Effects of New Nultidrug - Resistance Reversing Agent, KR-30035, on Tumoral Uptake of Tc-99m MIBI In-vitro and In-vivo / 대한암학회지

PURPOSE: Verapamil is one of the most extensively characterized modulators of P-glyco- protein (P-gp) mediated multi-drug resistance (MDR), but its plasma concentration required to reverse MDR can cause cardiovascular toxicity. KR-30035 is a newly synthesized verapamil analogue with more potent cytostatic effects, but has lower cardiovascular effects than verapamil. We have assessed the MDR reversing effects of KR-30035 by measuring Tc-99m MIBI uptake in cultured tumor cells and in nude mice bearing human tumor xenografts. MATERIALS AND METHODS: In-vitro uptake of Tc-99m MIBI was measured in murine leukemia cells (L-1210) and those MDR-positive variants after incubation with different concentrations of KR-30035. Results were compared to those with verapamil. Organ and tumoral uptake of Tc-99m MIBI was compared between P-gp (+) human colon cancer (HCT15 cells) and P-gp (-) lung cancer (A549 cells) in nude mice, treated with either KR-30035 or verapamil. RESULTS: There was no significant difference in in-vitro uptake of Tc-99m MIBI between verapamil and KR-30035 group at any concentrations. MIBI uptake in P-gp (+) cells continuously increased either with verapamil or KR-30035 in a dose-dependent manner. Tc-99m MIBI uptake ratios of the tumor [P-gp (+' tumor uptake divided by P-gp (-) uptake] were significantly higher with KR-30035 than with verapamil in tumor bearing nude mice. Washout rate of Tc-99m MIBI from P-gp (+) HCT15 cells was lower in verapamil or KR-30035 groups than in the control group, which was 0.19, 0.19 and 0.27 respectively. CONCLUSION: These studies revealed that KR-30035 can potentially be used as an active modulator of MDR, with its significantly lesser cardiovascular toxicity than verapamil. Our results warrants further evaluation of this novel agent.

Clinical and Histopathological Studies on Superficial Lymphadenopathy in Pediatric Ages

The superficial lymph nodes may be enlarged in consequence of biologic or non-biologic antigenic stimuli, lymphoreticular maligna ntneoplasm, metastatic tumor or infiltrative disorders such as histiocytosis-X, and biopsy of the enlarged superficial lymph node is a time-honored diagnostic, therapeutic and follow-up tool. At present it is performed with ease and wideness. But in Korea there is no comprehensive studies about the diseases involving superficial ly-mph nodes of pediatric ages based on clinical and histopathological aspects. The present study is an sttempt to research for the histopathological aspects. The present study is an attempt to research for the histopathological findings of the superficial lymphadenopathy in correlation with the clinical characteristics. The histopathological findings of enlarged superficial lymph nodes, biopsied in Yonsei Univ-ersity Hospital for a 5year-period from 1976 to 1980, were reviewed. All patients were under 15year-old age, whose chief complaints were palpable lymph node with or without other sympt-oms. The results were as follows; 1. Of the 150 enlarged superficial lymph nodes, the male to female ratio was 1.68:1. Most of the biopsies were performed after the preschool age group and only 8 were of neonate or inf-ancy. 2. Of the 150 enlarged superficial lymph nodes, 79(52.7%) showed reactive hyperplasia, and inflammatory and malignant lymphadenopathies were 37.3% and 10.0% respectively. 3. Nonspecific reactive hyperplasia was the most common cause of the superfical lymphad-enopathy in pediatric ages, being 52.1% of total. Tuberculous lymphadenitis comprised 26.7%, being the 2nd most common cause, and of the 15 malignant lymphadenopathy 11 were primary lymphoreticular and 6 of the latter were histiocytic medullary reticulosis. 4. Ten percent of the patients with tuberculous lymphadenitis were of infancy, but none of those with both primary and metastatic malignant lymphadenopathy was of that age group. 5. The clinical symptoms and signs observed were fever, hepatosplenomegaly, gastrointest-inal symptoms and signs, rash, upper respiratory infection and others, irrespective of the histol-ogical classification. 6. The duration of superficial lymphadenopathy was less than 6 months in most cases of fu-ngal, acute and subacute nonspecific inflammatory and malignant origin, whereas it was more than 6 months in 38.5% of tyberculous lymphadentis and 41.7% of nonspecific reactive. 7. Superficial lymph node enlargement was most frequently found at cervical area which was followed by inguinal and axillary areas. 8. The superficial lymphadenopathy involved a single node in 63.9% of tuberculous origin but it tended to involve multiple ondes of one or more anatomical sites in nonspecific inflamm-ation, fungal infection, nonspecific reactive hyperplasia and malignancy. 9. The enlarged superficial lymph noded tendes to be soft and nontender in tuberculosis and nonspecific reactive hyperplasia, in contrast to the acute and subacute lymphadenitis and mali-gnant lymphadenopathy where they were more commonly hard with variable tenderness.