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M Falchetti

Publications and source records attributed to M Falchetti.

17 recordsLinked to original sources
PubMed2006

Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients.

Human papillomaviruses (HPVs), particularly HPV-16/18, are linked to cervical cancer development. Full-length, recombinant HPV-16/18 E7 oncoproteins were used in a new streptavidin-biotin capture ELISA method to investigate anti-HPV E7 antibody prevalence in serum. Sera from 99 healthy women, 70 cervical cancer patients, and 30 patients with cervical pre-invasive neoplasia were analyzed. Anti-HPV-16/18 E7 positivity was found in 53% of cervical cancer patients, in 40% with cervical pre-invasive neoplasia, and in 8% of healthy women. Serum samples from 12 cervical cancer patients were obtained at different time intervals during the treatment. Eleven out of 12 showed a correspondence between HPV-E7 antibody levels (decreasing versus increasing) and the type of response (clinically complete or partial response versus progression or stable disease) at each serological evaluation. Five patients with recurrent HPV-16/18-positive cervical carcinoma were analyzed before and after vaccination with HPV-16/18 E7-pulsed autologous dendritic cells; anti-HPV-16/18 E7 positivity was found in 3 out of 5 women. In conclusion, this assay could potentially be used as an adjunctive tool to monitor the type of response to treatment and possibly to detect antibody induction in cervical cancer patients after vaccination, as a potential marker to evaluate its efficacy.

Antibodies, Viral↗
PubMed2006

Patterns of genomic instability in gastric cancer: clinical implications and perspectives.

In gastric cancer (GC) the loss of genomic stability represents a key molecular step that occurs early in the carcinogenesis process and creates a permissive environment for the accumulation of genetic and epigenetic alterations in tumor suppressor genes and oncogenes. It is widely accepted that GC can follow at least two major genomic instability pathways, microsatellite instability (MSI) and chromosome instability (CIN). MSI is responsible for a well-defined subset of GCs. CIN represents a more common pathway comprising heterogeneous subsets of GC. In addition to MSI and CIN, the CpG islands methylator phenotype (CIMP) plays an important role in gastric carcinogenesis. CIMP may lead to the transcriptional silencing of various genes in gastric carcinogenesis. Intriguingly, more recently in addition to CpG island hypermethylation, a global DNA demethylation, that precedes genomic damage, has been observed in GC. Thus, epigenetic alterations may play a relevant role in gastric carcinogenesis as alternative mechanisms. Evidence suggests that although MSI, CIN and CIMP phenotypes can be distinguished from one another, there might be some degree of overlap. This review describes our current knowledge of the instability pathways in gastric carcinogenesis and the potential clinical applications for different forms of genomic instability in GC.

Chromosomal Instability↗
PubMed2001

Red meat, family history, and increased risk of gastric cancer with microsatellite instability.

Microsatellite instability (MSI) occurs frequently in sporadic gastric cancer (GC) and may define a distinctive molecular pathway of carcinogenesis. We evaluated the role of dietary risk factors in GC according to MSI status. A large series of 382 GC cases and 561 controls were originally identified in a population-based case-control study carried out in the high-risk area around Florence, Italy; 126 GC patients were typed for MSI status. A MSI+ phenotype was detected in 43 of 126 cases (34.1%), whereas 83 cases were classified as MSI-. A multinomial logistic regression model was used to compare the two subgroups of GC classified according to MSI status in the same analysis, with all of the available population controls. A case-case approach was also used. The risk of MSI+ tumors was positively associated with high consumption of red meat and meat sauce and negatively associated with consumption of white meat. A positive association was also seen with total protein and nitrite intake, whereas no relation was found with micronutrient intake. Risk was especially high among subjects reporting both a positive GC family history and a high consumption of red meat (odds ratio, 25.7; 95% confidence interval, 6.4-102.8). For MSI- tumors, a significant protective effect was associated with frequent consumption of citrus and other fresh fruit, garlic, legumes, vegetables, and olive oil and with high intake of beta-carotene and other antioxidants and sugar, whereas positive associations were seen with protein and sodium intake. In summary, a specific dietary pattern emerged for MSI+ gastric tumors, suggesting that factors related to red meat consumption are involved in this pathway, particularly among individuals with a positive family history. In contrast, the risk of MSI- tumors was strongly reduced by the frequent consumption of fresh fruit and vegetables.

Aged↗
PubMed2001

Instability at sequence repeats in melanocytic tumours.

To obtain information on the prevalence of microsatellite mutations in melanomas, we analysed the status of 14 repetitive loci characterized by structurally different non-coding and coding sequence repeats in a panel of 34 primary melanocytic tumours and in lymph node metastases matched to 13 cases. Instability at one or more of the non-coding dinucleotide repeats D2S123, D3S1611, D5S107 and D18S34 was detected in ten out of the 34 primary tumours (29%) and in ten of the 13 metastases (77%). There was no instability at the non-coding mononucleotide repeats BAT25, BAT26 and APDelta3 or at the coding mononucleotide runs within the TGFbetaRII, IGFIIR, BAX, hMSH3 and hMSH6 genes. A five-repeats expansion of the coding E2F4(CAG)n run was found in the only malignant melanoma of soft parts examined, which also showed instability at two dinucleotide loci, and in a superficial spreading melanoma, which was stable at the mononucleotide and dinucleotide repeats but was the only tumour that manifested instability at the SCA1(CAG)n repeat. The absence of mutations at mononucleotide tracts indicates that, in the malignant melanomas tested, microsatellite instability was not associated with the microsatellite mutator phenotype characteristic of mismatch repair-deficient tumours. On the other hand, our results confirm that microsatellite instability at dinucleotide repeats increases with melanoma progression, and indicate that expansions of triplet repeats may occur in melanocytic tumours.

Adult↗
PubMed2000

Instability at dinucleotide and trinucleotide repeats in breast cancer.

We analyzed 7 mono-, 6 di- and 2 trinucleotide repeat loci in a well characterized series of 69 breast cancer cases, treated in the period 1985-1986 and followed for 12 years. Tumor-associated allele contractions or expansions were observed only at di- and trinucleotide repeats, and were detected in 14/69 cases (20%), of which 7 (10%) showed instability at 2 or more loci (10%). No alterations were detected at mononucleotide repeats known to be unstable in gastrointestinal tumors with the microsatellite mutator phenotype. Disease-free survival at 5 years, overall survival at 12 years of follow-up, tumor stage, estrogen/progesteron receptor status, and expression of the Ki-67 proliferation marker were independent of microsatellite status.

Adult↗
PubMed1999

Successful application of indirect in-situ polymerase chain reaction to tissues fixed in Bouin's solution.

AIMS: To evaluate the value of polymerase chain reaction-in situ hybridization (PCR-ISH) for the detection of human papillomaviruses (HPV) in paraffin sections of cervical biopsies fixed either in 10% formalin or in Bouin's solution. METHODS AND RESULTS: We analysed 40 biopsies from Italian women infected with the human immunodeficiency virus type 1 (HIV 1). In-situ hybridization techniques were performed with commercial biotinylated probes. The PCR-ISH was carried out by the 'hot start modification'. Cervical intraepithelial neoplasia (CIN) was found in 23 of 40 patients (57. 5%); eight cases showed condylomatous features. Human papillomavirus was detected in 42.5% by ISH and in 65% by PCR-ISH. Sixty-nine per cent of positive biopsies contained HPV 16, 18, 31 and 33. HPV 6 and 11 were found only in condylomata acuminata samples. CONCLUSIONS: The results point to a high incidence of HPV infection as well as of CIN in HIV-positive patients. Human papillomavirus type 16 appears to be most frequently associated with CIN. Polymerase chain reaction-ISH is more sensitive than ISH in the detection and typing of HPV DNA both in clinical and in 'latent' infections. The two techniques yielded the same results with either formalin- or Bouin's-fixed material.

Acetic Acid↗
PubMed1998

Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype.

We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding repeats were associated with microsatellite instability (MSI). The tumors included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI = two loci and 13 cases with MSI > or = 3 loci. We investigated coding repeats within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%), four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6 were strongly associated to hMSH6 mutations, suggesting a key role of this gene. The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI-positive GCs and were in most cases associated with mutations at coding repeats. Further investigations with BAT-40 confirmed that four cases manifested mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta RII. A subset of tumors with MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats.

Aged↗
PubMed1997

Microsatellite instability in gastric cancer is associated with tumor location and family history in a high-risk population from Tuscany.

We studied the presence of microsatellite instability (MSI) in a series of 108 gastric cancers (GCs) previously identified in an epidemiological study carried out in a high-risk area around Florence. To investigate associations between MSI and GC family history, 34 cases (31.5%) who had a GC-affected first-degree relative were included in the series. A family history positive for colorectal cancer was reported quite rarely (5.6%). The analysis of 6 microsatellite loci in DNA from paired normal tissue and tumor samples microdissected from paraffin-embedded specimens revealed varying degrees of instability: 56 cases (51.8%) did not show instability at any of the 6 loci; 19 (17.6%) showed instability at 1 locus; 16 (14.8%) showed instability at 2 loci; 11 (10.2%) showed instability at 3 loci; 4 (3.7%) showed instability at 4 loci; and 2 (1.9%) showed instability at 5 loci. The replication error-positive (RER+) phenotype, defined as the presence of MSI at 2 or more loci, had a frequency of 30.6% (33 of 108) and tended to be positively associated with female sex, intestinal histological type, advanced tumor stage, vascular invasion, positive GC family history, and blood group of A type. No correlation emerged between age at diagnosis and RER+ phenotype, whereas a significant association with the RER+ phenotype was shown by the antral location. A multivariate analysis adjusting for a selected group of potential confounding factors confirmed the strong association of the RER+ phenotype with the antral location (P = 0.001) and with a positive GC family history (P < 0.05). Survival analyses at 5 and 8 years showed no difference between RER+ and RER- patients, even when corrected for stage distribution. By the microdissection technique, we also used microsatellite allele patterns to investigate intratumoral heterogeneity and genetic relationships between tumors and adjacent dysplasia and/or intestinal metaplasia. Areas of metaplasia and dysplasia demonstrated MSI only in cases with MSI-positive tumors. In MSI-positive tumors, there was consistent evidence of intratumoral microsatellite allele heterogeneity, indicating the presence of genetically divergent tumor cell clones within the same neoplasm.

Age Factors↗
PubMed1994

Glomus tumour: the immunohistochemical characteristics of twenty-three cases.

Twenty-three cases of glomus tumour were investigated with the antibodies keratin, vimentin, neurofilaments, desmin, actin, S100, Factor VIII-related antigen, substance P and KP1/CD68. It will be shown that the glomus cells were vimentin-positive in 11 out of 23 cases (48%), actin-positive in 16 out of 23 cases (70%) and desmin-positive in 9 out of 23 cases (39%). The KP1 monoclonal antibody demonstrated the presence of numerous mast cells in some cases. The substance P was only occasionally positive in six cases (26%). No positive staining was seen with keratin, neurofilaments, S100 and Factor VIII-related antigen. It is confirmed that glomus cells can be considered as elements of smooth muscle origin. Our study suggests a possible explanation of the mechanism which induces paroxysmal attacks in patients with glomus tumours.

Glomus Tumor↗
PubMed1989

Nasopharyngeal cysts. Report of seven cases with review of the literature.

A series of seven patients with nasopharyngeal cysts is presented. A review of the pertinent literature and a description of the clinical, radiologic, and pathologic features of these lesions are also included. The role of computed tomography in differentiating nasopharyngeal cysts from other pathologic entities, as well as the importance of surgery as an elective method of treatment, is specifically emphasized.

Adult↗
PubMed1989

Neuroendocrine tumour of the uterine cervix. Cytomorphologic, histochemical and immunohistochemical aspects.

We report a case of neuroendocrine tumour of the uterine cervix (carcinoid) with spread to the corpus and adnexa, and hepatic metastases. Carcinoid represents a rare entity among tumours of the uterine cervix, and is now included among the APUD system-derived tumours (apudomas). Gross examination revealed an enlarged uterus (11 x 7 cm) with neoplastic infiltration of the endocervical canal and uterine corpus, and yellowish-white nodules in both ovaries. Microscopic features were those of a malignant trabecular carcinoid (Morson's type I-II). Morphological, histochemical, immunohistochemical and ultrastructural studies were performed. Grimelius stain and antisera to NSE and bombesin yielded positive reactions. Focal positivity was seen with EMA, and probably expressed an epidermoid component. On the basis of a review of the literature, we classify our case within the differentiated neuroectodermic tumours, despite the extremely aggressive biologic behavior already present at surgery. Combined use of histochemical, immunohistochemical and ultrastructural techniques is the correct approach to the histopathologic diagnosis of malignancies with rare and difficult features.

Carcinoid Tumor↗
PubMed1987

Ultrastructural renal findings in allografted kidneys of patients treated with ciclosporin A.

22 renal biopsies of 22 patients with 6-month-old transplants have been examined at the light- and electron-microscopic level to demonstrate the toxic effects induced by ciclosporin A (CS). These patients presented stable renal function and were exempt from acute rejection symptoms or nephrotoxicity. Interstitial fibrosis, tubular atrophy and interstitial lymphocytic infiltration were the lesions most often observed by light microscopy. In a single case an arteriolar lesion suggestive of arteriolopathy due to Cs was seen. Ultrastructural observations of renal tubular cells showed a tendency of rough and smooth endoplasmic reticulum to microdilate and microvacuolize. In 4 out of 22 cases there were mitochondrial alterations with giant mitochondria. In only 1 case, clusters of cilia were seen. Clinical histological correlations show that interstitial fibrosis is directly proportional to CS blood level. CS higher blood levels suggest a higher risk of nephrotoxicity.

Basement Membrane↗
PubMed1984

Steroids and Adriamycin nephrosis.

Adriamycin induces a nephrotic syndrome in rats characterized by severe ultrastructural changes of visceral epithelial cells similar to those observed in puromycin aminonucleoside (PA) nephrosis and in human 'minimal changes' glomerulopathy. Since steroids have been shown to be effective in human 'minimal changes' glomerulopathy and in PA nephrosis, we undertook the present study to assess whether steroids had a therapeutic effect on adriamycin nephrosis. Groups of rats injected with different doses of adriamycin were subsequently treated with prednisolone. No significant differences were observed in proteinuria and in ultrastructural findings between the control and the steroid-injected animals. This study suggests that the mechanism underlying adriamycin-induced nephrotic syndrome might be different from that responsible for PA nephrosis or human 'minimal changes' glomerulopathy.

Animals↗
PubMedDate not supplied

[Bone marrow biopsy in HIV-positive patients with thrombocytopenia. Light and electron microscopy].

Isolated thrombocytopenia (platelets less than 100,000 mmc) may be the first clinical symptom in HIV positive patients or occur in all the evolutive phases up to overt AIDS. In this paper bone marrow lesions are evaluated at light and electron microscopy in 32 HIV positive patients with isolated thrombocytopenia (group II and III CDC 1986). At light microscopy an increase in megakaryocytes with small dysplastic changes, plasmacytosis and hypereosinophilia were the bone marrow lesions detected. Electron microscoy revealed megakaryocytes with focal nuclear alterations (hypolobation and dilatation of the perinuclear cisternae) and abnormalities in the maturation of platelets associated with cytoplasmic micro-macrovacuolation, absence of viral particles or of virus correlated structures. About 9% of HIV positive patients presented with isolated thrombocytopenia as a first clinical symptom: thrombocytopenia is not believed to have unfavourable prognostic significance in the evolution to overt AIDS.

Biopsy↗