Biomedical subjects
Publications and source records attributed to P Veraguth.
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A small number of patients with lung cancer will have a tumour invading the chest wall. Pre-operative radiotherapy and surgical resection provide the best results in patients with Pancoast's tumours, although chest wall invasion is often considered to indicate incurability. We reviewed the outcome in 46 patients with bronchogenic carcinoma and non-apical chest wall invasion and have tried to clarify the role of adjuvant pre-operative radiotherapy. All patients underwent combined chest wall and lung resection for treatment of lung cancer which had extended grossly and microscopically into the chest wall. In this retrospective study, we identified two groups of patients, those (n = 21) who received and those (n = 25) who did not receive pre-operative radiotherapy. Curative resection had been possible in 80% of the patients. There was one early post-operative death, due to pneumonia. The survival in all 46 patients is 32% at 5 years. In the most favourable cases, those without nodal involvement and who received pre-operative radiotherapy, the 5-year survival is 56%. In our series, there was a notable difference in 5-year survival between irradiated and non-irradiated patients at every stage of disease.
Serum-free supernatants of peripheral blood mononuclear cell cultures significantly stimulated [3H]thymidine incorporation of human hematopoietic and nonhematopoietic tumor cell lines. For assay we used a low number of tumor cells per well and medium enriched with dithiothreitol-treated fetal calf serum. The growth-stimulatory activity was detected in the supernatant of peripheral blood mononuclear cell culture within the first 24 h and decreased thereafter. Treatment of mononuclear cells with OKT3 monoclonal antibodies and rabbit complement decreased only moderately the factor production while treatment with anti-Leu-M2 and rabbit complement decreased it significantly. Supernatants of concanavalin A-stimulated peripheral blood mononuclear cell cultures enhanced nonsignificantly [3H]thymidine incorporation by tumor cell cultures unless antibodies against tumor necrosis factor alpha and gamma-interferon were added to the supernatants. Growth-stimulatory activity was heat inactivated partially at 60 degrees C and totally at 80 degrees C. It was abolished at pH 2.5 within 2 h as well as by treatment with dithiothreitol and partially lost by dialysis.
Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.
By measuring in vitro migration of [3H]leucine-labeled granulocytes from agarose containing capillary tube fragments, the migration inhibitory activity of supernatants of Con A-Sepharose stimulated MNC cultures was tested. The sensitivity of the method was increased by using higher dilutions of granulocytes in agarose (from 10(7)/1 microliter to 10(7)/3-4 microliter). Serum-free assays have been used for characterizing the migration inhibitory activity in this system. The migration inhibitory activity was abolished by absorption on granulocytes or by heating (56 degrees C, 80 degrees C). Other factors such as L-fucose, N-acetyl-D-glucosamine, DFP or BAEE showed only moderate or insignificant impairing effects on migration inhibitory activity of crude supernatants of Con A-Sepharose stimulated MNC cultures.
From 1980 to 1984 fifty-four patients with advanced ovarian carcinoma after operation and concluding chemotherapy with alkeran (n = 7) or cis-platin/alkeran +/- hexamethylmelamine (n = 47) as well as second-look laparotomy received follow-up radiotherapy either with the moving-strip technique (n = 35) or later the open-field technique (n = 19). 32 patients in CR received radiation therapy. 15 patients in CR are without relapse after undergoing open-field radiation therapy and a mean observation period of 25 months. At this point of time 5 of 17 patients had relapses under the moving-strip radiation treatment. The frequency of the relapses is apparently due to the very long periods of radiation and numerous interruptions in treatment. If residual tumors were present at the begin of ray therapy, a CR could only be achieved in cases where the previous monotherapy was with alkeran.
Forty-three patients with ovarian carcinoma were treated with whole-abdomen radiation (moving strip +/- pelvic radiation), 15 patients had not received prior chemotherapy, and 28 patients were irradiated following chemotherapy and second-look laparotomy. Ten of these had been treated with a variety of chemotherapy regimens (L-PAM, CHAD, Hexa-CAF). Eighteen patients were treated in an ongoing prospective trial with combination chemotherapy consisting of melphalan, cis-platinum, and hexamethylmelamine++ (HexaPAMP). Thrombocytopenia was the limiting toxicity. A temporary pause in the radiation schedule allowing platelets to recover made it possible to complete treatment in 80% of the patients. The acute toxic effects, which included the expected side effects of radiation therapy on intestine, liver and lung, were not more frequent or more severe in the patients who had received prior chemotherapy than in those who had radiation therapy alone. Thirty-four of 43 patients (stage I, seven patients; stage II, seven patients; stage III, 27 patients; stage IV, two patients) are alive and without evidence of disease 26 + months (range 7 to 64 months) after entering the postsurgical treatment program.
LIF activity in the supernatants of one way MLR, one MNC population being irradiated, was significantly increased as compared to that produced in two way MLR. Puromycin treatment of the irradiated cells decreased LIF response while puromycin treatment of the non-irradiated cells had no detectable effect. A similar increase of LIF activity was achieved by removing either OKT8+ or OKT4+ cells from one cell component before performing the mixed culture. Recombination of the depleted cell samples followed by MLR decreased LIF response except when belonging to allogeneic donors. Mostly, irradiation of OKT8 depleted mononuclear cells before recombination with OKT4 depleted cells prevented LIF suppression in MLR. The suppressor function of OKT4+ cells seems to be more radiosensitive than that of OKT8+ cells in this system. It is suggested that LIF production in MLR is regulated by a suppressor circuit which is histocompatible restricted and requires interaction of both OKT4+ and OKT8+ cells.
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By measuring granulocyte migration from clotted plasma droplets placed in Microtest II plates, leucocyte migration inhibitory factor (LIF) production by concanavalin A (ConA) stimulated mononuclear cell (MNC) cultures was tested. Moderate LIF production was observed when mononuclear cells were pulsed with ConA at 0 h, as compared with cells stimulated after 24 h culture which produced a significantly increased amount of LIF. Fresh adherent cells, when added to 24 h incubated MNC cultures before ConA stimulation, decreased LIF production, in contrast to in vitro irradiated or overnight cultured adherent cells. Indomethacin, when present during exposure to a ConA pulse of either MNC or of adherent cell-rich 24 h incubated MNC cultures, improved LIF activity significantly. This suggests that prostaglandin producing adherent cells, presumably cooperating with radiosensitive short-lived immunoregulatory T cells, are involved in suppression of LIF production by MNC cultures stimulated by ConA at 0 h.
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LIF activity production by ConA-stimulated mononuclear cells was tested by measuring granulocyte migration from clotted plasma droplets placed in Microtest II plates. 90 min. incubation of MNC cultures with ConA assured a significant LIF activity in the 24 h. culture supernatants. Removal of the adherent cells after ConA pulse exposure improved (p less than 0.05) LIF production. Enrichment with adherent cells of MNC cultures before ConA stimulation decreased LIF release. Irradiation (600 rad) of ConA stimulated MNC cultures, however, abrogated both phenomena induced by either removal or enrichment of the adherent cells. Indomethacin, when added during ConA pulse exposure to adherent cell rich MNC cultures, also increased LIF activity production. Both, PGE1 and supernatants of ConA-pulsed monocyte rich cultures had similar LIF impairing effects but the suppressive activity was abolished either by supernatants dialysis or by irradiation of stimulated MNC cultures.
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A cell migration inhibitory effect was evidentiated in normal guinea pig serum as compared with heat inactivated serum. Granulocytes when used as target showed a greater sensitivity to this effect than lymphomonocytes or macrophages. The migration inhibitory activity of GPS is abrogated or decreased by using complement destroying agents such as: heating at 56 degrees C for as little as 5 min, absorption on immune complexes in presence of calcium, on zymosan, on Sephadex G-50 or by adding EDTA or heparin to culture medium. The GPS dialysation fractions while exhibiting neither complement haemolytic effect nor migration inhibitory activity when tested alone, restored these functions by recombination. Absorption of GPS on homologous blood cells abrogated the migration inhibitory effect but retained the complement haemolytic function. When GPS absorbed on homologous blood cells mixed 1:5 with heat-inactivated serum (5 min at 56 degrees C), the migration inhibitory activity was regained, suggesting that the complement factors from the first sample were necessary for manifestation for the migration inhibitory activity from the heat-inactivated serum.