Studies on two new mixed ligand platinum compounds with a trans-geometry

In this paper we report the synthesis and in vitro activity of two new mixed ligand platinum complexes: trans-[PtCl?(thiazole)(imidazole) [JH3] and trans-[PtCl?(thiazole)(3-hydroxypyridine) [JH4]. Although the compounds are less active than cisplatin against the parent ovarian cancer cell line A2780, they are more active than cisplatin against the resistant cell lines A2780(cisR) and A2780(ZD0473R), thus indicating that JH3 and JH4 have been better able to overcome mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R). When Pt-DNA binding levels at 24 h in A2780, A2780(cisR) and A2780(ZD0473R) cell lines are compared it is found that whereas for cisplatin the values in resistant cell lines are significantly lower than that in the parent cell line, for JH3 and JH4 Pt-DNA binding levels in the parent and resistant cell lines are comparable, thus providing an explanation for variations in activity of the compounds in the three cell lines.     

Antitumor activity of a Brucella abortus preparation.

Mice injected intraperitoneally with sarcoma-180 cells develop ascites and eventually die. Intraperitoneal injection of a nonviable, aqueous... ether-extracted Brucella abortus preparation (BRU-PEL) as early as 7 days before or as late as 7 days after injection of tumor cells significantly inhibited development of ascites and protected against death. BRU-PEL was not effective if injected after ascites was grossly apparent. BRU-PEL was significantly more active than a Corynebacterium parvum preparation administered in the same way.     

Antitumor activity of Listeria monocytogenes on a guinea pig fibrosarcoma.

Listeria monocytogenes-mediated tumor inhibition was studied in strain 13 guinea pigs by using a methylcholanthrene-induced fibrosarcoma (MCA-1). Mixtures of Listeria and tumor cells in ratios of 1:100, 1:200, or 1:400 (Listeria:MCA-1 cells) led to significant suppression of tumor growth. Intralesional injection of tumors on day 6 posttransplantation led to the regression of a highly significant number of tumors. Animals receiving injections of Listeria, either in a mixture with tumor cells or intralesionally, displayed enhanced skin test reactivity to a tumor extract. Tumor regressors were resistant for at least 2 to 3 months after the initial transplant to rechallenge with MCA-1 cells. Thus, with this particular tumor-host system, Listeria was successfully employed as an antitumor agent with no visibly detrimental side effects to the host.     

Antitumor activity of mycobacterial glycolipid A1.

Glycolipid A1 isolated from Mycobacterium bovis BCG, when dissolved in olive oil and injected together with Line 10 transplantable hepatoma cells, is able to elicit a host response which results in the abrogation or retardation of tumor growth in syngeneic guinea pigs. Glycolipid A1 does not have adjuvant activity for delayed type hypersensitivity, and antibodies to A1 have not been detected in the sera of guinea pigs during or after the tumor abrogation induced by A1 injection Glycolipid A1 does not share antigenic determinants with Line 10 cell lipid fractions. The possible role of the granuloma response elicited by A1 in controlling tumor growth is discussed.     

Antiviral activity of platinum (II) and palladium (II) complexes of pyridine-2-carbaldehyde thiosemicarbazone.

A heterocyclic compound, pyridine-2-carbaldehyde thiosemicarbazone (HFoTsc), and its six metal coordinated bound complexes, three with platinum (II) and three with palladium (II), were studied for their activity against herpes simplex virus 1 (HSV-1) infection in cultured cells. According to their cytotoxicity the compounds were divided into two groups. Group I (cytotoxic compounds) included all three palladium complexes and [Pt(HFoTsc)2] Cl2, with maximum non-toxic concentration (MNC) of 1-10 micromol/l and a 50% cytotoxic concentration (CC50) of 20-100 micromol/l. Group 2 (low cytotoxic compounds) with MNC of 100 micromol/l and CC50 of 548-5820 micromol/l included compounds in the following order: [Pt(HFoTsc)2] Cl2相似文献   

Antitumor activity of NK cells

NK cells have been shown to play an important role in the lungs with regards to tumor cell clearance and resistance of this organ to metastases. Here, we have investigated whether NK cells play a similar role in organs other than the lungs. We conclude that while organ-resistance to metastases correlates well with the NK activity of the host, a clear correlation between NK activity and clearance of tumor cells is found only in the lungs. We also demonstrate that activation of NK cells with the TLR 3 ligand poly I:C results in a substantial increase in the number of organ-associated NK cells. This increase may explain the increased resistance to metastasis seen in many organs after poly I:C treatment. Finally, we present data showing that NK cells activated ex vivo with IL-2 are able to localize to lung tumors following iv adoptive transfer and to significantly reduce the tumors they infiltrate. We conclude that NK cells, which currently are under intense investigation owing to their newly discovered immunoregulatory functions, remain very potent antitumor killer cells capable of killing not only circulating tumor cells, but also well-established micro metastases.     

二氢槲皮素与二氢杨梅素的抗肿瘤活性对比

目的:研究二氢槲皮素和二氢杨梅素对H22 荷瘤小鼠抑瘤作用。方法:建立小鼠H22 移植性肿瘤模型(除空白外)。造模24 h 后分成6 组:模型组,阳性对照组(环磷酰胺25 mg/ kg),二氢槲皮素和二氢杨梅素高、低剂量组(30、10 mg/kg),除阳性对照组腹腔给药,其余各组均灌胃给药,测定其对H22 荷瘤小鼠抑瘤率、免疫器官指数、生化指标和细胞因子含量的影响,并通过HE 染色,观察瘤组织内坏死程度。结果:二氢槲皮素和二氢杨梅素高、低剂量组(30 mg/ kg、10 mg/ kg)均对肿瘤具有一定抑制作用,且均可提高H22 荷瘤小鼠胸腺指数和脾指数,其中二氢槲皮素高剂量组(30 mg/ kg)抑瘤效果最佳,其抑瘤率为58.8%。二氢槲皮素和二氢杨梅素高、低剂量组均可升高H22 荷瘤小鼠细胞因子白细胞介素鄄2(IL-2)和肿瘤坏死因子 (TNF)的水平,升高超氧化物歧化酶(SOD)的水平,降低丙二醛(MDA)水平。此外,二氢槲皮素和二氢杨梅素高、低剂量组对H22 荷瘤小鼠肝肾功能没有毒理作用。结论:二氢槲皮素和二氢杨梅素高、低剂量组均对肿瘤具有一定抑制作用,其中二氢槲皮素组的作用较明显,且呈剂量依赖性,其作用机制可能与增强抗氧化能力、提高机体免疫功能和升高细胞因子水平有关。     

Radioconglutinin-binding azssay for circulating immune complexes: a new method.

A new method for the detection of circulating immune complexes using radiolabelled conglutinin as a marker for complement-bound complexes precipitated in low concentrations (3.5%) of polyethylene glycol is described. The optimal laboratory conditions for the test have been defined and certain limitations studied. The technique is simple with good reproducibility and high degree of specificity. In a double-blind study of eighty-seven samples of sera from normals, patients with glomerulonephritis, post-renal transplantation, rheumatic diseases, breast tumours, multiple sclerosis and infections the method was compared and correlated to the Clq-binding assay and the Raji cell test. The radioconglutinin-binding assay was most discriminative for cases of glomerulonephritis, renel transplantation, breast carcinoma and multiple sclerosis and least for rheumatoid arthritis.     

Antitumor activity of normal bone marrow cells

After separation of normal murine bone marrow cells in a Percoll density gradient cellular fractions with densities of 1.076 and 1.060 g/ml are capable of suppressing thein vitro growth of leukemia cells. The cytostatic activity of these fractions, however, does not surpass the level of antitumor antiproliferative activity intrinsic to intact bone marrow cells. These cells were found to be capable of joining the splenocytes, thymocytes, and lymph node cells in effector cytostatic cooperation and thus enhance the final antitumor effect. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 181–183, August, 1995     

Antibacterial activity of five cephalosporins

The in vitro susceptibilities of 7 commonly isolated species of bacteria to cephalothin, cefoxitin, and 3 new cephalosporins--cephamandole, cefuroxime, and cefoperazone--were studied using an agar dilution method. Cephalothin and cephamandole were the most active agents against staphylococci. Against members of the Enterobacteriaceae all the newer agents were more active than cephalothin; however, important individual differences emerged. Only cefoperazone had significant activity against Pseudomonas aeruginosa.     

Antitumor activity of thalidomide in refractory multiple myeloma

BACKGROUND: Patients with myeloma who relapse after high-dose chemotherapy have few therapeutic options. Since increased bone marrow vascularity imparts a poor prognosis in myeloma, we evaluated the efficacy of thalidomide, which has antiangiogenic properties, in patients with refractory disease. METHODS: Eighty-four previously treated patients with refractory myeloma (76 with a relapse after high-dose chemotherapy) received oral thalidomide as a single agent for a median of 80 days (range, 2 to 465). The starting dose was 200 mg daily, and the dose was increased by 200 mg every two weeks until it reached 800 mg per day. Response was assessed on the basis of a reduction of the myeloma protein in serum or Bence Jones protein in urine that lasted for at least six weeks. RESULTS: The serum or urine levels of paraprotein were reduced by at least 90 percent in eight patients (two had a complete remission), at least 75 percent in six patients, at least 50 percent in seven patients, and at least 25 percent in six patients, for a total rate of response of 32 percent. Reductions in the paraprotein levels were apparent within two months in 78 percent of the patients with a response and were associated with decreased numbers of plasma cells in bone marrow and increased hemoglobin levels. The microvascular density of bone marrow did not change significantly in patients with a response. At least one third of the patients had mild or moderate constipation, weakness or fatigue, or somnolence. More severe adverse effects were infrequent (occurring in less than 10 percent of patients), and hematologic effects were rare. As of the most recent follow-up, 36 patients had died (30 with no response and 6 with a response). After 12 months of follow-up, Kaplan-Meier estimates of the mean (+/-SE) rates of event-free survival and overall survival for all patients were 22+/-5 percent and 58+/-5 percent, respectively. CONCLUSIONS: Thalidomide is active against advanced myeloma. It can induce marked and durable responses in some patients with multiple myeloma, including those who relapse after high-dose chemotherapy.     

Phosphoenolpyruvate-dependent sucrose phosphotransferase activity in five serotypes of Streptococcus mutans.

An inducible phosphoenolpyruvate-dependent sucrose phosphotransferase system has been demonstrated in decryptified cell suspensions of the various common serotypes of the cariogenic microorganism Streptococcus mutans.     

Establishment and characterization of five new human renal tumor xenografts.

Ten different human renal cell carcinoma (RCC) primary tumors were xenografted into BALB/c nu/nu mice. Five of the tumors (NU-10, NU-12, NU-20, NU-22, and NU-28) gave rise to serially transplantable tumors that were further characterized. Histology, DNA index, immunohistochemical characteristics, growth rate, and clonogenic potential were followed from primary tumor to the 5th to 15th transplant passage. Only one of the tumors (NU-20) showed remarkable instability for all tested parameters in the first five transplant passages. Histology of the other tumors was essentially the same to the histology of the primary tumors, although differences between human and host-derived vessels were apparent. DNA index values in general showed a trend toward an aneuploid character of the xenografts. Immunohistochemical analyses showed a loss of intensity of staining but a concomitant rise in the fraction of positively staining cells with antibodies against cytokeratins, vimentin, tumor-associated antigens, and human leukocyte antigen (HLA) class I antigens. Human leukocyte antigen class II antigen expression showed a loss of intensity as well as a decrease in the fraction of positive cells. Tumor doubling time was lowest in transplant passage number 0, and stable growth was noticed in transplant passages 1 through 4. Clonogenic potential of four of the lines was higher for the xenografts than for the primary tumors. The authors conclude that, on xenografting, histologic characteristics of the primary tumor are essentially conserved. Progression in the first transplant passages, however, results in tumors with a more aggressive character.     

Control pathways of the 67 kDa laminin binding protein: surface expression and activity of a new ligand binding domain

A number of papers have been published on the clinical correlation of the expression of the 67 kDa laminin binding protein (LBP) with the metastatic potential of solid tumors. Both mRNA and protein expression levels have been reported, but both the relationship between them and the molecular nature of the 67 kDa surface product remain unclear. We have utilized a homotypic overexpression system to investigate the cell surface presentation of the 67 kDa LBP and the contribution of this protein to the invasive phenotype of cultured cell lines. We report here that the cellular mRNA levels do not directly reflect the levels of the 67 kDa LBP observed on the cell surface in this overexpression system. Methotrexate amplification of transfected plasmids expressing the 67 kDa LBP leads to an initial elevation of both the LBP mRNA and surface protein levels. This is accompanied by an altered, more flattened, cell morphology. Later, apparent adaptation of the cells to methotrexate is accompanied by a down-regulation of the surface expression of the protein. mRNA levels, however, remain elevated. A nine amino acid sequence, CDPGYIGSR (peptide 11), within the chain of laminin 1 has been identified as a probable binding domain for the 67 kDa LBP. Previous studies have identified a region of the 67 kDa LBP which may be involved in laminin interaction, although not necessarily via the peptide 11 domain. We have identified a second site within the amino acid coding sequence of the 67 kDa LBP which also shows biological activity both in vitro and in vivo. A peptide with this sequence, LBP residues 205-229, binds laminin-1 in a peptide 11 inhibitable manner. The receptor-derived peptide modulates invasion of basement membrane matrix in vitro and inhibits experimental lung colony formation when injected along with B16BL6 mouse melanoma cells. However, pretreatment of the melanoma cells with the peptide enhances lung colony formation. Thus, the interaction of the 67 kDa LBP with basement membrane matrix appears to involve a complex series of events including multiple adhesive sites and tight regulation of cell surface expression.