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Biomedical subjects

L Perey

Publications and source records attributed to L Perey.

35 records · Page 2Linked to original sources
PubMed1996

[Hereditary breast cancers].

Recently, genetic analyses in high risk families with several members suffering of breast and/or ovarian carcinoma led to the discovery of two genes, called BRCA1 and BRCA2, clearly responsible for hereditary predisposition of breast carcinoma. Another gene, p53, was also shown to be involved in hereditary predisposition of breast and other tumors in the setting of Li-Fraumeni syndrome. It is very important that women at risk could be seen by a specialized team for genetic counselling and explanation of advances and limits of molecular genetics. Such a team should be multidisciplinary in order to cover genetic, oncological, social, psychological and economical aspects of hereditary cancer predisposition. Prevention interventions and early detection methods are still investigational and definitely need to be performed in the setting of protocols in order to better evaluate their long term efficacy.

Adult↗
PubMed1995

[High-dose chemotherapy with hematopoietic salvage in patients with breast cancer].

During the last years, high-dose chemotherapy with autologous hematological rescue has been increasingly used not only in the treatment of patients with relapsing lymphoma but also in ovarian and breast carcinoma. In this manuscript we present results in patients with high-risk primary breast cancer, and in those with metastatic tumors. When high-dose chemotherapy is given in the adjuvant setting for women presenting with > or = 10 metastatic axillary nodes, results are very promising since 72% of the patients are alive without evidence of disease more than 3 years after operation. In patients with inflammatory breast carcinoma, high-dose chemotherapy induces 80% of complete remissions. Considering patients with metastatic disease, high-dose, chemotherapy increases the complete remission rate and duration of response. In several studies, survival exceeding 5 years without relapse is seen in 10 to 15% of the patients. Toxic death rate globally is 10% and is decreasing progressively since the first studies. However, in order to really determine the value of high-dose chemotherapy with autologous hematological support, randomized trials will be needed, comparing this new approach to conventional treatment. Such studies are already going on in the USA and in Europe and results are awaited with great interest.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Intensification of chemotherapy for the treatment of solid tumours: feasibility of a 3-fold increase in dose intensity with peripheral blood progenitor cells and granulocyte colony-stimulating factor.

Dose intensity may be an important determinant of the outcome in cancer chemotherapy, but is often limited by cumulative haematological toxicity. The availability of haematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and of peripheral blood progenitor cell (PBPC) transplantation has allowed the development of a new treatment strategy in which several courses of high-dose combination chemotherapy are administered for the treatment of solid tumours. PBPCs were mobilised before chemotherapy using 12 or 30 micrograms kg-1 day-1 G-CSF (Filgrastim) for 10 days, and were collected by 2-5 leucaphereses. The yields of mononuclear cells, colony-forming units and CD34-positive cells were similar at the two dose levels of Filgrastim, and the numbers of PBPCs were sufficient for rescue following multiple cycles of chemotherapy. High-dose chemotherapy (cyclophosphamide 2.5 g m-2 for 2 days, etoposide 300 mg m-2 for 3 days and cisplatin 50 mg m-2 for 3 days) was administered sequentially for a median of three cycles (range 1-4) to ten patients. Following the 30 evaluable cycles, the median duration of leucopenia < or = 0.5 x 10(9) l-1 and < or = 1.0 x 10(9) l-1 was 7 and 8 days respectively. The median time of thrombopenia < or = 20 x 10(9) l-1 was 6 days. There was no cumulative haematological toxicity. The duration of leucopenia, but not of thrombopenia, was inversely related to the number of reinfused CFU-GM (granulocyte-macrophage colony-forming units). In the majority of patients, neurotoxicity and ototoxicity became dose limiting after three cycles of therapy. However, the average dose intensity delivered was about three times higher than in a standard regimen. The complete response rate in patients with small-cell lung cancers was 66% (95% CI 30-92%) and the median progression-free survival and overall survival were 13 months and 17 months respectively. These results are encouraging and should be compared, in a randomised fashion, with standard dose chemotherapy.

Adult↗
PubMed1995

Expression of the DF3-P epitope in human ovarian carcinomas.

Recent studies have described the generation of a mAb, designated DF3-P, which reacts with underglycosylated precursors of the DF3/MUC1 mucin-like glycoprotein. The present work demonstrates that the epitope recognized by mAb DF3-P is expressed by cell lines derived from human epithelial ovarian carcinomas and not a teratocarcinoma. Indirect immunofluorescence assays of single-cell suspensions support expression of the DF3-P epitope on the surface of ovarian carcinomas. Immunofluorescence studies on chamber slides further demonstrate that the mAb DF3-P-reactive cells are present in clusters. We also demonstrate that 125I-labeled mAb DF3-P selectively localizes to human ovarian carcinoma xenografts in athymic mice. The percentage of injected 125I dose/g tissue ranged between 10 and 17% for implanted CAOV-3 and OVCAR-3 tumors. Finally, the results of immunoperoxidase staining studies demonstrate that the DF3-P epitope is detectable in formalin-fixed sections of ovarian tumors and that mAb DF3-P exhibits little if any reactivity with normal surrounding tissues. Selective expression of the DF3-P epitope may be useful as a target for radioimaging or immunotherapeutic approaches to ovarian cancer.

Animals↗
PubMed1994

[Primary and adjuvant treatment of breast cancer: an update].

Several articles covering treatment of mammary carcinoma in situ and invading mammary cancer have been published recently. This article delivers a short description of the clinical picture and the treatment of a noninvasive tumor as well as of the mainly conservative primary treatment of invasive carcinoma in common use since 20 years. Systemic adjuvant treatment is discussed in the context of results from a meta-analysis publishes two years ago in 'Lancet'. Finally, various directives for the execution of an adjuvant treatment are given that are offered today outside of a study protocol.

Adult↗
PubMed1992

Effects of differentiating agents on cell surface expression of the breast carcinoma-associated DF3-P epitope.

The DF3 antigen is a member of a family of high-molecular-weight glycoproteins aberrantly expressed in human breast carcinomas. Recent work has described the generation of a monoclonal antibody (MAb), designated DF3-P, that reacts with immature, underglycosylated precursors of DF3 antigen. Immunoperoxidase staining studies have demonstrated that MAb DF3-P exhibits selective reactivity with malignant mammary epithelium. Using flow cytometry and live cell radioimmunoassays, the present studies demonstrate that the epitope recognized by MAb DF3-P is expressed on the surface of MCF-7 and other human breast carcinoma cell lines. We also demonstrate that treatment of MCF-7 cells with 12-O-tetradecanoylphorbol-13-acetate, an agent known to induce a more differentiated mammary cell phenotype, is associated with increased expression of the DF3-P epitope. Similar findings were obtained with sodium butyrate. The results indicate that these agents increase both cell surface DF3-P antigen density and the percentage of DF3-P-positive cells. Immunofluorescence studies performed on chamber slides further demonstrate that MAb DF3-P-reactive cells are detectable in small clones or clusters. Similar studies with 12-O-tetradecanoylphorbol-13-acetate- and butyrate-treated cells demonstrate increases in the size and number of these clusters. Taken together, these results indicate that the DF3-P epitope is expressed on the surface of human breast carcinoma cell lines and that the heterogeneity of this expression is related to the presence of differentiating signals.

Antigens, Neoplasm↗
PubMed1992

Tumor selective reactivity of a monoclonal antibody prepared against a recombinant peptide derived from the DF3 human breast carcinoma-associated antigen.

The DF3 antigen is a member of a family of high molecular weight glycoproteins aberrantly expressed in malignant mammary epithelium. We have generated a monoclonal antibody (MAb), designated DF3-P, against a recombinant DF3/beta-galactosidase fusion protein. Characterization of this MAb has demonstrated reactivity with immature precursors of DF3 antigen and not with the secreted form. These findings are in contrast to those obtained with MAb DF3, a previously described antibody with predominant reactivity against the mature glycoprotein. The finding that deglycosylation of secreted DF3 antigen with neuraminidase and endo-alpha-N-acetylgalactosaminidase is associated with increased MAb DF3-P reactivity provided additional support for the selectivity of this antibody against the protein core. Epitope mapping studies demonstrate that both the DF3-P and DF3 epitopes are located at a TRPAPGS domain in the 20-amino acid tandem repeat. The results of competition studies with synthetic peptides indicate that the proline in this domain is involved in both epitopes, while the potential glycosylation sites at threonine and serine may contribute to the differential reactivity of MAbs DF3 and DF3-P. Taken together, these findings suggest that both antibodies react with a similar epitope that is modified by the presence of carbohydrate moieties. The results of immunoperoxidase staining studies further demonstrate that while MAb DF3-P reacts with formalin-fixed sections of breast carcinomas, this antibody exhibits little if any reactivity with normal mammary epithelium. Selective expression of the DF3-P epitope in malignant breast cells may be useful in identifying this transformed phenotype.

Animals↗
PubMed1991

Treatment of bone metastases from breast cancer and myeloma with pamidronate.

28 patients with progressing painful bone metastases (18 breast cancer, 9 myeloma and 1 low grade lymphoma) received pamidronate 60 mg by 24 h continuous infusion for at least 2 courses (range 2-12). In patients urinary calcium and hydroxyproline excretion significantly decreased in relation to diminution of bone resorption. 9 of 18 breast cancer patients and 8 of 9 evaluable patients with myeloma had symptomatic improvement. Sclerotic areas of previously lytic lesions appeared in 8 breast cancer patients and in 1 myeloma patient. Transient fever developed in 1 patient and local phlebitis in 2. Among the 28 patients, 15 did not receive any anticancer treatment or have any change of the anticancer therapy during pamidronate administration. Of 7 with breast cancer, 4 had an improvement of symptoms and 4 sclerosis on radiographs. Impressive control of symptoms was the major feature of 8 myeloma patients, but only 1 had radiographic sclerosis.

Adult↗
PubMed1991

Cisplatin, vindesine, and 96-h continuous infusion of 5-fluorouracil as initial chemotherapy for locally advanced head and neck carcinoma.

The combination of cisplatin (80 mg/m2, i.v., day 1), 96-h infusion of 5-fluorouracil (5-FU) (30 mg/kg/24 h) and vindesine (3 mg/m2 days 1 and 8) was evaluated in 31 patients with histologically proven epidermoid carcinoma of the head and neck. All patients were nonpretreated and had measurable lesions. Three (10%) of the 29 evaluable patients achieved a complete response (CR) and 19 (66%) had partial response (PR) with an overall response rate (CR + PR) of 76%. The major toxicity was leukopenia. Median overall survival was 14.5 months. It is concluded that the combination of cisplatin, 96-h infusion of 5-FU, and vindesine was as effective as other regimens including 5-FU and cisplatin reported in the literature, with a similar toxicity. The low CR rate in this trial is related to the high percentage of T4 N3 disease.

Adult↗
PubMed1989

Treatment of tumor-induced osteolysis by APD.

Bisphosphonates, associated with rehydration, became the treatment of choice of malignant hypercalcemia when it became apparent that these compounds normalized plasma calcium in most cases within a few days and with almost no side effects, and that their effect was prolonged. Dichloromethylene bisphosphonate and aminobisphosphonate, especially APD, were shown to inhibit bone resorption with no noticeable inhibition of bone formation, and were highly effective in the long-term treatment of Paget's disease. APD was used in almost 300 patients with malignant hypercalcemia published in the literature and has been used in the medical clinic at Lausanne for several years. When given to 14 patients with malignant hypercalcemia at the dose of 25 mg/day until plasma calcium became normal for two consecutive days, APD had to be given for 4-11 days, severe hypercalcemia needing longer treatment than mild hypercalcemia (Adami et al. 1982). When given for a fixed period of 6 days, again plasma calcium normalized in all patients, whether APD was given i.v. (30 mg/day, ten patients) or orally (1200 mg/day, ten patients) (Adami et al. 1985). Further shortening of the treatment to one single infusion given over 24 h did not decrease the efficacy, as long as high enough doses were given (Blomqvist 1986). For severe hypercalcemia of above 3.5 mmol/liter 60-90 mg had to be given, while 30-45 mg was sufficient in milder cases (Body 1984). Otherwise, mild, transient, and asymptomatic hypocalcemia could occur. Normalization of plasma calcium went along with clinical improvement, sometimes even with correction of coma. Renal function was improved, even when the initial plasma creatinine levels were up to twice normal. Hypercalcemia could reoccur, but the duration of the effect of APD (1 week to several months) depended among other things on the dose administered. The decrease in plasma calcium was accompanied by a decrease in urinary calcium and hydroxyproline, both showing inhibition of bone resorption. In the case of recurrency, the treatment could be repeated with almost unaltered efficacy, except in end-stage cancer disease. When given to 13 normocalcemic patients with bone metastases from breast cancer, hydroxyproline and urinary calcium again decreased. Bone pains and radiologic signs of metastatic bone resorption also showed significant improvement, although these latter effects could also be explained by the antitumoral treatment, in this uncontrolled open trial.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Histopathology of bone marrow in human immunodeficiency virus infection.

The clinical and haematological findings in 18 patients with human immunodeficiency virus (HIV) infection were correlated with the histological features of plastic embedded bone marrow biopsies. Fifteen patients presented with peripheral cytopaenia of one or several cell lines. Twelve (66%) of the 18 patients exhibited bone marrow findings including normo- to hypercellularity, myelodysplasia, lymphocytosis with or without plasmacytosis and fibrosis of the reticulin type. Seventeen patients had myelodysplastic features, 5 of the 3 haematopoietic lines, 10 of 2 lines and 2 of 1 line. Dysmegakaryocytopoiesis and dyserythropoiesis, seen in 88% and 83% of the 18 patients respectively, were the most common myelodysplastic features. Bone marrow gelatinous transformation (serous atrophy) was a conspicuous finding in 7 (38%) of the 18 patients. The constellation of histological features here described, although not pathognomonic, is highly suggestive of HIV infection. The pathogenesis of the haematological abnormalities in HIV infection is discussed.

Acquired Immunodeficiency Syndrome↗