• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1803-1808
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• 2012

This study aimed to investigate the effects of Ser/Cys polymorphism in hOGG1 gene, Arg/Pro polymorphism in p53 gene, smoking and their interactions on the development of lung cancer. Ser/Cys polymorphism in hOGG1 and Arg/Pro polymorphism in p53 among 124 patients with lung cancer and 128 normal people were detected using PCR-RFLP. At the same time, smoking status was investigated between the two groups. Logistic regression was used to estimate the effects of Ser/Cys polymorphism and Arg/Pro polymorphisms, smoking and their interactions on the development of lung cancer. ORs (95% CI) of smoking, hOGG1 Cys/Cys and p53 Pro/Pro genotypes were 2.34 (1.41-3.88), 2.12 (1.03-4.39), and 2.12 (1.15-3.94), respectively. The interaction model of smoking and Cys/Cys was super-multiplicative or multiplicative, and the OR (95% CI) for their interaction item was 1.67 (0.36 -7.78). The interaction model of smoking and Pro/Pro was super-multiplicative with an OR (95%CI) of their interaction item of 5.03 (1.26-20.1). The interaction model of Pro/Pro and Cys/Cys was multiplicative and the OR (95%CI) of their interaction item was 0.99 (0.19-5.28). Smoking, hOGG1 Cys/Cys, p53 Pro/Pro and their interactions may be the important factors leading to the development of lung cancer.

• Tuberculosis and Respiratory Diseases
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• 제52권1호
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• pp.5-13
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• 2002

연구배경 : 폐암의 80-90 %는 흡연과 관계가 있으나 흡연자의 일부에서만 폐암이 발생하는 현상은 개체의 유전적 소인이 폐암발생을 결정하는 주요 요인임을 시사한다. 저자들은 한국인에서 DNA 회복 유전자인 hOGG1 유전자의 codon 326 다형성과 폐암의 위험도를 조사 하였다. 방 법 : 1998년 1월부터 1998년 12월까지 경북대학교병원 내과에서 병리학적으로 폐암으로 확진된 환자를 대상으로 하였으며 악성종양으로 진단받은 과거력이 있는 사람은 제외하였다. 대조군은 1998년 1월부터 1999년 12월까지 경북대학교병원 건강검진센터를 방문한 40세 이상의 검진자들을 대상으로 하였으며 호흡기질환이나 악성종양이 있는 경우는 제외하였다. 대상인의 나이, 성, 홉연력, 과거력 등은 면접이나 병력지를 통해 얻었으며, 시료는 전혈 5cc에서 DNA를 추출하고 PCR 과 RFLP 법을 통해 hOGG1 유전자 다형성을 조사하였다. 결 과 : hOGG1 Ser326Cys 유전자형은 폐암군의 경우 Ser/Ser, Ser/Cys, Cys/Cys 형이 각각 23.4%, 51.8%, 24.8%였고 대조군은 각각 22.6%, 52.1%, 25.3% 로 두 군 사이에 유의한 차이가 없었으며, Ser/Ser 형에 비해 Ser/Cys 형과 Cys/Cys 형의 OR는 1.00 (95 % CI, 0.63-1.60)와 0.94(95% CI, 0.56-1.61)으로 통계적으로 유의한 의미가 없었다. Ser/Ser형 + Ser/Cys 형에 대한 Cys/Cys 형의 폐암의 위험도는 연령, 성별, 흡연력 등으로 구분한 경우에도 유의한 차이가 없었다. 폐암의 조직형을 구분하여 비교한 경우에도 hOGG1 유전자형과 폐암의 위험도는 유의한 관계가 없었다. 결 론 : 한국인에서 hOGG1 codon 326 유전자형은 폐암의 위험도를 결정하는 주요 인자는 아닌 것으로 생각된다.

• Clinical and Experimental Pediatrics
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• 제52권6호
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• pp.680-688
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• 2009

목 적 : 류코트리엔은 천식의 병태생리에 중요한 향염증성 매개체이며, 천식이나 운동유발성 천식에서 증가되어 있다. Leukotriene C4 synthase (LTC4S)의 A(-444)C 유전자 다형성과 cysteinyl leukotriene receptor 1 (CysLTR1) T(＋927)C 유전자 다형성이 한국 소아의 천식, 아토피 천식 및 운동유발성 천식과 연관이 있는지 알아보고, 폐기능, 기관지과민성, 총IgE 치에 영향을 미치는지 알아보고자 하였다. 방 법 : 총 856명의 천식 환자와 254명의 천식이 없는 정상아를 대상으로 하여 피부반응검사, 폐기능, 메타콜린 기관지 유발검사, 총 IgE 검사를 실시하였고, 천식 환자를 아토피 천식(699명), 운동유발성 천식(277명)으로 나누어 유전자 다형성과의 연관성을 조사하였다. LTC4S A9-444)C, CysLTR1 T(＋927)C 유전자형은 PCR-restriction fragment length polymorphism 방법으로 분석하였다. 결 과 : LTC4S A(-444)C 및 CysLTR1 T(＋927)C 유전자 다형성은 천식, 아토피 천식, 운동유발성 천식과의 연관성이 없었고, 폐기능, $PC_{20}$, 총IgE에도 차이를 보이지 않았다. 아토피 천식에서 총 호산구수는 변종형 LTC4S 유전자형에서 야생형 보다 높았다. LTC4S A(-444)C와 CysLTR1 T(＋927)C의 유전자-유전자 상호 작용도 천식, 아토피 천식, 운동유발성 천식과의 연관이 없었다. 결 론 : 한국 소아 천식의 표현형, 폐기능, 기관지과민성, 총IgE 농도는 LTC4S A(-444)C와 CysLTR1 T(＋927)C 유전자 다형성, 혹은 유전자-유전자 상호작용과 연관이 없는 것으로 생각된다.

• BMB Reports
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• 제41권2호
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• pp.139-145
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• 2008

We cloned and pharmacologically characterized the guinea pig cysteinyl leukotriene (CysLT) 2 receptor (gpCysLT2). gpCysLT2 consists of 317 amino acids with 75.3%, 75.2%, 73.3% identity to those of humans, mice and rats, respectively. The gpCysLT2 gene is highly expressed in the lung, moderately in eosinophils, skin, spleen, stomach, colon, and modestly in the small intestine. CysLTs accelerated the proliferation of gpCysLT2-expressing HEK293. Leukotriene C4 (LTC4) and Leukotriene D4 (LTD4) enhanced the cell proliferation higher than Bay-u9773, a CysLT2 selective partial agonist and a nonselective antagonist for CysLT receptors. Bay-u9773 did not antagonize the cell proliferation by LTC4 and LTD4. Despite the equipotency of the mitogenic effect among these chemicals, calcium mobilization (CM) levels were variable (LTC4 > LTD4 >> Bay-u9773), and Bay-u9773 antagonized the CM by LTC4. Moreover, the Gi/o inhibitor pertussis toxin perfectly inhibited agonist-induced cell proliferation. These results reveal that cell proliferation via CysLT2 signaling was mediated by Gi/o signaling but independent of calcium mobilization.

• Genomics & Informatics
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• 제21권3호
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• pp.30.1-30.13
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• 2023

Ephs belong to the largest family of receptor tyrosine kinase and are highly conserved both sequentially and structurally. The structural organization of Eph is similar to other receptor tyrosine kinases; constituting the extracellular ligand binding domain, a fibronectin domain followed by intracellular juxtamembrane kinase, and SAM domain. Eph binds to respective ephrin ligand, through the ligand binding domain and forms a tetrameric complex to activate the kinase domain. Eph-ephrin regulates many downstream pathways that lead to physiological events such as cell migration, proliferation, and growth. Therefore, considering the importance of Eph-ephrin class of protein in tumorigenesis, 7,620 clinically reported missense mutations belonging to the class of variables of unknown significance were retrieved from cBioPortal and evaluated for pathogenicity. Thirty-two mutations predicted to be pathogenic using SIFT, Polyphen-2, PROVEAN, SNPs&GO, PMut, iSTABLE, and PremPS in-silico tools were found located either in critical functional regions or encompassing interactions at the binding interface of Eph-ephrin. However, seven were reported in nonsmall cell lung cancer (NSCLC). Considering the relevance of receptor tyrosine kinases and Eph in NSCLC, these seven mutations were assessed for change in the folding pattern using molecular dynamic simulation. Structural alterations, stability, flexibility, compactness, and solvent-exposed area was observed in EphA3 Trp790Cys, EphA7 Leu749Phe, EphB1 Gly685Cys, EphB4 Val748Ala, and Ephrin A2 Trp112Cys. Hence, it can be concluded that the evaluated mutations have potential to alter the folding pattern and thus can be further validated by in-vitro, structural and in-vivo studies for clinical management.

• Journal of Chest Surgery
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• 제28권12호
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• pp.1188-1191
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• 1995

Taumatic pulmonary pseudocyst is a rare complication of chest bunt trauma. Recently, we experienced a case of traumatic pulmonary pseudocyst in right lower lobe. The patient`s anterior chest was directly strucken by steering wheel and his car was intervened between two cars. He complained of both chest pain and dyspnea. He was diagnosed as multiple rib fractures with pulmonary contusion, initially. And then the right pulmonary lesion changed to traumatic pulmonary pseudocyst in 10 days after trauma. He was treated sucessfully with conservative management. In this article, we present the case and review the traumatic pulmonary pseudocyst with related articles.

• Biomolecules & Therapeutics
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• 제2권4호
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• pp.303-309
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• 1994

The analysis of membrane receptors for hormones and neurotransmitters has progressed considerably by pharmacological and biochemical means and more recently through the use of specific antibodies. Two kinds of antibodies could be produced, one is from synthetic peptides and the other from proteins such as purified receptor. Anti-peptide antibodies gave some advantages; epitope is evident and also receptor purification in quantity is not prerequisite. It can be also applied to the study of receptor structure-activity relationship. The purpose of the present study was 1) to produce and characterize a polyclonal antibody against a synthetic $\beta$2-adrenergic receptor peptide(Phe-Gly-Asn-Phe-Trp-Cys-Phe-Trp-Thr-Ser-Ile-Asp-Val-Leu) and 2) to determine the effects of this antibody on the $\beta$-adrenergic receptor ligand interaction. The peptide sequence contains an amino acid residue such as Asp-113 which was identified as one of important component for receptor-ligand interaction in site-directed mutagenesis studies. Production of antibody was performed by immunization of rabbits through popliteal lymph node with the peptide coupled with Keyhole Limpet Hemocyanin (KLH). The titer of antibody against this peptide was 1 : 1000. The anti-peptide antibody was able to detect a 67 kDa protein band in western blot corresponding to the molecular weight of the $\beta$-adrenergic receptor in partially purified receptor fraction derived from guinea pig lung. The antisera inhibited the specific binding of [$^3$H]dihydroalprenolol to $\beta$-adrenergic receptor in a concentration-dependent manner. The results from this study suggest that the peptide sequence selected in the present study is important for the receptor ligand interaction.

• Biomolecules & Therapeutics
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• 제3권4호
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• pp.266-272
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• 1995

The analysis of membrane receptors for hormones and neurotransmitters has progressed considerably by pharmacological and biochemical means and more recently through the use of specific antibodies. To generate and characterize a moloclonal antibody against $\beta$-adrenergic receptor, a synthetic $\beta$2-adrenergic receptor peptide (Phe-Gly-Asn-Phe-Trp-Cys-Phe-Trp-Thr-Ser-lle-Asp-Val-Leu) which may comprise part of $\beta$-adrenergic receptor ligand binding pocket was coupled to Keyhole Limpet Hemocyanin (KLH) and used as an immunogen. Male BALB/C mice were immunized with this antigen and the immunized spleen was fused with myeloma SP2/0-Ag14 cells to produce monoclonal antibodies. Two clones were obtained but one of monoclonal antibodies, mAb5G09, was used throughout in this study because the other clone, mAb5All showed weak immunoreactivity against KLH as well. The mouse monoclonal antibody mAb5G09 produced in this study showed immunoreactivity to peptide-KLH conjugates and also to human A43l cells and guinea pig lung $\beta$2-adrenergic receptor as revealed by ELISA and western blot. In the course of determination of the effects of mAb5G09 on $\beta$-receptor ligand binding, it was observed that mAb5G09 specifically bound $\beta$-adrenergic radioligand [$^3$H]dihydroalprenolol (DHA) with a dissociation constant (Kd) of 60 nM. The [$^3$H]DHA binding activity of mAb5G09 had characteristics of immunoglobulins and the binding activity was not observed in the control anti-KLH monoclonal antibody. The monoclonal antibody, mAb5G09 produced in this study may provide useful models for the study of the structure of receptor binding sites.