Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suspensions of fresh tumor-infiltrating lymphocytes (TIL) were prepared from 30 human breast ductal adenocarcinomas. To evaluate the phenotypic pattern of the isolated TIL, lymphocyte surface markers including CD19, CD3, CD4, CD8, CD16 and HLA-DR were examined by flow cytometry. Lymphocyte recovery ranged from 1.1% to 44%, independent of tumor size. TIL most often scored high for CD3+ with a varying number of CD4+ and CD8+ cells. Three samples out of 30 expressed up to 44% of CD19+ B cells, while CD3-CD16+ NK cells were rare. CD4 and CD8 expression was significantly different between the lymph node metastases group and the lymph node negative group (p < 0.01). 67% of the TIL with a CD4/CD8 ratio greater than 1 showed lymph node metastases. Furthermore, the CD4 expression of TIL and CD4/CD8 ratio correlated with tumor size (p < 0.01), but not with tumor differentiation and hormone receptor expression. Although there was considerable diversity of TIL among breast tumors, our data suggest that a high expression of CD4+ T cells may imply progression of the tumor, and an increased CD4/CD8 ratio of the TIL isolated from human breast adenocarcinoma may indicate development of metastases.
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PMID:Phenotypic analysis of tumor-infiltrating lymphocytes from human breast cancer. 133 79

HIV-1-related neurological diseases, excluding opportunistic infections and HIV encephalitis, are considered here. Most occur in severely immunosuppressed patients, with CD4 counts of under 200 x 10(6) l-1. Primary brain lymphoma and metastases from systemic non-Hodgkin's lymphoma, the second commonest cause of cerebral mass lesions in AIDS, are usually aggressive B cell tumours. Their poor median survival after treatment, compared with that of lymphomas in non-AIDS patients, seems related to systemic complications, particularly opportunistic infections. Kaposi's sarcoma produces neurological symptoms exceptionally. Cerebral infarction is often unrecognized clinically but large vessel arteritic occlusions may occur. Intracranial haemorrhages occur mostly in thrombocytopenic patients. Seizures are frequently referred to the neurologist; investigation may lead to a diagnosis of AIDS. Nearly 50% of patients with seizures have cerebral toxoplasmosis or cryptococcal meningitis; HIV-1 encephalitis is presumed to be the cause in 30%. A subacute or chronic vacuolar myelopathy with pyramidal and posterior column signs is the commonest form of spinal cord involvement in AIDS; its cause remains unknown. Peripheral nerve syndromes occur at all stages of HIV-1 infection. Distal symmetrical peripheral neuropathies are the most frequent, particularly a painful form with axonal atrophy, associated with CMV infection, and seen during ARC or AIDS. Mononeuritis multiplex due to vasculitis, CMV, or lymphoma and a serious lumbosacral polyradiculopathy due to CMV are infrequent. The commonest myopathy is due to zidovudine (AZT); it usually responds to drug withdrawal. The nature, prognosis and optimal management of most other myopathies is yet to be determined.
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PMID:Other neurological diseases in HIV-1 infection: clinical aspects. 134 49

The systemic administration of human rIL-6 to mice resulted in the regression of established, 3-day pulmonary micrometastases from two weakly immunogenic tumors, but not from a nonimmunogenic tumor, in the absence of observable toxicity. Although IL-6 alone failed to have a significant therapeutic impact on advanced, 10-day pulmonary macrometastases from weakly immunogenic tumors, substantial cure rates of mice could be achieved when this cytokine was combined with cyclophosphamide. Histologic analysis of the lungs of mice receiving IL-6 revealed infiltration with lymphoid cells during the regression of pulmonary nodules from a weakly immunogenic tumor. IL-6-mediated tumor regression could be abrogated after selective in vivo depletion of either CD4 or CD8 T cell subsets by the systemic administration of specific mAb. In vivo generation of tumor-specific CTL, but not of lymphokine-activated killer cells, was detected in the lungs of IL-6-treated mice during regression of pulmonary metastases. Collectively, these findings demonstrate a role for IL-6 in the treatment of established solid tumors that have the capacity to elicit T cell responses in the host. Differences in host cellular mechanisms involved in tumor regression mediated by immunotherapy using IL-6 vs IL-2 are discussed.
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PMID:Cellular mechanisms of the antitumor activity of recombinant IL-6 in mice. 134 21

Thymomas are cytologically benign epithelial neoplasms of the thymus gland. They compose 10% of mediastinal tumors, and are most common in the anterosuperior compartment. Seven to 36% of thymomas are malignant, as determined by tissue invasion, yet they metastasize in less than 3% of cases. Distinguishing lymphoma from lymphocyte-predominant thymoma is imprecise due to their histologic similarities. We present a 45-year-old man with intracranial metastatic thymoma. The lesion was interpreted radiographically as meningioma, and as possible lymphoma by frozen section. Flow cytometry proved this neoplasma to be a metastatic thymoma. Sixteen monoclonal antibodies were used to immunophenotype the CD45+ component of this tumor. Coexpression of CD4 and CD8 along with CD1 demonstrated lymphocytes of late cortical thymocyte origin; a second component was cytokeratin positive. This is the first reported case of extrathoracic metastases of thymoma diagnosed using flow cytometry. We propose this method as an invaluable technique to diagnose these histologically difficult neoplasms.
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PMID:Diagnosis of metastatic thymoma using flow cytometry. 137 81

Tumor infiltrating lymphocytes (TIL) play an important role in the host immune response to cancer. When these cells are reinfused into cancer patients after in vitro expansion with lymphokines such as interleukin 2 (rIL-2), they often induce regression of tumor metastases. We obtained TIL of enzymatic digestion of 7 human solid tumors and then cultured them with rIL-2 and interleukin 4 (IL-4) at different concentrations for about 36 days. Immunophenotypic analysis was performed at the end of the second and fourth week; cytotoxic activity against autologous and heterologous targets was assessed on the 30th day of culture. The best lymphocytic growth was observed when we used rIL-2 and IL-4 for the first two weeks of culturing and then continued with rIL-2 alone. CD3 and CD56 cells formed the majority of TIL in all cultures. In 4 cases CD4 cells predominated at the initial stage of culturing, with CD8 cells gradually increasing and finally inverting the CD4/CD8 ratio. Autologous cytotoxicity (3/4 cases) appeared to be better in those patients in whom the CD4/CD8 ratio was inverted. These data enable identification of the combination of lymphokines that will will best provide expansion of live TIL active against tumoral cells. This procedure must be followed before in vivo reinfusion of expanded lymphocytes is carried out.
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PMID:[Analysis of growth, phenotype and cytotoxic activity of tumor infiltrating lymphocytes expanded in vitro with interleukin-2 and interleukin-4: preliminary results]. 138 39

T-lymphocyte subsets (CD4/CD8 antigen positive cells) were determined in peripheral lymphocytes from 48 patients with breast cancer of different stages by flow immunocytometry with the aid of anti-CD4 and CD8 monoclonal antibodies. A broad individual variability of the CD4/CD8 ratio among both healthy donors and breast cancer patients was observed. The average value of CD4/CD8 ratio decreased in groups as follows: Healthy donors and Stage I patients, Stage IIA, IIB and Stage IV breast cancer patients. These differences were generally statistically not significant. The difference between healthy donors and Stage IV breast cancer patients was statistically significant (p < 0.01), if one exceedingly elevated value of the CD4/CD8 ratio was excluded from statistical evaluation. The average CD4/CD8 value in the group of breast cancer patients with lymph node or distant metastases was lower than that of patients without metastases, but their difference was not statistically significant either.
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PMID:T-lymphocyte subsets (CD4/CD8 ratio) in breast cancer patients. 143 31

Between January, 1990 and May, 1991, we administered LAK immunotherapy using the intralymphatic route to 25 patients with metastatic cancer resistant to conventional therapies. In the preparation of the immunotherapy, we followed the technique described by Pizza G. et al. The age of our patients ranged between 50 and 75 years and their Karnofsky's indexes were above 70%. The histological type of the metastasis were determined by Rx, ECO and/or CAT before and after the administration of the immunotherapy. In the intralymphatic administration, we followed the technique described by Pizza G. et al. The immunological therapy was administered on days 1, 21, 90 and 111 and the clinical response was assessed by RC, RP, EE and F. The immunological behaviour of the host was assessed through the determination of lymphoid populations (CD2, CD4, CD5 and CD8) and cytolytic cells were studied with monoclonal antibodies CD and CD16. Such immunological study was carried out before the administration of each immunotherapy series. In 7 out of 25 patients (28%), we were able to administer the four LAK series. Such patients were subsequently studied, observing that, although tumoral lesions did not increase in size, they did not disappear and, thus, they were classified as clinically stable. Clinical and analytical toxicity was null. The immunological study did not show any statistically significant changes and the activity of cytotoxic cells (NK) was not modified.
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PMID:[Intralymphatic administration of adoptive (LAK) immunotherapy in the treatment of patients with metastatic cancer resistant to conventional therapies]. 150 2

We developed a syngeneic mouse IgG2a monoclonal antibody (MAb) A9D41 directed against the Friend leukemia virus envelope gp70 antigen present on the cell surface membranes of virus producer 3C18 Friend leukemia cells (FLC). A9D41 showed a marked antitumor activity in DBA/2 mice given injections of gp70 positive 3C18 FLC, but it was ineffective in mice given injections of gp70 negative 745 FLC or unrelated tumor cells. A9D41 was particularly effective in inhibiting the development of 3C18 FLC liver and spleen metastases. MAb was also effective as adjuvant therapy in inhibiting visceral metastases after excision of an established s.c. FLC tumor, and combined therapy of A9D41 with mouse interferon alpha/beta was more effective than MAb or interferon alpha/beta alone. The immune system of the host played a decisive role in the antimetastatic action of A9D41. Thus, although MAb was cytotoxic for 3C18 FLC in vitro in the presence of rabbit complement, the F(ab')2 fragment was ineffective in vivo, and the antitumor effect of MAb was abolished in mice treated with an antibody to CD4 and diminished in natural killer cell-deficient beige and athymic nude mice. MAb-treated mice surviving injection of FLC developed an immune response to 3C18 FLC.
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PMID:Inhibition of Friend leukemia cell visceral metastases by a new monoclonal antibody and role of the immune system of the host in its action. 158 3

Peritumoral injection of recombinant human interleukin 1 beta (IL-1 beta) in mice transplanted subcutaneously with Friend erythroleukemia cells (FLC) resulted in a marked increase in survival time and inhibition of metastatic tumor growth in liver and spleen. In contract, IL-2 treatment alone did not significantly inhibit the development of FLC metastases. A synergistic antitumor effect was observed after combined IL-1/IL-2 therapy of these mice. The antitumor action of IL-1/IL-2 treatment was abolished or markedly reduced in mice treated with antibodies to CD4 or CD8 antigens, whereas antibodies to asialo-GM1 were ineffective. A clear-cut increase in the percentage of CD4+ cells was observed in the spleens of cytokine-treated mice on days 17 and 23. On day 23 of cytokine therapy, CD8+ cells were increased in both spleens and lymph nodes. On day 17, infiltrates of host-reactive cells (i.e., lymphocytes, granulocytes, and monocytes) were observed in both spleen and liver from FLC-injected mice treated with IL-1/IL-2, in association with tumor cells. On days 17 and 23, spleen cells and cells recovered from mesenteric lymph nodes of IL-1/IL-2-treated mice exerted a potent antitumor effect as determined by Winn assay experiments. This antitumor activity was abolished by preincubation of spleen cells with anti-CD8 antibody, but not by treatment with antibodies to asialo-GM1; antibodies to CD4 exerted only a slight effect. Combined IL-1/IL-2 therapy was more effective on established (i.e., 6-7-d) FLC tumors than on early (i.e., 1-d) tumor-transplanted mice. IL-1/IL-2 treatments were also highly effective in increasing survival time of mice from which the subcutaneous primary tumors were excised 7 d after FLC injection. These data indicate that in mice injected with FLC, the antitumor effects of IL-1/IL-2 are mediated by CD4+ and CD8+ cells (but not NK cells), and suggest that this combined cytokine treatment may be effective against established metastatic tumors.
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PMID:Combined interleukin 1/interleukin 2 therapy of mice injected with highly metastatic Friend leukemia cells: host antitumor mechanisms and marked effects on established metastases. 167 Oct 80

We have previously demonstrated that interferon (IFN) treatment of mice bearing the spontaneously metastasizing B16F10L murine melanoma on days -5 to -1 prior to surgical removal (day 0) of the primary tumor resulted in survival of greater than 50% of treated mice. The antitumor effect was correlated with an early increase of natural killer (NK) cell cytotoxicity followed by a later developing specific cytolytic T-cell response. The purpose of this study was to establish definitively the roles of NK, CD4, and CD8 cells as mediators of the antitumor/antimetastatic effects of IFN treatment by administration of anti-asialo-GM1, anti-L3T4, and/or anti-Lyt-2 antisera. Depletion of NK cells, alone or in combination with T-cells, eliminated the protective effect of IFN treatment. Depletion of both CD4 and CD8 cells, however, did not significantly alter the therapeutic effect of IFN therapy. Collectively, these data conclusively demonstrated the importance of NK cells as mediators of the IFN induced antitumor state. However, in mice depleted of CD4 cells alone, the protective effect of IFN was eliminated, in spite of the presence of intact NK cells. In vitro analysis of NK cytotoxicity on day 1 after surgery demonstrated (a) a lack of IFN induced stimulation of NK activity in CD4 depleted mice and (b) a significant increase in both baseline and IFN induced NK cytotoxicity in CD8 depleted mice. These data suggested a CD8 cell mediated inhibition of NK activity/stimulation in CD4 depleted mice, possibly responsible for the lack of response to IFN therapy in that group. These results demonstrate the importance of not only individual components of the immune system but also the interaction of these components in both the natural and IFN induced control of spontaneous B16F10L metastases.
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PMID:Role of natural killer and T-cells in interferon induced inhibition of spontaneous metastases of the B16F10L murine melanoma. 170 66


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