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Biomedical subjects

X Sastre

Publications and source records attributed to X Sastre.

35 records · Page 2Linked to original sources
PubMed1995

Adhesion systems in normal breast and in invasive breast carcinoma.

To analyze the role of various elements of the adhesion system in the organization of the normal mammary gland and in breast carcinoma, we have studied simultaneously the expression of integrins, E- and P-cadherins, and cytoplasmic constituents of adherens junctions. In the normal gland, E-cadherin and alpha-catenin are present in luminal epithelial and myoepithelial cells, whereas integrins are more abundant in acinar epithelial and in myoepithelial cells. We demonstrate here that, in addition, myoepithelial cells express much more vinculin and alpha-actinin than luminal epithelial cells, whereas talin and focal adhesion kinase (pp125FAK) are restricted to the basal cell layer. In invasive carcinoma, E-cadherin is usually present although often in reduced amount; different integrin subunits are expressed either by a fraction or by all of the cells or are absent. However, the cytoplasmic components of adherens junctions, such as alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK, are expressed at low levels or cannot be detected in the carcinoma cells. Our data suggest that 1), in the normal mammary gland, the myoepithelial cells, being particularly rich in integrins and cytoplasmic components of the adherens junctions, play an important role in the maintenance of tissue integrity; 2), in invasive carcinoma, cell aggregates may be maintained due to varying levels of expression of E-cadherin and/or integrins; and 3), interaction of the transmembrane adhesion molecules with the cytoskeleton in carcinoma may be impaired as revealed by reduced levels of expression of alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK. Importantly, carcinoma cells, when exposed to stroma during invasion, do not acquire the adhesion apparatus characteristic of normal cells in contact with the extracellular matrix.

Breast↗
PubMed1993

Expression of smooth muscle-specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant human breast tissue.

The expression of several differentiation markers in normal human mammary gland myoepithelium and in certain stromal fibroblasts ("myofibroblasts") associated with breast carcinomas was studied by immunofluorescence microscopy of frozen sections. Several antibodies to smooth muscle-specific proteins (smooth muscle alpha-actin, smooth muscle myosin heavy chains, calponin, alpha 1-integrin, and high molecular weight caldesmon) and to epithelial-specific proteins (cytokeratins, E-cadherin, and desmoplakin) were used to show that myoepithelial cells concomitantly express epithelial and smooth muscle markers whereas adjacent luminal cells express only epithelial markers. The same antibodies were used to establish that stromal myofibroblasts exhibit smooth muscle phenotypic properties characterized by the expression of all the smooth muscle markers examined except for high molecular weight caldesmon. In addition, both myoepithelium and myofibroblasts show a significant degree of heterogeneity in smooth muscle protein expression. Thus, myoepithelial cells and stromal myofibroblasts are epithelial and mesenchymal cells, respectively, which coordinately express a set of smooth muscle markers while maintaining their specific original features. The dual nature of myoepithelial cells and the phenotypic transition of fibroblasts to myofibroblasts are examples of the plasticity of the differentiated cell phenotype.

Antigens, Differentiation↗
PubMed1993

Visualization of the plasmin receptor on sections of human mammary carcinoma cells.

In previous studies we observed the presence of an antigen reacting with anti-plasminogen serum on tumor cells found in sections of human colorectal and mammary carcinomas, using immunofluorescence. This antigen could be plasminogen, or plasmin or both. These results led us to surmise that carcinoma cells, and not normal epithelial cells, had a receptor for plasmin and plasminogen. We demonstrated the existence of such a receptor on cells of established tumor cell lines of colonic and mammary origin. We observed that binding of plasmin(ogen) to its receptor was inhibited by lysin and its analogs. We undertook to characterize the plasmin receptor on sections of human mammary carcinomas (18 series of sections, originating from 15 infiltrating ductal carcinomas). In our immunofluorescence studies, we observed that the fluorescence induced by anti-plasminogen serum was suppressed by pre-treatment of the sections with tranexamic acid, a lysin analog. Furthermore, when parallel sections were incubated with tranexamic acid, then with solutions of plasminogen, tumor cells were made fluorescent again. Another important finding was the strong increase of labelling observed when sections were incubated with plasminogen or plasmin before reaction with anti-plasminogen serum. This labelling disappeared when tranexamic was added to plasminogen. As a whole, these results confirm the existence of plasmin receptors on tumor cells in mammary carcinoma sections. They also show that these receptors are not saturated in vivo and may bind, in vitro, additional amounts of ligand.

Breast Neoplasms↗
PubMed1992

[Ewing's tumor].

Ewing's tumour is an undifferentiated round-cell sarcoma of children and adolescents arising from the skeleton. The translocation (11; 22) (q24; q12) is specific and could serve as a diagnostic marker. It has also enabled this tumour to be classified in the group of primary neuro-ectodermal tumours. Concerning treatment, intensive chemotherapy alternating with local therapy has improved the prognosis of localized Ewing's sarcoma of the limbs and, to a lesser degree, of the axial skeleton.

Bone Neoplasms↗
PubMed1992

Phenotypic and functional analysis of tumour-infiltrating lymphocytes from patients with melanoma and other metastatic cancers.

Thirty tumour specimens, among which were 17 melanomas, were cultured with recombinant interleukin-2 (IL-2) in order to produce tumour-infiltrating lymphocytes (TIL). In the melanomas, three categories of TIL were characterised. The first, containing mostly CD3+ and CD8+ cells, lysed only autologous tumour cells; the second, containing mostly CD3+ and CD4+ cells, lysed both autologous tumour cells and allogeneic cells lines; the third, with mixed phenotype although cytotoxic for K562 targets, did not kill melanoma cells. The optimal conditions for a good development of TIL were established: we found that the lymph node or cutaneous origin of the tumour was unimportant, a 2 h enzymatic treatment was optimum and that TIL grew well in AIM V serum free medium. Therefore the easiness and the reproducibility of the TIL cultures from melanoma tumour samples allows the rapid development of therapeutic trials in metastatic melanoma.

Adult↗
PubMed1992

[Treatment of metastatic malignant melanoma with interleukin-2].

Between April 1988 and December 1990, 37 patients with progressive histologically proven metastatic melanoma were treated with interleukin-2 according to three multicentric successive protocols. Eighteen males and 19 females entered the trial. Mean age was 44 years (range 20-66); none of the patients had severe visceral disease or brain metastasis. Superficial and visceral metastatic sites were equally distributed. Interleukin-2 was administered as a 3 to 5 day continuous intravenous infusion, at a dose varying from 16 to 24 million international units/m2/day, as previously described by West. The second course was given after a 9 to 16 day free interval and one to seven courses were administered (mean three courses). A total of 132 courses has been given to the 37 patients. All are evaluable for toxicity and efficacy. Toxicity was tolerable and not different from that presented in recent reports. Only four patients had to definitively stop therapy for toxicity, one of them for cardiotoxicity; a dose modification or a transient suspension of therapy occurred in 18% of treatment cycles. One hypothyroidism with anti-thyroglobulin and anti-microsome antibodies was observed. We observed eight major responses (21.6%), usually of short duration (2-6 months). Most responses occurred in superficial lesions. One patient remains in complete remission, as therapy is stopped for 40 months. Immunological parameters, although demonstrating induced immunostimulation, did not correlate with clinical outcome. With an overall response rate of 21.6%, we confirm the activity of interleukin-2 in melanoma, as previously reported by others.

Adult↗
PubMed1991

Estrogen and progesterone receptors in cervical human papillomavirus related lesions.

According to recent studies showing that human papillomavirus (HPV) infections can be influenced by sex steroid hormones, we performed estrogen (ER) and progesterone (PgR) receptor assays in fresh frozen biopsies of genital-HPV-related lesions. Seventy-three women with normal cervix, condyloma, low- and high-grade CIN and squamous carcinoma were evaluated in comparison with 15 persons with vulvar and 9 with penile papillomavirus-associated lesions. HPV genotypes were determined by dot-blot hybridization. Non-cervical lesions did not express HR. Condyloma on squamous metaplasia of the cervix and high-grade CIN expressed high levels of HR, particularly PgR (mean 4,086 and 4,518 fmoles/g tissue, respectively). Cervical squamous carcinoma expressed very low concentrations of PgR in a limited number of cases. High levels of PgR were correlated with high-grade CIN (p less than 0.05), HPV16-18-associated lesions (p less than 0.01) and ER were correlated to HPV6-11-related lesions (p less than 0.01). The levels were independent of age, cycle stage and oral contraception. Morphological localization of PgR, using an immunocytochemical method using a monoclonal antibody (MAb) (PR-ICA), showed intense homogeneous staining in the nuclei of the stromal fibroblasts underlying dysplastic epithelium and condyloma on squamous metaplasia. These results suggest that, under in vivo conditions, sex steroid hormones, particularly progesterone, may act indirectly on HPV-infected epithelial cells and be implicated as co-factors in HPV-related cervical neoplasia. They could explain the relative predisposition to malignant transformation of the cervix as compared with vulvar and penile mucosa.

Adult↗
PubMed1990

Oncogene amplification correlates with dense lymphocyte infiltration in human breast cancers: a role for hematopoietic growth factor release by tumor cells?

One hundred six primary breast cancer samples were analysed for c-erbB2, int-2, and c-myc gene amplification. Surgically confirmed nodal involvement was observed in 42%. Level of gene amplification was studied by Southern and/or slot blot techniques. Amplified c-erbB2 gene sequences were present in 21.5% of all samples. Int-2 was amplified in 13.1% and c-myc was amplified in 10.3%. In a non-parametric test (Kruskal-Wallis) a strong negative association was found between high levels of c-erbB2 amplification and absence of estrogen receptor (ER) (P = .0009) or progesterone receptor (PR) (P = .011) expression. No correlations were found between all or high levels of amplification of each oncogene separately or combined with T, N, grade, multifocality of tumor, or associated carcinoma in situ. There was a trend approaching statistical significance for patients with c-erbB2 amplifications to have positive lymph nodes at surgery (P = 0.09). A somewhat surprising finding however was a very strong association between oncogene amplification and dense lymphocyte infiltration of the tumor (P = .05). This correlation is even stronger when only high levels of amplification are considered, either for each oncogene separately (P = .0048) or in combination (P = .0007). We propose that malignant cell cytokine production may help explain this observation.

Breast Neoplasms↗
PubMed1990

[Intra-epithelial cancer of the anal canal. Pathogenic study apropos of 5 cases].

Anal carcinomas are rare and their precancerous conditions are not well known. Two populations at risk are described, elderly women and, recently, homosexual males. Early detection of dysplastic lesions or intraepithelial carcinoma in the anal mucosa could lead to preservation on the anal sphincter and consequently to improvement of quality of survival. The present study included 3 women and 2 men. The pathological examination of the surgical specimens in these 5 cases (hemorrhoidal procidence, rectal prolapsus, fibrous polyps, fissure) showed, in all cases, an intraepithelial carcinoma developed in the squamous epithelium of the anal canal. In one of the 5 cases, the anal lesion was concomitant with an intraepithelial carcinoma of the uterine cervix. Complete local resection of the lesions were performed in all cases, associated with complementary radiotherapy in one patient. On follow-up, we observed one recurrence after 8 months in one out of 5 patients. All patients are alive. Histogically, the specimens showed an intraepithelial carcinoma in all 5 cases, with a microinvasive carcinoma in one case. The transitional mucosa of the anal canal showed dysplatic modification in all cases. Immunohistochemical study of the 5 cases did not discern the papilloma virus antigene. In the one case where it was performed, molecular hybridization showed a type 33 papillomavirus. The risk factors of anal carcinomas seems to be changing, in particularly the incidence is increasing in the homosexual patients. In this particular population, as in the uterine cervix, the human papilloma virus is probably one of the main etiological factors. The management of these lesions is not well-defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Multiple genetic alterations in distal and proximal colorectal cancer.

Multiple genetic alterations were investigated in colorectal cancer, including changes in DNA content, mutations in ras oncogenes, and deletions involving chromosomes 5, 17, and 18. A non-random association of deletions and mitotic abnormalities by site was seen, with both types of alterations occurring significantly more frequently in distal tumours. In contrast, the frequency of c-Ki-ras mutations did not differ between proximal and distal cancers. In addition, deletions were significantly associated with each other and with change in DNA content. The data provide strong support for the hypothesis that proximal and distal colon carcinoma might differ in the genetic mechanisms in their initiation and/or progression.

Adenocarcinoma↗
PubMed1989

Presentation of axillary lymphadenopathy without detectable breast primary (T0 N1b breast cancer): experience at Institut Curie.

Between 1960 and 1985, 31 patients presented to Institut Curie with isolated axillary lymphadenopathy, of probable metastatic origin from the breast, but without clinical or radiological evidence of a breast tumor and no other primary tumor. The mean age was 54.6 years (range 39-79 years). Histological diagnosis was obtained by axillary surgery (22 cases), drill biopsy (6 cases), and cytology (3 cases). All slides were reviewed for the present study. Treatment consisted of axillary surgery followed by radiotherapy in 22 patients, radiotherapy followed by axillary surgery in 6 patients, radiotherapy followed by modified radical mastectomy in one patient, and radiotherapy alone in 2 patients. Systemic adjuvant treatment was given to 11/31 patients. The median follow-up was 9 years (range 2-26 years). Eight recurrences have appeared. Four patients recurred in the breast only (mean time to relapse: 112 months, range 63-162 months). The four other patients recurred both in breast and/or axilla (mean time to relapse: 23 months, range 7-46 months). Nine patients have developed distant metastases, of whom three also had locoregional recurrence. Among the 11 patients who had had systemic treatment, 5/11 had recurrence or metastases. The overall 5 and 10 year actuarial survival rates were 76 and 71%, respectively. The metastasis-free 5 and 10 year actuarial survival rates were 73 and 71%, respectively. Axillary metastases without clinical or radiological evidence of a primary breast tumor represents a discrete clinical entity, the prognosis of which appears to be better than that of clinical invasive breast cancer with associated lymph node involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Axilla↗
PubMed1989

[Immunohistochemistry of epidermal growth factor receptors in human meningioma].

EGF receptors were assayed by immunohistochemistry using a monoclonal antibody against EGF-R in 32 surgical samples of meningioma. EGF-R were found in all samples (32/32). Only tumor cells were stained and staining was homogenous in tumor tissue. EGF-R was simultaneously assayed by 125I-EGF binding on membrane preparation and immunohistochemistry on frozen sections in 10 meningiomas. Results were qualitatively equivalent in 9 cases. Staining intensity was not correlated with the histological type, the proliferative status of the tumor or the age and hormonal status of the patients. The immunohistochemical data are in agreement with previous biochemical assays on tissue homogenates.

ErbB Receptors↗
PubMed1986

[Immunoperoxidase study of 18 malignant lymphoblastic lymphomas (LMLbl) in children].

Eighteen cases of malignant lymphoblastic lymphomas in children were studied by immunoperoxidase technique on frozen tissue sections and/or cytological samples. Different monoclonal or polyclonal antibodies were used: OKT8, OKT11, OKB2, OKIal, anti immunoglobulins (mu, kappa, lambda chains). The results were compared with those of classical histology: three histologically unclassified malignant lymphoblastic lymphomas were linked to a Bor T line (one pre-B lymphoma and two T lymphomas). One diagnosis of T lymphoma could not be confirmed by immunoperoxidase technique. The technique did not reveal any surface immunoglobulins in two cases of malignant lymphomas of Burkitt type. Every one of the remaining 12 cases gave concordant results between morphological and immunological studies. In 12 cases it was possible to compare the results of immunological typing on tissue sections and cell suspension. The results were concordant in 11/12 cases. An advantage of this immunochemical technique on frozen sections and/or cytological samples is that it gives good visualisation of the cells and their reactivity with the antibodies.

Adolescent↗