Search PubMed⌕ Search

Biomedical subjects

D Moro

Publications and source records attributed to D Moro.

At least 55 records · Page 3Linked to original sources
PubMed1996

Apoptosis-related factors p53, Bcl2, and Bax in neuroendocrine lung tumors.

Neuroendocrine (NE) lung tumors comprise four classes of progressive aggressiveness for which proliferation and apoptosis rates could both contribute to their distinctive behavior. As p53 mutations may favor escape from apoptosis through changes in Bcl2-Bax expression balance, which are survival and apoptotic genes, respectively, we studied 121 NE lung tumors (16 typical carcinoids (TC), 5 atypical carcinoids (AC), 29 large-cell NE carcinomas (LCNECs), and 71 small-cell lung carcinomas (SCLCs) using immunohistochemistry. We quantified apoptosis by terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) in 31 of these cases. There was a significant increase of p53 mutant immunophenotype (defined as immunoreactivity with at least two antibodies for at least 20% of tumor cells) between atypical/typical carcinoids group and the LCNEC/SCLC group (P = 0.0003). There was an inverse correlation (P < 0.0001) between the scores of Bax and Bcl2 expression in individual tumors and a significant inversion of the Bcl2. Bax ratio between low-grade (typical and atypical carcinoids) and high-grade (LCNECs and SCLCs) tumors with a predominant Bax expression in the first group and predominant Bcl2 expression in the second. Whereas carcinoids had variable apoptotic indexes, LCNECs had high indexes (1.3 to 6.8%), Bcl2 overexpression, Bax down-regulation, and Bcl2.Bax ratio > 1 correlated with lower apoptotic index in both LCNEC and the pool of LCNECs and SCLCs (P < 0.05) and a lower survival rate in the group of atypical and typical carcinoids and LCNECs (P < 0.002). The highest levels of Bcl2 expression and Bcl2.Bax ratios were associated with p53 mutant immunophenotype (P = 0.02). Our results suggest that aggressiveness in NE lung tumors could be linked, in addition to proliferation, to apoptosis-related factors.

Apoptosis↗
PubMed1996

[Effect of sex on the increase of GH induced by galanin, alone or in combination with GHRH with or without pyridostigmine in pubescent subjects].

Growth hormone response to galanin (GAL) and growth hormone releasing hormone have been demonstrated to be higher in females than in males, and moreover the cholinergic system appears to be able to enhance them. On the basis of this presumption, we evaluated the GH response (expressed as area under the curve: AUC-GH) to galanin (GAL, 10 mg/kg i.v.) or GHRH (1 mg/kg i.v.) either alone or associated together and with pyridostigmine (PD, 60 mg p.o.), and to saline infusion as a control, in 5 males and 5 females, in puberty, aged 16 +/- 0.4 years old (mean +/- SD). In females tests were performed during the follicular phase of the menstrual cycle. GAL alone cannot provoke a response from GH unless associated with GHRH. The contemporary administration of PD does not increase the extent of the response. The latter did not differ between sexes. The GHRH-GAL association induced a higher response in GH compared to GAL alone and GAL-PD, without any differences between the sexes. Lastly, the combination GHRH-GAL-PD induced responses that were comparable to GHRH and GAL alone. Therefore GAL does not act alone but enhances the effect of GHRH and the cholinergic system appears to be involved as a modulator. Moreover, the effect of GAL is comparable in both sexes.

Acetylcholine↗
PubMed1995

Thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone in juvenile obesity before and after hypocaloric diet.

This study was performed on 36 obese subjects aged 8.5-17.4 yr, 14 boys and 22 girls (prepubertal: 5 boys and 5 girls [stage I, according to Tanner]; BMI: 35.5 +/- 1.4 [mean +/- SEM] and 35 +/- 1.3 respectively; pubertal: 9 boys and 17 girls [stage IV-V]; BMI: 36.2 +/- 1.8 and 36 +/- 1.5 respectively) before and after 8 weeks of a 1000 kCal/day diet. The responses of serum TSH and PRL to TRH (200 micrograms iv as a bolus) were evaluated as Area Under the Curve (AUC) and net increase in respect to basal values (delta TSH and delta PRL). Serum T4, fT4 and rT3 were assayed at the baseline and T3 and fT3 at the baseline and 120' after TRH injection. A similar analysis was performed on 14 age- and sex-matched lean subjects as controls. In females at baseline fT4 serum levels were greater than controls and were significantly reduced after weight loss; rT3 increased after weight loss in the whole study group. In patients of both sexes the PRL peak after TRH injection was earlier but not greater (15') than in controls (30'). After weight loss PRL peak after TRH was found at 30' (as controls) in females only. Taking into consideration the stage of pubertal development, the results were the following: a) in puberal girls, after weight loss, TSH and PRL peaks after TRH were delayed with respect to baseline and to the other considered subgroups; b) in prepubertal girls TSH and PRL peaks, delta TSH, delta PRL, AUC-TSH and AUC-PRL were blunted with respect to pubertal ones; c) the other considered variables were unchanged after the period of caloric deprivation. No correlation between BMI and the AUC of TSH and PRL was found. These data suggest that thyroid function is substantially normal in adolescent obese subjects and not influenced by a prolonged period of caloric restriction, even though a reduced hypothalamic dopaminergic tone on pituitary thyreotrophs and lactotrophs could cause subtle alterations on TSH and PRL release, partially influenced by gender and sexual development.

Adolescent↗
PubMed1995

CEA, CYFRA21-1 and SCC in non-small cell lung cancer.

CEA, SCC and CYFRA 21-1 were measured in samples of serum coming from 105 'Non small cell lung cancer' (NSCLC) patients. The present study has been carried out to compare these markers, to analyse their prognostic significance and to determine the best combination of tumor markers. The median value and interquartile range were: CYFRA 21-1: 2,3 ng/ml, CEA: 3,7 ng/ml, SCC: 1,2 ng/ml. CEA demonstrated higher values in adenocarcinomas (P = 0.04). SCC and CYFRA 21-1 were comparable in the different histologic groups. CYFRA 21-1 and CEA values were dependant on tumor stage. Advanced tumors (T3 and T4) demonstrated higher serum CYFRA 21-1 level (P = 0.0006). CYFRA 21-1 was higher than 3,3 ng/ml in 36% of patients. CEA was higher than 5 ng/ml in 38% of patients and SCC was higher than 2 ng/ml in 27% of patients. Patients with a high CEA and CYFRA21-1 serum level had a shorter survival than those with a normal serum level. In a Cox regression analysis four variables (TNM stage, age, CYFRA 21-1 and CEA level) were found to be significant in the prediction of survival; CYFRA 21-1 level had the lowest P value (P = 0.0002). The current study suggests the use of a combination of CEA and CYFRA 21-1 in the clinical care of NSCLC.

Adult↗
PubMed1995

Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for stage IIIA and stage IIIB non-small cell lung cancer: results of a phase I-II study by the GOTHA group. Group d'Oncologie Thoracique des Régions Alpines.

The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. 65 patients received 3 cycles of cisplatin 60 mg/m2 and mitomycin C 8 mg/m2 on day 1, and vindesin 3 mg/m2 on days 1 and 8 in weeks 1-2, 5-6 and 9-10, alternating with AHRT, 2 daily 1.5 Gy fractions, 5 days/week, in weeks 2-3 (30 Gy) and weeks 6-7 (33 Gy). The dose actually delivered was > 98% for RT, and 85-100% for CT. Mean duration before last CT cycle was 9.5 weeks. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. 1 patient died of bronchial haemorrhage at the end of RT. 1 of 5 patients, who underwent secondary pulmonary resections, died of acute respiratory distress syndrome. Evaluation of tumour response was hampered by lung condensations in radiation fields. Some long-term survivors had an initial tumour response assessed as partial response or no change. First failures were more frequent outside (34) than within (21) radiation fields. The median survival was 15.7 months and the 5 year survival rate was 15% (95% CI = 6-26%). 1 patient died of bladder cancer and another of myocardial infarction. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy.

Adult↗
PubMed1995

Gadolinium-based MR contrast media: potential for growth of microbial contaminants when single vials are used for multiple patients.

OBJECTIVE: To assess potential risk if single-dose vials of gadolinium-based contrast media are used for multiple patients. The use of multidose vials can pose a significant risk if contaminants are accidentally introduced into the vials and proliferate. Therefore, we tested the ability of gadolinium-based contrast to support the growth of a variety of microbial pathogens. MATERIALS AND METHODS: We collected the unused portions of 15 single-use vials of gadolinium-based contrast media. The residual contrast material was refrigerated after use and checked for sterility prior to inoculation with a selection of gram-positive and gram-negative bacteria and yeast. Contrast material was incubated at room temperature and at 4 degrees C, and quantitative cultures were performed at 0, 24, 48, and 72 hr and at 7 days. RESULTS: No microbial growth occurred from cultures of the used contrast solutions prior to inoculation. None of the organisms tested in our study proliferated in the contrast material. All test organisms persisted at least 48 hr after inoculation at both temperatures. At 7 days, Staphylococcus aureus, Streptococcus epidermidis, and Corynebacterium jeikeium were recovered in significant quantities. Colony counts of Serratia odorifera rapidly decreased at room temperature but persisted beyond 7 days at 4 degrees C. CONCLUSION: The risk of contaminating vials of contrast agents punctured aseptically is small. Our study demonstrates a lack of proliferation of organisms in the two gadolinium-based compounds tested, suggesting that these solutions could be used for more than one procedure.

Candida albicans↗
PubMed1995

Expression of c-ets-1, collagenase 1, and urokinase-type plasminogen activator genes in lung carcinomas.

The c-ets-1 transcription factor has been involved in the in vitro transactivation of matrix-degrading protease genes that might play an important role in tumor invasion. Using in situ hybridization, we analyzed serial frozen sections for c-ets-1, collagenase 1, and urokinase-type plasminogen activator gene expression in 54 lung carcinomas including 34 non-neuroendocrine carcinomas (18 squamous carcinomas, 10 adenocarcinomas, 3 large cell carcinomas, and 3 basaloids) and 20 neuroendocrine carcinomas (7 small cell lung carcinomas, 4 large cell neuroendocrine carcinomas, 4 well differentiated neuroendocrine carcinomas, and 5 carcinoids). c-ets-1 gene was expressed in stromal cells in 44/54 lung carcinomas including one metastasizing carcinoid. c-ets-1 transcripts were also detected in cancer cells more frequently in neuroendocrine than in non-neuroendocrine carcinomas (P = 0.0059) and in stages III and IV and metastasis more frequently than in stages I and II ( P = 0.0065). Collagenase 1 gene was expressed in 16/34 non-neuroendocrine tumors and in 1/20 neuroendocrine tumors, either in stromal (12/17) or in cancer cells (6/17). Urokinase-type plasminogen activator mRNAs were expressed in 45/54 lung carcinomas in stromal and/or cancer cells. In non-neuroendocrine tumors, c-ets-1 and collagenase 1 gene expressions in stromal cells were correlated. These results demonstrate that the transcription factor c-ets-1, collagenase 1, and urokinase-type plasminogen activator are involved in lung cancer invasion and suggest that c-ets-1 protein might transactivate collagenase 1 gene during tumor invasion.

Carcinoma↗
PubMed1995

[Basal cell (basaloid) carcinoma of the bronchi].

Basal cell carcinomas (BCC) have been described in various locations such as skin, anal canal, tongue, larynx and recently the lungs. These tumors seem to have a poor prognosis. A series of 115 surgically resected lung tumors, previously classified as poorly or undifferentiated carcinoma was retrospectively reviewed. From those 37 cases were reclassified as BCC and were compared in terms of clinical features and survival with 40 cases reclassified as poorly differentiated squamous cell carcinoma (PDSC) of the lung. There was no difference between the groups with respect to age, clinical presentation, pattern of relapse and cause of death. Median and overall survival were different between the 2 groups, especially for stage I and II patients: 5 years actuarial survival in BCC was 15% and in PDSC 47% p = 0.009). There was also a difference in survival when we studied the patients alive 4 weeks after surgery (p = 0.04). This subset of non small cell lung cancer (NSCLC) has a worse prognosis than other NSCLC.

Actuarial Analysis↗
PubMed1995

Birthweight and breast feeding of babies born during the war in one municipal area of Sarajevo.

OBJECTIVE: To monitor the birthweight of children and the breast feeding practices of their mothers in one municipal area of besieged Sarajevo (Dobrinja) during the war. DESIGN: A sample of babies born in Dobrinja in the period 1 April 1992 to 1 April 1994 were monitored. SETTING: Data were collected at the paediatric clinic, Dobrinja, Sarajevo. SUBJECTS: The sample included 70 of the babies born in Dobrinja during the survey period who attended the paediatric clinic. INTERVENTIONS: Babies were weighed and medically examined immediately after birth. Data on breast feeding practices of all children were gathered by interviewing the mothers. RESULTS: Ten out of 70 babies (14.3%) were low birth weight ( < 2500 grams). Half of the low birth weight babies had doubled their weight by three months of age. None of the low birth weight babies suffered from severe infections (only sporadic cases of enterocolitis) or psychomotor disorders in the first year of life. A total of 61 babies were breast fed until approximately one year of age, 17 children continued to breast feed after one year of age. CONCLUSIONS: Despite the adverse influence of the war on living conditions and the stress experienced by pregnant women and babies, levels of perinatal mortality and severe child morbidity were not uncommonly high in Dobrinja. A relatively high percentage of babies born during the war were of low birth weight but most achieved catch-up growth during the first year of life. The findings suggest that babies were adequately protected. This is probably due in part to the promotion of breast feeding and the distribution of supplementary food commodities to mothers and children initiated by the United Nations Children's Fund (UNICEF) and other humanitarian organisations.

Birth Weight↗
PubMed1994

Loss of heterozygosity at the RB locus correlates with loss of RB protein in primary malignant neuro-endocrine lung carcinomas.

RB protein expression and loss of heterozygosity (LOH) in the RB gene were studied in 77 primary lung carcinomas of all histological types. RB protein expression was studied by immunohistochemistry with 3 anti-RB antibodies, and was found altered in 23/29 (79%) neuro-endocrine (NE) carcinomas and in 18/48 (37%) non-NE carcinomas. RB gene allele status was studied with 3 probes detecting RFLP in RB locus. Fifty-five patients were informative, and loss of heterozygosity was detected in 29 (52%) of the corresponding tumors with 1 of the 3 probes used; 89% of the informative NE carcinomas, excluding carcinoids, and only 13% of the non-NE carcinomas exhibited LOH and loss of RB-protein expression. LOH at the RB locus was strongly correlated with the absence of RB protein in malignant NE carcinomas, and this association was strongly correlated with the neuro-endocrine phenotype. Inactivation of the RB protein in primary NE carcinomas, excluding carcinoids, therefore seems to imply in the majority of cases the mutation of one allele and loss of the remaining allele of the RB gene, leading to loss of RB-protein expression. In contrast, RB-protein expression was independent of allele status in non-NE carcinomas and carcinoids.

Gene Deletion↗
PubMed1994

p53 genetic abnormalities and myc activation in human lung carcinoma.

p53 mutations and myc gene amplification and expression were studied in 119 lung carcinomas of all histological types. A mutant p53 immunophenotype was previously found in 47% of these tumors by immunohistochemical analysis. Seven cases exhibited p53 genomic rearrangements on Southern blots. Elevated levels of p53 transcript were found in 12 carcinomas (10%) and decreased levels in 27 carcinomas (23%) on Northern blots. In most of the cases, low levels of transcript were associated with negative immunostaining, whereas elevated levels of mRNA were related to positive immunostaining (mutant immunophenotype). p53 RT/PCR analysis in 10 tumors with absence of transcript on Northern blots revealed only weak or absent expression of normal and/or altered size transcripts. These abnormal transcripts showed deletions, insertions or splicing abnormalities. Taken together, p53 abnormalities were found in 66% of lung carcinomas [52% of neuroendocrine (NE) carcinomas and 75% of NSCLC]. c-myc was found to be activated in 24% (10/42) of these NE and in 48% (33/69) of these NSCLC carcinomas using Southern- and Northern-blot techniques. In addition, L- and N-myc genes were also activated in 26% (10/42) of NE carcinomas. No correlation was found between p53 mutations and myc activation in SCLC or in NSCLC, but their association was significantly more frequent in NSCLC than in SCLC. These results indicate that the p53-positive immunophenotype uncovers the occurrence of p53 point mutations in lung cancer and that p53 and c-myc gene alterations are important but represent independent occurrences in the development of lung tumors.

Base Sequence↗
PubMed1994

Basaloid bronchial carcinoma. A histologic group with a poor prognosis.

BACKGROUND: Basal cell carcinomas (BCCs) have been described in various locations, such as skin, anal canal, tongue, larynx, and recently, the lungs. These tumors seem to have a poor prognosis. METHODS: A series of 115 surgically resected lung tumors, previously classified as poorly or undifferentiated carcinoma, were reviewed retrospectively. From these, 37 cases were reclassified as BCCs and were compared in terms of clinical features and survival, with 40 cases reclassified as poorly differentiated squamous cell (PDSC) carcinoma of the lung. RESULTS: There was no difference between the groups regarding age, clinical presentation, pattern of relapse, and cause of death. Median and overall survival were different between the two groups, especially for Stage I and II patients: 5-year actuarial survival in the BCC group was 15% and in the PDSC group 47% (P = 0.004). CONCLUSIONS: This subset of non-small cell lung cancer (NSCLC) has a worse prognosis than other NSCLC, and this should be considered in survival studies and new treatment trials.

Adult↗
PubMed1994

Immunoscintigraphy using 111in-labelled F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody for staging of non-small cell lung carcinoma.

28 patients with primitive lung cancers were imaged by immunoscintigraphy (IS) with 111indium-labelled F(ab')2 anti-carcinoembryonic antigen (CEA), to assess this technique for mediastinal staging. IS revealed primitive tumours in 21 cases in whom mediastinal extension was assessed. There was concordance between clinical staging and IS confirmed by surgery in 17 cases, and discordance in 4. After surgery, discordance was in favour of IS in 2 cases (1 true positive and 1 true negative) and in favour of clinical staging in 2 (false positive of immunoscintigraphy). Anti-CEA IS could be useful for improving mediastinal staging of lung cancer.

Antibodies, Monoclonal↗
PubMed1994

Vinorelbine versus vinorelbine plus cisplatin in advanced non-small cell lung cancer: a randomized trial.

PURPOSE: The purpose of the study was to assess the possible benefit of the combination vinorelbine (NVB)-cisplatin (DDP) in comparison with NVB alone in advanced non-small cell lung cancer (NSCLC), not treated previously. It also involved confirmation of the efficacy of vinorelbine as monotherapy. PATIENTS AND METHODS: In this phase III trial, 231 eligible patients were stratified by centre and randomized to receive either NVB alone, 30 mg/m2/week or the combination of NVB 30 mg/m2/week and DDP 80 mg/m2/3 weeks. Patients were to be treated for a minimum of 6 weeks, with the first response assessment performed 9 weeks after the beginning of treatment. RESULTS: The two groups differed in terms of objective response rates (16% and 43%, respectively, p = 0.0001) and median time to progression (10 weeks and 20 weeks, p = 0.0001). However, the difference was not significant for median survival time (32 weeks, 33 weeks, p = 0.48). The addition of DDP resulted in an increase in toxicity, in particular renal, hematologic, neurologic and emetic. This toxicity led to treatment discontinuation in 8% and 21% of patients, respectively. Respectively 3% and 13% of patients stopped treatment early during objective response (toxicity or refusal). CONCLUSIONS: The NVB-DDP combination increased objective response rates and time to progression in comparison with NVB alone, but did not influence the survival of patients. The activity of NVB in the treatment of advanced NSCLC was confirmed.

Antineoplastic Agents↗
PubMed1994

[Respective roles of the products of the mdr1 and p53 genes in drug resistance of bronchial cancers].

Expression of mdr1 and p53 was assessed on 119 cases of bronchial carcinomas, and compared with clinical chemoresistance. mdr1 expression was evaluated by immunohistochemistry (IHC), using the monoclonal antibody JSB1. The study of p53 expression was performed by both IHC, using six different antibodies, and Northern blotting. We observed a correlation between the expression of mdr1 and the presence of a mutation of p53 in neuro endocrine (NE) carcinomas (P = 0.02). Correlation was not observed when non NE carcinomas were evaluated, nor was found any correlation between mdr1 expression and clinical chemoresistance in patients with small cell lung carcinoma (SCLC). The frequency of complete response however was significantly higher in patients whose tumor did no express mdr1 (P = 0.02). Chemoresistance correlated well with the phenotype of p53 mutant in SCC (P = 0.015). We conclude that p53 mutation is a better predictive factor of clinical chemoresistance in SCLC than mdr1 IHC detection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

[Chemotherapy of small-cell lung cancer by a combination of teniposide, ifosfamide and carboplatin].

Thirty six SLC patients have been treated with a combination therapy of ifosfamide 2 g/m2, D1 and D2, carboplatin 300 mg/m2 D1 and teniposide 100 mg/m2 D1 to D3. All patients were younger than 70 years, 31 males, five females, ten limited diseases, 26 extended diseases (without brain metastasis) Performance status 0, 1 or 2, mean weight loss 3.7 kg. Thirty six patients were evaluable for response. We have noted three complete response and 28 partial response (objective response rate 86%). The main toxicity of this combination therapy was myelo-suppression (86% of grade 3 and 4). Twenty seven patients have relapsed, the median relapse free survival time is 310 days. The median survival of the 36 patients is 340 days, one patient is alive more than 30 months after the diagnosis. The ifosfamide-carboplatin-teniposide combination is an effective treatment in small cell lung cancer, its toxicity remains tolerable.

Adult↗