• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6255-6259
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• 2015

Purpose: To evaluate the prognostic value of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) in gallbladder cancer (GBC). Materials and Methods: Serum ALP and GGT levels and clinicopathological parameters were retrospectively evaluated in 199 GBC patients. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values of ALP and GGT. Then, associations with overall survival were assessed by multivariate analysis. Based on the significant factors, a prognostic score model was established. Results: By ROC curve analysis, $ALP{\geq}210U/L$ and $GGT{\geq}43U/L$ were considered elevated. Overall survival for patients with elevated ALP and GGT was significantly worse than for patients within the normal range. Multivariate analysis showed that the elevated ALP, GGT and tumor stage were independent prognostic factors. Giving each positive factor a score of 1, we established a preoperative prognostic score model. Varied outcomes would be significantly distinguished by the different score groups. By further ROC curve analysis, the simple score showed great superiority compared with the widely used TNM staging, each of the ALP or GGT alone, or traditional tumor markers such as CEA, AFP, CA125 and CA199. Conclusions: Elevated ALP and GGT levels were risk predictors in GBC patients. Our prognostic model provides infomration on varied outcomes of patients from different score groups.

• The Journal of Korean Medicine
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• v.30 no.5
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• pp.163-173
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• 2009

Objective: This study sought a clinical analysis of hepatobiliary cancer patients treated by oriental medical therapy. Methods: 312 hepatobiliary cancer patients treated in East-west Cancer Center of Dunsan Oriental Hospital from October 2004 to September 2008 were reviewed. These patients' general characteristics and clinical change after treatment were investigated. Results: 83.3% of patients' tumors were stage IV. The median survival period of stage IV patients was 107.0$\pm$82.2 (IVa), 207.0$\pm$26.8 (IVb) days (hepatocellular carcinoma), 132.0$\pm$15.8 days (cholangiocarcinoma), and 203.0$\pm$24.6 days (gallbladder carcinoma). Conclusions: This study presents the general characteristics of hepatobiliary cancer patients treated by Oriental medical therapies, and thus would be valuable for further studies of Oriental medicine-based cancer treatments.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.559-562
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• 2012

Serum alpha-fetoprotein (AFP) is a significant marker for clinical diagnosis and prognosis evaluation in hepatocellular carcinoma (HCC) patients. However, some proportion of liver cancer patients are AFP-negative (AFP ${\leq}$20ng/ml). In order to study the differences between clinicopathological factors and prognosis of alpha-fetoprotein negative and positive patients, a total of 114 cases (41 AFP-negative and 73 AFP-positive) were selected for our research. By systematically statistical analysis, the results demonstrated that compared with AFP-negative patients, AFP-positive examples were more likely to feature cirrhosis nodules, non-complete neoplasm capsules, and a poor Edmondson-steiner grade. Furthermore, AFP-negative patients demonstrated a favorable long-term prognosis. By univariate analysis and multivariate analysis with Cox's proportional hazards model, multiple tumors were found to be independent risk factors for worse survival of AFP negative patients; however, less tumor-free margins, multiple tumors and Edmondson-steiner grades III/IV, proved to be independent risk factors leading to a poor prognosis of AFP positive cases. Finally, we can infer that high levels of AFP signify a highly malignant tumor and unfavorable prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4161-4165
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• 2013

Objective: To investigate discriminating protein patterns and potential biomarkers in serum samples between pre/postoperative pancreatic cancer patients and healthy controls. Methods: 23 serum samples from PC patients (12 preoperative and 11 postoperative) and 76 from healthy controls were analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique combined with magnetic beads-based weak cation-exchange chromatography (MB-WCX). ClinProTools software selected several markers that made a distinction between pancreatic cancer patients and healthy controls. Results: 49 m/z distinctive peaks were found among the three groups, of which 33 significant peaks with a P < 0.001 were detected. Two proteins could distinguish the preoperative pancreatic cancer patients from the healthy controls. About 15 proteins may be potential biomarkers in assessment of pancreatic cancer resection. Conclusion: MB-MALDI-TOF-MS method could generate serum peptidome profiles of pancreatic cancer and provide a new approach to identify potential biomarkers for diagnosis and prognosis of this malignancy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5181-5185
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• 2015

Background: CCAT1 has been reported to be linked with pathogenesis of malignancies including colon cancer and gastric cancer. However, the regulatory effect of CCAT1 in hepatocellular carcinoma (HCC) remains unclear. The purpose of this research was to identify any role of CCAT1 in the progression of HCC. Materials and Methods: Real time-PCR was performed to test the relative expression of CCAT1 in HCC tissues. A computation screen of CCAT1 promoter was conducted to search for transcription-factor-binding sites. The association of c-Myc with CCAT1 promoter in vivo was tested by Pearson correlation analysis and chromatin immunoprecipitation assay. Additionally, Kaplan-Meier analysis and Cox proportional hazards analyses were performed. Results: c-Myc directly binds to the E-box element in the promoter region of CCAT, and when ectopically expressed increases promoter activity and expression of CCAT1. Moreover, Kaplan-Meier analysis demonstrated that the patients with low expression of CCAT1 demonstrated better overall and relapse-free survival compared with the high expression group. Cox proportional hazards analyses showed that CCAT1 expression was an independent prognostic factor for HCC patients. Conclusions: The findings demonstrated CCAT1, acting as a potential biomarker in predicting the prognosis of HCC, is regulated by c-Myc.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2099-2102
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• 2015

Objective: To explore the expression of $laminin{\gamma}2$ in extrahepatic cholangiocarcinoma (EHCC) tissues and its influence on tumor invasion and metastasis. Materials and Methods: Paraffin embedding samples of cancer, para-cancer, lymph node metastatic and hepatic metastatic tissues from 79 patients undergoing EHCC resection were collected. Expression of $laminin{\gamma}2$ was detected by immunohistochemistry and its relationship with clinical pathological characteristics and the prognosis of EHCC patients were analyzed. Results: $Laminin{\gamma}2$ showed negative staining in para-cancer tissues, but demonstrated a 51.9% (41/79) positive expression rate in extracellular matrix (ECM) or cytoplasm of EHCC tissues. In lymph node metastatic and distant metastatic nidi, expression of $laminin{\gamma}2$ was significantly higher than in the primary nidi (${\chi}^2=7.4173$, P=0.0065; ${\chi}^2=4.0077$, P=0.0453). The expression was in obvious association with lymph node metastasis (P<0.01), but had no relevance with age, gender, tumor location, tumor stage, differentiation and distant metastasis in ECM (P>0.05), whereas it was in marked connection with lymph node and distant metastasis (P<0.05 or P<0.01), but had no relationship with age, gender, tumor location, tumor stage and differentiation in cytoplasm (P>0.05). However, the median survival time and median recurrent period of patients with positive expression of $laminin{\gamma}2$ in both cytoplasm and ECM of tumor cells, only in ECM and only in cytoplasm, were evidently lower than with negative expression of $laminin{\gamma}2$ in RCM and cytoplasm (P<0.05 or P<0.01). Further Cox regression analysis showed that the positive expression of $laminin{\gamma}2$ and the tumor differentiation were independent risk factors influencing the prognosis of EHCC patients. Conclusions: Abnormal expression of $laminin{\gamma}2$ may be closely associated with invasion and metastasis of tumor cells, and thus a potential molecular marker for prognosis of EHCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2453-2459
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• 2013

Bevacizumab has been approved for use in combination with chemotherapy to treat many types of cancer but associated neutropenic events, including febrile neutropenia, have been reported. To estimate the incidence and relative risk of neutropenic events in cancer patients treated with bevacizumab combination therapy, we searched PubMed, EMBASE, and Web of Science literature databases, as well as abstracts presented at the American Society of Clinical Oncology conferences, to identify relevant studies published from January 1966 to December 2011. Studies that compared bevacizumab plus chemotherapy or biological therapy with chemotherapy or biological therapy alone, and that had adequate safety data profiles, were selected for analysis. Statistical analyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effects models. A total of 22 clinical trials involving 15,056 patients were included in the analysis. The summary incidences of high-grade neutropenia (HGN) and high-grade febrile neutropenia (HGFN) in patients receiving bevacizumab was 27.3% (95% CI: 26.4%-28.3%) and 3.91% (95% CI: 3.51%-4.37%), respectively. The risks of HGN (RR=1.10; 95% CI: 1.02-1.19; P=0.02) and HGFN (RR=1.31; 95% CI: 1.08-1.59; P=0.005) were significantly increased in bevacizumab-treated patients, compared to those who did not receive bevacizumab. The RR of bevacizumab-associated HGN, but not HGFN, varied significantly with tumor types (P=0.005). The increased risk of bevacizumab-associated neutropenic events was dose-dependent, as the RR was greater at a dose of 5 mg/kg/week than at 2.5 mg/kg/week. Our findings suggest that bevacizumab addition to cancer therapy significantly increases the risk of serious neutropenic events, and this risk may be dose-dependent.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1917-1921
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• 2012

Background: Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysis studies have identified sequence mutations causing loss-of-function that are associated with disease occurrence and severity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but have yet to be examined in the East Asian population of colorectal cancer patients. Methods: Biopsies of tumors and matched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphite conversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27 BeadChip. Results: Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared to the individual's matched control tissue. Interestingly, three genes that exhibited hypermethylation in their promoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectal cancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated genes were identified as significantly differentially methylated genes in the tumour tissues. Conclusions: Genome-wide methylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identify methylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show the promise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2185-2190
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• 2013

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1015-1018
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• 2012

Objective: To improve the diagnosis of primary gallbladder carcinoma (GBC) with/without hepatic metastases by analyzing our experience of different GBC treatment in our patients. Methods: A retrospective study was carried out to analyze the clinical data of the 139 patients with GBC who underwent hepatic resection in our unit from January 2003 to December 2007. Patients were divided into two groups according to whether they demonstrated hepatic invasion. Tumor presentation, surgical modes, and prognosis of each patient were retrospectively reviewed. Kaplan-Meier curves and log-rank tests were employed to compare the survival rates of those patients undergoing different surgical procedures. Results: Of the 139 patients, 46 were men and 93 were women with the male to female ratio of 1:2.0. Their ages were ranged from 35 to 86 years with a mean age of $62.8{\pm}10.4$ years. There were 73 patients complicated with hepatic invasion (group A), and no hepatic invasion occurred in the other 66 patients (group B). Compared with the group B, the patients with hepatic invasion suffered lower differentiation of tumor (p=0.000), more advanced Nevin staging (p=0.008) and poorer prognosis (p=0.013). Radical resection were more frequently performed in group B (75.76%) than in group A (45.20%) with better outcomes (p=0.000). Conclusion: GBC patients complicated with hepatic invasion had poorer prognosis than those without invasion in long-term follow-ups. Radical resection might result in a satisfied prognosis in patients without hepatic invasion, but appears less favorable than palliative resection in those who were complicated with hepatic invasion.