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Biomedical subjects

P Pujol

Publications and source records attributed to P Pujol.

48 records · Page 3Linked to original sources

William L. McGuire Memorial Symposium. The role and prognostic significance of p53 gene alterations in breast cancer.

Alterations in the p53 tumor suppressor gene are the most frequent genetic changes found in breast cancer, with an incidence reported in a range of 15 to 50%. The incidence of p53 alterations is approximately 15% for in situ carcinoma, while for invasive node-positive disease it is 2 to 3 times higher. This high rate of alteration suggests that the gene plays a central role in the development of breast cancer. The p53 gene functions as a negative regulator of cell growth. Alterations in the gene lead to loss of its usual negative growth regulation and more rapid cell proliferation. Since p53 alteration can reflect a more advanced state of progression and a higher rate of proliferation, breast tumors that have a p53 alteration could have a greater probability of having micrometastasis. p53 alterations could therefore be a prognostic factor for recurrence after primary local therapy. Consistent with this hypothesis, several independent studies using different methodologies have found that breast tumors with altered p53 have a worse prognosis and are also more likely to have other poor prognostic factors.

Amino Acid Sequence↗

[Barret's esophagus and acid gastroesophageal reflux. Two-channel pH-metric measurements and manometric study].

Although the pathogenic role of gastroesophageal reflux in Barrett's esophagus (BE) is now widely accepted, the pattern of pH profile in the esophagus of patients with BE is not well documented. The aim of this study was to assess the severity and "extent" of acid exposure in patients with BE using an automated single or two-channel 24-hour pH monitoring system. Eighteen patients with histologically proven BE were compared with 3 other groups: a) 100 patients with clinical symptoms and pHmetrically proven acid reflux divided in 2 sub-groups: 38 patients without esophagitis at endoscopy, and 62 patients with esophagitis (Savary-Miller classification; grade I: n = 24, grade II: n = 27, grade III: n = 8, grade IV: n = 3) and b) 9 healthy volunteers. In 17 patients with BE, and in 14 patients with reflux and healthy volunteers, 2 electrodes were placed 5 (electrode E1) and 10 cm (electrode E2) above the lower esophageal sphincter. In the other patients, pH was monitored using a single pH electrode (E1) only. The mucosal acid exposure at E1 (percentage of time below pH 4 on total period, day and night), the number of reflux episodes longer than 5 min were significantly higher in the BE group when compared with the other groups. The number of patients with abnormal acid exposure at E2 was significantly higher (P less than 0.01) in the BE group (15/17 cases) than in the reflux group (5/14 cases). The mean duration of acid reflux was significantly longer in BE than in other groups at both recording sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prevention of recurrent variceal bleeding in alcoholic cirrhotic patients: prospective controlled trial of propranolol and sclerotherapy.

We conducted a prospective randomized controlled study to evaluate the effectiveness of propranolol and sclerotherapy, compared to a control group, in the prevention of variceal rebleeding in alcoholic cirrhotic patients. Among the 79 patients included, the distribution of patients according to Child-Pugh classification was: A, 22%; B, 40%; and C, 38%. Propranolol was given twice daily with a mean final dose of 54 +/- 16 mg/day, this resulted in a mean reduction in resting heart rate of 26 +/- 7%. Sclerotherapy was performed weekly using 1% polidocanol. End points were rebleeding or death. During the mean follow up of 19 +/- 16 months, 43 patients bled and 22 patients died. The cumulative percentages of patients free of rebleeding at 1 year were: propranolol, 81% (95% confidence interval (CI): 63-92); sclerotherapy, 64% (95% CI: 45-82); control, 54% (95% CI: 36-71); these differences did not reach statistical significance. The cumulative percentages of patients alive at 1 year were: propranolol, 92% (95% CI: 76-98); sclerotherapy, 79% (95% CI: 58-91); control, 81% (95% CI: 60-93); these differences were not statistically significant. Alcohol withdrawal, which occurred in 66% of patients, was an independent predictive factor associated with a decreased risk of rebleeding or death. In conclusion, a life table analysis of patients free of rebleeding, as well as of patients surviving, revealed a tendency in favour of propranolol. The lack of a statistical support for these two favorable effects could be due to poor statistical power.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗

p53 mutations in ovarian cancer: a late event?

Using a combination of polymerase chain reaction and single-strand conformation polymorphism techniques we analyzed 34 ovarian cancer samples (30 primary tumors and four matched metastases) for the presence of mutations in exons 5, 6, 7, 8 and 9 of the p53 gene. Mutations in this portion of the gene are known to lead to the loss of the oncosuppressive potential of p53. Thirty-six percent (11/30) of the ovarian carcinomas tested presented a mutated p53 allele. Mutations were clustered in exons 5 and 7 to the exclusion of the other exons screened. Most mutations (10/11) were point mutations, but no preferential pattern of nucleotide substitution could be observed. In three tumors the mutation of one allele was concomitant with the loss of the wild-type counterpart. Another sample presented both alleles independently mutated. These observations are in agreement with the recessive nature of the p53 mutation. However, analysis of tissue sections from two tumors showed that the portion composed of 100% cancer cells could hold both the mutated and the wild-type form. Moreover analysis of serial sections gave evidence of a heterogeneous cellular content in one of these tumors, suggesting that p53 mutations may, in some cases, occur late during ovarian cancer evolution. It is, moreover, noticeable that, in matched sets of primary tumors and metastases, the same mutation was observed in both tumor samples. Therefore, even as a late event, p53 mutation occurs before metastatic spread.

Amino Acid Sequence↗

Overexpression of transfected cathepsin D in transformed cells increases their malignant phenotype and metastatic potency.

Cathepsin D, an aspartic lysosomal proteinase, is overexpressed by breast cancer cells and highly correlated with the occurrence of metastasis in patients. We used an adenovirus transformed rat cell line that does not secrete cathepsin D, to study the consequences of transfecting human cathepsin D cDNA. Overexpression of human cathepsin D in stable transfectant clones, results in higher initial growth rates in low serum conditions, overgrowth at high cell densities resulting in stellate aggregates, and greater anchorage-independent growth in soft agar. The metastatic activity (mostly in liver) of cathepsin D clones injected into athymic mice was significantly higher than that of control clones. These results show that overexpression of cathepsin D increases the transformed phenotype of malignant cells in vitro and their metastatic potency in vivo.

Animals↗

[Digital storage and semi-automatic analysis of esophageal pressure signals. Evaluation of a commercialized system (PC Polygraft, Synectics)].

The aim of this work was to evaluate a new commercially available pressure recording system (PC Polygraf, Synectics) and to compare this system with a classical method using perfused catheters. The PC Polygraf uses microtransducers and allows direct digitized storage and semi-automatic analysis of data. In the first part of this study, manometric assessment was conducted using only perfused catheters. The transducers were connected to both an analog recorder and to a PC Polygraf. Using the two methods of analysis, contraction amplitudes were strongly correlated (r = 0.99; p less than 0.0001) whereas durations were significantly but loosely correlated (r = 0.51; p less than 0.001). Resting LES pressure was significantly correlated (r = 0.87; p less than 0.05). In the second part of this study, simultaneous recordings of esophageal pressure were conducted in 7 patients, by placing side by side the two tubes (microtransducers and perfused catheters) with the sideholes at the same level. The characteristics of the waves were determined both by visual analysis of analog tracing and by semi-automatic analysis of digitized recording with adequate program. Mean amplitude was lower with the microtransducers than with the perfused catheters (60 vs 68 cm H2O; p less than 0.05), but the duration of waves was not significantly different when using both systems. Values obtained for each of these parameters using both methods were significantly correlated (amplitude: r = 0.74; duration: r = 0.51). The localization and the measure of the basal tone of sphincter were found to be difficult when using microtransducers. These results show that PC Polygraf allows a satisfactory analysis of esophageal pressure signals. However, only perfused catheters offer an excellent reliability for complete studies of both sphincter and peristaltism.

Adult↗

A method for the measurement and characterization of protease activities responsible for extracellular or intracellular degradation of collagen precursors.

The first method for the qualitative and quantitative evaluation of extracellular and intracellular protease activities responsible for degradation of newly synthesized collagen is described. In a double incubation method, underhydroxylated collagen chains (protocollagen) serve as substrate for protease extract and then for the indicator enzyme, 4 prolyl hydroxylase. It was possible to characterize at least four types of protocollagen sites sensible to these proteases. The microsomal fraction of chick embryo liver contained a protease active on protocollagen and whose activity was similar to that of purified human synovial collagenase.

Animals↗

[A dengue epidemic at Futuna].

During an outbreak occuring in Futuna (Horne Islands) from October 1976 to January 1977, II strains quite similar to dengue virus type I were isolated from blood of patients in acute phase. Immunitary responses were noted on 8/12 paired sera submitted to IH test; 4/17 serum samples showed antibody titer presumptive of a recent infection. Entomological survey gave evidence that virus was transmitted by Aedes polynesiensis and confirmed that Futuna is free of A.E. aegypti; other species found were: Culex annulirostris, C. pipiens fatigans, C. sitiens. A viral strain was isolated from Ae. polynesiensis only.

Adolescent↗

Why are estrogen-receptor-negative breast cancers more aggressive than the estrogen-receptor-positive breast cancers?

It is well established that some of the hormone-resistant breast cancers lack functional estrogen receptor (ER) and exhibit a more aggressive metastatic phenotype. The estrogen activation of ER in ER-positive breast cancers enhances their aggressiveness, while the activation of exogenously introduced ERs into aggressive ER-negative cells diminishes their aggressiveness. The basis of the protective effect of the ER appears complex and could be due to the altered expression of genes involved in cell proliferation, differentiation and invasiveness. In this review, we propose different mechanisms for the higher aggressiveness of most of the ER-negative breast cancers.

Animals↗