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      • Immunoregulatory Function of HLA-G in Gastric Cancer

        Tuncel, Tolga,Karagoz, Bulent,Haholu, Aptullah,Ozgun, Alpaslan,Emirzeoglu, Levent,Bilgi, Oguz,Kandemir, Emin Gokhan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

        Background: Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. Materials and Methods: We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. Results: There were 29 cancer-related deaths during the follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors for patient survival. Conclusions: We found a significant positive correlation between HLA-G expression and the number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T lymphocytes.

      • Poster Session : PS 0722 ; Rheumatology ; SystemIc Lupus Erythematosus and Castleman Disease Co-Existence in a Patient with Weight Loss and Lymphadenopathy

        ( Yusuf Hancerli ),( Veysel Ozalper ),( Abdullah Haholu ),( Ramazan Arikan ),( Emrullah Solmazgul ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

        Objective: Castleman`s disease (CD) is quite rare and its etiology is not clearly unravelled yet. It is a lymphoproliferative disease with giant lymph node hyperplasia. This report presents newly diagnosed SLE and CD association on a 21 year old male who was transferred to our hospital with weight loss, fatigue and multiple lymphadenopathy (LAP) complaints along with the pre-diagnosis of lymphoma. Case Report: In September 2013, the patient was admitted to our Hematology Clinic with the complaints of weakness, neck and arm pit swelling and weight loss. The patient was at 68 kg in November 2012, while admitted to the hospital in September 2013 he was at 47 kg. On physical examination, bilateral cervical, supraclavicular, inguinal and axillary LAP which reached 3-4 cm in size and hepatomegaly was identifi ed. He had pain in both hand`s mid-interfalengeal joints and was unable to move comfortably. Labarotary fi ndings were hemoglobin:10. 5 g/dl, direct coombs +2 positive, platelet 79100 u/l, sedim 96, C-reactive protein 26. 6, ANA: 2. 672 (cut off<0,896), AntidsDNA:2. 517 (cut off<0,947), nRNP/Sm positive, C3: 0. 675 g/dl, C4 :0. 0871 g/ dl,24- hour urine protein 1481. 24 mg. The patient was diagnosed as SLE with the present fi ndings. The excisional biopsy from the right axillary lymph node area which showed the highest activity in PET CT ( SUVmax : 6. 4) was considered signifi cant inthe terms of CD. Conclusion: Altough LAP`s most common causes are malignancy, autoimmune diseases and infections, it would be appropriate to take into consideration lymphoproliferative diseases such as CD in the stage of diagnosis evaluation in spite of very rare occurence.

      • CYP1A1 (Ile<sup>462</sup>Val), CYP1B1 (Ala<sup>119</sup>Ser and Val<sup>432</sup>Leu), GSTM1 (null), and GSTT1 (null) Polymorphisms and Bladder Cancer Risk in a Turkish Population

        Berber, Ufuk,Yilmaz, Ismail,Yilmaz, Omer,Haholu, Aptullah,Kucukodaci, Zafer,Ates, Ferhat,Demirel, Dilaver Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

        We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

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        miR-205 and miR-200c: Predictive Micro RNAs for Lymph Node Metastasis in Triple Negative Breast Cancer

        Ufuk Berber,Ismail Yilmaz,Gizem Narli,Aptullah Haholu,Zafer Kucukodaci,Dilaver Demirel 한국유방암학회 2014 Journal of breast cancer Vol.17 No.2

        Purpose: We examined expression profiles of 16 micro RNAs(miRNAs) in triple negative breast cancers to identify their potentialas biomarkers for lymph node metastasis. Methods: The expressionprofiles of miR-9, miR-21, miR-30a, miR-30d, miR-31,miR-34a, miR-34c, miR-100, miR-122, miR-125b, miR-146a,miR-146b, miR-155, miR-181a, miR-200c, and miR-205 wereexamined by using real-time quantitative reverse transcriptionpolymerase chain reaction in tumor samples and correspondingbenign breast tissues. Their associations with histopathologicalfeatures and prognostic parameters were assessed. Results:When compared with the expression in benign breast tissues,seven of the miRNAs (miR-31, miR-205, miR-34a, miR-146a,miR-125b, miR-34c, and miR-181a) were downregulated morethan 1.5-fold in tumor tissues, whereas, only miR-21 was foundto be upregulated more than 1.5-fold in tumor tissues. AlthoughmiR-200c levels were decreased only 1.12-fold in tumor tissues,the reduced expressions of miR-200c and miR-205 were significantlyassociated with lymph node metastasis (p=0.021 and p=0.016, respectively). Conclusion: Our results demonstrate thatmiR-205 and miR-200c expression levels may be useful in predictinglymph node metastasis in triple negative breast cancerpatients.

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