脑瘤消胶囊对荷S180肉瘤小鼠的抗肿瘤作用

目的　观察脑瘤消胶囊对实验性荷S180肉瘤小鼠的抗肿瘤作用 ,探讨脑瘤消胶囊治疗颅内肿瘤的作用机制。方法　随机将小鼠分为 6组 :正常对照组、荷S180肉瘤模型组、模型 +环己亚硝脲组和模型 +脑瘤消小、中、大剂量组。小鼠皮下接种S180肉瘤后开始灌胃给药 ,每天一次 ,连续 8天。停药后次日处死小鼠 ,称瘤重后计算瘤重抑制百分率 ,并对瘤组织进行病理学检查 ,实验共重复三次。结果　与模型组 (ig生理盐水 )比较 ,脑瘤消胶囊各剂量组小鼠肿瘤明显缩小 (P <0 .0 1)。结论　 0 .5～ 2 .0g/kg脑瘤消胶囊灌胃给药可明显抑制小鼠荷S180实体瘤的生长和浸润。     

Differential expression of intermediate-filament proteins in murine sarcoma 180 ascites or solid tumor

The intermediate-filament proteins in Sarcoma 180 ascites cells and solid tumors generated by s.c. injection of ascites cells in NMRI or nude mice were analyzed by one- and two-dimensional gel electrophoresis and identified by immunological methods. The ascites form of Sarcoma 180 coexpresses keratin and vimentin, whereas the solid tumor ceases to synthesize keratins but continues to express vimentin. These reversible changes in the expression of intermediate-filament proteins may be due to a change in the differentiation program induced by environmental conditions like growth with or without cell contact.     

Tumor inhibition by titanocene complexes: activity against sarcoma 180

The antitumor activity of various titanocene derivatives was examined against ascitic and solid, subcutaneously growing sarcoma 180. The complexes investigated were two dihalide compounds, (C5H5)2TiCl2 (I) and (C5H5)2TiBr2 (II), two carboxylato complexes, (C5H5)2Ti (cis-OOCCH = CHCOOH)2(III) and (C5H5)2Ti(OOCCCl3)2(IV), and the p-aminothiophenolate hydrochloride (C5H5)2Ti(p-SC6H4NH3+Cl-)2(V). Against ascitic sarcoma 180, best results were obtained for I; an injection of 50 mg/kg resulted in the survival of 40-50% of the animals (ILS, 161-184%). A similar result was recorded for cis-diamminedichloroplatinum(II), whereas the compounds II-IV induced a maximum cure rate of 20% (ILS, 95-139%). Against solid sarcoma 180, triple injections of I-V caused reduction of mean tumor weight to 23-53% of control values, the dichloro complex I exhibiting most pronounced activity. These results clearly underline antitumor potency for titanocene complexes (C5H5)2TiX2 modified at the acido ligand X.     

Anticancer activity of docetaxel in murine salivary gland carcinoma.

PURPOSE: The purpose of this study was to evaluate the biological mechanisms of docetaxel (TXT) on salivary gland carcinoma. EXPERIMENTAL DESIGN: The effects of TXT on a spontaneous murine salivary carcinoma were determined. Proliferation, cell cycle regulation, connexin43 expression, gap-junctional intercellular communication, apoptosis, and Fas receptor (FasR) expression were measured. RESULTS: We characterized a spontaneous mouse salivary gland carcinoma (SGC1). SGC1 is a poorly differentiated carcinoma that originated from the parotid gland of a BALB/c mouse. SGC1 cells were cultured and found to be immortal past 30 passages. Initially, cells formed tumor nodules in severe combined immunodeficient (SCID) mice. Afterward, SGC1 cells that were subcultured from SCID tumors readily formed colonies in soft agar and were highly tumorigenic in SCID mice and immune-competent BALB/c hosts. Dose response for TXT with respect to growth suppression, G(2)-M cell cycle arrest, and apoptosis was found. Induction of apoptosis by TXT coincided with an increase in cell surface FasR expression. Up-regulation of FasR with lower doses of TXT rendered cells susceptible to FasR agonist antibody-mediated apoptosis. In the absence of TXT, anti-FasR antibodies were completely without effect, suggesting that TXT is critical for priming apoptosis mediated through the Fas pathway. In addition, gap-junctional intercellular communication was augmented by TXT in SGC1 cells concomitant with increased connexin43 expression and membrane localization. CONCLUSIONS: We have identified several novel targets of TXT that contribute to its antitumor activity in poorly differentiated salivary gland carcinoma. These results suggest that TXT may be appropriate for additional in vivo studies and clinical trials in patients with salivary cancers.     

Antitumor activity of tritiated tumor polysaccharide substance (H3-TPS) in sarcoma 180 of mice

Small doses of H3-TPS given to newborn mice have been found to induce protection in 70% of mice transplanted with sarcoma (Sa) 180. Mice rendered tolerant with large doses of TPS and DNA from Sa 180 in early life developed large tumors after transplantation with Sa 180. Subsequent treatment with H3-TPS gave rise to 90% cure, the result of "reverse tolerance" (Makari JG: Nature 205:1178, 1965). Macrophages (M phi s) selectively phagocytose polysaccharides and are thus labeled by H3-TPS. Radioisotope studies showed that the greater the tritium level in a tumor, the smaller its size, with the highest levels found at the cured tumor area (CTA). The radioactivity in progressively deeper samples of tumors demonstrated a bimodal peak in activity in large tumors, indicating inability of most M phi s to pierce the tumor, and a peak in small tumors indicating penetration of tumor by M phi s. Mice whose M phi s have already been stimulated by microbial infection have much higher cure rates and much higher H3-TPS uptake at the CTA. The local increase of uptake of H3-TPS at the CTA in the immunostimulated groups (whether by experimental stimulation or by natural infection) is believed to reflect increased proliferation and increased phagocytosis leading to M phi stimulation and tumoricidal activity. In the "reverse tolerant" group, in which the uptake of H3-TPS is low despite a high ratio of of H3-TPS uptake in CTA/tumor, the mechanism of cure seems to be one of marked stimulation by H3-TPS of the M phi surface membrane without phagocytosis, resulting in the activation of M phi s to tumoricidal activity. Thus M phi stimulation and M phi activation seem to be the basis for the antitumor effect of H3-TPS.     

Mechanism of resistance of Yoshida sarcoma to nitrogen mustard. 3. Mechanism of suppressed transport of nitrogen mustard

Mechanism of decreased transport of nitrogen mustard (HN₂) in HN₂-resistant Yoshida sarcoma cells was investigated. HN₂ uptake by Yoshida sarcoma cells proved to be temperature sensitive, saturable, affected by metabolic inhibitors, and also repressed competitively by choline chloride. In resistant cells, the uptake of choline was markedly depressed. Kinetics of choline transport in resistant cells was comparatively examined, and decreased V_max and increased K_m were observed in some resistant sublines. Accordingly, decrease in choline uptake may be due to decreased activity of choline transport-carrier, both qualitatively and quantitatively. Decreased HN₂ uptake by resistant cells seemed to be produced by the same mechanism.     

Synergistic effect of ultrasound and hematoporphyrin on sarcoma 180

The antitumor effects of combined use of ultrasound (US) and a photosensitizer, hematoporphyrin (Hp), were determined in mice bearing sarcoma 180. In order to find the optimum timing of the US irradiation after the administration of Hp, the Hp concentrations in the tumor and in the plasma were determined and were analyzed pharmacokinetically. Antitumor effects were evaluated by measuring the tumor size and the tumor weight. Hp alone showed no antitumor effect but US alone showed a slight antitumor effect. The combined treatment with US and Hp showed marked synergistic effects on sarcoma 180 (inhibition ratio was 74% of the control). From these results, the enhancement of antitumor effect is thought to be caused by the sensitization of tumor cells to US mediated by Hp.     

Anticancer effects of the p53 activator nutlin-3 in Ewing's sarcoma cells

Mutation of p53 is rare in Ewing’s sarcoma (ES), suggesting that targeting and activation of wild-type p53 may be an effective therapeutic strategy for ES. The recently developed small-molecule MDM2 inhibitor nutlin-3 restores wild-type p53 function, resulting in the inhibition of cancer cell growth and the induction of apoptosis. In the present study, we explored the responsiveness of ES cell lines with wild-type or mutated p53 to nutlin-3. We found that treatment with nutlin-3 increased p53 level and induced p53 target gene expression (MDM2, p21, PUMA) in ES cells with wild-type p53, but not in ES cells with mutated p53. Consistently, nutlin-3 elicited apoptosis only in wild-type p53 cells, as assessed by caspase-3 activity assay and flow cytometric analyses of mitochondrial depolarisation and DNA fragmentation. In addition, we found nutlin-3 to evoke cellular senescence, indicating that nutlin-3 induces pleiotropic anticancer effects in ES. Furthermore, combined treatment with nutlin-3 and an inhibitor of NF-κB produced synergistic antineoplastic activity in ES cells. Our findings suggest that the direct activation of p53 by nutlin-3 treatment may be a useful new therapeutic approach for patients with ES.     

Antitumor activity of interferon against murine osteogenic sarcoma cells in vitro.

Murine interferon inhibited the growth of a continuous line of osteogenic sarcoma (OGS) cells in tissue culture. Inhibition of tumor cell growth by interferon was demonstrated by: a) decreased colony formation in soft agar, b) suppression of clone formation in liquid medium, and c) reduction of tumor cell counts in monolayer cultures. This inhibition of cell growth was further documented by suppression of [3H]thymidine uptake by OGS cells exposed to interferon, which suggested inhibition of DNA synthesis of tumor cells. Exposure of tumor cells for 4 hours, 24 hours, and 2,3,4,6, and 8 days demonstrated greater activity with prolonged exposure to interferon. Inhibition of cell growth was significantly greater for OGS cells than for normal mouse embryo fibroblasts. Finally, the antitumor activity of the interferon preparation could be reversed by anti-interferon antibody.