• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6375-6378
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• 2013

Background: The glutathione S transferase (GST) family of enzymes plays a vital role in the phase II biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and polymorphisms in GST genes have been associated with cancer susceptibility and prognosis. GSTP1 is associated with risk of various cancers including bladder cancer. A case control study was conducted to determine the genotype distribution of GSTP1 A>G SNP, to elucidate the possible role of this SNP as a risk factor in urinary bladder cancer (UBC) development and to examine its correlation with clinico-pathologic variables inUBC cases. Materials and Methods: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, we tested the genotype distribution of 180 bladder cancer patients in comparison with 210 cancer-free controls from the same geographical region with matched frequency in age and gender. Results: We did not observe significant genotype differences between the control and bladder cancer patients overall with an odds ratio (OR)=1.23 (p>0.05). The rare allele (AG+GG) was found to be present more in cases (28.3%) than in controls (24%), though the association was not significant (p<0.05). However, a significant risk of more than 2-fold was found for the variant allele (AG+GG) with smokers in cases as compared to controls (p>0.05). Conclusions: Thus, it is evident from our study that GSTP1 SNP is not implicated overall in bladder cancer, but that the rare, valine-related allele is connected with higher susceptibility to bladder cancer in smokers and also males.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.293-297
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• 2016

TRAIL, tumor necrosis factor (TNF)-related apoptosis-inducing ligand belongs to one of important cytokine superfamilIES, tumor necrosis factor ($TNF{\alpha}$). TRAIL-2 receptor agonists activate several cell signaling pathways in cells in different manners and could lead to apoptosis or necrosis. Agonistic egg yolk antibodies like IgY which have been developed in a selective manner could activate TRAIL death receptors such as TRAIL-2 (DR5) and thus apoptosis signaling. We here investigated induction of apoptosis in human breast cancer cells (MCF7 cell line) by an IgY produced against an 21 aminoacid epitope of the human TRAIL-2 receptor. As the first step a small peptide of 21 aminoacids choosen from the extracellular domain of DR5 protein was produced with a peptide synthesizer. After control assays and confirmation of the correct amino acid sequence, it was injected to hens immunized to achieve high affinity IgYs. At the next step, the produced IgYs were extracted and examined for specificity against DR5 protein by ELISA assay. Subsequently, the anticancer effect of such IgYs was determined by MTT assay in the MCF7 human breast cancer cell line. The produced peptides successfully immunized hens and the produced antibodies which accumulated in egg yolk specifically recognized the DR5 protein. IgYs exerted significant toxicity and killed MCF7 cells as shown by MTT assay.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4187-4193
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• 2013

Background: Evaluation of Human papilloma virus (HPV) and its association with promoter methylation of candidate genes, p53 and Aurora A in esophageal cancer. Materials and Methods: One hundred forty-one esophageal tissue samples from different pathologies were evaluated for HPV infection by PCR, while the promoter methylation status of p53 and Aurora A was assessed by methylation-specific restriction based PCR assay. Statistical analyses were performed with MedCalc and MDR software. Results: Based on endoscopy and histopathology, samples were categorized: cancers (n=56), precancers (n=7), esophagitis (n=19) and normals (n=59). HPV infection was found to be less common in cancers (19.6%), whereas its prevalence was relatively high in precancers (71.4%), esophagitis (57.8%) and normals (45.7%). p53 promoter methylation did not show any significant difference between cancer and normal tissues, whereas Aurora A promoter methylation demonstrated significant association with disease (p=0.00016, OR:5.6452, 95%CI:2.18 to 14.6) when compared to normals. Aurora A methylation and HPV infection was found in a higher percentages of precancer (66.6%), esophagitis (54.5%) and normal (45.2%) when compared to cancers (14.2%). Conclusions: Aurora A promoter methylation is significantly associated with esophageal cancer, but the effect of HPV infection on this epigenetic alteration is not significant. However MDR analysis showed that the hypostatic effect of HPV was nullified when the cases had Aurora methylation and tobacco exposure. Further HPV sub-typing may give an insight into its reduced prevalence in esophageal cancer verses normal tissue. However, with the present data it is difficult to assign any significant role to HPV in the etiopathology of esophageal cancer.

• Korean Medical Education Review
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• v.16 no.1
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• pp.50-54
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• 2014

It is becoming increasingly important for medical doctors to have a thorough understanding of human genetics and the ethical, legal, and social implications of genetic testing, counseling, and treatment. As genetic engineering and technology evolves, medical doctors will find themselves called in to counsel patients about a rapidly increasing number of diseases for which genetic testing and treatments are available. Medical doctors will need to master a new set of principles and clinical skills. A lack of knowledge about these issues and problems may lead to serious, lifelong or even fatal negative effects on patients. Medical genetics has moved from the study of rare conditions to the illumination of disorders that impact the entire spectrum of medical practice. This study demonstrates several areas in which medical genetics is clearly an important tool in medical practice and the necessity of establishing new curriculum for clinical genetic education in Korea. Medical students nearing graduation may lack genetic knowledge that is essential for daily practice because genetics has little or no place in clinical teaching. Medical schools should make extensive curriculum changes to increase students' awareness of clinical genetics and its ethical implications. The medical school curriculum will need creative new approaches to keeping up with the rapid pace of evolution of clinical genetics.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.2
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• pp.225-230
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• 1999

In mouse, the heat shock protein 70-2 (hsp70-2) is found to have special function in spermatogenesis. Based on the observation, the hypothesis that human hspA2 (human gene; 98.2% amino acid homology with hsp70-2) might have important function in spermatogenesis in human testes was proposed. To test the hypothesis, we examined the expression of hspA2 in human tissues. Expression vector pDMC4 for expression of the human hspA2 protein using pTricHisB (invitrogen, USA) was constructed and the expressed hspA2 protein was cross-reacted with antiserum 2A raised against mouse hsp70-2 protein. Based on the cross-reactivity, we determined the expression level of hspA2 protein in human tissues by western blot analysis using the antiserum 2A. We demonstrated that antiserum 2A antibodies detected human hspA2 protein with specificity which was produced in the E.coli expression system. On Western blot analyses, significant hspA2 expression was observed in testes with normal spermatogenesis, whereas a low level of hspA2 was expressed in testis with Sertoli-cell only syndrome. Also, a small amount of hspA2 was detected in breast, stomach, prostate, colon, liver, ovary, and epididymis. These results demonstrate that the hspA2 protein is highly expressed in male specific germ cells, which in turn suggests that hspA2 protein might playa specific role during meiosis in human testes as suggested in the murine model. However, further studies should be attempted to determine the function of hspA2 protein in human spermatogenesis.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.42.1-42.20
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• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9557-9565
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• 2014

MiRNAs are endogenous, single stranded ~22-nucleotide non-coding RNAs (ncRNAs) which are transcribed by RNA polymerase II and mediate negative post-transcriptional gene regulation through binding to 3'untranslated regions (UTR), possibly open reading frames (ORFs) or 5'UTRs of target mRNAs. MiRNAs are involved in the normal physiology of eukaryotic cells, so dysregulation may be associated with diseases like cancer, and neurodegenerative, heart and other disorders. Among all cancers, lung cancer, with high incidence and mortality worldwide, is classified into two main groups: non-small cell lung cancer and small cell lung cancer. Recent promising studies suggest that gene expression profiles and miRNA signatures could be a useful step in a noninvasive, low-cost and repeatable screening process of lung cancer. Similarly, every stage of lung development during fetal life is associated with specific miRNAs. Since lung development and lung cancer phenomena share the same physiological, biological and molecular processes like cell proliferation, development and shared mRNA or expression regulation pathways, and according to data adopted from various studies, they may have partially shared miRNA signature. Thus, focusing on lung cancer in relation to lung development in miRNA studies might provide clues for lung cancer diagnosis and prognosis.

• International Journal of Oral Biology
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• v.39 no.4
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• pp.221-228
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• 2014

Glucosamine is commonly taken by the elderly without prescription as a nutritional supplement to attenuate the progression or symptoms of osteoarthritis. Previous studies demonstrated that glucosamine shows anti-inflammatory effects in tissues such as blood vessels and the heart. However, there have been few reports about the effects of glucosamine on oral inflammatory diseases. Therefore, in this study, the effects of glucosamine on lipopolysaccharide (LPS)-induced inflammatory responses were investigated using human periodontal ligament fibroblasts (HPDLFs). HPDLFs were incubated in the presence and absence of glucosamine (10 mM) for 24 h, followed by treatment with E. coli LPS (100 ng/ml) or vehicle. Quantitative RT-PCR and ELISA results showed that LPS exposure significantly increased the levels of IL-6 and IL-8 mRNA and protein, while the effect was significantly suppressed by glucosamine treatment. Glucosamine did not attenuate, but slightly increased, the LPS-induced activation of mitogen activated kinases (ERK, p38, JNK). However, it suppressed the LPS-induced increase in the DNA binding affinity and transcriptional activity of NF-${\kappa}B$. These results suggest that glucosamine exerts anti-inflammatory effects on HPDLFs exposed to LPS via inhibition of NF-${\kappa}B$ activity, necessitating further studies using animal periodontitis models.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7243-7248
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• 2015

Background: Monocyte chemoattractant protein-1 (MCP-1) is a major chemokine thought to be responsible for monocyte and T-lymphocyte recruitment in acute inflammatory conditions and recruitment of macrophages in tumors. It is also implicated in cardiovascular disease, rheumatoid arthritis and chronic obstructive pulmonary disease. The aim of the present study was to investigate the correlation between MCP-1 -2518 A/G polymorphism and breast cancer risk in patients from Amritsar city of Punjab state in North-West India. Materials and Methods: We screened DNA samples of 200 sporadic breast cancer patients and 200 age and gender matched unrelated healthy individuals for MCP-1 -2518 A/G polymorphism using the PCR-RFLP method. Results: A significantly increased frequency of the GG genotype was observed in patients as compared to controls. Individuals carrying the MCP1 -2518GG genotype had a two fold risk for breast cancer (OR=2.06, 95%CI, 1.06-3.98; p=0.03). Genetic models analysis revealed a significant association between MCP-1 -2518 A/G polymorphism and cancer risk in homozygous co-dominant (OR=2.06, 95%CI, 1.06-3.98; p=0.03) and recessive (OR=1.97, 95%CI, 1.05-3.70; p=0.03) models. Conclusions: We conclude that the GG genotype of the MCP-1-2518 A/G polymorphism is associated with increased risk to breast cancer in Punjab, North-West India.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.257-263
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• 2014

Background: Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, has been implicated as a critical factor influencing tumor related angiogenesis. The aim of present study was to evaluate the relationship between VEGF +936C>T and +405C>G polymorphisms of VEGF with risk of breast cancer in Punjab, India. Materials and Methods: We screened DNA samples of 192 sporadic breast cancer patients and 192 unrelated healthy, gender and age matched control individuals for VEGF +936C>T and +405C>G polymorphisms using the PCR-RFLP method. Results: For the VEGF +405C>G polymorphism, we observed significantly increased frequency of GG genotype in cases as compared to controls and strong association of +405GG genotype was observed with three fold risk for breast cancer (OR=3.07; 95%CI 1.41-6.65; p=0.003). For the +936C>T polymorphism, significant associations of CT and combined CT+TT genotypes were observed with elevated risk of breast cancer (p=0.021; 0.023). The combined genotype combinations of GG-CC and GG-CT of +405C>G and +936C>T polymorphisms were found to be significantly associated with increased risk of breast cancer (p=0.04; 0.0064). Conclusions: The findings of the present study indicated significant associations of VEGF +936C>T and +405C>G polymorphisms with increased breast cancer risk in patients from Punjab, North India.