer, and it is necessary to perform CPN within the appropriate time by establishing a system of interdepartmental cooperation.

• Radiation Oncology Journal
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• v.34 no.1
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• pp.34-44
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• 2016

Purpose: A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. Materials and Methods: Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. Results: A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. Conclusion: Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4131-4136
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• 2016

Background: The population in northeast Thailand continues to present with hepatobiliary abnormalities, particularly periductal fibrosis (PDF) which is the result of chronic infection with liver fluke (Opisthorchis viverini; OV) and may lead to the development of cholangiocarcinoma (CCA). Although the prevalence of OV infection has been decreased due to a liver fluke control program over decades, the prevalence of PDF remains high. This study aimed to investigate demographic factors associated with PDF risk based on ultrasonography (US) screening. Materials and Methods: This cross-sectional study is part of the Cholangiocarcinoma Screening and Care Program (CASCAP), a prospective cohort study. Multiple logistic regression was used for data analysis. Results: In 55,246 subjects, the overall prevalence of PDF was 33.0% (95%CI: 32.6 - 33.4). Males (33.9 %) were at higher risk for developing PDF than females (32.2 %) (ORcrude = 0.93; 95%CI: 0.89 - 0.96; p-value < 0.001). Factors associated with an increased PDF risk, in addition to OV infection, included old age (${\geq}70$ years) (ORadj = 1.28, 95% CI: 1.14 - 1.44, p < 0.001) and hepatitis B infection (ORadj = 1.31, 95% CI: 1.11 - 1.55, p = 0.001). In contrast, number of praziquantel treatments (> 2 times) (ORadj = 0.54, 95% CI: 0.47 - 0.63, p < 0.001) and diabetes mellitus (ORadj = 0.57, 95% CI: 0.49 - 0.65, p < 0.001) were significantly associated with a decreased PDF risk. Conclusions: Future US screening should closely examine older people and hepatitis B subjects for the purpose of PDF surveillance among high risk groups for CCA. However, the results of inverse associations require further investigation in order to confirm our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1235-1240
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• 2012

Background: Opisthorchis viverrini infection is a serious public-health problem in Southeast Asia. It is associated with a number of hepatobiliary diseases and the evidence strongly indicates that liver fluke infection is the etiology of cholangiocarcinoma. Objectives: This study aimed to investigate Opisthorchis viverrini metacercarial infection in cyprinoid fish collected from 32 districts of Nakhon Ratchasima province, Northeastern Thailand during one year period from February 2010 to February 2011. Methods: A cross-sectional study was conducted, data being collected with pepsin-HCl digestion and stereomicroscope, respectively. Analysis was performed using SPSS Windows Version 12.0. Results: A total of 640 Cyprinidae family fish including 5 species were collected from different study sites, and investigated for O. viverrini metacercariae. The infection rate was 12.3% (79/640), predominantly in Cyclocheilichthys armatus, C. repasson, Puntioplites proctzysron, Hampala macrolepitota and Hampala dispar, respectively. The prevalence of O. viverrini metaceria in Nakhon Ratchasima area was 78.1%, predominantly in Sida and KiaKham Thale So. Conclusion: This findings stress that natural fish species in rural communities are still a source of O viverrini infection and put local people at risk, therefore public awareness and prevention campaigns are urgently required.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5245-5249
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• 2012

Background: Opisthorchis viverrini infection is a serious public-health problem in Southeast Asia especially in Lao PDR and Thailand. It is associated with a number of hepatobiliary diseases and the evidence strongly indicates that liver fluke infection is the major etiology of cholangiocarcinoma. Objectives: This study aimed to determine actual levels of Opisthorchis viverrini infection in Nakhon Ratchasima province, Northeast Thailand. Methods: A cross-sectional survey was conducted during a one year period from October 2010 to September 2011. O. viverrini infection was determined using a modified Kato's thick smear technique and socio-demographic data were collected using predesigned semi-structured questionnaires. Results: A total of 1,168 stool samples were obtained from 516 males and 652 females, aged 5-90 years. Stool examination showed that 2.48% were infected with O. viverrini. Males were slightly more likely to be infected than females, but the different was not statistically significant. O. viverrini infection was most frequent in the 51-60 year age group and was found to be positively associated with education and occupation. Positive results were evident in 16 of 32 districts, the highest prevalence being found in Non Daeng with 16.7%, followed by Pra Thai with 11.1%, Kaeng Sanam Nang with 8.33%, and Lam Ta Men Chai (8.33%) districts. Conclusion: This study indicates that O viverrini is still a problem in some areas of Nakhon Ratchasima, the patients in this study bing suitable for the purpose of monitoring projects.