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Biomedical subjects

M Mousseau

Publications and source records attributed to M Mousseau.

At least 37 records · Page 2Linked to original sources
PubMed1997

Decreased folylpolyglutamate synthetase activity in tumors resistant to fluorouracil-folinic acid treatment: clinical data.

Thymidylate synthase (TS) is the main target for fluorouracil (FU). Optimal cellular concentrations of reduced folates in polyglutamated forms [via folylpolyglutamate synthetase (FPGS)] are necessary for achieving maximal TS inhibition. The aim of this multicentric prospective study was to analyze the link between clinical response to FU therapy for liver metastases of colorectal carcinoma and tumoral TS and FPGS activities. Forty-four advanced colorectal cancer patients (15 women and 29 men; median age 63, range, 27-78 years) receiving a standard FU-folinic acid protocol were included. A single hepatic tumoral biopsy was obtained systematically at the time of diagnosis. For 24 patients, a biopsy in the primary colon tumor was available. TS and FPGS activities were measured by radioenzymatic assays. Clinical response on hepatic metastases was 1 complete response, 12 partial responses, 14 stabilizations, and 17 progressions. In hepatic biopsies, TS activity (median, 185; range, <10-3111 fmol/min/mg protein) and FPGS activity (median, 1270; range, <400-3730 fmol/min/mg protein) exhibited a wide variability. TS activity in primary tumors (median, 461; range, 35-2565 fmol/min/mg protein) was significantly higher than in hepatic metastases. No difference was observed between primaries and metastases for FPGS. FPGS activity expressed in liver metastases was significantly correlated to that expressed in primaries. The distribution of TS activity in liver metastases was not significantly different between responsive and nonresponsive patients. However, FPGS activity measured in liver metastases was significantly higher in responsive patients (median, 1550 fmol/min/mg protein) than in nonresponsive patients (median, 1100 fmol/min/mg protein). A discriminant analysis revealed that 24 of the 25 patients exhibiting a liver FPGS activity </=1100 fmol/min/mg protein and/or a liver TS >320 fmol/min/mg protein were nonresponding patients. These data establish for the first time the potential importance of tumoral FPGS activity for assessing FU-folinic acid responsiveness in the clinical setting.

Adult↗
PubMed1996

5-Hydroxymethyluracil excretion, plasma TBARS and plasma antioxidant vitamins in adriamycin-treated patients.

The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)-was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR-mainly its cardiotoxicity-may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly .OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and alpha-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.

Adult↗
PubMed1996

Effects of elevated CO(2) concentration on leaf characteristics and photosynthetic capacity of beech (Fagus sylvatica) during the growing season.

Two-year-old beech (Fagus sylvatica L.) saplings were planted directly in the ground at high density (100 per m(2)), in an experimental design that realistically mimicked field conditions, and grown for two years in air containing CO(2) at either ambient or an elevated (ambient + 350 ppm) concentration. Plant dry mass and leaf area were increased by a two-year exposure to elevated CO(2). The saplings produced physiologically distinct types of sun leaves associated with the first and second growth flushes. Leaves of the second flush had a higher leaf mass per unit area and less chlorophyll per unit area, per unit dry mass and per unit nitrogen than leaves of the first flush. Chlorophyll content expressed per unit nitrogen decreased over time in plants grown in elevated CO(2), which suggests that, in elevated CO(2), less nitrogen was invested in machinery of the photosynthetic light reactions. In early summer, the photosynthetic capacity measured at saturating irradiance and CO(2) was slightly but not significantly higher in saplings grown in elevated CO(2) than in saplings grown in ambient CO(2). However, a decrease in photosynthetic capacity was observed after July in leaves of saplings grown in CO(2)-enriched air. The results demonstrate that photosynthetic acclimation to elevated CO(2) can occur in field-grown saplings in late summer, at the time of growth cessation.

Journal Article↗
PubMed1996

Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy.

PURPOSE: The purpose of this study was to evaluate the efficacy and tolerance of recombinant human interferon gamma (rIFN-gamma) as second-line treatment in patients with persistent disease at second-look laparotomy. PATIENTS AND METHODS: One hundred eight patients with residual disease at second-look laparotomy were treated with rIFN-gamma (20 x 10(6) IU/m2) administered intraperitoneally (IP) twice a week for 3 to 4 months. In the absence of clinically assessable disease, response to rIFN-gamma was assessed with a third-look laparotomy. RESULTS: Of 98 assessable patients, 31 (32%) achieved a surgically documented response, including 23 patients (23%) with a complete response (CR). The age and size of residual tumor were significant prognostic factors for the response to rIFN-gamma. A 41% CR rate was observed in 41 patients younger than 60 years and with residual tumor less than 2 cm. The probability of response was independent of previous response to first-line chemotherapy. The median duration of response was 20 months and the 3-year survival rate in responders was 62%. Response to rIFN-gamma was the most significant prognostic factor for survival of patients with residual disease. Adverse events included fever, flu-like syndrome, neutropenia, and liver enzyme disturbances. No significant peritoneal fibrosis was noted. CONCLUSION: These results support the potential interest of IP rIFN-gamma as adjuvant treatment in ovarian cancer. Controlled prospective trials are required to determine its place in the therapeutic strategy of this malignancy.

Adult↗
PubMed1995

A recent increase in the incidence of prostatic carcinoma in a French population: role of ultrasonography and prostatic specific antigen.

Between 1979 and 1990, the incidence rate (World Standard) for cancer of the prostate in the region of Isère (France) increased from 22.1 to 45.0 cases per 100,000 men, although there was no concurrent increase in mortality (16.0 to 17.6 cases per 100,000 men). This represents a mean increase per year of 6.3% for incidence, compared with 1.3% (NS) for mortality. Incidence of cases with metastases at diagnosis also remained stable with time. In this area, Prostatic Specific Antigen assays began in 1987, and rectal ultrasonography was implemented in 1984, but activity peaked only in 1988. Thus, during 1986-1988, there was both an implementation of new diagnostic procedures and an increase in the incidence of prostatic carcinoma, which suggests that the latter was the result of increased detection of small latent carcinomas. This has implications for public health since apart from increasing costs, it might unduly disturb the life of otherwise healthy people.

Adult↗
PubMed1994

[Drug resistance of human tumors: from the laboratory to the clinic].

Chemoresistance of human malignant tumors causes the failure of anticancer agents for most carcinomas and for some hematological tumors. It is due to bad pharmacological conditions and also to resistance mechanisms at the cellular and at the molecular level. The identification and the comprehension of these resistance mechanisms as well as the possibility of circumventing them or preventing them might be responsible of a therapeutic progress in the next few years. However, at the present time, methodological process of identification and quantification of these mechanisms persist and the preliminary results of clinical trials with revertant drugs are still weak.

Antineoplastic Agents↗
PubMed1994

[Methods for diagnosing MDR: immunohistochemistry versus molecular biology].

The methods of multidrug resistance (MDR) detection in human malignant tumors are numerous. The process of molecular biology (Slot Blot, Northern Blot, Reverse Transcription Polymerase Chain Reaction, PCR) and the process of in situ hybridization or immunohistochemistry are complementary. The process of molecular biology are quantitative and especially sensitive for PCR, by contrast they fail in specificity. This specificity is obtained by in situ hybridization and immunohistochemistry. However, none of these methods give knowledge of GP170 functional activity. The detection of functional GP170 can be identified by rhodamine or daunorubicin intracellular accumulation with flux cytometry or by scintigraphically imaging GP170 expression in vivo with Tc-Sestamibi. The multiplicity of methods for detecting multidrug resistance show that there is no consensus about the best process to employ commonly. In consequence, the alone MDR biological diagnosis should not be the rationale of choice for second line chemotherapy or for using MDR revertant agents. In other words, the MDR biological diagnosis, keeping in mind that other chemoresistant mechanisms (topoisomerases, glutathione system, etc) could be present simultaneously or successively during tumor spreading or during successive antineoplastic treatments.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

[Modulation of indications of adjuvant hormone therapy with tamoxifen in T1T2/N0N1 breast cancers. Preliminary results of a multicenter study with 695 cases].

From 1982 to 1990, patients less than 75 years, without any previous or synchonous carcinoma, suffering from an invasive breast cancer classified as T1T2/N0N1/MO according to clinical TNM staging, were enrolled in this study; 82.4% underwent a breast conservative procedure and 17.2% a modified radical mastectomy followed by a postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade, estradiol receptor content, were used to define three groups of patients. The breakdown of patients is not well balanced: 416 women were included in group I (N-, grade I II, ER+) when there was no adjuvant medical treatment, 110 in group II (N-, grade III, ER+), 169 in group III (N+ < or = 3, grade I II, ER+). Patients from the latter two groups were receiving tamoxifene, 20 mg per day for 2 years; Those women not menopaused received first a pelvic irradiation. With a median follow-up of 35 months (1-138) the overall survival is respectively for the three groups 95%, 96%, 96% (P = 0.5) and the disease free survival 86%, 93%, 90% (P = 0.1). The actuarial local regional remission rate is 94%, 97%, 99% (P = 0.07). Such results need to be updated with a longer follow-up, but they show the ability of adjuvant hormonotherapy to tailor the short term survival thanks to prognostic factors.

Adult↗
PubMed1994

[Chemotherapy of brain tumors: biological basis of its limited efficacy].

Chemotherapy is often the only treatment for relapse of brain tumors and should increase the survival of patients with gliomas. Although new anticancer drugs have been discovered, the number of active drugs in these tumors is very low. Several biological mechanisms decrease the efficacy of chemotherapy: cellular kinetics, heterogeneity and micro-environment of brain tumors, and the classical blood-brain barrier. Moreover, several mechanisms of chemoresistance, identified in other tumors, should be involved in intrinsic chemoresistance. These biological factors, which are involved simultaneously or successively suggest that the chemotherapy currently used in brain tumors cannot increase the response rate; even if high dose chemotherapy with autologous bone marrow transplantation or intratumor administration of drugs are used.

Adolescent↗
PubMed1994

[Chemotherapy of small-cell lung cancer by a combination of teniposide, ifosfamide and carboplatin].

Thirty six SLC patients have been treated with a combination therapy of ifosfamide 2 g/m2, D1 and D2, carboplatin 300 mg/m2 D1 and teniposide 100 mg/m2 D1 to D3. All patients were younger than 70 years, 31 males, five females, ten limited diseases, 26 extended diseases (without brain metastasis) Performance status 0, 1 or 2, mean weight loss 3.7 kg. Thirty six patients were evaluable for response. We have noted three complete response and 28 partial response (objective response rate 86%). The main toxicity of this combination therapy was myelo-suppression (86% of grade 3 and 4). Twenty seven patients have relapsed, the median relapse free survival time is 310 days. The median survival of the 36 patients is 340 days, one patient is alive more than 30 months after the diagnosis. The ifosfamide-carboplatin-teniposide combination is an effective treatment in small cell lung cancer, its toxicity remains tolerable.

Adult↗
PubMed1993

A study of the expression of four chemoresistance-related genes in human primary and metastatic brain tumours.

We investigated four mechanisms of intrinsic chemoresistance in a series of 67 human brain tumours including 31 gliomas (one grade I ganglioglioma, nine grade II and 10 grade III astrocytomas, 11 glioblastomas), 13 cerebral metastases, one medulloblastoma, one malignant teratoma, three ependymomas and 18 meningiomas. We studied four genes by northern blotting: multidrug-resistance (MDR 1), glutathione-s transferase (GST pi), dihydrofolate reductase (DHFR), and topoisomerase II (Topo II). The Topo II gene was absent in the normal adult brain (100%) and in 64% of the tumour samples tested. A second gene, GST pi, was found to be overexpressed in 38% of brain tumours. The two other chemoresistance-related genes were occasionally overexpressed in brain tumours (2% for MDR1, 9% for DHFR). Our results provide evidence that chemoresistance is intrinsic to the brain tissue and seems likely to be a multifactorial process.

Blotting, Northern↗
PubMed1991

[Hepatic metastasis of unknown primary site].

In this retrospective study, 91 patients (30%) out of a series of 304 with metastatic cancer of unknown primary site were found to have liver metastases. The liver was the only metastatic site in 28 (31%) cases and was associated with other sites in 63 (69%) cases. Median age was 62 yr in 61 male patients and 59 yr in 30 female patients. Thirty patients were submitted to an extensive investigation in search of the primary tumor, including systematic endoscopies: no primary cancer was found in these patients. In 61 other patients, only symptom-oriented investigations were performed and the primary cancer was found in 11 cases. The histologic type was adenocarcinoma in 71 (78%) cases, undifferentiated in 11 (12%) cases, epidermoid in 5 (6%) cases and determined by cytology alone in 4 cases. The median survival was 4 months in patients with metastases in the liver only, and 5 months in the other patients. This difference was not significant, so prognostic factors such as the Karnofsky index, weight loss, CEA and LDH levels were evaluated in the entire group; these factors do not have significant prognostic value. By contrast, when patients were able to receive chemotherapy, median survival was better (4 months) than without (median survival: 1 month; P = 0.005). In addition, in the case of objective response to chemotherapy, the median survival was 9 months versus 3.5 months for patients without objective response (P = 0.001). Seventy-three out of 91 patients (80%) were treated with chemotherapy regimen; 65 patients were evaluable: the objective response rate was 11 +/- 7% (7/65). Different regimens were used. With a non-toxic combination of fluorouracil, vinblastine and cyclophosphamide, 3 partial responses greater than or equal to 50% out of 43 patients (7 +/- 8%) were obtained. No significant advantage was observed when adriamycin was added to FU (4/13): 31 +/- 25%. Second- or third line chemotherapy regimen due to progression of the disease after the first-line combination provided only one objective response out of 36 patients. According to this retrospective study we recommend that overinvestigation be avoided in patients, with liver metastases of unknown primary site and that these patients be treated with non-toxic drug combinations.

Adenocarcinoma↗
PubMed1990

[Association of 5-FU, CDDP and hypofractionated radiotherapy in recurrences of subtentorial astrocytomas and malignant gliomas in adults].

Twenty-seven patients who had a relapse of astrocytomas or supra-tentorial malignant gliomas, previously treated by radio-surgical combination or exclusive irradiation, underwent a combination of 3 courses of 5-FU, cis-platyl and hypofractionated irradiation. No objective response was observed, but there was a progression of the tumor in 33% of the cases, and no change in 67%. Overall median survival was 7 +/- 1.5 months. The 20 patients with grade III or IV astrocytomas had a lower median rate than the 7 patients with grade II astrocytomas or oligodendrogliomas: 6 +/- 1.8 months versus 18 +/- 3.2 (P = 0.16). Median survival was 14 +/- 2.7 months for neurological responders and 6 +/- 2.1 months for non-responders (P = 0.017).

Adult↗
PubMed1987

[Prognostic value of estradiol and progesterone receptors in stage I and II breast cancer with an adjuvant treatment].

Forty-seven stage T1, 225 stage T2, treated from January 1977 to December 1982 were studied. The median followup is 31 months (18-92) and the median age 57.5 years (26-92). On the 247 axillary clearances performed, there were 53% N- and 47% N+. The dextran coal method was used for the receptors dosage with R 2858 as ligand for estradiol and R 5020 for progesterone: positivity threshold was set at 10 fmoles. The RE+/RP+ group represents 40%, the RE+/RP- group 30%, the RE-/RP- group 7%, the RE-/RP- group 23%. The radio-surgical combination was systematic, with or without conservative treatment, followed by an adjuvant chemotherapy (15%), an hormonotherapy (34%), a chemohormonoprophylaxy (23%), within a protocol balancing the systemic treatment according to the following poor prognosis factors: axillary clearance positivity, grade 3 SBR, cytological grade 3. The crude actuarial survival is 96 +/- 4% (RE+ RP+); 73 +/- 15% (RE+ RP-); 78 +/- 12% (RE- RP-) and the disease-free survival was 84 +/- 9% (RE+ RP+); 68 +/- 15% (RE+ RP-), 67 +/- 14% (RE- RP-) with a significant difference between RE+ RP+ and RE+ RP- (P less than 10(-3)) and RE+ RP+ and RE- RP- (P less than 10(-5)). The crude actuarial survival and the disease free survival are studied according to menopausal status, Scarff-Bloom grade, and N+/N- axillary status. For N- patients, there is no significant difference for the disease-free survival, 84 +/- 14% (RE+ RP+); 85 +/- 11% (RE+ RP-); 79 +/- 15% (RE- RP-), as there is no difference for the five year disease-free survival between N- RE+ RP+ patients (84 +/- 14%) and N+ RE+ RP+ patients (84 +/- 13%).

Adult↗
PubMed1984

Doppler waveform analysis versus segmental pressure and pulse-volume recording: assessment of occlusive disease in the lower extremity.

In a prospective study, the accuracy of combined segmental pressure measurements and pulse-volume recordings was compared with Doppler waveform analysis in evaluating peripheral arterial occlusive disease. Before arteriography, 50 patients (100 limbs) underwent vascular assessment which included measurement of the segmental pressure and pulse volume at the thigh, calf and ankle. Analogue Doppler waveform tracings were obtained from the femoral, popliteal and tibial arteries and used to calculate the pulsatility index and inverse damping factor. Results of each method were assessed by independent observers and compared with the arteriographic data. No appreciable difference was demonstrated between the two methods, both giving an overall accuracy in the 90% to 95% range. Both accurately predicted the severity of iliac and superficial femoral artery obstruction and distinguished iliac from proximal disease of the superficial femoral artery. Outflow disease (tibial arteries) was better assessed by measurement of segmental pressures than by Doppler waveform analysis or pulse-volume recording alone.

Angiography↗