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Biomedical subjects

F A Soares

Publications and source records attributed to F A Soares.

At least 19 recordsLinked to original sources
PubMed2005

Prognostic and predictive value of the thymidylate synthase expression in patients with non-metastatic colorectal cancer.

AIMS: To assess the value of thymidylate synthase (TS) expression as a predictive factor in the efficacy of adjuvant chemotherapy in colorectal cancer, as well as its independent prognostic value for survival. METHODS: We studied 114 high risk colorectal carcinoma patients (high risk stage II and stage III), distributed in two treatment groups: surgery alone (61 patients) or surgery followed by 5-FU-based chemotherapy (53 patients). TS protein expression in the tumour tissue was assessed by immunohistochemistry. RESULTS: In the surgery alone subgroup, overall survival (OS) at 5 years were 77.5% for the patients with low TS expression, against 57.7% for the patients with high TS expression (p=0.006). Among patients with low TS, there was no difference in OS as a result of whether adjuvant chemotherapy was carried out or not (65.8 vs 77.5%, p=0.29). Among the patients with high TS, there was a significant gain in OS in favor of chemotherapy (87.8 vs 57.7%, p=0.04). Analyzing the complete sample, TS expression was not shown as an independent prognostic factor for survival in the multivariate analysis. CONCLUSIONS: The immunohistochemical TS expression may be used for selecting patients for better adjuvant chemotherapy protocols. In this sample, TS expression was not an independent prognostic factor for survival.

Aged↗
PubMed2004

2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid, and meso-2,3-dimercaptosuccinic acid inhibit delta-aminolevulinate dehydratase from human erythrocytes in vitro.

The effects of dithiol chelating agents meso-2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane-1-sulfonic acid (DMPS), and 2,3-dimercaptopropanol (BAL) on delta-aminolevulinate dehydratase (delta-ALA-D) from human erythrocytes were evaluated. Furthermore, possible protective effects of zinc chloride (ZnCl(2)), dithiothreitol (DTT), and cysteine were studied. delta-ALA-D activity from human erythrocytes was inhibited by dithiol chelating agents in a concentration-dependent manner. Cysteine, at all concentrations tested, did not protect the inhibitory effect of 1 and 4 mM DMPS and DMSA, but protected 1 mM BAL inhibition. Dithiotreitol was able to protect the inhibition caused by 1 mM BAL (28%), DMPS (56%), and DMSA (40%) in a concentration-dependent manner. Zinc chloride protected and restored 1 mM BAL inhibitory effect on delta-ALA-D. Zinc chloride at 500 microM and 1 mM, respectively, protected inhibitory effects of DMPS and DMSA (1 and 4 mM), but did not reverse its effects. The preincubation of dithiol chelating agents with enzyme demonstrated that DMSA was the most potent delta-ALA-D inhibitor of human erythrocytes. These data are in agreement with delta-ALA-D activity from purified enzyme. ZnCl(2) (1 microM) added, in the reaction mixture, increased enzyme activity and DTT (100 microM) totally restored the enzyme activity for all chelating agents tested.

Chelating Agents↗
PubMed2003

2,3-Dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid increase mercury- and cadmium-induced inhibition of delta-aminolevulinate dehydratase.

Compounds derived from Dimercaprol, such as meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS), are becoming common agents for treating humans exposed to heavy metals. Heavy metals such as Pb(2+), Hg(2+) and Cd(2+) can inhibit delta-aminolevulinate dehydratase (delta-ALA-D) activity. Delta-ALA-D catalyzes the condensation of two delta-aminolevulinic acid (delta-ALA) molecules with the formation of porphobilinogen, a heme precursor. The effects of DMSA and DMPS alone or in combination with Cd(2+), Hg(2+), or Pb(2+) on hepatic delta-ALA-D were examined. DMPS and DMSA caused a dose-dependent inhibition of hepatic delta-ALA-D. In the presence of Hg(2+) or Cd(2+) the inhibitory potency of DMPS increased. Similarly, the inhibitory effects of Hg(2+) and Cd(2+) were markedly increased in the presence of DMSA. In contrast, the inhibitory effect of DMPS was not changed by inclusion of Pb(2+). As observed with DMSA, Zn(2+) did not modified the inhibitory effect of DMPS. Data of the present report support the idea that the complexes formed (metals-DMSA or DMPS) were more inhibitory than the metal (Hg(2+) and Cd(2+)) or the chelating agent alone to the hepatic delta-ALA-D activity, in vitro. The mechanism of hepatic delta-ALA-D inhibition by Hg(2+)-DMPS/DMSA and Cd(2+)-DMPS/DMSA complexes involve the essential thiol groups of the enzyme.

Animals↗
PubMed2003

Using the laser-induced fluorescence spectroscopy in the differentiation between normal and neoplastichuman breast tissue.

This article reports results of the in vitro study for potential evaluation of the laser-induced fluorescence spectroscopy in the differentiation between normal and neoplastic human breast tissue. A coumarine dye laser pumped by nitrogen laser generated an excitation light centered at 458 nm. In order to collect the fluorescence signal was used an optical fiber catheter coupled to a spectrometer and CCD detector. Fluorescence spectra were recorded from normal and neoplastic (benign and malignant) human breast tissue, adding up 94 different areas. The discrimination between normal and neoplasm groups reach a sensitivity and specificity of 100%.

Breast Diseases↗
PubMed2003

Tumour angiogenesis as a prognostic factor for disease dissemination in retinoblastoma.

AIM: To evaluate tumour angiogenesis as a predictor of prognosis in retinoblastoma. METHODS: This was a retrospective, non-randomised comparative clinicopathological study. The histopathology from 24 cases of Reese-Ellsworth (RE) group V unilateral retinoblastoma treated by enucleation alone was reviewed. Group I consisted of five patients (four RE group Vb and one group Va) who developed disseminated disease at a mean of 10.4 months after enucleation. The remaining 19 patients constitute group II (18 RE group Vb and 1 group Va), none of whom had developed metastatic disease with a mean follow up of 54 months. None of the 24 patients had evidence of extraocular disease at enucleation. The surgical specimens from patients with unilateral retinoblastoma treated by enucleation at Hospital do Cancer AC Camargo between January 1992 and December 1995 were identified, reviewed and the clinical data recorded. Two subsequent histological sections were prepared. One stained with haematoxylin and eosin for assessment of choroidal and optic nerve invasion, and the other for immunoreaction with an endothelium specific marker (antibody anti-CD 34). The main outcome measures were choroidal and/or optic nerve invasion and quantification of the tumour's relative vascular area (TRVA) obtained by Chalkley counting. RESULTS: Choroidal invasion was present in three eyes of group I (all massive) and six eyes of group II (two focal and four massive). Optic nerve invasion was found in two eyes of group I (all post-laminar) and four eyes of group II (three prelaminar and one post-laminar). There was no statistical difference regarding choroidal or optic nerve between the two groups. The TRVA was the only independent variable found to predict disease dissemination (p = 0.008 by Cox analysis). A TRVA equal to or greater than 3.9% had 100% sensitivity and 79% specificity in predicting disease dissemination. CONCLUSIONS: Quantification of angiogenesis, through measurement of the TRVA, can help to identify patients with retinoblastoma at high risk for disease dissemination after enucleation.

Adult↗
PubMed2003

Salivary duct carcinoma: immunohistochemical profile of an aggressive salivary gland tumour.

BACKGROUND: Salivary duct carcinoma (SDC) is considered to be a distinct malignancy of the major salivary glands, because of its highly aggressive behaviour, and the high rate of recurrence, metastasis, and disease related death. AIMS: To investigate expression of the proteins involved in the retinoblastoma (pRb) and p53 pathways, which control cell cycle progression at the G1/S checkpoint, and also expression of the c-erbB-2 oncoprotein in SDCs. METHODS: Using a streptavidin-biotin method, five cases of SDC were evaluated immunohistochemically for the presence of cyclin D1, CDK4 (cyclin dependent kinase 4), p16 (CDK2A), pRb (retinoblastoma protein), E2F-1, p53, mdm2 (murine double minute 2), bcl-2, and the c-erbB-2 oncoprotein to determine whether there was a correlation between the expression of these proteins and patient outcome. RESULTS: All of the cases showed deregulation of the pRb and p53 pathways. Of the five patients analysed, only the patient with longterm survival (10 years) was not positive for c-erbB-2 expression. CONCLUSIONS: c-erbB-2 overexpression was associated with a poor prognosis. Aggressive behaviour, recurrence, and metastatic potential do not appear to be related to cell cycle deregulation, but seem to be associated with the c-erbB-2 oncoprotein, which is involved in matrix degradation and proteolitic activity, in addition to increases in vessel permeability, endothelial cell growth, proliferation, migration, and differentiation. There was a correlation between c-erbB-2 oncoprotein expression and aggressive behaviour in SDCs.

Aged↗
PubMed2001

Schirrous invasive ductal carcinoma of the breast overexpress p53 oncoprotein.

CONTEXT: Breast cancer is the most important neoplasm in adult women, and its worldwide incidence is growing. The tumoral stroma is very important for modulating the growth and invasion of the tumor itself. The relationship between these two components is not completely understood. Schirrous carcinoma is a variant of ductal invasive carcinoma in which the stroma is very desmoplastic, and the importance of this finding still a motive for debate in the literature. OBJECTIVE: To compare the desmoplastic reactions against biological markers, such as estrogen and progesterone receptors, oncoprotein c-erbB-2 and oncoprotein p53, with the objective of studying the relationship between the tumoral stroma and epithelial cancer cells. TYPE OF STUDY: Retrospective study. SETTING: Cancer Hospital A C Camargo and Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. SAMPLE: 107 adult women operated because of ductal invasive carcinoma. The cases were separated into 4 groups according to the desmoplastic reaction - less than 15 per cent, between 15-50 per cent, 51-85 per cent, and more than 85 per cent fibrosis. The grade of fibrosis was determined by picrus-sirius staining and quantified by using a microscope with a stereo-imaging grid. Immunohistochemical methods were used to determine the expression of the hormonal receptors and c-erbB-2/p53 oncoprotein. MAIN MEASUREMENTS: Extent of desmoplastic reaction versus expression of estrogen and progesterone receptors, oncoprotein c-erbB-2, and oncoprotein p53. RESULTS: The results showed that schirrous carcinoma expresses oncoprotein p53 more frequently than other carcinomas with less extensive desmoplastic reaction. There were no differences between the grade of fibrosis and the other biological markers. CONCLUSION: The intense stromal reaction in invasive ductal carcinoma may modulate the expression of p53. Further investigations should be made with the aim of understanding how this expression determines the proliferative activity in schirrous carcinoma, and whether this overexpression is secondary to mutation of the p53 gene or due to modulation of other molecules of the stroma.

Adult↗
PubMed2001

Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B-cell non-Hodgkin's lymphomas and multiple myeloma.

AIMS: Nitric oxide synthases (NOS) are isoenzymes that catalyse the synthesis of nitric oxide (NO). The three main NOS isoforms are: NOS1 or neuronal, NOS2 or inducible, and NOS3 or endothelial. NO plays both physiological and pathological roles, depending on its rate of synthesis and concentration, cellular source and microenvironment. Apoptosis is an important biological factor in low-grade lymphomas, and NO is able to prevent apoptosis. In-situ expression of NOS and synthesis of NO have been shown in several malignant tumours, but not in lymphoid neoplasms. This study evaluates whether human B-cell neoplasms express NOS isoforms, and nitrotyrosine (NY), which is usually interpreted as a marker of NO. METHODS AND RESULTS: We studied the expression of NOS-IR isoforms and NY-IR in 16 cases of B-cell non-Hodgkin's lymphoma (NHL) (five follicle centre cell lymphoma, four small lymphocytic/CLL, and seven diffuse large cell lymphoma), and 10 cases of multiple myeloma (MM). NOS1 was expressed in 5/10 cases of MM, and 15/16 cases of NHL. NOS2 was detected in all cases of MM, and in 14/16 cases of NHL, whereas NOS3 was positive in 3/10 of MM and in only in 1/16 cases of NHL. The expression of NY-IR was observed in 70% of MM cases, and in all cases of B-cell NHL, in a dot-like pattern in few tumour cells. CONCLUSIONS: B-cell neoplasms express neuronal and inducible NOS, and nitrotyrosine. Taken together, our results suggest that B-cell neoplasms can produce NO. The role of NO in the biology, diagnosis and prognosis of B-cell neoplasms remains to be established.

Adult↗
PubMed2000

Investigations into the mechanism of 2,3-dimercaptopropanol neurotoxicity.

2,3 dimercaptopropanol (BAL), is a dithiol chelating agent, used for the treatment of heavy metal intoxication; however, this compound has low therapeutic efficacy and in some situations may cause neurotoxic effects. In experimental models, administration of high doses of BAL produces seizures that culminate in animal death. However, investigations on the modulation of neurotransmitter system(s) involved in BAL-induced seizures are still lacking in the literature. In the present study, the neurotoxicity of BAL, as measured by the manifestation of seizures was examined and the modulation of glutamatergic and GABAergic receptors and ion channels potentially involved in BAL-induced seizures was investigated. The results demonstrated that BAL (18.6 mg/kg) induced seizures and all mice died within one day. GABAergic allosteric modulators (3 or 12 mg/kg diazepam and 50 mg/kg phenobarbital) blocked the appearance of seizure and reduced almost completely the death caused by BAL. Carbamazepine (5 mg/kg) significantly reduced the incidence of BAL-induced seizures, while sodium valproate and MK-801 were not effective in reducing the incidence of seizures. Valproate (300 mg/kg) and MK-801(0.5 mg/kg) prolonged the latencies for onset of seizures; however, all animals died within one day after BAL administration. High doses of ZnCl2 (135 mg/kg) blocked the appearance of seizures episodes, but no animal survived more than one day. The content of total non-protein -SH in brain of mice treated with 18.6 and 124 mg/kg BAL increased from 0.9+/-0.3 nmol/g (control animals) to 1.7+/-0.3 and 3.5+/-0.8 nmol/g, respectively. In vitro, 0.1-1 mM concentrations of BAL inhibited [3H]glutamate and [3H]MK-801 binding, but increased the binding of [3H]muscimol to brain synaptic plasma membrane. The results reported here demonstrate that GABAergic allosteric modulators (diazepam and phenobarbital) and carbamazepine, a compound that acts by prolonging the recovery of voltage-activated ion channels from inactivation, are able to abolish BAL-induced seizures, while the NMDA antagonist (MK-801) prolonged the latencies for onset of seizures suggesting that modulators of this subtype of glutamate receptor have a modest role on BAL-induced seizures. The results of the present study suggest that allosteric modulators of GABAergic system and carbamazepine, a voltage-gated Na+-channel antagonist, should be considered for the treatment of animals or patients intoxicated with BAL.

Animals↗
PubMed2000

Vascular density (tumor angiogenesis) in non-Hodgkin's lymphomas and florid follicular hyperplasia: a morphometric study.

Tumor angiogenesis is required for tumor growth and metastasis. A statistically significant correlation has been demonstrated between prognosis and the microvessel density (a measure of tumor angiogenesis) of solid tumors, particularly of the breast and prostate, and lymphoid neoplasms. The aim of this study was to establish whether a correlation exists between vascular density and the malignant category of Non-Hodgkin's Lymphoma (NHL) defined by two classification systems (Kiel and Working Formulation). We also tested whether florid follicular hyperplasia (FFH) and follicular lymphomas (FL) behave as new vessel stimulating conditions. Eighty-nine NHL lymph node biopsies were reviewed and categorized according to the Kiel Classification and Working Formulation. Twelve FL were also selected and compared to 12 FFH biopsies. Vessels were highlighted by immunostaining with anti-Factor VIII antibody and quantified both by counting higher vascular density fields and by estimating the proportional vascular area. The results showed a statistically significant difference between low and high grade NHL, when classified in either the Working Formulation (p=0.0015) or the Kiel Classification (p=0.002). No differences were found in vessel counts between Working formulation intermediate and high grade lymphomas. Vascular density is similar when FFH and FL interfollicular areas are compared.

Biopsy↗
PubMed1998

Generalized cutaneous leishmaniasis in acquired immunodeficiency syndrome.

BACKGROUND: Leishmaniasis associated with HIV/AIDS has been reported in the last decade. CASE REPORT: A case of generalized cutaneous leishmaniasis in a patient with AIDS is described. The case is paradoxical in that the cutaneous lesions resemble anergic leishmaniasis caused by Leishmania (L.) amazonensis and Jorge Lobo's disease, but the positive Montenegro test and the clinical improvement with antimonial are more commonly observed in leishmaniasis caused by L.(V.) braziliensis. COMMENT: The immunosuppression due to HIV/AIDS seen in this patient may explain the dissemination of the lesions, but the positive specific response to leishmanial antigen may explain the good response to the antimonial treatment.

AIDS-Related Opportunistic Infections↗
PubMed1997

Immunotherapy of metastases with lymphocytes treated with exogenous RNA in mice bearing B16 melanoma.

Subline B16-F10, a variant cell line of B16 melanoma, is highly metastatic to the lung when injected intravenously into C57BL/6 mice. This experimental metastasis model was used to test the anti-tumor effect of exogenous RNA extracted from the lymphoid organs of immunized animals with B16-F10 cells. This RNA preparation is referred to as B16-RNA. Adoptive immunotherapy with lymphocytes treated with B16-RNA was effective in reducing significantly the number of pulmonary metastatic nodules. Lymphocytes incubated with medium alone or with RNA from non-immunized animals (N-RNA) were used as controls. The ability of B16-RNA in modulating antimetastatic activity of normal lymphocytes is abolished by hydrolysis with KOH. This finding indicates that the integrity of the polynucleotide chain is essential for the activity of B16-RNA. The anti-tumor effect of lymphocytes treated with B16-RNA was enhanced by incubation with a low dose of interleukin-2 (IL-2). A possible role of the double-stranded RNA dependent protein kinase in this phenomenon is discussed.

Animals↗
PubMed1996

Translocation (1;5)(q32;q35) in CD30+ anaplastic large cell non-Hodgkin lymphona of childhood. A case report.

The authors studied cytogenetically a case of CD30+ anaplastic large cell non-Hodgkin lymphoma previously diagnosed as malignant histiocytosis and detected a translocation involving chromosomes 1 and 5, t(1;5)(q32:q35). After comparing their findings with those from reports in the literature, they comment about the importance of breakpoint q35 on chromosome 5 and point out the importance of associating morphologic, immunoperoxidase, and cytogenetic findings to confirm the diagnosis of this tumor.

Chromosome Fragility↗