• 제목/요약/키워드: Germline

검색결과 138건 처리시간 0.025초

Guided Selection of Human Antibody Light Chains against TAG-72 Using a Phage Display Chain Shuffling Approach

  • Kim, Sang-Jick;Hong, Hyo-Jeong
    • Journal of Microbiology
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    • 제45권6호
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    • pp.572-577
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    • 2007
  • To enhance therapeutic potential of murine monoclonal antibody, humanization by CDR grafting is usually used to reduce immunogenic mouse residues. Most humanized antibodies still have mouse residues critical for antigen binding, but the mouse residues may evoke immune responses in humans. Previously, we constructed a new humanized version (AKA) of mouse CC49 antibody specific for tumor-associated glycoprotein, TAG-72. In this study, to select a completely human antibody light chain against TAG-72, guided selection strategy using phage display was used. The heavy chain variable region (VH) of AKA was used to guide the selection of a human TAG-72-specific light chain variable region (VL) from a human VL repertoire constructed from human PBL. Most of the selected VLs were identified to be originated from the members of the human germline VK1 family, whereas the VL of AKA is more homologous to the VK4 family. Competition binding assay of the selected Fabs with mouse CC49 suggested that the epitopes of the Fabs overlap with that of CC49. In addition, they showed better antigen-binding affinity compared to parental AKA. The selected human VLs may be used to guide the selection of human VHs to get completely human anti-TAG72 antibody.

Screening of 185DelAG, 1014DelGT and 3889DelAG BRCA1 Mutations in Breast Cancer Patients from North-East India

  • Hansa, Jagadish;Kannan, Ravi;Ghosh, Sankar Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권11호
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    • pp.5871-5874
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    • 2012
  • Around 1.35 million people of worldwide suffer from breast cancer each year, whereas in India, 1 in every 17 women develops the disease. Mutations of the Breast Cancer 1 (BRCA1) gene account for the majority of breast/ovarian cancer families. The purpose of study was to provide a prevalence of BRCA1 germline mutations in the North-East Indian population. In relation to the personal and family history with the breast cancer, we found mutations in 6.25% and 12.5% respectively. Three mutations, 185DelAG, 1014DelGT and 3889DelAG, were observed in our North-East Indian patients in exons 2 and 11, resulting in truncation of the BRCA1 protein by forming stop codons individually at amino acid positions 39, 303 and 1265. Our results point to a necessity for an extensive mutation screening study of high risk breast cancer cases in our North-East Indian population, which will provide better decisive medical and surgical preventive options.

Pattern-Recognition Receptor Signaling Initiated From Extracellular, Membrane, and Cytoplasmic Space

  • Lee, Myeong Sup;Kim, Young-Joon
    • Molecules and Cells
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    • 제23권1호
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    • pp.1-10
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    • 2007
  • Invading pathogens are recognized by diverse germline-encoded pattern-recognition receptors (PRRs) which are distributed in three different cellular compartments: extracellular, membrane, and cytoplasmic. In mammals, the major extracellular PRRs such as complements may first encounter the invading pathogens and opsonize them for clearance by phagocytosis which is mediated by membrane-associated phagocytic receptors including complement receptors. The major membrane-associated PRRs, Toll-like receptors, recognize diverse pathogens and generate inflammatory signals to coordinate innate immune responses and shape adaptive immune responses. Furthemore, certain membrane-associated PRRs such as Dectin-1 can mediate phagocytosis and also induce inflammatory response. When these more forefront detection systems are avoided by the pathogens, cytoplasmic PRRs may play major roles. Cytoplasmic caspase-recruiting domain (CARD) helicases such as retinoic acid-inducible protein I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5), mediate antiviral immunity by inducing the production of type I interferons. Certain members of nucleotide-binding oligomerization domain (NOD)-like receptors such as NALP3 present in the cytosol form inflammasomes to induce inflammatory responses upon ligand recognition. Thus, diverse families of PRRs coordinately mediate immune responses against diverse types of pathogens.

Cowden 증후군 환자에서 발생한 캔디다 식도염 1예 (Candida Esophagitis in a Patient with Cowden's Syndrome: A Case Report)

  • 강경지;윤혜정;류성렬;류남희;강유나;황진복
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제12권1호
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    • pp.46-50
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    • 2009
  • Cowden 증후군으로 진단되어 추적 관찰 중인 21세 여자에서 위장관 용종의 정기적 관찰을 위하여 시행한 내시경 검사 중 캔디다 식도염이 발견되어 문헌 고찰과 함께 보고한다. 면역학적 이상, 진균 식도 감염의 선행 질환, 투약의 병력이 없었고, 뚜렷한 식도 감염의 임상 증상도 없었다.

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Lac Z 유전자가 전이된 원시생식세포 주입에 의한 병아리 생식기내 유전자 발현 (Expression of Lac Z Gene in Young Chick Gonad by the Transtected Primordial Germ Cell Injection)

  • 한재용;서동삼;홍영호;정동기;최강덕;신영수
    • 한국가금학회지
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    • 제23권2호
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    • pp.61-69
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    • 1996
  • Primordial germ cells (PGCs) were manipulated as part of the system to produce transgenic chickens. PGCs were isolated from the germinal crescent of developmental stage 6 to 8 donor emhryos of the Korean Native Ogol Chickens (KNOC). These PGCs were transfected with plasmid DNA containing the lac Z gene by liposome mediated transfection methods. The lac Z gene was transfected and expressed in the PGCs. These transfected PGCs were injected into the germinal crescent of White Leghorn embryos (stage 6 to 8). The injected transfected PGCs migrated via the circulatory system into the future gonad and expression observed in the gonads of 3 day old chick. Of the 47 embryos and 3 day old chickens, one positive PGCs gonad from sacrificed young chickens was detected by appearance of blue cells. Plasmid DNA with the foreign gene was incorporated into the population of germ cells in the gonad. These results demonstrate that PGCs can he transfected and then transferred for colonization into the gonad, and show the potential to ultimately manipulate the genetic material of the chicken gernline.

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Brca2 Deficiency Leads to T Cell Loss and Immune Dysfunction

  • Jeong, Jun-Hyeon;Jo, Areum;Park, Pilgu;Lee, Hyunsook;Lee, Hae-Ock
    • Molecules and Cells
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    • 제38권3호
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    • pp.251-258
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    • 2015
  • Germline mutations in the breast cancer type 2 susceptibility gene (BRCA2) are linked to familial breast cancer and the progressive bone marrow failure syndrome Fanconi anaemia. Established Brca2 mouse knockout models show embryonic lethality, but those with a truncating mutation at the C-terminus survive to birth and develop thymic lymphoma at an early age. To overcome early lethality and investigate the function of BRCA2, we used T cell-specific conditional Brca2 knockout mice, which were previously shown to develop thymic lymphoma at a low penetrance. In the current study we showed that the number of peripheral T cells, particularly na$\ddot{i}$ve pools, drastically declined with age. This decline was primarily ascribed to improper peripheral maintenance. Furthermore, heterozygous mice with one wild-type Brca2 allele manifested reduced T cell numbers, suggesting that Brca2 haploinsufficiency might also result in T cell loss. Our study reveals molecular events occurring in Brca2-deficient T cells and suggests that both heterozygous and homozygous Brca2 mutation may lead to dysfunction in T cell populations.

One Case of BRCA2 Germline Mutation Ovarian Cancer Mother and Carrier Daughter found by Genetic Counseling

  • Lee, Eun Jung;Jeong, Hee Jeong;Kim, Min Kyu
    • Journal of Genetic Medicine
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    • 제10권2호
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    • pp.124-127
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    • 2013
  • Among cause of carcinogenesis, heredity is believed to take about 10 percent in ovarian cancer. BRCA1 or BRCA2 account for largest portion of Hereditary Breast and Ovary Cancer (HBOC). Frequency of BRCA1/2 germ line mutations varies according to region and ethnicity from 1.1-39.7 percent. The identification of ovarian cancers with a BRCA mutation is will be more and important due to the possibility to offer a genetic counseling and also due to potential beneficial treatment effects with a poly-ADP-ribose polymerase inhibitor in some individuals. We report the case of a 41 year old woman with a stage Ic mucinous ovarian adenocarcinoma and carrier daughter found on family genetic counseling. We indentified other family members with a history of breast cancer of 1st degree and pancreatic cancer of 2nd degree relative. After a screening with immunohistochemistry, the absence of nuclear expression for BRCA1 and BRCA2 was revealed. The gene sequencing confirmed heterozygous mutations of BRCA2 gene. The daughter of the case subject consented for a test. This test was shown the daughter is positive for BRCA2 mutation. Regular surveillance, chemoprophylaxis with oral contraceptive and prophylactic surgery after childbearing were offered to her.

Unusual Intronic Variant in GSTP1 in Head and Neck Cancer in Pakistan

  • Masood, Nosheen;Malik, Faraz Arshad;Kayani, Mahmood Akhtar
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권4호
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    • pp.1683-1686
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    • 2012
  • In the present case control study mRNA expression of the GSTP1 gene, encoding a phase II enzyme that detoxifies via glutathione conjugation, was investigated using semiquantitative PCR followed by SSCP for 49 confirmed head and neck (HN) cancer and 49 control samples. It was found that GSTP1 was upregulated in significantly higher number of cancers (OR 4.2, 95% CI 1.2-15.3). Grade wise correlation was also observed with more up regulation in patients with more advanced grades of HN carcinomas. We also found that 5 patients showed variation in mRNA with a larger product size than expected. Sequencing revealed insertion of an intronic segment between the $6^{th}$ and $7^{th}$ exon of the GSTP1 gene. Germline screening was performed showing mobility shifts which suggested mutation at the DNA level resulting in intronic portion retention. This study is of prime importance for drug design and treatment selection to overcome increased resistance of HN cancers to drugs due to alteration in the GSTP1 gene.

닭에서 원시생식세포의 효율적 분리 및 외래 유전자 전이에 관한연구 (Studies on the Efficient Separation of Primordial Germ Cells and Introduction of Foreign DNA in the Chicken)

  • 정동기;한재용
    • 한국가금학회:학술대회논문집
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    • 한국가금학회 1999년도 제16차 정기총회및학술발표회
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    • pp.11-33
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    • 1999
  • This study was conducted to determine the embryonic stages for the isolation of the highest number of PGCs and to improve PGCs enrichment method. The primordial germ cells(PGCs) from different sources of chick embryos were isolated. The embryonic stage having the highest number of PGCs from each sources was selected ; 1-day-old embryos for germinal crescent (stage 6-8), 2.5-day-old embryos for blood (stage 17-18) and 5.5-day-old embryos for gonad (stage 27-28). The number of PGCs from one embryonic germinal crescent, blood and gonad was about 87$\pm$1.8, 103$\pm$4.0, and 932$\pm$10.9, respectively. The viability of PGCs after Ficoll from each sources was similar, showing approximately 70%. the PGCs enrichment method was improved using Ficoll density gradient centrifugation. After this step the purity of PGCs from germinal crescent, blood, and gonad was 45$\pm$9.10%, 85$\pm$1.18%, and 86$\pm$0.19%, respectively. Also, PGCs were picked up by mouth pipette to improve the purity. This improved method for the separation of PGCs from different sources will serve as a useful too to preserve the foundation stocks of poultry and to produce germline chimeras.

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Impressive effect of cisplatin monotherapy on a patient with heavily pretreated triple-negative breast cancer with poor performance

  • Baek, Dong Won;Park, Ji-Young;Lee, Soo Jung;Chae, Yee Soo
    • Journal of Yeungnam Medical Science
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    • 제37권3호
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    • pp.230-235
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    • 2020
  • Systemic therapy for metastatic triple-negative breast cancer (TNBC) still remains challenging because there are no targeted agents or endocrine therapies currently available. The present case report documents the successful use of cisplatin monotherapy to manage a heavily pretreated TNBC patient showing poor response to therapy. The patient was a 51-year-old woman who had already undergone several lines of systemic chemotherapy for widespread TNBC. Although the mutation analysis performed on DNA isolated from blood cells and progressed lesion samples confirmed the tumor to be germline BRCA wild-type, cisplatin monotherapy was administered based on the increasing evidence of safety and efficacy of platinum for breast cancer. After three cycles of cisplatin treatment, the patient's metastatic lesions dramatically improved without any major toxicity, and she completed 17 cycles with good response. This case study indicates that patients with heavily pretreated TNBC can potentially achieve a good response to cisplatin monotherapy.