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41.
Sean Clark Michael A. McGuckin Terry Hurst Bruce G. Ward 《Cancer immunology, immunotherapy : CII》1994,39(2):100-104
This study aimed to investigate whether the biological response modifiers (BRM) interferon (IFN) and tumour necrosis factor (TNF) could enhance the cytotoxic action of cisplatin on ovarian tumour cells in vitro. The sensitivity of four cell lines (OAW42, GG, JAM and PE01) to drugs and drug combinations was tested by a radiolabelled-thymidine incorporation assay. Cell lines demonstrated a range of sensitivity to cisplatin and the innate cytotoxic effect of each of the BRM. When IFN was used in combination with cisplatin, a significant enhancement of cisplatin toxicity occurred in three of four cell lines. TNF demonstrated such an effect in two cell lines but diminished the toxicity of cisplatin in one cell line. A purely additive effect of the agents may explain the enhanced toxicity of cisplatin in some of these cases. However, in one cell line at least (PEO1), both TNF and IFN demonstrated a clearly synergistic effect with cisplatin. These BRM used in conjunction with cisplatin may provide better antitumour regimen than cisplatin alone in some patients with ovarian cancer, but the response is likely to be heterogeneous between patients. 相似文献
42.
Low-dose melphalan-induced shift in the production of a Th2-type cytokine to a Th1-type cytokine in mice bearing a large MOPC-315 tumor 总被引:4,自引:0,他引:4
Leonid Gorelik Anna Prokhorova Margalit B. Mokyr 《Cancer immunology, immunotherapy : CII》1994,39(2):117-126
The current studies demonstrate that MOPC-315 tumor cells secrete large amounts of interleukin-10 (IL-10), which contributes to the inhibitory activity of MOPC-315 culture supernatants for the in vitro generation of antitumor cytotoxicity by MOPC-315-immune spleen cells. Moreover, addition of neutralizing monoclonal anti-IL-10 antibody to the in vitro stimulation cultures of cells from the tumor infiltrated spleens of mice bearing a large MOPC-315 tumor resulted in the generation of enhanced anti-MOPC-315 cytotoxicity. In contrast, addition of monoclonal anti-IL-10 antibody to the in vitro stimulation cultures of splenic cells from mice that are in the final stages of immune-mediated tumor eradication as a consequence of low-dose melphalan (l-phenylalanine mustard; L-PAM) therapy (and whose spleens no longer contain metastatic tumor cells) did not lead to enhancement in the in vitro generation of antitumor cytotoxicity. The cessation of IL-10 secretion as a consequence of low-dose L-PAM therapy of MOPC-315 tumor bearers was found to be accompanied by the acquisition of the ability to secrete interferon (IFN) by the splenic cells. In addition, by day 2 after low-dose L-PAM therapy a drastic decrease in the amount of IL-10 secreted by the s.c. tumor nodules was noted, which preceded the accumulation of tumor-infiltrating lymphocytes capable of secreting IFN. Thus, low-dose L-PAM therapy of mice bearing a large MOPC-315 tumor leads to a shift in cytokine production from a Th2-type cytokine to a Th1-type cytokine, and it is conceivable that this shift in cytokine production plays an important role in the low-dose L-PAM-induced acquisition of antitumor immunity by hitherto immunosuppressed mice bearing a large MOPC-315 tumor.Supported by research grant IM-435 from the American Cancer Society and CA54413 from the National Cancer InstituteIn partial fulfillment of the requirements for the Doctor of Philosophy DegreeRecipient of career development award CA-01350 from the National Cancer Institute 相似文献
43.
Brian Duff Sloley 《Neurochemical research》1994,19(2):217-222
The conversion of 5-hydroxytryptamine to several potential metabolites was examined in the annelid earthworm (Lumbricus terrestris). 5-hydroxytryptamine and some related amines were found to be present in several tissues of the earthworm. Injection of 5-hydroxytryptamine into the body cavity of the earthworm resulted in the production of a -glutamyl conjugate of 5-hydroxytryptamine. Incubations of the anterior nerve cord of the earthworm resulted in the accumlation of considerable amounts of 5-hydroxytryptamine and -glutamyl 5-hydroxytryptamine in the incubation medium. The earthworm did not produce any N-acetyl 5-hydroxytryptamine and only very little 5-hydroxyindoleacetic acid. Experiments involving the injection of radiolabeled 5-hydroxytryptamine or coninjection of radiolabeled glutamic acid with unlabeled 5-hydroxytryptamine into the earthworm resulted in the production of radiolabeled -glutamyl 5-hydroxytryptamine. This work demonstrates that the enzymatic conversion of 5-HT in the earthworm is markedly different from that of vertebrates and insects. 相似文献
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45.
Isabelle Chevalot Athanase Visvikis Pierre Nabet Jean-Marc Engasser Annie Marc 《Cytotechnology》1994,16(2):121-129
Recombinant Chinese Hamster Ovary (CHO) cells, engineered for the production of human gamma-glutamyl transferase (GGT), have been grown on Cytodex 1 microcarriers, as aggregates, or as single cells in suspension after adaptation. GGT is a membrane bound enzyme which was not secreted during the culture period. The maximal enzyme activity was found to be directly related to the achieved maximal cell density. Culture of CHO on microcarriers yielded the fastest growth, with a specific growth rate of 0.04 h–1, the highest cell density (near 1.3×106 cells ml–1), and the highest enzyme activity around 300 mU ml–1, which corresponded to a specific cellular level of 20 mU 10–5 cells. GGT could also be produced by growing CHO cells in suspension as single cells or as aggregates. Under these conditions, however, the specific CHO growth rate was significantly slower and the GGT level per cell was divided by a factor 6. Growing CHO cells without microcarriers also resulted in differences in cell metabolism, with a higher conversion yield of glutamine into ammonia, and a higher cell lysis. The catalytic kinetic constants of the enzyme were found identical for the three culture systems. 相似文献
46.
Rationale and objective Interferon alpha (IFN-) has anti-retroviral activity and is a possible HIV infection-limiting factor. The aim of this work is to prevent or delay disease progression in asymptomatic Human Immunodeficiency Virus (HIV) carriers.Design and interventions Recombinant IFN alpha-2b (3×106 IU 3 times weekly) was compared. to no treatment (control) in a randomized trial. Endpoints were: (i) appearance of any CDC group IV symptoms and (ii) disease progression (which excluded shifts to group IVC2 or reversible IVA, or IVB). The trial lasted from October 1987 to February 1992.Setting The trial was performed at the Santiago de las Vegas sanatorium, a specialized institution for the care of HIV-infected and AIDS patients.Population Subjects were anti-HIV-1 seropositive, Western blot-confirmed, asymptomatic (CDC group II), or with generalized lymphadenopathies (CDC group III). The groups had 79 (control) and 71 (IFN) patients.Main results Long-term IFN- treatments significantly reduced the proportion of patients who shifted to any group IV (control: 46/79; IFN: 14/71;p<0.001) or developed AIDS (control: 27/79; IFN: 12/71;p<0.05). IFN also delayed progression to AIDS (95% confidence interval for 0.5 probability of progression) from 67–83 to 116–180 months after infection. The IFN group had significantly less opportunistic infections and non-infectious complications. CD4 cell count and hemoglobin decreased in the control but not in the IFN group. Fewer IFN-treated patients developed positive serum HIV antigen detection.Conclusion IFN alpha treatment during the early stages of infection seems to be beneficial to the patients.Abbreviations CI
confidence interval
- AIDS
Acquired Immunodeficiency syndrome
- HIV
Human Immunodeficiency Virus
- IFN
Interferon
- CDC
Center for Disease Control (USA)
- SD
standard deviation 相似文献
47.
HBIG,无环鸟苷,干扰素联合对慢性乙型肝炎抗病毒效应观察 总被引:1,自引:0,他引:1
本文报道血清HBV复制标志阳性的慢乙肝54例,随机分为治疗组及对照组各27例进行HBIG、无环鸟苷、干扰素联合近、远期抗病毒效应观察。治疗组为无环鸟苷第一周按25~20mg/kg/d计后改17~15mg/kg/d×53天,共60天;人白细胞干扰素1×106U肌注每周3次×4周,后改1.0×106U肌注每周2次×6周,共10周;HBIG400U肌注隔日1次,共10周,对照组仅给予一般“保肝”药物。其中治疗组18例,对照组19例进行治后半年到2年追踪观察,结果近、远期HBcAg、DNAP、HBV-DNA阴转率治疗组均高于对照组,其中治疗组近、远期HBcAg,HBV-DNA阴转率均达40%以上,明显高于对照组(P<0.05~0.01),治疗组近、远期各有4例及2例HBsAg阴转,而对照组则无一例阴转,从近、远期综合抗病毒效应观察,治疗组全阴率分别为33.3%、44.4%,而对照组分别为3.79%及0%,P<0.01,治疗组无明显毒副反应。对比单用无环鸟苷,全阴率31.8%;无环鸟苷加干扰素两药联合全阴率37.5%,均有所提高,达到44.4%,值得进一步研究。 相似文献
48.
49.
Richard Darley Alan Morris James Passas Wendy Bateman 《Cancer immunology, immunotherapy : CII》1993,37(2):112-118
The cell-surface expression of major histocompatibility (MHC) antigens and the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) is essential for target cell recognition by T lymphocytes. The expression of both classes of molecule is induced by various cytokines, notably interferon (IFN). Since transforming growth factor (TGF) has been recently reported to antagonise HLA-DR induction by IFN we have examined, using a number of murine and human cell lines, the effect of TGF on IFN-induced MHC class I and class II and ICAM-1 expression. All of the cell lines tested expressed elevated class I MHC following IFN treatment. Class II MHC induction was seen on most but not all of the cells, the exceptions being among a panel of human colorectal carcinoma cell lines. A striking difference between cells of different origin was noted in the response to TGF. TGF was found to antagonise IFN-induced class I and class II MHC expression on C3H 10T1/2 murine fibroblasts, early-passage BALB/c mouse embryo fibroblasts, a murine oligodendroglioma cell line, and on MRC5 human fibroblasts and two human glioblastoma cell lines. Class II MHC was much more strongly inhibited (sometimes completely) than class I MHC. TGF also inhibited induction of class I MHC expression by IFN. However, TGF did not inhibit class I or class II MHC induction by IFN in any of the nine colorectal carcinoma cell lines, although two of five of the lines tested were growth-inhibited by TGF. On the other hand, human ICAM-1 induction by IFN was not affected by simultaneous treatment with TGF in any of the cell lines. The down-regulation of IFN-induced MHC antigens by TGF is not, therefore, the result of a general antagonism of IFN. Retinoic acid has recently been reported to induce ICAM-1 expression on human tumour cells. We have confirmed this observation on MRC5, and the two human glioblastoma cell lines, however six colorectal carcinoma cell lines tested did not respond. In contrast to IFN-induced ICAM-1 expression, retinoic-acid-induced ICAM-1 expression was inhibited by TGF on two of the three responsive lines. 相似文献
50.