Enhancement of the antitumor effect of cyclophosphane in an experiment

A significant antitumor effect of acetylcellulose microsphere-encapsulated cyclophosphamide was observed in the course of the studies carried out in 105 male Wistar rats bearing Walker's carcinosarcoma and PC-1 carcinoma. The effect is due to a high tissue level of the drug maintained for a long time as the drug uniformly passes through the porous microsphere wall. Local (intratumoral) treatment with cyclophosphamide is more effective than standard methods. The inhibitory effect of microsphere-enclosed cyclophosphamide on neoplastic growth is potentiated by tumor ischemia.     

Experimental use of low-energy infrared laser radiation to stimulate antitumor effect of cyclophosphane

The potential of increased antitumor effect of cyclophosphane used in conjunction with low-energy infra-red laser radiation was studied in sarcoma-45--bearing rats. Exposure to certain modes stimulated non-specific antitumor resistance and enhanced antitumor influence of the drug by reducing its damaging effect. Also, it inhibited refractory leukopenia and marked intoxication induced by antistressor reactions.     

Importance of the cyclophosphane administration regimen for its immunomodulating and antitumor effect in experimental chemotherapy

Cytological examinations and evaluation of the proliferative response of lymph node lymphocytes to T- and B-cell mitogens in vivo were carried out to identify the immunomodulating effect of cyclophosphamide (CP) versus the scheme of treatment. Using the system of adoptive transfer of splenic lymphocytes from experimental animals to intact syngeneic recipients, it was found that the scheme-dependent differentiated effects of CP on the antigen-specific tumor-associated and nonspecific suppressive activity of spleen cells provides an important pathway of CP action on the organism. A relationship between CP immunomodulating effects and lymphocyte antitumor activity was demonstrated in experiments using diffusion chambers.     

The effect of mexidol on the myelosuppressive toxicity, and on the antitumor and antimetastatic effectiveness of cyclophosphane

Mexidol therapy inhibited cyclophosphamide-induced myelosuppression in C57B1/6 line mice with Lewis lung carcinoma without affecting antitumor action of the latter. Mexidol plus cyclophosphamide proved more effective in prophylaxis of metastasis as compared with the cytostatic alone.     

Effect of cyclophosphane on lipid peroxidation

Single and repeated treatment with toxic doses of cyclophosphamide was shown to activate peroxidation of lipids of myocardial, pulmonary, hepatic and renal cell membranes. An antioxidant-silymarin-inhibited the prooxidating effect of cyclophosphamide thus suggesting further studies of antioxidants as means for counteracting the adverse effects of cytostatic drugs.     

Pharmacological, molecular, and cytogenetic analysis of "atypical" multidrug-resistant human leukemic cells

We previously described the cross-resistance patterns and cellular pharmacology of a human leukemic cell line, CEM/VM-1, selected for resistance to the epipodophyllotoxin teniposide (M. K. Danks et al., Cancer Res., 47: 1297-1301, 1987). Compared to CEM/VLB100, which is a well characterized "classic" multidrug-resistant (MDR) cell line, the CEM/VM-1 cells display "atypical" multidrug resistance (at-MDR) in that they are cross-resistant to a wide variety of natural product antitumor drugs, except the Vinca alkaloids, and they are not impaired in their ability to accumulate radiolabeled epipodophyllotoxin. We have extended our characterization of this at-MDR cell line in the present study. In comparison to CEM/VLB100 cells, we found that CEM/VM-1 cells are not cross-resistant to either actinomycin D or colchicine. Verapamil and chloroquine, which enhance the cytotoxicity of vinblastine in CEM/VLB100 cells, had little or no ability to do so in the CEM/VM-1 cells. Membrane vesicles of the two resistant sublines were examined for overexpression of the MDR-associated plasma membrane protein (P-glycoprotein, Mr 170,000 protein, or 180,000 glycoprotein) by photoaffinity labeling with the vinblastine analogue N-(p-azido[3-125I]salicyl)-N'-beta-aminoethylvindesine. We were unable to visualize the MDR-associated protein in the CEM/VM-1 membranes with this photoaffinity probe under conditions in which the P-glycoprotein was readily seen in the membranes of CEM/VLB100 cells. Furthermore, no hybridization of the pMDR1 complementary DNA was seen in slot-blot analyses of the RNA from at-MDR cells, indicating that the mdr gene coding for P-glycoprotein is not overexpressed as is the case in the classic MDR cells. However, cytogenetic analysis indicated that the CEM/VM-1 cells contained an abnormally banded region on chromosome 13q, suggesting that a gene other than mdr may be amplified in these cells. Thus, despite the two cell lines having approximately equal degrees of resistance to epipodophyllotoxins, our data indicate that the mechanism(s) responsible for at-MDR is different from that for classic, P-glycoprotein-associated MDR.     

Inhibition of the depressive action of cyclophosphane on immunity and hematopoiesis

Experiments demonstrated sodium nucleinate treatment to inhibit the cytotoxic and immunosuppressive effect of cyclophosphamide. This is an effective treatment for hemopoietic disturbances induced by cyclophosphamide.     

Effect of the combined use of pyrogenal and cyclophosphane on experimental tumors

The effect of the combined administration of cyclophosphane and pyrogenal was studied on mice with sarcoma 37 and Ehrlich carcinoma. It has been found that pyrogenal potentiates the antitumor effect of cyclophosphane and reduces the toxic action of this drug, thus making the survival of animals longer.     

羧甲基茯苓多糖抗小鼠白血病凋亡药理学研究

目的研究羧甲基茯苓多糖对p388小鼠白血病的抗癌效果并探讨其治疗的分子机制。方法建立p388白血病动物模型、随机分组并给予治疗。采用流式细胞术、m R N A原位杂交和S蛳P法免疫细胞化学技术对小鼠外周血淋巴细胞的凋亡和bcl蛳2基因的m R N A和bcl蛳2蛋白进行检测。结果羧甲基茯苓多糖组(C M P)能使荷瘤小鼠生命延长35.88%,与化疗药物环磷酰胺(C TX)合用后可使小鼠的生存期延长70.05%。C M P组的生存期与模型组比较有统计学意义(P<0.05)。C M P可通过下调bcl蛳2基因诱导癌细胞凋亡,C M P与C TX合用后可显著下调bcl蛳2基因m R N A和蛋白的表达来诱导癌细胞凋亡(与C TX比较,P<0.05)。结论C M P有很好的抗白血病作用;C M P与C TX合用后可产生协同抗癌作用。     

Changes in lysozyme activity in the blood and organs of white rats exposed to cyclophosphane

The lysozyme activity was estimated in the tissue and organs of white non-inbred rats. Cyclophosphane was injected trice intramuscularly in a single dose of 40 mg/kg of weight with a 4-day interval. The lysozyme activity was studied by a diffusion method in agar. The level of the enzyme was found to rise in the lung, blood serum, leucocytes and spleen. The most pronounced changes were noted 24 hours following its administration. Increased lysozyme activity may cause the enhanced digestive function of leucocytes and bactericidal properties of blood serum.     

Pharmacological and cost effectiveness bases of the use of categel and categel S [correction of F] in urological practice

Preparations catedgel and catedgel S made in Austria (Montavit) was tried in Moscow hospital N 50. Categel is a sterile gel of methylcellulose with 2% lidocain and 0.05% chlorhexidine, catedgel S contains the same components but lidocain. Categel significantly reduces the risk of infectious-inflammatory complications after endourological manipulations, improves endoscopic diagnosis and makes some manipulations less painful. Comparative pharmacological cost-effect assessment of categel S and glycerine effects in prostatic transurethral resection. Categel was found 2.11 times more effective. It also improves quality of life of the patients. Categel can be recommended for wide use in urology.     

Impact of cytogenetic and molecular cytogenetic studies on hematologic malignancies

Conventional cytogenetic analysis of chromosome abnormalities in hematologic malignancies is hampered by the low mitotic index and poor quality of metaphases. A range of techniques based on fluorescence in situ hybridization (FISH) has greatly enhanced the identification of non-random translocations and deletions, pinpointing regions which contain genes involved in leukemogenesis. One of the main advantages of FISH is its ability to use non-dividing interphase cells as DNA targets, enabling the screening of large numbers of cells and providing access to a variety of cells with different hematopoetic activity. Furthermore, multicolor FISH (SKY, M-FISH and CGH microarrays) combines the screening potential of cytogenetics with the accuracy of molecular genetics, allowing the visualization of the entire human genome in 24 different colors.