• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.168-184
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• 2001

Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.485-495
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• 1998

Purpose : The major goal of the therapy in the soft tissue sarcoma is to control both local and distant tumor. However, the technique of obtaining local control has changed significantly over the past few decades from more aggressive surgery to combined therapy including conservative surgery and radiation and/or chemotherapy. We retrospectively analyzed the treatment results of the postoperative radiation therapy of soft tissue sarcoma and its prognostic factor. Materials and Methods : Between March 1983 and June 1994, 50 patients with soft tissue sarcoma were treated with surgery and postoperative radiation therapy at Kang-Nam St. Mary's hospital. Complete follow up was possible for all patients with median follow up duration 50 months (range 6-162 months). There were 28 male and 32 female patients. Their age ranged from 6 to 83 with a median of 44 years. Extremity (58$\%$) was the most frequent site of occurrence followed by trunk (20$\%$) and head and neck (12$\%$). Histologically malignant fibrous histiocytoma (23$\%$), liposarcoma (17$\%$), malignant schwannoma (12$\%$) constitute 52$\%$ of the patients. Daily radiation therapy designed to treat all areas at a risk for tumor spread upto dose of 4500-5000 cGy. A shrinking field technique was then used and total 55-65 Gy was delivered to tumor bed. Twenty-five patients (42$\%$) received chemotherapy with various regimen in the postoperative period. Results : Total 41 patients failed either with local recurrence or with distant metastasis. There were 29 patients (48$\%$) of local recurrence. Four patients (7$\%$) developed simultaneous local recurrence and distant metastasis and 8 patients (13$\%$) developed only distant metastasis. Local recurrence rate was rather higher than of other reported series. This study included patients of gross residual, recurrent cases after previous operation, trunk and head and neck Primary This feature is likely explanation for the decreased local control rate. Five of 29 Patients who failed only locally were salvaged by re-excision and/or re-irradiation and remained free of disease. Factors affecting local control include histologic type, grade, stage, extent of operation and surgical margin involvement, lymph node metastasis (p<0.05). All 21 patients who failed distantly are dead with progressive disease at the time of this report. Our overall survival results are similar to those of larger series. Actuarial 5 year overall survival and disease free survival were 60.4 $\%$, 30.6$\%$ respectively. Grade, stage (being close association with grade), residual disease (negative margin, microscopic, gross) were significant as a predictor of survival in our series (p<0.05). Conclusion : Combined surgery and postoperative radiation therapy obtained 5 year survival rate comparable to that of radical surgery.