• Asian Pacific Journal of Cancer Prevention
• /
• 제16권9호
• /
• pp.3849-3856
• /
• 2015

Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. Materials and Methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-${\alpha}$ and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. Results: After comparing the proteomics profile of TNF-${\alpha}$ induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-${\alpha}$ stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA- and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-${\alpha}$. Conclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권12호
• /
• pp.6221-6225
• /
• 2012

Background: To determine the frequency of HER-2 overexpression in colorectal cancer (CRC) patients, and to explore the relationship between clinicopathological prognostic factors and their effects on survival, based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis. Materials and Methods: The study included 80 patients with a histologically proven diagnosis of CRC that received adjuvant FOLFOX-4 chemotherapy at our department between March 2006 and September 2010. Patient data were analyzed retrospectively. Results: The median follow-up period and age of the patients were 24 months and 59 years, respectively. In immunohistochemical staining, 3+ staining was found in 2 patients (2.5%) while 2+ was in 13 (16%). FISH for HER-2 was performed for all of these 15 patients; samples which were 3+ showed positivity but the ones with 2+ were negative. There was no significant correlation between HER-2 expression and age, gender, tumor localization, histological subtype, grade, lymphovascular and perineural invasion, or pTN stage (P>0.05), even when the patients with HER-2 overexpression were analyzed separately. There was also no significant relationship between progression-free survival (PFS) and overall survival (OS), and HER-2 expression, gender, tumor localization, obstruction-perforation, bleeding, histological type, grade, lymphovascular and perineural invasion, or pT staging (P>0.05); however, there was a significant relationship between lymph node involvement, and PFS and OS (P<0.05). Conclusions: Evaluation of HER-2 overexpression in a more comprehensive, multi-center, prospective trial with standardized methods will be an appropriate approach.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권17호
• /
• pp.7129-7135
• /
• 2014

Background: In this study, we aimed to evaluate the growth inhibitory effect of the combination of ethaselen (BBSKE) and low fixed dose of selenite against A549 human non-small cell lung cancer cells in vitro. Materials and Methods: Growth inhibitory effects against A549 cells were determined by SRB assay. Combination index (CI) values were calculated based on Chou-Talalay median-effect analyses. Dose reduction index (DRI) values were applied to calculate dose reduction of selenite. Contents of free thiols and GSH were determined by DTNB assay and intracellular ROS levels by DCFH-DA fluorescence labeling. Results: Compared with BBSKE or selenite single treatment, the combined application of ethaselen and a low fixed dose of selenite shortened the onset time of sodium selenite, reduced $IC_{50}$ values, and increased the maximum inhibition rates, suggesting a possible molecular mechanism of the synergism. Obvious synergistic effects were observed after different times of combination treatment, especially after 24 h. Compared with selenite single treatment, dosage of selenite could be remarkably reduced in combination therapy to gain the same inhibitory effect on cell proliferation. Compared with BBSKE single treatment, the content of free thiols and GSH were significantly reduced and ROS levels greatly elevated in the combination group. For the combination treatment, cell viability increased as greater concentrations of GSH were added. Conclusions: All these results indicate that the combination treatment of BBSKE and selenite showed synergism to inhibit A549 cell proliferation in vitro, and also reduced the selenite dosage to mitigate its toxicity which is very meaningful for combination chemotherapy of lung cancer. The synergism was probably caused by the accelerated exhaustion of intracellular reductive substances, such as free thiols and GSH, which ultimately leads to enhanced oxidative stress and apoptosis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권11호
• /
• pp.7029-7032
• /
• 2013

Background: Cholangiocarcinoma (CCA) is a very common cancer in Northeastern Thailand. Most CCA patients see a physician at a late stage when curative surgery is not possible. After diagnosis, they generally are treated by partial surgery/percutaneous drainage, chemotherapy and supportive treatment. Objective: This study aimed to assess the survival rates of CCA patients after supportive treatment. Methods: A retrospective cohort design was applied in this study. Data for 746 CCA patients were extracted from the hospital-based cancer registry of Srinagarind Hospital, Khon Kaen University. The patients were diagnosed (at least by ultrasonography) between 1 January, 2009 and 31 December, 2009 and then followed up for current status until 30 June, 2011. The cumulative survival rate was calculated by the Kaplan-Meier method, and independent prognostic factors were investigated using Cox regression. Results: The total follow-up time was 5,878 person-months, and the total number of deaths was 637. The mortality rate was therefore 10.8 per 100 person-year (95%CI : 10.1-11.7). The cumulative 3, 6, 9, 12 and 24 month survival rates were 59%, 39%, 31%, 24% and 14%, respectively. The median survival time after supportive treatment was 4 months. After adjusting for gender, age, stage, distant metastasis, histological grading and treatment, stage was a significant predictor of survival of CCA patients. Those in stage III and stage IV had a 6.78 fold higher mortality than the stage I and stage II cases (95% CI : 1.6-28.7). Conclusion: It is very important to encourage patients to see health personnel at an early stage.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권11호
• /
• pp.6321-6326
• /
• 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
• /
• 제14권7호
• /
• pp.4365-4368
• /
• 2013

Background: Bronchioloalveolar carcinoma (BAC) is considered a subtype of adenocarcinoma of the lung. Recently BAC has been variously termed adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant invasive adenocarcinoma, and invasive mucinous adenocarcinoma. The aim of the study was to analyze and detect prognostic factors of patients with BAC over a 7-year period. Materials and Methods: This retrospective single-center study included 44 patients with BAC. The impact on survival of fifteen variables (gender, age, smoking status, cough, dyspnea, hemoptysis, fever, chest pain, sputum, metastasis number, Karnofsky performance status, pT, pN, TNM stage, cytotoxic chemoterapy) were assessed. Results: Median age was 55 years (38-83). Most patients were male (63.6%) and stage IV (59.1%). Twenty-one patients (47.7%) received cytotoxic chemotherapy (platinum-based regimens) for metastatic disease. Objective response rate was 33.3% (4 partial, 3 complete responses). Stable disease was observed in nine in patients (42.8%). Disease progression was noted in 5 (23.8%). The median OS for all patients was 12 months (95%CI, 2.08-22.9 months). Independent predictors for overall survival were: Karnofsky performance status (HR:3.30, p 0.009), pN (HR:3.81, p 0.018), TNM stage (HR:6.49, p 0.012) and hemoptysis (HR:2.31, p 0.046). Conclusions: Karnofsky performance status, pN, TNM stage and hemoptysis appear to have significant impact on predicting patient survival in cases of BAC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권7호
• /
• pp.4151-4155
• /
• 2013

Background: To compare response evaluation criteria in solid tumours (RECIST) and volumetric evaluation (VE) for colorectal cancer with liver-limited metastasis. Patients and Methods: VE of liver metastases was performed by manual contouring before and after chemotherapy on 45 pairs of computed tomography (CT) images in 36 patients who suffered from metastatic colorectal cancer (mCRC) with liver metastasis only. Cohen kappa was used to compare the agreement between VE and RECIST. Pearson correlation was performed for their comparison after cubic root transformation of the aggregate tumor volumes. Logistic regression was done to identify clinical and radiographic factors to account for the difference which may be predictive in overall response (OR). Results: There were 16 partial response (PR), 23 stable disease (SD) and 6 progressive disease (PD) cases with VE, and 14 PR, 23 SD and 8 PD with RECIST. VE demonstrated good agreement with RECIST (${\chi}$=0.779). Discordant objective responses were noted in 6 pairs of comparisons (13.3%). Pearson correlation also showed excellent correlation between VE and RECIST ($r^2$=0.966, p<0.001). Subgroup analysis showed that VE was in slightly better agreement with RECIST for enlarging lesions than for shrinking lesions ($r^2$=0.935 and $r^2$=0.780 respectively). No factor was found predictive of the difference in OR between VE and RECIST. Conclusions: VE exhibited good agreement with RECIST. It might be more useful than RECIST in evaluation shrinking lesions in cases of numerous and conglomerate liver metastases.

• 대한한방내과학회지
• /
• 제29권3호
• /
• pp.827-834
• /
• 2008

Papillary thyroid carcinoma is the most common type of thyroid malignancy. It has better prognosis and rarer incidence of distant metastasis than other types of thyroid malignancy. However, once distant metastasis happens, its result will be bad. They mostly spread to the lungs and bones. and rarely to the brain. We report a patient with a papillary thyroid carcinoma metastasis to the lymph nodes. the ribs. the brain, and the lungs. The patient underwent total thyroidectomy, radioiodine ablation, rib partial resection, and lung wedge resection. However, upon progress of metastasis. the patient insisted on being treated with traditional Korean medical treatment using allergen-removed Rhus Verniciflua Stokes (A-RVS) instead of the conventional treatment including chemotherapy. The size of the tumor partly decreased, and the patient showed no side effects. This case report brings forth the importance of a thorough study in papillary thyroid carcinomas and their metastasis from the traditional Korean medical point of view, along with the long-term effect of allergen-removed Rhus Verniciflua Stokes (A-RVS).

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권13호
• /
• pp.5191-5197
• /
• 2015

A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권20호
• /
• pp.8823-8828
• /
• 2014

Objective: To explore the most appropriate treatment for patients with hepatocellular cancer (HCC) >10 cm by using the Barcelona Clinic Liver Cancer (BCLC) classification. Materials and Methods: A total of 124 HCC patients undergoing surgery were selected. Disease-free survival (DFS), overall survival (OS) and prognostic factors were respectively assessed. Results: This study showed that the cumulative 1-, 3-, 5-year survival rates were 79.7%, 59.8% and 41.6% in BCLC-A patients, 76.2%, 9.5% and 0% in BCLC-B patients and 44.9%, 0% and 0% in BCLC-C patients, respectively. The 1-, 3-, 5-year DFS rates were 49%, 24.5% and 9.1% in BCLC-A patients, 7.5%, 0% and 0% in BCLC-B patients, respectively. No BCLC-C patients survived 1 year after surgery. Multivariate analysis indicated that hepatitis B surface antigen (HBsAg), vascular invasion, intra-hepatic metastasis, curative resection, tumor rupture and pathologic differentiation were independent prognostic factors. Conclusions: Surgery is effective and safe for patients with HCC >10 cm with sufficient hepatic reserve.