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)

The effect of intraperitoneal instillations of interleukin-2 (IL-2) and/or lymphokine-activated killer (LAK) cells on the ascites formation and the survival time was examined using nude mice as a model, with malignant ascites produced by intraperitoneal inoculation of human ovarian cancer cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. Twenty-eight days after tumor inoculation, all nude mice in the untreated group and in the group treated with spleen cells alone formed ascites. Two of ten nude mice treated with IL-2 alone after tumor inoculation survived without forming ascites during the experimental period. On the other hand, all nude mice treated with LAK cells alone had formed ascites 14 days after tumor inoculation. When LAK cells and IL-2 were combined, five of ten mice survived without forming ascites during the experimental period. The survival time of the group treated with IL-2 alone was significantly prolonged compared to the groups that received medium alone, spleen cells alone and LAK cells alone. When administration of LAK cells was followed by IL-2, the survival time was further prolonged.
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PMID:Effects of lymphokine-activated killer cells and interleukin-2 on the ascites formation and the survival time of nude mice bearing human ovarian cancer cells. 278 97

Recent reports suggest that recombinant interleukin-2 may be effective in the treatment of cancer patients with low tumor burden. Considering the poor long-term survival, 11 ovarian cancer patients with minimal residual disease at second-look have so far been selected for rIL-2 intravenous continuous infusion therapy: two induction courses (3 x 10(6) U/m2/day: 120 h + 108 h) followed by three maintenance courses (3 x 10(6) U/m2/day: 120 h) and third-look laparotomy. At present, three patients are still on treatment, three have completed it, and five have discontinued treatment. Sixty-seven per cent of the planned dose was administered in 49 cycles of which 42 (86%) required dose modifications due to hypotension (greater than or equal to grade III) and nephrotoxicity (greater than grade I). CNS and GI toxicity, allergies and fever, even though requiring dose modifications in a few cases, significantly affected patient compliance. The rebound lymphocytosis was clearly dose-related and a significant percentage increase after rIL-2 was detected only for IL-2 receptor positive cells. To date, four patients are evaluable for response after a median follow-up of 7 months, two progressed during the maintenance period, while one CR and one progression were detected in the two patients so far submitted to third-look laparotomy.
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PMID:Recombinant interleukin-2 continuous infusion in ovarian cancer patients with minimal residual disease at second-look. 278 2

A better understanding of the immunobiology of tumor-associated lymphocytes (TAL) may have considerable bearing on the therapeutic perspective of human neoplasia. We have identified ovarian cancer as a clinical condition privileged for studies on immunity and its in vitro and in vivo modulation. Our previous studies on the mechanisms of natural resistance have shown that TAL from ovarian carcinoma have defective natural killer cell activity when compared to peripheral blood lymphocytes from the same patient. This low natural killer cell activity could be stimulated in vitro by biological response modifiers (e.g. interferons) and these findings led us and others to design clinical trials based on intraperitoneal infusions of these agents. Interleukin-2 was extremely effective at inducing or augmenting cytotoxicity in TAL (lymphokine-activated killer cell activity). TAL-generated lymphokine-activated killer cells were cytotoxic against autologous and allogeneic fresh carcinoma cells. This finding provides a rationale for direct intraperitoneal infusion of this cytokine in ovarian cancer.
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PMID:Lymphocytes infiltrating ovarian carcinoma: modulation of functional activity by intraperitoneal treatment with biological response modifiers. 307 Mar 72

The effects of PSK on OKT 4/OKT 8 cell ratio, interleukin-2 (IL-2) production and expression of IL-2 receptor were examined in peripheral blood lymphocytes (PBL) from patients with advanced ovarian cancer during the course of chemotherapy. Preoperative levels of OKT 4/OKT 8 cell ratio and IL-2 production in PBL from patients with advanced ovarian cancer were significantly lower than those in cases of benign ovarian tumor. However, the expression of IL-2 receptor did not show any significant difference between ovarian cancer and benign ovarian tumor patients. When a combination chemotherapy of cisplatin, adriamycin and cyclophosphamide was given, the OKT 4/OKT 8 cell ratio was significantly increased with a significant decrease of the absolute number of the OKT 8 cell subset, while the expression of IL-2 receptor and the absolute number of the OKT 4 cell subset remained unchanged. In contrast, the IL-2 production was markedly depressed after the first course of chemotherapy. When PSK was combined with combination chemotherapy, the degree of inhibition of IL-2 production was reduced (though the effect was not statistically significant). If treatment with PSK was initiated after completion of combination chemotherapy, in addition to a significant elevation of OKT 4/OKT 8 cell ratio the depressed IL-2 production was restored to benign control levels. On the other hand, the expression of IL-2 receptor remained unchanged even if PSK was given after completion of chemotherapy.
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PMID:Effects of PSK on interleukin-2 production by peripheral lymphocytes of patients with advanced ovarian carcinoma during chemotherapy. 312

The present study was designed to elucidate the effect of cimetidine on CD4 and CD8 positive cells, interleukin-2 (IL-2) production and IL-2 receptor expression in peripheral blood lymphocytes (PBL) from patients with advanced ovarian carcinoma during the course of combination chemotherapy. The absolute number of CD8 (but not CD4) positive cells in PBL from patients with advanced ovarian carcinoma before surgery was significantly higher than that with benign ovarian tumor, while the IL-2 productivity was significantly lower. However, the IL-2 receptor expression was comparable to that with benign ovarian tumor. When a combination chemotherapy consisting of cisplatin, adriamycin and cyclophosphamide was given to these ovarian cancer patients, the IL-2 production was markedly depressed. If cimetidine was given with the combination chemotherapy, the inhibition of IL-2 production by chemotherapy was significantly diminished with a significant increase of CD4 positive cells. On the other hand, the IL-2 receptor expression was not affected by this treatment. When treatment with cimetidine was initiated after completion of chemotherapy, the depressed IL-2 production was restored to the level of control patients with benign ovarian tumor. The restoration seemed to result from an increase in proportion of CD4 positive cells. However, the expression of IL-2 receptor remained unchanged even if cimetidine was given.
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PMID:Effects of cimetidine on interleukin-2 production by peripheral blood lymphocytes in advanced ovarian carcinoma. 313 20

The purpose of this study was to investigate the effect of dose and duration of infusion of recombinant interleukin-2 (IL-2) on toxicity and immunomodulation. In a phase I/II study, IL-2 was administered intravenously (IV) daily for five consecutive days every other week for 4 weeks of treatment to 23 patients with progressive melanoma, renal, colon, or ovarian cancer by one of four regimens: groups I and II received 3 X 10(5) U/m2/d by two-hour or 24-hour infusion, respectively; groups III and IV received 3 X 10(6) U/m2/d by two-hour or 24-hour infusion, respectively. In a subsequent study, six patients (group V) received a single priming cycle of daily IL-2 for five days at 3 X 10(6) U/m2/d in divided 15-minute infusions every eight hours, before undergoing leukapheresis for lymphokine-activated killer (LAK) cell generation. Toxicity was mild with 3 X 10(5) U/m2/d, but severe chills and fever, moderate hypotension (not requiring IV pressors), and weight gain were observed with 3 X 10(6) U/m2/d. Toxicity was also related to the duration of infusion. In group IV (continuous infusion), fluid retention, weight gain, and azotemia were more frequent and severe than in groups III or V, in which the same total dose was administered by two-hour infusion or in three divided 15-minute infusions. IL-2 induced rebound lymphocytosis, which was directly dose-related and significantly higher in group IV (continuous infusion) than in groups III or V. Dramatic increases in the percentage and absolute number of cells expressing the IL-2 receptor were also most pronounced in group IV. With the higher dose of IL-2, LAK cells appeared in the circulation, and natural killer (NK) cytotoxicity was augmented. The results showed that the toxicity and immunomodulation by IL-2 are dose-dependent and are maximal by continuous infusion compared with two-hour or divided every eight hours infusions.
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PMID:Influence of dose and duration of infusion of interleukin-2 on toxicity and immunomodulation. 325 31

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

Ascitic fluid form ovarian cancer patients (n = 16), but not from patients with other cancers or with benign diseases, contains a growth-promoting activity which induces the proliferation of both fresh ovarian cancer cells (n = 5) and the ovarian cancer cell line HEY. The ascitic fluid growth factor(s) appears to signal cells through binding and activation of specific, saturable, high-affinity cell surface receptors. Incubation of fresh or cultured ovarian cancer cells with a partially purified preparation of ascitic fluid stimulates phosphatidylinositol turnover and increases cytosolic-free calcium. Each of these biochemical events has been implicated in the action of growth factors. Purified preparations of previously identified growth factors including epidermal growth factor, transforming growth factor-beta, tumor necrosis factor, platelet-derived growth factor, thrombin, insulin, interleukin-1, interleukin-2, vasopressin, angiotensin, alpha- and gamma-interferons, and fibroblast growth factor did not increase cytosolic-free calcium in either fresh ovarian cancer cells or HEY cells. Therefore, ascitic fluid appears to contain one or more previously unidentified growth factors which activate ovarian cancer cells through phosphatidylinositol hydrolysis and resultant changes in cytosolic-free calcium.
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PMID:A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization, and mechanism of action. 342 89

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

Adoptive immunotherapy involving bolus-dose recombinant interleukin-2 (rIL-2) has been reported to induce tumor regression in some patients with cancer, but has been associated with severe fluid retention and cardiopulmonary stress. In an effort to preserve the efficacy but reduce the toxicity of this treatment, we used escalating doses of rIL-2 as a constant infusion rather than as a bolus dose. Forty-eight patients with advanced cancer received rIL-2 as a 24-hour infusion in five-day cycles separated by five-day periods of rest and leukapheresis. Eight patients were removed from the study before receiving cells activated in vitro. In the 40 who could be evaluated for their response, there were 13 partial responses (32.5 percent) and 2 minor responses. Partial responses were observed in Hodgkin's disease (one of one), non-Hodgkin's lymphoma (one of one), lung cancer (one of five), ovarian cancer (one of one), parotid cancer (one of two), renal cancer (three of six), and melanoma (five of ten). Responses were associated with a good performance status, a base-line lymphocyte count above 1400 per cubic millimeter, and an rIL-2-induced lymphocyte count of at least 6000. Optimal lymphocytosis required a priming dose of rIL-2 of 3 X 10(6) U per square meter of body-surface area per day, and 15 of 28 patients receiving this priming dose responded to treatment. A weight gain of more than 10 percent of total body weight (five patients) and dyspnea at rest (six patients) were unusual events restricted to patients with poorer pretreatment performance. We conclude that the administration of rIL-2 as a constant infusion may preserve the antineoplastic activity of adoptive immunotherapy while increasing the safety and comfort of patients.
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PMID:Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. 349 33


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