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Biomedical subjects

R Plagne

Publications and source records attributed to R Plagne.

At least 55 records · Page 3Linked to original sources

Disposition of new sulphur-containing 2-(chloroethyl)nitrosoureas in rats.

N'-(2-Chloroethyl)-N-[2-(methylsulphinyl) ethyl] and N'-(2-chloroethyl)-N-[2-(methylsulphonyl) ethyl]-N and N'-nitrosoureas (CMSOEN1, CMSO2EN1, CMSOEN2 and CMSO2EN2) are new nitrosoureas derived from cysteamine. Two of them (CMSOEN2 and CMSO2EN2) have shown excellent efficacy against several murine tumours. The inactive agents (CMSOEN1 and CMSO2EN1) display low alkylating activity but high carbamoylating activity. In contrast, the active agents (CMSOEN2 and CMSO2EN2) are strong alkylating agents but relatively weak carbamoylators. The disposition of CMSOEN2 and CMSO2EN2 was studied in rat, using two differently labelled species of each compound, administered i.v. (60 mumol/kg). Plasma disappearance, tissue distribution (with the exception of the brain) and elimination of radioactivity are similar for the two compounds similarly labelled. In contrast, these parameters are strongly influenced by the label position used. Plasma disappearance of unchanged CMSOEN2 and CMSO2EN2 follows a first-order kinetic process with the same half-life for both compounds (30-31 min). More unchanged CMSO2EN2 is found in brain compared to its congener (55 nmol/g and 37 nmol/g respectively at five minutes). This is most likely the consequence of the higher lipophilic character of the former compound. The breakdown product 2-chloroethanol was identified in plasma.

Alkylation↗

[Current role of oncostatic chemotherapy in malignant testicular tumors].

Recent results with the therapeutic strategy for malignant testicular tumors are presented. Nearly 80% of these tumors can be cured by the coordinated therapeutic efforts of a surgeon and medical oncologist. Cis-platinum chemotherapy regimens are widely used and intensive chemotherapy followed by autologous bone marrow transplantation should enable to cure poor prognosis forms in the near future.

Antineoplastic Combined Chemotherapy Protocols↗

[Therapeutic problems posed by hemiballism of metastatic origin].

A 40 year old woman undergoing treatment for cancer of the breast presented with metastatic hemiballism. Diagnosis was supported by the presence of bone and liver metastases and by CT-scan showing an enhanced rapidly growing lesion in the subthalamic region contralateral to hemiballism. Treatment by corticotherapy and neuroleptics was ineffective. Radiotherapy was unsuccessful. Metastatic hemiballism is a rare disease with no effective treatment.

Adult↗

[Treatment of epithelial cancers of the ovary in advanced stages with surgery and cisplatin chemotherapy].

Seventy-one patients with advanced epithelial ovarian carcinoma were treated at the Centre Jean Perrin between May 1979 and December 1983. Following an initial laparotomy performed for staging and maximum cytoreductive surgery, six to twelve courses of chemotherapy were delivered with cis-platinum; 43 patients underwent a second look operation (S.L.O.). The results of initial surgery, chemotherapy and S.L.O. are discussed: survival rate is 57% at 3 years for stage III. 38% complete remission induced by chemotherapy were proved by negative S.L.O. after primary surgery with residual disease. Initial complete debulking and negative S.L.O. were significant factors that improved prognosis. Improvement of survival expectancy by removal of all macroscopic residual disease at S.L.O. remains to be proved. Treatment after S.L.O. is still under discussion.

Adult↗

Second-look laparotomy in managing epithelial ovarian carcinoma.

Fifty-one patients treated for an epithelial ovarian carcinoma underwent a second-look operation (SLO) from August 1979 to December 1984. Previously, an initial laparotomy had been performed for staging and maximum cytoreductive surgery. This was followed by 6 to 12 courses of combination chemotherapy including cisplatin. Findings at SLO and outcome are discussed as regards extent of initial surgery, preoperative assessment and secondary debulking procedure. In this work, the findings at SLO were often predictable, and related to the adequacy of initial surgery and to a clinical complete response. Nevertheless, after incomplete initial cytoreductive surgery, SLO appears the best procedure to assess the status of the peritoneal cavity and the efficacy of chemotherapy. Negative SLO after incomplete initial surgery assessed a complete response rate of 34% induced by the cisplatin-based chemotherapy. Survival rate of patients with a negative SLO was 93% at 3 years, which demonstrated the highly significant value of SLO in prognosis. Conversely, patient survival with positive findings at SLO was very low, whatever resection can be made. As this work and similar studies by others showed that it could improve patient survival, an attempt should be made to a secondary debulk of residual tumor, and it seems interesting to perform further such secondary resections until definite conclusions can be drawn about this procedure.

Actuarial Analysis↗

N-nitroso-N-methylurea-induced mammary carcinogenesis: effect of prolactin on expression of Ia antigen by tumor cells.

Prolactin (PRL) increases of Ia antigen (Ia Ag) expression in female Sprague-Dawley rats with N-nitroso-N-methylurea [(NMU) CAS: 684-93-5]-induced mammary tumors were studied. The effectiveness of PRL was examined when cancers appeared about 2-3 months after the first NMU administration. Rats with NMU-induced mammary tumors were divided into 3 groups: Group 1 was treated with 30 micrograms ovine PRL (o-PRL) in daily sc injections for 5 days. Group 2 received 0.5 mg 2 alpha-bromoergocryptine (CB-154), a known inhibitor of pituitary gland secretion, daily in sc injections for 6 days. Group 3 was the control group. Ia Ags expressed by NMU-induced mammary tumor cells were then quantified successively by double labeling [protein membrane cells with iodine-131 and anti-Ia monoclonal antibody (MoAb) with iodine-125]; then isolation and quantification of the doubly labeled immune complex were performed by affinity chromatography and chromatofocusing successively. When the specific activity of glycoproteins is known, the amount of glycoproteins that bind specifically to the anti-Ia MoAb can be deduced. In NMU-induced rat mammary tumor controls, about 5% of the purified glycoproteins bound specifically to the MoAb, and the amount increased to 8% for NMU-induced rat mammary tumors treated with 30 micrograms o-PRL daily for 5 days and decreased to 2.5% in NMU-induced rat mammary tumors treated with 0.5 mg CB-154 daily for 6 days. Total PRL receptor levels were measured in all tumors tested. For control NMU-induced rat mammary tumors, total PRL receptor levels were 6.35 +/- 1.40 fmol/mg protein, 7.20 +/- 2.40 fmol/mg protein for NMU-induced rat mammary tumors treated with o-PRL, and 6.81 +/- 2.34 fmol/mg protein for NMU-induced rat mammary tumors treated with CB-154. Our results demonstrated that treatment of NMU-induced rat mammary tumors with PRL increased the amount of Ia Ag expression by tumor cells and should prove very useful to the understanding of the biology of PRL in the tumorogenesis of the mammary gland.

Animals↗

Breast tumours: a review of adjuvant chemotherapy trials.

Updated randomized trials using adjuvant chemotherapy for breast cancer have generally shown significantly improved disease-free survival in young women. Nevertheless, this improvement does not appear to be lasting in locally advanced disease. The effects on overall survival remain controversial and have been observed in only five trials. Except for three trials, results in postmenopausal women have also been disappointing. The best regimen of adjuvant chemotherapy and, more importantly, its timing are still not well defined, although early or perioperative treatments seem to have a fair chance of success.

Antineoplastic Agents↗

Adriamycin, vincristine, cyclophosphamide and 5-fluorouracil (AVCF) compared with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in premenopausal breast carcinoma. Personal results.

Adjuvant treatment of breast cancer with AVCF gave significantly longer disease-free survival than CMF in the group of patients taken as a whole, in the subgroup with lymph node involvement and in the premenopausal subgroup. No significant difference was found regarding overall survival.

Antineoplastic Combined Chemotherapy Protocols↗

Breast tumours: adjuvant radiotherapy trials.

According to controlled trial results, adjuvant radiotherapy associated with radical surgery has significantly decreased local recurrences of breast tumours, but with no effects on survival. Nowadays, in controlled trials, the advantages of associating radiotherapy with surgery and adjuvant chemotherapy are not clear. A non-significant trend towards better control of local disease is observed in some trials, mainly in locally advanced disease. In most of the other trials no benefit has been found. Although some detrimental effects have been observed when adjuvant chemotherapy was delayed or reduced by radiotherapy, on the whole radiotherapy does not appear to have any harmful effects on final results.

Antineoplastic Agents↗

Oncogenes.

Oncogenes or genes involved in malignant development are presented. Detection procedures, gene activation, action mechanisms, and problems involving gene molecular function as well as precise role of oncogenes are discussed.

Animals↗

beta-Thromboglobulin in patients with breast cancer.

beta-Thromboglobulin (beta TG) plasma levels were determined in 52 female breast cancer patients at different stages and in 39 healthy controls (22 women and 17 men) of similar age distribution. Beta TG levels were high (mean +/- SD:61.6 +/- 59.1 ng/ml) in patients before any treatment compared to controls (mean +/- SD:21.2 +/- 7.4 ng/ml) and the difference was statistically significant (p less than 0.001). No correlation with disease stage was observed. No other coagulation parameters were abnormal except fibrinogen, which increased. Fibrinogen degradation products (FDP) also increased but only in metastatic patients. Chemotherapy appeared to induce a considerable decrease in initial values at the end of the first cycle without modifying the platelet count. In addition, an attempt was made to correlate the beta TG plasma level investigated serially for several months with disease evolution.

Adult↗

New cysteamine (2-chloroethyl)nitrosoureas. Synthesis and preliminary antitumor results.

Three chemical pathways were used for the synthesis of four new N'-(2-chloroethyl)-N-[2-(methylsulfinyl)ethyl]- and N'-(2-chloroethyl)-N-[2-(methylsulfonyl)ethyl]-N- or N'-nitrosoureas. These compounds are plasma metabolites of CNCC, a promising antineoplastic (2-chloroethyl)nitrosourea. Preliminary antitumor evaluation was performed against L1210 leukemia implanted intraperitoneally in mice. Among these compounds, two of them exhibited a greater antitumor activity compared to that of the parent mixture.

Animals↗

Comparison of Class II HLA antigen expression in normal and carcinomatous human breast cells.

Class II HLA antigen expression in breast carcinoma and normal breast gland cells was compared using a method more accurate than immunofluorescence. This new method involves labeling membrane proteins with 131I and the anti-Class II HLA monoclonal antibody with 125I. The isolation and purification of the doubly labeled (125I-131I) immune complex was performed by affinity chromatography and chromatofocusing successively. When the specific activity of glycoproteins is known, the amount of glycoproteins which bind specifically to the anti-Class II HLA monoclonal antibody can be deduced. In breast carcinoma cells, 1.5 to 2% of the purified glycoproteins bind specifically to the monoclonal antibody, whereas less than 0.3% of normal breast gland cells binds. In contrast, leukemic cells, of which 80 to 90% possess Class II HLA antigens, 2 to 3% of Class II HLA glycoproteins bind specifically with the anti-Class II HLA monoclonal antibody.

Antibodies, Monoclonal↗

Presence of HLA-D/DR antigens on the membrane of breast tumour cells.

HLA-D/DR (Ia) glycoproteins were identified in human breast carcinoma and normal mammary gland cells by means of an anti-Ia monoclonal antibody. Two techniques were used: (1) immunoperoxidase staining performed on histological sections and (2) Ia glycoproteins were isolated as follows: firstly by radioactive labelling of isolated cells, then by filtration on Sephadex G25, followed by Lens culinaris chromatography, and immune complex formation and then elution on protein A-Sepharose. Lastly, the immune complex was studied by chromatofocusing. Both techniques revealed that Ia expression was found in carcinoma cells, but not in normal cells.

Adenofibroma↗

Variations in committed stem cells (CFU-GM and CFU-TL) in the peripheral blood of cancer patients treated by sequential combination chemotherapy for breast cancer.

The present work compared the blood variations in some committed stem cells (CSC), and corresponding differentiated WBC during the first three courses of a 6-day sequential chemotherapy given to 16 breast cancer patients for 28 days each. The granulomonocytic and lymphocytic colony-forming unit levels in blood were significantly lowered in cancer patients before treatment. These CSC appeared to have cyclic variations following each course of chemotherapy. In granulomonocytic colony-forming units, a nadir was observed by Day 15, followed by a sharp rebound above the initial values by Days 22 to 24, which was not affected in magnitude by the continuation of treatment. In lymphocytic colony-forming units, the Day 1 level increased with the continuation of chemotherapy. The initial decrease was less marked, but by Day 15 a minimal level was also observed, followed by a progressive increase to reach a maximum by Day 28. Leukocytes and granulocytes reached a nadir by Days 16 to 17 and recovered by Day 25. The cyclic evolution of monocytes was less apparent as was that of lymphocytes; however, there was less restoration of monocytes and lymphocytes than of granulocytes at the end of the resting period. This study showed: (a) an apparent relationship between the level of CSC in blood, and subsequent variations in the corresponding mature cells of the same lineage; and (b) a weak interval of time between the nadir and peaks of CSC and the corresponding mature cells, which was more evident in the granulocytic lineage. These observations seemed to be of physiological importance, but the possible prediction value of peripheral granulomonocytic colony-forming unit peak magnitude following treatment remains to be established.

Adult↗

[In vitro cloning of human tumor stem cells].

This study summarizes a one-year work experience in the area of human tumor stem cells cloning techniques. We found that it was more advisable to use an enzymatic method for dissociating solid tumors. The breast tumors possessing an unfavourable histoprognostic grade were found to grow up more easily in culture, which is a confirmation of known relationships between cell differentiation degree and cell proliferation. The high frequency of failures in the obtention of colonies did not allow to use this technique in daily clinical practice to study the in vitro sensitivity to drugs of a definite tumor. An improvement in the conditions of culture and the comparison with other in vitro methods for the prediction of response to oncostatics--particularly the incorporation of radioactive precursors (Livingston and coll., 1980)--will be attempted in future work.

Cell Separation↗