악성종양에서 혈청 Intercellular Adhesion Molecule-1의 혈청

조덕연,김현수,박상준,김종숙,최지영,윤환중,김삼용 충남대학교 의과대학 지역사회의학연구소 1995 충남의대잡지 Vol.22 No.1

Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein serving as ligands for leukocyte intergrin receptors, i.e. LFA-1, MAC-l. It has been suggested that the expression of ICAM-1 and the levels of circulating ICAM-1 were increased in several malignancies. We measured serum ICAM-1 by ELISA in patients with stomach cancer (n=25), acute lymphoblastic leukemia (n=7), non-Hodgkin's lymphoma (n=14), and metastasis of unknown origin (n=5). Serum levels of circulating ICAM-1 in all malignancies were significantly higer than in normal controls. And serum level of ICAM-1 in stomach cancer ptients having metastatic disease was higher than in patients with localized disease (p=0.027). These results suggest that elevated serum ICAM-1 is a rather common feature for malignancies, not unique for certain types of cancer such as malignant melanoma. It remains to be clalified whether marked increase of serum ICAM-1 in metastatic stomach cancers simply reflect tumor burden or this molecule plays a role in progression in stomach cancer.

위암에 대한 복합치료 성적

조덕연,김삼용 충남대학교 의과대학 지역사회의학연구소 1988 충남의대잡지 Vol.15 No.1

Combined radiotherapy(RT, 4500-5400 rad) plus systemic chemotherapy(CT) using FAM regimen(5-FU 600 mg/m²iv days 1, 8, 29, 36, Doxorubicin 30mg/m²iv days 1, 29, MitomycinC 10mg/m²iv day 1) 2-6 cycles were given to 5 patients with high risk resected stomach cancer and 2 patients with advanced stomach cancer. 4 of 5 patients with resected stomach cancer fares well 21 months, 16 months, 12 months and. 6 months after diagnosis without evidence of disease. 1 patient with resected cancer died of stomach outlet obstruction (without tumor recurrence by endoscopy) 19 months after diagnosis. 1 patient with recurrent stomach cancer is alive 9 months after diagnosis but shows porgressive disease. 1 case of advanced stomach cancer died of disease at 7 months. The toxicity from combined RT and CT were moderate. In 7 patients, 2 cases showed grade 2 GI toxicity, 4 cases showed grade 1 GI toxicity. For granulocyte level, there was one grade 1 toxicity, 4 with grade 2 toxicity and one with grade 3 toxicity. For platelet level, 4 cases showed grade 1 toxicity and 2 cases showed grade 2 toxicity. The effect of combined adjuvant therapy in high risk resected stomach cancer must be followed by further observations. For selected patients with locally advanced GI cancer, combined RT and CT might be effective measures, without significant toxicities.

항암화학요법을 받는 암 환자에 대한 Nucare^R의 영양지지효과

조덕연,김현수,곽상혁,강정현,김철희,배광봉,김종숙,박상준,윤환중,김삼용 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.1

Purpose : The purpose of this study was to evaluate the effect of nutritional support with enteral liquid supplement in cancer patients receving chemotherapy for possible benefit in nutritional, immunologic and golbal function of patients. Patients and Methods : From October 1995 to February 1997, 30 advanced cancer patients receving chemotherapy were divided two roups. The Nycare group, in addition to normal diet, Nucare^R enteral supplement was given for 1week right after chemotherapy for the duration of 2 chemotherapy cycles. Control group received only normal diet without parenteral fluid supplement for 2 chemotherapy cycles. Results : Median ages were 53 end 56 years for Nucare group and Contrl group respectively. Performance scores was less than 2 by ECOG scale. All patients were stage Ⅲ or Ⅳ. The physical parameters, such as weight, arm muscle circumference(AMC) and triceps skin fold(TSF) were decreased in both groups after 2 cycles of anticancer therapy. but it was less severe in Nucare group(p<0.05). Serum transferrin was maintained in mild deficit state in Nucare group, whereas it aggravated form mild to moderate deficit in Control group(p<0.05). Serum albumin level increased in Nucare group without statistical significance. but it decreased from normal to mild deficit in Control group. Serum total protein did not change significantly in Nucare group. but in Control group, serum total protein was decreased from 7.24±0.9 to 6.52±0.5(P<0.05). Total lymphocyte count did not change significantly in both groups. Conclusion : This study shows that the nutritional support with Nucare^R was effective in the prevention of nutritional deficit status in patients receving a nticancer chemotherapy.

急性骨髓性 白血病에서의 試驗管內 集落細胞 形成에 관한 연구

고석만,조덕연,박철신,강원권,김민범,김삼용,노흥규 충남대학교 의과대학 지역사회의학연구소 1988 충남의대잡지 Vol.15 No.2

To evaluate the in vitro granulocyte-macrophage colony formation in acute myfloblastic leukemia and the prognostic implications of these results, the author performed the in vitro agar culture of bone marrow cells in 10 patients with acute myeloblastic leukemia (AML) and 5 control subjects. Culture medium was composed of 20% fetal calf serum(FCS), 50% Iscove's medium, 0.3% agar, 10% colony stimulation factor (CSF), and 2 × 10 exp (5) cells/ml. Human placental conditioned medium (HPCM) and phytohemagglutinin-leukocyte conditioned medium (PHA-LCM) were used as colony stimulating factor. Colony counting was done on 7th day of culture. Colony was defi ned as containg 20 or more cells, and cluster was defined as containing 3-19 cells. The results were as followings, 1. In control subjects, the number of clusters formed was 3-47/2 × 10 exp (5) cells (20±19)and that of colonies was 5-24/2 × 10 exp (5) cells (14±9) when stimulated with HPCM. When stimulated with PHA-LCM, the number of clusters formed 5-39/2 × 10 exp (5) cells(18±16) and that of colonies was 6-13/2 × 10 exp (5) cells (9±3). 2. In AML patients, 3 groups were recognized according to pattern of colony formation: 1) non-forming 2) cluster forming 3) both cluster and colony forming. Of 10 cases, 5 cases Were `non-forming', 2 cases were `cluster forming'; and 3cases wer cluster and `colony forming'; 3. All 5 cases 'non-forming' cases, one of 2 cases of `cluster forming'; and none of 3 cases of `cluster and colony forming' achieved complete remission. So, there was significa nt difference in remission rate in the different growth types. These results suggest that granulopoiesis in AML patients is impaired and the pattern of in vitro CFU-L(colony forming unit-leukemia) formation has prognostic significance.

진행위암에 대한 병합화학요법

김삼용,조덕연 충남대학교 의과대학 지역사회의학연구소 1987 충남의대잡지 Vol.14 No.2

Twenty-three patients with advanced stage metastatic or unresectable gastric cancer were given combination chemotherapy consisting of Fluorouracil, Doxorubicin, and Cisplatin(FAC) or Mitomycin(FAM). 5 patients receiving FAC and 6 patients receiving FAM were evaluable. 3 patients receiving FAC and 3 patients receiving FAM achieved partial response. So, overal response rate was 60% for FAC and 50% for FAM. Median duration of response was 13 weeks for FAC and 20 weeks for FAM. 1 patient receiving FAC and 2 patients receiving FAM who achieved partial response are alive. Median survival was 8 months for FAC and 7 months for FAM. Responders had a longer survival than nonresponder in both regimens. There was no difference in response and median survival between 2 regimens. Toxicities were mainly gastrointesinal and hematologic, but were moderate and well tolerated in both groups. In conclusion, these regimens have substantial effects on advanced or unresectable gastric cancer without severe toxicities.

대량화학요법을 위한 G-CSF를 이용한 말초조혈모세포의 구동

김삼용,조덕연 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.2

This study probed the effective and economic method for mobilizing the hemopoietic stem cells for the support of high-dose chemotherapy. Eleven trials of Hemopoietic mobilization was performed in 10 patients. A total of 36 leukapheresis was performed(median; 3, range; 2 - 6). Cytotoxic chemotherapy plus G-CSF(300μg/day x 7 days) or G-CSF alone was given to mobilize hemopoietic stem cells. A median of 5.4 x (3.3 - 9.47) x 10 ^8/kg mononuclear cells and 5.1(1.3 - 43) x 10^4/kg GM-CFU was obtained. Nine courses of high-dose chemotherapy was performed in 8 patients. Days with absolute neutrophil count less than 1000/㎣ was 8.5(range ; 3-26) and days with platelet count less than 50.000/㎣ was 14(range; 0-46). Days G-CSF required was 12.5(range ; 9-27) and a median of 100units(range; 10-250) of platelet transfusion was required. Days with antibiotic coverage was 7. 5(0-30) and days of admission was 24(range; 17-51). We can conclude in this study that cyclophosphamide 2g/㎡ and G-CSF 300μg x 7days, or G-CSF for 7 days arc sufficient for the mobilization of hemopoietic stem cells for the high-dose chemotherapy.

急性骨髓性 白血病에서의 試驗管內 集落細胞 形成에 관한 연구

고석만,조덕연,박철산,강원권,김민범,김삼용,노홍규 忠南大學校 癌共同硏究所 1991 癌共同硏究所 硏究誌 Vol.1991 No.-

急性骨髓性 白血症에서의 試驗管內 集落細胞 形成에 관한 연구

고석만,조덕연,박철신,강원권,김민범,김삼용,노흥규 忠南大學校 癌共同硏究所 1991 癌共同硏究所 硏究誌 Vol.1 No.1

To evaluate the in vitro granulocyte-macrophage colony formation in acute myeloblastic leukemia and the prognostic implications of these results, the author performed the in vitro agar culture of bone marrow cells in 10 patients with acute myeloblastic leukemia (AML) and 5 control subjects. Culture medium was composed of 20% fetal calf serum(FCS), 50% Iscove's medium, 0.3% agar, 10% colony stimulation factor (CSF), and 2×105 cells/ml. Human placental conditioned medium (HPCM) and phytohemagglutinin-leukocyte conditioned medium (PHA-LCM) were used as colony stimulating factor. Colony counting was done on 7th day of culture. Colony was defined as containg 20 or more cells, and cluster was defined as containing 3 - 19 cells. The results were as followings, 1. In control subjects, the number of clusters formed was 3-47/2×10^(5) cells (20±19)and that of colonies was 5-24/2×10^(5) cells (14±9) when stimulated with HPCM. When stimulated with PHA-LCM, the number of clusters formed 5-39/2×10^(5) cells(18±16) and that of colonies was 6-13/2×10^(5) cells (9±3). 2. In AML patients, 3 groups were recognized according to pattern of colony formation : 1) non-forming 2) cluster forming 3) both cluster and colony forming. Of 10 cases, 5 cases were 'non-forming', 2 cases were 'cluster forming'; and 3cases wer cluster and 'colony forming'; 3. All 5 cases 'non-forming' cases, one of 2 cases of 'cluster forming'; and none of 3 cases of 'cluster and colony forming' achieved complete remission. So, there was significant difference in remission rate in the different growth types. These results suggest that granulopoiesis in AML patients is impaired and the pattern of in vitro CFU-L(colony forming unit-leukemia) formation has prognostic significance.

과립구감소증의 발열환자에 대한 Teicoplanin을 포함하는 제 2선 경험적 항생요법

이강욱,조덕연,김삼용 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.1

Background and Purpose : In recent years, the frequency of isolation of Gram-positive organisms, including coagulase negative Staphylococci and Streptococci, is increasing in neutropenic febrile patients. So, it seems reasonable to expect that at least a sub-population of these patients might benefit from the addition of a glycopeptide to the standard empiric regimen. Teicoplanin is a new glycopeptide with comparable activity to vancomycin, which needs be given only once daily. We therefore conducted a study to evaluate the efficacy and safety of teicoplanin as a second-line empiric therapy in neutropenic febrile patients. Patients and Methods : Neutropenic patients were given a empiric antibiotic regimen consisting of cephalosporin, aminoglycoside, and antipseudomonal penicillin when a significant febrile episode occurred. In cases of no clinical improvement after 72 hours of this therapy, cephalosporin was replaced with teicoplanin. Teicoplanin was administered initially 400mg intravenously at 12 hour-interval 2 times and then once daily. Results : 17 neutropenic febrile patients who did not respond to first line empiric antibiotic therapy were enrolled in this study. Infections were documented clinically or microbiologically in 10 of 15 assessable cases(67%). Infection sites were bacteremia in 4 cases, chest 1, Hickman catheter 2, and others 4. Staphylococcus epidermidis was the most frequently isolated organism(5/9, 56%). The others included Staphylococcus hemolyticus(11 %), Streptococcus group A(11%), Pseudomonas species(11%), and Candida tropicalis(11%). In 6 of 9 cases with microbiologically documented infection, causative organisms were eradicated with teicoplanin rescue(response rate 67%). 11 of 15 evaluable patients were cured clinically (response rate 73%). 2 patients were cured after the addition of amphotericin B and 2 patients died of infection (failure rate 13%). Mild elevations of liver enzymes were observed in 3 cases. The relationship of these abnormalities to teicoplanin was uncertain due to concurrent use of anticancer and/or antifungal agents. Any other toxicities requiring cessation of teicoplanin rescue were not observed. Conclusions : These results show that a large proportion of febrile episodes in neutropenic patients is related to infection caused by Gram positive organisms and that teicoplanin has high efficacy in the management of febrile episodes in neutropenic patients without significant toxicity.

항암제 처리한 백혈병 세포주에서의 Apoptosis 발현

김삼용,윤소현,김현수,김종숙,윤환중,김진경,조덕연 충남대학교 암연구소 1998 癌共同硏究所 硏究誌 Vol.2 No.1

The bcl-2 proto-oncogene encodes a 26 kD protein that promotes cell survival by blocking apoptosis. The bax protein is a member of the bcl-2 familly, now known to form heterodimers with the bcl-2 protein. The ratio of bax to bcl-2 is be critical in determining the fate of the cell in response to stimuli that can induce apoptosis. Extract of Pulsatilla Koreana (SB-31) showed promising antitumor activity in vitro with Topo I inhibitory action. In the present study, the relationship between apoptosis and the apoptosis related proteins, bcl-2 and bax were investigated in human leukemic cell lines HL-60, U-937 and CEM-CM3. All anticancer drugs(adriamycin, etoposide, camptothecin, SB-31) induced extensive apoptosis in HL-60, U-937 cells and CEM-CM3 cells. The expression of bcl-2 and bax protein were determined in cell lines by western blotting before and after incubation with anticancer drugs at different time points. 1) In HL-60 or U-937 cell lines, down regulation of bcl-2 and up-regulation of bax were found after incubation with ADR, VP-16 or camptothecin. 2) In HL-60 or U-937 cell lines, no significant change in bcl-2 or bax protein expression resulted after incubation with SB-31. 3) In CEM-CM3 cells, virtually no change was noted in bcl-2/bax expression after incubation with ADR, VP-16, camptothecin or SB-31. It is suggested that different leukemic cell lines use different pathways of apoptosis activation and a given cell may utilize different pathways of apoptosis activation in response to different cytotoxic agents.