• Asian-Australasian Journal of Animal Sciences
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• 제31권9호
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• pp.1393-1400
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• 2018

Objective: This study was carried out to assess the haplotype diversity and population dynamics in cattle populations of Ethiopia. Methods: We sequenced the complete mitochondrial cytochrome b gene of 76 animals from five indigenous and one Holstein Friesian${\times}$Barka cross bred cattle populations. Results: In the sequence analysis, 18 haplotypes were generated from 18 segregating sites and the average haplotype and nucleotide diversities were $0.7540{\pm}0.043$ and $0.0010{\pm}0.000$, respectively. The population differentiation analysis shows a weak population structure (4.55%) among the populations studied. Majority of the variation (95.45%) is observed by within populations. The overall average pair-wise distance ($F_{ST}$) was 0.049539 with the highest ($F_{ST}=0.1245$) and the lowest ($F_{ST}=0.011$) $F_{ST}$ distances observed between Boran and Abigar, and Sheko and Abigar from the indigenous cattle, respectively. The phylogenetic network analysis revealed that all the haplotypes detected clustered together with the Bos taurus cattle and converged to a haplogroup. No haplotype in Ethiopian cattle was observed clustered with the reference Bos indicus group. The mismatch distribution analysis indicates a single population expansion event among the cattle populations. Conclusion: Overall, high haplotype variability was observed among Ethiopian cattle populations and they share a common ancestor with Bos taurus.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3507-3511
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• 2014

Background: The prostaglandin-endoperoxide synthase 2 [PTGS2, commonly known as cyclooxygenase-2 (COX-2)] is an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue and involved in the synthesis of prostaglandins and thromboxanes, regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether a functional genetic polymorphism, rs5277, in COX-2 may have a risk-modifying effect on sporadic colorectal cancer in an Iranian population. Materials and Methods: We conducted a case-control study on 167 patients with colorectal cancer and 197 cancer-free controls in Taleghani Hospital in Tehran, Iran, between 2007 and 2011. Peripheral blood samples of both groups were processed for DNA extraction and genotyping of the COX-2 gene polymorphism (rs5277) using PCR-RFLP. RFLP results were confirmed by direct sequencing. Logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results: There was no significant difference in the distribution of COX-2 gene rs5277 polymorphism genotype and the allelic form, among CRC patients compared with the healthy control group (p: 0.867). Conclusions: Our results suggest that rs5277 polymorphism in COX2 could not be a good prognostic indicator for patients with CRC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6089-6094
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• 2013

Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.

• BMB Reports
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• 제37권5호
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• pp.603-611
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• 2004

Fluorescence probes located in different membrane regions were used to evaluate the effects of chlorpromazine HCl on structural parameters (transbilayer lateral mobility, annular lipid fluidity, protein distribution, and lipid bilayer thickness) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortex. The experimental procedure was based on the selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, radiationless energy transfer from the tryptophan of membrane proteins to Py-3-Py, and energy transfer from Py-3-Py monomers to 1-anilinonaphthalene-8-sulfonic acid (ANS). In this study, chlorpromazine HCl decreased the lateral mobility of Py-3-Py in a concentration dependent-manner, showed a greater ordering effect on the inner monolayer than on the outer monolayer, decreased annular lipid fluidity in a dose dependent-manner, and contracted the membrane lipid bilayer. Furthermore, the drug was found to have a clustering effect on membrane proteins.

• BMB Reports
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• 제36권6호
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• pp.533-537
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• 2003

The nonsyndromic cleft lip and palate (NSCL/P) is a congenital deformity of multifactorial origin with a relatively high incidence in the oriental population. Various etiologic candidate genes have been reported with conflicting results, according to race and analysis methods. Recently, the ablation of the TGF-${\beta}3$ gene function induced cleft palates in experimental animals. Also, polymorphisms in the TGF-${\beta}3$ gene have been studied in different races; however, they have not been studied in Koreans. A novel A $\rightarrow$ G single nucleotide polymorphism (defined by the endonuclease SfaN1) was identified in intron 5 of TGF-${\beta}3$ (IVS5+104 A > G). It resulted in different genotypes, AA, AG, and GG. The objective of this study was to investigate the relationship between the SfaN1 polymorphism in TGF-${\beta}3$ and the risk of NSCL/P in the Korean population. The population of this study consisted of 28 NSCL/P patients and 41 healthy controls. The distribution of the SfaN1 genotypes was different between the cases and controls. The frequency of the G allele was significantly associated with the increased risk of NSCL/P [odds ratio (OR) = 15.92, 95% confidence interval (CI) = 6.3-41.0]. The risk for the disease increased as the G allele numbers increased (GA genotype: OR = 2.11, 95% CI = 0.38-11.68; GG genotype: OR = 110.2, 95% CI = 10.67 - 2783.29) in NSCL/P. A stratified study in patients revealed that the SfaN1 site IVS5+104A > G substitution was strongly associated with an increased risk of NSCL/P in males (p < 0.001), but not in females. In conclusion, the polymorphism of the SfaN1 site in TGF-${\beta}3$ was significantly different between the NSCL/P patients and the control. This may be a good screening marker for NSCL/P patients among Koreans.

• BMB Reports
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• 제29권5호
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• pp.405-410
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• 1996

Previous studies have shown that transforming growth factor beta ($TGF-{\beta}$) is a potent regulator of cell growth and differentiation. To study the effects of $TGF-{\beta}$ on cell morphology and cytoskeleton reorganization, we conducted a survey using Mv1Lu mink lung epithelial cells with antibodies to cytoskeletal proteins and an extracellular matrix protein. While the untreated cells showed a cuboidal shape of typical epithelia, the Mv1Lu cells displayed a drastic shape change in the presence of $TGF-{\beta}$. This alteration was most prominent when near-confluent cells were treated with $TGF-{\beta}$. Since the morphology alteration is known to be accompanied by the reorganization of cytoskeletal proteins in other cell types, we investigated the intracellular distribution of the three major cytoskeletal structures: microfilaments, microtubules, and intermediate filaments. In the microfilament system, $TGF-{\beta}$ induced new stress fiber formation, which was caused primarily by the polymerization of cytoplasmic G-actin. However, $TGF-{\beta}$ appeared not to induce any significant changes in microtubular structures and vimentin filaments as determined by indirect fluorescence microscopy. Finally we confirmed the rapid accumulation of fibronectin by immunoblot analysis and chased the protein locations by immunofluorescence microscopy.

• Asian-Australasian Journal of Animal Sciences
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• 제28권5호
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• pp.686-690
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• 2015

The adrenergic receptor beta 2 (ADRB2) plays a role in various physiological responses of the muscle to exercise, such as contraction and relaxation. Given its important role in muscle function, we investigated the structure of the horse ADRB2 gene and its expression pattern after exercise to determine if it can serve as a putative biomarker for recovery. Evolutionary analyses using synonymous and non-synonymous mutation ratios, were compared with other species (human, chimpanzee, mouse, rat, cow, pig, chicken, dog, and cat), and revealed the occurrence of positive selection in the horse ADRB2 gene. In addition, expression analyses by quantitative polymerase chain reaction exhibited ubiquitous distribution of horse ADRB2 in various tissues including lung, skeletal muscle, kidney, thyroid, appendix, colon, spinal cord and heart, with the highest expression observed in the lung. The expression of ADRB2 in skeletal muscle was significantly up-regulated about four folds 30 minutes post-exercise compared to pre-exercise. The expression level of ADRB2 in leukocytes, which could be collected with convenience compared with other tissues in horse, increased until 60 min after exercise but decreased afterward until 120 min, suggesting the ADRB2 expression levels in leukocytes could be a useful biomarker to check the early recovery status of horse after exercise. In conclusion, we identified horse ADRB2 gene and analyzed expression profiles in various tissues. Additionally, analysis of ADBR2 gene expression in leukocytes could be a useful biomarker useful for evaluation of early recovery status after exercise in racing horses.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1219-1224
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• 2015

Background: To date several common mutations in BRCA1 and BRCA2 associated with breast cancer have been reported in different populations. However, the common BRCA1 and BRCA2 mutations among breast cancer patients in Iran have not been described in detail. Materials and Methods: To comprehensively assess the frequency and distribution of the most common BRCA1 and BRCA2 mutations in Iranian breast cancer patients, we conducted this meta-analysis on 13 relevant published studies indentified in a literature search on PubMed and SID. Results: A total of 11 BRCA1 and BRCA2 distinct common mutations were identified, reported twice or more in the articles, of which 10 (c.2311T>C, c.3113A>G, c.4308T>C, c.4837A>G, c.2612C>T, c.3119G>A, c.3548A>G, c.5213G>A c.IVS16-92A/G, and c.IVS16-68A/G) mutations were in BRCA1, and 1 (c.4770A>G) was in BRCA2. The mutations were in exon 11, exon 13, intron 16, and exon 20 of BRCA1 and exon 11 of BRCA2. All have been previously reported in different populations. Conclusions: These meta analysis results should be helpful in understanding the possibility of any first true founder mutation of BRCA1/BRCA2 in the Iranian population. In addition, they will be of significance for diagnostic testing, genetic counseling and for epidemiological studies.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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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.