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Biomedical subjects

G Bolis

Publications and source records attributed to G Bolis.

At least 55 records · Page 3Linked to original sources
PubMed1982

Antibody-dependent and -independent cytotoxicity of human mononuclear phagocytes: defective stimulation of tumoricidal activity in milk macrophages.

Human peripheral blood monocytes, milk macrophages and peritoneal exudate macrophages were purified by adherence. antibody-dependent cellular cytotoxicity (ADCC) was measured using the murine TLX9 lymphoma pre-labelled with 3H-thymidine. Direct, antibody-independent tumoricidal activity was measured against the murine TU5 line pre-labelled with 3H-thymidine. All mononuclear phagocyte populations tested were similarly effective in mediating ADCC against TLX9 cells. In the absence of deliberate stimulation blood monocytes and peritoneal macrophages had appreciable spontaneous cytotoxicity against the susceptible TU5 line. In contrast, four out of 10 milk macrophage preparations lacked detectable spontaneous killing activity on this target. In vitro exposure to partially purified fibroblast interferon (IFN) or to lymphokine supernatants from PHA stimulated lymphocytes augmented the direct tumoricidal activity of blood monocytes and peritoneal exudate macrophages. Milk macrophages were completely unresponsive to IFN and lymphokines. therefore the capacity to mediate antibody-dependent and -independent cytotoxicity against tumour cells can be dissociated to some extent in human mononuclear phagocyte populations from diverse anatomical sites.

Animals↗
PubMed1980

Natural killer activity of lymphoid cells isolated from human ascitic ovarian tumors.

Lymphocytes and tumor cells were isolated from the carcinomatous ascites of 24 patients with epithelial ovarian tumors by stepwise application of density and velocity sedimentation on discontinuous Ficoll-Isopaque gradients and fetal bovine serum. Tumor-associated lymphocytes showed a lower percentage of cells with receptors for sheep erythrocytes (E) or for complement than did peripheral blood lymphocytes from the same patients. NK activity was measured, 51Cr-labelled K562 cells being used as targets in a 20-h assay. Tumor-associated lymphocytes showed significant NK activity. Cytotoxicity levels were lower than for peripheral blood effector cells from the same patients, and these in turn showed significantly lower cytotoxic capacity than peripheral blood lymphocytes from 64 control subjects. Similar results were obtained when lysis was measured after 4 h of incubation. Tumor-associated lymphocytes forming E rosettes were at least as effective as the unseparated population. When tumor-associated lymphocytes were mixed with normal effector cells, in three of six preparations with low NK activity tested, significant inhibition of normal lymphocyte NK activity was observed. Adherent macrophages from carcinomatous ascites, which contained lymphocytes that had suppressive activity, showed no inhibitory activity. Interferon (IF) boosted the NK activity against K562 of tumor-associated lymphocytes. Purified ovarian carcinoma cells were relatively resistant to lysis by normal lymphocytes. However, they inhibited lysis of K562 cells in cold target competition assays, though less efficiently than K 562 itself, and were consistently lysed when effector cells were stimulated with IF. It is therefore suggested that ovarian carcinoma cells express NK-relevant recognition structures, but are relatively resistant to cytolysis by unstimulated effector cells.

Ascitic Fluid↗
PubMed1980

Low-dose cyclophosphamide versus adriamycin plus cyclophosphamide in advanced ovarian cancer. A randomized clinical study.

After intensive staging 74 ovarian cancer patients were randomized to two arms balanced for stage and post-surgery residual tumor. The two regimens were CTX 100 mg/day continuously and ADM 50 mg/m2 IV every 4 weeks plus CTX 100 mg/day. The response rates were respectively 42% and 52%. Median survival times were 13 and 14 months. The incidence of side effects was significantly higher in the combination-treatment arm. No other statistical differences were found.

Adult↗
PubMed1980

Cytotoxicity on tumor cells of peripheral blood monocytes and tumor-associated macrophages in patients with ascites ovarian tumors.

Mononuclear phagocytes were isolated from the peripheral blood (PB) and ascites tumors of 35 patients with epithelial ovarian tumors. After 48 hours of incubation with the TU5 tumor, tumor-associated macrophages (TAM) and PB monocytes from cancer patients showed lower cytolytic activity than did control cells, but by 72 hours there was little difference between control and ovarian cancer effector cells. Primary ovarian carcinoma cultures were heterogeneous in their susceptibility to macrophage cytotoxicity. Tumor cells from 7 patients were significantly lysed by monocytes and macrophages, whereas four ovarian cancer cell preparations were resistant to cytotoxicity. A "feeding" effect of mononuclear phagocytes on non-lysable tumor cells was detected in terms of both lower [3H]thymidine-release values in the cytolysis assay and increased proliferation in cytostasis assays. Thus patients with ovarian carcinomatous ascites PB monocytes and TAM had impaired cytotoxicity against a tumor cell line, and primary ovarian carcinoma cultures were heterogeneous in their interaction with mononuclear phagocytes.

Adenocarcinoma↗
PubMed1979

Effects on in vitro tumor growth of macrophages isolated from human ascitic ovarian tumors.

Macrophages were isolated from 22 human ascitic ovarian epithelial tumors and their growth-inhibitory capacity was tested using as targets the following in vitro tumor cell lines: murine TLX9 lymphoma and FS6 sarcoma; human myeloid K562 leukemia and human E cell line derived from an ovarian carcinoma. Macrophage preparations were heterogeneous in their interaction with tumor target cells, and assay conditions, such as the type of target cell, incubation time, and attacker to target cell (A:T) ratio critically affected the evaluation of the cytotoxic potential of tumor-associated macrophages. At an A:T ratio of 7:1 no cytostatic activity on TLX9 and K562 cells was ever observed, but in the presence of specific antibody 8 out of 12 macrophage preparations tested showed significant antibody-dependent cytotoxicity on TLX9 lymphoma cells. Macrophage preparations from two patients significantly inhibited growth of the FS6 sarcoma and a cytostatic activity on E cells was observed in five additional patients. Significant stimulation of the proliferative capacity of at least one of the target cell lines was observed in 11 subjects at an A:T ratio of 7:1. In 12 patients, macrophage cytostatic activity on E cells was also tested at an A:T ratio of 35:1; eight out of 12 preparations showed significant cytotoxicity under these conditions. When the same subject was repeatedly tested at short intervals the same pattern of inhibition or stimulation of tumor growth was observed.

Animals↗
PubMed1979

Pharmacokinetics of cyclophosphamide after prolonged low dose treatment in ovarian cancer patients.

We have studied Cyclophosphamide (Cy) pharmacokinetics in 9 patients after their first intravenous dose of 100 mg, and in 9 patients after 6--13 months of continual treatment with the same dose every day. The half-life of Cy was shorter (p less than 0.05) in the latter group, the Co was greater (less than 0.01) and the Vd was clearly less (p less than 0.01). The AUC was unchanged.

Cyclophosphamide↗
PubMed1979

Hexamethylmelamine in ovarian cancer resistant to cyclophosphamide and adriamycin.

Thirty-four patients resistant to cyclophosphamide and Adriamycin received hexamethylmelamine at one of two dose regimens: 6 mg/kg/day orally for 21 days every 4 weeks or 8 mg/kg/day orally for 21 days every 6 weeks. Only five patients responded. Tolerance to the drug was, however, satisfactory; nausea, pyrosis, and vomiting were the only frequent side effects. Myelosuppression occurred in only one case.

Adult↗
PubMed1978

Variable oral absorption of hexamethylmelamine in man.

Plasma levels of hexamethylmelamine were measured by a sensitive and specific gas chromatographic assay in 11 patients after they received oral doses ranging from 120 to 300 mg/m2. Peak levels were reached in 0.5--3 hours and ranged from 0.2 to 20.8 micrograms/ml. The area under the curve ranged from 70.2 to 3606.6 micrograms/ml x minute. The half-life of the beta-phase of elimination also showed considerable variability, ranging between 4.66 and 10.2 hours. These parameters were not related to the dose administered. No plasma accumulation of the drug was observed after daily treatment with hexamethylmelamine for 14--21 days.

Absorption↗
PubMed1978

The lymphatic spread of ovarian germinal and stromal tumors.

This paper reports the results of lymphography in germinal and stromal tumors of the ovary. The group of patients is made up of 30 cases of germ cell tumors (70% dysgerminomas) and 29 cases of stromal tumors (62% granulosa cell tumors). The overall incidence of metastases was 29%; 37% in germ cell and 21% in stromal tumors. There was bilateral involvement in 41% of the patients with metastases. The para-aortic region alone was involved in 23%, the iliac alone in 18% and both the regions were simultaneously involved in 59%. In 17/30 operated patients (57%) retroperitoneal node biopsies were performed and diagnostic accuracy was 9/10 in the radiographically positive and 6/7 in the negative cases.

Adolescent↗
PubMed1977

Lymphangiography in patients with ovarian epithelial cancer: an evaluation of 289 consecutive cases.

From January, 1973, to June, 1976, 226 patients with palpable ovarian masses were evaluated preoperatively by lymphography. Histology showed 166 cases of malignant epithelial tumors, 26 benign tumors, and 34 malignant special tumors (not included in this report). Furthermore, the group of patients included 99 recurrences of ovarian epithelial cancer and 24 patients who underwent restaging diagnostic procedures without clinical evidence of disease. Lymphography was negative in all patients with benign tumors. In the 289 cases of epithelial cancer, lymphangiography gave evidence of nodal metastases in 88 (30%). When the histological subtype was considered, the highest incidence of metastases was in undifferentiated carcinoma (50%) and the lowest, in mesonephroid carcinoma (14%). According to the stage before lymphography, nodal metastases were found in 8% of Stage I, 0% of Stage II, 29% of Stage III, and 53% of Stage IV cases. The incidence of metastases was 46% in patients studied for recurrent disease and 17% in patients studied for restaging. Fifty-four percent of patients had metastases only in the pelvic nodes and 18% only in the para-aortic chains; in 28% both chains were involved simultaneously. Bilateral involvement was found in 63% of the positive cases. Retroperitoneal node biopsies were performed in 68 patients (36%). The radiologic/histologic correlation was 100% in the lymphangiographically positive cases; 81% in the negative cases, with nine false-negative reports; and 87% in all cases.

Carcinoma↗