• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3197-3203
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• 2013

Background: microRNAs (miRNAs) that regulate proliferation, invasion and metastasis are considered to be the principal molecular basis of tumor heterogeneity. Breast cancer is not a homogeneous tissue. Thus, it is very important to perform microarray-based miRNA screening of tumors at different sites. Methods: Breast tissue samples from the centers and edges of tumors of 30 patients were classified into 5 clinicopathological subtypes. In each group, 6 specimens were examined by microRNA array. All differential miRNAs were analyzed between the edges and centers of the tumors. Results: Seventeen kinds of miRNAs were heterogeneously distributed in the tumors from different clinicopathological subtypes that included 1 kind of miRNA in Luminal A and Luminal B Her2+ subtypes, 4 kinds in Luminal A and Her2 overexpression subtypes, 6 kinds in Luminal B Ki67+ and Luminal B Her2+ subtypes, 2 kinds between Luminal B Ki67+ and triple-negative breast cancer (TNBC) subtypes, 2 kinds between Luminal B Her2+ and TNBC subtypes, and 2 kinds between Luminal B Ki67+, Luminal B Her2+, and TNBC subtypes. Twenty kinds of miRNAs were homogenously distributed in the tumors from different clinicopathological subtypes that included 6 kinds of miRNAs in Luminal B Ki67+ and Luminal B Her2+ subtypes, 1 kind in Luminal B Ki67+ and Her2 overexpression subtypes, 10 kinds between Luminal B Ki67+ and TNBC subtypes, 2 kinds in Luminal B Her2+ and TNBC subtypes, and 1 kind between Luminal B Ki67+, Luminal B Her2+, and TNBC subtypes. Conclusions: A total of 37 miRNAs were significantly distributed in tumors from the centers to edges, and in all clinicopathological subtypes.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4113-4117
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• 2012

Breast cancer is a prevalent heterogeneous malignant disease. Gene expression profiling by DNA microarray can classify breast tumors into five different molecular subtypes: luminal A, luminal B, HER-2, basal and normal-like which have differing prognosis. Recently it has been shown that immunohistochemistry (IHC) markers including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2), can divide tumors to main subtypes: luminal A (ER+; PR+/-; HER-2-), luminal B (ER+;PR+/-; HER-2+), basal-like (ER-;PR-;HER2-) and Her2+ (ER-; PR-; HER-2+). Some subtypes such as basal-like subtype have been characterized by poor prognosis and reduced overall survival. Due to the importance of the ER signaling pathway in mammary cell proliferation; it appears that epigenetic changes in the $ER{\alpha}$ gene as a central component of this pathway, may contribute to prognostic prediction. Thus this study aimed to clarify the correlation of different IHC-based subtypes of breast tumors with $ER{\alpha}$ methylation in Iranian breast cancer patients. For this purpose one hundred fresh breast tumors obtained by surgical resection underwent DNA extraction for assessment of their ER methylation status by methylation specific PCR (MSP). These tumors were classified into main subtypes according to IHC markers and data were collected on pathological features of the patients. $ER{\alpha}$ methylation was found in 25 of 28 (89.3%) basal tumors, 21 of 24 (87.5%) Her2+ tumors, 18 of 34 (52.9%) luminal A tumors and 7 of 14 (50%) luminal B tumors. A strong correlation was found between $ER{\alpha}$ methylation and poor prognosis tumor subtypes (basal and Her2+) in patients (P<0.001). Our findings show that $ER{\alpha}$ methylation is correlated with poor prognosis subtypes of breast tumors in Iranian patients and may play an important role in pathogenesis of the more aggressive breast tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6109-6113
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• 2014

Background: Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. They are classified into luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes. Most of breast cancers reported in Indonesia are already large size, with high grade or late stage but the clinicopathological features of different molecular subtypes are still unclear. They need to be better clarified to determine proper treatment and prognosis. Aim: To elaborate the clinicopathological features of molecular subtypes of breast cancers in Indonesian women. Materials and Methods: A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast cancer samples from Dr. Sardjito General Hospital in Central Java, Indonesia was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The relation of clinicopathological features of breast cancers with molecular subtypes of luminal A, luminal B, Her-2 and triple negative/basal-like were analyzed using Pearson's Chi-Square test. A p-value of <0.05 was considered statistically significant. Results: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal-like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant difference was found in breast cancer molecular subtypes in regard to age, histological grade, lymph node status and staging. However it showed insignificant result in regard to tumor size. Luminal A subtype of breast cancer was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09), negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the difference was insignificant, luminal A subtype breast cancer was mostly found in small size breast cancer (p:0.129). Her-2+ subtype breast cancer was more commonly diagnosed with large size, positive lymph node metastasis and poor grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old women. Conclusions: This study suggests that immunohistochemistry-based subtyping is essential to classify breast carcinoma into subtypes that vary in clinicopathological features, implying different therapeutic options and prognosis for each subtype.

• The Korean Journal of Zoology
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• v.31 no.2
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• pp.133-141
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• 1988

These studies have been carried out to examine the stability of enzyme activity of PGM$_1$subtypes in seminal stains and vaginal stains according to the period of storage time by means of polyacryiamide gel(PAG) isoelectric focusing. The results from the experiments were as follows. (1) The stabflity of enzyme activity of PGM$_1$subtypes was detennined from seminal stains and vaginal stains according to the period of storage time. The PGM$_1$ subtypes of seminal stains stored at room temperature could be detennined 86% after 7 days and 15% after 14 days, but almost impossible after 21 days. (2) In the case of vaginal stains stored at room temperature, PGM$_1$ subtypes could be determined 67% after 7 days, but almost impossible after 14 days. On the other hand, when the vaginal fluid was mixed with seminal fluid, PGM$_1$ subtypes of the seminal fluid could be postulated by the determination of PGM$_1$ subtypes from the vaginal fluid.These results lead to the possibility of application in forensic biology.

• Communications for Statistical Applications and Methods
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• v.26 no.4
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• pp.411-430
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• 2019

Tumor development is driven by complex combinations of biological elements. Recent advances suggest that molecularly distinct subtypes of breast cancers may respond differently to pathway-targeted therapies. Thus, it is important to dissect pathway disturbances by integrating multiple molecular profiles, such as genetic, genomic and epigenomic data. However, missing data are often present in the -omic profiles of interest. Motivated by genomic data integration and imputation, we present a new statistical framework for pathway significance analysis. Specifically, we develop a new strategy for imputation of missing data in large-scale genomic studies, which adapts low-rank, structured matrix completion. Our iterative strategy enables us to impute missing data in complex configurations across multiple data platforms. In turn, we perform large-scale pathway analysis integrating gene expression, copy number, and methylation data. The advantages of the proposed statistical framework are demonstrated through simulations and real applications to breast cancer subtypes. We demonstrate superior power to identify pathway disturbances, compared with other imputation strategies. We also identify differential pathway activity across different breast tumor subtypes.

• Phonetics and Speech Sciences
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• v.2 no.2
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• pp.93-100
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• 2010

The purpose of this study was to investigate the differences of feeding ability and articulatory function in the children with spastic cerebral palsy and typically developing children according to feeding subtypes. The feeding subtypes were limited by chewing, cup drinking and spoon feeding. 14 children with spastic cerebral palsy and 14 typically developing children were participated in this study. The results were following as; First, there were significant differences in overall articulatory function between two groups Second, all scores of articulators' function according to feeding subtypes in children with cerebral palsy was significantly higher than typically developing children Third, chewing mode in feeding subtypes was highly correlated with lip and tongue movement. compared to another Finally, the correlation between spoon feeding and mobility of lip and tongue was high in both groups. These results suggested that These results suggest that the effort to find out the differences feeding ability and appliances for articulatory function in CP children are meaningful in catching their speech ability indirectly. Moreover, the more organized feeding skills should be discussed in the relationship with verbal and nonverbal development.

• Journal of Microbiology and Biotechnology
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• v.20 no.1
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• pp.63-70
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• 2010

Novel influenza A (H1N1) is a newly emerged flu virus that was first detected in April 2009. Unlike the avian influenza (H5N1), this virus has been known to be able to spread from human to human directly. Although it is uncertain how severe this novel H1N1 virus will be in terms of human illness, the illness may be more widespread because most people will not have immunity to it. In this study, we compared the codon usage bias between the novel H1N1 influenza A viruses and other viruses such as H1N1 and H5N1 subtypes to investigate the genomic patterns of novel influenza A (H1N1). Totally, 1,675 nucleotide sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of influenza A virus, including H1N1 and H5N1 subtypes occurring from 2004 to 2009, were used. As a result, we found that the novel H1N1 influenza A viruses showed the most close correlations with the swine-origin H1N1 subtypes than other H1N1 viruses, in the result from not only the analysis of nucleotide compositions, but also the phylogenetic analysis. Although the genetic sequences of novel H1N1 subtypes were not exactly the same as the other H1N1 subtypes, the HA and NA genes of novel H1N1s showed very similar codon usage patterns with other H1N1 subtypes, especially with the swine-origin H1N1 influenza A viruses. Our findings strongly suggested that those novel H1N1 viruses seemed to be originated from the swine-host H1N1 viruses in terms of the codon usage patterns.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7819-7824
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• 2015

Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal-like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p<0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p<0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5811-5816
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• 2013

Background: Breast cancer is the most common cancer among women. Molecular subtypes are important in determining prognosis. This study evaluated five-year disease-free survival among four molecular subtypes in patients with early stages of breast cancer. Materials and Methods: In this retrospective descriptive-analytical study, information on patients with breast cancer between 2001-2010 was evaluated. Five hundred ninety two patients in the early stages of breast cancer (stages 1 and 2) were selected to undergo anthracycline-based chemotherapy. Relapse, death or absence (censor) were considered as the end of the study. Patients based on ER, PR and HER-2 expression were divided into four subtypes (luminal A, luminal B, HER-2 enriched and triple negative). Information based upon questionnaire was analysed. To show the patients survival rate, life table and Kaplan-Meyer methods were used, and for comparing mean survival among different groups, the Log-Rank test was utilized. Results: Mean age at diagnosis was $47.9{\pm}9.6$. Out of the 592 patients, 586 were female (99%) and 6 were male (1%). Considering breast cancer molecular subtypes, 361 patients were in the luminal A group (61%), 49 patients in the luminal B group (8.3%), 48 patients in the HER-2 enriched group (8.1%) and 134 in the triple negative group (22.6%). Mean disease-free survival was 53.7 months overall, 55.4 months for the luminal A group, 48.3 months for the luminal B group, 43 months for the HER-2enriched group and 54.6 months for the triple negatives. Disease free survival differed significantly among the molecular subtypes (p value=0.0001). Conclusions: The best disease-free survival rate was among the luminal A subgroup and the worst disease-free survival rate was among the HER-2 enriched subgroup. Disease free survival rate in the HER-2 positive groups (luminal B and HER-2 enriched) was worse than the HER-2 negative groups (luminal A and triple negative).

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1881-1886
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• 2012

Breast cancer is a heterogeneous disease that is affected by ethnicity of patients. According to hormone receptor status and gene expression profiling, breast cancers are classified into four molecular subtypes, each showing distinct clinical behavior. Lack of sufficient data on molecular subtypes of breast cancer in Iran, prompted us to investigate the prevalence and the clinicopathological features of each subtype among Iranian women. A total of 428 women diagnosed with breast cancer from 2002 to 2011 were included and categorized into four molecular subtypes using immunohistochemistry. Prevalence of each subtype and its association with patients' demographics and tumor characteristics, such as size, grade, lymph-node involvement and vascular invasion, were investigated using Chi-square, analysis of variance and multivariate logistic regression. Luminal A was the most common molecular subtype (63.8%) followed by Luminal B (8.4%), basal-like (15.9%) and HER-2 (11.9%). Basal-like and HER-2 subtypes were mostly of higher grades while luminal A tumors were more of grade 1 (P<0.001). Vascular invasion was more prevalent in HER-2 subtype, and HER-2 positive tumors were significantly associated with vascular invasion (P=0.013). Using muti-variate analysis, tumor size greater than 5 cm and vascular invasion were significant predictors of 3 or more nodal metastases. Breast cancer was most commonly diagnosed in women around 50 years of age and the majority of patients had lymph node metastasis at the time of diagnosis. This points to the necessity for devising an efficient screening program for breast cancer in Iran. Further, prospective surveys are suggested to evaluate prognosis of different subtypes in Iranian patients.