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P Weynants

Publications and source records attributed to P Weynants.

At least 37 records · Page 2Linked to original sources
PubMed1994

Expression of mage genes by non-small-cell lung carcinomas.

Human gene MAGE-I codes for an antigen that is recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). This antigen is potentially useful as a target for cancer immunotherapy because gene MAGE-I is not expressed in any normal tissues except the testis. We tested 46 surgical samples of non-small-cell lung carcinomas and observed MAGE-I expression in 16 of them (35%). Genes MAGE-2 and 3, which are closely related to MAGE-I, were expressed by a similar proportion of these tumors. Some small-cell lung tumors also express MAGE genes. The proportion of tumors expressing MAGE-I suggests that lung tumor patients may constitute the largest group of patients potentially eligible for pilot studies involving MAGE-I immunization.

Base Sequence↗
PubMed1993

Genes coding for tumor antigens recognized by human cytolytic T lymphocytes.

In order to define the antigens recognized by cytolytic T lymphocytes (CTLs) on autologous tumors, we derived tumor-specific CTL clones from autologous mixed lymphocyte tumor cell cultures. The gene coding for a tumor rejection antigen expressed on a melanoma was isolated by transfecting genomic DNA of the tumor into an antigen-loss variant of the melanoma. Transfectants were identified on the basis of their ability to stimulate tumor necrosis factor release by the CTL clone. The gene that transferred the expression of the antigen was named MAGE-1. It is a new gene, silent in normal tissues with the exception of testis, but expressed in several types of tumors. The antigen recognized by the CTL clone is a nonapeptide derived from the protein encoded by gene MAGE-1, and presented by the HLA class I molecule HLA-A1. Using two other antimelanoma CTL clones, we identified the tyrosinase gene as coding for an antigen presented by HLA-A2 on this type of tumors. The identification of these tumor rejection antigens open new possibilities for the specific immunotherapy of cancer.

Antigen-Antibody Reactions↗
PubMed1993

Dose-dependent interleukin-3 stimulation of thrombopoiesis and neutropoiesis in patients with small-cell lung carcinoma before and following chemotherapy: a placebo-controlled randomized phase Ib study.

PURPOSE: To evaluate the safety, tolerance, and hematologic effects of recombinant human interleukin-3 (IL-3) in patients with small-cell lung cancer (SCLC) before and following multiagent antineoplastic therapy in a placebo-controlled, randomized, double-blind study. PATIENTS AND METHODS: Twenty-eight patients (22 men and six women; median age, 60 years) with previously untreated SCLC entered the study. Patients were assigned to six groups of escalating-dose IL-3 ranging from 0.25 to 10 micrograms/kg/d administered by continuous infusion for 7 days, with one patient in each group receiving placebo. After a 1-week interval, the first of three cycles of carboplatin, etoposide (VP16), and epirubicin (CVE) given every 3 weeks was administered. The second cycle of CVE was followed by 7 days of IL-3 administered at the same daily dose as administered during the first infusion. RESULTS: The maximum-tolerated dose was not encountered in this study. Fever was the most frequently observed side effect. Before any chemotherapy, World Health Organization (WHO) grade II fever only appeared at doses > or = 2.5 micrograms/kg/d. Other side effects included rash, headache, and myalgia. During the first infusion of IL-3, before administration of chemotherapy, dose-dependent increases in peripheral-platelet counts (r = .613; P < .001) and neutrophil counts (r = .505; P = .007) were observed. Following the second cycle of CVE, recovery of peripheral platelet counts was faster as compared with the first cycle of CVE for patients treated with 7.5 and 10 micrograms/kg of IL-3 (P = .021). Chemotherapy postponements due to myelotoxicity were also less frequent following the second cycle of CVE as compared with the first for patients treated with > or = 2.5 micrograms/kg of IL-3 (P = .036). Compared with an age-matched historical group receiving identical chemotherapy (n = 191), administration of IL-3 did not modify either disease-free survival or overall patient survival rates. CONCLUSION: IL-3 is well tolerated at doses up to 10 micrograms/kg/d. In the absence of chemotherapy, biologic effects on both neutrophils and platelets were seen at doses > or = 2.5 micrograms/kg/d. IL-3 infusion following the second cycle of CVE appears to reduce chemotherapy-induced myelosuppression, but does not alter tumor response or patient survival rates.

Adult↗
PubMed1992

Treatment of relapse of small cell lung cancer in selected patients with the initial combination chemotherapy carboplatin, etoposide, and epirubicin.

BACKGROUND: Relapse of small cell lung cancer is not usually treated with further chemotherapy as results are considered to be disappointing. METHODS AND RESULTS: Six patients with relapse of small cell lung cancer after a complete initial response and remission of more than one year responded to repeat treatment with the initial chemotherapy comprising carboplatin, etoposide, and epirubicin. The second remission ranged from six months to more than 15 months. CONCLUSION: In patients with a relapse of small cell lung cancer after a complete initial response and prolonged remission retreatment with the initial combination chemotherapy cannot be dismissed and requires further study.

Aged↗
PubMed1990

Antigens recognized on a melanoma cell line by autologous cytolytic T lymphocytes are also expressed on freshly collected tumor cells.

Peripheral blood lymphocytes of a melanoma patient were stimulated in vitro with a permanent cell line derived from the autologous tumor. Stable cytolytic T lymphocyte (CTL) clones were obtained that lysed the melanoma cell line and did not lyse autologous Epstein-Barr virus-transformed B lymphocytes or K-562 cells. These CTL clones were directed against two distinct antigens on the melanoma line. In view of the possibility that these antigens could be culture artefacts, we tested the stimulatory ability of tumor cells that had been freshly collected from metastatic relapses on the CTL clones. A considerable CTL proliferation was observed and it appeared to be specific. We conclude that the antigens recognized by the autologous CTL clones on the permanent melanoma cell line were expressed by the tumor cells in the patient.

Antigens, Neoplasm↗
PubMed1990

Carboplatin in combination with etoposide in inoperable non-small-cell lung cancer (NSCLC).

Carboplatin, a second generation platinum complex, is less nephrotoxic and emetogenic than its parent compound. We have tested the objective response to and the toxicity of the combination carboplatin 330 mg m-2 on day 1 with etoposide 120 mg m-2 on days 1, 3 and 5, administered every 3 weeks in histologically proven inoperable non-small-cell lung cancer (NSCLC) patients with a good performance status. Thirty-one patients entered the study; 29 were evaluable for response, 24 after 3 courses and 5 after 2 courses of chemotherapy. An overall response rate of 21% was found including zero complete response and 6 partial responses. In addition, 3 minor responses (10%), 12 stable diseases (38%), and 9 progressive diseases (39%) were observed. The median survival was 48 weeks, including 68 weeks for non-metastatic (M0) patients and 27 weeks for metastatic (M+) patients. This regimen was well tolerated. Gastrointestinal toxicity never exceeded WHO grade II and renal function remained in the normal range for all cases. Haematological toxicity was low in the majority of the cases; nevertheless it proved to be the dose limiting toxicity as illustrated by two grade III anemia, one grade III leucopenia, one grade III and one grade IV thrombocytopenia. Carboplatin-etoposide combination is not more active, but clearly much less toxic than cisplatin-etoposide in NSCLC.

Adenocarcinoma↗
PubMed1990

Biology of small cell lung cancer: an overview.

Despite disappointing results in the treatment of small cell lung cancer (SCLC), major progress in our understanding of SCLC biology has occurred in the past decade. Advances in the technique for culturing SCLC tumours in vitro have greatly facilitated the study of the biological properties of this tumour. The major progress in our understanding of SCLC includes: 1) the availability of nonspecific biological tumour markers such as neuron-specific enolase (NSE), the BB isoenzyme of creatine phosphokinase (CPKBB), bombesin/gastrin releasing peptide (GRP) and chromogranin A; 2) the generation of monoclonal antibodies raised against the neural and epithelial features of SCLC tumours; 3) the identification of several autocrine growth factors such as bombesin/GRP, insulin-like growth factor (IGF), transferrin and physalaemin; 4) the close study of cytogenetic abnormalities leading to the discovery of a unique chromosomal deletion of the short arm of chromosome 3 (del 3p 14-21), and to changes in oncogenic expression, e.g. c-myc, L-myc and N-myc, accounting for known biological and treatment results. These data suggest that all lung cancers arise from a common stem cell of endodermal origin. The information derived from these biological studies represents the most promising avenue towards new treatment strategies in SCLC.

Antibodies, Monoclonal↗
PubMed1989

Presence on a human melanoma of multiple antigens recognized by autologous CTL.

We derived from blood lymphocytes of a melanoma patient a large number of cytolytic T-cell clones directed against a cell line of the autologous tumor. Three distinct groups of antigens were recognized by these CTL on the autologous melanoma cells: group A consisted of stable antigens present on all sublines, whereas antigens B and C appeared unstable and were expressed by distinct sublines. In vitro immunoselections with various anti-A CTL clones were applied to the melanoma cells and variants resistant to 3 different CTL clones were obtained. These variants remained sensitive to other anti-A CTL clones, indicating that group A comprises at least 4 different antigens (D, E, F and A'). From a total of 76 CTL clones obtained from lymphocytes collected from the patient at various times, we found that 45 were anti-B, 17 were anti-C, 2 were anti-D, 9 were anti-E, 2 were anti-F and I was anti-A'. It is therefore likely that the 6 antigens identified by these CTL clones represent all or nearly all the transplantation antigens recognized by autologous CTL on this human melanoma.

Antigens, Neoplasm↗
PubMed1989

Carboplatin in association with etoposide and either adriamycin or epirubicin for untreated small cell lung cancer: a dose escalation study of carboplatin. UCL Clinical Oncology Group.

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)] received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m-2 in 60 courses, 300 mg m-2 in 69, 330 mg m-2 in 236 and 350 mg m-2 in 11, with 120 mg m-2 etoposide on days 1, 3 and 5 and either 40 mg m-2 adriamycin or 60 mg m-2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m-2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m-2 carboplatin had a neutropenia below 200 microliters-1 and a thrombopenia below 100,000 microliters-1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Early detection of doxorubicin cardiotoxicity: interest of Doppler echocardiographic analysis of left ventricular filling dynamics.

Doxorubicin (Adriamycin) is an effective anticancer agent but its therapeutic value is limited by its myocardial cardiotoxicity. To improve early detection of doxorubicin cardiotoxicity, studies were performed in patients with long-term doxorubicin treatment using pulsed Doppler echocardiography to assess the changes in left ventricular (LV) diastolic filling dynamics. M-mode echocardiographic systolic parameters and Doppler transmitral flow velocities were analyzed in two groups of patients. In group A (45 patients, mean age 45 +/- 13 years), the results were compared with those of a control group of 35 normal subjects matched for age. In group B (19 patients, mean age 44 +/- 12 years), the pretreatment results were prospectively compared with those obtained during treatment protocol. The patients received a cumulative dosage of 253 +/- 125 mg/m2 of doxorubicin for group A and 240 +/- 135 mg/m2 for group B. After doxorubicin treatment, in the two groups there were no significant changes in LV dimensions, shortening fraction, and mean velocity of circumferential fiber shortening (VCF). In contrast, Doppler echocardiographic parameters of diastolic function were significantly modified after doxorubicin in the two groups:isovolumic relaxation period was prolonged by 32% in group A (p less than 0.001) and by 22% in group B (p less than 0.005).2+ The early peak flow velocity was reduced by 18% in group A (p less 0.002) and by 13% in group B (p less than 0.04), and the ratio early peak flow velocity/atrial peak flow velocity also decreased significantly, by 23% in group A (p less than 0.001) and by 20% in group B (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Serum level of neuron-specific enolase: value as tumor marker of microcellular bronchial cancer].

This study analyses retrospectively the plasma level of neuron-specific enolase (NSE) performed in 236 patients presenting for the diagnosis of a bronchopulmonary disease. Taking a cut off on 15 micrograms/L, 61 (64%) of the 95 patients sharing a small cell lung cancer (SCLC) (45% of those with a limited disease and 90% with an extensive disease) but 8 (13%) of 60 with a non small cell lung cancer patients and 0% of those with a benign bronchopulmonary disease showed an abnormal value of NSE. Therefore in this group of patients, the diagnosis of SCLC could be assessed with a sensitivity of 64% and a specificity of 94% in patients with an NSE plasma level above 15 micrograms/L. In addition, the interest of sequential dosages of NSE for the monitoring of SCLC patients is also stressed.

Biomarkers, Tumor↗
PubMed1989

Indoor radon exposure and lung cancer in Belgium.

Indoor radon is the most important source of ionising radiation for the general public and is estimated to be a causal factor for lung cancer. Most risk assessment for low doses are based upon extrapolations of the observations among high exposed groups. As the validity of such procedure is still a controversal matter and in order to obtain direct epidemiological evidence, a case-control study about radon and lung cancer was set-up in southern Belgium. All subjects are recruited at the department of pneumology of the clinic of the catholic university of Louvain at Mont Godinne. In the first year some 130 persons entered the study. Preliminary analysis of the data gives an odds ratio of 4.2 for the exposed group of male smoking cases compared to the matched non exposed control group.

Aged↗
PubMed1988

Cytolytic response of human T cells against allogeneic small cell lung carcinoma treated with interferon gamma.

Human lymphocytes stimulated in vitro by allogeneic small cell lung carcinoma cell lines did not show any significant cytolytic activity against the stimulator tumor cells. However, a high level of lysis was observed when both stimulator and target small cell lung carcinoma cells were pretreated with interferon gamma, which increased considerably the expression of major histocompatibility class I molecules by these cells. The demonstration that small cell lung carcinoma cells can be lysed by cytolytic T lymphocytes, suggests that it will be feasible to study the autologous T cell response of patients against this tumor.

Carcinoma, Small Cell↗
PubMed1987

Production of stable cytolytic T-cell clones directed against autologous human melanoma.

We have attempted to optimize the production of stable human cytolytic T lymphocyte clones directed against autologous melanoma cell lines. MLTC were restimulated every week with irradiated melanoma cells in medium containing human serum and IL-2. After 21 to 35 days, in 5 out of 6 patients, these cultures expressed a preferential cytolytic activity against the autologous melanoma cells, as compared to autologous EBV-B cells or NK target K562. Limiting dilution of MLTC responder cells was performed at times varying from days 7 to 28, in medium containing IL-2 and allogeneic EBV-B cells as feeders. Approximately 1% of these responder cells gave rise to CTL clones that lysed the autologous melanoma cells, but did not lyse K562 or autologous B cells. It was possible to maintain in culture for several months a large number of CTL clones that retained this specificity with high activity, and multiplied more than 5-fold every week. Some of these CTL clones were dependent on the presence of the autologous melanoma cells for their growth. With one melanoma, the use of autologous CTL clones made it possible to identify 3 different antigens on the tumor cells.

Antigens, Neoplasm↗