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Biomedical subjects

M Hebbar

Publications and source records attributed to M Hebbar.

At least 37 records · Page 2Linked to original sources
PubMed1998

[The correlation between salivary endothelial expression of E-selectin and clinical and biological parameters in systemic scleroderma].

OBJECTIVES: A body of evidence suggests the pivotal role of endothelial cells in the pathophysiology of systemic sclerosis. E-selectin is an adhesion molecule specifically expressed by activated endothelial cells. In previous studies we noticed that E-selectin was frequently expressed in the salivary gland tissue of patients with systemic sclerosis. Moreover, E-selectin expression was detectable very early in the course of the disease. To better define the role of E-selectin in the pathogenesis of systemic sclerosis, we conducted a study aimed at determining whether E-selectin expression was correlated to clinical and biological features in patients with systemic sclerosis. METHODS: Thirty-one patients presenting with systemic sclerosis were included in the study. The following parameters were systematically assessed: duration and cutaneous extent of the disease, presence of secondary Sjögren's syndrome, antinuclear antibodies, and pulmonary and esophagus involvement. E-selectin expression was assessed by immunocytochemistry on minor labial salivary glands. RESULTS: E-selectin expression was detected in 21 out of 31 patients (67%). The disease duration was significantly shorter in patients with E-selectin expression (mean 9.1 +/- 8.5 years versus 4.2 +/- 3.3 years, P < 0.05). No significant difference was found for other features. CONCLUSIONS: This study shows that endothelial E-selectin expression is mainly detectable early in the course of systemic sclerosis, when active and non-cicatrical sclerosis may be evidenced. No correlation was found between E-selectin expression and immunological disorders (antinuclear antibodies, secondary Sjögren's syndrome).

Adolescent↗
PubMed1998

The relationship between concentrations of circulating soluble E-selectin and clinical, pathological, and biological features in patients with breast cancer.

Increasing evidence suggests that E-selectin contributes to tumor growth and metastasis. E-selectin may increase tumoral angiogenesis and the adhesion of tumoral cells to endothelial cells at distant sites. The aim of this study was to assess the relationship between concentrations of circulating soluble E-selectin (sE-selectin) and clinical, pathological, and biological features in patients with breast cancer (BC). Concentrations of sE-selectin were analyzed by an ELISA method in sera from 113 patients with metastatic BC, 30 patients with primary inflammatory BC, 105 patients with primary noninflammatory BC, and 42 healthy controls. These concentrations were analyzed in terms of the clinical and pathological features of the tumors as well as in terms of the concentrations of serum inflammatory parameters (erythrocyte sedimentation rate, C reactive protein, interleukin 1 beta, and tumor necrosis factor alpha), the response to chemotherapy or hormone therapy, and the survival duration. Tumoral angiogenesis was also assessed in 68 patients with primary noninflammatory BC who had had primary surgery. The mean concentration of sE-selectin in the metastatic BC group was significantly higher than the mean concentration found in the healthy control group (33.5 versus 21.8 ng/ml; P < 0.01). In metastatic BC, the mean concentration of sE-selectin was significantly higher in patients with liver metastasis than in patients without liver metastasis (55.3 versus 26.0 ng/ml; P < 10(-5). The univariate analysis showed that high concentrations of sE-selectin were associated with reduced overall survival (P < 0.05), but this probably reflected the association between high concentrations of sE-selectin and liver metastasis. In patients with primary noninflammatory BC, a negative correlation was found between sE-selectin concentrations and the tumoral microvessel count (r = -0.47; P = 10(-4). In patients with primary inflammatory or noninflammatory BC, no correlation was found between concentrations of sE-selectin and tumor size, lymph node involvement, response to chemotherapy or hormone therapy, and survival. No correlation was found between the concentrations of sE-selectin and serum inflammatory parameters in any of the patient groups. This study suggests that in patients with metastatic BC, levels of sE-selectin are higher in the presence of liver metastasis. In patients with primary BC, high concentrations seem to be associated with reduced tumoral angiogenesis. Although several studies have previously demonstrated that the expression of cell surface E-selectin enhances the metastatic process, the shedding of sE-selectin in circulation may be considered a mechanism of inhibition of tumor progression.

Adult↗
PubMed1998

Basic fibroblast growth factor receptors and their prognostic value in human breast cancer.

We performed a saturation binding study with 125I-labeled FGF (fibroblast growth factor)-2 in a nonselected series of 250 human primary breast cancers. Two hundred twenty-five breast cancer biopsies possessed bFGFR (basic FGF receptor). The median dissociation constant was 0.35 nM (range, 0.014-1.9), and the median concentration was 1126 fmol/mg protein (range, 49-7328). FGFR-1 was localized, using a specific monoclonal antibody, in cancerous cells and in epithelial cells in normal breast or in benign tumors. In all of the tissues studied, light stromal cell staining was also observed. Thus, the localization of FGFR-1 in carcinoma cells supports the hypothesis that an important part of FGF-2 binding reflects binding to FGFR-1. bFGFR concentrations were positively correlated to estrogen receptor and progesterone receptor levels. Cox univariate analyses showed that the bFGFR (> or = upper quartile) was associated to longer relapse-free survival [P = 0.004; RR (risk ratio), 0.46] and overall survival (P = 0.001; RR, 0.35); age, estrogen receptor levels, progesterone receptor levels, node involvement, tumor diameter, and histoprognostic grading were prognostic, also. In Cox multivariate analyses, only the bFGFR, age, node involvement, and histoprognostic grading were prognostic factors; the bFGFR was associated with longer relapse-free survival (P = 0.03; RR, 0.4) and overall survival (P = 0.009; RR, 0.3). The present study confirms that FGF could be an important regulator of human breast cancer growth and that patients with a high level of bFGFR had a better prognosis.

Adult↗
PubMed1997

[Systemic scleroderma and cancer. Search for predictive factors of cancer in 123 patients with scleroderma].

Several studies have suggested an increased risk of cancer in patients with systemic sclerosis, but the potential risk factors for these cancers remain unknown. The aim of this study was to identify, among patients with systemic sclerosis, factors associated with the development of cancer, with attention to clinical (age, sex, cutaneous sclerosis), immunological (antinuclear antibodies, anticentromere antibodies, anti-Scl-70 antibodies) and histological (pulmonary fibrosis) features. We retrospectively studied 123 patients with systemic sclerosis. The median follow-up period was 4 years. Fourteen cases of cancer (11.3%) were found (lung n = 3, breast n = 2, ovarian n = 2, skin n = 1, thyroid n = 1, rectum n = 1, uterine cervix n = 1, larynx n = 1, pancreas n = 1, myelodysplasia n = 1). The characteristics of systemic sclerosis were similar in patients with and patients without cancer. Yet, the three cases of lung cancers occurred in association with CREST syndromes and anticentromere antibodies.

Adolescent↗
PubMed1997

[Role of first-line palliative chemotherapy in metastatic colorectal cancer].

The prognosis of metastatic colorectal cancer remains poor. The 5-year survival rate is indeed 0 to 7%. The median survival duration is 8 months in patients without disease-related symptoms, and 6 months in patients with disease-related symptoms. The true benefit of palliative chemotherapy to increase the overall survival, and the symptom-free survival, has been largely discussed. In patients with disease-related symptoms, combinations of 5 fluoro-uracil (5-FU) and a biomodulator (leucovorin or methotrexate) have demonstrated a benefit on overall survival. In patients with asymptomatic disease, the advantage of systematic chemotherapy is more debatable. Two randomized studies have recently demonstrated that early chemotherapy yielded increased overall survival, disease-free symptom survival, and quality of life. Consequently, in patients with metastatic colorectal cancer, palliative chemotherapy must be performed even at early stages, before the onset of disease-related symptoms. Several regimens can be used as first line chemotherapy. In patients with good general status, and patients in whom a further resection of metastatic tumors could be possible, intensive regimens seem to be more appropriate. In the other patients, 5-FU-based regimens or raltitrexed can be proposed. Generally, the "standard" first line regimen seems to currently be LV5FU2 (bolus and continuous infusion of 5FU and leucovorin).

Antineoplastic Agents↗
PubMed1997

Glutathione S transferase theta 1 gene defects in myelodysplastic syndromes and their correlation with karyotype and exposure to potential carcinogens.

Glutathione S transferase theta 1 (GSTT1) is implicated in the detoxification of different substances, including carcinogens. Recently, an increased incidence of GSTT1 null genotype was found in myelodysplastic syndromes (MDS) by comparison with a control population. We analyzed GSTT1 gene by PCR in 174 MDS cases and 100 controls. The incidence of GSTT1 null genotype was 22% in MDS in 19% in controls (P = 0.53). The incidence of GSTT1 null genotype in MDS did not differ according to gender, FAB classification, karyotype and whether MDS were therapy related or 'de novo'. In 86 of the de novo cases, data on previous occupational and environmental exposure to a list of 170 substances were available. In those MDS patients, a significantly lower frequency of GSTT1 null genotype was seen in cases with previous jobs exposed to chemicals, and with previous exposure to mineral dusts and exhaust gases. A lower frequency (but with only borderline significance) was seen in MDS patients who had been coal miners and those who had been exposed to any of the 70 substances analyzed. Overall, GSTT1 null genotype occurred at a similar incidence (19%) in controls and in MDS cases previously exposed to any substance, but tended to be higher in unexposed MDS patients (40%, P = 0.07). Our results do not confirm the higher incidence of GSTT1 null genotype observed in MDS. The lower incidence of GSTT1 null genotype in MDS cases exposed to some compounds previously found associated with MDS is apparently unexpected. However, it could be explained by the fact that GSTT1 enzyme, which has a detoxification role for some compounds, could also have an activating role for other substances, including solvents.

Carcinogens↗
PubMed1997

Association between myelodysplastic syndromes and inflammatory bowel diseases. Report of seven new cases and review of the literature.

We report seven patients with both myelodysplastic syndrome (MDS) and inflammatory bowel disease (IBD): Crohn's disease in six cases, ulcerative colitis in one case. We describe their characteristics, and those of 10 previously published similar cases are presented here. Median age at diagnosis of IBD (61 years) was high, as compared to the usual age at diagnosis of IBD. IBD was diagnosed first in nine cases, MDS first in one patient, and both diseases were diagnosed simultaneously in seven cases. Concerning IBD, there was a strong predominance of Crohn's disease (15/17 cases), with an unusually high frequency of colonic involvement (11/15 cases). MDS, in 12/17 cases, showed no excess of marrow blasts. Cytogenetic analysis was abnormal in five of the 13 evaluable cases. These observations suggest that the association between MDS and IBD may not be fortuitous in some cases, and that, in particular, patients with IBD and anemia of nonobvious origin should be evaluated for MDS. The pathogenesis of those associations, however, remains unclear.

Adult↗
PubMed1997

Assessment of anti-endothelial cell antibodies in systemic sclerosis and Sjögren's syndrome.

OBJECTIVES: Anti-endothelial cell antibodies (AECA) have been detected in 19 to 30% of patients with systemic sclerosis (SSc). The objective of this study was first to assess the role of a secondary Sjögren's syndrome (SS) in the occurrence of AECA in SSc. Secondly, we researched AECA in patients with primary SS, and investigated whether AECA were associated with vascular manifestations (Raynaud's phenomenon and vasculitis). METHODS: IgG-AECA were tested by an ELISA method in serum samples from 50 patients with SSc (16 of them had also a secondary SS), 50 patients with primary SS, and 50 healthy controls. RESULTS: AECA levels were significantly higher in patients with SSc or primary SS than in healthy controls (p < 0.01 and p < 0.01, respectively). In patients with SSc, AECA values were significantly higher in patients with secondary SS (p < 10(-5)). In patients with primary SS, AECA levels were significantly higher in patients with Raynaud's phenomenon (p < 0.01), but not in patients with vasculitis. CONCLUSION: In patients with SSc, AECA are associated with a secondary SS. In patients with primary SS, AECA are associated with Raynaud's phenomenon, but not with vasculitis.

Adolescent↗
PubMed1996

Early expression of E-selectin, tumor necrosis factor alpha, and mast cell infiltration in the salivary glands of patients with systemic sclerosis.

OBJECTIVE: To assess the predictive value of early endothelial E-selectin and tumor necrosis factor alpha (TNF alpha) expression, as well as mast cell infiltration, in the subsequent progression to systemic sclerosis (SSc) in patients with Raynaud's phenomenon (RP) and abnormal nailfold capillaroscopic findings. METHODS: Clinical criteria were evaluated, and immunostaining was performed on lip biopsy samples from 22 patients with RP and abnormal capillaroscopic results. None of these patients initially fulfilled the American College of Rheumatology criteria for SSc. RESULTS: E-selectin, TNF alpha, and mast cell infiltration were found in 9, 10, and 8 of 11 patients, respectively, whose disease progressed to SSc, and in 0, 2, and 1 of 11 patients, respectively, whose disease did not progress to SSc (P < 0.001, P < 0.01, and P < 0.01, respectively). CONCLUSION: E-selectin, TNF alpha, and mast cell infiltration are detectable in the very early stages of SSc, prior to the onset of skin changes.

Adult↗
PubMed1996

Plasma c-erbB2 concentrations in relation to chemotherapy in breast cancer patients.

Amplification and overexpression of the C-ERBB2 oncogene have been associated with a poor prognosis and a lower response to chemotherapy in human breast cancer. In this study, plasma c-erbB2 concentrations were determined using an enzyme immunoassay in patients with breast cancer. The links between c-erbB2 concentration and tumoral response to chemotherapy were established. The patients with a c-erbB2 concentration higher than the cut-off value (27 U/ml) were considered as c-erbB2+. Ten of the 33 metastatic breast cancers were c-erbB2+. No statistically significant difference in response to chemotherapy was noted between c-erbB2+ and c-erbB2- patients (4/10 objective responses versus 10/23). Variations in c-erbB2 concentrations during treatment were not related to response to treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Prognostic factors in myelodysplastic syndromes: critical analysis of the impact of age and gender and failure to identify a very-low-risk group using standard mortality ratio techniques.

We studied the prognostic value of age and gender by survival, and by standard mortality ratio (SMR) analyses, in 203 untreated patients with myelodysplastic syndromes (MDS); 57 refractory anaemia (RA), 23 refractory anaemia with ringed sideroblasts, 41 refractory anaemia with excess blasts (RAEB), 3 RAEB in transformation (RAEB-T) and 79 chronic myelomonocytic leukaemia (CMML), aged 23-89 years (median 69, M/F 0.5), who were all karyotyped. Median survival was 36 months. Adverse prognostic factors were: high bone-marrow blast percentage, complex karyotype, low platelet count, age > 60 years, low or high WBC count, haemoglobin < 10 g/dl, male gender. However, the standard mortality ratio (i.e. mortality compared to that of an age- and sex-adjusted population) was not different between male and female patients. Patients < 60 had a higher SMR than older patients. Therefore the prognostic values of age and gender for survival in MDS patients may reflect, at least in part, a characteristic of the population. Furthermore, even in low-risk groups defined by scoring system we were unable to define a subgroup of patients with a mortality similar to that of the normal population, especially in MDS patients aged < 60.

Adult↗
PubMed1996

Low incidence of specific anti-platelet antibodies detected by the MAIPA assay in the serum of thrombocytopenic MDS patients and lack of correlation between platelet autoantibodies, platelet lifespan and response to danazol therapy.

We prospectively studied the mechanism of thrombocytopenia in 30 patients with myelodysplastic syndrome (MDS), who had a platelet count <or= 70 x 10(9)/l, and marrows blasts <or= 10% by analysis of platelet lifespan, platelet-bound IgG antibodies by platelet radioactive antiglobulin test (PRAT), and circulating and platelet-bound autoantibodies specifically directed against platelet glycoproteins by indirect and direct MAIPA test. PRAT analysis was positive in 21/30 patients (70%), but antiplatelet antibodies were found in only eight by the MAIPA test. Platelet lifespan was shortened in five cases, only one of whom had a positive MAIPA test. Patients were treated by danazol (600 mg/d), and 9/26 evaluable patients (35%) responded, including three of the five patients with shortened platelet lifespan. No correlation between platelet lifespan, results of PRAT and MAIPA tests, and response to danazol was found. In conclusion, specific antiplatelet autoantibodies, reduced platelet lifespan, and efficacy of androgen therapy on platelets were seen in 20%, 17% and 35% of MDS with thrombocytopenia, respectively, but no correlation between these findings was found in this study.

Adolescent↗
PubMed1995

E-selectin expression in salivary endothelial cells and sera from patients with systemic sclerosis. Role of resident mast cell-derived tumor necrosis factor alpha.

OBJECTIVE: To assess endothelial cell activation in patients with systemic sclerosis (SSc). METHODS: Concomitant study of salivary gland biopsy tissues and sera for expression of E-selectin and its potent activator tumor necrosis factor alpha (TNF alpha), using immunostaining and enzyme-linked immunosorbent essay. RESULTS: E-selectin was overexpressed in SSc patients, but not in controls. TNF alpha was detected in mast cells. CONCLUSION: Mast cell-derived TNF alpha may contribute to endothelial cell activation in SSc.

Adolescent↗
PubMed1995

[Immunotherapy of malignant melanoma. New prospects].

Malignant melanoma is an immunogenic tumor which can induce host humoral and cellular responses, and is a good model for development of anti-cancer immunotherapy. During the last decade systemically-administrated interferon and interleukin-2 have been used. Advances in immunology and molecular biology could allow a more specific and active immunotherapy. Perspectives include chemo-immunotherapy, monoclonal antibodies alone or in combination with cytotoxic agents, adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL), gene therapy designed to increase tumor immunogenicity, and active immunotherapy with vaccines.

Animals↗