摘要:

Summary:The increasing conccrn for the early detection and treament of cervical intraepithelial neoplasia (CIN) set up the basis for this study, which also considers some epidemiological factors which seem to be related to the genesis of an abnormal uterine cervical colposcopic pattern, the mosaic pattern. We have observed that women with a mosaic pattern show an increasing frequency of premalignant and/or malignant histologic changes up to 40 years of age which then falls abruptly. Sterility and hirsutism were frequent associations, these features suggesting an abnormal hormonal status. An association with infection byGardnerella vaginalis(15.3%) was noted, and dysplasia increased in frequency to 53% whenG. vaginaliswas associated with mosaic. Also, 67.25% of women with mosaic showed other concomitant diseases of allergic, immunologic, or infectious type. Based upon these observations, and in an attempt to explain further interrelationships among several factors in the pathogenesis of CIN, an integrated hypothesis which may lead to new therapeutic avenues, both in the prevention and treatment of early cervical cancer, is advanced.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:Recently many findings about the physiological and biochemical functions of recombinant human tumor necrosis factor (rHu‐TNF) have been reported. In the present study, the effect of rHu‐TNF on serum iron in C3H/HeN and C57BL/6 mice was determined. Blood samples were obtained before intravenous injection of rHu‐TNF, and also at various times after the injection. Results from five experiments showed that the serum iron was depressed between ⅓ to ⅕ of that of untreated mice 4 to 24 h after injection of 5 or 10 &mgr;g of rHu‐TNF. The low level persisted for 33 h, rebounded at 48 to 72 h, and returned to normal by 96 h after the injection. Serum iron was determined by the colorimetric method using the sensitive reagent, ferrozine (3‐(2‐pyridyl)‐5, 6‐bis(4‐sulfophenyl)‐1,2,4‐triazine. We believe that this is the first report of depression of serum iron in mice by intravenous injection of rHu‐TNF. The physiological role of repressed serum iron in the in vivo response to TNF remains to be established.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:The effects of systemic administrations of immune complex, complement activators, and insoluble particies on endogenous production of tumor necrosis factor (TNF) were investigated in mice. Production of serum TNF was triggered by i.v. injection of OK‐432, a streptococcal preparation, and measured by in vitro L‐929 cytotoxicity assay. Intravenous injection of IgG‐opsonized sheep red blood cells (108/mouse) enhanced OK‐432‐triggered TNF production significantly. This effect was maximal (about 30‐fold enhancement) 1.5 to 3h after the injection and disappeared within 10h. Complement activators other than immune complex also possessed this activity. Zymosan (0.1 mg/mouse) enhanced OK‐432‐triggered TNF production maximally (about 25‐fold) 3 to 6h after its i.v. injection, its effect lasting for 10h, and disappearing within 24h. Heat‐aggregated IgG and cobra venom factor also had similar enhancing effects. In addition, systemic pretreatment with insoluble particles enhanced OK‐432‐triggered TNF production. The enhancement by latex beads (2 &mgr;l volume of solid/mouse) was maximal (about 60‐fold) 3 to 6h after their i.v. injection, was sustained for at least 20h, and disappeared within 48h. Glass beads, dextran beads, alum, silica, and carbon particles all had similar enhancing effects. Based on these results, the in vivo scavenger function of macrophages, as well as direct activation with cytokines, may participate in priming for endogenous production of TNF; alternatively, particles or macromolecules which can be scavenged by macrophages may activate macrophages and prime for TNF production.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:The priming effect of endogenous biological response modifiers (BRMs), interferons (IFNs), and interleukin‐2 (IL2), and the triggering effect of BRMs of bacterial origin, OK‐432 andCorynebacterium parvum, on endogenous production of the tumor necrosis factor (TNF) were investigated in mice. TNF activity in serum was measured by in vitro cytotoxicity assay with L‐929 cells as a target. The i.v. injection of OK‐432 (3KE per mouse) triggered TNF maximally (mean value: 30 U/ml) after 2 h, with a similar time course to that of triggering by lipopolysaccharide. The priming activities of IFNs and IL2 were examined in the system of TNF‐triggering by OK‐432. The i.v. injection of recombinant IFN‐&ggr; (rIFN‐&ggr;, 104U per mouse) increased TNF production to 790 U/ml; this priming effect was observed just after its injection, was maximal after 2 to 6 h, and disappeared after 24 h. Other types of interferon, rIFN‐&agr;A/D(Bgl) (2 × 105U per mouse), rIFN‐&bgr; (106U per mouse), and natural IFN‐&agr;/&bgr; (106U per mouse) showed maximal priming activity 6 h after their injection (200 to 800 U/ml) but no effect just after their injection. Recombinant IL2 (106U per mouse) had priming activity that showed a similar time course to that of interferons other than IFN‐&ggr; (a maximal TNF production: 100 U/ml). The i.v. injection ofC. parvum, like OK‐432, triggered TNF production at doses of 0.06 and 0.3 mg per mouse 2 h after its injection and the triggered TNF activity was enhanced by rIFN‐&ggr;. These findings suggest that combinations of the above endogenous BRMs as priming agents and OK‐432 orC. parvumas a triggering agent could induce endogenous production of TNF even in human cancer patients. In fact, combined administration of rIFN‐&ggr; and OK‐432 produced TNF in human cancer patients. The advantage of this method for treatment of human cancer patients is discussed.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:The antitumor effect of combined natural human interferon‐alpha (IFN) and mismatched double‐stranded RNA (dsRNA) treatment against the human malignant melanoma cell line, BRO, was studied. In vitro results, using a tissue culture antiproliferative assay, indicated that these cells were moderately sensitive to IFN‐alpha. In contrast, mismatched dsRNA had no antitumor effect, and a minimal stimulation of cell growth, over part of the concentration range tested, was observed. Mismatched dsRNA did not potentiate the antitumor effect of IFN‐alpha in cells receiving combination treatment. Xenografts of BRO cells, inoculated subcutaneously into nude mice, were used to evaluate the antitumor effects of IFN‐alpha and mismatched dsRNA. Growth of the primary tumor was inhibited by both drugs alone or in combination (p < 0.001), but the combined treatment was most effective and appeared to be additive. The number of spontaneous lung metastases was also inhibited (p < 0.02) in all treatment groups. Survival, however, was significantly increased only in the IFN‐alpha/mismatched dsRNA group (p < 0.02 compared to controls, p < 0.05 compared to mismatched dsRNA alone). Determination of splenic natural killer (NK) cell activity against BRO cells demonstrated that mismatched dsRNA (p < 0.002), or IFN‐alpha/mismatched dsRNA (p < 0.05), significantly augmented NK activity to the same extent, but that the IFN‐alpha alone had no effect. These results indicate that IFN‐alpha worked through direct antiproliferative mechanisms while mismatched dsRNA stimulated host immunomodulatory effects. The increased tumor growth inhibition and survival in the dual treatment group appears to result from the combined direct antiproliferative and indirect immunomodulatory effects.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:Monensin is a carboxylic ionophore which dissipates proton gradients across cell membranes. Monensin is known to potentiate the cytotoxic activity of immunotoxins (antibody‐toxin conjugates) directed against several human tumor‐associated antigens. We have investigated the effect of monensin on an immunotoxin cytotoxic to the human breast cancer cell line MCF‐7. This immunotoxin is composed of an antibody directed against a human breast cancer membrane antigen, and ricin A chain, which has been produced by recombinant DNA techniques. In a 16‐hour cytotoxicity assay, monensin reduced 34‐fold the median inhibitory dose, from 1.4 × 10‐8M (without monensin) to 4.1 × 10‐10M (with monensin). In timed cytotoxicity assays, 50% of control protein synthesis was reached in immunotoxin treated cells 8‐fold faster in the presence of monensin (0.5 hours) than in its absence (4 hours). Monensin produced no enhancement of immunotoxin effect on a control cell line, nor on a control immunotoxin on MCF‐7 cells, demonstrating specificity of monensin effect. In addition, specific immunotoxin alone or with monensin produced no toxicity on MCF‐7 cells maintained at 23°C. These results suggest that both binding and internalization of immunotoxin are necessary for the monensin effect. Monensin was a potent enhancer of immunotoxin effect on human breast cancer cells. This effect occurs without the presence of ricin B chain in the conjugate.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:Interferon treatment has been shown to cause myelosuppression in man and in a mouse model. Combinations of interferon‐gamma (IFN‐&ggr;) with either interferon‐alpha (IFN‐&agr;) or interferon‐beta (IFN‐&bgr;) cause the synergistic enhancement of interferons' antiviral, antiproliferative, antitumor, and immunoregulatory activities. Thus, combinations of MuIFN‐&bgr; and either natural or recombinant DNA‐derived MuIFN‐&ggr; were evaluated for their ability to cause the synergistic enhancement of interferon's myelosuppressive activity. The combinations of interferons were evaluated in vitro in bone‐marrow colony‐stimulating assays. They were seen to potentiate the in vitro myelo‐suppressive effect of the interferons. The combinations were evaluated for their in vivo myelosuppressive effect in mice. Treatment with the separate interferons caused a significant reduction in the number of circulating leukocytes, suggesting a potent myelosuppressive effect. However, treatment with the interferons in combination caused an antagonism and led to a myelosuppressive effect which was no greater than that of the interferons alone. The combinations of interferons were employed at concentrations which have been shown to provide substantial potentiation of the antitumor action of the interferons against B‐16 melanoma. Thus, the data suggest that combination interferon therapy employing IFN‐&ggr; together with either IFN‐&agr; or IFN‐&bgr; provide a potentiated antitumor activity without increasing the myelosuppressive side effect of the therapy.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:We prepared large unilamellar vesicles containing the cell‐free culture supernatant of a human T cell hybridoma rich in macrophage activating factor (MAF) and bearing monoclonal antibodies against human melanoma A375 tumor cells; their antitumor activity against A375 cells was examined in vitro and in vivo. Both MAF‐immunoliposomes (bearing antibodies) and MAF liposomes (not bearing antibodies) showed macrophage‐mediated cytotoxicity in vitro at a high E/T ratio (about 40). But at a low E/T ratio (about 15), only MAF‐immunoliposomes showed tumoricidal activity, their activity being more than ten thousand‐fold stronger compared with a soluble MAF preparation (MAF solution). MAF‐immunoliposomes not only showed tumor neutralization mediated by macrophages in vivo when a mixture of tumor cells, macrophages, and MAF‐immunoliposomes was locally injected, but also showed significant inhibition of tumor growth on repeated i.v. systemic administration of them. On the other hand, other samples (MAF‐liposomes without the antibody, a MAF solution, and immunoliposomes without MAF) were not significantly effective against tumor growth. These results may constitute evidence that the delivery of lymphokines to the tumor sites is important or even critical when an attempt is made to treat cancer with lymphokines with the expectation of the potentiation of the host's immune system.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID