双苄基异喹啉化合物Ys-96与阿霉素或长春新碱联合用药对体外培养人癌细胞的抗癌增效作用

目的:研究双苄基异喹啉化合物Ys96与阿霉素或长春新碱联合用药对体外培养人癌细胞系MCF7和KB的抗癌增效作用。方法:在体外培养的敏感株人乳腺癌细胞MCF7及其阿霉素耐药株MCF7/Adr和敏感株人口腔粘膜上皮样癌细胞KB及其长春新碱耐药株KBv200的体外试验系统中,采用Berenbaum所报道的评价二药相互作用性质的试验方法,对源于中药汉防己的双苄基异喹啉化合物Ys96与阿霉素或长春新碱联合用药的抗癌作用进行了研究。结果:3种不同比例混合的Ys96和阿霉素或长春新碱联合用药对敏感株MCF7或KB以及耐药株MCF7/Adr或KBv200的IC50分数值之和(SFIC)均小于1.0,而且所有联合用药的等效曲线形态均为凹型。结论:Ys96与阿霉素或长春新碱联合用药对上述体外培养的人癌细胞具有抗癌增效作用。     

ECHOCARDIOGRAPHIC ASSESSMENT OF LEFT VENTRICULAR FUNCTION DURING THE INJECTION OF ADRIAMYCIN

Abstract. Echocardiography was used to evaluate left ventricular function in 8 children treated with adriamycin for malignant disease. Preejection period (PEP), left ventricular ejection time (LVET) and percent change in left ventricular internal dimension with systole (ALVID) were measured before, during and immediately after 22 injections of adriamycin as well as 14 injections of other cytotoxic drugs and physiologic saline. No immediate effects on left ventricular function could be discerned. When functional parameters were evaluated longitudinally in patients with relatively higher cumulative doses of adriamycin, percent change in left ventricular internal dimension with systole showed some tendency to decrease, while the other parameters remained essentially unchanged.     

Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): Addition of an anthracycline to vincristine and prednisone

Fifty-six untreated patients with childhood with acute lymphoblastic leukemia (ALL) were randomized to receive one of three remission induction regimens: vincristine and prednisone (VP), vincristine, prednisone and daunorubicin (VPD), or vincristine, prednisone and adriamycin (VPA). The complete remission rate was similar for all three groups. Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group, this difference was not significant. Labeling index reduction between study days 1 and 5 was significantly greater (p < 0.001) with an anthracycline than for the VP group, but there was no difference between the two anthracyclines. Granulocytopenia during induction was significantly increased (p < 0.05) in both the VPD and VPA groups as compared with VP alone. A significantly higher rate of infectious morbidity (p < 0.01) was associated with the addition of either anthracycline, but to date no significant differences in remission duration or survival have been observed. The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages, but may be undesirable because of increased morbidity.     

A kinetically designed chemotherapeutic regimen for advanced refractory lymphoma patients

Three patients with Hodgkin disease, eight with non-Hodgkin lymphoma, and one with chronic lymphocytic leukemia refractory to conventional combination chemotherapy were treated for remission induction with a new kinetically designed four-drug combination consisting of bleomycin, vincristine, adriamycin, and prednisone and given the acronym “BOAP.” Eight patients had prior radiotherapy, including two who had total nodal irradiation. Eight patients (all three with Hodgkin disease and five of eight with non-Hodgkin lymphoma) achieved complete remission (73% of the lymphoma patients). An additional two patients with non-Hodgkin lymphoma sustained partial remissions, for an overall response rate of 91%. Toxicity caused the interruption of therapy in three patients and an additional patient might have sustained a drug-related death. This study compares favorably with other studies investigating primary or secondary combination chemotherapy of advanced lymphomas.     

Natural killer and lymphokine-activated killer activities in stomach cancer patients with special emphasis on the effect of 5-fluorouracil, adriamycin and mitomycin-C chemotherapy

The cytotoxicities of peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells were studied to evaluate the effect of chemotherapy on cellular immunity, in 18 patients with unresectable stomach cancer before and after chemotherapy with 5-fluorouracil, adriamycin and mitomycin-C (FAM), and in 21 healthy volunteers. LAK cells were generated in vitro by culturing PBL with 100 U recombinant human interleukin-2 (rH-IL-2)/ml for 72 h. K562 (human myelogenous leukemia), MKN-45 (human stomach adenocarcinoma) and PC-14 (human pulmonary adenocarcinoma) were used as target cells. The cytotoxicity of PBL to K562 and MKN-45 was suppressed in patients with stomach cancer before chemotherapy, compared with that in healthy volunteers (P less than 0.05). The cytotoxicity of LAK cells was significantly higher to all three cell lines tested than that of PBL in both the healthy volunteers and stomach cancer patients (P less than 0.01); however, a lower level of LAK activity was generated in patients with cancer compared to that in the healthy volunteers. FAM therapy did not suppress the cytotoxicities of PBL and LAK cells. The surface markers of PBL and LAK cells were measured, demonstrating that there was no significant change in the percentage of lymphocytes with CD3+, CD4+, CD8+, CD16+ or CD19+ after chemotherapy. The ratios of CD4+ to CD8+ cells in PBL and LAK cells were also not significantly changed after chemotherapy. In the present study, we have demonstrated that the PBL of stomach cancer were defective in generating LAK activity compared to those of controls, but the LAK activity generated from PBL receiving chemotherapy was similar to that from PBL without chemotherapy in stomach cancer patients.     

明胶-阿霉素抗癌缓释剂对膀胱肿瘤细胞株BIU-87的生长抑制研究

应用含２０ｍｌ／Ｌ小牛血清的完全培养基浸泡明胶－阿霉素抗癌缓释剂，每隔２４ｈ重复更换培养基，而后将每ｄ浸泡所得的培养基与ＢＩＵ－８７细胞混合培养。结果发现，直至第１９ｄ经抗癌缓释剂浸泡过的培养基仍对ＢＩＵ－８７细胞具有生长抑制作用，其中第１ｄＢＩＵ－８７细胞生长率仅为１０％，第５ｄＢＩＵ－８７细胞生长率为６０％，第１９ｄＢＩＵ－８７细胞生长率仍低于８０％。这为明胶－阿霉素抗癌缓释剂应用于临床治疗膀胱肿瘤提供了实验依据。     

生脉注射液对损伤心肌细胞乳酸脱氢酶及心肌细胞超微结构的影响

本实验运用体外培养心肌细胞,观察了中药生脉注射液对阿霉素引起心肌细胞损伤时,心肌细胞内乳酸脱氢酶释放及超微结构的影响。结果表明,生脉注射液30、100、300mg/L 对阿霉素1 mg/L 作用4 h 引起的培养心肌细胞乳酸脱氢酶释放没有影响;对其引起的心肌细胞超微结构损伤也无改善作用。结果提示:生脉注射液对阿霉素引起的心肌损害的保护作用,可能是在整体情况下产生的。     

REGIONAL DISTRIBUTION OF THE CARDIAC OUTPUT AND RENAL RESPONSES TO ATRIAL ATRIURETIC PEPTIDE INFUSION IN RABBITS WITH CONGESTIVE HEART FAILURE

1. A biventricular, low-output congestive cardiomyopathy was induced in 19 rabbits by administering adriamycin (16 mg/kg). The effects of alpha-rat atrial natriuretic peptide (ANP) infused at 0.1, 0.2 and 0.4 micrograms/kg per min, were then examined in terms of (i) central haemodynamics (ii) regional blood flow (iii) renal function and (iv) plasma norepinephrine and plasma renin. 2. In this dose range, ANP produced progressive and significant falls in stroke volume, cardiac output and mean arterial pressure, owing to a fall in venous return. The heart rate response to this was blunted. 3. Using radiolabelled microspheres, significant falls in the perfusion of cutaneous, gastrointestinal and musculoskeletal tissues were observed, due to reduced vascular conductances in these beds. These changes were accompanied by activation of the sympathetic nervous system as evidenced by a progressive rise in plasma norepinephrine. A significant increase in plasma renin was only observed with the highest infusion of ANP. 4. Renal blood flow was maintained in the face of a falling mean arterial pressure and cardiac output, but diuretic and natriuretic effects were absent. 5. It was concluded that the dominant influence of ANP infusion in this model of heart failure appeared to be a reduction in cardiac preload with detrimental overall haemodynamic consequences.     

Absence of correlation between cytotoxicity and drug transport by P-glycoprotein in clinical leukemic cells.

Development of resistance to cytotoxic agents is a common problem in the treatment of acute leukemia. In cell lines having multidrug resistance (MDR) phenotype, a decrease in the intracellular accumulation of drugs has been closely related to the overexpression of P-glycoprotein/mdr1 genes. We analyzed the relationship between the cytotoxicity of adriamycin (ADR) in vitro, intracellular accumulation of ADR, and the expression of P-glycoprotein on fresh leukemic cells from 19 patients at their initial presentation and from 9 relapsed patients. Pretreatment patients showed significantly higher ratio of complete remission than relapsed patients, and mean value of IC50 for adriamycin in initial presentation was higher than at relapse. But we found no significant relationship between in vitro cytotoxicity and drug transport. In addition, only 2 of the 5 relapsed patients examined by monoclonal antibody C219 expressed the P-glycoprotein. These results suggest that the acquisition of clinical drug resistance may involve various mechanisms other than the reduction of drug accumulation with P-glycoprotein expression.     

控释缓释微球制剂的研究进展

讨论了国内外用白蛋白，明胶，聚丙交酯，聚乙烯，萄聚糖与乙基纤维素等所制微球的研究进展情况。