Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bispecific murine monoclonal antibody 2B1, possessing dual specificity for the human c-erbB-2 protooncogene product and human Fc gamma receptor III (CD16) was evaluated for the ability to promote specific lysis of c-erbB-2-positive tumor cells in vitro. In short-term 51Cr release assays with human mononuclear cells as effectors and SK-Br-3 human breast cancer cells as targets, neither parental antibody of 2B1 mediated significant specific lysis, but bispecific antibody was as active as a chemical heteroconjugate, with 5 ng/ml of 2B1 causing half-maximal lysis at an effector/target ratio of 20:1 and 2 ng/ml 2B1 causing half-maximal lysis at an E/T ratio of 40:1. The cytotoxic targeting activity of 2B1 F(ab')2 fragment was the same as that of whole bispecific antibody, and the activity of whole 2B1 was not reduced when assays were performed in 100% autologous human serum, indicating that 2B1 binds effector cells through the CD16-binding site derived from parental antibody 3G8 rather than through its Fc portion. Variable inhibition of 2B1-mediated lysis was observed when autologous polymorphonuclear leukocytes from different donors were added to mononuclear effector cells at a 2:1 ratio; this inhibition was overcome at higher antibody concentration. 2B1 bispecific monoclonal antibody was also able to mediate targeted cytolysis using whole human blood as a source of effector cells or using effector or target cells derived from ovarian cancer patients.
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PMID:In vitro cytotoxic targeting by human mononuclear cells and bispecific antibody 2B1, recognizing c-erbB-2 protooncogene product and Fc gamma receptor III. 136 Aug 72

Monoclonal antibodies (MoAbs) specific for surface molecules involved in lymphocyte activation, represent an useful tool for the analysis of the activation pathways of different effector lymphocytes. We have analyzed the ability of MoAbs directed against "triggering" surface molecules, such as CD3/TCR, CD2 and CD16 to induce activation of the lytic machinery in T and NK lymphocytes, using a redirected killing assay. In addition, we have constructed bispecific monoclonal antibodies (BiMoAbs) directed against both the CD3/TCR complex (or the CD16 molecule) and a tumor associated antigen expressed on the surface of ovarian cancer cells. BiMoAbs were constructed by two different approaches: a) conjugation of two distinct MoAbs by a chemical heterobifunctional agent; b) selection of hybrid-hybridomas secreting BiMoAbs. BiMoAbs were able to focus appropriate lymphoid effector cells on tumor cells expressing the relevant antigen, and to induce tumor cell lysis. Therefore, these reagents were able to confer a new specificity for a given antigen to effector lymphocytes, independently from the original one. For these properties, BiMoAbs may represent a suitable tool for new strategies of adoptive immunotherapy, based on the use of effector cells that have been specifically armed by BiMoAbs against the tumor.
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PMID:Induction of functional activities of human lymphocytes by monoclonal antibodies. 183 70

Comparison was made between lymphocyte subsets in peripheral blood from patients with benign ovarian tumor and those with advanced ovarian carcinoma. In addition, changes of lymphocyte subsets of patients with ovarian carcinoma before and after operation were also examined. The percentage and absolute number of CD3-/HLA-DR+ (B cells) in peripheral blood from patients with advanced ovarian carcinoma were significantly lower than values from patients with benign ovarian tumor, whereas both percentage and absolute number of CD3-/HLA-DR- (null cells) cells in patients with advanced ovarian carcinoma were significantly higher. Although there was no significant difference in natural killer (NK) cell subsets (CD57+ CD16- and CD57+ CD16+ cells) between patients with benign ovarian tumor and ovarian carcinoma, the percentage and absolute number of CD57-/CD16+ (highly differentiated NK cells) cells in patients with ovarian carcinoma were significantly higher than those in patients with benign ovarian tumor. Both the absolute number and percentage of CD3+/HLA-DR+ (activated T cells) cells in ovarian cancer patients with minimal residual tumors after operation were significantly increased, compared to the levels before operation, while the values in the patients with large residual tumors were significantly decreased. In addition, the percentage and absolute number of CD3-/HLA-DR- (null cells) cells in the patients with minimal residual tumors were significantly decreased after operation, while values in the patients with large residual tumors remained unchanged before and after operation. The patients with minimal residual tumors after operation were characterized by a significant increase in the percentage of CD57- CD16+ (highly differentiated NK cells) cells. On the other hand, in the patients with large residual tumors no change of the NK cell subsets was observed before and after operation.
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PMID:Changes of lymphocyte subsets in peripheral blood before and after operation of patients with advanced ovarian carcinoma. 214 87

We investigated the ability of endogenous and recombinant interleukin-2 (IL-2)-stimulated NK cells from normal donors and ovarian cancer patients to mediate lysis of ovarian tumors, and found that peripheral blood (PB) mononuclear cells of normal donors or cancer patients did not display tumoricidal activity against ovarian cell line or fresh ovarian tumors. In addition, ovarian cancer patients displayed a defect in NK-cell activity against the highly NK-sensitive target, K-562. However, lytic activity against ovarian tumors (including cultured and primary tumors) was induced and that against K-562 was potentiated in PB of normal donors and PB and peritoneal cavity of ovarian cancer patients after enrichment of LGL on Percoll density gradient or after stimulation of effector cells with recombinant IL-2 in vitro. The IL-2-generated cytotoxic cells in PB were characterized as NK cells displaying CD16+, NKH1 (Leu-19)+, CD3- and CD5- phenotype, while those in the peritoneal cavity were predominantly CD16-, NKH1+, CD3- and CD5-. Studies on the mechanism of IL-2-dependent generation of cytotoxicity showed that such an effect was mediated via recruitment of tumor-binding cells as well as by an increase in the frequency of cytotoxic cells.
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PMID:Recombinant IL-2-activated NK cells mediate LAK activity against ovarian cancer. 326 Dec 80

In patients with extensive chemotherapy, G-CSF abrogated leukopenia following administration of cytotoxic agents. Six women with ovarian cancer and chemotherapy-induced leukopenia received 300 micrograms Filgrastrim (r-metHuG-CSF, Neupogen 30; AMGEN, Germany) daily for 10 days. Leukocytes and lymphocyte subsets of peripheral blood were determined before, throughout and after subcutaneous injections of G-CSF by flow cytometry using monoclonal antibodies to CD3, CD4, CD8, CD14, CD16/56, CD19 and CD45. It could be observed that not only neutrophils (23 fold) but also lymphocytes (6 fold) and monocytes (10 fold) showed a dramatic increase in cell counts throughout and after G-CSF administration. This is in contrast to previous reports, where only effects on neutrophils were described. In spite of the increase in lymphocytes the relative percentage of CD3+, CD19+, CD3-CD16/CD56+, CD3+, CD8+ and CD3+ CD4+ lymphocyte subsets did not change throughout and after therapy, except for an increased expression of HLA-DR on CD3+ lymphocytes.
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PMID:[Effect of granulocyte colony stimulating factor (G-CSF) on peripheral blood leukocytes and lymphocytes in patients with chemotherapy-induced leukopenia]. 753 60

Ascites and peripheral blood of 12 patients with advanced ovarian cancer (stage IV) have been investigated by two-color flow cytometry for leukocytes and lymphocyte subsets with monoclonal antibodies, against CD3, CD4, CD8, CD14, CD16/56, CD19, CD25, CD45, CD57, and HLA-DR. Ascites compared with blood showed a significant raise of CD3-positive lymphocytes (80 +/- 14% vs. 69 +/- 8%) and a significant reduction of CD57-positive lymphocytes (13.6 +/- 13% vs 24 +/- 21%). There was an increased expression of HLA-DR on CD3-positive lymphocytes in malignant ascites. The results are discussed with regard to a supposedly defective local immune defense against the tumor.
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PMID:[Leukocyte and lymphocyte populations in peripheral blood and malignant ascites in patients with ovarian carcinoma]. 753 61

We evaluated the immunological reconstitution of patients who underwent high-dose chemotherapy and autologous blood stem cell transplantation (ABSCT) for advanced ovarian cancer. Sixty days after transplantation a complete reconstitution of lymphocytes and of the CD3, CD4, CD8, CD19, and CD16/56 subsets was observed in this series. A significant increase in the count of interleukin-2 receptor expressing lymphocyte (CD25) was found on day +60 after transplantation compared to that obtained at diagnosis and before transplantation. A significantly higher lymphokine-activated killer (LAK) precursor activity was seen on day +60 compared to the values obtained at diagnosis and before transplantation while natural killer activity did not show any significant variation. We conclude that ABSCT gives prompt and complete immunohaematopoietic reconstitution after high-dose treatment. Moreover, our data support the feasibility of interleukin-2/LAK therapy as consolidative therapy after ABSCT.
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PMID:Immunological reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation for advanced ovarian cancer. 810 37

Tumor specimens and ascites of patients with advanced ovarian cancer were utilized to obtain both primary ovarian carcinoma cell cultures and lymphocytes: tumor-infiltrating lymphocytes (TILs) from solid tumor tissue and tumor-associated lymphocytes (TALs) from peritoneal fluid. Tumor lymphocytes were grown in coculture with autologous tumor cells and recombinant human IL-2 (rhIL-2) for up to 4 weeks and at weekly intervals these were examined with respect to phenotype and cytotoxicity. The phenotype was studied using flow cytometry for a variety of human immunocompetent cell surface markers (CD3, CD4 CD8, CD16, CD56, TCR alphabeta, TCRgammadelta). Cytotoxicity was investigated using 4-hr 51Cr-release assays with the primary ovarian carcinoma cell cultures and the K562 cell line as target cells. The tumor lymphocytes did not demonstrate any obvious trend in phenotype changes during culture, although for different cultures a large range was noted for the various lymphocyte populations studied. Cytotoxicity against both autologous and allogeneic targets declined with culture length for the majority (6/7) of the lymphocyte cell lines tested (greatest at 1 week and least at 3 weeks). These initial results indicate that an in vitro non-MHC-restricted cytotoxic function of peritoneal lymphocytes can be effectively activated with IL-2 and autologous tumor cells. However, if activated lymphocytes are to be employed as a form of immunotherapy, they should be given within the first week of culture for maximum cytotoxic effect.
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PMID:Tumor lymphocytes in patients with advanced ovarian cancer: changes during in vitro culture and implications for immunotherapy. 919 Sep 63

Peripheral blood lymphocytes (PBL) from patients with ovarian or breast cancer or benign lesions of the breast, respectively, have been analysed for expression of phenotypic and activation markers by flow cytometry. The results were compared with those of a control group of healthy women. The relative proportion as well as the absolute counts of B lymphocytes were similar in both groups and in the control group. The absolute number of T cells was decreased in breast cancer patients (p < 0.05). The CD4+/CD8+ ratio was significantly depressed in ovarian cancer patients (p < 0.05), but not in breast cancer patients. In the ovarian cancer group, the percentage of CD3+ T cells expressing HLA-DR (p < 0.05) as well as CD3+ T cells expressing CD16 and CD56 (p < 0.05) was significantly higher. The relative proportion as well as the absolute counts of CD3+ T cells expressing the IL-2 receptor (CD25) were significantly higher (p < 0.001), respectively, in breast cancer patients (p < 0.05). These results suggest that gynaecological cancer is associated with specific alterations in the T cell population.
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PMID:Lymphocyte subsets in patients with ovarian and breast cancer. 944 13

Tumor-associated lymphocytes (TALs) freshly isolated from patients with cancer usually manifest reduced proliferative and cytolytic functions. To determine whether alterations in signal transduction contribute to functional impairments seen in TALs, we purified populations of T and natural killer (NK) cells by negative selection from ascites of seven patients with ovarian carcinoma. The average purity was 84 +/- 5% for CD3(+) TALs and 77 +/- 10% for CD3(-)CD56(+)CD16(+) TALs. Expression of several signal transduction molecules, including the CD3-epsilon, CD3-zeta, and FcepsilonRI-gamma chains, p56(lck) protein tyrosine kinase, and phospholipase C-gamma1, was studied in these cells using Western blotting. A marked decrease in expression of zeta and FcepsilonRI-gamma associated with CD3 or FcgammaRIIIA was observed in T or NK cells obtained from TALs, as compared to T or NK cells purified from normal peripheral blood. Expression of CD3-epsilon, as assessed using flow cytometry, Western blotting, or ELISA was also reduced in purified TAL-T cells relative to that in normal peripheral blood T cells. Surface expression of CD3 on T cells and FcgammaRIIIA on NK cells obtained from TALs was significantly decreased in comparison to normal peripheral blood lymphocytes (PBLs): the mean fluorescence intensity of CD3 was 277 +/- 18 for TAL-T (n = 7) versus 349 +/- 13 for PBL-T (n = 9) and that of CD16 was 58 +/- 1 for TAL-NK (n = 7) versus 385 +/- 55 for PBL-NK (n = 23) cells. These observations suggest a defect in assembly of T cell receptor and FcgammaRIIIA multicomponent transmembrane receptors, which are zeta and gamma dependent. In addition to alterations in expression, the function of these receptors was also modified, since cross-linking of CD3 on TAL-T and CD16 on TAL-NK cells with the respective monoclonal antibodies resulted in a pattern of protein phosphorylation that was distinct from that observed in normal PBLs. Expression of tyrosine kinase p56(lck) and its kinase activity were also depressed, while expression of phospholipase C-gamma1 appeared to be normal in most preparations of the TALs tested. In vitro proliferation of TAL-T in response to anti-CD3 monoclonal antibody and TAL-NK cells to interleukin 2 were significantly depressed as was the ability to produce IFN-gamma. In contrast, TAL-T cells were able to produce interleukin 10 at levels similar to those secreted by normal PBLs. Thus, in TALs obtained from patients with advanced ovarian cancer, alterations in expression and activity of signaling molecules were associated with reduced cellular functions such as proliferation and production of certain cytokines.
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PMID:Alterations in expression and function of signal-transducing proteins in tumor-associated T and natural killer cells in patients with ovarian carcinoma. 981 3


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