Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of gamma-interferon (IFN-gamma) on the induction of interleukin-2 (IL-2) activated killer cell activity was studied: (I) in peripheral blood lymphocytes (LAK cells) from cancer patients and healthy donors, (II) in lymphocytes infiltrating solid tumors (TIL) from melanoma and breast cancer patients, and (III) in pleural effusion associated lymphocytes (EAL) from patients with lung adenocarcinoma. The coculture of LAK, TIL and pleural effusion mononuclear cells (MNC) with several doses of IFN-gamma (10, 50, 250, and 1250 U/ml) and a low dose of IL-2 (10 U/ml) for 5 days resulted in a synergistic effect on the cytotoxicity of these cells against several tumor cell lines. Furthermore there was a potentiation in the proliferation of MNC after a 5-day culture. The induction of lymphocyte cytotoxicity by a combination of IFN-gamma with low doses of IL-2 may be helpful in designing more effective cancer immunotherapeutic protocols with LAK, TIL or EAL.
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PMID:Gamma-interferon enhances the cytotoxic activity of interleukin-2-induced peripheral blood lymphocyte (LAK) cells, tumor infiltrating lymphocytes (TIL), and effusion associated lymphocytes. 128 41

The immunosuppressive nature of the human breast cancer microenvironment was investigated. The soluble fraction of individual tumours was tested for its ability to influence the activation of peripheral blood lymphocytes (PBL) by interleukin-2 (IL-2) and to effect the continued proliferation of cells which had been pre-activated with IL-2. In all cases, both assays were profoundly inhibited (90-100%). None of this inhibition was due to cell killing by the tumour-derived soluble material (TDS). Sixty-two percent of TDS tested contained measurable transforming-growth factor-beta (TGF-beta) activity; following acidification TGF-beta was present in all TDS. However, in neither case was this material present in sufficient amounts to account for the degree of inhibition observed. In addition, neutralisation experiments failed to demonstrate consistent relief of inhibition in the presence of excess anti-TGF-beta antisera. These results demonstrate that TGF-beta s are not the major soluble immunosuppressive materials within human breast tumours.
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PMID:Transforming growth factor-beta is not the major soluble immunosuppressor in the microenvironments of human breast tumours. 129 57

KM2210, a conjugate of estradiol and chlorambucil (CBL), which was originally developed as an anti-breast cancer agent, inhibits proliferative response of human mononuclear cells to alloantigens in mixed lymphocyte culture in a dose-dependent manner, but has no effect on their response to phytohemagglutinin. Neither estradiol benzoate nor CBL alone showed these unique actions. The suppressive effect of KM2210 on MLC was abrogated by adding of anti-transforming growth factor-beta (TGF-beta) antibody to the culture, but was not affected by the addition of interleukin-2, suggesting that KM2210, unlike CBL, displays its actions via TGF-beta. In experimental allogeneic bone marrow transplantation using mice, daily oral administration of KM2210 (2 mg/kg/day) for 30 days posttransplant significantly inhibited the alloantigen-specific immune reactions. Furthermore, the survival rate of the KM2210-treated mice was significantly higher than that of the cyclosporine-treated (2 mg/kg/day, p.o.) mice, and no adverse effect of KM2210 on hematopoietic recovery was found. These results strongly suggest possible clinical benefits of KM2210 as a new immunosuppressive agent for the prevention and treatment of graft-versus-host disease and other allospecific immune reactions.
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PMID:The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil conjugate (KM2210) and its beneficial effect on allogeneic bone marrow transplantation in mice. 138 90

Combinations of chemotherapeutic agents with recombinant interleukin-2 are currently under investigation in Phase I/II clinical trials as a possible means of improving response rates for metastatic melanoma, breast cancer, non small cell lung and head/neck carcinomas. As chemotherapy often induces marked immune suppression in vivo, the way in which these agents are combined may be of critical consideration to the therapeutic outcome. Using a rat tumour model, this study aimed to define an optimal schedule for the combined administration of doxorubicin (DOX) with interleukin-2 (IL-2). DOX (4.5 mg/kg bolus i.v.) was administered 24 hours before, during, or 24 hours after, IL-2 immunotherapy (1 x 10(5) Cetus U/rat/day for 5 days continuous i.v. infusion) to WAG rats bearing hind limb solid colonic adenocarcinoma implants. Tumour measurements taken over the 4 weeks study period revealed that there was no significant difference in tumour growth inhibition between the three schedules. Furthermore, DOX invariably caused a marked suppression in the rebound lymphoproliferation after cessation of IL-2 therapy (P less than 0.001). These results demonstrate that the therapeutic efficacy of the DOX/IL-2 combination is not influenced by the schedule for the administration of these agents within the times of administration investigated in this study.
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PMID:Influence of schedule on the therapeutic efficacy of chemoimmunotherapy with doxorubicin and interleukin-2. 152 51

We undertook a preliminary study to examine the response rate of recombinant interleukin-2 (rIL-2) in patients with advanced measurable breast cancer, in a phase II clinical trial. The regimen we utilized was designed to allow outpatient administration. A treatment cycle consisted of low-dose cyclophosphamide (350 mg/m2) given on day -3 followed by the bolus administration of rIL-2 (3.6 x 10(6) Cetus units/m2) on days 1-5, and 8-12. Toxicity was significant but acceptable. One partial remission was seen in 13 evaluable patients. In 2 additional patients clear evidence of an antitumor response was observed. The study was terminated prematurely owing to a shortage of rIL-2. Additional evaluation of rIL-2 in breast cancer appears warranted.
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PMID:Low-dose recombinant interleukin-2 and low-dose cyclophosphamide in metastatic breast cancer. 153 23

There are four classical forms of immunotherapy: active, adoptive, restorative, and passive, and perhaps a fifth form, cytomodulatory, the upregulation of tumor-associated and HLA antigens to make tumors more recognizable by the immune system. Our 5-year experience with low-dose cyclophosphamide (CY) (350 mg/m2) before low-dose interleukin-2 (IL-2) (21.6 million IU/m2/d x 5 d/wk x 2 wk per course by IV bolus) is reviewed as an example of combination chemotherapy and immunotherapy. Twenty-six percent (10 of 39 evaluable patients) of patients with melanoma had major clinical responses; one other patient (2%) has had more than 48 months of response after a 40% regression of all tumors. Median survival was 18 months for responders and 8 months for the group as a whole. Eleven of 41 patients (27%) lived at least 12 months and four (10%) lived at least 2 years. Liver metastases regressed in 4 of 10 cases, with responses in lung, adrenal, skin, and lymph nodes but no bone. Toxicity was tolerable. A correlation between cytolysis of lymphocytes against a natural killer-resistant melanoma cell line (LAK-like activity) was found, but the role of LAK cells in vivo remains uncertain. No effect was noted in 15 patients with renal cancer, but regressions of breast cancer were found in a shortened trial with 13 patients. While the necessity for CY has not been established in these studies, the regimen of CY + IL-2 as it stands appears to have some clinical efficacy in at least two cancers.
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PMID:Chemotherapy in combination with biomodulation: a 5-year experience with cyclophosphamide and interleukin-2. 155 79

The National Biotherapy Study Group (NBSG) conducted a broad phase II trial using interleukin-2 (IL-2) by continuous infusion and alpha interferon (IFN) subcutaneously in 267 patients with a variety of advanced cancers, including 29 with breast cancer, 89 with renal cancer, and 69 with melanoma. IL-2 [18 million international units (MIU)/m2] was given by continuous infusion for 108 hours with 3 mu/m2 subcutaneous IFN every other day during the IL-2 infusion. The patients were treated for 1 week followed by a 2-week rest. After two cycles of treatment, patients were evaluated for response. Of the 237 patients evaluable for response, 20 (8%) had a complete or partial response and 128 (54%) were stable. Therefore, 62% of the evaluable patients were nonprogressive during the first 90 days of IL-2/IFN therapy. The objective response rate was 11% in melanoma, 7% in renal cancer, 14% in breast cancer, and 3% in patients with a variety of malignancies for an overall response rate of 7% in these patients with advanced cancer. The patients were treated on a general medical ward and tolerated treatment well with fatigue and fever being nearly universal. Dyspnea, pruritus, chills, and elevated creatinines were frequent but less common. This combination biotherapy regimen has minimal activity in a variety of advanced cancers and must be compared with the best existing chemotherapy for each cancer type in randomized, prospective trials.
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PMID:Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group Trial. 162 72

The design of combination hormonal and immunotherapeutic protocols for breast cancer patients may be facilitated by analysis of preclinical in vitro model systems. Estrogen receptor positive (ER+: MCF-7) and negative (ER-: MDA-MB-231) human breast cancer cell lines were utilized to evaluate the effects of tamoxifen (TAM) and estradiol (E2) on modulation of breast cancer target susceptibility to lysis by lymphokine-activated killer (LAK) cells. E2-stimulated ER+ cells were more susceptible to lysis by LAK cells than corresponding TAM-treated or control cells, while treatment of ER- cells with either E2 or TAM alone did not alter from control their susceptibility to this immune-mediated lysis. All ER+ and ER- cells tested remained sensitive after treatment with TAM to lysis by LAK cells. In addition, an adenocarcinoma reactive human-mouse chimeric monoclonal antibody (ING-1) was able to significantly boost in vivo generated LAK cell-mediated lysis of control, E2-treated, and TAM-treated ER+ and ER- cells. These in vitro results provide a preclinical rationale for in vivo testing of TAM, interleukin-2 (IL-2), and breast cancer reactive antibody-dependent cellular cytotoxicity facilitating antibody in patients with refractory or high risk breast cancer.
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PMID:Influence of estradiol and tamoxifen on susceptibility of human breast cancer cell lines to lysis by lymphokine-activated killer cells. 173 46

It is known that interleukin-2 (IL-2) plays a fundamental role in the generation of immune cells capable of mediating tumor regression. Since IL-2 may be often reduced in patients with disseminated cancer, a pilot study was started to evaluate which relation exists between IL-2 levels and survival in metastatic solid neoplasms. The study included 25 patients with metastatic disease (breast cancer: 12; non-small-cell lung cancer: 13). Serum IL-2 levels were measured by radioimmunoassay on venous blood samples collected before the start of chemotherapy. Breast cancer was treated with weekly epirubicin and lung cancer with cisplatin plus etoposide. Low levels of IL-2 were seen in 10/25 patients. Irrespectively of response to therapy and of dominant metastasis sites, the mean survival time was significantly lower in patients with reduced IL-2 concentrations than in those with normal values. These results would suggest that the evidence of low IL-2 levels negatively influences the clinical course of patients with metastatic solid neoplasms.
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PMID:Lower survival in metastatic cancer patients with reduced interleukin-2 blood concentrations. Preliminary report. 199 35

It has been generally agreed that the prognosis of widely spreaded "surgically unresectable" metastatic liver tumor originated from breast cancer is very poor. We reported here the result of clinical efficacy of sequential immunotherapy with intra-tumoral injection of large dose OK-432, after oral administration of cyclophosphamide during 7-10 days, and continuous perfusion of purified human recombinant interleukin-2 (rIL-2) from hepatic artery for the breast cancer patients with unresectable metastatic liver tumors. In all of 3 cases, metastatic liver tumor revealed overwhelming tumor reduction more than 50% of preoperative total tumor burden evaluated by computed tomography. Only 1 day after operation, large doses of OK-432 was injected intratumorally, both activity of Natural Killer (NK) cells and lymphokine activated killer (LAK) cells in peripheral blood lymphocytes were 5-20 folds augmented in all clinical trials. Serum tumor markers, i.e., Carcinoembryonic Antigen (CEA) and CA15-3, were rapidly decreased in all cases, respectively. Our clinical data indicate that intratumoral injection of large dose OK-432 and continuous administration of rIL-2 via hepatic artery, pretreated with cyclophosphamide, were clinically effective immunotherapy for reduction of metastatic liver tumor.
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PMID:[Improved therapeutic effect of sequential immunotherapy with cyclophosphamide, large doses of OK-432 and recombinant interleukin-2 in breast cancer patients with disseminated metastatic liver tumors]. 201 29


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