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Biomedical subjects

F Buttitta

Publications and source records attributed to F Buttitta.

At least 19 recordsLinked to original sources
PubMed2006

Is transcutaneous oxygen and carbon dioxide monitoring indispensable in short- and long-term therapeutic management of non-reconstructable lower critical limb ischemia?

AIM: The aim of this study was to evaluate the capacity of transcutaneous partial pressure of O(2) (TCpO(2)) and CO(2) (TCpCO(2)) to predict clinical response to pharmacological treatment in short- and long-term follow-up of unreconstructable critical limb ischemia (CLI) treated with prostanoids; to suggest a diagnostic and therapeutic algorithm able to define the possibility of prostanoid therapy in unreconstructable CLI at high risk of limb loss. METHODS: Twenty-six consecutive patients with CLI (21 with distal trophic lesions, 31 symptomatic limbs) considered unreconstructable after peripheral angiography and with a history of type 2 diabetes mellitus underwent daily parenteral Iloprost treatment for 2-3 weeks. RESULTS: Transcutaneous gas-analytic monitoring (TGM) in non-reconstructable CLI treated with Iloprost divided patients into 2 groups: early responders (ER) with increased TcpO(2) and normalization of TcpCO2, and non responders (NR) with unchanged TcpO(2) and TcpCO(2) parameters. In the NR who underwent a second cycle of Iloprost within a few months of the first, TGM further divided the patients into another subgroup of late responders (LR) with TcpO(2) and TcpCO(2) similar to the ER group and a subgroup of NR, who, after pharmacological treatment failure, should undergo eventual surgical re-timing and/or spinal cord stimulation in a final attempt to save the limb. CONCLUSIONS: In the short-term follow-up of CLI, a marked reduction in supine/dependent TcpO(2) and a marked increase in supine TcpCO(2) at the symptomatic forefoot proved to be significant predictors of major amputation risk. In the long-term follow-up period, TGM showed that, in ER and in LR, the favourable effect of pharmacological therapy observed in the first 6 months will disappear over the next 6 months, suggesting an algorithm of 2- to 3-week cycles of prostanoid therapy repeated every year. In NR treated with surgical and/or alternative therapies who did not undergo major amputations, prolonged instrumental TGM will provide a constant evaluation of metabolic parameters, thus providing the possibility to save the limb with additional pharmacological therapy.

Aged↗
PubMed2001

mRNA markers of breast cancer nodal metastases: comparison between mammaglobin and carcinoembryonic antigen in 248 patients.

Histological detection of axillary lymph node metastases is still the most valuable prognostic parameter for breast cancer, but about 30% of node-negative patients relapse within five years, suggesting that current methods are inadequate for identifying metastatic disease. More sensitive, PCR-based methods for the detection of metastatic cells are now available, enabling the amplification of cancer cell-specific mRNA messages by the RT-PCR assay. An ideal tumour marker, consistently expressed in tumour samples and not at all in normal lymph nodes, remains to be identified. The present study first investigated the expression of seven mRNA markers, CEA, CK19, c-Met, mammaglobin, MUC-1, beta1-->GalNAc-T and p97, selected on the basis of their previously reported specificity for breast cancer cells. Eighteen lymph nodes were examined from patients without tumours. Only mammaglobin mRNA and CEA mRNA were not expressed in normal nodes. All of the other markers showed a band of expression in 17%-55% of cases, indicating that they are not breast cancer-specific. CEA mRNA and mammaglobin mRNA expression could be detected in 15/20 (75%) and 19/20 (95%) primary breast carcinomas, respectively. The expression of mammaglobin mRNA and CEA mRNA was then compared in axillary lymph nodes from 248 consecutive breast cancer patients, 89 with histologically documented lymph node metastasis and 159 without histological evidence of metastatic disease. Ninety-seven per cent of the patients with histologically involved nodes showed expression of mammaglobin mRNA, whereas CEA mRNA was expressed in 79% of these cases. In the group of patients with histologically negative lymph nodes, 46 (29%) and 32 (20%) were found to be positive for mammaglobin and CEA expression, respectively, indicating the presence of metastases not detected by routine histological examination of one lymph node section. These results show that both mammaglobin RT-PCR and CEA RT-PCR are useful tools for the detection of breast cancer metastases in axillary lymph nodes. The detection sensitivity of the mammaglobin RT-PCR is far superior to that of the CEA RT-PCR, allowing the diagnosis of occult metastases in nearly one-third of cases.

Axilla↗
PubMed2001

Reduced expression of INT-6/eIF3-p48 in human tumors.

The int-6 gene, originally identified as a common integration site for the mouse mammary tumor virus (MMTV) in mouse mammary tumors, encodes the p48 component of the eukaryotic translation initiation factor-3 (eIF3-p48). Int-6/eIF3-p48 is expressed in all adult tissues which have been tested and early in embryonic development. Int-6/eIF3-p48 has been highly conserved throughout evolution and the deduced amino acid sequence of the human gene product is identical to the mouse protein. Viral insertions at the Int-6/eIF3-p48 locus in mouse mammary tumors result in production of chimeric Int-6/eIF3-p48/MMTV products that may act as dominant negative oncoproteins. Int-6/eIF3-p48 has also been identified as a human protein that binds to the human T-cell leukemia virus type I Tax oncoprotein. The role of Int-6/eIF3-p48 in human carcinogenesis is unknown at the present time. In this study we have examined Int-6/eIF3-p48 gene status and expression in two of the most common forms of cancer in humans, breast and lung tumors. Sixty-two breast carcinomas and 78 non-small cell lung carcinomas (NSCLC) were investigated. LOH at the Int-6/eIF3-p48 locus was observed in 5 (21%) of 24 informative breast tumors and 10 (29%) of 34 informative lung tumors. A reduced expression of Int-6/eIF3-p48 was seen in 23 (37%) of breast cancer samples and 24 (31%) of NSCLC samples. An association between Int-6/eIF3-p48 expression and LOH at the Int-6/eIF3-p48 locus was observed. Int-6/eIF3-p48 expression was not related to commonly used pathological parameters in breast cancer patients, while in NSCLC patients int-6/eIF3-p48 expression was mainly seen in adenocarcinomas (P<0.0001). In conclusion, our data show for the first time a decreased expression of Int-6/eIF3-p48 in a consistent portion of human breast and lung carcinomas, frequently associated with LOH at the Int-6/eIF3-p48 locus. Additional studies on larger series of tumor specimens with long-term follow-up are needed to determine whether Int-6/eIF3-p48 expression may represent a new prognostic or predictive marker.

Biomarkers, Tumor↗
PubMed2000

Usefulness of carotid intima-media thickness measurement and peripheral B-mode ultrasound scan in the clinical screening of patients with coronary artery disease.

Previous observational studies have shown a relationship between carotid intima-media thickness (IMT) and coronary artery disease (CAD). In this study the authors evaluated the accuracy of the common carotid IMT measurement in predicting the presence and severity of CAD and the additional information offered by the detection of carotid, iliac, and lower limb plaques. One hundred and fifty consecutive patients were subjected to coronary angiography and carotid, iliac, and lower limb ultrasound scan. The mean value of six IMT measurements of the far wall of the common carotid artery was calculated in each patient. The mean IMT was significantly correlated to the number of stenosed coronary vessels (r = 0.43, p<0.001), although the positive and negative predictive value of mean IMT in identifying patients with CAD was low (81% and 46%, respectively). The combined information offered by IMT measurements and peripheral (carotid, iliac, and lower limb) plaque detection was then used to obtain the best multivariate regression model able to predict CAD status. The multivariate model showed a highly significant multiple correlation coefficient (r = 0.60, p<0.0001) and a sharp improvement in the negative predictive value (92%) with respect to the univariable model. B-mode ultrasound scan including common carotid IMT measurement and peripheral plaque detection may be of clinical value in the screening of patients with CAD.

Adult↗
PubMed1999

Assessment of the prognostic relevance of serum anti-p53 antibodies in epithelial ovarian cancer.

The objective of this study was to assess the prognostic relevance of preoperative serum anti-p53 antibodies in epithelial ovarian cancer. These autoantibodies were detected with a new generation enzyme-linked immunosorbent assay in blood samples preoperatively drawn from 86 patients with this malignancy. Serum anti-p53 antibodies were found in 3 (10.0%) of the 30 patients with stage I-II and 15 (26.8%) of the 56 patients with stage III-IV epithelial ovarian cancer (P = 0.09). We assessed in detail 44 patients with stage III-IV disease who underwent six cycles of first-line platinum-based chemotherapy. A pathological complete response at second-look was achieved by none of the 15 patients with serum anti-p53 antibodies compared to 24.1% of the 29 patients without autoantibodies (P = 0.09). However, the preoperative serum anti-p53 antibody status had no prognostic relevance for progression-free survival and survival. In conclusion, the assessment of preoperative serum anti-p53 antibodies seems to have a limited clinical value in the management of patients with advanced epithelial ovarian cancer.

Autoantibodies↗
PubMed1999

Lung tumours from non-smoking subjects: A p53-related genetic instability in a subset of cases.

Tumours developed in non-smoking patients represent about 10% of all lung neoplasms and show peculiar morphologic and genetic features. In a previous study, we found a constant association between p53 gene alterations and loss of heterozygosity (LOH) at the FHIT locus in a subset of non-smoking tumours (7 cases out of 35 analyzed), so we hypothesized that a genomic instability associated with p53 mutations could be the cause of FHIT LOH in these neoplasms. To test this hypothesis, in the same panel of tumours, we investigated the presence of LOH at 7 other microsatellite loci located on different chromosomes. Interestingly we found that all of the tumours with p53 alterations and LOH at the FHIT locus showed loss of heterozygosity at all of the informative tested loci. This association was statistically significant (p=0.0001). Our data indicate the presence of a generalized genomic instability in this subset of lung tumours. Since p53 alterations were mostly G:C --> A:T transitions and frameshift deletions, we are tempted to hypothesize that the genomic instability observed in non-smoking patients could be caused by particular p53 alterations. In fact, other kind of p53 mutations (G:C --> T:A transversions), frequently found in a series of 35 tumours of smokers used as control, were not associated with LOH at microsatellites loci. However, we cannot exclude that p53 alterations are a consequence and not the cause of the genomic instability. In this case, we have to admit that a gene(s), upstream of p53, is implicated in genome destabilisation in a subset of lung adenocarcinomas developed in non-smoking patients.

Female↗
PubMed1999

Telomerase activity as a prognostic indicator in stage I non-small cell lung cancer.

Patients with stage I non-small cell lung cancer (NSCLC) are typically treated with surgical resection alone. However, about one-third of such patients develop disease recurrence and die within 5 years after complete resection. The ability to predict recurrence could represent an important contribution to treatment planning. This study evaluates the presence of telomerase activity in tumor cells as a predictor of disease recurrence and cancer-related death after operation for stage I NSCLC patients. The activity of the telomerase enzyme was investigated by telomeric repeat amplification protocol (TRAP) in tumors and matching normal lung tissue samples obtained from 107 consecutive operable patients with pathological stage I NSCLC. Telomerase activity was detected in 66 (62%) of the 107 tumors examined and in none of the corresponding adjacent noncancerous lung tissue samples. Correlation with pathological parameters showed that telomerase activity was associated with histopathological grade (P = 0.0135) but not with tumor size or histological type. Univariate survival curves, estimated using the method of Kaplan and Meier, defined a significant association between telomerase activity and both disease-free survival (P = 0.0115) and overall survival (P = 0.0129). In multivariate analyses, performed by Cox's proportional hazards regression models, the presence of telomerase activity was the only strong predictor of disease-free survival (P = 0.0173) and overall survival (P = 0.0187). Our data indicate that telomerase activity can be an important prognostic factor that should be considered in future prospective trials of adjuvant therapy for high-risk stage I NSCLC patients.

Adenocarcinoma↗
PubMed1998

Microsatellite alterations and p53, TGFbetaRII, IGFIIR and BAX mutations in sporadic non-small-cell lung cancer.

Fifty-two sporadic primary non-small-cell lung carcinomas (NSCLC) were examined for microsatellite instability. Six different microsatellite markers localized on chromosomes 2, 5, 8, 10, 11 and 17 were used. Genomic instability was observed in 35% (18/52) of NSCLC at single or multiple loci. The tumors were also analyzed for p53-gene mutations by PCR-SSCP analysis. Polynucleotide stretch frameshift mutations of TGFbetaRII (transforming-growth-factor-beta receptor II), IGFIIR (insuline growth-factor II receptor) and BAX genes were also analyzed. RER+ (replication-error-positive) tumors appear not to be affected by a higher rate of point mutations in coding sequences: no correlation was found between microsatellite instability and point mutations in the p53 gene, and the RER+ tumors showed no alterations in stretches of nucleotide inside TGFbetaRII, BAX or IGFIIR.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Cyclin D1 and retinoblastoma susceptibility gene alterations in non-small cell lung cancer.

Among the major regulators of the G1 restriction point are cyclin D1 and the retinoblastoma gene product (RB). In non-small cell lung cancer (NSCLC), the cyclin D1 gene is amplified/over-expressed in almost 50% of cases, and RB is inactivated in 6-32% of cases. It is of interest to evaluate concurrently the alterations of both genes on the same series of NSCLCs, to investigate whether cyclin D1 and RB alterations are alternative pathways leading to inactivation of the G1 restriction point or if they can occur in the same tumor, possibly exerting an additive effect on cancer progression. We investigated a series of 57 NSCLCs, analyzing cyclin D1 and RB at the gene and protein levels by Southern blot, Northern blot and immunohistochemistry. The cyclin D1 gene was amplified in 18 cases, cyclin D1 immunoreactivity was seen in 25 tumors. Amplification and expression were significantly associated. RB immunohistochemical expression was absent in 9 of 42 informative cases. RB mRNA expression was low to absent in 9 of 45 informative cases, cyclin D1 amplification was associated with normal RB mRNA, and cyclin D1 over-expression was associated with normal RB immunoreactivity, supporting the hypothesis that alterations of cyclin D1 and RB are alternative mechanisms by which tumor cells may escape the G1 restriction point. A concurrent alteration of RB and cyclin D1 was seen in a small subset of NSCLCs. Abnormalities of cyclin D1 and/or RB at the gene and/or expression level were present in more than 90% of cases, stressing that cyclin D1 and/or RB alterations represent an important step in lung tumorigenesis.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

FHIT and p53 gene abnormalities in bronchioloalveolar carcinomas. Correlations with clinicopathological data and K-ras mutations.

Bronchioloalveolar carcinoma (BAC) is a particular type of adenocarcinoma of the lung which accounts for up to 9 per cent of pulmonary malignancies. The aetiology and pathogenesis of this unique neoplastic disease are still unclear. Three histological subtypes of BAC have been recognized: mucinous, non-mucinous, and sclerosing. Of these, mucinous and sclerosing BAC have a worse prognosis than non-mucinous tumours. The different morphological patterns and clinical outcomes of the subtypes of BAC suggest differences in their biological behaviour. Previous reports have shown that the mucinous form of BAC is characterized by constant mutations at codon 12 of the K-ras gene, whereas the other two histotypes show a frequency of K-ras mutations which is not different from that observed in conventional lung adenocarcinomas. The present study of a series of 51 BACs, previously investigated for K-ras gene mutations, has evaluated the status of two other genes, p53 and FHIT, known to be frequently altered in non-small cell lung cancer. Loss of heterozygosity at microsatellite-containing loci located within the FHIT gene was observed in 22 (43 per cent) BACs. The distribution of FHIT gene abnormalities was not statistically different in the three histological subtypes. p53 mutations were present in 13 (32 per cent) non-mucinous/sclerosing BACs, while no mutations were seen in mucinous tumours (P = 0.039). Correlations with clinicopathological parameters showed that p53 mutations in BACs are associated with more aggressive tumours. No correlations were observed between FHIT or K-ras gene abnormalities and clinicopathological data. In conclusion, these results indicate that FHIT alterations are frequently involved in BAC tumourigenesis and that genetic changes in the p53 and K-ras genes can distinguish between different histotypes of BAC.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1998

Evaluation of FHIT gene alterations in ovarian cancer.

The FHIT gene, recently cloned and mapped on chromosome 3p14.2, has frequently been found to be abnormal in several established cancer cell lines and primary tumours. As alterations of chromosome 3p are common events in ovarian cancers with breakpoint sites at 3p14.2, we decided to investigate the role of FHIT in human ovarian tumorigenesis. Fifty-four primary ovarian carcinomas were studied by reverse transcription of FHIT mRNA followed by polymerase chain reaction (PCR) amplification and sequencing of products. The same tumours and matched normal tissues were also investigated for loss of heterozygosity using three microsatellite markers located inside the gene. We found an abnormal transcript of the FHIT gene in two cases (4%) and allelic losses in eight cases (15%). Twelve (22%) of the 54 tumours investigated belonged to young patients with a family history of breast/ovarian cancer. In none of these cases was the FHITgene found to be altered. Our results indicate that FHITplays a role in a small proportion of ovarian carcinomas.

Acid Anhydride Hydrolases↗