ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:A randomized Phase II study was planned to test two doses of human lymphoblastoid interferon (Wellferon) in patients with metastatic breast cancer. Thirty‐seven patients were entered and received either 0.5 or 3.0 million units three times a week for three months. The dose selection was based on earlier Phase I studies in order to maximize NK (natural killer) stimulation and the amount tolerated without undue toxicity. Twenty‐nine patients were evaluable. There was only one excellent partial remission, sustained for one year. There were small and statistically insignificant NK increases in both groups. From this and a review of the literature, we conclude that alpha interferon has negligible activity in breast cancer.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:A polyvalent melanoma tumor antigen vaccine was prepared from antigens shed by a pool of human melanoma cells cultured in serum‐free medium. The vaccine contained multiple melanoma associated antigens (MAAs) and was free of detectable fetal calf serum (FCS) proteins and Dr antigens. Three batches of vaccine prepared several months apart contained the same spectrum of tumor antigens. Thirteen patients with metastatic malignant melanomas were immunized intradermally with escalating doses of the vaccine in a Phase I study. There was no toxicity other than transient urticaria at the injection site. Humoral immunity, assayed by indirect immunoprecipitation, was augmented in five (38%) patients. Cellular immunity, assayed by delayed‐type cutaneous hypersensitivity, was induced in four (31%) patients. Skin tests to a control vaccine prepared from pooled allogeneic lymphocytes were negative. Cutaneous metastases regressed completely in one patient who is now disease free after 2 years, and multiple cutaneous metastases have remained stable for 14 months in another patient. These results indicate that active immunization to a partially characterized polyvalent melanoma antigen vaccine is safe and can increase immunity to melanoma in some patients.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:Marked tumor‐regressing activity was induced in the serum of S180 tumor‐bearing mice by injection of an antitumor polysaccharide, CM‐TAK [carboxymethylated &bgr;(1‐3)glucan]. Maximal activity was induced 7‐14 days after the tumor transplantation and 10‐12 h after CM‐TAK treatment. A quantitative assay for the activity was established on the basis of the initial decrease in the number of the tumor cells within 24 h. The factor with tumor‐regressing activity was purified 10,000‐fold by the series of hydroxylapatite chromatography, ammonium sulfate precipitation, anion‐exchange chromatography, gel filtration, and boronate‐mediated affinity chromatography. The molecular weight was estimated to be 250,000 by gel filtration. The activity was proteinase K sensitive, but relatively resistant to trypsin. Neuraminidase did not affect the activity. It is believed that the tumor‐regressing factor is different from the tumor necrosis factor.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:Fifteen patients with disseminated melanoma were treated by intravenous administration of recombinant alpha‐2 interferon (rIFN‐&agr;2) on 5 consecutive days every 2 weeks. Immunological studies on approximately 50% of the patients revealed no significant changes in lymphocyte numbers or T‐cell subsets. Natural killer (NK) activity against the K562 target cell and a melanoma cell was increased in the first treatment cycle, but in subsequent treatment cycles it tended to decrease against the melanoma cell and to show either no change or moderate increases against the K562 target cell. Interleukin‐2 (IL‐2) production from mitogen‐stimulated lymphocytes was decreased in most patients in each treatment cycle. This also applied to immunoglobulin production in vitro from pokeweed mitogen (PWM)‐stimulated B and T cells. The latter was not due to the induction of radiation‐sensitive suppressor T cells and may reflect effects on B cells or helper T cells. The repeated inhibition of IL‐2 production with each cycle of treatment and the decrease in NK activity against the melanoma target cells after the first treatment cycle contrasted with the return to at or above pretreatment values of these tests when rIFN‐&agr;A was given intramuscularly on an alternate‐day basis. It is suggested that these effects may be due to the relatively greater increase in endogenous cortisol production at the beginning of each treatment cycle in patients given rIFN‐&agr;2 intravenously compared to that observed in patients treated with rIFN‐&agr;A on alternate days intramuscularly. Immunosuppression resulting from the increase in cortisol production may be one of the factors accounting for the low tumor response rate of patients in this study and may emphasize the possible importance of the schedule of rIFN‐&agr; administration for obtaining optimal antitumor responses.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:K562 is a human leukemic cell line used as model of hematopoietic differentiation. A variety of differentiation‐inducing agents was used in this study, and the expression of surface membrane antigens associated with specific lineages of differentiation and changes in the cytochemistry of the induced cells were monitored. Sodium butyrate, hemin, retinoic acid, dimethyl sulfoxide (DMSO), phorbol myristate acetate (PMA), and interferon induced unique alterations in the binding of monoclonal antibodies specific for erythroid, granulocytic, monocytic, and megakaryocytic lineages. Hemoglobinization, Sudan Black B, glycogen content, nonspecific esterase, alkaline phosphatase, and 5′‐nucleotidase staining were also altered. K562 cells were terminally differentiated with PMA to nitroblue tetrazolium‐(NBT) positive macrophages. Expression of 3‐fucosyl‐N‐acetyl lactosamine, previously thought to be myeloid specific but found on all early hematopoietic progenitors, was modulated during differentiation to nonmyeloid lineages. Lineage infidelity was noted during functional differentiation along all hematopoietic lineages. The presence of multiple lineage surface markers and cytoplasmic characteristics in leukemic cells is not indicative of lack of potential to differentiate. K562 cells cannot be compared to any normal stage of hematopoietic differentiation, but they do have the capacity to differentiate along erythroid, macrophage, and megakaryocytic lineages.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:In search of potential therapeutic agents for the acquired immunodeficiency syndrome (AIDS) among homosexual males, we studied in vitro the immunorestorative effect of azimexon in patients with this syndrome. Since a reduction in the ratio between helper inductor and suppressor/cytotoxic T‐cell subsets (OKT‐4/OKT‐8) seems to be the hallmark of the syndrome, we measured azimexon‐induced numerical changes in T‐cell subsets and correlated them with changes in a simultaneously tested T‐cell function as measured by the xenogeneic local graft‐versus‐host reaction (GVHR). Following incubation of peripheral blood mononuclear cells from 10 homosexual subjects with 10 &mgr;g/ml of azimexon at 37°C for 1 h, the median number of T cells defined by the OKT‐8 phenotype declined from 0.6 × 103to 0.33 × 103/mm3(p < 0.02), resulting in an increase in the OKT‐4/OKT‐8 ratio from 0.65 to 1.37 (p < 0.01). There were no numerical changes in T cells defined by OKT‐3 and OKT‐4 phenotypes. Similar decreases in OKT‐8‐defined T cell occurred among eight heterosexual controls. The restoration of the OKT‐4/OKT‐8 ratio among the homosexual subjects was associated with a significant improvement in their T‐cell function. Thus, the median volume of the local GVHR increased from 38.2 to 63.5 mm3(p < 0.02). Parallel changes in OKT‐4/OKT‐8 ratio and changes in local GVHR following incubation with azimexon were observed.These results suggest that azimexon may be an important immunorestorative agent. Clinical trials with this agent in patients with AIDS or its preclinical complex of symptoms seem warranted.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:A striking clinical response of hairy cell leukemia (HCL) to alphainterferon (&agr;‐IFN) has recently been reported. To explain its efficacy on HCL, we investigated the ultrastructural changes caused by &agr;‐IFN in hairy cells. Mononuclear cells (MNCs) were separated from the peripheral blood of eight HCL patients in the leukemic phase. Aliquots of 1 × 106MNCs in 2.5 ml of RPMI 1640 medium were cultured with a recombinant DNA‐derived alpha‐2 interferon (RD&agr;2‐IFN) for 1, 3, and 7 days. The concentrations of IFN added were 10, 100, 1,000, and 10,000 IU/ml culture medium. Electron microscopic examination revealed that RD&agr;2‐IFN induced the formation of tubuloreticular structures in cultured hairy cells and increased the frequency of hairy cells having annulate lamellae (ALs), probable precursors of the nuclear pore. Hairy cells from various patients showed a variability in the extent of tubuloreticular structure (TRS) formation. Excellent clinical responses, as judged by hematologic parameters, were observed among patients whose leukemic cells were susceptible to RD&agr;2‐IFN with respect to TRS formation in vitro. From these findings, we propose that the induction of TRS formation, in combination with the increase of ALs, may be a morphologic expression of a direct antitumor action of IFN on malignant cells.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID