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Biomedical subjects

F Soares

Publications and source records attributed to F Soares.

14 recordsLinked to original sources

Carcinoma ex pleomorphic adenoma (CXPA): immunoprofile of the cells involved in carcinomatous progression.

AIMS: To characterize the cellular component in pleomorphic adenoma (PA) that undergoes malignant transformation in carcinoma ex pleomorphic adenoma (CXPA). METHODS AND RESULTS: A panel of antibodies against cytoskeletal proteins was applied in 16 cases of CXPA: intracapsular carcinoma (five cases), minimally invasive (four cases) and frankly invasive (seven cases). The CXPAs were classified into two main groups according to their predominant cellular component as detected by the panel of antibodies: (i) carcinomas with only epithelial differentiation (75% of the cases), and (ii) carcinomas with a myoepithelial component (25%). CXPA with only epithelial differentiation showed two types of malignant areas in the part of the tumour that was confined by the PA capsule: (i) intraductal carcinoma areas characterized by ductal structures containing both benign myoepithelial cells positive for alpha-smooth muscle actin (alpha-SMA), vimentin and cytokeratin (CK)14 and proliferating atypical luminal cells reactive for CK7, CK8 and CK19, and (ii) carcinoma areas composed only of epithelial cells reactive for CK7, CK8 and CK19. In the latter, the cells presented morphological and immunohistochemical characteristics similar to those found in areas of invasive carcinoma outside the PA capsule. CXPAs with a myoepithelial component were composed mainly or exclusively of cells that expressed vimentin and alpha-SMA. In this group, ductal structures reminiscent of PA filled by malignant cells were not identified. CONCLUSION: Most CXPAs consist only of epithelial cells that have an immunoprofile comparable to ductal luminal cells of PA. These malignant luminal cells arise in the duct-like structures as intraductal carcinoma and probably only at this early stage of development should the lesion be considered as a non-invasive carcinoma.

Actins↗

Correlation of p53 status with outcome of neoadjuvant chemotherapy using paclitaxel and doxorubicin in stage IIIB breast cancer.

BACKGROUND: The role of p53 in modulating apoptosis has suggested that it may affect efficacy of anticancer agents. We prospectively evaluated p53 alterations in 73 patients with locally advanced breast cancer (IIIB) submitted to neoadjuvant chemotherapy. PATIENTS AND METHODS: Patients received three cycles of paclitaxel (175 mg/m2) and doxorubicin (60 mg/m2) every 21 days. Tumor sections were analyzed before treatment for altered patterns of p53 expression using immunohistochemistry and DNA sequencing. RESULTS: An overall response rate of 83.5% was obtained, including 15.1% complete pathological responses. The regimen was well tolerated with 17.7% grade 2/3 nausea and 12.8% grade 3/4 leukopenia. There was a statistically significant correlation between response and expression of p53. Of the 25 patients who obtained a complete clinical response, two were classified as positive (P = 0.004, chi-square). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099, chi-square). Discussion The combination is highly effective in locally advanced breast cancer. A negative expression of p53 indicates a higher chance of responding to this regimen. The p53 status may be used as a biological marker to identify those patients who would benefit from more aggressive treatments.

Adult↗

Salivary duct carcinoma: cytokeratin 14 as a marker of in-situ intraductal growth.

AIMS: The aim of this study was to determine the immunoprofile of salivary duct carcinoma and to differentiate intraductal growth from invasive growth. METHODS AND RESULTS: We applied a panel of antibodies (cytokeratins 7, 8, 13, 14, 19, vimentin and alpha-smooth muscle actin) in five cases of salivary duct carcinoma. This panel is currently used for identification of different components of salivary gland tumours in our laboratory. All tumour cells were positive for cytokeratins 7 and 8. Few neoplastic structures expressed cytokeratin 14 in cells surrounding tumour islands. CONCLUSION: The finding of cytokeratin 14 was important to confirm the in-situ intraductal growth, which probably characterizes this low-grade neoplasm.

Adenocarcinoma↗

Significant overexpression of oligophrenin-1 in colorectal tumors detected by cDNA microarray analysis.

The human oligophrenin-1 gene is ubiquitously expressed at low levels and expressed at high levels in the developing neuroepithelium of the neural tube. Mutations in this gene have been related to the X-linked mental retardation. Using cDNA microarrays, we found evidence that oligophrenin-1 is strongly up-regulated in colorectal tumors. Semiquantitative reverse transcriptase polymerase chain reaction confirmed this finding. Thus, a well-known nervous system-associated human gene transcript may also be an important colorectal tumor marker and potential therapeutic target.

Biomarkers, Tumor↗

A polymorphism in endostatin, an angiogenesis inhibitor, predisposes for the development of prostatic adenocarcinoma.

We have performed association studies between a novel coding single nucleotide polymorphism (D104N) in endostatin, one of the most potent inhibitors of angiogenesis, and prostate cancer. We observed that heterozygous N104 individuals have a 2.5 times increased chance of developing prostate cancer as compared with homozygous D104 subjects (odds ratio, 2.4; 95% confidence interval, 1.4-4.16). Modeling of the endostatin mutant showed that the N104 protein is stable. These results together with the observation that residue 104 is evolutionary conserved lead us to propose that: (a) the DNA segment containing this residue might contain a novel interaction site to a yet unknown receptor; and (b) the presence of N104 impairs the function of endostatin.

Adenocarcinoma↗

The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome.

Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription-PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.

Expressed Sequence Tags↗

HITS in internal carotid dissections.

Carotid dissections can cause neurological deficits either by hemodynamic or embolic mechanisms. Anticoagulants are often used in this setting to prevent neurological deterioration and stroke recurrence. High-intensity transient signals (HITS) detected by transcranial Doppler may be due to microembolism. We investigated the presence and number of HITS in a series of 27 patients with carotid dissection. HITS were detected in 14 (52%) patients and only in cases with a less than 7-day evolution. No association was found between HITS and clinical or imagiological features of the dissection nor with neurological aggravation or treatment type. We failed to demonstrate any relevant clinical significance of HITS in carotid dissection.

Adult↗

Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.

Theoretical considerations predict that amplification of expressed gene transcripts by reverse transcription-PCR using arbitrarily chosen primers will result in the preferential amplification of the central portion of the transcript. Systematic, high-throughput sequencing of such products would result in an expressed sequence tag (EST) database consisting of central, generally coding regions of expressed genes. Such a database would add significant value to existing public EST databases, which consist mostly of sequences derived from the extremities of cDNAs, and facilitate the construction of contigs of transcript sequences. We tested our predictions, creating a database of 10,000 sequences from human breast tumors. The data confirmed the central distribution of the sequences, the significant normalization of the sequence population, the frequent extension of contigs composed of existing human ESTs, and the identification of a series of potentially important homologues of known genes. This approach should make a significant contribution to the early identification of important human genes, the deciphering of the draft human genome sequence currently being compiled, and the shotgun sequencing of the human transcriptome.

Animals↗

Histochemistry of carbohydrates, proteins and lipids during swimbladder development in seabream, Sparus aurata and seabass, Dicentrarchus labrax.

Some histochemical aspects of carbohydrates, proteins and lipids were studied in the swimbladder of seabream, Sparus aurata and seabass, Dicentrarchus labrax. In both species, swimbladder development occurs in two stages: (1) inflation and (2) expansion, respectively. No important differences in histochemical distribution of glucidic, proteic and lipidic macromolecules were observed during the swimbladder development. Glycoproteins containing mannose and/or glucose sugar are present in the swimbladder (gas gland, wall and rete mirabile) of both species, but glycogen was observed only in the gas gland of Sparus aurata swimbladder. Proteins rich in different aminoacids, except those rich in tryptophan, as well as carboxyl but not sulphated glycoconjugates were observed in both species. Neutral lipids and phospholipids are also important compounds of the swimbladder. Abnormalities such as hyperinflation and non inflation are common for both species, but no important histochemical differences were detected in normal and abnormal seabream and seabass swimbladder.

Air Sacs↗

Morphine reduces social cohesion in rats.

The effect of low (1 mg/kg) doses of morphine on maintenance of physical proximity were evaluated in paired rats observed in a 4 square foot test arena. Morphine reliably reduced proximity maintenance time, and this was apparently not due to sedation, since the effect was unmodified by doses of amphetamine which substantially increased motor activity. The effects of naloxone were inconsistent on this measure of social motivation. In general, the results are consistent with the theoretical proposition that a brain neurochemical change which might lead to social attraction is the activation of endogenous opioid systems. When opiate activity is exogenously sustained, animals exhibit a subnormal tendency to be gregarious.

Amphetamine↗

[Diabetes mellitus and intracranial stenosis].

INTRODUCTION: The risk of having a cerebrovascular accident (CVA) is approximately 3 to 5 times greater in the diabetic population than in non-diabetics. The physiopathological mechanisms of CVAs in patients with diabetes mellitus are not well-known, since few studies of this have been done. OBJECTIVES: To verify the hypothesis that intracranial arteriosclerosis, interpreted from findings of stenosis on intracranial Doppler studies, is greater in diabetics than in non-diabetics, independently of other vascular risk factors. PATIENTS AND METHODS: Patients were selected from the Register of Cerebrovascular Diseases of the Neurology Department of the Hospital de Santa Maria as having had an ischemic cerebrovascular accident (CVA)/transient ischemic accident (TIA), assessed by a colour codified vertebral carotid eco-Doppler and transcranial Doppler. Intracranial changes in the diabetic and non-diabetic groups of patients were compared with relation to the presence of risks such as hypercolestrolaemia, arterial hypertension and smoking. RESULTS: 384 patients were included, 71 were diabetic and 313 non-diabetic. The two groups were comparable with regard to average age and sex. Intracranial stenosis was approximately 3.13 (95% CI = 1.69-5.79) times more frequent in the diabetic population than in non-diabetics. This difference persisted independently of the presence or absence of other vascular risk factors. CONCLUSIONS: Diabetes mellitus is an important independent risk factor of alterations in the intracranial blood vessels and therefore of CVA. The intracranial circulation should be studied in these patients in view of the great frequency of intracranial stenoses and possible future improvements with therapeutic intervention.

Brain↗

Solitary plasmocytoma of bone in an adolescent.

PURPOSE: To describe an adolescent with solitary plasmocytoma of bone and compare the pathologic and radiographic findings with osteomyelitis. PATIENT AND METHODS: A 17-year-old girl had a 3-year history of swelling of the right tibia, local pain, and hyperemia. RESULTS: Initial biopsy was interpreted as osteomyelitis. The lesion was rebiopsied 3 years later and showed a plasma cell neoplasm. A review of the first biopsy confirmed a similar histologic picture. CONCLUSION: Although solitary plasmocytoma of bone is a rare neoplasm in adolescence, it must be considered in the differential diagnosis of chronic osteomyelitis.

Adolescent↗