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Short-term Clinical Experience on Interferon gamma-1b Therapy for Idiopathic Pulmonary Fibrosis (특발성 폐섬유화증에서 Interferon gamma-1b 치료의 단기 임상경험)

  • Hwang, Jung Hye;Chung, Man Pyo;Kang, Eun Hae;Kim, Kyung Chan;Lee, Byoung-Hoon;Koh, Won-Jung;Suh, Gee Young;Kim, Hojoong;Lee, Kyung Soo;Han, Joungho;Kwon, O Jung
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.6
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    • pp.619-627
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    • 2004
  • Background : Corticosteroids in combination with cytotoxic drugs are the mainstays of therapy for idiopathic pulmonary fibrosis (IPF). However, there has been no regimen showing any survival benefit. The aim of this study was to describe a short-term clinical experience on interferon gamma-1b (IFN-${\gamma}1b$) therapy for IPF, as an antifibrotic agent. Methods : Medical records of 27 patients who were treated with IFN-${\gamma}1b$ (2 million IU, 3 times a week, subcutaneous injection) were retrospectively reviewed. Treatment response was assessed using ATS/ERS criteria in 17 patients who received IFN-${\gamma}1b$ for more than 6 months. In addition, we compared the efficacy of IFN-${\gamma}1b$ therapy with that of cyclophosphamide${\pm}$prednisolone therapy (n=26). Results : The median age of IFN-${\gamma}$ treated group (M:F=19:8) was 59 years (44-74 years). Compared to the patients who showed a stable response at 6 months (n=12), the deteriorated group (n=5) had worse baseline lung function (FVC, $55.4{\pm}11.3%$ vs. $70.7{\pm}10.9%$, p=0.019; DLco, $50.3{\pm}7.3%$ vs. $76.9{\pm}19.6%$, p=0.014). Lower baseline $PaO_2$ on room air breathing was observed in the deteriorated group ($68.6{\pm}7.8mmHg$ vs. $91.4{\pm}6.6mmHg$ p=0.001). Subcutaneous IFN-${\gamma}1b$ did not show better efficacy than prednisolone. Five patients discontinued IFN-${\gamma}$ because of severe side effects. ARDS developed in one patient, who eventually died. Conclusion : The administration of IFN-${\gamma}1b$ is not desirable for patients diagnosed with IPF with poor lung function. Long-term and large-scaled clinical studies are needed for its efficacy in IPF.

Clinical Features of Sulfite-Sensitive Asthmatics (설파이트(Sulfite) 과민성 천식 환자의 임상적 특성에 관한 연구)

  • Cho, Young-Soo;Baik, Su-Hum;Park, Hae-Sim;Rhu, Nam-Soo;Cho, Dong-Ill;Kim, Jae-Won
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.2
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    • pp.159-166
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    • 1992
  • Background:Sulfiting agents are widely used as preservatives and antioxidants in foods, beverages and drugs including bronchodilators. There have been reports of sulfite-related reactions such as anaphylaxis, urticaria, angioedema, abdominal discomfortness as well as bronchospasm. Several investigators reported that sulfite-sensitive asthmatic patients comprised from 3.9% to 8.2% of all asthmatic patients and its prevalence was higher in steroid-dependent group than in steroid-independent group. Subjects and Method:We performed oral provocation test with sodium bisulfite and aspirin in 17 asthmatic patients who have experienced aggravation of their symptoms after administration of drugs or foods. All of them were steroid dependent asthmatics. We observed clinical symptoms and steroid requirements from 1 to 18 months. Result:Ten of them showed severe bronchoconstriction after the ingestion of sodium bisulfite (50 to 200 mg) within 30 minutes. Concurrent aspirin intolerance was noted by oral provocation test in four cases (40%). Three of them showed positive responses on skin prick test with sulfite (10 or 100 mg/ml). Mean total eosinophil counts was $844/mm^3$ at asthmatic attack. And there was no significant responses on skin prick test and IgE-RAST to common inhalant allergens. After complete avoidance from sulfite containing foods and drugs as well as antiasthmatic medication for 1 to 18 months, nine of them (90%) could stop or reduce the steroid requirements. ConcIusion:It was suggested that severe steroid dependent and intrinsic type of asthmatic patients should be evaluated for sulfite-sensitivity.

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Antiemetic Effect of Dolasetron Mesylate in the Prevention of Acute and Delayed Nausea and Vomiting due to Moderately Emetogenic Chemotherapy (악성종양환자에서 중등도 이상의 오심, 구토를 유발하는 항암화학요법 시급성 및 지연성 오심, 구토의 예방에 대한 Dolasetron의 효과)

  • Kim, D.S.;Sung, H.Y.;Choi, K.M.;Paik, J.Y.;Roh, S.Y.;Moon, H.;Kim, C.C.;Hong, Y.S.
    • Journal of Hospice and Palliative Care
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    • v.7 no.2
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    • pp.248-257
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    • 2004
  • Purpose: To evaluate the efficacy of dolasetron mesylate in controlling nausea and vomiting in the first 24 hours and to extend these comparisons over the next 4 days in patients receiving moderately emetogenic chemotherapy. Methods: This was a single center, open-labeled study with single arm. Dolasetron (1.8 mg/kg) was given intravenously (I.V.) prechemotherapy with 10 mg of dexamethasone IV, followed 24 hours later by oral dolasetron (200 mg once daily) for the subsequent 4 days. The frequency of vomiting, severity of nausea and the presence of rescue antiemetics were assessed daily. Results: Of 30 patients enrolled, 28 were eligible and evaluable for the efficacy. Four out of 28 patients had complete control of nausea and vomiting without any rescue antiemetics through 5 days. The complete control got better as time went by with the rates of 17.9/46.4/42.9/53.6/60.7% on days 1 to 5. Vomiting was better controlled than nausea in both cisplatin-containing and non-containing chemotherapy. The adverse events were mild to moderate degrees of headache, diarrhea and fever, but were recovered spontaneously. Conclusion: Dolasetron was effective and safe for the control of nausea and vomiting in the patients with moderately emetogenic chemotherapeutic agents.

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Comparative Studies on the Enzymatic Properties of Trypsins from Cat-shark and Mackerel -1. Purifications and Reaction Conditions of the Trypsins- (복상어와 고등어의 Trypsin에 관한 비교 효소학적 연구 -1. Trypsin의 정제와 반응조건-)

  • PYEUN Jae-Hyeung;CHO Deuk-Moon;HEU Min-Soo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.24 no.5
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    • pp.273-288
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    • 1991
  • To elucidate the physiological and biochemical differences between chondrichthyes and osteichthyes, the properties of the specific digestive enzymes in cat-shark, Cephaloscyllium umbratile, and mackerel, Scomber japonicus, were studied. Homogenous trypsin proved through the disc-electrophoresis, SDS-PAG electrophoresis and gel filtration was obtained from the pancreas of cat-shark by $50-70\%$ saturated ammonium sulphate fractionation, DEAE-Sephadex A-50 column chromatography, benzamidine-Sepharose 6B affinity chromatography and Sephadex G-75-120 gel filtration. Two types of trypsins were also obtained from the pyloric caeca of mackerel by $30-70\%$ saturated ammonium sulphate fractionation and the slightly modified procedure from the method adopted in the purification of cat-shark trypsin. The two trypsins, designated trypsin A and B, were proved their homogeneity by disc- and SDS-PAG electrophoresis and gel filtration. The molecular weights of the trypsins were estimated to be 31,700 for cat-shark trypsin, 30,000 for mackerel trypsin A and 29,000 for mackerel trypsin B by SDS-PAG electrophoresis, but those were estimated to be 21,500 for cat-shark trypsin, 23,700 for mackerel trypsin A and 21,500 for mackerel trypsin B by gel filtration. The trypsins exhibited their optimum conditions at pH 9.0 and on temperature ranged from $45^{\circ}C\;to\;50^{\circ}C$ for cat-shark, and at pH 8.0 and a temperature of $50^{\circ}C$ for mackerel trypsin A and B, respectively. The cat-shark trypsin was stable at pH 10.0 and the temperature below $10^{\circ}C$, whereas the mackerel trypsin A and B, were stable in the range over pH 7.0 to pH 9.0 below $10^{\circ}C$ and at pH 8.0 below $35^{\circ}C$, respectively. The mackerel trypsins were severely inhibited by some heavy metal ions such as $Ag^{2+},\;Cu^{2+}\;and\;Hg^{2+}$ compared to cat-shark trypsin. All of the enzymes were also inhibited by antipain, leupeptin, TLCK(tosyllysine chloromethyl ketone) and SBTI(soybean trypsin inhibitor) remarkably. The inhibitory effects of PMSF(phenylmethane sulphonylfluoride), DFP(diisopropyl fluorophosphate) and benzamidine were indicated that these enzymes belong to serine-proteases.

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Experimental Model of Cardiac Xenograft, Mouse Heart to Rat. (이종이형의 심장이식의 실험적 모델)

  • Kim, Byung-Il;Sohn, Sang-Tae;Shin, Sung-Ho;Chung, Won-Sang;Kim, Hyuk;Kim, Young-Hak;Kang, Jung-Ho;Jee, Heng-Ok;Lee, Chul-Burm;Seo, Jung-Kuk
    • Journal of Chest Surgery
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    • v.32 no.1
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    • pp.1-4
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    • 1999
  • Background: The transplantation of organs between phylogenetically disparate or harmonious species has invariably failed due to the occurrence of hyperacute rejection or accerelated acute rejection. But, concordant cardiac xenograft offer us an opportunity to study xenotransplantation in the absence of hyperacute rejection. Current therapeutics for the prolongation of survival of rodent concordant xenotransplantation are not ideal with many regimens having a high mortality rate. Cyclosporine A & Mycophenolate Mofetil are new immunosuppresive agent which has been shown to be effective at prolonging survival of allograft, as purine synthesis inhibitor. Material and Method: We used white mongrel rats as recipient and mice as donor, divided 4 groups(n=6), control group(Group 1) has no medication or pretreatment, Group 2 has splenectomy as pretreatment 7∼10 days before transplantation, Group 3 has Cyclosporine A treatment group, Group 4 has combined treatment of Cyclosporine A & Mycophenolate Mofetil(RS 61443). We compared survival time. Reuslt: We can't find significant difference of survival time between each groups. Conclusion: We concluded that rejection of cardiac xenograft was different from rejection of allograft, and new immunossuppresive Agent(Mycophenolate Mofetil, Cyclosporine A) was not effective for prolongation of survival time after cardiac xenograft.

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Phase II Study of Induction Irinotecan + Cisplatin Chemotherapy Followed by Concurrent Irinotecan + Cisplatin Plus Twice-Daily Thoracic Radiotherapy (유제한성 병기의 소세포 폐암에서 3주 간격으로 시행된 irinotecan과 cisplatin을 이용한 과다분할 방사선 동시 요법)

  • Lee, Jeong Eun;Park, Hee Sun;Jung, Sung Soo;Kim, Ju Ock;Cho, Moon June;Kim, Jin Hwan;Lee, Choong Sik;Kim, Sun Young
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.2
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    • pp.154-164
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    • 2007
  • Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. Methods: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan $60mg/m^2$ was administered intravenously on days 1 and 8 in combination with cisplatin $60mg/m^2$ on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. Results: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin $19.6mg/m^2$/week and irinotecan $38.2mg/m^2$/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. Conclusion: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.

The Immunogenicity and Safety Study of 47 Passaged Oka Strain Live Attenuated Varicella Vaccine in Healthy Children (건강한 소아에서의 47계대 Oka주 수두약독화 생백신의 면역원성 및 안전성에 관한 연구)

  • Kang, Jin Han;Kim, Jong Hyun;Suh, Byung Kyu
    • Pediatric Infection and Vaccine
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    • v.4 no.2
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    • pp.257-264
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    • 1997
  • Purpose: We performed this study to find out short period humoral immunogenicity and safety of 47 passaged Oka strain live attenuated varicella vaccine(1,400PFU) in 12 months to 15 years aged healthy children. Methods: Ninety nine healthy chidren, who have no histories of varicella vaccination, recent chicken pox illness and contact, allergy to other vaccines and underlying severe diseases, were involved in this study from April 1997 to August 1997. 5ml blood were collected before vaccination and after vaccination from all vaccinees to measure varicella membrane antibody by FAMA, and varicella IgG antibody by EIA. And immediate reactions within 30 minutes after vaccination, local and systemic reactions within 3 days after vaccination and vaccine induced systemic illness during 6 weeks postvaccination period were observed in all vaccinees to identify side effects of study vaccine. Results: 1) 49 seronegative and 50 seropositive vaccinees were identified in both prevaccination serologic tests. 2) Serologic responses after vaccination measured by the FAMA in seronegative group showed that the mean GMT level revealed 64.0, and seroconversion rate was 97.9%. And serologic responses after vaccination measured by the FAMA in seropositive group showed that the mean GMT level(242.2) was markedly elevated comparing with the mean GMT level(9.2) of pre vaccination. 3) The results of EIA in seronegative group revealed that postvaccination mean GMT was 435.2(prevaccination GMT; 78.7), and 100% seroconversion rate. Also, the results of EIA in seropositve group showed that the mean GMT level(769.9) of postvaccination was almostly two fold hihger than the mean GMT level(419.7) of prevaccination. 4) Observed local reactions like injection sites redness, pain, hardness and itching sense were mild and disappeared within 3 days, also shorterm systemic reactions like irritability, lethargy, poor appetites and rash were not remarkable. And there were no remarkable side effects due to vaccine during study period in all vaccinees. Conclusion: We confirmed that 47 paasaged Oka strain live attenuated varicella vaccine has high shorterm humoral immunogenicity and safety. However, we need more detail and longterm humoral and cell mediated immunogenicity studies of this vaccine including clinical field trials.

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Experimental Studies on the Antitumor Effects of Jinryungtang Gagambang Extract (진령탕가감방의 항종양효과(抗腫瘍效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Jeong, Jun-Tak;Moon, Goo;Moon, Suk-Jae
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.4 no.1
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    • pp.37-53
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    • 1998
  • The sprig of Jinryungtang Gagambang has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Jinryungtang Gagambang extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell liens (A549, hep3B, Caki-1, Sarcoma 180) after exposure to Jinryungtang Gagambang extract using in ILS, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Jinryungtang Gagambang extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Jinryungtang Gagambang extract showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Jinryungtang Gagambang decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Jinryungtang Gagambang also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Jinryungtang Gagambang extract into TBM. 4. Jinryungtang Gagambang extract also increased NK cell activities. According to the above results, it could be suggested that Jinryungtang Gagambang extract has prominent antiutmor effect.

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Comparative Uptake of Tc-99m Sestamibi and Tc-99m Tetrofosmin in Cancer Cells and Tissue Expressing P-Glycoprotein or Multidrug Resistance Associated Protein (P-Glycoprotein과 Multidrug Resistance Associated Protein을 발현하는 암세포와 종양에서 Tc-99m Sestamibi와 Tc-99m Tetrofosmin의 섭취율 비교)

  • Cho, Jung-Ah;Lee, Jae-Tae;Yoo, Jung-Ah;Seo, Ji-Hyoung;Bae, Jin-Ho;Jeong, Shin-Young;Ahn, Byeong-Cheol;Sohn, Sang-Gyun;Ha, Jeoung-Hee;Lee, Kyu-Bo
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.1
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    • pp.34-43
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    • 2005
  • Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.

Induction Chemotherapy and Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (국소 진행된 비소세포성 폐암에서 유도 화학요법 및 방사선치료)

  • Yun, Sang-Mo;Kim, Jae-Cheol;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.17 no.3
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    • pp.195-202
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    • 1999
  • Purpose : We peformed this study to evaluate the prognostic factors and the effect of induction chemotherapy in locally advanced non-small cell lung cancer (NSCLC). Materials and Methods : A retrospective analysis was done for 130 patients with locally advanced NSCLC treated with curative radiotherapy alone or induction chemo-radiotherapy from January 1986 to October 1996. Eighty-five patients were treated with radiotherapy alone, forty-five with induction chemotherapy and radiotherapy. Age, sex, performance status, histopathologic type, and stage were evenly distributed in both groups. The patients were treated with 6 MV or 10 MV X-ray. Conventional fractionation with daily fraction size 1$.8\~2.0$ Gy was done. Of the patients, 129 patients received total dose above 59.6 Gy ($56\~66$ Gy, median 60 Gy). Induction chemotherapy regimen were CAP (Cyclo-phosphamide, Adriamycin, Cisplatin) in 6 patients, MVP (Mitomycin, Vinblastine, Cisplatin) in 9 patients, MIC (Mitomycin, Ifosfamide Cisplatin) in 13 patients, and EP (Etoposide, Cisplatin) in 17 patients. Chemotherapy was done in $2\~5$ cycles (median 2). Results : Overall 1-, 2-, and 3-year survival rate (YSR) for all patients were $41.5\%,{\;}13.7\%,{\;}and{\;}7\%$, respectively (median survival time 11 months). According to treatment modality, median survival time, overall 1-, 2-, and 3-YSR were 9 months, $32.9\%,{\;}10.\5%,{\;}6\%$ for radiotherapy alone group, and 14 months, $57.8\%,{\;}20\%,{\;}7.6\%$ for induction chemotherapy group, respectively (f=0.0005). Complete response (CR) to overall treatments was $25\%$ (21/84) in radiotherapy alone and $40.5\%$ (17/42) in induction chemotherapy group (p=0.09). The Prognostic factors affecting overall survival were hemoglobin level (p=0.04), NSE (neuron-specific enolase) level (p=0.004), and respense to overall treatment(p=0.004). According to treatment modalities, NSE (neuron-specific enolase) (p=0.006) and response to overall treatment (p=0.003) were associated with overall survival in radiotherapy alone group, and response to overall treatment (p=0.007) in induction chemotherapy group. The failure Pattern analysis revealed no significant difference between treatment modalities. But, in patients with CR to overall treatment, distant metastasis were found in 11/19 patients with radiotherapy alone, and 3/13 patients with induction chemotherapy and radiotherapy (p=0.07). Locoregional failure patterns were not different between two groups (10/19 vs 6/13). Conclusion : Induction chemotherapy and radiotherapy achieved increased 2YSR compared to radiotherapy alone, At least in CR patients, there was decreased tendency in distant metastasis with induction chemotherapy. But, locoregional failures and long-term survival were not improved. Thus, there is need of more effort to increasing local control and further decreasing distant metastasis.

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