Search PubMed⌕ Search

Biomedical subjects

J L Balibrea

Publications and source records attributed to J L Balibrea.

At least 37 records · Page 2Linked to original sources
PubMed1999

LOH at the APC/MCC gene (5Q21) is frequent in early stages of non-small cell lung cancer.

Lung cancer is the leading cause of death in both women and men in the United States and many European countries. Molecular cytogenetic and LOH analyses of non-small cell lung cancer have shown somatic genetic alterations in a variety of chromosomes, such as 1p, 3p, 5q, 8p, 9p, 11p, 11q and 17p. Allelic deletions of the known tumor suppressor gene APC at 5q21 are frequently observed in advanced stages of lung cancer and have been correlated with poor prognosis in previous reports. We investigated 33 cases of NSCL for LOH at 5q21: 22 squamous cell and 11 adenocarcinomas. Normal and tumor cells were microdissected from paraffin embedded tissues and PCR amplification was performed utilising the specific markers D5S299 and D5S346 at 5q21 and PYGM at 11q13, respectively. Clinicopathological data, survival and recurrence rates were obtained in all cases. We detected LOH at 5q21 in 4/9 (44%) informative adenocarcinomas and in 13/16 (81%) informative SCC. LOH was frequent in early stages (12/15 stage I cases) and did not correlate with recurrence or poor survival. Our results show that LOH at 5q21 is more frequent in squamous cell carcinomas than in adenocarcinomas, is frequent in early stages of the disease, and does not have prognostic significance.

Adenocarcinoma↗
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

Expression of high p53 levels in colorectal cancer: a favourable prognostic factor.

The expression of p53 protein was examined in a series of 111 colorectal cancer adenocarcinomas with a long follow-up. A quantitative luminometric immunoassay (LIA) was used for the measurement of wild-type and mutant p53 protein in extracts from colorectal tumour cytosols, p53 being detected in 42% of the samples (range 0.0-52 ng (mg-1)). Using an arbitrary cut-off value of 2.7 ng mg(-1), 25% of the tumours were classified as manifesting high p53 levels. There was no association of p53 expression with patient age, sex, serum preoperative carcinoembryonic antigen (CEA) levels, tumour site and size, nodal status or TNM stage. Significant and independent correlation was found to exist between high p53 levels and prolonged disease-free survival (P = 0.05) at a median follow-up of 60 months. This survival advantage was most apparent among stage III cancer patients. The results from this study would suggest that expression of high p53 levels appear to be useful in selecting a group of colorectal cancer patients with a better prognosis.

Adenocarcinoma↗
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↗
PubMed1998

p53 exon 7 mutations as a predictor of poor prognosis in patients with colorectal cancer.

We have studied 61 resected colorectal adenocarcinomas in order to investigate p53 mutations as a prognostic factor for this pathology. Mutations in exons 5-9 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing. Our data indicate that p53 exon 7 mutations were prevalent in the latest stages of colorectal carcinogenesis and patients bearing this alteration had the worst prognosis. Therefore, according to our results, mutations affecting exon 7 of the p53 gene could be considered as a useful marker of biological aggressiveness for colorectal cancer.

Aged↗
PubMed1998

Prognostic value of genomic damage in non-small-cell lung cancer.

Genomic alterations have been analysed in 65 non-small-cell lung cancer (NSCLC) tissue samples by using the arbitrarily primed polymerase chain reaction (AP-PCR), which is a PCR-based genomic fingerprinting. We have shown that AP-PCR may be applied as a useful and feasible practical method for detection of the genomic alterations that accompany malignancy in NSCLC. Genomic changes detected by us consisted of: allelic losses or gains in anonymous DNA sequences, homozygously deleted DNA sequences and polymorphic DNA sequences. According to these genomic changes, lung tumours evaluated in the present study have been scored into three groups: low, moderate and high genomic damage tumours. The aim of this study was to investigate the effect of genomic damage on patient survival. Survival analysis was carried out in 51 NSCLC patients. Our results revealed that high genomic damage patients showed a poorer prognosis than those with low or moderate genomic damage (P = 0.038). Multivariate Cox regression analysis showed that patients with higher genomic alterations displayed an adjusted-by-stage risk ratio 4.26 times higher than the remaining patients (95% CI = 1.03-17.54). We can conclude that genomic damage has an independent prognostic value of poor clinical evolution in NSCLC.

Adult↗
PubMed1998

Genetic abnormalities and microsatellite instability in colorectal cancer.

Our purpose was to investigate different genetic abnormalities, such as K-ras mutations, p53 alterations, and c-myc RNA overexpression, as well as microsatellite instability in 63 colorectal tumors obtained from patients that had undergone surgery. K-ras point mutations were analyzed by PCR-RFLP technique, followed by sequencing; p53 protein accumulation by immunohistochemistry; p53 gene mutations in exons 5-9 were studied by the SSCP and sequencing techniques, and c-myc overexpression by Northern blot. Microsatellite instability was performed at chromosomes 2p, 3p, and 11p by a PCR-based technique. Our data indicate a trend toward a poorer prognosis in patients who had K-ras transversions; besides, we have obtained a prevalence of c-myc RNA overexpression and p53 exon 7 mutations in the latest stages of tumor progression. In conclusion, our findings suggest that the recognition of molecular abnormalities might be used in colorectal cancer as a prognostic indicator or to determine the metastatic potential of colorectal adenocarcinomas.

Aged↗
PubMed1997

Carbon monoxide contributes to the cytokine-induced inhibition of surfactant synthesis by human type II pneumocytes.

BACKGROUND: An increase in cyclic guanosine 3',5'-monophosphate (cGMP) due to nitric oxide generation is known to participate in the mediation of the tumor necrosis factor alpha (TNF-alpha) effect in type II cells. Because guanylyl cyclase can be activated also by carbon monoxide (CO), in this study we examined the ability of human type II pneumocytes to produce CO in the presence of cytokines and the relative contribution of this molecule to the TNF-alpha and interleukin 1 effects. DESIGN: Type II pneumocytes were isolated from cadaveric multiple-organ donors by enzymatic digestion, adherence separation of macrophages, and gradient purification. After preculture for 24 hours, cells were cultured for 24 hours in the presence or absence of TNF-alpha, interleukin 1, sodium nitroprusside, N(omega)-nitro-1-arginine, CO, hemin, zinc-protoporphyrin type IX, deferoxamine mesylate, S-adenosyl-L-methionine, alpha-tocopherol, methylene blue (a guanylyl cyclase inhibitor), 8-bromine-cGMP, and combinations of these reagents. Both CO (picomole per microgram of protein) and nitric oxide release to the medium and the cGMP (picomole per microgram of protein) content of the cells were measured. In a different set of experiments, D-glucose labeled with radioactive carbon (14C) was added to the medium, and the labeling of several lipid fractions was determined (picomole per microgram of protein). RESULTS: D-[14C]glucose incorporation into phosphatidylcholine, the main surfactant component, was selectively inhibited in the presence of cytokines, CO, sodium nitroprusside, or 8-bromine-cGMP. The inhibitory effect of TNF-alpha was partially reversed by N(omega)-nitro-L-arginine, deferoxamine, or alpha-tocopherol and totally reversed by methylene blue. Tumor necrosis factor alpha induced an increase in cGMP cell content and in the CO and nitric oxide release to the medium. Hemin increased CO and cGMP production and decreased phosphatidylcholine synthesis. Zinc-protoporphyrin type IX, an inhibitor of heme oxygenase, and all 3 antioxidants, which inhibited CO production, also antagonized the TNF-alpha effect on cGMP and phosphatidylcholine synthesis. CONCLUSIONS: Intracellular cGMP increase due to an endogenous generation of both CO and nitric oxide mediates the cytokine-induced inhibition of surfactant synthesis by type II pneumocytes. Both lipid peroxidation and heme oxygenase activity are sources for the observed CO production.

Adolescent↗
PubMed1997

Prediction of recurrence by quantification of p185neu protein in non-small-cell lung cancer tissue.

The concentration of c-erbB-2 oncogene-encoded protein (p185neu) in fresh tumour samples obtained at the time of surgery from 94 non-small-cell lung cancer patients (NSCLC) was determined by an enzyme immunoassay. The relative prognostic importance was estimated, and the influence of other predictors was assessed by means of a Cox's proportional regression model. Median concentration of p185 in tumour tissues was 206 U mg(-1) (range 21-1050 U mg(-1)). p185 level did not differ significantly among subgroups defined by TNM classification, histological type, sex and age. Categorization of patients by p185 level, with 206 U mg(-1) and 343 U mg(-1) taken as cut-off values (corresponding to the 50th and 80th percentiles of the frequency distribution), showed that the recurrence rate, cumulative disease-free likelihood at the 36-month follow-up and median time from surgery to the diagnosis of recurrence worsened progressively as the level of p185 increased. Multivariate analysis confirmed the independent prognostic value of p185 level. Risk of recurrence increased by 1.304 for every increase of 100 units in p185 concentration (95% CI 1.141-1.490) (P<0.001). These findings encourage the inclusion of p185 concentration assay in a future predictive multifactorial prognostic index in NSCLC.

Adult↗
PubMed1997

p53 exon 5 mutations as a prognostic indicator of shortened survival in non-small-cell lung cancer.

Inactivation of the tumour-suppressor gene p53 has been described as one of the most common molecular changes found in lung tumours. Our purpose was to study the prognostic value of p53 alterations and to determine whether some specific mutation type in the p53 gene could be associated with poor clinical evolution in non-small-cell lung cancer (NSCLC) patients. To this end, we studied 81 resected primary NSCLCs in order to detect p53 alterations. p53 protein accumulation was analysed using immunohistochemistry methods; p53 gene mutations in exons 5-9 were studied using polymerase chain reaction-single-strand conformation polymorphism and sequencing techniques. p53 protein was immunodetected in 46.9% of lung carcinomas and 44.7% of p53-immunopositive tumours showed p53 mutations. Survival analysis was performed on 62 patients. No survival differences were found for patients with or without p53 immunopositivity. A shorter survival was found in patients with underlying p53 gene mutations, mainly in patients with squamous cell lung tumours; the worst prognosis was found when mutations were located in exon 5 (P = 0.007). In conclusion, the location of p53 mutations might be considered as a prognostic indicator for the evaluation of poor clinical evolution in NSCLC patients.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Local production of oxygen free radicals and nitric oxide in rat diaphragm during sepsis: effects of pentoxifylline and somatostatin.

OBJECTIVE: To investigate the effect of giving lipopolysaccharide (LPS) on lipid peroxidation, and myeloperoxidase (MPO), nitric oxide (NO) synthase, and phospholipase A2 (PLA2) activities in rat diaphragm, and see whether they could be modified by giving pentoxifylline (PTXF) or somatostatin. DESIGN: Randomised experimental study. SETTING: Teaching hospital, Spain. MATERIAL: 76 Wistar rats divided into 4 groups of 19: control (saline/saline), LPS/saline, LPS/PTXF and LPS/somatostatin. INTERVENTIONS: The LPS was given intraperitoneally either 30 minutes (early, n = 10 in each group) or 120 minutes (late, n = 9 in each group) before treatment with saline, PTXF (45 mg/kg) or somatostatin (200 microg/kg) given intraperitoneally. Rats were killed 120 minutes after treatment. MAIN OUTCOME MEASURES: Malondialdehyde (MDA) and conjugated dienes content, and MPO, NO synthase, and PLA2 activities in diaphragmatic tissue. RESULTS: Conjugated dienes and MDA content, as well as MPO, NO synthase, and PLA2 activities were significantly increased in the rats given LPS. Independently of the timing of treatment, both PTXF and somatostatin completely prevented these increases. CONCLUSION: It is possible that treatment with PTXF or somatostatin may reduce the risk of ventilatory failure and speed recovery in septic patients.

Analysis of Variance↗
PubMed1996

Analysis of the prognostic significance of cytosolic determination of CA 125 tumor-associated antigen, carcinoembryonic antigen and squamous cell carcinoma antigen in patients with nonsmall cell lung carcinoma.

BACKGROUND: The use of new prognostic factors as guidelines for the indication of treatment ancillary to surgery has been advocated for patients with nonsmall cell lung carcinoma (NSCLC). This article is an analysis of the prognostic information derived from determination of tumor-tissue cytosolic concentration of CA 125 tumor-associated antigen (CA 125), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC) in patients with NSCLC. METHODS: Tumor samples were obtained from 97 patients who successfully underwent surgery for NSCLC with curative intent. CA 125 and CEA were determined by enzyme immunoassay. SCC was determined by radioimmunoassay. The relationship between the tumor-tissue marker level and survival or likelihood of disease free survival was analyzed. RESULTS: Thirty-month survival post-treatment in patients registering CA 125 levels less than 26 U/mg was 68%, versus 30% among patients with levels of CA 125 greater tha 26 U/mg (P < 0.005). For SCC, these values were 57% and 39%, respectively (P = 0.07). No significant difference was seen for CEA (60% versus 44%; P = 0.3). Patients whose tumors had CA 125 levels lower than cutoff recorded a disease free survival rate of 61% versus 29% (P < 0.001); with SCC, likelihood of remaining free of tumor recurrence was 55% versus 34% (P < 0.05). Again, no significant difference was seen for CEA (49% versus 45%; P = 0.5). For CA 125 and SCC, the relationship between marker level and outcome held only with the most favorable histologic types. For CA 125 however, this relationship also held for Stage I tumors (P < 0.005). CONCLUSIONS: Ascertainment of concentrations of CA 125 and SCC in tumor tissue is useful parameter in the determination of postoperative prognosis for patients with NSCLC.

Adult↗
PubMed1996

S-adenosylmethionine protects hepatocytes against the effects of cytokines.

Cytokines are thought to play an important role in the hepatocellular dysfunction that occurs during sepsis. Some cytokines have been shown to increase lipogenesis and to induce toxicity in isolated hepatocytes. Oxygen free radicals have been implicated as mediators of some cytokine effects. In this study we investigate a possible protection action of S-adenosyl-L-methionine against the toxic effects of cytokines on isolated hepatocytes. Isolated rat hepatocytes were precultured for 24 hr and then cultured for 1, 2, 3, 6, 12, or 24 hr in the presence or absence of S-adenosyl-L-methionine (12 micromol/l0) and/or either tumor necrosis factor (100, 200, or 500 ng/ml) or interleukin-1 (30, 60, or 120 IU/ml). Lactate dehydrogenase (media), and malondialdehyde, reduced glutathione, and the incorporation of D-[U- 14 C] glucose into different lipid fractions (cells) were determined. Both cytokines significantly increased hepatocyte malondialdehyde content, lactate dehydrogenase release, and triacylglycerol synthesis. None of these effects were observed in the presence of S-adenosyl--L-methionine. In addition, S-adenosyl-L-methionine was able to attenuate the decrease in phosphatidylcholine labeling also induced by both cytokines, and to prevent the increase in free fatty acid synthesis induced by tumor necrosis factor. Incubation in the presence of S-adenosyl-L-methionine also increased hepatocyte glutathione content (7.1 +/- 0.7, after 24 hr, vs 3.6 +/- 0.3 nmole/mg protein, P < 0.01), and prevented the decrease in glutathione induced by tumor necrosis factor (5.4 +/- 0.2 vs 2.1 +/- 0.1 nmole/mg protein, 100 ng/ml TNF alpha at 24 hr, P < 0.01). Our results show that S-adenosyl-L-methionine has a protective effect on hepatocytes against the in vitro effect of cytokines.

Animals↗