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Biomedical subjects

M Monzo

Publications and source records attributed to M Monzo.

14 recordsLinked to original sources
PubMed2001

Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers.

The etiology of lung tumors arising in nonsmokers remains unclear. Although mutations in the K-ras and p53 genes have been reported to be significantly higher in smoking-related lung carcinomas, in the present study we performed a more comprehensive analysis in search of additional genetic changes between lung adenocarcinoma from tobacco- and non-tobacco-exposed patients. We selected a matched cohort of 18 lifetime nonsmoking and 27 smoking patients diagnosed with primary adenocarcinoma of the lung and searched for chromosomal alterations in each tumor by testing normal and tumor tissue with 54 highly polymorphic microsatellite markers located on 28 different chromosomal arms. Allelic losses or gains at chromosomal arms 3p (37 versus 6%), 6q (46 versus 12%), 9p (65 versus 22%), 16p (28 versus 0%), 17p (45 versus 11%), and 19p (58 versus 16%) were present significantly more often in adenocarcinomas from smokers than from nonsmokers. Chromosomal arms showing allelic imbalance in lung tumors from nonsmokers were rare but occurred more often at 19q (22%), 12p (22%), and 9p (22%). The FAL (fractional allelic loss or gain) is defined as the percentage of chromosomal arm losses/gains among the total informative chromosomal arms. Tumors from smokers harbored higher levels of FAL (13 (48%) of 27 showed FAL > or = 0.3) compared with the lung tumors from the nonsmoker patients (2 (11%) of 18 showed FAL > or = 0.3; P = 0.02; odds ratio, 0.13; 95% confidence interval, 0.01-0.79). Our data demonstrate that widespread chromosomal abnormalities are frequent in lung adenocarcinoma from smokers, whereas these abnormalities are infrequent in such tumors arising in nonsmokers. These observations support the notion that lung cancers in nonsmokers arise through genetic alterations distinct from the common events observed in tumors from smokers.

Adenocarcinoma↗
PubMed2001

Types and localisation of p53 gene mutations: a report on 332 non-small cell lung cancer patients.

Mutations of p53 suppressor gene are among the most common molecular abnormalities in human malignancies. We demonstrated earlier significant differences in mutational profiles between NSCLC patients from Poland and Spain. These differences were most probably related to ethnic and/or geographical factors. In the present study we analyzed the types and location of p53 gene mutations in a large group of 332 operated NSCLC patients from two institutions in Northern Poland. Within the last decades this region has been characterized by the highest incidence of lung cancer in Poland. We used both frozen and paraffin-embedded tumor samples and the screened region included exons from 5 to 8. A total of 96 samples (29%) were positive for p53 gene mutation. The proportion of mutations in particular exons was as follows: exon 5-33%, exon 6-22%, exon 7-16%, and exon 8-29%. Three 'hot spots' were located in codons 176,245 and 248. Evolutionary conserved domains were much more frequently affected than the regions outside domains. The majority of mutations (73%) were missense type, followed by null and silent mutations (21 and 6%, respectively). In all six silent mutations substituted was the third base in codon. There were no major differences in the types and locations of mutations between patients from the two institutions. This homogeneity, together with our earlier findings, may confirm the impact of ethnic and geographical factors on the mutational profile of p53 gene in NSCLC.

Aged↗
PubMed2001

Drug resistance in non-small cell lung cancer.

There is an underlying feeling in the oncology community that chemotherapy has reached a therapeutic glass ceiling in non-small cell lung cancer (NSCLC) and that we will never attain the acceptable survival rates that are just beyond our reach. Multiple clinical trials have tested doublets, triplets and sequential chemotherapy in what is often regarded as a futile attempt to break through this ceiling. Recent large randomized trials have not demonstrated that any of these combinations is superior to any of the others. Nevertheless, the analysis of DNA or RNA from patients can permit us to assess genes that may be specific targets of certain cytotoxic agents and others that may be markers of multidrug resistance. With this in mind, the Spanish Lung Cancer Group has designed a trial to test the involvement of various genes in resistance to gemcitabine and cisplatin.

Adult↗
PubMed2001

The role of chemotherapy in early non-small-cell lung cancer management.

Great advances have been made in chemotherapy in advanced and metastatic non-small-cell lung cancer (NSCLC), and a major milestone was reached with the administration of neoadjuvant chemotherapy in stage IIIA N2 disease. The systemic nature of lung cancer has been confirmed by many genetic analyses documenting micrometastases in negative lymph nodes and bone marrow, and mRNA gene overexpression as a surrogate of cancer cells has been identified in peripheral blood. Furthermore, serum or plasma cell-free tumor DNA has been observed even in tumors with a diameter of less than 2 cm. Pharmacogenetic screening can lead to tailored chemotherapy even in patients with early disease through the use of a genetic tool kit that will allow us to optimize the use of chemotherapy by using serial measurements of serum DNA that can help to detect residual disease and re-assess the chemosensitivity of sub-clinical micrometastatic disease. The ongoing (neo)adjuvant taxol/carboplatin hope (NATCH) trial is testing the value of three cycles of chemotherapy given pre- or post-operatively compared with surgery alone and will analyze genetic abnormalities in serum DNA at three different points during patient follow-up. Our major concern in this review is to analyze the pros and cons of chemotherapy in NSCLC. Although this review is not a formal meta-analysis, we have discussed the most relevant published studies in this field. We conclude that not only is there no evidence of detrimental effects of chemotherapy, in fact, there are many indications that chemotherapy induces response in up to 80% of patients and downgrades N2 disease in up to 50% of patients. This translates into significantly better survival when accompanied by complete resection. Since at least 50% of patients with stage IB disease develop distant metastases, it seems logical to explore the role of chemotherapy in early disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Evaluation of the prognostic significance of P53 mutation in patients with non-small cell lung cancer].

Prognostic value of p53 gene mutation was determined in 95 radically operated non small cell lung cancer patients (78 males and 17 females, mean age 57.8 years). Study group included 62 cases of squamous cell carcinoma, 30--adenocarcinoma and 3--large cell carcinoma. There were 52 patients in stage I disease, 16--in stage II, 26--in stage IIIa and one--in stage IIIb. Paraffin-embedded samples of resected tumors were assayed for p53 mutations with the use of PCR/SSCP analysis. p53 mutation were present in 22 cases (23%). The median survival in patients with and without p53 mutations were 49 and 75 months (p = 0.46), respectively, and the five-year survival rate 53% and 50%, respectively. In stage I disease the median survival for patients with p53 mutation was 53 months and for those without mutations the median survival could not be determined as more then a half of them were alive. Median survival in stage II patients with and without mutations was 35 months and 44 months (p = 0.62), and in stage IIIA--9.5 months and 17 months, respectively (p = 0.37). The results of this study indicate that p53 gene mutation is not correlated with prognosis in non-small cell lung cancer patients.

Adult↗
PubMed1995

K-ras genotypes and prognosis in non-small-cell lung cancer.

BACKGROUND: Despite major advances in the treatment of many kinds of cancer over the past 25 years, the overall 5-year survival of non-small-cell lung cancer patients has scarcely improved. Even in stage I which has the best outcome long-term survival still falls below 70%. Since intriguing data suggest that the identification of genetic markers might allow prognosis to be assessed case by case. We were prompted to evaluate K-ras gene mutations as a putative prognostic marker in this neoplasm. MATERIALS AND METHODS: We used the polymerase chain reaction (PCR) followed by allele specific oligonucleotide (ASO) hybridization or single-strand conformation polymorphism (SSCP) assays, to detect K-ras mutations in DNA from formalin-fixed, paraffin-embedded tumor samples. K-ras mutations were examined in 192 stage I to IV non-small-cell lung cancer patients. RESULTS: K-ras mutations were detected in 51 of 192 of the cases studied (27%). All K-ras mutations detected by PCR/ASO hybridization were also identified by SSCP. In stage I disease, the median survival was 46 months in those patients whose tumors had no K-ras mutations and 21 months in those with aspartic acid and serine mutations at K-ras codon 12; in patients with stage IIIA disease, median survival time was 16 months in the K-ras negative group and 7 months in the aspartic acid and serine mutation group. No significant differences were observed for the remaining amino acid substitutions of K-ras, nor were they observed at all in more advanced disease. CONCLUSIONS: K-ras gene status has strong prognostic value in patients with stage IIIA non-small-cell lung cancer. The survival curve for patients with stage I and K-ras codon 12 aspartic or serine mutations is close to that of patients with stage IIIA without K-ras mutations. However, a non-small-cell lung cancer K-ras genotypic classification should be validated in larger studies.

Aged↗
PubMed1994

Growth control of embryonic stem cells injected into mouse uterus on fifth day of pregnancy.

Previous studies have shown that embryonic stem cells (ES) may participate in normal embryonic development when they are injected into the blastocyst. In contrast, ES cells develop into tumors if injected in ectopic sites in adult mice. In this study we injected ES-D3 cells, with the LacZ gene incorporated, into 5-day pregnant mouse uteri, into pregnant unilaterally salpingectomized uteri, into pseudopregnant uteri and into non-pregnant uteri. X-gal staining enabled us to identify injected ES cells on the 7th, 9th, 10th, 12th and 15th days post-injection. In pregnant decidua, the ES cells were located initially in the mesometrial decidua and later distributed in the basal and capsular decidua and in the endodermic layer of the visceral yolk sac. In pregnant, unilaterally salpingectomized mouse uteri, ES cells were mainly located in the uterine lumen and tumors were not observed in either case. In contrast, ES cells injected into pseudopregnant uteri often developed into tumors and those injected into non-pregnant uteri always developed into teratocarcinomas. We conclude that the pregnant-uterine microenvironment may participate in the control of ES cell growth.

Animals↗
PubMed1994

K-ras gene point mutation: a stable tumor marker in non-small cell lung carcinoma.

K-ras gene point mutation is a highly frequent event in human malignancy. About one third of non-small cell lung cancer (NSCLC) patients harbor K-ras gene point mutational activations. This study investigates the prevalence of K-ras mutation in autopsy tumors with NSCLC, and the correlation of K-ras gene point mutations between primary tumors and metastases in NSCLC. Formalin-fixed, paraffin-embedded tissue sections of 15 primary lung tumors and their metastases, (obtained from autopsy), were examined for the presence of point mutations in K-ras gene codon 12, 13 and 61 by oligodeoxynucleotide hybridization analysis of DNA fragments, amplified by polymerase chain reaction (PCR). K-ras gene point mutations were detected in five cases of lung carcinoma, of which four were adenocarcinomas and one was squamous cell carcinoma. In each of these cases, identical K-ras gene mutations were found in the DNA of both the primary tumor and its corresponding distant metastases. Activating K-ras base-substitutions correlate well between the primary tumor and its corresponding metastases in NSCLC. In the negative cases where no K-ras mutation was found in the primary tumors, no newly acquired K-ras mutation appeared in the metastases. Our study indicates that K-ras point mutation serves as a stable tumor marker in NSCLC.

Adenocarcinoma↗
PubMed1993

Specific expression in adult mice and post-implantation embryos of a transgene carrying the histone H1(0) regulatory region.

Histone H1(0), a variant of the H1 group, has been found associated with the repressed state of chromatin and its content is increased in terminally differentiated cells. We have cloned a mouse H1(0) histone gene and introduced the promoter region, ligated to the beta-galactosidase reporter gene, into transgenic mice. By histochemistry we demonstrated a strong expression of the transgene in adult kidney, testis and brain. Intestine, uterus and ovarium were also positive. This expression followed the same pattern as that of the endogenous H1(0) gene, as demonstrated by in situ hybridization with a non-coding fragment of the mRNA, by Northern analysis, and by immunofluorescence with specific antibodies. In post-implantation embryos, the expression was very low up to day ten p.c. At this time, most of the X-Gal staining was found in the brain, retina and some of the large blood vessels. Hence, expression of the transgene as well as of the endogenous H1(0) gene is not exclusively linked to a differentiated phenotype or to a reduced cell proliferation capacity.

Animals↗
PubMed1991

Laminin and fibronectin expression during in vivo growth of embryoid bodies derived from teratocarcinoma.

Embryoid bodies (EB) derived from teratocarcinoma OTT6050 are a useful model for the study of early embryogenesis and tumorigenesis and are found in two forms: cystic and simple. After injection of cystic EB intraperitoneally into isogenic 129/Sv mice, their growth and the expression of laminin (LAM) and fibronectin (FN) were studied at 5, 7 and 9 days post-injection. LAM was highly expressed on the internal face of endodermal and on some internal cells in cystic type EB and in both endodermal cell faces in simple EB. Only slight FN expression was observed in cystic and simple EB. Extracellular matrix proteins can be studied in this model.

Animals↗
PubMed1988

Flecainide acetate: critical care administration guidelines.

Flecainide may play an important role in the treatment of ventricular arrhythmias because of its convenient dosing regimen and high rate of efficacy in controlling ventricular ectopic activity. In stable patients with normal or mildly reduced left ventricular function, flecainide has proved to be promising. In those patients with severe left ventricular dysfunction, lethal arrhythmias, and preexisting conduction system disease, caution must be exercised.

Arrhythmias, Cardiac↗
PubMed1988

Cytodifferentiation of mouse visceral endoderm: study with a teratocarcinoma antiserum.

In this work we separated homogeneous embryoid bodies (EB); this population is composed of only endodermal vesicles of a visceral type. These EB were used to immunize rabbits. After absorption, the antisera were analyzed immunohistochemically in sections of 7.5- and 9-day-old mouse embryos, which showed a selective reaction to visceral endoderm. The cytodifferentiation of the visceral endoderm was studied.

Animals↗
PubMed1983

[Morphological study of a homogenous population of teratocarcinoma cells].

When an experimental teratocarcinoma was injected into the peritoneal cavity of isogenous 129/Sv mice, ascites developed and cell aggregates known as embryoid bodies were isolated from the ascitic fluid. Ficoll gradients have been used to seperate the embryoid bodies and their evolution in the peritoneal cavity has been followed by scanning electron microscopy.

Animals↗