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Biomedical subjects

E Antoine

Publications and source records attributed to E Antoine.

36 records · Page 2Linked to original sources
PubMed1994

[CA 15-3 and breast cancer].

The precise clinical value of CA 15-3 antigen has yet to be determined. With no role in screening for early breast cancer and, even if CA 15-3 seems to be correlated with bulky initial tumor burden, it appears to have no independent prognostic value. The clinical interest of CA 15-3 remains the early detection of the first recurrence. In this regard, more than 75% of first recurrences (all sites included) are associated with a significant rise in CA 15-3 levels, with a particular sensitivity for bone, liver, and lung metastases but which appears lower for locoregional recurrences. More sensitive and specific than CEA, and this whatever the site of recurrence, the rise of CA 15-3 may precede the clinically or radiologically diagnostic of recurrence by a mean lead time from 6 to 9 months. Furthermore CA 15-3 is a reliable marker for clinical course and seems to be of potential interest in monitoring disease follow-up during therapy. In the situation of a clinically isolated elevation of CA 15-3, which investigations, if any, have to be done?, and if negative must do we initiate a treatment for a "biological recurrence"? All these questions remain still opened, and today on consensual attitude can be recommended. In this issue, only results of well-designed prospective trials could help us to determine more rationally, an optimal diagnostic and therapeutic strategy.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Phase II trial of vinorelbine/doxorubicin as first-line therapy of advanced breast cancer.

PURPOSE: The study investigated the therapeutic effects of a combination of Navelbine (vinorelbine or 5'noranhydrovinblastine; Pierre Fabre Médicament, Boulogne, France) and doxorubicin in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Ninety-seven patients with progressive and assessable advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered onto the study. Eighty-nine patients were assessable for toxicity and response by World Health Organization (WHO) criteria; the other eight patients were excluded because they did not meet entry criteria or because of protocol violations. Navelbine was administered at 25 mg/m2 by 30-minute intravenous (IV) infusion on days 1 and 8, and doxorubicin at 50 mg/m2 by slow IV infusion on day 1, with each course repeated at 3-week intervals. Patients were treated for a maximum of 11 cycles or until progression or major toxicity. RESULTS: Objective responses were observed in 66 of 89 assessable patients (74%; 95% confidence interval, 63% to 85%). There were nineteen (21%) complete responses (CRs) and 47 (53%) partial responses (PRs). In addition, 20 patients (22.5%) had stable disease and three (3.5%) progressed while on treatment. Responses were observed at all sites of metastatic disease. Forty-one of 58 patients with visceral disease responded (71%) and 25 of 31 with soft tissue and bone disease experienced an objective response (81%). The median duration of response was 12 months (range, 2.4 to 40.5), and the median overall survival was 27.5 months (range, 4 to 46). Neutropenia was dose-limiting, with 36 patients (41%) experiencing grade 3 or 4 toxicity. Of 727 cycles administered, there were 20 admissions (3%) for treatment of febrile neutropenia, involving 14 of 89 patients (16%). Treatment-related cardiotoxicity at grade 2 to 4 was experienced by 10% of patients and necessitated the interruption of treatment in 1.5% of cycles. Other side effects were uncommon or manageable by conventional means. CONCLUSION: The encouraging response rates and duration achieved with this combination of Navelbine/doxorubicin under the conditions of this study deserve further randomized comparative trials with standard regimens.

Adenocarcinoma↗
PubMed1993

Chemoimmunotherapy of metastatic malignant melanoma. The Salpétrière Hospital (SOMPS) experience.

Optimistic results were obtained in the treatment of 39 patients with surgically incurable metastatic malignant melanoma using a regimen including 2 to 3 monthly induction cycles of cis-diamminedichloroplatinum (CDDP), recombinant interleukin-2 (rIL-2) and interferon alpha-2a (IFN alpha-2a). 33 of 39 patients were pretreated with chemotherapy (dacarbazine and/or fotemustine:31, CDDP:6) and 17 of 39 with IFN alpha-2a. Overall response rate was 54% with 13% achieving a complete response for up to 59+ weeks. Moderate to severe side-effects were reversible on rIL-2 cessation and toxicity was manageable in a routine inpatient setting. These results are especially encouraging as they were seen in previously treated patients, classically low responders, including 3 who were resistant to cisplatin or other platinum complexes. The question remains if this regimen bypasses traditional mechanisms of drug resistance.

Adult↗
PubMed1993

Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma.

PURPOSE: To evaluate the activity and the toxicity of the combination of cisplatin (CDDP)/recombinant interleukin-2 (rIL-2) and interferon alfa-2a (IFN alpha) in disseminated malignant melanoma (DMM). PATIENTS AND METHODS: Between December 1990 and March 1992, 39 patients with biopsy-proven metastatic malignant melanoma (MM), bidimensionally measurable lesions and an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2 entered this protocol. Seventy-nine percent had received previous chemotherapy including platinum complex (15%) and alpha interferon (44%). They received CDDP (100 mg/m2 on day 0) followed by IL-2 18.10(6) IU/m2/d continuous intravenous (IV) infusion from day 3 to day 6 and from day 17 to day 21. The cycle was repeated on day 28. Subcutaneous IFN alpha 9.10(6) IU three times weekly was administered throughout the treatment period. From day 66 or 94, patients were administered a maintenance cycle with CDDP 100 mg/m2, subcutaneous IL-2 5.10(6) IU/m2/d from day 15 to day 19 and from day 22 to day 26 and IFN alpha 9.10(6) IU three times weekly repeated every 5 weeks (maximum four cycles). RESULTS: Among 39 assessable patients, five patients achieved complete responses (CRs). Sixteen patients had partial responses (PRs). The overall objective response rate was 53.8%. The number of metastatic sites was the only response-predictive factor. Toxicity was manageable in a routine patient setting and there was no life-threatening toxicity. CONCLUSION: These results seem to indicate a possible synergy between CDDP/rIL-2 and IFN alpha in MM.

Adult↗
PubMed1992

Antitumoral activity of bombesin analogues on small cell lung cancer xenografts: relationship with bombesin receptor expression.

Gastrin releasing peptide (GRP), the human homologue of bombesin (BN), is an autocrine growth factor for small cell lung cancer (SCLC) cells. The synthetic octapeptides [D-cpa1-beta-Leu8-des-Met9]litorin (BIM 26182) and [D-Phe6-Leu13-CH2NH-Cpa14]bombesin(6-14)NH2 (BIM 26189) are potent GRP/BN antagonists of the proliferation of 3T3 and rat pancreas cells. The effect of these analogues on the proliferation of four SCLC cell lines (SCLC 6, SCLC 41, SCLC 75, SCLC 74R) was tested in vitro and in vivo. Two of these SCLC lines (SCLC 41M and SCLC 75) had receptors for BN/GRP and expressed the prepro-GRP mRNA. BIM 26182 and BIM 26189 inhibited [3H]thymidine incorporation into the DNA of SCLC 41 cells, stimulated [3H]thymidine incorporation in SCLC 6, and had no effect on the two other cell lines. The SCLC implanted s.c. in nude mice were treated with either BIM 26182 or BIM 26189. BIM 26182 and BIM 26189 injected at the doses of 50 micrograms twice a day (s.c.) around the tumor for 10 to 21 days delayed the growth of SCLC 41 and of SCLC 75. The maximal effect was observed during the treatment period, after which the tumors regrew, suggesting a cytostatic effect of these peptides. No inhibitory effect of the peptides on SCLC 74R or SCLC 6 growth was observed. These data suggest that GRP antagonists are able to inhibit the in vitro and in vivo growth of BN/GRP receptors-positive SCLC.

Animals↗
PubMed1990

Methionine dependency of malignant tumors: a possible approach for therapy.

When methionine (Met), an essential amino acid, was substituted for by its precursor homocysteine (Hcy) in the culture medium, normal cells such as fibroblasts proliferated normally. In contrast, many tumor cells failed to grow or grew at a lower rate. Met dependency is acquired simultaneously with cell transformation, as observed with HBL 100, a human mammary epithelial cell line that acquired increased malignancy as a function of in vitro passage number, and NIH/3T3 (J10), a mouse fibroblast line transformed by transfection with the human HRAS oncogene. A relationship was observed between Met dependency and metastatic potential of the RMS-21, RMS-S4T, and RMS-J1 sublines derived from RMS-0, a rat rhabdomyosarcoma cell line: the higher the metastatic potential of the cell line, the higher the concentration of Met required to maintain its proliferation. Met-independent cells derived from the RMS-0 line, obtained by a progressive decrease of Met in the culture medium lost their tumorigenicity when injected into rats fed with Met-deprived diets. In addition, the in vitro motility of RMS-S4T tumor cells, a marker of metastatic capability, decreased in Met-free Hcy-complemented (Met- Hcy+) medium. Similarly, RMS-0 tumor cells, preincubated in a Met- Hcy+ culture medium for 24 hours, evidenced a decreased capacity to form lung colonies when injected into syngeneic rats: the median number of lung colonies was 27 and 3 (P less than .05) for cells cultivated in Met+ Hcy- and Met- Hcy+ media, respectively. An amino acid-defined mixture reproducing casein composition was used as a protein source in the diets fed to RMS-J1 tumor-bearing rats. Dietary substitution of Hcy for Met (i.e., met deprivation) resulted in decreased tumor growth (from 44.4 +/- 1.0 to 40.6 +/- 1.4; P less than .05) and prevention of metastatic spread (from 37 to 0; P less than .05). In conclusion, exogenous Met can be substituted for Hcy to maintain the survival of normal cells but is essential for tumor cell growth in vivo as well as in vitro. Therefore, this defect of cancerous versus normal cells could be used for a therapeutic purpose.

Adenocarcinoma↗
PubMed1989

Binding and internalization of exogenous glycosaminoglycans in weakly and highly metastatic rhabdomyosarcoma cells.

The fate of exogenous glycosaminoglycans in cultures of strongly (RMS 0) and weakly (RMS 8) metastatic rat rhabdomyosarcoma cells was studied. The time course and concentration dependence of binding and internalization of the radiolabeled sulfated glycosaminoglycans were determined. Weakly metastatic cells took up heparin, heparan and dermatan sulfates into their pericellular compartment at a higher rate than the strongly metastatic RMS 0 cells. The RMS 8 cells exhibited about two times more binding sites for these iduronic acid containing glycosaminoglycans, and internalized higher amounts of them than the RMS 0 cells. The uptake of the chondroitin sulfate into the peri- and intracellular compartments of both cell types was about 5-15% of that of the other glycosaminoglycans studied. The specificity of displacement of the pericellular heparin and dermatan sulfate by the unlabeled glycosaminoglycans indicates the involvement of specific structural features of the polysaccharide chains in the interactions of glycosaminoglycans with the surface of rhabdomyosarcoma cells, beside ionic forces due to the polyanionic character of the glycosaminoglycans. Heparin and heparan sulfate degradation products, mainly large oligosaccharides, were recovered from the surface of RMS 0 cells but were absent on the surface of the RMS 8 cells. About 30% of the internalized heparin and heparan sulfate was present in the partially degraded form in both cell types. Oligosaccharides derived from glycosaminoglycans were not released into the medium. The decrease in the amount of iduronic acid containing glycosaminoglycans internalized by the highly invasive cells seems to be correlated with an increased cell-associated degradation and with an apparent loss of glycosaminoglycan binding sites on the cell surface.

Animals↗
PubMed1989

Promotion of micrometastasis proliferation in a rat rhabdomyosarcoma model by epidermal growth factor.

Using a rat rhabdomyosarcoma 9-4/0, we investigated the role of epidermal growth factor (EGF) in tumor dissemination. In vitro, we detected high-affinity EGF receptors on tumor cells and stimulation of their proliferation by EGF. When injected iv, EGF-pretreated cells demonstrated an increased capacity to form lung colonies and to invade lymphatic tissue. In vivo, EGF treatment led to increased metastatic spread of subcutaneous tumors. When primary tumors were ablated, and the treatment was given from the time of graft until ablation (seeding step), no effect on metastatic spread was noticed. When treatment was given from the time of ablation until death (growth step), EGF increased the number of lung metastases and of invaded lymph node sites.

Animals↗
PubMed1988

In vivo emergence of a highly metastatic tumour cell line from a rat rhabdomyosarcoma after treatment with an alkylating agent.

Rats bearing a transplanted nickel-induced rhabdomyosarcoma (RMS 9-4/0), treated with chlorozotocin (CZT), an alkylating agent, showed an amplified metastatic invasion of the lung (median of 165 lung tumour nodules, compared to 3 for untreated controls). A higher level of metastatic invasion (200 nodules) was reached spontaneously after the grafting of the S4T line, which was obtained by successive in vivo passages of RMS 9-4/0 cells in CZT treated rats. S4T tumour cells also invaded the liver and a considerable proportion of the lymph nodes. The NT4T line, obtained by successive in vivo passages in untreated rats, showed a lesser degree of enhancement of metastatic capacity (57 nodules). Both derived lines proved to be more aggressive than the parental, proliferated more rapidly, and were resistant to CZT toxicity. Only the non-treated lineage became more resistant to NK lysis. The S4T line lost its myogenic differentiation and was best described as a fibrohistiosarcoma, whereas NT4T did not. Chromosome analysis demonstrated a reduced range of chromosome number per cell in both lines. We conclude that both S4T and NT4T tumours became more metastatic than RMS 9-4/0 as the result of tumour progression through in vivo passages, and that in addition S4T acquired a spontaneously higher metastatic potential, similar to that which occurred in rats grafted with RMS 9-4/0 or NT4T tumours and treated by CZT. This suggests an inheritable mutation in the S4T line.

Animals↗
PubMed1988

[Antithyrotropin receptor antibodies in a series of Basedow's disease].

Thyrotrophin binding inhibiting immunoglobulins (TBII) were tested in 40 Graves' disease patients with hyperthyreosis, by an isotopic receptor assay (TRAK-Assay Behring). The samples were taken before, during and at the end of the hyperthyroid treatment. TRAb were present in serum of 86.67% of the patients before the treatment and in none of the 20 healthy control volunteers. There was no correlation between TRAb values and either the clinical signes of the disease neither the other thyroidal antibodies. After discontinuation of the antithyroid therapy (18 to 24 months after the onset) TRAb were negative in 71.4% of the patients; among this group 33% had a late relapse of the disease. In the positive TRAb group after discontinuation of the antithyroid therapy, 83.3% had a relapse of the disease and this relapse occurred shortly. There is a significant correlation between the TRAb values and the occurrence of relapse. In conclusion, TRAb values at the end of hyperthyroid treatment in Graves' disease patients seems to be a useful predictor value of the clinical course of the disease. This may be also a good help in the decision to continue or discontinue antithyroid therapy in Graves' disease patients with hyperthyreosis.

Adolescent↗
PubMed1987

[Hepatic involvement in secondary syphilis].

A case of secondary syphilitic hepatitis is reported. A 49-year old woman was admitted for weight-loss, fever, hepatomegaly and splenomegaly. Diagnosis of syphilitic hepatitis was based on cholestasis associated with positive serologic tests for syphilis without other immunological disturbances. Biopsy of the liver showed a moderate infiltration in and around the portal tracts. Immunofluorescence study for treponema was negative. Rapid improvement was obtained with penicillin initially associated with steroid therapy. Liver involvement in secondary syphilis is characterized by anicteric cholestasis, an inflammatory syndrome, and periportal infiltrate inconstantly associated with centrilobular necrosis, granulomatous reaction and presence of treponemas in the lesions. Due to the increasing frequency of sexually transmitted diseases, this diagnosis could become more frequent.

Female↗
PubMed1984

Amplified pulmonary metastases of a rat rhabdomyosarcoma in response to nitrosourea treatment.

Repeated observations in our laboratory show that the chloroethylnitrosourea of cysteamine ( CNCC ) induces slowed tumor growth rate and decreased lymph node metastasis in rats bearing a rhabdomyosarcoma but concomitantly enhances metastatic dissemination in the lung. Tumors obtained by sc graft of tumor cells, in syngeneic rats, gave a reproducible pattern of metastases at nodal and pulmonary sites after a 60-80-day period. CNCC was administered orally at a dose of 50 mg/kg once a week for 5 weeks beginning at the time of tumor appearance. Forty-five of 46 CNCC -treated rats had lung metastases with 95 (+/- 9.7) nodules; in the control group 29 of 41 rats had lung metastases with 7 (+/- 1.5) nodules. This amplifying effect was found after treatment with two other nitrosoureas (chlorozotocin and hydroxyethylchloroethylnitrosourea ) but not with cyclophosphamide and methotrexate. Lung metastatic amplification was also observed after treatment of the 13762 mammary adenocarcinoma in Fischer rats and treatment of nickel-induced soft tissue tumor. Several hypotheses have been proposed. The dissociated effect of nitrosourea on local tumor, lymph nodes, and pulmonary metastases does not support the concept of systemic immunosuppression as the main mechanism of this phenomenon, but a decrease of local immunological defenses exerted by NK cells, for example, could be possible. Alternatively, a direct effect of the drug on lung tissue, especially lesions of endothelial tissue, could be responsible for the observed effect. Nitrosourea treatment of rats after surgical excision of the tumor, as adjuvant chemotherapy, was responsible for an amplification effect in association with local recurrences. From this fact we hypothesized that nitrosourea treatment could modify the equilibrium of cell subpopulations in the tumor by selecting highly metastatic drug-resistant variants. Although the mechanism of the amplifying effect of nitrosoureas has not been elucidated, our study shows a possible risk in the use of these drugs for inductive or adjuvant chemotherapy.

Adenocarcinoma↗
PubMedDate not supplied

DNA topoisomerase I: customs officer at the border between DNA and RNA worlds?

DNA topoisomerase I is required for the normal development of multicellular organisms, probably because it plays a role in controlling gene activity, in addition to its function in relieving tortional stress during DNA replication and transcription. The discovery of DNA topoisomerase I as a specific kinase that phosphorylates serine-arginine rich (SR) splicing factors may provide new insights into their precise function in regulating gene expression. It is clear that the splicing factors phosphorylated by DNA topoisomerase I can modulate gene expression by changing the splicing pattern of structural genes. Studies of the splicing mechanism suggest that the phosphorylation of serine residues of SR proteins contribute to their activity. As this phosphorylation can be accomplished by several kinases, it remains to be determined whether phosphorylation by DNA topoisomerase I protein kinase is the limiting step in regulating this process. The availability of specific inhibitors of DNA topoisomerase I, structurally related to the alkaloid camptothecin, have made it possible to address this question experimentally. These inhibitors, which hold great promise as antineoplastic drugs, lead to specific inhibition of SR protein phosphorylation in cultured cells. This observation will hopefully lead to improved understanding of the mechanism by which these drugs act at cellular level.

Animals↗