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Biomedical subjects

M Monzó

Publications and source records attributed to M Monzó.

27 records · Page 2Linked to original sources
PubMed1997

Microsatellite alterations at 5q21, 11p13, and 11p15.5 do not predict survival in non-small cell lung cancer.

We investigated the clinical implications of allelic deletions at three common sites of loss of heterozygosity (LOH) in regions 5q21, 11p15.5, and 11p13 in 86 patients with non-small cell lung cancer (NSCLC). We performed a PCR-based microsatellite polymorphism assay for detection of LOH. The microsatellite markers used were D5S82 (proximal to the APC gene), MCC (within the MCC gene), D11S904 (11p13), HRAS (within the H-ras gene), and D11S860 (11p15.5). Of the 68 informative cases at 5q21 loci, LOH was found in 14 cases (20%), whereas LOH frequency in 11p15.5 and 11p13 was 31% (19 of 61 informative cases) and 19% (12 of 63 informative cases), respectively. There was a significant correlation between 5q21 LOH and mediastinal lymph node involvement (P = 0.03). However, no differences were observed in median survival times (26 months in patients with 5q21 LOH versus 37 months in the remainder; P = 0.33) nor in patients with 11p LOH (38 months versus 32 months, respectively; P = 0.72). Cox's proportional hazards model predicted that stage was the only independent poor prognostic marker in the entire cohort of NSCLC patients. Thus, the present study revealed two important abnormalities, LOH at chromosome 5q21 and LOH at chromosome 11p, both implied in NSCLC development.

Adult↗
PubMed1996

Molecular staging of non-small cell lung cancer according to K-ras genotypes.

We have previously demonstrated a strong association between K-ras gene mutations, as determined by PCR followed by allele-specific oligonucleotide hybridization (ASO-h), and survival in non-small cell lung cancer patients. The purpose of this study was to determine the relationship between tumor aggressiveness and specific-type K-ras point mutations in non-small cell lung cancer. We developed procedures to examine the status of the K-ras gene by ASO-h and by single-strand conformation polymorphism assay of DNA obtained from formalin-fixed paraffin-embedded tumors. K-ras point mutations at codons 12 and 61 were assessed in 275 consecutively treated stage I-IV non-small cell lung cancers. Among patients with stage I disease, median survival time was 41.5 months in those whose tumors had no evidence of K-ras mutations and 27 months in those with K-ras 12 mutations; among patients with stage IIIA disease, median survival time was 7 months in those with K-ras codon 12 aspartic and serine mutations and 15 months for those with other K-ras mutations (P = 0.01). In a multivariate analysis, specific-type K-ras codon 12 point mutation remained a strong predictive factor (hazard ratio for death, 2.06; 95% confidence interval, 1.11-3.81; P = 0.02) after adjustment for other evaluated factors, including TNM stage and histology. Thus, we concluded that in patients with non-small cell lung cancer, specific K-ras 12 point mutations detected by DNA amplification and either ASO-h or single-strand conformation polymorphism methods predicted a significantly increased risk of recurrence and death, independently of stage and histology.

Adult↗
PubMed1995

Single-agent paclitaxel by 3-hour infusion in the treatment of non-small cell lung cancer: links between p53 and K-ras gene status and chemosensitivity.

Currently available cytotoxic drugs are only moderately active in non-small cell lung cancer (NSCLC) and prolong survival only slightly. In two published trials, single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was reported to have significant activity in NSCLC, with response rates of 21% and 24%. Treatment-limiting hypersensitivity reactions, however, were noted in a phase I trial of paclitaxel given as a 3-hour infusion at doses > or = 190 mg/m2. We report the results of a phase II trial of paclitaxel given by 3-hour intravenous infusion at 210 mg/m2 every 3 weeks in an outpatient setting. The study was conducted simultaneously at three centers and included chemotherapy-naive patients with unresectable locoregional or metastatic NSCLC. The study objectives were to evaluate response rate, the potential link between p53 and K-ras gene mutations and increased paclitaxel resistance, and toxicity. Sixty-two patients were eligible for this study. All patients were premedicated with dexamethasone 20 mg given orally or intravenously 12 and 6 hours before paclitaxel infusion and cimetidine 300 mg and diphenhydramine 50 mg, both given 60 minutes prior to initiation of paclitaxel infusion. Of the 62 patients who were initially enrolled, 50 (44 men and six women) were evaluable for toxicity at interim analysis; 47 of these patients were evaluable for response. Twenty-four had squamous cell carcinoma, 20 had adenocarcinoma, and six had undifferentiated large cell carcinoma. The median age was 61 years (age range, 36 to 75 years). The median Zubrod performance status was 1 (range, 0 to 2). Seventeen (36%) patients achieved either partial or complete response. Among 24 patients with squamous cell carcinoma, eight (33%; 95% confidence interval, 15% to 61%) had a partial response. Seven (41%; 95% confidence interval, 18% to 64%) of 17 patients with adenocarcinoma had a partial or complete response. Tissue blocks were obtained for analysis of K-ras and p53 gene mutations by means of polymerase chain reaction followed by single-strand conformation polymorphism assay. Our findings indicate that mutations are associated with a poor clinical course and may be prognostic of paclitaxel resistance. Paclitaxel was well tolerated. None of the patients experienced allergic reactions. Granulocytopenia was generally mild. Therapy was interrupted in only two patients because of the development of grade 3 neuropathy. In our experience, paclitaxel is one of the most active cytotoxic drugs targeting NSCLC.

Adult↗
PubMed1994

Transcriptional activation of histone H1 zero during neuronal terminal differentiation.

We have examined the central nervous system (CNS) of developing and adult transgenic mice carrying sequences upstream of the histone H1 zero gene fused to the E. coli beta-galactosidase gene (lac Z). The transgene is induced in a subset of the neuronal population during postnatal development, coinciding with neuronal terminal differentiation. At postnatal day 9, the earliest time at which the transgene product can be detected, positive neurons are observed in the granular layer of the cerebellar cortex and in the pyramidal fields of the hippocampus. The transgene is then induced in other areas of the CNS, such as the neocortex, thalamus, hypothalamus, olfactory bulb, globus pallidus superior and inferior colliculus, substantia nigra, pontine nuclei and brain stem. Induction is unrelated with determination and quiescence, which are essentially prenatal. The overlapping of the temporal and regional patterns of transgene activity with those of the endogenous protein shows that the accumulation of H1 zero in differentiating neurons is at least in part under transcriptional control. In the light of these results, the H1 zero gene appears as the only mammalian histone gene that specifically responds to terminal differentiation. However, not all terminally differentiated neurons express H1 zero at detectable levels. For instance, Purkinje cells are negative. In neurons, terminal differentiation appears thus as a necessary, but not a sufficient condition for increased H1 zero expression.

Animals↗
PubMed1992

Effect of ascitic liquid on growth in vitro of embryoid bodies derived from teratocarcinoma.

Embryoid bodies (EB) derived from teratocarcinoma (TC) OTT6050 were cultured with ascitic liquids (AL) from animals carrying 16-, 22- and 35-day evolved EB. At the same time the presence of fibronectin (FN) in AL were analyzed by immunoblotting. Results indicate the probable existence of growth-stimulatory factors for EB, as well as the presence of FN in the 22-day AL.

Animals↗
PubMedDate not supplied

Alpha-fetoprotein in tumours derived from cystic and simple embryoid bodies.

Cellular aggregates called embryoid bodies (EB) have been obtained from the experimental teratocarcinoma (TC) 0TT6050. Two morphological types of EB can be differentiated, which are injected subcutaneously into isogenic 129/Sv mice. The tumors are collected 20 and 30 days after EB injection and processed histologically, and immunohistochemically with anti-alpha-fetoprotein (alpha-FP) antibodies. Our results indicate that the histological pattern of the tumors is related to the degree of morphological organization of the EB used.

Animals↗