• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.124-124
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• 1995

Cisplatinum is often effective in cancer treatment, but potent nephrotoxicity limits its clinical use. We have, therefore, developed new anticancer drugs that contain platinum. We have synthesized six new platinum compounds based on Figure 1. Drugs were initially administrated at 5${\times}$10$\^$-4/M with 48 hours exposure in monolayer cultures of primary rabbit proximal tubular cells and human renal cortical cells with the M.T.T. endpoint to measure toxicity. Drug concentrations of 10$\^$-3/M, 10$\^$-4/M, and 10$\^$-5/M with 72 hours exposure were used for human renal cortical tissues in 7 weeks histoculture with toxicity measured by the glucose-consumption endpoint. From these studies, we determined that the new platinum drugs have lower nephrotoxicity than cisplatinum. Drugs D, E, and H. have lower nephrotoxicity than the other new drugs. We are currently measuring the anticancer efficacy of drugs D, E, and H.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.55-61
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• 1995

Purpose : Despite a development of therapeutic machines and advance in modern radiation therapy techniques, locally advanced cervical carcinoma has shown high rate of local failure and poor survival rate, Combination of chemotherapy and radiotherapy demonstrated benefit in improving local control and possibly the overall survival. Our study was performed to evaluate effect of concurrent chemoradiation on locally advanced uterine cervical cancer. Methods and Materials : Twenty six patients with locally advanced stage(FIGO stage IIB with ${\geq}5cm$ in diameter, III, IVA) were treated with combination of radiation therapy and concurrent cisplatinum between May of 1988 and September of 1993 at our hospital. Radiation therapy consisted of external irradiaton and 1-2 sessions of intracavitary irradiation. Cisplatinum was administered in bolus injection of 25mg/$m^2$ at weekly intervals during the course of external radiation therapy. Results : Of the 26 Patients, twenty-five patients were evaluable for estimation of response. Median follow-up period was 25 months with ranges from 3 to 73 months. Stage IIB, III, and IVA were 16, 5, 4 patients, respectively, Twenty patients were squamous cell carcinoma. Response was noted in all 25 patients: complete response(CR) in 17/25($68\%$), Partial response(PR) in 8/25($32\%$). Of the 24 patients except one who died of sepsis at 3 months follow-up, seventeen patients($70.8\%$) maintained local control in the pelvis: 16/17($94.1\%$) in CR, 1/17($14.3\%$) in PR. Fourteen of the 17 patients with CR are alive disease free on the completion of follow-up. Median survival is 28 months for CR and 15 months for PR. Analysis of 5-year survival by stage shows 11/16($59.8\%$) in IIB, 3/5($60.0\%$) in III, and 1/4($25.0\%$) in IVA. Overall 5-year survival rate was $55.2\%$. Ten patients recurred: 4 at locoregional, 3 in distant metastasis and 3 with locoregional and distant site. Toxicity by addition of cisplatinum was not excessive. Conclusion : Although the result of this study was obtained from small number of patients, it is rather encouraging in view of markedly improved response rate compared with the results of historical group.

• The Journal of the Korean bone and joint tumor society
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• v.4 no.1
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• pp.13-21
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• 1998

Taxol, the extract from the Taxus brevifolia which is a Pacific yew tree has aroused the interest of the tumor investigators since the 1960s. As well, it is shown to have broad antitumor activity in preclinical experimental models. Its action mechanism is an anti-microtubule effect by duplication of tubulin. The most impressive antitumor activity of taxol has been observed in advanced ovarian cancer and metastatic breast cancer. The purpose of this study was to determine how taxol acts on malignant bone tumor cell lines, to compare its cytotoxic effect with those of other chemotherapeutic agents, and to ascertain the its combination effect with adriamycin. Cell lines used in this study were G-292(osteosarcoma, human), SaOS-2(osteosarcoma, primary, human), and HT-1080(fibrosarcoma, human). Methotrexate, adriamycin, cisplatinum, ifosfamide and taxol were used as testing chemotherapeutic agents and their maximum test concentration were $500{\mu}g/ml$, $200{\mu}g/ml$, $500{\mu}g/ml$, $1000{\mu}g/ml$, and $600{\mu}g/ml$, respectively. The media for cell culture was RPMI-1640 with 10% fetal bovine serum and gentamycin. The results were as follows. The $IC_{50}$ of methotrexate, ifosfamide, cisplatinum, adriamycin and Taxol in G-292 were $2.3{\times}10^{-1}{\mu}g/ml$, $8.0{\times}10^0{\mu}g/ml$, $3.5{\times}10^0{\mu}g/ml$, $9.8{\times}10^{-1}{\mu}g/ml$, $2.7{\times}10^{-2}{\mu}g/ml$ respectively, in SaOS-2 $3.5{\times}10^{-1}{\mu}g/ml$, $1.5{\times}10^1{\mu}g/ml$, $2.8{\times}10^0{\mu}g/ml$, $9.9{\times}10^{-2}{\mu}g/ml$, $1.0{\times}10^{-2}{\mu}g/ml$, respectively, in HT-1080 $4.2{\times}10^{-2}{\mu}g/ml$, $5.4{\times}10^1{\mu}g/ml$, $3.8{\times}10^0{\mu}g/ml$, $5.5{\times}10^{-3}{\mu}g/ml$, $1.1{\times}10^{-3}{\mu}g/ml$, respectively. In conclusion, taxol had very potent cytotoxic effect on the malignant bone tumor cell lines with adriamycin, and was more potent than methotrexate, cisplatinum and ifosfamide. There were synergistic antitumor effects on G-292 and SaOS-2 cell lines in combination test of taxol and adriamycin. From the above results, it would be estimated that taxol could be a new antitumor drug for the malignant bone tumors, providing measures against the side effects and followed by the clinical tests.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2467-2471
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• 2012

Introduction: Although bleomycin/etoposide/cisplatinum (BEP) chemotherapy is established as the standard treatment for germ cell tumours, it requires significant experience in administration and toxicity management to maintain optimal dose intensity. A retrospective review of 30 patients was conducted at UKMMC to study treatment outcomes. Methods & Materials: Patients with GCTs and treated with at least two cycles of BEP chemotherapy between January 2003 and Oct 2009 were eligible for this study. Patients received 4-6 cycles of bleomycin 30,000IU IV D1, D8 & D15 and either etoposide $100mg/m^2$ IV D1-D5 and cisplatin $20mg/m^2$ IV D1-D5 (5 day BEP regimen) or etoposide $165mg/m^2$ D1-D3 and cisplatin $50mg/m^2$ D1-3 (3 day BEP regimen) every three weeks per cycle. All patients received prophylactic granulocyte colony-stimulating factor (GCSF) from days 6 to 10 of each cycle. The overall response rates, 2 year progression-free survival and overall survival of the whole cohort were assessed. Results: Thirty patients fulfilled the inclusion criteria. Non-seminomatous GCTs comprised 93.3% of cases and gonadal and mediastinal primary sites were the most common. Sixty percent were classified as IGCCCG poor risk disease. Median follow-up was 26.6 months. The overall response rate (CR+PR) was 70%. The two year PFS and OS were 70% and 66%. There was a significant difference in terms of the overall response rate (85% vs 40%, p = 0.03) and in PFS (94.7% vs 50%, p = 0.003) between gonadal and extragonadal primary sites. Conclusion: It is possible to achieve outcomes similar to those in international clinical trials with close monitoring and good supportive care of patients undergoing BEP chemotherapy. There is a strong argument for patients with IGCCCG poor prognosis disease to be treated in specialist tertiary centres to optimize treatment outcomes.

• 대한두경부종양학회:학술대회논문집
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• 2006.11a
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• pp.216-216
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• 2006

• Advances in pediatric surgery
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• v.6 no.2
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• pp.139-142
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• 2000

Pancreatoblastoma is uncommon in children and is exceedingly rare in adults. Prognosis is good if the tumor is removed prior to metastasis. Complete tumor resection is the most important factor for long survival. We report two cases of pancreatoblastoma in 4 and 7 years old girls. Palpable abdominal mass was accidentally found by their parents. Abdominal CT scan showed a huge retroperitoneal mass of unknown origin in one case and a mass involving the pancreas in the other case. At laparotomy, well encapsulated tumor mass($10{\times}10$ cm in maximum dimension) was noted in the body of pancreas in one case, and in the tail of pancreas in the other case( $8{\times}7$ cm). We resected the tumor and preserved the spleen in both cases. Histological examination revealed that the tumors were pancreatoblastoma. Patients received postoperative chemotherapy with 6 cycles of cisplatinum, adriamycin, ifosfamide and etoposide and are alive in good condition 19 months and 17 months after operation.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.181-189
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• 1995

Pupose: Radiation therapy(RT) is conventionally standard treatment for locally advanced stage for uterine cervix cancer. Recently to improve treatment results, combined chemotherapy and radiation therapy was tried We retrospectively analysed our experience of 122 patients. Comparision of the results in 45 patients treated with RT alone and 77 patients treated with RT plus chemotherapy was made Materials and Mathods: From January 1985 to December 1991 122 patients with cervix cancer were treated with whole pelvic external RT and ICR(34 1 ICR, 77 2 ICR, 11 high dose rate ICR) in our department. Forty five patients were treated with RT alone, and 77 patients were treated with combined RT plus chemotherapy Mean age was 58 years(range:29-81). Histologic types were 111 squamous cell carcinoma, 5 large cell carcinoma, 3 adenocarcinoma, and 2 adenosquamous cell carcinoma. According to the FIGO stage 6 had stage $IA(4.9\%),$ 11 had $IIA(9.0\%),$ 37 had $IIB(30.3\%),$ 3 had $IIIA(2.5\%),$ 63 had $IIIB(51.6\%).$ and 2 had stage $IV(1.6\%).$ In 77 patients with RT Plus chemotherapy, 36 patients were treated with VBP(vinblastin, bleomycin, cisplatinum) , 39 patients with cisplatinum plus 5-FU and 2 patients with 5-FU. Results: Complete response after external RT (3960cGy-5500cGy) was achieved in 61 patients$(50\%).$ The actuarial 5 year and 9 rear survival rate was $57.8\%\;and\;53.9\%,$ respectively. Five rear actuarial survival rate was $63.1\%$with RT alone(n=45) and $55.9\%$ with RT plus chemotherapy(n=77). The 5 rear survival rate was $35.5\%$ for 1 course of ICR and $67\%$ for 2 courses of ICR. There was statistically significant advantage of survival with RT alone group who were treated with 2 courses of ICR and dose to the A Point)=8000cGy (4/25 died). In RT plus chemotherapy group, dose response was not seen and there was no difference in 5 year survival between 1 course and 2 course of ICR $(50\%\;vs\;56.8\%),$ and dose to point A less than 8000 cGy and more than 8000 $cGy(55.6\%\;vs\;55.7\%).$ There was no significant difference in survival between RT alone and RT plus chemotherapy for patients with tumor size greater than 3cm in size. Five year survival rate for early stage (Stage IB and IIA) with RT alone group and with RT Plus chemotherapy group was $60\%\;and\;77.0\%,$ respectively In advanced stage (stage IIB, IIIA, IIIB, IVA) the 5 year actuarial survival rate were $62.6\%,$ for RT alone group vs $53.6\%$ for RT plus chemotherapy group. Conclusion: Present study demonstrates that there is no survival advantage with adding chemotherapy in advanced stage of uterine cervix cancer. RT alone is considered as treatment of choice for patients with locally advanced cervix cancer. There was increased survival in RT alone group treated with RT dose above 8000 cGy to point A and 2 course of ICR. but 2 course of ICR and RT dose above 8000 cGy to point A did not affect survival advantage in RT plus chemotherapy group.

• Tuberculosis and Respiratory Diseases
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• v.53 no.1
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• pp.46-51
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• 2002

Numb chin syndrome is a rare clinical manifestation, characterized by focal sensory loss and paresthesia of the chin. It is more often associated with cancer than with benign disorders, and can be the first manifestation of a cancer. A 60-year-old man presented with focal numbness of right chin and gingiva for 10 days. Chest computed tomograghy showed a 3 cm sized mass on the distal left main- stem bronchus. Squamous cell carcinoma was diagnosed on bronchoscopic biopsy. However, bony metastasis of mandible was not evident on reontgenogram, CT scan, bone scintigram and positron emission tomography. Despite the chemotherapy with three cycles of paclitaxel and cisplatinum, the cancer was progressed and pain on the right chin was developed 4 months later. Bone scintigram showed multiple bony metastasis including mandible. Here we report this case with a brief review of the appropriate literature.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.125-138
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• 1998

Purpose : To evaluate the late effect(3 and 6 months) of cis-diarnrninedichlo-roplatinum(II)(cisplatin) on the radiation brain damage when the cisplatin was intraperitoneally infused immediately after whole brain irradiation in the rats. Materials and Methods : The histolopathological findings of the brain were examined in rat brains at 3 and 6 months after the treatment. The rats were irradiated(20 or 22.5 Gy, RT) or cisplatin was injected intraperitoneally(2,4, or 8mg/kg, CT) and in combined treatment group, cisplatin(2mg/kg) was injected immediately after irradiation(20 or 22.5 Gr). Histopathological examination was done mostly in irradiation or cisplatin alone groups, because the rats in combined group died during experimental period except 2 rats. Results : The rats treated with cisplatin showed marked epithelial vacuolation with perivascular edema and vascular dilatation in choroid plexus at 3 months as well as multifocal necrosis involving fimbria and cerebellar hemispheres at 3 and 6 months. The changes were more prominent in rats with 2mg/kg injection compared to rats with 8mg/kg injection. The rats with RT and combined CT and RT showed characteristic delayed irradiation effects such as focal coagulation necrosis and vascular changes, which were more marked than previous reports Prominent perivascular and leptomenin-geal astrocytic Proliferation was well documented by anti-GFAP antibody. Cisplatin treatment did not enhance the effect of radiation-induced changes of blood vessels and astrocytic proliferation. Conclusion : The focal necrosis was the most consistently noted finding in this study, it suggested the possibility to use this as an evaluation factor for combined effects of RT and cisplatin.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1982.05a
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• pp.17.1-17
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• 1982

In 1965, Rosenberg reported that platinum compounds not only inhibit growth and cell division of E. coli but also has anti-tumor activity. Since then, through animal and clinical experiments by Welsch(1971), Speer(1972), Rossof(1972), Hill(1974), and Wittes(1975), it was proved that Cis-platinum has excellent supressive effects on malignant tumor, especially on head and neck cancer. Accordingly, Cis-platinum is now widely used, sometimes without any other durg, or sometimes with Bleomycin and Methotrexate etc. Inspite of the strong anticancer effect, the use of Cis-platinum is quite often discouraged because of the reports that Cis-platinum causes auditory impairment at high frequencies above the speech range due to inner ear damage and irreversible change in the renal tubules. Since Kohonen et al(1965), Standnicki et al(1974) reported that Cisplatinum has toxic effects at the basal turn of the cochlea using guinea pig, many studies on ototoxicity after infusion of Cis-platinum have been carried out using animals. But the studies on ototoxicity in human beings can hardly be found except in reports by Piel et al(1974) and Hong et al (1979). So the authors did a study which tried to clarify the ototoxic effect by comparing the hearing level after infusion of Cis-plastinum with the hearing level before infusion of Cis-plastinum in 30 patients who was treated with Cis-platinum and admitted to the dept. of otolaryngology of Yonsei University Hospital during 2 years and a half from July. 1979 to March. 1982 and the following results were obtained. 1) The results of auditory evaluation, using the pure tone average, hearing loss of 4kHz and 8kHz, Speech Reception Threshold, PB score, SISI showed that the difference of dosage does not change the hearing level after infusion of Cis-platinum and before infusion of Cis-platinum. 2) Cis-platinum had no effect on the hearing level of patients with conductive hearing loss, or with sensorineural hearing loss, as well as with normal hearing level. 3) The infusion of Cis-platinum did not cause any change in creatinine clearance, creatinine, uric acid, but only one case showed that Cis-platinum caused severe nephrotoxicity. 4) The infusion of Cis-plastinum did not cause any change in hemoglobin, leukocyte count, platelet count and there was no correlation with the amount of infusion. 5) To see the side effect of hydration practiced with the infusion of Cis-platinum, the electrolytes, particularly the K level in the serum was measured. But the results did not show any change. 6) Judging from the results of this study mentioned above, ototoxicity caused by infusion of Cis-platinum can be prevented by sufficient hydration. Also the results might say that the appropriate method of infusion of Cis-platinum might be effective in the patients with head and neck cancer who had sensorineural hearing loss for whom the infusion of Cis-platinum has been absolutely cotraindicated.