• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5971-5976
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• 2015

Background: Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC. Materials and Methods: This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis. Results: The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was $3.2{\pm}1.7g/dL$ (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC. Conclusions: This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5773-5777
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• 2015

Background: Oral squamous cell carcinoma (OSCC) is thought to develop from precancerous dysplastic lesions through multistep processes of carcinogenesis involving activation of oncogenes and loss of tumor suppressor genes. The human epidermal growth factor receptor 2 (Her-2/neu [erbB-2]), a cell membrane glycoprotein, is a growth factor receptor that has receptor tyrosine kinase activity. Her2/neu activation plays a central role in cell proliferation and survival. It has been shown that overexpression of Her2/neu increases the rate of cell division and growth, leading to precancerous changes. The aim of the present study was to compare the serum and salivary Her2/neu levels between cases with premalignant and malignant oral lesions. Materials and Methods: Fasting blood samples and unstimulated saliva by passive drooling were collected from three groups of healthy control (n=20), premalignant disorder (PMD) (n=20) and OSCC (n=25) subjects. The HER2 extracellular domain (HER2 ECD) levels were measured using ELISA. Results: The levels of serum Her2/neu showed no significant differences between any of the groups but on the other hand salivary Her2/neu levels were found to be significantly (p<0.05) higher when compared between control (median 68.7 pg/ml, range: 21.5 - 75.8) and OSCC (median 145.6 pg/ml, range: 45.1-191.1). A similar trend was observed when comparing between PMD (median 43.3, range: 22.1 -94.7) and OSCC with a statistical significance of p<0.05. Conclusions: Our study provided evidence of increased salivary Her2/neu in OSCC when compared to PMD and control which was not the case for serum levels. This suggests that probably Her2/neu is not highly amplified as in breast cancer so as to be reflected in serum. Since saliva is in local vicinity of the OSCC, even a mild increase might be mirrored. On the whole, this study proposes Her2/neu as marker for distinguishing premalignant and malignant conditions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.9005-9008
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• 2014

Background: Gastric cancer is the second leading course of cancer death worldwide and H. pylori infection is an important risk factor for gastric cancer development. This study was design to evaluate the clinical, pathological features, survival rate and prevalence of H. pylori infection in gastric cancer in Thailand. Materials and Methods: Clinical information, histological features, endoscopic findings and H. pylori status were collected from gastric cancer patients from Thammasat university hospital during June 1996-December 2011. H. pylori infection was assessed by histological evaluation, rapid urease test and serological test. Clinical information, endoscopic findings and histopathology of all patients were recorded and compared between patients with active or non-active H. pylori infection. Results: A total of 100 gastric cancer patients (55 men and 45 women with mean age of $55{\pm}16.8years$) were enrolled in this study. Common presenting symptoms were dyspepsia (74%), weight loss (66%), anemia (63%) and anorexia (38%). Mean duration of symptoms prior to diagnosis was 98 days. Overall prevalence of H. pylori infection was 83% and active H. pylori infection was 40%. 1-year and 5-year survival rates were 43% and 0%. There was no significant difference between active H. pylori infection in different locations (proximal vs non-proximal: 47.1% vs 48.5%; P-value = 0.9, OR=0.9; 95%CI=0.3-3.1) and histology of gastric cancer (diffuse type vs intestinal type: 47.4% vs 50%; P-value = 0.8, OR=0.9, 95%CI=0.3-2.7). However, linitis plastica was significantly more common in non-active than active H. pylori infection (27.9% vs 0%; P-value<0.0001, OR=13.3, 95%CI=3.2-64.5). Moreover, gastric cancer stage 4 was higher in non-active than active H. pylori infection (93% vs 50%, P-value<0.001). Conclusions: Prevalence of H. pylori infection in Thai gastric cancer patients was high but active infection was low. Most gastric cancer patients presented in advance stage and had a grave prognosis. Screening for gastric cancer in high risk individuals might be an appropriate tool for early detection and improve the treatment outcome for this particular disease in Thailand.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5915-5920
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• 2013

Aim: Although aberrant miRNA expression has been documented, altered miR-101 expression in cervical cancer and its carcinogenic effects and mechanisms remain unexplored. The aim of our study was to investigate the role of miR-101 alteration in cervical carcinogenesis. Methods: Expression of miR-101 was examined by quantitative real-time reverse transcriptase PCR (qRT-PCR) in Hela cells. After modulating miR-101 expression using miR-101 mimics, cell growth, apoptosis and proliferation, and migration were tested separately by MTT or flow cytometry and cell wound healing assay and protein expression was detected by qRT-PCR. The expression of COX-2 in Hela cell was also examined by immunohistochemical staining and the correlation with miR-101 expression was analysed. Results: The miR-101 demonstrated significantly low expression in Hela cell. When we transfected miR-101 mimics into Hela cells, the modulation of miR-101 expression remarkably influenced cell proliferation, cycling and apoptosis: 1) The expression of microRNA-101 tended to increase after transfection; 2) Overexpression of miR-101 was able to promote cell apoptosis, the apoptosis rate being markedly higher (97.6%) than that seen pre-transfection (12.2%) (P<0.05); 3) The miR-101 negatively regulates cell migration and invasion, scratch results being lower ($42.7um{\pm}2um$) than that observed pre-transfection ($181.4um{\pm}2um$); 4) miRNA-101 inhibits the proliferation of Hela cells as well as the level of COX-2 protein, which was negatively correlated with miR-101 expression. Conclusions: Overexpression of miR-101 has obvious inhibitory effects on cell proliferation, migration and invasion. Thus reduced miR-101 expression could participate in the development of cervical cancer at least partly through loss of inhibition of target gene COX-2, which probably occurs in a relative late phase of carcinogenesis. Our data suggest an important role of miR-101 in the molecular etiology of cancer and indicate potential application of miR-101 in cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6165-6171
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• 2013

This study aimed to analyze the expression and clinical significance of cyclin G2 (CCNG2) in thyroid carcinoma and the biological effects of CCNG2 overexpression in a cell line. Immunohistochemistry and Western blotting were used to analyze CCNG2 protein expression in 63 cases of thyroid cancer and normal tissues to allow the relationship with clinical factors to be assessed. CCNG2 lentiviral and empty vectors were transfected into the thyroid cancer K1 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were applied to detect the mRNA and protein levels of CCNG2. MTT assay and cell cycle were also conducted to assess the influence of up-regulated expression of CCNG2 on K1 cell biology. The level of CCNG2 protein expression was found to be significantly lower in thyroid cancer tissue than normal tissues (P<0.05). Western blot: The relative amount of CCNG2 protein in thyroid cancer tissue was respectively found to be significantly lower than in normal tissues (P<0.05), correlating with lymph node metastasis, clinic stage and histological grade (P<0.05), but not gender, age or tumor size (P>0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time on Kaplan-Meier analysis (P<0.05). The results for biological functions showed that K1 cell transfected CCNG2 had a lower survival fraction, a greater percentage in the G0/G1 phases, and lower cyclin-dependent kinase 2 (CDK2) protein expression compared with K1 cells non-transfected with CCNG2 (P<0.05). CCNG2 expression decreased in thyroid cancer and correlated significantly lymph node metastasis, clinic stage, histological grade and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator in thyroid cancer K1 cells by promoting degradation of CDK2.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1917-1923
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• 2016

Background: Lynch Syndrome (LS) is a familial cancer condition caused by germline mutations in DNA mismatch repair genes. Individuals with LS have a greatly increased risk of developing colorectal cancer (CRC) and it is therefore important to identify mutation carriers so they can undergo regular surveillance. Tumor DNA from LS patients characteristically shows microsatellite instability (MSI). Our aim here was to screen young CRC patients for MSI as a first step in the identification of unrecognized cases of LS in the Saudi population. Materials and Methods: Archival tumor tissue was obtained from 284 CRC patients treated at 4 institutes in Dammam and Riyadh between 2006 and 2015 and aged less than 60 years at diagnosis. MSI screening was performed using the BAT-26 microsatellite marker and positive cases confirmed using the pentaplex MSI analysis system. Positive cases were screened for BRAF mutations to exclude sporadic CRC and were evaluated for loss of expression of 4 DNA mismatch repair proteins using immunohistochemistry. Results: MSI was found in 33/284 (11.6%) cases, of which only one showed a BRAF mutation. Saudi MSI cases showed similar instability in the BAT-26 and BAT-25 markers to Australian MSI cases, but significantly lower frequencies of instability in 3 other microsatellite markers. Conclusions: MSI screening of young Saudi CRC patients reveals that approximately 1 in 9 are candidates for LS. Patients with MSI are strongly recommended to undergo genetic counselling and germline mutation testing for LS. Other affected family members can then be identified and offered regular surveillance for early detection of LS-associated cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3223-3227
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• 2015

Objective: We evaluated the association of body mass index (BMI) with perioperative outcomes in patients who underwent laparoscopic or open radical nephroureterectomy. Materials and Methods: This retrospective single-center study included 113 patients who had been diagnosed with upper urinary tract cancer from January 1998 to June 2013 and were treated with laparoscopic nephroureterectomy (Lap group, n=60) or open nephroureterectomy (Open group, n=53). Laparoscopic nephroureterectomy was performed via a retroperitoneal approach following an open partial cystectomy. The two surgical groups were stratified into a normal-BMI group (<25) and a high-BMI group ($BMI{\geq}25$). The high-BMI group included 27 patients: 13 in the Lap group and 14 in the Open group. Results: Estimated blood loss (EBL) in the Lap group was much lower than that in the Open group irrespective of BMI (p<0.01). Operative time was significantly prolonged in normal-BMI patients in the Lap group compared to those in the Open group (p=0.03), but there was no difference in operative time between the Open and Lap groups among the high-BMI patients. Multivariate logistic regression analysis of the data for all the cohorts revealed that the open procedure was a significant risk factor for high EBL (p<0.0001, hazard ratio 8.02). Normal BMI was an independent predictor for low EBL (p=0.01, hazard ratio 0.25). There was no significant risk factor for operative time in multivariate analysis. There were no differences in blood transfusion rates or adverse event rates between the two surgical groups. Conclusions: Laparoscopic radical nephroureterectomy via a retroperitoneal approach can be safely performed with significantly reduced EBL even in obese patients with upper urinary tract cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.691-694
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• 2014

Background: Tumor length in patients with esophageal cancer (EC) has recently received great attention. However, its prognostic role for EC is controversial. The purpose of our study was to characterize the prognostic value of tumor length in EC patients and offer the optimum cut-off point of tumor length by reliable statistical methods. Materials and Methods: A retrospective analysis was conducted on 71 consecutive patients with EC who underwent surgery. ROC curve analysis was used to determine the optimal cut-off point for tumor length, measured with a handheld ruler after formalin fixation. Correlations between tumor length and other factors were surveyed, and overall survival (OS) rates were compared between the two groups. Potential prognostic factors were evaluated by univariate Kaplan-Meier survival analysis. A P value less than 0.05 was considered significant. Results: There were a total of 71 patients, with a male/female divide of 43/28 and a median age of 59. Characteristics were as follows: squamous/adenocarcinoma, 65/6; median tumor length, 4 (0.9-10); cut-off point for tumor length, 4cm. Univariate analysis prognostic factors were tumor length and modality of therapy. One, three and five year OS rates were 84, 43 and 43% for tumors with ${\leq}4cm$ length, whereas the rates were 75, 9 and 0% for tumors >4 cm. There was a significant association between tumor length and age, sex, weight loss, tumor site, histology, T and N scores, differentiation, stage, modality of therapy and longitudinal margin involvement. Conclusions: Future studies for modification of the EC staging system might consider tumor length too as it is an important prognostic factor. Further assessment with larger prospective datasets and practical methods (such as endoscopy) is needed to establish an optimal cut-off point for tumor length.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2717-2722
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• 2013

Background: The objective of this research is the computed axial tomography (CT) imaging grading of radiation induced pneumonitis (RP) and its correlation with clinical and radiotherapeutic parameters. Materials and Methods: The chest CT films of 20 patients with non-small cell lung cancer who have undergone threedimensional conformal radiation therapy were reviewed. The proposed CT grading of RP is supported on solely radiological diagnosis criteria and distinguishes five grades. The manifestation of RP was also correlated with any positive pre-existing chronic obstructive pulmonary disease (COPD) history, smoking history, the FEV1 value, and the dosimetric variable V20. Results: The CT grading of RP was as follows: 3 patients (15%) presented with ground glass opacity (grade 1), 9 patients (45%) were classified as grade 2, 7 patients (35%) presented with focal consolidation, with or without elements of fibrosis (grade 3), and only one patient (5%) presented with opacity with accompanying atelectasis and loss of pulmonary volume (grade 4). Both univariate and multivariate analysis revealed as prognostic factors for the radiological grading of RP the reduction of FEV1 and the V20 (P=0.026 and P=0.003, respectively). There was also a significant (P<0.001) correlation of radiological grading of RP with FEV1 and V20 (spearman rho 0.92 and 0.93, respectively). Conclusions: The high correlation of the proposed radiological grading with the FEV1 and the V20 is giving a satisfactory clinical validity. Although the proposed grading scale seems relevant to clinical practice, further studies are needed for the confirmation of its validity and reliability.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3431-3436
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• 2016

Background: Carcinogenesis is a multifaceted intricate cellular mechanism of transformation of the normal functions of a cell into neoplastic alterations. Metastasis may result in failure of conventional treatment and death Hence, research on metastatic suppressors in cancer is a high priority. The metastatic suppressor gene CD82, also known as KAI1, is a member of the transmembrane 4 superfamily which was first identified in carcinoma of prostate. Little work has been done on this gene in breast cancer. Herein, we aimed to determine the gene and protein level expression of CD82/KAI1 in breast cancer and its role as a prognosticator. Materials and Methods: In this study, 83 histologically proven cases of breast cancer and a similar number of controls were included. Patient age ranged from 18-70 years. Quantitative Real Time Polymerase Chain Reaction (q-RT PCR) and immunohistochemistry (IHC) were used to investigate KAI1 expression at gene and protein levels, respectively. Statistical analysis was done to correlate expression of KAI1 and clinicopathological parameters. Results: It was revealed that: (i) KAI1 was remarkably diminished in metastatic vs non metastatic breast cancer both at the gene and the protein levels (P < .05); (ii) KAI1 expression levels were strongly correlated with TNM staging, histological grade and advanced stage (p<0.001) and no association was found with any other studied parameter; (iii) Lastly, a significant correlation was observed between expression of KAI1 and overall median survival of BC patients (P = 0.04). Conclusions: Our results suggest that lack of expression of the KAI1 might indicate a more aggressive form of breast cancer. Loss of KAI1 may be considered a significant prognostic marker in predicting metastatic manifestation. When evaluated along with the clinical and pathological factors, KAI1 expression may be beneficial to tailor aggressive therapeutic strategies for such patients.