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J Jacquemier

Publications and source records attributed to J Jacquemier.

At least 145 records · Page 8Linked to original sources

Estrogen response of MCF-7 cells grown on diverse substrates and in suspension culture: promotion of morphological heterogeneity, modulation of progestin receptor induction; cell-substrate interactions on collagen gels.

In this study we observed the incidence of hormone sensitivity in the response of MCF-7 cells to estrogen stimulation when the cells were cultured in different contact environments (hydrophilic plastic, bovine corneal extracellular matrix, type I collagen and in suspension culture). The major purpose was to describe the influence of cell to cell and cell to substrate contacts on the morphological response to estrogen treatment. However, other parameters including growth and induction of progestin receptor were also explored, keeping in mind that the MCF-7 cell line, although representative of normal mammary epithelium in that it contains a similar hormone receptivity, was selected in vitro from a metastatic population in a pleural effusion. Although substrate conditions did not modify growth enhancement by estrogens, progestin receptor levels were significantly higher in three-dimensional spheroid cultures in which cell to cell contacts were optimal due to elimination of basal contact. A careful morphological survey of large surfaces lead to an objective opinion of the overall effect of the hormone treatment on the non-cloned cell line in which a marked heterogeneity in the response of individual cells was observed. In terms of morphofunctional differentiation, the edification of acini with dense microvillus coating was best in suspension culture. When sections were made perpendicular to the plane of cultures on collagen gel rafts two other phenomena were noted: decrease in intercellular junctions, resulting in reduced cell to cell cohesion, and accumulation biodegradation products in the collagen lattice. This suggested a hormone-mediated interaction between the metastatic cells and the fibrillar substrate, collagen I, one of the major constituents of tissue stroma. This estrogen response might be related to the metastatic phenotype and must be distinct from their hormone sensitivity in terms of growth and differentiation since hormone receptivity is generally considered to be a favorable prognosis for breast cancer.

Breast Neoplasms↗

How culture conditions modulate the morphofunctional differentiation of the human estradiol-sensitive mammary cell line (MCF-7).

The MCF-7 cell line grown on plastic surfaces is widely accepted as a model for hormone sensitivity in molecular biology. However, in vitro results concerning estrogen sensitivity remain controversial. In search of culture conditions most closely simulating the in vivo microenvironment we cultured MCF-7 cells on diverse substrates and in suspension culture. The different factors of the contact environment: (A) influence of diffusive medium, (B) influence of cell to cell contacts, and (C) influence of cell to substrate contacts were considered. Using morphological criteria:phase contrast microscopy, scanning and transmission electron microscopy we observed MCF-7 morphofunctional differentiation under the different culture conditions. Plastic, corneal endothelial cell extracellular matrix, and attached collagen gels imposed a planar medium-aggregate interface. The impermeability of the free surface and the intense basal tension antagonized epithelial polarization. Only at post-confluence did domes and clusters appear above the monolayer. On floating collagen gels and in suspension culture the cells established intimate cell-cell contacts over large surfaces and reconstituted tissular architecture. Three-dimensional growth conditions which approach the in vivo contact environment of epithelial cells should be used instead of the traditional monolayer cultures for assessing hormonal and pharmacological responses of human breast carcinomas.

Breast Neoplasms↗

Histological differentiation in human breast cancer is related to steroid receptors and stromal elastosis.

In 503 cases of human breast cancer, the stroma reaction of elastosis was investigated with respect to histological differentiation, pathological and biochemical prognostic factors, and steroid receptor (SR) content. Unlike perivascular elastosis, gland-related (ductal + interstitial) elastosis was not related to age, menopausal status, and number of pregnancies of each patient, and could thus be considered a histological feature characteristic of mammary cells. Elastosis was encountered most frequently in histologically differentiated lesions and in lesions of histoprognostic grades I and II (low degree of malignancy). Elastosis-positive lesions thus seem to constitute a good prognosis. Elastosis was related to the presence of estrogen and progestin receptors (ER and PR), and in menopausal patients it was observed mostly when both ER and PR were present concurrently, i.e., under conditions reflecting the hormone-dependence of neoplastic cells better than the presence of ER alone. Taken together, these results suggest that the presence of hormone-dependent cells in breast carcinomas can be demonstrated by both biochemical and morphological features. Since each of these factors has its own prognostic value, prognosis could probably be by the assessed more accurately if all these parameters were examined at the same time.

Age Factors↗

Prostaglandin in human breast cancer: Evidence suggesting that an elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells.

Prostaglandin (PG) production by human breast cancers was investigated in 91 lesions selected so that the distribution of histologic type was similar to that of the general population of mammary carcinomas. With regard to the shape characteristics of the tumors, PG production was higher in lesions classified T1 and T2 than in lesions classified T3 and T4 (T-classification is based on extent of tumor as graded by the International Union Against Cancer), higher in tumors exhibiting a high cellularity than in lesions with a low tumor cell density and higher in tumors in which the cells were still adherent to each other. A high PG production was associated with the presence of neoplastic cells in tumor lymphatic and blood vessels and in axillary lymph nodes. PG production by node metastases was always higher than that by the primary tumor sites. The analysis of the stroma reaction and the presence of edema and necrosis suggest that an active PG synthesis occurred in lesions in which the tumor cell-surrounding stroma presented characteristics of low resistance to invasive growth of cancer cells. With regard to histologic differentiation and histoprognostic grade of lesions, PG production was elevated in carcinomas that retained a minute part of the acinoductal differentiation and in tumors with a moderate or high degree of cancer. A lesion containing a steroid receptor (SR) tended to produce less PG than did an SR-negative tumor. PG production increased slightly according to ages and times of menopause of the patients. PG production occurred early in the natural course of breast cancer and was elevated in tumors at a time when active tumor invasion proceeded. By contrast, PG production decreased later in the course of tumor development. These results indicated that elevated PG production can be used as a marker of high metastatic potential for neoplastic cells in breast cancer.

Adult↗

Multiple steroid receptors in human breast cancer. III. Relationships between steroid receptors and the state of differentiation and the activity of carcinomas throughout the pathologic features.

Histopathologic features (tumor cell density, histological type, and histoprognostic grade) were analyzed in 314 breast cancers investigated for estrogen (E) and progestin (P) receptors (R). The presence of PR is associated with the presence of ER. A relationship was found between the acinoductal differentiation of the lesions and the presence of SR: the more differentiated the carcinoma, the higher the frequency of ER. HPG III carcinomas have the lowest frequency of positive ER and HPG I tumors the opposite: the likelihood of the presence of SRs is inversely correlated with HPG. No statistically significant relationship existed between tumor cell density (TCD) and the presence of ER or ER content. Similar findings were observed for the stromal reaction. The results are discussed with respect to the biological significance of SR and histopathologic features: SR presence could be correlated with (1) a differentiated state of the tumors and (2) a slow rate of cellular replication.

Aged↗

Routine analysis of multiple steroid receptors in human breast cancer.--I--Technological features.

The technological features of multiple and simultaneous assays of steroid receptors (estrogen and progestagens) have been considered in human mammary carcinomas. Most of the parameters involved in the accuracy and the fiability of S-R determination have been investigated : the stability of S-R proteins (collection and storage of sample, cytosol preparation and buffer components, endogenous steroid problem), the specificity and precise quantitation of the binding (conditions of incubations, use of steroid analogs, dextran-coated charcoal method and treatment of binding data by the Scatchard analysis), the identification of the binding (vertical sucrose density gradients) and the interferences in DCC assays. The routinely adopted protocol has been experienced in 650 cases of S-R assay. It is concluded that when performed under appropriate and properly controlled conditions and even in a small sample, multiple S-R assay could result in a precise quantitation and identification of the pathological state of the S-R system in a tumor at time of surgery. Considered with regards to actual knowledges in cell biology, that is of importance and could provide even more information about therapeutic guidance.

Breast Neoplasms↗

[Human mammary carcinoma: relationship between steroid hormone receptors and histopathology. An hypothesis, the prognostic value of hormone receptors (author's transl)].

In 318 cases of human primary breast carcinoma, the presence and content of estrogen receptor (ER) have been correlated to histopathological features of these carcinomas. We have evidenced that: a) there is a relationship between the ER presence, the histoprognostic grade and the histological type; b) there is no correlation between the frequency of ER presence, the neoplasic cellularity and the stromal reaction. The presence of ER appears to be related to a differentiated state of the carcinoma and to a moderate neoplasic activity. These data show that ER, correlated with histopathological features, could be used as an estimation's factor of the cellular activity of a human mammary carcinoma, thus as a factor of better prognostic value for the evolution of this tumor.

Adult↗

[Histology of precancerous lesions of the breast].

The authors are dealing with the problem of pre-cancerous lesions from data contained in the pathological archives of the Institut Gustave-Roussy. One series consists of 320 cases operated upon for benign lesions or tumors of the breast (Fibroadenomas appearing at a relatively advanced age) of which 4 developed cancers. The past histories of another series of 730 patients having had mastectomies for cancer are examined; 24 of these had been operated upon previously for benign tumours or lesions of the breast. Attention is drawn to a number of histological signs the presence of which in an "a priori" benign lesion should evoke caution: multilayered epithelium of the galactophores glands with an "en flammèche" appearance, tubular adenomatous hyperplasia, irregular lobular hyperplasia, microcalcifications... Despite careful examination of multiple sections, the pathologists decision between benign and malignant lesion continue to be difficult.

Adenofibroma↗

[Local recurrences after conservative treatment of breast cancer: risk factors and influence on survival].

AIMS OF THE STUDY: To determine the risk factors for local and distant failure in node-negative breast cancer treated with breast-conservative surgery and radiotherapy and to determine the relationship between these two events. MATERIAL AND METHODS: We retrospectively selected 908 patients who received conservative surgery and radiotherapy but no chemotherapy between 1980 and 1995, for a node-negative breast cancer. Patients were divided in two groups according to the status of the margins of resection. All pathology specimens were reviewed. RESULTS: In case of negative margins, the risk factors for local recurrences picked up by the Cox model were histologic multifocality (P = 0.0076), peritumoral vessel invasion (P = 0.021) and age < or = 40 years (P = 0.024), and in case of involved margins, negative oestrogen receptors (P = 0.0012), histologic multifocality (P = 0.0028), and absence of hormonal therapy (P = 0.017). The 10-year local recurrence rate was 18% in case of negative margins and 29% in case of involved margins, although in the latter case patients received high-dose adjuvant radiotherapy. Accordingly, the 10-year distant failure rates were 16% and 27%, respectively. Many arguments suggest that local and distant failures are closely related. CONCLUSION: Patients with histologic multifocality or positive margins are at high risk of local failure and then of distant failure, and require a more aggressive initial treatment.

Adult↗

Prognostic value of simultaneous expression of p21 and mdm2 in breast carcinomas treated by adjuvant chemotherapy with antracyclin.

One hundred and sixty-two breast carcinomas treated by adjuvant chemotherapy were investigated in immunohistochemistry for expression of p53 and two wild-type p53-regulated induced proteins, mdm2 and p21/waf1. p21 and mdm2 were expression stongly correlated with Ki67 but not with survival. The p53+/p21+, p53+/p21- and p53+/mdm2- phenotypes were associated with the worst prognosis. The p53+/p21+/ mdm2+ tumors were associated with a better outcome than the other phenotypes, they may be tumors expressing wild-type p53 and p21, and a form of mdm2 that might lead to the stabilization of p53. It is suggested that p21/mdm2 expression should be investigated in all cases of p53 positive breast cancer.

Antibiotics, Antineoplastic↗

Peritumoral vascular invasion in women with node-negative breast cancer, receiving no adjuvant therapy.

BACKGROUND: The prognostic value of peritumoral vascular invasion (PVI) in node negative breast cancer (N-) is a controversial issue. Considerable debate has focused on how PVI should be defined, and the techniques used to detect them have differed considerably from one study to another. MATERIAL AND METHODS: In our study, 167 cases of N- breast cancers were reviewed, with a view to determining whether or not PVI, as defined in the recently published European recommendations, were present. RESULTS: Based on the results of the subsequent statistical study, the presence of PVI was not found to constitute a reliable prognostic index to the outcome of N- breast cancer. CONCLUSION: Referring each case to the data available in the literature, the difficulties encountered when searching for PVI of this kind are described, the results of various studies on the topic are reviewed and whether it is worth pursuing studies along these lines is discussed.

Adult↗

High-dose chemotherapy with hematopoietic stem cell support in patients with advanced epithelial ovarian cancer: analysis of 67 patients treated in a single institution.

BACKGROUND: Advanced ovarian carcinoma is a chemosensitive tumor, but its prognosis is poor with 20 to 30% 5-year survival using conventional therapy. Increasing doses of chemotherapy might improve the prognosis because of the dose-effect. MATERIALS AND METHODS: Between 1980 and 1994 at Institut Paoli-Calmettes, 67 patients with advanced ovarian cancer were treated with different alkylating agents-based regimens of high dose chemotherapy (HDC) and hematopoietic stem cell support (HSCS). The population was divided in 2 groups: a salvage group (n = 30) including initial conventional chemotherapy-refractory patients, and a consolidation group (n = 37) including patients whose disease was sensitive to classical first-line chemotherapy after debulking surgery. RESULTS: Toxicity was essentially hematological (severe aplasia) and digestive (mucositis). Four toxic deaths occurred related to infection during immunosuppression. In the salvage group, 9 out of 22 evaluable patients responded (41%), but the duration of responses was short (median range of 6 months) and the 2-year overall survival rate was 13%. In the consolidation group, 17 patients are still alive, 12 with progression with a median follow-up of 63 months. The 5-year disease-free survival rate was 32% while the 5-year overall survival rate was 46%. CONCLUSIONS: Toxicity of HDC with HSCS is acceptable for poor-prognosis patients. In the long term, this therapy is not beneficial for chemotherapy refractory patients, despite objective response rates better than the conventional treatment, confirming the dose-effect for alkylating agents in ovarian cancer. On the other hand, the results seem better than classical therapy in case of chemosensitive disease and should be confirmed prospectively in a larger cohort of patients.

Antineoplastic Agents, Alkylating↗