Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular immune responses to ovarian cancer patients treated with viral oncolysates (VO) ovarian tumor vaccines to vaccines are described. CD3+ cells proliferated after stimulation with the tumor vaccines in a dose-dependent manner. The proliferation of CD3+ cells stimulated with the tumor vaccine was blocked by anti-HLA-DR monoclonal antibody and anti-CD4 mAb indicating that CD3+ CD4+ cells from the blood of the patients treated with VO recognize tumor derived determinants in conjunction with MHC class II antigens. The regulatory activity of the T cells collected after VO treatment was assayed by co-cultivation with PBMC collected before VO treatment. These cells demonstrated increased helper activity for immunoglobin production by cells collected before vaccination and secreted IL-2 in response to stimulation by vaccine. Finally, when biochemical fractionation of the components of VO was attempted, PBMC from VO treated patients responded by proliferation to several fractions suggesting that they recognize multiple epitopes in the ovarian tumor vaccine. Therefore, these data provide novel evidence for the involvement of the T cells in response to ovarian tumor vaccines.
 ...
PMID:T cell responses to ovarian tumor vaccines: identification and significance for future immunotherapy. 168 43

We studied lung and blood lymphocytes from 12 asymptomatic patients with peripheral bronchogenic carcinoma. Bronchoalveolar lavage was performed in the lung segment with tumor and a contralateral uninvolved lung segment and analyzed separately. After partial removal of macrophages by plastic adherence, cells were labeled with markers for CD4 and CD8 and analyzed by flow cytometric analysis. We found no significant difference in the percentages of mononuclear cells in either immune subset when comparing the lung containing tumor with the uninvolved lung. We did find, however, a depressed CD4/CD8 ratio in the peripheral blood. We conclude that a lung carcinoma does not change the local immunologic milieu of the lung parenchyma containing the carcinoma. It is not clear if the immunologic findings in the lungs and blood are due to the bronchogenic carcinoma, smoking, or the underlying chronic obstructive pulmonary disease.
 ...
PMID:Regional and systemic CD4 and CD8 subsets in bronchogenic carcinoma. 168 75

Acquired cell-mediated immunity to intracellular parasites like mycobacteria is dependent on antigen-specific T lymphocytes. We have recently found that mycobacteria not only induce helper T cells but also cytotoxic CD4+ and/or CD8+ T cells as well as nonspecific killer cells that lyse human macrophages in vitro. In addition, we have described that the recombinant heat-shock protein (hsp) 65 of Mycobacterium bovis BCG/M, tuberculosis is an important target antigen for CD4+CD8- cytotoxic T cells. We have now further investigated the cytotoxic effector cells that are induced by the hsp65 of BCG. Purified protein derivative of tuberculin (PPD)- or hsp65-specific cytotoxic T cells specifically lysed PPD, hsp65 of BCG and hsp65 of M. leprae-pulsed macrophages in an HLA-DR-restricted manner. Nonpulsed macrophages were lysed to a much lower but still significant extent. hsp65-induced effector cells expressed CD3, CD5, CD4, CD8 and CD56 markers. Depletion experiments showed that the antigen-specific HLA-DR-restricted killer cell was of the CD5+CD4+CD8-CD56- phenotype. Experiments using N-terminal truncated hsp65 fusion (cro-lacZ) proteins suggested that the N-terminal 65 amino acid residues of the 540 amino acid molecule are critical for the expression of the cytotoxic target epitope(s) in two individuals tested. In addition to inducing antigen-specific cytotoxic effector cells, the hsp65 also triggered nonspecific nonrestricted effector cells with lytic activity against nonpulsed autologous or allogeneic macrophages as well as K-562 and Daudi tumor cells. hsp65-stimulated effector cells produced both interferon and tumor necrosis factor-alpha. An important finding was that hsp65-stimulated effector cells strongly inhibited colony-forming unit formation from live BCG-infected autologous macrophages.
 ...
PMID:Induction of antigen-specific CD4+ HLA-DR-restricted cytotoxic T lymphocytes as well as nonspecific nonrestricted killer cells by the recombinant mycobacterial 65-kDa heat-shock protein. 169 Jan 36

Eighteen patients with disseminated AIDS-related Kaposi's sarcoma (KS) and compromised bone marrow function were treated with a relatively non-myelosuppressive regimen of bleomycin and vincristine (BV). At study entry, the patients presented with the following median laboratory values: hemoglobin of 9.5 g/dl, granulocyte counts of 1,173/mm3, platelet counts of 218,000/mm3, and CD4 lymphocyte counts of 58/mm3. All patients had extensive Kaposi's sarcoma. Nine patients had visceral involvement: four with pulmonary involvement, two with gastrointestinal involvement, and three with both. Following a median number of seven cycles of biweekly chemotherapy, complete or partial tumor responses were achieved in 13 patients (72%). Two patients experienced bleomycin-induced skin toxicities, whereas 10 others (55%) experienced peripheral sensory neuropathy requiring vincristine dose reductions. Opportunistic infections had occurred in 11 patients prior to initiation of chemotherapy and in 16 after initiation of chemotherapy. Despite the frequent development of opportunistic infections, BV chemotherapy was relatively well tolerated and resulted in a high response rate in this patient population that presented with suboptimal marrow function and extremely low CD4 lymphocyte counts.
 ...
PMID:Treatment of advanced Kaposi's sarcoma using a combination of bleomycin and vincristine. 169 66

The tumor-infiltrating lymphocytes (TILs) were cultured with interleukin 2 (IL-2) to induce the activated killer cells possessing autologous tumor-killing activity, and analysed their cell surface phenotypes and assessed anti-tumor killing activity. Furthermore, the activated TILs were transferred into 7 patients adoptively resulting in complete remission in a patient with pancreatic cancer and partial remission in another patient with gastric cancer. The cytotoxic activities of activated TILs at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 25 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. The negative selection method, indicated that the killer cells recognizing autologous tumor cells consisted of CD4- or CD8-positive T lymphocytes and CD16- or CD56-positive natural killer cells. The activated TILs could not only lyse cultured tumor cell lines, but also autologous tumor cells.
 ...
PMID:Functional and phenotypic analyses of interleukin 2-activated tumor-infiltrating lymphocytes. 169 23

Peripheral blood monocytes (PBM) can selectively lyse malignant or virus-infected cells. We investigated the effects of target cell infection with HIV-1 on PBM cytolytic function. Cytokine-activated PBM lysed uninfected, HSV-1-infected or vaccinia virus-infected tumor cells, but did not lyse the same cell lines when infected with the human immunodeficiency virus type 1 (HIV-1). HIV did not impair PBM viability, and actinomycin D (Act D) pretreatment of HIV-infected target cells restored their susceptibility to PBM-mediated lysis. Either antibody to CD4 (Leu3a) or a recombinant vaccinia virus that induces expression of the HIV envelope protein, also inhibited target cell lysis by PBM. These studies indicate that CD4 can function as a mediator of PBM cytolytic function, and that target cell expression of the HIV-1 envelope protein may inhibit monocyte-mediated antitumor responses.
 ...
PMID:Monocyte-mediated lysis of HIV-infected tumor cells. 169 72

Guanine ribonucleosides, substituted at the C8 position with either a bromine or a thiol group, have recently been shown to regulate several immunologic responses. We have previously shown that 8-mercaptoguanosine (8MG) can replace the requirement for cytokines in the generation of MHC-restricted CTL. In this paper, we examined the ability of 8MG to induce MHC-nonrestricted killer cells. We found that 8MG did not induce significant lytic activity from normal resting lymphocytes. However, 8MG was able to synergize with minimal amounts of IL-2 in inducing lytic activity similar to lymphokine-activated killers (LAK) in that both NK-sensitive and NK-resistant tumor cells were killed. Both the precursors and effectors of 8MG-LAK activity were similar to NK cells and were CD4- CD8- asialo-GM1+ NK1.1+. Similar to IL-2-induced LAK, 8MG-LAK were B220+. 8MG appeared to "stage" these precursor lymphocytes to become more responsive to IL-2 because optimal induction of 8MG-LAK required preincubation with 8MG before the addition of IL-2. This "staging" appeared to be due to the release of a "second signal" since it was readily inhibited by cyclosporine A. Anti-IFN-alpha beta was as efficient as cyclosporine A in inhibiting 8MG-LAK generation, whereas anti-IFN-gamma and anti-IL-1 did not exhibit significant inhibition. These findings suggest that 8MG can be of possible utility as an IL-2-sparing agent in LAK generation from NK cells.
 ...
PMID:Lymphokine-activated killer (LAK) cells. V. 8-Mercaptoguanosine as an IL-2-sparing agent in LAK generation. 170 14

The chimeric mouse MHC class I gene derived from a recombinant H-2Kb gene, in which the coding region for a large part of alpha 1 and alpha 2 extracellular domains was replaced with a partial avian erythroblastosis virus erbB gene segment encoding the kinase domain, was successfully introduced into a mouse mastocytoma line P1.HTR (H-2d) and transcribed to mRNA. The transfectant cells expressed the chimeric gene product, which was reactive to a phosphotyrosine-specific antibody. When the chimeric gene transfectant was inoculated into CDF1(H-2d) or BDF1(H-2d/b) mice, it grew at an early time but regressed thereafter. Transfectant-specific as well as parental P1.HTR-specific antibody activities were demonstrated in the sera of these mice. Transfectant-specific cytotoxic T lymphocytes (CTL) were generated in the antigen-sensitized culture of spleen cells from the transfectant-immune mice. The CTL-mediated lysis of target chimeric gene transfectant cells was poorly inhibited by anti-H-2d antiserum, which blocked the lysis of parental P1.HTR cells by anti-tumor CTL developed in parallel. The former was, however, inhibited by either anti-transfectant antiserum or anti-phosphotyrosine antibody, which was ineffective for blocking the latter. Target cell lysis by either anti-transfectant or anti-tumor CTL was blocked by anti-CD8 monoclonal antibody but not by anti-CD4 antibody. It was suggested from these results that the H-2K-erbB hybrid gene product, which lacks complete three-domain class I structure, was recognized by CTL in a manner that was endogenous H-2 class I-independent but CD8-dependent.
 ...
PMID:Cytotoxic T lymphocyte recognition of the H-2-erbB hybrid gene product lacking the complete H-2 domain structure. 170 75

Sixty-three cases of Hodgkin's disease in intravenous drug users (IVDUs) have been collected by the Italian Cooperative Group on AIDS-Related Tumors (GICAT). In most patients (74%) the histological pattern was that of mixed cellularity and lymphocyte depletion. In 39% of patients the initial symptom was a persistent lymph node enlargement due to persistent generalized lymphadenopathy (PGL). Unusual presentations included Waldeyer's ring, skin, meninges, colon, and pleura. After MOPP alternated or followed by ABVD, MOPP alone, or ABVD alone, 15 of 32 patients (47%) had a complete remission (CR) and 15 of 32 (47%) had a partial remission (PR). The median duration of CR was 14 months, while the median survival of patients with CR has not been reached; the median survival of patients treated with chemotherapy who had CD4 levels at presentation greater than or equal to 400/mm3 was significantly superior to that of those who had CD4 less than 400/mm3. The overall median survival was only 14 months. Forty-four percent of patients receiving chemotherapy, with or without radiotherapy, developed opportunistic as well as nonopportunistic infections. Lethal hepatic toxicity was observed in one patient. Among IVDUs, unusual presentations of Hodgkin's disease occurred at a lower rate than was previously reported for homosexuals. Complete remissions could be achieved in almost half the patients, but non opportunistic infections, in addition to parenchymal function impairment due to drug abuse, may limit treatment administration in IVDUs.
 ...
PMID:Hodgkin's disease in 63 intravenous drug users infected with human immunodeficiency virus. Gruppo Italiano Cooperativo AIDS & Tumori (GICAT). 171 Sep 20

We have developed a culture system for "long-term" growth of human lymphokine-activated killer (LAK) cells exhibiting an elevated, wide-spectrum anti-tumor cytotoxicity. The system allows the exponential growth of monocyte- and B-lymphocyte-depleted CD4-CD8- lymphocytes in the presence of human AB serum and recombinant human interleukin-2 (IL-2) (2 x 10(2) U/ml) combined with interleukin (IL-1) beta (50 ng/ml). After 21 days in culture, these cells undergo massive amplification (i.e., the cell yield rises up to 30-120 times the starting values), and exhibit a marked anti-tumor cytotoxic activity against a panel of natural killer (NK)-resistant tumor cell lines. Interestingly, this activity correlates with the high level of perforin RNA. The membrane phenotypes of the final cell population, assessed by a panel of monoclonal antibodies (MoAbs) indicate a mixed population comprising two cell types in variable proportions (i) NKH-1+, T cell receptor (TCR) alpha/beta-, TCR gamma/delta-, CD3-, Leu 23+; (ii) NKH-(+), TCR alpha/beta-, TCR gamma/delta+, CD3+, Leu 23+. This culture system may provide a tool for cellular and molecular studies on the mechanisms of anti-tumor cytotoxicity, as well as the basis for new adoptive immunotherapy protocols in advanced cancers.
 ...
PMID:Long-term culture growth of CD4-CD8- lymphocytes exhibiting elevated non-MHC-restricted cytotoxic activity. 171 35


<< Previous 1 2 3 4 5 6 7 8 9 10