• Title/Summary/Keyword: bleomycin

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Cloning of the Genomic DNA Which Complements the Drug-Hypersensitivity of Saccharomyces cerevlsiae

  • Lee, Yun-Sik;Park, Kie-In
    • BMB Reports
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    • v.30 no.3
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    • pp.167-172
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    • 1997
  • The yeast Saccharomyces cerevisiae, mutant CH117, shows a drug-hypersensitivity (dhs) to cycloheximide, bleomycin, actinomycin D, 5-fluorouracil. nystatin, nigericin and several other antibiotics. CH 117 was also temperature-sensitive (ts). being unable to grow at $37^{\circ}C$ and secreted more invertase and acid phosphatase into the medium than the parent yeast. CH117 grows very slowly and the cell shape is somewhat larger and more sensitive to zymolyase than the wild type cells. Light microscopic and electron microscopic observation also revealed abnormality of the mutant cell wall. These characteristics indicate that CH117 has a defect in an essential component of the cell surface and that the cell wall which performs barrier functions has become leaky in the mutant. We screened a genomic library of wild type yeast for clones that can complement the mutation of CH117. A plasmid, pCHX1, with an insert of 3.6 kilobases (kbs) could complement the dhs and ts of CH117. Deletion and subcloning of the 3.6 kb insert showed that a gene for the complementation of mutant phenotypes was located in 1.9 kbs Puvll-Hindlll fragment.

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The Effects of Inhibitors of DNA Polymerases and Topoisomerase on Chromosome Aberrations Induced by Mutagens in Synchronized Mammalian Cells (동시화된 포유동물 세포에서 돌연변이원에 의해 유발된 염색체 이상에 미치는 DNA중합효소와 DNA위상이성질화효소의 저해제의 효과)

  • 엄경일;신은주;권영순
    • Environmental Mutagens and Carcinogens
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    • v.10 no.2
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    • pp.85-92
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    • 1990
  • The effects of aphidicolin (APC), 2`,3`-dideoxythymidine 5`-triphosphate (ddTTP), and novobiocin (NOV) on the frequencies of chromosome aberrations induced by ethyl methanesulfonate (EMS) or bleomycin (BLM) were examined in synchronized Chinese hamster ovary (CHO)-K$_1$ cells. The cells were synchronized by the thymidine double block method. APC, ddTTP and NOV alone did not affect the frequencies of chromosome aberrations. The cells in late G$_1$ and early S phases were sensitive to the induction of chromosome aberrations by EMS, wherase cells in G$_2$ phase were most sensitive to chromosme aberration by BLM.

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Interaction of ${\varepsilon}-L-{\beta}-lysine$ as a Tail Analogy of Tallysomycin-A to a Double Helical DNA Oligonucletide $d(CGCTTCGAAGCG)_{2}$, was investigated by NMR

  • Lee, Chang-Jun;Won, Ho-Shik
    • Journal of the Korean Magnetic Resonance Society
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    • v.11 no.2
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    • pp.129-137
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    • 2007
  • During the screening of material which has the antimicrobial activity against aminoglycoside-resistant bacteria, A new material ${\varepsilon}-(L-{\beta}-lysine)$ polypeptide from a culture medium of Streptomyces sp.(DWGS2) was isolated, and the structure and the physicochemical properties of the new material were elucidated. The new material was separated by column chromatography of the culture medium using Dowex $1{\times}2$, Silica gel, and Sephadex LH20 etc. The structure and molecular weight were determined with the data of NMR, MALDI mass, and ESI mass experiments. And the monomer obtained by hydrolysis of the new material with 6N-HCI was identified as a $L-{\beta}-lysine(T_2)$, which is a tail of bleomycin. As tail-region analogy, $T_2({\beta}-lysine$ derivatives from streptomyces) interactions with a self-complementary oligonucleotides, $d(CGCTTCGAAGCG)_2$, was investigated by NMR.

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Environmental Toxic Agents on Genetic Material and Cellular Activity IV. Novobiocin-Mediated Inhibition of DNA Repair Synthesis in Synchronized Chinese Hamster Ovary Cells

  • 엄경일;김춘광;신은주;문용석;이천복
    • Environmental Mutagens and Carcinogens
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    • v.9 no.1
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    • pp.13-22
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    • 1989
  • The effect of novobiocin (NOV), and inhibitor of topoisomerase II, on ethyl methanesulfonate (EMS)-or bleomycin (BLM)-induced DNA repair synthesis was examined during the cell cycle of Chinese hamster ovary (CHO)-K1 cells. Three assays were employed in this study: cell survival, alkaline elution and unscheduled DNA synthesis. EMS was effective at killing CHO cells in G1 phase, wheras BLM preferentially killed cells in G2 and S phases. EMS induced the much more amount of DNA damage in G1 phase, while BLM induced in G2 phase than the other phases. The both of pre- and post-treatment with BOV inhibitied EMS- or BLM-induced DNA repair synthesis in G1 and G2 phases, and pretreatment with NOV inhibited more effectively than the post-treated group. These results suggested that CHO cells exhibited a differential sensitivity to cell lethality and DNA damage in relation to cell cycle according to used chemical agents, and that DNA topoisomerase II participated in an initial stage of DNA repair.

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Environmental Toxic Agents on Genetic Material and Cellular Ativity V. The Roles of DNA Polymerases on Mutagen-Induced DNA Repair Synthesis in Relation to Cell Cycle in Chinese Hamster Ovary Cells (환경성 유해요인이 유전물질과 세포활성에 미치는 영향 V. CHO세포에서 세포주기에 따라 돌연변이원에 의해 유발된 DNA회복합성에 미치는 DNA중합효소의 역할)

  • 엄경일;김춘광;신은주;문용석;이천복
    • Environmental Mutagens and Carcinogens
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    • v.9 no.1
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    • pp.23-32
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    • 1989
  • Chinese hamster ovary (CHO)-K1 cells echibited a differential sensitivity in the process of DNA repair synthesis induced by ethyl methanesulfonate (EMS) or bleomycin (BLM) in relation to cell cycle. Two assays were employed in this study: alkaline elution and unscheduled DNA synthesis. The post-treat-ment with aphidicolin (APC), an inhibitor of DNA polymerase alpha, inhibited DNA repair synthesis induced by EMS in G2 phase, while APC did not show any effect on BLM-induced DNA repair synthesis in all phases. On the other hands, the 2', 3'-dideoxythymidine (ddTTP), an inhibitor of DNA polymerase beta, inhibited DNA repair synthesis induced by EMS or BLM in both of G1 and G2 phases. These results suggested that the involvement of DNA polymerase alpha and beta in DNA repair was dependent on cell stage or used chemical agent.

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Identification of Derivatives of Cobalt-binding BLM-A2 by NMR

  • Lee, Seongeon;Shin, Donghyuk;Woo, Sunhee;Won, Hoshik
    • Journal of the Korean Magnetic Resonance Society
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    • v.16 no.2
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    • pp.133-146
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    • 2012
  • Three different derivatives were obtained in the synthesis of cobalt-binding BLM-A2 and characterized by NMR and Mass spectrometry. It was found that Component 1 is Co(II)($2H_2O$)(BLM-A2), component 2 is Co(III)($OOH^-$)(BLM-A2) and component 3 is Co(III)($H_2O$)($OH^-$)(BLM-A2), respectively. Component 2 and 3 were interestingly dominated when CoBLM-A2 complex was synthesized under basic condition. In this experiment, it was revealed newly that the brown form (component 1) was 6-coordinated structure composed with not 5 ligands but 4 ligands from BLM-A2 and with $2H_2O$ as the axial ligands. The component 3 exhibiting a novel ligand configuration is found, and the structure of component 3 was observed to be very similar to that of component 1 in the kind of their ligands but one of the axial ligand is $OH^-$ instead of $H_2O$. These ligand configurations are different from the green form (component 2) exhibiting 6-coordinate structure composed of 5 ligands from BLM-A2 and one ligand of $OOH^-$, being consistent with former studies.

DNA Double-Strand Breaks Serve as a Major Factor for the Expression of Arabidopsis Argonaute 2

  • Lee, Sungbeom;Chung, Moon-Soo;Lee, Gun Woong;Chung, Byung Yeoup
    • Journal of Radiation Industry
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    • v.10 no.4
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    • pp.243-248
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    • 2016
  • Argonaute 2 (AtAGO2) is a well characterized effector protein in Arabidopsis for its functionalities associated with DNA double-strand break (DSB)-induced small RNAs (diRNAs) and for its inducible expression upon ${\gamma}$-irradiation. However, its transcriptional regulation depending on the recovery time after the irradiation and on the specific response to DSBs has been poorly understood. We analyzed the 1,313 bp promoter sequence of the AtAGO2 gene ($1.3kb_{pro}$) to characterize the transcriptional regulation of AtAGO2 at various recovery times after ${\gamma}$-irradiation. A stable transformant harboring $1.3kb_{pro}$ fused with GUS gene showed that the AtAGO2 is highly expressed in response to ${\gamma}$-irradiation, after which the expression of the gene is gradually decreased until 5 days of DNA damage recovery. We also confirm that the AtAGO2 expression patterns are similar to that of ${\gamma}$-irradiation after the treatments of radiomimetic genotoxins (bleomycin and zeocin). However, methyl methanesulfonate and mitomycin C, which are associated with the inhibition of DNA replication, do not induce the expression of the AtAGO2, suggesting that the expression of the AtAGO2 is closely related with DNA DSBs rather than DNA replication.

Korean Medicine Treatments with Joripewon-tang for Chemotherapy-Induced Peripheral Neuropathy of Ovarian Cancer : Case Report (난소암의 항암화학요법 유발 만성 말초신경병증의 조리폐원탕 및 복합한의치료 치험 1례)

  • Ji-yoon, Yeum;Su-hyun, Kim;Seung-yun, Oh;Soo-jung, Park
    • Journal of Korean Traditional Oncology
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    • v.27 no.1
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    • pp.49-56
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    • 2022
  • Objective: This case report represented that Korean traditional medicine therapies can make effective results for chemotherapy-induced peripheral neuropathy(CIPN) patients. Methods: A 63-year-old female patient has been diagnosed with ovarian cancer(Sertoli-Leydig cell tumor). Total excision of uterus and appendages was operated, and Bleomycin, etoposide and cisplatin combination therapy was applied. After three cycles of chemotherapy, the severe side effects of neutropenia and CIPN occurred. Chemotherapy was terminated, but numbness and tingling pains in the limbs persisted for several months. We provided Korean medicine treatments including herbal medicine, pharmacopuncture, acupuncture, moxibustion and physiotherapies. Results: After treatments, the numbness and pain were reduced from 10 to 1 in hand and 6 to 0 on the numeric rating scale(NRS). Functional assessment of cancer therapy/Gynecologic oncology group neurotoxicity (FACT/GOG-NTX) score was improved from 58 to 97. Conclusion: According to these results, Korean medicine treatments could be considered effective for CIPN. Prospective studies are needed to confirm and expand these findings.

Porokeratosis ptychotropica: a case report

  • Young-Wook Ryoo;Yura Kim;Ji-Min Yun;Sung-Ae Kim
    • Journal of Yeungnam Medical Science
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    • v.40 no.4
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    • pp.423-425
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    • 2023
  • Porokeratosis ptychotropica is an uncommon form of porokeratosis, which was initially described in 1995. It is clinically characterized by symmetrical reddish to brown-colored hyperkeratotic, verrucous, or psoriasiform plaques on the perianal and gluteal regions. The lesions tend to integrate and expand centrally, with small peripheral satellite lesions. Early skin biopsy and appropriate diagnosis are essential because malignant change occurs in 7.5% of porokeratotic lesions. Conventional treatment options include topical steroid, retinoid, imiquimod, 5-fluorouracil, isotretinoin, excimer laser, photodynamic therapy, intralesional steroid or bleomycin injection, cryotherapy, carbon dioxide (CO2) laser, and dermatome and excision, but none seem to achieve complete clearance. A 68-year-old woman presented with diffuse hyperkeratotic scaly lichenoid plaques on the buttocks that had persisted for several years. A skin biopsy of the buttocks revealed multiple cornoid lamellae and intense hyperkeratosis. There were some dyskeratotic cells beneath the cornoid lamellae and the granular layer was absent. Porokeratosis ptychotropica was diagnosed based on the characteristic clinical appearance and typical histopathological manifestations. She was treated with a CO2 laser in one session and topical application of urea and imiquimod cream for 1 month. The lesions slightly improved at the 1-month follow-up. We herein present a rare case of porokeratosis ptychotropica.

Clinical Review and PCNA Expressions of Teratomas in Pediatric Patients (소아 기형종의 임상적 고찰 및 PCNA 발현율에 관한 연구)

  • Joo, J.H.;Choi, S.J.N.;Chung, S.Y.;Kim, S.K.
    • Advances in pediatric surgery
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    • v.1 no.2
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    • pp.122-132
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    • 1995
  • Teratoma contains elements derived from all three embryonic germ layers and mature teratomas are entirely composed of mature differentiated tissues, while immature types always contain additional embryonic tissues of variable degree of immaturity, especially neuroepithelial elements. Twenty cases of teratoma in infancy and childhood were reviewed and the clinical features and pathologic findings including PCNA expression were studied. Sacrococcygeal teratomas were the most common type(45%), followed by retroperitoneal and ovarian teratomas. There was a predilection of females in a ratio of 4:1 and age distribution was most prevalent below the first year of age(45%). But in ovarian teratomas, the age at diagnosis was above 4 years of age in all cases. Serum alpha-fetoprotein levels were checked in 18 cases. In all mature teratomas and 1 of 5 immature teratomas, the levels were normal. But in 4 of 5 immature teratomas, the serum levels were elevated and progressively declined to normal range after mass excision. Radiologically, calcifications in tumor were found in 60.0% of teratomas and was higher in mature teratomas(69.2%) than immature teratomas(42.9%). Immunohistochemical staining for PCNA(proliferating cell nuclear antigen) was done in 16 cases and PCNA expression was higher in grade III immature teratomas than grade I and II. The operative modes were complete mass excisions. Five immature teratomas were treated with multiagent PEB(Bleomycin, Etoposide, Cisplatin) adjuvant chemotherapy, 3 tolerated well without significant complications, but in one case, severe bone marrow suppression was developed and died of sepsis. In conclusion, grade III immature teratoma showed higher PCNA expression than mature or lower grade immature teratoma, which suggests that chemotherapy after surgical excision may be effective modality for grade III immature teratoma. We think, however, multicenter study is necessary because of low incidence of immature teratoma.

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