• 제목/요약/키워드: host factors

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Human Surfactant Protein-A(SP-A) Gene Locus Associated with Mycoplasma pneumoniae Pneumonia in Korean Children (Mycoplasma pneumoniae 폐렴과 관련된 폐 표면 활성제 단백-A(Human Surfactant Protein-A) 유전자 대립 형질)

  • Kim, Seung Soo;Lee, In Kyu;Ko, Jung Ho;Oh, Myung Ho;Bae, Chong Woo
    • Clinical and Experimental Pediatrics
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    • v.48 no.4
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    • pp.376-379
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    • 2005
  • Purpose : Mycoplasama pneumoniae is a leading cause of pneumonia and exacerbates other respiratory conditions such as asthma. Surfactant protein A(SP-A) is involved in surfactant physiology and surfactant structure, and plays a major role in innate host defense and inflammatory processes in the lung. In this study, SP-A mediated mycoplasma cidal activity. The candidate-gene approach was used to study the association between the SP-A gene locus and Mycoplasama pneumoniae pneumonia in the genetically homogeneous Korean population. Methods : PCR-cRFLP-based methodology was used to detect SP-A genotype. The forty nine children with Mycoplasama pneumoniae pneumonia were matched to 50 nomal neonates. Results : The specific frequencies for the alleles of the SP-A1 and SP-A2 gene in the study population were : $6A^2=21$ percent, $6A^3=45$ percent, $6A^4=11$ percent, $6A^8=9$ percent, $6A^{14}=8$ percent, 1A=11.3 percent, $1A^0=38$ percent, $1A^1=12.7$ percent, $1A^2=9.2$ percent, $1A^5=15.5$ percent, $1A^7=2.9$ percent, $1A^8=4.9$ percent, $1A^9=2.2$ percent, others=3.3 percent. The frequencies of specific genotypes such as $1A^2$ was higher than control group, significantly. Conclusion : $1A^2$ are susceptible factors for Mycoplasama pneumoniae pneumonia. We conclude that the SP-A gene locus($1A^2$) is an important determinant for predisposition to Mycoplasama pneumoniae pneumonia in children.

Delineating Transcription Factor Networks Governing Virulence of a Global Human Meningitis Fungal Pathogen, Cryptococcus neoformans

  • Jung, Kwang-Woo;Yang, Dong-Hoon;Maeng, Shinae;Lee, Kyung-Tae;So, Yee-Seul;Hong, Joohyeon;Choi, Jaeyoung;Byun, Hyo-Jeong;Kim, Hyelim;Bang, Soohyun;Song, Min-Hee;Lee, Jang-Won;Kim, Min Su;Kim, Seo-Young;Ji, Je-Hyun;Park, Goun;Kwon, Hyojeong;Cha, Sooyeon;Meyers, Gena Lee;Wang, Li Li;Jang, Jooyoung;Janbon, Guilhem;Adedoyin, Gloria;Kim, Taeyup;Averette, Anna K.;Heitman, Joseph;Cheong, Eunji;Lee, Yong-Hwan;Lee, Yin-Won;Bahn, Yong-Sun
    • 한국균학회소식:학술대회논문집
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    • 2015.05a
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    • pp.59-59
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    • 2015
  • Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but the treatment of cryptococcosis remains challenging. To develop novel therapeutic targets and approaches, signaling cascades controlling pathogenicity of C. neoformans have been extensively studied but the underlying biological regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs) in this basidiomycetous fungus. In this study, we constructed a high-quality of 322 signature-tagged gene deletion strains for 155 putative TF genes, which were previously predicted using the DNA-binding domain TF database (http://www.transcriptionfactor.org/). We tested in vivo and in vitro phenotypic traits under 32 distinct growth conditions using 322 TF gene deletion strains. At least one phenotypic trait was exhibited by 145 out of 155 TF mutants (93%) and approximately 85% of the TFs (132/155) have been functionally characterized for the first time in this study. Through high-coverage phenome analysis, we discovered myriad novel TFs that play critical roles in growth, differentiation, virulence-factor (melanin, capsule, and urease) formation, stress responses, antifungal drug resistance, and virulence. Large-scale virulence and infectivity assays in insect (Galleria mellonella) and mouse host models identified 34 novel TFs that are critical for pathogenicity. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and ubiquitous human fungal pathogens.

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Serum and Cerebrospinal Fluid(CSF) Nitric Oxide, Macrophage Inflammatory Protein-1 α and Lactoferrin Levels in Aseptic Meningitis (무균성 뇌수막염 환자의 뇌척수액과 혈청에서 Nitric Oxide, Macrophage Inflammatory Protein(MIP)-1α, Lactoferrin 값의 비교)

  • Seo, Young;Sim, Jung Yeon;Shim, Jae Won;Kim, Deok Su;Jung, Hye Lim;Park, Moon Soo
    • Clinical and Experimental Pediatrics
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    • v.48 no.1
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    • pp.48-54
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    • 2005
  • Purpose : The pathologic mechanisms of central nervous system(CNS) injuries in human meningitis are not yet completely understood. Recent studies indicate that the host inflammatory responses are as important in brain damage as the infecting organisms and toxins. There have been some reports on the relationship of nitric oxide(NO), macrophage inflammatory protein-$1{\alpha}$(MIP-$1{\alpha}$), and lactoferrin in bacterial meningitis, but few reports in aseptic meningitis. Thus, we investigated the concentrations of NO, MIP-$1{\alpha}$ and lactoferrin in cerebrospinal fluid(CSF) and serum of patients with aseptic meningitis and control subjects and evaluated their relationship with other parameters of meningitis. Methods : CSF and blood were obtained from 25 subjects with aseptic meningitis and 15 control subjects. After centrifugation, supernatants were stored at $-70^{\circ}C$ and we assayed the concentrations of NO, MIP-$1{\alpha}$ and lactoferrin with the ELISA method. There were no patients with neurologic sequelae after being recovered from aseptic meningitis. Results : Concentrations of CSF and serum NO, MIP-$1{\alpha}$ were not increased in aseptic meningitis subjects compared to control subjects. Concentration of CSF lactoferrin was significantly elevated in patients with aseptic meningitis and concentration of serum lactoferrin was significantly decreased in patients with aseptic meningitis compared with those in control subjects(P<0.05). CSF lactoferrin level was positively correlated with CSF WBC counts($r_s=0.449$, P=0.007), especially with neutrophil counts($r_s=0.574$, P<0.001) and CSF protein level($r_s=0.508$, P=0.002). Conclusion : Lactoferrin plays an important role in aseptic meningitis and may be released from neutrophils recruited from blood to the CSF through breakdown of blood-brain barrier. NO and MIP-$1{\alpha}$ may not be important factors in the pathogenesis of aseptic meningitis without neurologic sequelae.

A Study on Actual Conditions for Prevention of Infections by Dental Hygienists (치과위생사의 감염 예방 실태 조사)

  • Nam, Young-Shin;Yoo, Jung-Sook;Park, Myung-Suk
    • Journal of dental hygiene science
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    • v.7 no.1
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    • pp.1-7
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    • 2007
  • This study aimed to provide basic information on dental hygienists' practicing the prevention of infections by figuring out their actual conditions in dental clinics. The subjects of the study were the dental hygienists who participated in the continuing medical education of Incheon & Gyeonggi-do association and Seoul city association in October and November 2005 and the self-administered surveys were used for the prevention of infections. The results were as below. 1. In terms of education experiences of infection prevention, those who answered "there were" were 72 persons (42.9%) and those who followed the educational route for infection prevention were "through the in-house education from the hospital" and they were 42 persons (58%), which were highest. 2. In terms of the injury experiences, those who answered "there were" were 147 persons (87.5%) and the number of annual injury out of 147 persons with injury experiences was 7.7 time. For the tools that were damaged, 125 persons (75%) damaged the "explorer," which was highest. 3. For the experiences of being infected with contagious diseases, those who answered "there were" were 6 persons (3.6%) and there were four persons for "hepatitis B", one person for "rubella" and one person for "TB." 4. The questions with high practice scores were as in the following: "2. I wash my hands after conducting medical examinations (1.86 points)," "7. I always close the lid of a shot of Novocain after doing local anesthesia (1.86 points)" and "20. I separate and collect the wastes and give them to those who treat accumulated materials (1.85 points)". Meanwhile, the questions with low practice scores were as below: "16. I change my medical gowns (doctor wears) once a day (0.24 point)" and "I wash my medical gowns every time after examining patients with contagious diseases (0.52 points)." 5. The question with high knowledge was as below: "1. The contagion during the dental treatment is determined by source of infection, infection methods, infection routes and the host that is prone to infection (0.95 point)" and the question with the lowest knowledge was "5. HBV(hepatitis B) is destroyed after adding 95oC of heat for more than 5 minutes (0.27 points)." 6. The question with the highest organization-related factors was "I am always ready to use a mask, gloves, etc. if necessary" (0.89 points)" and the question with the lowest score was "There is a guideline that I can refer when I am exposed to dangerous situations related to the contagion in my workplace (0.33 point)." 7. In terms of the equipment conditions of protectors in medical environments, 168 persons for (disposable) mask (100%), 167 persons for disposable gloves (Latex) (99.4%), which meant that most of them were equipped with them. On the contrary, 108 persons (64.3%) are equipped with the protectors for frontal faces, which is the lowest and 165 persons (98.2%) said that they had autoclave in their disinfecting and sterilizing devices.

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Relations between Polymorphism of NRAMP1 Gene and Susceptibility to Pulmonary Tuberculosis (NRAMP1 유전자 다형성과 폐결핵의 감수성과의 관계)

  • Lee, Ji Seok;Cho, Jin Hoon;Kim, Ki Uk;Park, Hye-Kyung;Kim, Yun Seong;Lee, Ho Seok;Kim, Yeong Dae;Jeon, Doo Soo;Park, Seung Kyu;Lee, Min Ki;Park, Soon Kew
    • Tuberculosis and Respiratory Diseases
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    • v.62 no.6
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    • pp.492-498
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    • 2007
  • Background: Several lines of evidence suggest that a host's genetic factors influence the outcome of exposure to Mycobacterium tuberculosis. The aim of this study was to determine whether polymorphism in NRAMP1 (natural resistance associated macrophage protein 1) gene is associated with the susceptibility or resistance to tuberculosis infection for patients with drug-sensitive pulmonary tuberculosis (DS-TB) and multi-drug resistant pulmonary tuberculosis (MDR-TB). Methods: Eight genetic polymorphisms of the NRAMP1 gene were investigated in patients suffering with DS-TB (n=100) or MDR-TB (n=102), and in healthy normal controls (NC, n=96). The genetic polymorphisms of NRAMP1 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of D543N A/G heterogygotes was significantly higher in the DS-TB subjects than the NCs (OR=2.10, 95% CI: 1.00 to 4.41, p=0.049). The frequency of 823C/T T/C heterozygotes was significantly higher in the DS-TB subjects (OR=2.79, 95% CI: 1.11 to 7.04, p=0.029) and the MDR-TB subject (OR=3.30, 95% CI 1.33 to 8.18, p=0.010) than in the NCs. However, the frequency of these genotypes was not different between the DS-TB and MDR-TB subjects. Conclusion: A significant association was found between NRAMP1 823 C/T polymorphism and pulmonary tuberculosis. This result suggests that NRAMP1 polymorphism may be involved in the development of pulmonary tuberculosis in Koreans.

Regulation of Tumor Neceosis Factor-${\alpha}$ Receptors and Signal Transduction Pathways

  • Han, Hyung-Mee
    • Toxicological Research
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    • v.8 no.2
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    • pp.343-357
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    • 1992
  • Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

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Seasonal Changes in Colonization and Spore Density of Arbuscular-Mycorrhizae in Citrus Groves (감귤뿌리에서의 Arbuscular-Mycorrhizae 형성과 감귤원 토양중 포자밀도의 계절적 변화)

  • Kim, Sang-Youb;Oh, Hyun-Woo;Moon, Doo-Khil;Han, Hae-Ryong;Chung, Jong-Bae
    • Korean Journal of Environmental Agriculture
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    • v.17 no.2
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    • pp.174-181
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    • 1998
  • In four citrus grow of Satsuma mandarin (rootstock of trifoliate orange) including two grove of organical management and two groves of conventional management, spores of arbuscular mycorrhizal(AM) fungi were identified and seasonal changes in spore density in soils and AM colonization of citrus roots were investigated. AM colonization in weeds found in the groves were also examined. Three species of Glomus (G.deserticola, G. vesiculiferum, G. rubiforme ) and one unknown species of Acaulospora were observed in all of the groves. Annual mean density of AM fungal spores were in the range of 10,000${\sim}$40,000 per 100g soil with more spores in the organically-managed groves. The least spores were observed in December in all groves, and the most spores in April in the organically-managed groves while in February or April in the conventionally- managed. Annual mean AM colonization more 27% of citrus root were observed in the organically-managed with the high peaks in April and October and the minimum in August, while mean colonization less than 15% in the conventionally-managed with the peak in February and the minimum in different times depending on groves and years. AM colonization corresponded to a sigmoidal curve consisting of a laf phase during winter and a subsequent increase in spring, then succeeded by a maximum, and then a decrease at the end of vegetation. Fungal spore density and AM colonization showed a parallel pattern during the sample period. The seasonality appeared to be related more to the phenology of the plant than to the soil factors. Generally more spore density and AM colonization were found in organically managed groves. AM colonization was not correlated with available P and organic matter content in soil in this field investigation. Among sixteen weed species found in the groves, Astrogalus sinicus of Leguminosae, Portulaca oleracea of Portulacaceae showed high colonization in all groves and they can be considered as a source of inoculumn and host plants for propagation of AM fungi.

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Polymorphisms of HLA-DRB1 and -DQB1 Genes in Korean Patients with Pulmonary Tuberculosis (한국인 폐결핵 환자에서 HLA-DRB1 및 -DQB1 유전자의 다형성에 관한 연구)

  • Park, Myoung Hee;Song, Eun Young;Kwon, Sung Youn;Park, He Jin;Han, Sung Koo;Shim, Young Soo
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.4
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    • pp.367-377
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    • 2003
  • Background : It is well known that only 10% of those infected with Mycobacterium tuberculosis actually develop clinical disease, indicating the existence of host genetic factors regulating disease expression. In this study, we investigated HLA-DRB1 and -DQB1 gene polymorphisms in Korean patients with pulmonary tuberculosis (PTB). Methods : HLA-DRB1 and -DQB1 gene polymorphisms were investigated in 67 PTB patients without previous treatment history, 38 drug-sensitive (DS) and 29 multidrug-resistant (MDR) cases, and 200 healthy controls. HLA-DRB1 typing was done using reverse SSO (sequence specific oligonucleotide) and PCR-SSCP (single strand conformational polymorphism) methods and DQB1 typing was done using PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP and PCR-SSP (sequence specific primer) methods. Results : Among the PTB patients, MDR-TB cases showed frequencies of DRB1*0701 and *08032 increased by about two-fold compared to those of normal controls, and likewise for their associated DQB1 alleles, DQB1*0202 and *0601 (15.5% vs. 34.5%, p=0.01). The frequency of HLA-DQB1*0609 was significantly increased in PTB patients (4.0% vs. 14.9%, p=0.004), showing similar increases in both DS and MDR cases. There was also an association of HLA alleles with the clinical severity of the disease according to the extent of lung lesion. Significantly increased frequencies of DRB1*08032 (4.2% vs. 32.6%, p=0.007) and DQB1*0601 (12.5% vs. 34.9%, p=0.047) were observed in more advanced (moderately & far advanced/DS and far advanced/MDR), compared with less advanced (minimal/DS and moderately advanced/MDR) lung lesions. Although DRB1*0701, DQB1*0202 and DQB1*0609 showed significant increases in different subsets of the disease, these HLA alleles did not show consistent association with disease severity. Conclusion : HLA-DRB1*08032 and DQB1*0601 alleles were associated with genetic susceptibility to MDR-TB in Korean patients, and also with disease severity and progression of PTB.

Endocrine dysfunction after bone marrow transplantation during childhood and adolescence (소아 및 청소년기에서 골수이식 후에 발생할 수 있는 내분비 기능 부전)

  • Jin, Hye Young;Choi, Jin-Ho;Im, Ho-Joon;Seo, Jong-Jin;Moon, Hyung-Nam;Yoo, Han-Wook
    • Clinical and Experimental Pediatrics
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    • v.53 no.3
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    • pp.420-427
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    • 2010
  • Purpose : Several complications can occur in patients who received bone marrow transplantation (BMT) during childhood and adolescence. This study aims to investigate endocrine dysfunctions after BMT so that better care can be provided to care for long-term survivors of BMT. Methods : One hundred patients (61 males, 39 females) were included in this study. Clinical parameters such as initial diagnosis, age at BMT, conditioning regimen, presence of graft-versus-host disease (GVHD), growth pattern, thyroid function, and pubertal status were retrospectively reviewed to evaluate risk factors associated with endocrine dysfunction. Results : Height standard deviation score (SDS) at BMT, after 1 year of BMT, and at the last visit were $0.08{\pm}1.04$, $-0.09{\pm}1.02$, and $-0.27{\pm}1.18$, respectively (P =0.001). Height SDS significantly decreased in patients who received total body irradiation (TBI) (P =0.017). One of the patients who received TBI demonstrated growth hormone deficiency. Thirty (31.9%) of 94 patients had compensated hypothyroidism. Incidence of compensated hypothyroidism was higher among those who had GVHD (odds ratio 2.82, P =0.025). Of the 32 patients (17 males, 15 females) who were over 14 years in male and 13 years in female at the last visit, 16 (3 males, 13 females) had increased luteinizing hormone (LH) or follicle-stimulating hormone (FSH). Abnormal elevation of LH or FSH was more common in females (odds ratio 30.3, P =0.001). Conclusion : The most common endocrine dysfunction was ovarian insufficiency. Regular check-up for endocrine function needs to be required due to high incidence of endocrine dysfunction in patients with BMT.

A Phase II Trial of Combination Chemotherapy with Cisplatin & Etoposide in Small Cell Lung Cancer (소세포폐암에 대한 Cisplatin과 Etoposide(PVP) 복합화학요법의 효과)

  • Cheon, Eun-Mee;Kim, Hyung-Gun;Son, Tae-Young;Yuh, Young-Jin;Lee, Sang-Goo;Lee, Choon-Taek;Kim, Young-Hwan;Lee, Jhin-Oh;Kang, Tae-Woong
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.6
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    • pp.632-643
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    • 1994
  • Background: The objective responses of cisplatin and etoposide (PVP) combination chemotherapy as second-line therapy following CAV was high (40~50%) and, in several reports, PVP yields survival results that are at least as good as those obtained with cyclophosphamide or doxorubicin-based regimens and with less host-related toxicity in chemotherapy-naive patients. We conducted a phase II study to evaluate the effect of a combination of cisplatin and etoposide as a fitst-line therapy in patients with small cell lung cancer. Methods: Sixty-one previously untreated small cell lung cancer patients with measurable lesion (s) received cisplatin(30 $mg/m^2$ IV, day 1~3) and etoposide(100 $mg/m^2$ IV, day 1~3). In patients with limited disease, after completion of 6 cycles of PVP chemotherapy, chest and prophylatic brain irradiation was performed in case of complete responder, chest irradiation on1y in partial responder. Results: 1) Of 55 evaluable patients, 13(24%) had a complete response and 29(53%) had a partial response. 2) The median survival time was 55.8 weeks for all patients(N=55), 61.1 weeks for limited disease(N=31), 51.3 weeks for extensive disease(N=24). 3) The response duration was 29.1 weeks for responders(N=42). 4) There was no significant prognostic factors influencing response rates. 5) The toxicity was tolerable and there was no treatment-related deaths. Conclusion: The PVP combination chemotherapy as a first-line therapy was effective and well-tolerated in patients with small cell lung cancer.

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