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)

Peripheral blood lymphocytes (PBLs) and tumor-associated lymphocytes (TALs) were isolated from 36 patients with advanced ovarian adenocarcinoma and peritoneal effusions for study of lymphokine-activated killer activity. PBLs and TALs cultured in vitro for 3-5 days in the presence of interleukin-2 (IL-2, supernatant of the MLA 144 gibbon cell line, or human recombinant IL-2) expressed higher levels of cytotoxicity as compared to cells cultured in medium alone, against natural killer (NK)-susceptible (K562) or NK-resistant targets (Daudi and the human ovarian carcinoma cell line SW626). When ovarian tumor cells, freshly isolated from carcinomatous ascites or surgical specimens, were used as target cells in the cytotoxicity assay, 8 of 14 PBLs and 5 of 7 TAL preparations lysed the autologous tumor after treatment with IL-2, while no spontaneous reactivity was observed in any of the 14 patients tested. Although levels of lysis were usually relatively low, these data demonstrate that PBLs and TALs from ovarian cancer patients (TALs usually exhibiting low NK activity) when stimulated in vitro by IL-2 acquire some cytotoxic potential against the autologous tumor.
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PMID:Lymphokine-activated killer activity of tumor-associated and peripheral blood lymphocytes isolated from patients with ascites ovarian tumors. 348 56

A tumor-specific cytotoxic T lymphocyte (CTL) immune response has been well documented in melanoma, renal cell carcinoma, and ovarian cancer. Conflicting evidence exists regarding the existence of tumor-specific CTL populations in breast cancer. Tumor cells and tumor-associated lymphocytes (TAL) were isolated from the pleural effusions of six consecutive patients with metastatic breast cancer. After solid-phase anti-CD3 stimulation, TAL cultures were expanded with weekly autologous tumor stimulation and low-dose IL-2 for 3 wk. T cell populations were characterized using flow cytometric analysis and ranged from 49 to 91% CD8+, > 98% CD3+, and < 3% CD16+. Functionally, tumor-stimulated TAL showed tumor-specific recognition of autologous tumor cells (241 +/- 142 LU20/10(7)) and no detectable lysis of autologous fibroblasts, Daudi or K562. Cytotoxicity of TAL against HLA-A2+ allogeneic targets was significantly higher when compared with HLA-A2- tumor cell lines (127 +/- 76 vs 6 +/- 18 LU, p = 0.0001). This cytotoxicity against autologous and allogeneic tumor cells was blocked by anti-HLA-A2 mAb and cold HLA-A2+ targets in cold-target inhibition assays. TAL from all HLA-A2+ patients recognized GP2, a known, HER2/neu-derived tumor-associated peptide Ag that is HLA-A2 restricted. We have shown that TAL obtained from metastatic effusions of breast cancer patients contain lymphocytes that can recognize and lyse autologous and allogeneic tumor cells in a tumor-specific, HLA-A2-restricted fashion. In addition, tumor-specific TAL derived from breast cancer patients can selectively lyse HLA-A2+ pancreatic and ovarian tumor cell targets, suggesting a common HLA-A2-restricted tumor-associated Ag between these distinct epithelial cancers. Further elucidation of the cell-mediated immune response to breast cancer and the identification of shared TAA could result in the development of broadly applicable vaccine therapies for many cancers.
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PMID:Tumor-specific and HLA-A2-restricted cytolysis by tumor-associated lymphocytes in human metastatic breast cancer. 759 11

Tumor-associated lymphocytes (TAL) from the malignant ascites and tumor-infiltrating lymphocytes (TIL) from the solid tumor were isolated from six consecutive untreated ovarian cancer patients. Tumor-specific CTL were generated from both TAL and TIL using solid phase anti-CD3, low dose IL-2 (50 IU/ml), and repeated tumor stimulation. The specificity of TAL and TIL was tested in standard cytotoxicity assays using autologous tumor, several allogeneic ovarian tumors, and the NK-sensitive cell line, K562. Anti-HLA-A-B-C mAb, W6/32, was used to demonstrate that these tumor-specific TAL and TIL were HLA class I-restricted. The ability of the ascitic and solid tumor to present Ag by HLA class I was assessed using Brefeldin A, a fungal metabolite that blocks the endogenous Ag-processing pathway in the viral model. Brefeldin A significantly inhibited tumor-specific cytotoxicity as well as HLA class I expression on the cell surface, suggesting an endogenous source of tumor-associated Ag. Despite previous reports of antigenic heterogeneity in ovarian cancer, shared tumor-associated Ag were shown to exist in this disease as demonstrated by significant allogeneic recognition of HLA-A2-matched patients as opposed to unmatched controls. Specifically, CTL from HLA-A2+ patients lysed HLA-A2+ allogeneic targets significantly better than HLA-A2- allogeneic or HLA-A2+ melanoma targets. There was no such difference with HLA-A2- effectors. Furthermore, HLA-A2 was confirmed to be a major restriction element in ovarian cancer by the blocking of HLA-A2+ effectors against both autologous and allogeneic HLA-A2+ targets with the anti-HLA-A2 mAb, BB7.2. These findings verify a similar lymphocyte/tumor interaction as has been documented in melanoma, suggesting a common mechanism of recognition of these human tumors by lymphocytes.
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PMID:HLA-A2 presents shared tumor-associated antigens derived from endogenous proteins in ovarian cancer. 822 40

The bispecific antibodies (bs-mAbs) OV-TL 3/CD3 and OC/TR (MOv18/CD3) efficiently mediate ovarian tumor cell lysis by cytotoxic T cells and activated peripheral blood lymphocytes (PBL) in vitro. OV-TL 3/CD3 and OC/TR are reactive with tumor-associated antigens on ovarian carcinoma cells (OA3 and CA-MOv18, respectively), and CD3 on activated PBL, bridging both cells and simultaneously inducing activation of the effector cells. In a comparative study we investigated the therapeutic efficacy of OV-TL 3/CD3 and OC/TR by targeting activated PBL with the bs-mAbs against intraperitoneally growing NIH:OVCAR-3 human ovarian carcinoma cells. As they have good tumor localization characteristics, HPLC-purified bispecific F(ab')2 fragments were used to target highly active PHA and IL-2-stimulated PBL effector cells. The efficacy of OV-TL 3/CD3 was compared to OC/TR with respect to tumor-associated antigen (TAA) binding on NIH:OVCAR-3 ascites cells and NIH:OVCAR-3 tumor cell lysis in vitro. In this report we show that ip ovarian cancer-bearing nude mice treated with IL-2 and activated PBL coated with bispecific F(ab')2 had a significantly longer survival than the untreated mice. No significant difference in survival was found between the OC/TR or OV-TL 3/CD3 bispecific antibody, although MOv18 expression was higher on NIH:OVCAR-3 ascites cells and PBL targeted with OC/TR induced slightly higher tumor cell lysis in vitro. Thus, the therapeutic efficacy of these bs-mAbs in vivo could not be predicted by TAA expression or bs-mAb-mediated tumor cell lysis in vitro.
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PMID:Immunotherapy in a human ovarian cancer xenograft model with two bispecific monoclonal antibodies: OV-TL 3/CD3 and OC/TR. 831 39

The concentrations of various cytokines were examined by ELISA in blood and in ascites from 14 patients with advanced ovarian cancer (stage IV). The control group consisted of 6 patients with benign gynaecological disorders. Compared with patients with benign gynaecological disorders, ascites and/or plasma of patients with ovarian cancer showed significantly higher levels of IL-6, IL-8, IL-10, TNF-alpha, and sIL-2R. There were no increases of IL-1 alpha, IL-1 beta, IL-2, IFN-gamma, and sCD14 levels. The possible pathogenetic significance of cytokines in ovarian cancer is discussed.
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PMID:-Cytokine level in malignant ascites and peripheral blood of patients with advanced ovarian carcinoma-. 864 64

Protein 90K is a tumor-associated antigen, which is able to enhance the cytotoxic activity in lymphokine-activated and natural killer cells as well as the IL-2 release in peripheral blood lymphocytes. In our in vitro experiences we observed a stimulatory effect by IFN-alpha and IFN-gamma on 90K-specific mRNA expression and protein release in ovarian cancer cells, and 90K was furthermore found to be a potent stimulator of macrophage activity. Protein 90K seems to be involved in tumor immunology; it may represent a critical link between tumor and immune system.
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PMID:[Immunostimulating protein 90K in ovarian carcinoma]. 873 25

The host-tumor interaction may play an important role in determining tumor progress. Recent studies have shown that this interaction can be influenced by the release of soluble factors by tumor cells and tumor-infiltrating lymphocytes (TIL). The aim of our study is to characterize the nature of cytokines and growth factors and their relationship to the cellular infiltrates in 16 patients with ovarian cancer using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Total RNA from 20 malignant and 10 benign specimens were used to assay for expression of 12 cytokines. Additionally, monoclonal antibodies (MAbs) were used to detect T cells, CD4+ helper and CD8+ cytotoxic/suppressor T-cell subtypes, B cells, and macrophages. Our results showed the expression of transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in 19, 17, and 10 malignant specimens, P < .001, .001, and .05, respectively. Other cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), TNF-beta/LT, IL-2, and IL-6 were expressed in a few cases, and IL-1alpha and IL-4 expression were not detected. The benign samples did not express IL-10, but GM-CSF, TGF-beta1, and IL-8 were expressed in one, one, and four specimens, respectively. Interestingly, in four cases in which samples from the primary and relapse tumors were available for analysis, the tumors in relapse showed a significant increase for TGF-beta1 (P < .05) and a decreased trend in IL-10 mRNA levels. The source of these factors was tumor cells as detected immunohistochemically. This combined alteration of TGF-beta1 and IL-10 was associated with a significant reduction in number of TIL in general, and CD8+ and macrophages in particular (P = .036 and .049, respectively). Our findings suggest the important role of certain soluble factors in the complex process of tumor progression. Furthermore, understanding the tumor-host relationship and the factors influencing the interaction may be helpful in developing effective and innovative treatment methods.
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PMID:Tumor-host interaction: analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinomas. 904 97

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

Extensive research has led to accumulation of common hereditary evidence concerning ovarian and breast cancer, suggesting that these two cancers can be considered as one type. Subsequently, women with breast cancer are susceptible to the risk of developing ovarian cancer. Highly expressed oncogenes such as bcl-2, HER2/neu and others or mutated suppressor genes such as p53 or BRCA1 have been characterised as hereditary susceptibility genes leading to syndromes such as breast/ovarian cancer syndrome, Li-Fraumeni and others. Furthermore, these genetic alterations can cause potent chemoresistance by inhibiting induction of apoptosis after DNA damage caused by chemotherapy and/or radiotherapy. Presently, molecular onco-biology has enabled us not only to detect susceptibility to ovarian and breast cancer but also ways to inhibit their further progression or even circumventing chemoresistance mechanisms after their development by gene therapy using delivery vectors such as liposomes or viruses, by which we can replace wild-type tumour suppressor genes or by using antigene, antisense oligonucleotides and antisense RNA leading to reduced oncogene expression, enabling induction of apoptosis after DNA damage into chemoresistant tumour cells. Furthermore efflux-genes such as MDR-1 or MRP can be circumvented, suicide-genes can be employed which can facilitate sensitivity by encoding enzymes capable of converting inactive forms of a drug into toxic antimetabolites and immunotherapy can be achieved, by transfection of tumour cells with adenoviral vectors encoding immunomodulators such as IL-2 or MHC molecules. Thus, molecular biology appears to be a very strong element for the screening, diagnosis, therapy and prognosis of ovarian and breast cancer. However, consistent future research is greatly needed because many points concerning ovarian and breast cancer genetics are still unknown. Finally, we strongly believe that gene therapy could be extremely useful when is combined with conventional therapy against ovarian and breast tumours.
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PMID:Molecular aspects of breast and ovarian cancer. 937 59

The serum levels of interleukin-(IL-)1 alpha, IL-1 beta, IL-2, IL-6, TNF alpha, and sIL-2R and the proliferative response of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA), anti-CD3 monoclonal antibody (mAb), recombinant IL-2 (rIL-2), and the combination of PHA or anti-CD3 mAb with rIL-2 were studied and correlated with serum levels of C-reactive protein (CRP) in women with advanced epithelial ovarian cancer. The expression of CD25 and CD122 subunities of membrane-bound IL-2R on PHA- or anti-CD3 mAb-stimulated PBMC was also studied. In comparisons with the controls, PBMC response to PHA, anti-CD3 mAb, and rIL-2 was significantly lower in the cancer patients. The addition of exogenous rIL-2 to the PBMC cultures increased response in both controls and patients but did not modify the significance of the differences. After stimulation with PHA or anti-CD3 mAb, the percentage of PBMC CD25+ or CD122+ was significantly lower in patients. The serum levels of IL-1 alpha, IL-1 beta, IL-6, TNF alpha, sIL-2R, and CRP were significantly increased in patients compared to the controls. Instead, no differences were observed for serum levels of IL-2. A strong association was found between high serum levels of the above-mentioned cytokines, sIL-2R, and CRP. The results of our study on advanced stage (IIIb-IV) ovarian cancer patients are consistent with the previously reported hypothesis that high IL-6 and/or CRP serum levels may represent an important and independent prognostic factor of the likely outcome in cancer patients.
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PMID:High serum levels of soluble IL-2 receptor, cytokines, and C reactive protein correlate with impairment of T cell response in patients with advanced epithelial ovarian cancer. 964 96


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