• BMB Reports
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• v.39 no.5
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• pp.626-635
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• 2006

Lysophosphatidic acid acyltransferase (LPAAT) is an intrinsic membrane protein that catalyzes the synthesis of phosphatidic acid (PA) from lysophosphatidic acid (LPA). It is well known that LPAAT is involved in lipid biosynthesis, while its role in tumour progression has been of emerging interest in the last few years. To date, seven members of the LPAAT gene family have been found in human. Here we report a novel LPAAT member, designated as LPAAT-theta, which was 2728 base pairs in length and contained an open reading frame (ORF) encoding 434 amino acids. The LPAAT-theta gene consisted of 12 exons and 11 introns, and mapped to chromosome 4q21.23. LPAAT-theta was ubiquitously expressed in 18 human tissues by RT-PCR analysis. Subcellular localization of LPAAT-theta-EGFP fusion protein revealed that LPAAT-theta was distributed primarily in the endoplasmic reticulum (ER) of COS-7 cells. Furthermore, we found that the overexpression of LPAAT-theta can induce mTOR-dependent p70S6K phosphorylation on Thr389 and 4EBP1 phosphorylation on Ser65 in HEK293T cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1077-1082
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• 2016

Background: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer. Materials and Methods: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22. Results: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy. Conclusions: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1149-1155
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• 2016

Background: Examination of sentinel lymph node (SLN) biopsies provides accurate nodal staging for breast cancer and plays a key role in patient management. Procurement of SLNs and the methods used to process specimens are equally important. Increasing the level of detail in histopathological examination of SLNs increases detection of metastatic tumours but will also increase the burden of busy laboratories and thus may not be carried out routinely. Recommendation of a reasonable standard in SLN examination is required to ensure high sensitivity of results while maintaining a manageable practice workload. Materials and Methods: Twenty-four patients with clinically node-negative breast cancer were recruited. Combined radiotracer and blue dye methods were used for identification of SLNs. The nodes were thinly sliced and embedded. Serial sectioning and immunohistochemical (IHC) staining against AE1/AE3 were performed if initial H&E sections of the blocks were negative. Results: SLNs were successfully identified in all patients. Ten cases had nodal metastases with 7 detected in SLNs and 3 detected only in axillary nodes (false negative rate, FNR=30%). Some 5 out of 7 metastatic lesions in the SLNs (71.4%) were detected in initial sections of the thinly sliced tissue. Serial sectioning detected the remaining two cases with either micrometastases or isolated tumour cells (ITC). Conclusions: Thin slicing of tissue to 3-5mm thickness and serial sectioning improved the detection of micro and macro-metastases but the additional burden of serial sectioning gave low yield of micrometastases or ITC and may not be cost effective. IHC validation did not further increase sensitivity of detection. Therefore its use should only be limited to confirmation of suspicious lesions. False negative cases where SLNs were not involved could be due to skipped metastases to non-sentinel nodes or poor technique during procurement, resulting in missed detection of actual SLNs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6133-6137
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• 2012

Purpose: To study the effect of bolus versus no bolus in the coverage of the nodal tumour volume with intensity-modulated radiotherapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). Methods and Materials: This retrospective study used data from 5 consecutive patients with NPC who were treated with bolus for large neck nodes using IMRT from November 2011-January 2012 in our institute. All these patients were treated radically with IMRT according to our institution's protocol. Re-planning with IMRT without bolus for these patients with exactly the same target volumes were done for comparison. Comparison of the plans was done by comparing the V70 of PTV70-N, V66.5 of PTV70-N, V65.1 of PTV70-N and the surface dose of the PTV70-N. Results: The mean size of the largest diameter of the enlarged lymph nodes for the 5 patients was 3.9 cm. The mean distance of the GTV-N to the skin surface was 0.6 cm. The mean V70 of PTV70-N for the 5 patients showed an absolute advantage of 10.8% (92.4% vs. 81.6%) for the plan with bolus while the V66.5 of PTV70-N had an advantage of 8.1% (97.0% vs. 88.9%). The mean V65.1 also had an advantage of 7.1% (97.6% vs. 90.5%). The mean surface dose for the PTV70-N was also much higher at 61.1 Gy for the plans with bolus compared to only 23.5 Gy for the plans without bolus. Conclusion: Neck node bolus technique should be strongly considered in the treatment of NPC with enlarged lymph nodes treated with IMRT. It yields a superior dosimetry compared t o non-bolus plans with acceptable skin toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1453-1456
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• 2012

Background: Prostate cancer is the most common malignant tumour in men and the second most common cause of male cancer death. The study examines the clinicopathological features of patients with prostate cancer consecutively diagnosed at a private Diagnostic Radiology Centre in Western Jamaica over a 6-year period. Method: The medical records, including the pathology reports of 423 consecutive patients who had transrectal ultrasonography (TRUS) - guided prostate biopsy between January 2006 and December 2011 were reviewed. Results: The mean age at diagnosis of the 191 men with prostate adenocarcinoma was $68.5{\pm}0.59$ years with the majority in the 70 - 79 year age group (43.5%). Moderately differentiated carcinomas (Gleason score of 6) comprised the largest group with 72 cases (37.9%); poorly differentiated cancers with Gleason scores of 8 - 10 comprised 49 cases (25.8%). The PSA levels increased with Gleason score. The mean PSA levels for men with Gleason score of 6 was $50.1{\pm}30.0$ ng/mL compared with $136.5 {\pm}59.9$ ng/mL in patients with Gleason score of 8 and $140.5{\pm}31.8$ ng/mL in patients with Gleason score of 9. Perineural invasion was present in 7.85% of the cases overall; high-grade prostatic intraepithelial neoplasia (HGPIN) was present in 4.71% of the biopsies. Conclusion: Although the majority of patients had moderate, and moderate to poor differentiated carcinomas, the number with poorly differentiated carcinoma was high. This is a reflection of the patients' late clinical presentation at the time of diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3821-3824
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• 2012

Aim: SNPs of ERCC1 and ERCC2 genes have been found to be associated with response to platinum therapy in different clinical settings. In the current study, we investigated the relationship of SNPs in ERCC1 and ERCC2 to cisplain response and survival in osteosarcoma patients. Methods: 267 consecutive patients diagnosed with osteosarcoma between January 2003 to January 2005 were followed up until the end of January 2010. ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln polymorphisms were detected based upon the Sequenom MassARRAY platform.Results: For ERCC1 Asn118Asn, the variant genotype T/T was strongly significantly associated with a higher event free survival when compared with the wild-type C/C, with an adjusted OR (95% CI) of 0.39 (0.14-0.95). ERCC2 751 A/A genotype showed increased event free survival of osteosarcoma (HR=0.44; 95%CI=0.10-0.87). However, we did not find significant association of ERCC1 Gln504Lys and ERCC2 Asp312Asn polymorphisms with prognosis of osteosarcoma. Conclusions: We first report associations of four SNPs, ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln, with risk of death from osteosarcoma in a Chinese population, indicating ERCC1 118T/T and ERCC2 A/A may be used as surrogate markers for clinical outcome of osteosarcoma treatmetn with cisplain.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3863-3868
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• 2012

In this study mitochondrial D-Loop variations in Iranian prostate cancer and benign prostatic hyperplasia (BPH) patients were investigated. Tumour samples and corresponding non-cancerous prostate tissue from 40 prostate cancer patients and 40 age-matched BPH patients were collected. The entire mtD-loop region (16024-576) was amplified using the PCR method and products were gel-purified and subjected to direct nucleotide sequencing. A total of 129 variations were found, the most frequent being 263A${\rightarrow}$G and 310T${\rightarrow}$C among both BPH and prostate cancer patients. Variation of 309 C${\rightarrow}$T was significantly more frequent in prostate cancer patients (P value<0.05). Four novel variations were observed on comparison with the MITOMAP database. Novel variations were np16154delT, np366G${\rightarrow}$A, np389G${\rightarrow}$A and 56insT. There was no correspondence between the different variations and the age of subjects. Considering that D-loop variations were frequent in both BPH and prostate cancer patients in our study, the fact that both groups had high average age can be a possible contributing factor. D-loop polymorphisms and microsatellite instability can influence cell physiology and result in a benign or malignant phenotype. Significantly higher frequency of 309 C${\rightarrow}$T variation in cancer patients is a notable finding and must be a focus of attention in future studies.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3857-3862
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• 2012

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7281-7285
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• 2014

Background: Gastric cancer is the second most common gastrointestinal cancer and is more common in the East, compared to the West. This study assesses the trend of gastric cancers in Brunei Darussalam, a developing nation with a predominantly Malay population. Materials and Methods: The cancer registry from 1986 to 2012 maintained by the Department of Pathology, the only State Laboratory at the RIPAS Hospital, Ministry of Health, was reviewed and data extracted for analyses. The age standardised rate (ASR) and age specific incidence rate were calculated based on the projected population. Cancers diagnosed below 45 years were categorised as young gastric cancer. Results: Over the study period, there were a total of 551 cases of gastric cancer diagnosed. The most common type was adenocarcinoma (87.9%), followed by lymphoma (6.1%) and gastrointestinal stromal tumour (2.8%). The overall mean age at diagnosis was 61.9 years old (range 15 to 98) with an increasing trend observed, but this was not significant (ANOVA). There were differences in the mean age at diagnosis for the different races (p=0.003 for trend), but not the gender (p=0.105). Young gastric cancer accounted for 14.9%, being more common in women, and in Expatriate and Malay populations compared to the Chinese. There was a decrease in the ASR, from 17.3/100,000 in 1986-1990 to 12.5/100,000 in 2006-2010. Chinese had a higher overall ASR (20.2/100,000) compared to the Malays (11.8/100,000). The age specific rates were comparable between men and women until the age group 55-59 years when the rates started to diverge, becoming higher in men. Chinese men had higher rates then Malay men whereas, the rates were higher or comparable between the women until the age group >70 when the rate for Chinese women overtook their Malay counterpart. Conclusions: Our study showed that there is a declining trend in the incidence of gastric cancer and higher rates were observed in men and Chinese.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7563-7567
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• 2014

Background: Hepatocellular carcinoma (HCC) is the first cause of death in cirrhotic patients, mostly due to viral hepatitis with HCV or HBV infection. This study was performed to estimate the true prevalence of viral hepatitis-related HCC and the demographic and clinical-pathological associations with the two virus types. Materials and Methods: This cross sectional observational study enrolled clinical data base of 188 HCC patients and variables included from baseline were age, sex, area of residence, clinical-pathological features such as underlying co-morbidity, presence or absence of liver cirrhosis, macrovascular involvement, tumor extension and metastasis, liver lobes involved, serum alpha-fetoprotein level, and hepatitis serologies. Results: Overall prevalence of HCV- and HBV-related HCC was 66.0% and 34.0%, respectively. Patients with HCV were more likely to develop HCC at advanced age ($52.4{\pm}11.9$ vs. $40.7{\pm}12.09$ years), with highly raised serum AFP levels (${\geq}400ng/ml$) 78.2% (HBV 67.1%), large tumor size (HCV-66% >5 cm, HBV-59.3%), and presence of portal vein thrombosis (8.06%, HBV 1.56%). A binominal multivariate analysis showed that HCV-HCC group were more likely to be cirrhotic (OR=0.245, 95%CI: 0.117, 0.516) and had more than two times higher rate of solitary macrovascular involvement (OR=2.533, 95%CI: 1.162, 5.521) as compared with HBV associated HCC. Conclusions: Statistically significant variations were observed from baseline to clinical-pathological characteristics in HCV vs HBV associated HCC. Our study suggests prompt and early screening for high risk patients so that the rate of progression of these chronic viral diseases to cirrhosis and cancer can be decreased.