Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interferon production ability by leukocytes in vitro from 37 patients with mammary cancer was studied. The leukocytes were derived from patients between 27 and 80 years of age, 6 months and up to 28 years after removal of the primary tumor. The interferon titer of 34/37 human breast cancer leukocytes was 2-8 times lower than that of 35 normal donor leukocytes and 3 non-neoplastic diseases. No correlation between interferon titers, the patient's age, and the histologic tumor features was observed; however, interferon production was observed to return to normal in those patients who had a long remission period or whose tumors were locally confined. Interferon response of patients under different therapy was modified: radiotherapy affected interferon production more severely than chemotherapy. A tendency for association between the skin DNCB test and interferon response was found. An inverse correlation was observed between interferon titers and the PHA-induced transformation index.
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PMID:Interferon in breast cancer. 89 86

The concept of whether immune function was related to risk of recurrence was examined in patients with operable breast cancer in whom careful clinical and pathologic staging had been performed. Patients were classified according to the risk of recurrence. The "low risk" group included patients with minimal breast cancer, noninfiltrating cancer, or infiltrating cancer less than 1 cm with negative nodes. The "high ridk" group included patients with lesions greater than 1 cm or who had greater than or equal to 4 nodal metastases or who had macrometastases at Level II or III (apex). In the "intermediate risk" group were patients with infiltrating cancer less than 1 cm or with less than 4 nodal metastases at I only. Immune reactivity was assessed by skin tests, by measurement of absolute lymphocyte count, T and B cells, lymphocyte stimulation by mitogens and a battery of common antigens, serum immunoglobulins and complement levels. There were 134 patients with operable breast cancer and 63 patients with benign breast lesions. The breast cancer patients showed minimal or no impairment of DNCB skin test. Only patients with nodal metastases showed a slight but not significant impairment of DNCB responses (80% were DNCB positive compared to 90% in the controls.) The lymphocyte responses to mitogens were normal in the breast cancer patients, but there was a significant depression of lymphocyte responses to certain recall antigens such as Candida albicans and E coli. The absolute lymphocyte count and the T cell counts were normal, but B cells bearing complement receptors were decreased and B cells bearing sufface immunoglobulins were increased in the breast cancer patients. Analysis of immune function according to the pathologic stage of disease "risk of recurrence" categories showed no correlation with skin tests or lymphocyte levels. A striking and paradoxical finding was the demonstration that patients with "low risk" cancer overall had markedly lower responses to the battery of stimulating mitogens and antigens than found in patients with "high risk" or "intermediate risk" disease. Only the lymphocyte responses to PHA showed a significant linear correlation with increasing pathologic stage or "risk of recurrence." Current evidence from this study suggests that PHA response is markedly influenced by the primary tumor burdenand thus indirectly reflects the risk of recurrence.
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PMID:Immunobiology of operable breast cancer: an assessment of biologic risk by immunoparameters. 96 94

Previously we reported the antitumor activity of 4 kinds of Chinese herbs: A. capillaris, S. doederleinii, A. macrocephala and S. subprostrata. Evidence has been also presented that A. capillaris shows the activity mainly through a direct tumoricidal action and the others display the activity through the enhancement of tumor-immune response. The present results are as follows: A. capillaris did not affect Meth A tumor-neutralizing activity (Winn's assay) in spleen cells of BALB/c mice bearing the primary tumor. The other herbs enhanced the activity on days 10 and 15 and prevented the decay of the activity on day 20 after the Meth A tumor transplantation. However, none of them enhanced the local graft versus host reaction (GvHR) induced in CBF1 mice by spleen cells of BALB/c mice. A. capillaris hardly affected the humoral antibody formation against sheep red blood cells in mice. On the contrary, the other 3 herbs enhanced the formation. Blast transformation of murine lymphocytes with PHA-P or LPS was suppressed by 10(-5) to 10(-4) g/ml of A. capillaris. A. macrocephala enhanced the response by LPS. It should be noted that A. capillaris showed no immunosuppressive action in spite of having a direct tumoricidal action in vitro. Further investigations will be required on the latter 3 herbs to clarify the relationship between their humoral immunity-stimulating activity and their tumor immunity-enhancing activity.
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PMID:Mechanisms of antitumor activity of aqueous extracts from Chinese herbs: their immunopharmacological properties. 274 43

Human neuroblastoma is an immunogenic tumor for which therapy directed in an immunologic context may offer some advantage over conventional treatment. This study examines the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model. In vivo studies of primary tumor growth characteristics after treatment demonstrated no superiority of either therapeutic modality in control of local tumor or prolongation of host survival. However, irradiated hosts showed an increased ability to reject a secondary tumor challenge, compared to their surgical counterparts. That this phenomenon may be immune-related is suggested by in vitro studies of T lymphocyte function utilizing mixed lymphocyte-tumor cell cultures and PHA lymphoblastogenesis.
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PMID:Selection of optimal therapy for neuroblastoma: a study of the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model. 294 17

We studied the configuration and expression of the gene encoding the beta chain of the T cell receptor (TCR beta) in cell lines and primary tumor cells infected by the human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I). Most of the cell lines and all the primary tumor cells showed rearrangement of the TCR beta gene, and in each case the rearrangement was distinct. The majority of cases examined were clonal with respect to a particular TCR beta gene rearrangement. Primary tumor cells from one case (SD) were found to have a tandem duplication of a portion of chromosome 7; this appears to have resulted in the presence of three alleles of the TCR beta gene, each of which is arranged differently. This suggests that the chromosomal abnormality, and possibly infection by HTLV-I, occurred before TCR beta gene rearrangement. Cell lines infected by HTLV-I express levels of TCR beta mRNA similar to PHA stimulated lymphocytes, suggesting that this gene is not transcriptionally activated as a result of infection by HTLV-I. Cloned T cells of known antigen specificity that are infected by HTLV-I in vitro show impairment of immune function, including loss of antigen-specific responsiveness and the acquisition of alloreactivity. Comparison of the configuration of the TCR beta gene before and after infection revealed no changes detectable by Southern blot analysis. Levels of expression of the TCR beta gene at the mRNA level and surface expression of the T3 complex were also not significantly altered, suggesting that changes in immune function cannot be attributed to quantitative changes in the TCR molecule. The configuration of the TCR beta gene in primary tumor cells infected by HTLV-I was compared with that in the derived cell lines. In all pairs examined, the configuration in the primary tumor cells was different from that in the cell lines, strongly suggesting that the cells that grow in culture are not the original neoplastic cells.
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PMID:Configuration and expression of the T cell receptor beta chain gene in human T-lymphotrophic virus I-infected cells. 300 26

The proliferative response of peripheral blood mononuclear cells (PBMC) to the mitogens PHA and Con A significantly depressed in 86% of 45 head and neck cancer patients compared with 44 normal controls. This depression of immune competence was greatest in older patients and in those with more advanced disease stages. The abnormal mitogen responses could be restored toward normal (especially with Con A stimulation) by incubating the cells with either of two prostaglandin synthetase inhibitors (indomethacin or RO-205720). This augmentation of immune response was independent of other factors, including the primary tumor site, disease stage, treatment (surgery, radiation therapy, or chemotherapy) or the patients's age or race. The most likely explanation for this depressed level of immunocompetence was an excessive production of PGE2 by suppressor cells. This was confirmed by the finding that PBMC from patients produced more PGE2 than PBMC from normal individuals (8.4 ng/ml vs. 5.2 ng/ml, p=0.002). This difference was greatest among patients less than 60 years of age whose cultured PBMC produced 91% more PGE2 than controls (p less than 0.0007). Virtually all of the PGE2 was produced by a population of monocytes defined by a monoclonal antibody and purified with a fluorescence-activated cell sorter. Patients with epidermoid cancer of the head and neck thus have an abnormality of immunoregulatory monocytes that can contribute significantly to their depression of cellular immunity by elaborating prostaglandin E2. This abnormality could be partially corrected in vitro by incubating their PMBC with a prostaglandin synthetase inhibitor.
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PMID:Excessive prostaglandin E2 production by suppressor monocytes in head and neck cancer patients. 621 63

Comprehensive immune function by integrated score was assessed in 158 operable, 55 inoperable, and 52 metastatic breast cancer patients relative to 107 healthy controls. The score was derived from in vivo response to PPD and DNCB and in vitro lymphocyte stimulation by PPD and PHA. Proportion of E-RFC was significantly lower in patients than in controls but was not found to correlate directly with the above functional criteria. Fifty-one percent of the patients with early, operable tumors were shown to be at least partially immunosuppressed by integrated score achievement vs. 11% of controls. This proportion rises to 68% of inoperable and 89% of metastatic patients. Quantitative analysis by graded response revealed an additional, significant degree of immune impairment in the respective patient groups by all testing parameters. Depression of immune function in operable patients was not related to age nor influenced by surgery. Immunocompetence of patients with mammary dysplasia did not differ from controls. Increasing size of primary tumor (T) was not found to be matched by progressive degree of immunosuppression, excepting that associated with large T4 tumors. Patients with lymph node involvement (N+) were not significantly immunologically inferior to those without (N0) where the larger operable T2-3) tumors are concerned. In the smallest, T1 tumors, nodal involvement (N+) is accompanied by remarkable immunosuppression relative to T1N0 cases. This finding suggests a pre-existing immune defect inherent in T1N+ patients. It supports the hypothesis that the immunosuppression associated with early breast cancer is primary, patient related. Secondary tumor-induced depression of immune response characterizes advanced and metastatic human breast cancer.
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PMID:Immunocompetence, immunosuppression, and human breast cancer. II. Further evidence of initial immune impairment by integrated assessment effect of nodal involvement (N) and of primary tumor size (T). 737 Sep 52

Interleukin-12 (IL-12) is a heterodimeric cytokine originally defined by its ability to induce the maturation of cytolytic lymphocytes and by its capacity to effectively synergize with IL-2 in the induction of cytolytic activity. Recent studies in mice have demonstrated the ability of IL-12 to cause tumor regression and stimulate long-term antitumor immunity in treated animals. To examine the antitumor effect of direct gene transfer of IL-12 into tumors, we have developed retroviral vectors that coordinately express both subunits of IL-12. An MFG-based retroviral vector was used to generate a recombinant retrovirus in which a long terminal repeat (LTR)-driven polycistronic transcript encodes both subunits of human IL-12: hp35 and hp40 cDNAs are linked and coexpressed using the internal ribosome entry site (IRES) from the encephalomyocarditis virus (DFG-hIL-12). In addition, two IRES sequences were used to express both subunits of IL-12 and a neomycin resistance (neoR) selectable marker gene from the same polycistronic message (TFG-hIL-12). The amphotropic DFG-hIL-12 and TFG-hIL-12 viruses were used to infect both human and murine cell lines as well as primary tumor cultures. The production of human IL-12 by the nonselected, infected cells was measured in both a PHA blast proliferation bioassay and an ELISA and ranged from 15 to 40 ng/10(6) cells per 24 hr. Following G418 selection of TFG-hIL-12-infected cells, the level of expression of IL-12 was significantly higher (up to 120 ng/10(6) cells per 24 hr). The IL-12 protein secreted by the infected cells exhibited all of the biologic activities of recombinant hIL-12: proliferation of activated natural killer (NK) and T cells, stimulation of interferon-gamma (IFN-gamma) induction by NK and T cells, and enhancement of lymphokine-activated killer (LAK) activity. These retroviral vectors expressing human IL-12 should be useful in evaluating the biological properties of IL-12 as well as for use in clinical trials for gene therapy of patients with cancer.
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PMID:Construction and characterization of retroviral vectors expressing biologically active human interleukin-12. 771 Nov 42

Cancer cells frequently exhibit defects in apoptosis, which contribute to increased survival and chemotherapeutic resistance. For example, genetic mutations or abnormal proteasomal degradation can reduce expression of Bax which limits apoptosis. In cancers where abnormal proteasomal degradation of Bax occurs, we hypothesized that Bax peptides that bind to human leukocyte antigen (HLA) class I molecules would be generated for presentation to CD8(+) T cells. To test this hypothesis, we generated T cells against pooled Bax peptides, using the blood of healthy human donors. Although T-cell responses were of low frequency (0.15%), a CD8(+) T-cell clone (KSIVB17) was isolated that optimally recognized Bax(136-144) peptide (IMGWTLDFL) presented by HLA-A*0201. KSIVB17 was able to recognize and kill a variety of HLA-matched cancer cells including primary tumor cells from chronic lymphocytic leukemia (CLL). No reactivity was seen against HLA-matched, nontransformed cells such as PHA blasts and skin fibroblasts. Furthermore, KSIVB17 reactivity corresponded with the proteasomal degradation patterns of Bax protein observed in cancer cells. Taken together, our findings suggest a new concept for tumor antigens based on regulatory proteins that are ubiquitously expressed in normal cells, but that have abnormally enhanced degradation in cancer cells. Bax degradation products offer candidate immune antigens in cancers such as CLL in which increased Bax degradation correlates with poor clinical prognosis.
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PMID:A novel tumor antigen derived from enhanced degradation of bax protein in human cancers. 2169 78