Biomedical subjects

A Sánchez-Pernaute

Publications and source records attributed to A Sánchez-Pernaute.

18 recordsLinked to original sources

PubMed2005

Characterization of MDGA1, a novel human glycosylphosphatidylinositol-anchored protein localized in lipid rafts.

We report the characterization of the novel human protein MDGA1 encoded by MDGA1 (MAM domain containing glycosylphosphatidylinositol anchor-1) gene, firstly termed as GPIM. MDGA1 has been mapped to 6p21 and it is expressed in human tissues and tumors. The deduced polypeptide consists of 955 amino acids and exhibits structural features found in different types of cell adhesion molecules (CAMs), such as the presence of both immunoglobulin domains and a MAM domain or the capacity to anchor to the cell membrane by a GPI (glycosylphosphatidylinositol) motif. Our results demonstrate that human MDGA1 (hMDGA1) is localized in the membrane of eukaryotic cells. The protein follows the secretion pathway and finally it is retained in the cell membrane by a GPI anchor, susceptible to be cleavaged by phospholipase C (PI-PLC). Moreover, our results reveal that hMDGA1 is localized specifically into membrane microdomains known as lipid rafts. Finally, as other proteins of the secretory pathway, hMDGA1 undergoes other post-translational modification consisting of N-glycosylation.

Amino Acid Motifs↗

PubMed2005

Severe hypocalcemia following total thyroidectomy after biliopancreatic diversion.

Patients undergoing malabsoprtive operations for bariatric surgery are prone to disturbances of bone metabolism, but this does not commonly lead to clinical symptoms. We present a morbidly obese patient who had undergone the biliopancreatic diversion of Larrad, and presented clinical symptoms of severe hypocalcemia and tetany after total thyroidectomy. Very high doses of i.v. calcium and calcitriol and 10 days of hospitalization were required to control the symptoms and correct plasma levels. The physiological aspects that contribute to this situation are discussed.

Adult↗

PubMed2005

Overexpression of c-myc and loss of heterozygosity on 2p, 3p, 5q, 17p and 18q in sporadic colorectal carcinoma.

AIM: The aim of the present study is to evaluate the prognostic influence of loss of heterozygosity on 2p, 3p, 5q, 17p and 18q, and c-myc overexpression on surgically treated sporadic colorectal carcinoma. METHODS: Tumor and non-tumor tissue samples from 153 patients were analyzed. Fifty-one percent of patients were male, and mean age in the series was 67 years. Tumors were located in the proximal colon in 37 cases, in the distal bowel in 37, and in the rectum in 79 patients. c-myc overexpression was studied by means of Northern blot analysis, and loss of heterozygosity through microsatellite analysis. RESULTS: c-myc overexpression was detected in 25% of cases, and loss of heterozygosity in at least one of the studied regions in 48%. There was no association between clinical and pathologic features, and genetic alterations. The disease-free interval was significantly shorter for patients with both genetic alterations; the presence of both events was an independent prognostic factor for poor outcome in the multivariate analysis (RR: 4.34, p < 0.0001). CONCLUSIONS: The presence of both loss of heterozygosity and overexpression of the c-myc oncogene separates a subset of colorectal carcinoma patients who have a shorter disease-free interval after curative-intent surgery.

Adult↗

PubMed2005

Clinical relevance of MMP-9, MMP-2, TIMP-1 and TIMP-2 in colorectal cancer.

The main aim of this study was to evaluate the clinical relevance of Gelatinases in colorectal cancer (CRC). Ninety-five CRCs and their paired normal tissues were investigated to detect total levels of MMP-9, MMP-2, and the tissue inhibitors TIMP-1 and TIMP-2. Also, pro-MMP and MMP activity, and potential associations with clinical parameters were estimated. MMP-9, MMP-2 and TIMP-1 levels were greater in CRCs than in normal tissues, differences being significant for MMP-9 and TIMP-1. However, TIMP-2 showed significantly lower levels in tumour samples. Moreover, significant differences in the state of activation between gelatinases were found. TIMP-1 low levels were significantly associated with poor clinical outcome of patients. According to these data, different roles have to be attributed to MMP-2 and MMP-9 in CRC progression. Moreover, TIMP-1 level evaluation emerges as the main prognostic factor in relation to Gelatinases A and B activity in CRC.

Adenocarcinoma↗

PubMed2004

Relationship between 3p deletions and telomerase activity in non-small-cell lung cancer: prognostic implications.

3p deletions and telomerase reactivation are two of the most frequent events described in relation to non-small-cell lung cancer (NSCLC) pathogenesis. Moreover, a number of genes that map on 3p have been proposed as candidates to tumour-suppressor genes of importance in the lung cancer process. In this work, we analysed deletions at different 3p loci in relationship to telomerase activity in 66 NSCLCs obtained from patients who had suffered potentially curative surgery. Also, we evaluated prognostic implications. DNA samples were analysed for 3p deletions using five different polymorphic human dinucleotide repeat DNA markers (D3S1619 at 3p22.2, D3S3623 at 3p22.1, D3S1260 at 3p21.33, D3S3697 at 3p14.3, and D3S3722 at 3p21.2). Telomerase activity was investigated by a TRAP-based method. Possible correlations between the different molecular markers and distributions of disease-free survival were estimated. Our data revealed a significant correlation between telomerase activity and losses of heterozygosity (LOH) on D3S3697 (P=0.040), since all of the tumours showing deletion at this locus were positives for telomerase. Moreover, our results revealed clear associations with poor prognosis of patients, in the case of LOH at D3S1260 and D3S3697 (P=0.005 and 0.005, respectively). According to our data, potential repressors for telomerase may be located in chromosome 3p.

Aged↗

PubMed2003

Recurrence pattern of esophageal cancer after esophagectomy with two-field lymphadenectomy.

AIM: To analyze the pattern of recurrence of esophageal carcinoma after a curative-intention surgical resection. PATIENTS: Ninety-two patients with non-metastatic esophageal carcinoma were included. Ninety percent of patients were male, and the mean age of this series was 61 years. The most frequent histologic subtype was squamous cell carcinoma. Fifty percent of tumors were at or above the tracheal bifurcation. All patients were submitted for transthoracic subtotal esophagectomy plus two-field radical lymphadenectomy, leaving no apparent residual disease. No adjuvant therapy was applied to any patient. RESULTS: Follow-up was complete for 76 out of 80 patients surviving the operation. Thirty-four tumoral recurrences were detected for a disease-free survival af 39% at 9 years after surgery. All recurrences were detected during the first two years after treatment. Tumoral relapse was related to the presence of T3 or T4 tumors, with positive lymph nodes, squamous cell carcinoma subtype and supracarinal location. Nine percent of patients had a distant relapse, 15% had a locorregional relapse and 12% a combination of both. Distant relapse presented significantly earlier. There was no statistical association between type of recurrence and clinico-pathological or surgical features. CONCLUSIONS: After radical surgery for carcinoma of the esophagus, half of the patients relapse in the following two years. Distant metastases happen to appear earlier in the follow-up, but the most frequent recurrence is the locorregional one.

Adult↗

PubMed2001

Ischaemic colitis.

Explore the source record for details and available documents.

Colitis, Ischemic↗

PubMed2000

Loss of heterozygosity at 3p23 is correlated with poor survival in patients with colorectal carcinoma.

BACKGROUND: Loss of heterozygosity (LOH) of chromosome 3p has been observed commonly in carcinomas of various tumor tissues, including colorectal carcinoma (CRC). Because there is no report analyzing 3p deletions in relation to patient prognosis in CRC, the authors investigated the prognostic value of LOH on 3p in 87 patients with sporadic CRC. METHODS: DNA samples from tumor and nontumor tissues were amplified by using polymerase chain reaction (PCR) and were analyzed for LOH on 3p using four different polymorphic human dinucleotide repeat DNA markers that map on this chromosome arm. The correlations with prognosis were established by the Kaplan-Meier method, and the Cox proportional hazards model was used to identify which independent factors jointly had a significant influence on patient survival. RESULTS: Overall, allelic losses were detected in 19.5% of the patients evaluated. Only considering informative tumors, the data indicated that LOH was observed in 17 of 71 (29.4%) informative cases. Results from survival analysis showed a significant correlation between this molecular abnormality and both overall survival and disease free survival (P = 0.02 and P = 0.0005, respectively). The worst prognosis was found for the group of patients with LOH at 3p23: This alteration was an independent prognostic factor according to Cox multivariate analysis. CONCLUSIONS: This study is the first to demonstrate the prognostic significance of LOH at chromosome arm 3p for patients CRC and may help to identify patients who need an intensive postoperative follow-up protocol.

Adenocarcinoma↗

PubMed2000

Cefminox versus metronidazole plus gentamicin intra-abdominal infections: a prospective randomized controlled clinical trial.

BACKGROUND: The aim of this prospective study was to compare the safety and efficacy of a new cephamycin, cefminox 2 g/12 h, to those of the usual regimen combining metronidazole 500 mg/8 h and gentamicin 80 mg/8 h (M+G). PATIENTS AND METHODS: 160 patients with clinically proven intra-abdominal infection were prospectively included in an open parallel randomized comparative multicenter trial. Antibiotics were started preoperatively and discontinued after clinical and laboratory evidence of resolution of the infection. Serum and peritoneal fluid levels and serum bactericidal activities were also studied. RESULTS: 150 patients were clinically evaluable. There was one failure in the cefminox group and three in the M+G group (not significant, RR: 1.07, 95% CI: 1-1.15). No differences were found in the number of wound infections, length of stay or duration of antibiotic therapy. Adverse effects were reported in 11 cases, all of them mild to moderate. Escherichia coli and Bacteroides fragilis were the most frequently found microorganisms. CONCLUSION: Cefminox is as effective and as safe as M+G in the treatment of intra-abdominal infections.

Abdomen↗

PubMed2000

Detection of telomerase activity in human carcinomas using a trap-ELISA method: correlation with hTR and hTERT expression.

We have evaluated telomerase activity in a tumour population of 65 human cancers by using a TRAP-based method, in which detection is performed by an enzyme immunoassay (ELISA). We have corroborated that sensitivity and specificity of this new procedure can be considered similar to that of classical TRAP method, having the advantage of a rapid and reproducible analysis of large pools of samples. Thus, telomerase activity was detected in 83% of the tumours included in our population. Moreover, we found a significant association between enzyme activity and both hTR and hTERT expression (P=0.004 and P=0.04, respectively).

DNA-Binding Proteins↗

PubMed1999

[Prognostic value of heterozygosity loss in chromosome 3p in non-microcytic bronchogenic carcinoma].

BACKGROUND: Recent advances on carcinogenesis have led to the recognition of different patterns of behaviour of non-small cell lung cancers apart from those guided by the TNM staging system and the histologic subtype. The frequent genetic loss on chromosome 3p in all kinds of lung carcinoma leads to the suspect of the presence of a tumor suppressor gene located in that place. The aim of this work was to compare the different clinical features and evolution after treatment of the patients with non small cell lung carcinoma with and without loss of heterozygosity (LOH) on 3p. PATIENTS AND METHOD: Forty-five operated on non-small cell lung cancer patients were evaluated. The mean age was 64.4 years and all the patients were male. Seven patients had been previously treated for another epithelial neoplasm. 82.2% of the patients were heavy tobacco smokers. Most of the tumors (62.2%) were squamous cell carcinomas. Samples of tumoral and non tumoral lung tissue were immediately frozen after surgery. DNA from the tissue was extracted; then PCR amplification of microsatellites in regions 3p14 and 3p21 was performed. To determine the LOH in the regions analyzed a polyacrylamide gel electrophoresis was performed. RESULTS: Twenty-five percent of the informative samples for 3p14 and 21.9% for 3p21 showed LOH. There was an statistical relationship between the LOH on 3p14 and the history of tobacco smoking and the adenocarcinoma histologic subtype (p < 0.05). There was a higher number of relapses and a shorter disease-free interval in those patients harboring 3p21 LOH. CONCLUSIONS: LOH on 3p can be detected in non-small cell lung carcinoma. Patients with loss of heterozygosity on 3p21 have a worse evolution after a curative intended surgical resection.

Adult↗

PubMed1999

Differential prognosis of replication error phenotype and loss of heterozygosity in sporadic colorectal cancer.

Several distinct genetic alterations have been associated with colorectal tumorigenesis. This study investigated the frequency of microsatellite instability, also known as replication error (RER), and loss of heterozygosity (LOH) at six chromosome regions in sporadic colorectal cancer (CRC). Eighty-six tumour and paired normal mucosa samples were included in the study. A polymerase chain reaction (PCR)-based technique was performed to analyse six (CA)n dinucleotide repeats located near or within regions containing important genes implicated in the complex process of colorectal tumorigenesis (chromosomes 2p, 3p, 5q, 11p, 17p and 18q). Overall, LOH frequency was higher in RER-tumours (25/46, 54.3%) compared with RER+ tumours (9/40, 22.5) (P = 0.04). To investigate prognostic implications, survival analysis was performed for 66 patients. Compared with RER- tumours, patients with RER+ tumours at 2p, 3p, 5q, 11p or 18q were found to have an improved prognosis (overall survival, P = 0.02 and disease-free survival (DFS) P = 0.005) this variable being an independent prognostic factor by multivariate analysis (P = 0.001). Overall survival of patients whose tumours were LOH+ was significantly shorter compared with those without LOH (overall survival, P = 0.008 and DFS, P = 0.01). Thus, tumours displaying RER+ and LOH+ phenotype, as established by microsatellite analysis, show a differential prognosis. These data indicate that this may be a useful tool for the identification of patients at different risks affected by CRC.

Aged↗

PubMed1999

Multiple solitary leiomyomata of the esophagus.

The present report communicates a case of multiple solitary leiomyomata of the esophagus. This is an uncommon condition in which multiple, non-confluent, benign esophageal tumors arise in the same patient. The ideal treatment is enucleation of the lesions, but when these are--as in the case reported--huge and annular, or affect the gastroesophageal junction, resection of the gullet must be performed.

Adult↗

PubMed1999

Two-field radical lymphadenectomy in the treatment of esophageal carcinoma.

This paper retrospectively compares post-operative complications, mortality and long-term survival of patients with esophageal carcinoma who were treated with standard esophagectomy or with extended two-field lymph node clearance. Fifty-seven patients with resectable esophageal carcinoma were included in the study. Twenty-eight patients were submitted to a radical two-field esophagectomy and lymphadenectomy, while the remaining 29 were submitted to a standard, more conservative, esophagectomy performed mostly through a transhiatal route. The two groups of patients were similar in all clinical, laboratory and pathologic features. There was a significant lower anastomotic leakage rate in the group of patients submitted to a radical lymph node resection; post-operative respiratory complication rate and mortality were similar in both groups. The overall 5-year survival was 20%. When lymph node resection was performed, the 5-year survival rate rose to 36%; it was 44% when nodal involvement was negative and 19% for N1 patients; when standard esophagectomy was the procedure, these figures were 9% (p < 0.05), and 6% respectively.

Adenocarcinoma↗

PubMed1999

Heterotopic gastric mucosa in the upper esophagus ("inlet patch"): a rare cause of esophageal perforation.

We report the case of a 21-yr-old woman who presented with a perforation of an upper esophageal ulcer on a patch of gastric-type mucosa. Despite surgical closure of the perforation and reinforcement with a pleuro-muscular flap the patient developed an esophageal leakage and died in the postoperative period. Heterotopic gastric mucosa in the upper esophagus is usually an asymptomatic abnormality, discovered incidentally during endoscopic studies carried out for some other reason; however, complications secondary to the inlet patch acid secreting capacity can arise, and this has to be kept in mind to elude life-threatening conditions.

Adult↗

PubMed1994

[An adenocarcinoid tumor of the vermiform appendix].

Goblet cell carcinoids of the vermiform appendix are uncommon. A comprehensive review of the literature revealed about 100 reported cases. Clinical presentation included: asymptomatic patients, acute appendicitis, and/or chronic intermittent lower abdominal pain with or without a palpable mass. We report the case of a 57 year-old woman with lower abdominal pain, nausea and vomiting. Normal blood tests. X-ray of the abdomen showed dilated small bowel loops with fluid levels. Initially, conservative treatment was started. After three days with no clinical improvement, the patient was operated on. An appendicocecal inflammation was found and a terminal ileum plus cecal resection with an end-to-side anastomosis was performed. The pathological diagnosis was goblet cell carcinoid. The patient shows no evidence of recurrence after 1 year follow-up.

Appendiceal Neoplasms↗

PubMedDate not supplied

[Epidermal growth factor receptor in non-small cell cancer of the lung].

In this study we determined the concentration of epidermic growth factor receptors (EGFr) in non-small cell carcinoma of the lung (NSCCL) and analyzed its relation to the anatomical, pathological and clinical factors of these neoplasms. The concentration of EGFr in 62 tumor tissue samples was 9.9 +/- 14 fmol/mg, higher than that found in 14 tissue samples from cases of spontaneous pneumothorax (3.9 +/- 3.6 fmol/mg) (p = 0.005). EGFr concentration in lung tissue with no signs of neoplasm was 6.5 +/- 10 fmol/mg. In 21 (33%) cases of NSCCL the concentration exceeded the normal threshold of 10 fmol/mg. EGFr concentration was higher in cases of epidermoid carcinoma than in other tissue samples (p = 0.042). No significant association was found between EGFr levels and status of tumor node metastasis, degree of differentiation and mitotic index. The probability of remaining free of tumor recurrence and of survival after 24 months among patients whose tumoral EGFr concentration was below 10 fmol/mg was 34 and 40%, respectively. The rates for patients with concentrations that exceeded the threshold were 20% (p = 0.32) and 25% (p = 0.26), respectively. The results seem to indicate that the study of EGFr concentration alone does not yield practically important information for the management of patients with NSCCL who have undergone surgery. The concentration of EGFr marks degree of differentiation in NSCCL and has prognostic implications derived from its association with other factors.

Adenocarcinoma↗

PubMedDate not supplied

Prognostic significance of p53 gene mutations in squamous cell carcinoma of the lung.

The aim of the present study was to analyze the prevalence and clinical importance of p53 gene mutations in surgically treated squamous cell lung carcinoma. Sixty patients were included. Fifty-one patients in stages I to IIIa were submitted to radical resection. Twenty-five samples tested positive for the p53 immunohistochemistry assay, and were analyzed for p53 gene mutations. Eleven mutations were found. Patients harboring p53 gene mutations suffered a higher incidence of recurrence and a higher mortality rate. Disease-free interval and overall survival were shorter for patients with mutated p53 gene (p=0.03 and p=0.005, respectively).

Adult↗