Paramee Thongsuksai

Lifestyle habits and genetic susceptibility and the risk of esophageal cancer in the Thai population

The association of lifestyle habits and polymorphism of ADH2 and ALDH2 genes with the risk of esophageal cancer in Thai population was investigated in a hospital-based case-control study: 202 cases and 261 controls. The results of multivariate logistic analysis showed that alcohol consumption >60g/day, smoking >10 cigarettes/day and chewing betel >or=10 quids/day significantly increased risk (odds ratio (OR) 5.84, 95% confidence interval (CI) 3.15-10.83; 4.65, 95% CI 1.99-10.84; and 4.68, 95% CI 2.05-10.72, respectively). ADH2*1/*1 also increased the risk significantly (OR 1.56, 95% CI 1.01-2.39) while ALDH2 did not (OR of ALDH2*1/*2 1.57, 95% CI 0.89-2.76). However, the combined at risk genotypes, ADH2*1/*1 and ALDH2*1/*2 increased risk to four-fold. In addition, significant gene-environment interaction was found. Heavy drinkers >60g/d harboring ADH2*1/*1 or ALDH2*1/*2 had about an 11-fold increased risk.

Delay in breast cancer care: a study in Thai women.

BACKGROUND Breast cancer is the second most common cause of cancer death in Thai women. Cancer registry data reveal a high prevalence of late-stage disease at diagnosis. The factors resulting in delay in Thailand have not yet been investigated. OBJECTIVES To determine the extent of, and the factors contributing to, delay in breast cancer care. DESIGN Women with breast cancer who were first treated at Songklanagarind Hospital between June 1994 and June 1996 were interviewed with retrospective chart audits of care. MEASURES Dependent variables included patient delay (symptom recognition to first care) and system delay (first care to treatment). Independent variables tested included demographic factors, help-seeking behavior, and cancer knowledge. Nonparametric rank sum tests were used for univariate analysis, and Cox regression was used for multivariate analysis. RESULTS Ninety-four cases were included in the study. The median patient and system delays were 4 weeks; 26.6% and 24.4% of patients, respectively, experienced patient and system delay >12 weeks. Only marital status (unmarried compared with married women) was significantly associated with patient delay (hazard ratio [HR] 2.78, 95% CI 1.23-6.25). Contacting a provincial hospital instead of a university hospital as first medical care (hazard ratio 2.50, 1.23-5.26), being given a diagnosis rather than being told nothing (HR 2.04, 1.14-3.57) and being given treatment rather than being immediately referred (HR 4.55, 2.22-9.09) were associated with system delay. CONCLUSIONS Patient delay and system delay in breast cancer care are important weaknesses of disease control in Thailand. Educational programs should target unmarried women, who are at higher risk of delay. System delay in hospitals outside the university needs to be improved by a good referral system.

p53 expression related to the aggressive infiltrative histopathological feature of basal cell carcinoma

p53 expression related to the aggressive infiltrative histopathological feature of basal cell carcinoma

Survival and Prognostic Factors of Different Sites of Head and Neck Cancer: An Analysis from Thailand

BACKGROUND Head and neck cancers are prevalent in Thailand, in particular in the southern region of the country. However, survival with a large data set has not been reported. The purpose of the present study was to evaluate the survival figures and the prognostic factors in a cohort of patients treated in a university hospital located in the south of Thailand. PATIENTS AND METHODS Consecutive new cases of primary carcinoma of the oral cavity, oropharyx, hypopharynx and larynx, treated at Songklanagarind Hospital during 2002 to 2004, were analyzed. The 5-year overall survival rates were obtained by the Kaplan-Meier method. Prognostic factors were identified through multivariate Cox regression analysis. RESULTS A total 1,186 cases were analyzed. Two-thirds (66.6%) of the cases were at advanced stage (stage III and IV) at presentation. The five-year overall survivals for the whole cohort, oral cavity, oropharynx, hypopharynx and larynx were 24.1%, 25.91%, 19.2%, 13.4%, 38.0% respectively. Stage and treatment type were strong prognostic factors for all sites. An age ≥80 years was associated with poor survival in oral cavity and larynx cancer. CONCLUSIONS The results revealed remarkably poor outcomes of the patients in the series, indicating a strong need to increase the proportion of early stage presentations and maximize the treatment efficacy to improving outcomes. Very old patients are of particular concern for treatment care of oral cavity and larynx cancer.

p53 mutations in betel-associated oral cancer from Thailand

The p53 mutations in betel-related oral cancer have been studied but the results may be confounded by tobacco and alcohol due to tobacco components in the quid or concomitant habits of smoking and drinking. In this study, p53 mutations in tumors from Thai betel chewers who neither smoke nor drink were studied in comparison to tumors from smokers/drinkers. PCR-SSCP analysis and direct sequencing on exon 5-8 were performed. Mutations were detected in 11.8% (8/68) of betel-related tumors and 7 of 8 mutations were G:C to A:T transitions. By contrast, mutations were found in 22.4% (13/58) of smoking/drinking-related tumors with various base substitutions. The results demonstrated different mutation profiles between the two exposed groups. The type of mutation detected in betel chewers suggested a possible role of areca-specific nitrosamine as a causative carcinogen.

Prognostic significance of 14-3-3γ overexpression in advanced non-small cell lung cancer.

The 14-3-3 protein has been shown to be involved in the cancer process. However, there is no understanding of the relationship between 14-3-3γ (14-3-3 gamma) expression and prognosis in advanced non-small cell lung cancer. In this study, we therefore investigated the association between protein levels by immunohistochemistry and clinicopathological features of advanced NSCLC patients. Survival curves were estimated using the Kaplan-Meier method and tested by log-rank. Multivariate analysis was conducted with the Coxs regression model to determine independence of factors. p values less than 0.05 were considered significant. A total 153 patients were studied, with 54.3% being stage III and 45.8% stage IV. Fifty-one cases (33.3%) were squamous cell carcinomas, and 98 cases (64.1%) were adenocarcinomas. High 14-3-3γ expression was seen in 59.5% and significantly correlated with lymph node metastasis (p=0.010) and distant metastasis (p=0.017). On Kaplan-Meier analysis, high 14-3-3γ expression was associated with poorer survival with a marginal trend toward significance (p=0.055). On multivariate analysis, age, treatment, and 14-3-3γ expression proved to be independent prognostic parameters. In vitro experiments indicated that 14-3-3γ overexpression also played a potential role in cancer invasion. In conclusion, our data suggest that 14-3-3γ overexpression is associated with invasion and a poor prognosis. Therefore, 14-3-3γ may be a potential prognostic marker of advanced non-small cell lung cancer.

Comparative proteomic analysis of oral squamous cell carcinoma and adjacent non-tumour tissue from Thailand

OBJECTIVE The study was aimed at analysing and identifying the proteins that are differentially expressed in oral squamous cell carcinoma (OSCC) compared to adjacent non-tumour tissue. MATERIALS AND METHODS Two-dimensional (2D) sodium dodecyl sulphate-polyacrylamide gel electrophoresis accompanied by mass spectrometry (matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry) was used to analyse and identify the differentially expressed proteins in 10 pairs of tumours and adjacent non-tumour tissues from five cases of early-stage and five cases of late-stage OSCC. The statistical differences of the protein spots were analysed by the Wilcoxon signed-rank test. A validation study using immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed. RESULTS A total of 68 proteins (63 up-regulated, five down-regulated) were differentially expressed in early-stage disease, and 39 proteins (37 up-regulated, two down-regulated) were significantly altered in late-stage disease. Among these, 14 proteins were altered in both groups. A total of 44 proteins were identified, including heat shock proteins (HSPs: Hsp90, HSPA5 and HSPA8), keratins (K1, K6A and K17), tubulin, cofilin 1, 14-3-3σ and metabolic enzymes. These proteins are involved in various cellular processes essential for cell growth, survival and cell migration. The validation study on α-tubulin and 14-3-3σ using immunohistochemistry and KIAA1199 expression using real-time RT-PCR confirmed the results in proteomics analysis. CONCLUSIONS The study identified many proteins, both known and unknown, for cancer cell processes. At least two proteins, KIAA1199 and Horf6, are novel for oral cancer.

Methylation of 14‑3‑3σ gene and prognostic significance of 14‑3‑3σ expression in non‑small cell lung cancer

Loss of 14-3-3σ expression through DNA methylation has been associated with carcinogenesis and the prognosis for various cancer types. Detection of methylation of the gene in serum may be useful for diagnostic utility. The present study aimed to investigate the correlation between 14-3-3σ methylation level in 36 paired tumor tissues of non-small cell lung cancer (NSCLC) and matched serum using methylation-specific polymerase chain reaction. The prognostic significance of 14-3-3σ expression in 167 NSCLC was also evaluated using immunohistochemistry. Methylation of the 14-3-3σ gene was identified in all samples. The methylation level in the serum (mean 87.7%, range 64.6–100%) was higher compared with tumor (mean 46.7%, range 25.3–56.3%). However, no significant correlation between methylation levels in tissues and serums was observed (Spearmans correlation, −0.036; P=0.837). In the 167 tumor tissues, the majority of the cases (83.8%) exhibited negative expression. Adenocarcinoma is more likely to exhibit negative expression (91.4%) compared with squamous cell carcinoma (70.2%). No significant difference was identified in the overall survival according to 14-3-3σ expression status and 14-3-3σ expression did not demonstrated independent prognostic significance. In conclusion, NSCLC harbors certain levels of 14-3-3σ methylation in the tumor and the sera of patients. The clinical value of serum 14-3-3σ methylation should be further elucidated. Immunohistochemical expression 14-3-3σ protein has limited value on prognostic significance.

Chalkley Microvessel but not Lymphatic Vessel Density Correlates with Axillary Lymph Node Metastasis in Primary Breast Cancers

This study aimed to investigate tumor microvessel density (MVD) and lymphatic vessel density (LVD) using the Chalkley method as predictive markers for the risk of axillary lymph node metastasis and their relationship to other clinicopathological parameters in primary breast cancer cases. Forty two node-positive and eighty node-negative breast cancers were immunostained for CD34 and D2-40. MVD and LVD were counted by the Chalkley method at x400 magnification. There was a positive significant correlation of the MVD with the tumor size, coexisting ductal carcinoma in situ (DCIS) and lymph node metastases (P<0.05). In multivariate analysis, the MVD (2.86-4: OR 5.87 95%CI 1.05-32; >4: OR 20.03 95%CI 3.47-115.6), lymphovascular invasion (OR 3.46, 95% CI 1.13-10.6), and associated DCIS (OR 3.1, 95%CI 1.04-9.23) independently predicted axillary lymph node metastasis. There was no significant relationship between LVD and axillary lymph node metastasis. However, D2-40 was a good lymphatic vessel marker to enhance the detection of lymphatic invasion compared to H and E staining. In conclusion, MVD by the Chalkley method, lymphovascular invasion and associated DCIS can be additional predictive factors for axillary lymph node metastases in breast cancer. No relationship was identified between LVD and clinicopathological variables, including axillary lymph node metastasis.

Knockdown of 14-3-3γ Suppresses Epithelial–Mesenchymal Transition and Reduces Metastatic Potential of Human Non-small Cell Lung Cancer Cells

Background/Aim: 14-3-3γ is involved in the metastasis of lung cancer cells. However, its functional roles in tumor cell invasion and the underlying mechanisms are still not understood. In this study, the roles and molecular mechanisms of 14-3-3γ in epithelial–mesenchymal transition (EMT), migration, and invasion were investigated using A549 and H358 non-small cell lung cancer (NSCLC) cell lines. Materials and Methods: siRNA against 14-3-3γ was used to suppress 14-3-3γ expression. Expression levels of proteins were detected by western blotting. Activity of matrix metalloproteinases (MMP)-2 and MMP9 was determined by gelatin zymography. Cell migration and invasion were analyzed using the Transwell assay. Results: Knockdown of 14-3-3γ resulted in a significant reduction of expression of EMT-associated proteins in NSCLC cell lines, and led to significant reduction in invasion and migration by approximately 59% and 39% in A549 cells, and 65% and 62% in H358 cells, respectively. In addition, MMP2 and MMP9 activity was significantly reduced in both NSCLC cell lines after down-regulation of 14-3-3γ. Conclusion: Our results suggest that knockdown of 14-3-3γ may be a potential strategy for suppressing metastasis of lung cancer by inhibiting MMP2 and MMP9 through regulation of EMT.