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Biomedical subjects

M Fiorentino

Publications and source records attributed to M Fiorentino.

At least 19 recordsLinked to original sources
PubMed2005

Expression of connective tissue growth factor is a prognostic marker for patients with intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Connective tissue growth factor is a member of the 'CCN' protein family. Consistent with its profibrotic properties, it is over-expressed in several human epithelial malignancies. PATIENTS AND METHODS: We have retrospectively evaluated by immunohistochemistry the presence of connective tissue growth factor in archival tissues from 55 resected intrahepatic cholangiocarcinomas and compared its expression to the main pathological parameters, disease free and overall survival. RESULTS: Tumours were scored as high and low/absent expressers (> or =50%, 0-50% cells, respectively). Thirty-three of 55 cholangiocarcinomas (60%) were high and 22 (40%) low expressers. No significant correlation was found between connective tissue growth factor and tumour grade, tumour location, vascular and perineural invasion. Eighteen of 22 (82%) low/absent expressers and 12/33 (36%) high expressers had recurrence of disease (P=0.001). Low/absent expressers showed a poor disease free and overall survival compared with the higher expressers (P<0.001). Vascular invasion was related to tumour recurrence (P=0.025) and to decreased disease free survival (P<0.05). During proportional hazard regression analysis, only connective tissue growth factor was found to influence disease free survival (P=0.01). CONCLUSIONS: Expression of connective tissue growth factor is an independent prognostic indicator of both tumour recurrence and overall survival for intrahepatic cholangiocarcinoma patients regardless of tumour location, tumour grade, vascular and perineural invasion.

Adult↗
PubMed2005

Potential of real-time PCR assessment of granzyme B and perforin up-regulation for rejection monitoring in intestinal transplant recipients.

Granzyme B (GrB) and perforin are promising markers to predict acute rejection episodes of transplanted organs. Having recently reported that immunohistochemical expression of GrB/perforin correlates with histologically assessed acute cellular rejection (ACR) episodes in intestinal transplantation recipients, herein we have additionally explored the potential of real-time polymerase chain reaction (PCR) assessment of GrB/perforin gene up-regulation in peripheral blood mononuclear cells. Both immunohistochemical evaluation of GrB/perforin expression and real-time PCR assessment of up-regulation, which was defined as a 2-fold increase with respect to "basal" levels during maintenance immunosuppressive protocols, were performed among a population of 23 intestinal transplant recipients under routine surveillance, in addition to histological analysis of ACR. The ACR scores showed direct relationships both with GrB/perforin immunohistochemistry (IHC) scores (P < .001) and with gene up-regulation by real-time PCR (P = .004). Furthermore, real-time PCR upregulation was associated with the IHC score (P < .001). A preliminary analysis of diagnostic accuracy-performed to gain information to plan future studies-indicated that when using histological assessment as the reference technique, our current definition of PCR up-regulation provided good specificity (84%) but insufficient sensitivity (44%) for a noninvasive prediction of ACR. The results of this pilot study suggested that real-time PCR analysis of GrB/perforin upregulation may help therapeutic decision making, and have the potential for detection of presymptomatic rejection. More extensive studies must investigate strategies to improve the sensitivity of the analyses of GrB/perforin up-regulation.

Adolescent↗
PubMed2004

Endoscopic finding of granular cell tumour associated with leiomyomas in the oesophagus.

Following a single report in the literature of granular cell tumour associated with diffuse leiomyomatosis in the oesophagus, we describe the case of a 39-year-old man in whom a granular cell tumour and two leiomyomas were endoscopically removed from this site. This previously unreported association of granular cell tumour with isolated leiomyomas suggests the need to bear in mind the possibility of other mesenchymal lesions, including leiomyomas or leiomyomatosis, when a granular cell tumour is found in the oesophagus.

Adult↗
PubMed2003

Granzyme B and perforin as predictive markers for acute rejection in human intestinal transplantation.

In human heart and kidney transplantations, granzyme B (GrB) and perforin have both been shown to be predictive markers for acute cellular rejection (ACR). We investigated the tissue expression and possible relationship of GrB and perforin to the clinical outcome, histopathology, and function of intestinal transplants. In 13 consecutive patients undergoing small intestine transplantation, histologic/immunohistochemical rejection monitoring was performed together with GrB and perforin immunostaining (score "0", 0%-10% positive lymphocytes; "1", 10%-25%; "2", 25%-50%; "3", >50%). Eleven patients are currently alive and well. All 11 had at least one episode of ACR: one patient had 6 episodes of severe ACR requiring retransplantation; the remaining 10 experienced only mild or moderate rejection. Both GrB and perforin were always co-expressed. A highly significant correlation was observed between GrB/perforin scores and histological severity of ACR (Pearson's coefficient, R < 0.0009). Interestingly, score 3 GrB/perforin immunostaining was recorded only in the context of severe ACR; all the histologically negative or "indeterminate" biopsies (n = 6) taken from a single affected patient showed GrB/perforin scores of 1 or 2. By contrast, none of the other tested histologically negative/"indeterminate" biopsies (n = 350), including those performed during graft stabilization, had raised GrB or perforin scores. We conclude that in intestinal transplantation recipients, a direct correlation seems to exist between histologically confirmed ACR and raised GrB/perforin immunohistochemical scores. Our findings suggest the need to investigate the possibility of predicting ACR by routine serum polymerase chain reaction (PCR) monitoring, which would reduce discomfort to patients.

Acute Disease↗
PubMed2003

Investigation of ErbB1 and ErbB2 expression for therapeutic targeting in primary liver tumours.

BACKGROUND: Molecular targets are needed for primary liver tumours. AIMS: ErbB1 and ErbB2 expression was analysed in neoplastic and surrounding tissue in surgical specimens from 52 hepatocellular carcinomas and 48 intrahepatic cholangiocarcinomas, randomly chosen from cases surgically treated in this institution. METHODS: ErbB1 and ErbB2 expression were evaluated immunohistochemically, the latter by Herceptest. Gene amplification of ErbB2 was tested by chromogenic in situ hybridisation. RESULTS: In normal/cirrhotic non-neoplastic tissue, the ErbB1 (but not ErbB2) antibody commonly stained normal hepatocytes and mature intrahepatic ducts. In neoplastic tissue, moderate/strong ErbB1 immunostaining occurred in 43/52 (85%) hepatocellular carcinomas and 39/48 (81%) intra-hepatic cholangiocarcinomas. With ErbB2 Herceptest, 0/52 (0%) hepatocellular carcinomas and 2/48 (4%) intra-hepatic cholangiocarcinomas had treatable scores of 2+/3+ (chromogenic in situ hybridisation confirmed gene amplification in the latter two cases only). Neither ErbB1 nor ErbB2 expression correlated with any of the main clinical-pathologic features or survival. CONCLUSIONS: Although not related to prognosis, ErbB1 could be a molecular target in a large percentage of patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma. Inclusion of anti-ErbB1 drugs such as ZD 1839 and c225 (and possibly also anti-ErbB2 drugs like Trastuzumab for a small subset of patients) in clinical trials is suggested.

Adult↗
PubMed2001

FMRFamide in the amphibian brain: a comprehensive survey.

Mapping of FMRFamidergic neural circuitry in the amphibian brain has been done by immunohistochemical methods. Comparative evidence suggests that there are similarities and differences in the overall pattern of distribution of FMRFamide-ir elements in the brain among the three amphibian orders and within each order. FMRFamide is expressed in neurons in some circumscribed areas of the brain. A part of these neurons is concentrated in classical neurosecretory areas of the hypothalamus in a bilaterally symmetrical fashion. Similar neurons occur occasionally in the midbrain, but are virtually absent from the hindbrain. Anurans are unique among amphibians to show FMRFamide neurons in the medial septum and diagonal band of Broca. A viviparous gymnophione is known to possess a small population of such neurons in the dorsal thalamus. Together, the FMRFamide neurons contribute to an extensive fiber network throughout the amphibian brain. Descriptive developmental studies suggest that the rostral forebrain-located FMRFamide neurons originate in the olfactory placode and then migrate into the brain along the route of the vomeronasal-olfactory-terminal nerve complex. Olfactory placodal ablation in an anuran and a urodele provide experimental support to this contention. Other FMRFamide neuronal cell groups, in the hypothalamus and dorsal thalamus, are supposed to arise from non-placodal precursors. The neuroanatomical distribution (projection of immunoreactive processes to areas of the fore-, mid-, and hindbrain as well as to cerebrospinal fluid, co-localization with other neuropeptides, and presence in the median eminence) has furnished morphological correlates of possible functions of FMRFamide in the amphibian CNS. While amphibian FMRFamide-like or structurally related peptides remain to be isolated and characterized, the sum of the distribution pattern of FMRFamide-like immunoreactivity suggests that it may act as a neurotransmitter or a neuromodulator, and also may have endocrine regulatory functions.

Amphibians↗
PubMed2001

Development and distribution of FMRFamide-like immunoreactivity in the toad (Bufo bufo) brain.

By using immunohistochemistry, we studied the development and distribution of the FMRFamide-like immunoreactive (ir) neuronal system in the toad brain during the ontogeny. In addition to this, experimental evidence was provided to show that the rostral forebrain-located FMRFamide neurons originate in the olfactory placode and then migrate into the brain along the olfactory pathway. During early development, within the brain, FMRFamide-ir perikarya first appeared in the periventricular hypothalamus. Later in development, FMRFamide-ir cells were visualized in the rostralmost forebrain simultaneously with similar ir cells in the developing olfactory mucosa. Selective ablation of the olfactory placode(s), prior to the appearance of the first FMRFamide-ir cells in the brain, resulted in the total absence of ir cells in the telencephalon (medial septum and mediobasal telencephalon) of the operated sides(s). The preoptic-suprachiasmatic-infundibular hypothalamus-located FMRFamide-ir neurons were not affected by olfactory placodectomy, arguing that they do not originate in the placode. This result points to the placode as the sole source of such neurons in the rostral forebrain.

Animals↗
PubMed2001

Imbalance between cytoproliferation and apoptosis in hepatitis C virus related chronic liver disease.

An imbalance between cytoproliferation and apoptosis may be relevant in liver carcinogenesis. The aim of this study was to analyse these parameters in patients with chronic liver damage in relation to the aetiology of the disease. Forty-eight patients were studied: 23 had hepatitis C virus (HCV)- and 11 had hepatitis B virus (HBV)-related chronic hepatitis, seven had alcoholic liver disease, and seven had haemochromatosis. The biopsies were used for routine diagnosis, cytoproliferative indexing (MIB1, Ki67 monoclonal antibody), apoptosis (APO, in situ end labelling) and, in part, liver iron and malondialdehyde determination. Apoptosis was similar in all patient subgroups and correlated with hepatitis grading (P=0.002) and ALT levels (P=0.004); cytoproliferation (MIB1) levels were higher in HCV patients, both as a whole and in the periportal area (P=0.02 and P=0.03). MIB1 correlated with ALT levels (P=0.0001), hepatitis grading (P=0.02) and tissue iron (P=0.04). APO and MIB1 were higher in patients with than in those without cirrhosis (P=0.0006 and P=0.03, respectively). APO correlated with MIB1 (P=0.001), overall but not in HCV patients. The MIB1/APO ratio was significantly higher in HCV patients than in the other groups (P=0.02). In summary, cytoproliferation is more pronounced in chronic HCV-related hepatitis, while APO is not significantly higher than in other types of liver damage, suggesting an imbalance between the two. APO and MIB1 are directly related to the extent of liver damage and, from a biochemical point of view, to tissue iron levels.

Adult↗
PubMed2001

Expression of Epstein-Barr virus-encoded RNA and biological markers in Italian nasopharingeal carcinomas.

Nasopharingeal carcinoma (NPC) is frequently associated with Epstein-Barr virus (EBV), but little is known about its pathogenesis in Western countries, where its incidence is low and EBV is not endemic. We studied 26 Italian cases of NPC: 24 of the non-keratinizing subtype, and 2 keratinizing. We used immunohistochemistry to evaluate p53, bcl-2 and Ki-67 protein expression, and in situ hybridization (ISH) to assess bcl-2 mRNA and the EBV transcript, EBER1, with bcl-2 protein and mRNA expression being compared in serial sections. As regards bcl-2, the protein or mRNA was expressed in 15/26 (58%) and 17 (65%) cases respectively, with co-expression being found only in 9 (35%) cases; 23 (88%) cases were positive for one or the other. EBER1 was detected in 17/26 (65%) cases, of which 80% and 71% coexpressed bcl-2 protein or mRNA, respectively. Only 9/26 (35%) cases had a high Ki67 proliferative index; 3/26 (12%) overexpressed p53. This study of NPC in Italy confirms the importance of EBV and bcl-2 in Western cases. The discrepancy between bcl-2 mRNA and protein expression invites investigation into a possible internal bcl-2 regulation system.

Biomarkers↗
PubMed2001

Low p27 expression is an independent predictor of survival for patients with either hilar or peripheral intrahepatic cholangiocarcinoma.

PURPOSE AND EXPERIMENTAL DESIGN: The prognosis for intrahepatic cholangiocarcinoma (ICC) depends mainly on the feasibility of complete surgical resection. In the absence of demonstrated biological predictors of survival, we evaluated the prognostic value of the cyclin-dependent kinase inhibitor p27 by immunohistochemistry in a series of routine specimens from 47 ICC patients, 22 with the hilar and 25 with the peripheral subtype. Proliferation rate was also evaluated in the same cases by the MIB1 index. Tumors were scored as high, low, and negative p27 expressers (> or =50%, <50%, and no positive nuclei, respectively). RESULTS: High, low, and negative p27 expression was recorded in 18 (38%), 17 (36%), and 12 (26%) cases, respectively. No significant correlation was found between p27 expression and gender, age, tumor grade, tumor location, vascular or perineural invasion, or proliferative index. Tumors with low or absent p27 expression were associated with poor survival compared with the high-expresser group. Kaplan-Meier curves comparing different p27 expression levels with survival showed highly significant separation (P < 0.0001, log-rank test). With univariate Cox proportional hazard regression, only p27 score among all of the parameters was found to influence survival (P = 0.0003). CONCLUSION: We conclude that in ICC, low or absent p27 expression can predict poor survival, regardless of tumor location, pathological features, and tumor proliferation. Immunohistochemical detection of p27 on routine sections may provide the first biological prognostic marker for ICC, thus influencing the therapeutic strategies for these patients.

Cell Division↗
PubMed2000

Comparative immunocytochemical study of FMRFamide neuronal system in the brain of Danio rerio and Acipenser ruthenus during development.

The distribution of FMRFamide-like immunoreactive (ir) neurons and fibers was investigated in the central nervous system of developing zebrafish and juvenile sturgeon (sterlet). Adult zebrafish was also studied. In zebrafish embryos FMRFamide-ir elements first appeared 30 h post-fertilization (PF). Ir somata were located in the olfactory placode and in the ventral diencephalon. FMRFamide-ir fibers originating from diencephalic neurons were found in the ventral telencephalon and in ventral portions of the brainstem. At 48 h PF, the ir perikarya in the olfactory placode displayed increased immunoreactivity and stained fibers emerged from the somata. At 60 h PF, bilaterally, clusters of FMRFamide-ir neurons were found along the rostro-caudal axis of the brain, from the olfactory placode to rostral regions of the ventro-lateral telencephalon. At 60 h PF, numerous ir fibers appeared in the dorsal telencephalon, optic lobes, optic nerves, and retina. Except for ir fibers in the hypophysis at the age of 72 h PF, and a few ir cells in the nucleus olfacto-retinalis (NOR) at the age of 2 months PF, no major re-organization was noted in subsequent ontogenetic stages. The number of stained NOR neurons increased markedly in sexually mature zebrafish. In adult zebrafish, other ir neurons were located in the dorsal zones of the periventricular hypothalamus and in components of the nervus terminalis. We are inclined to believe that neurons expressing FMRFamide originate in the olfactory placode and in the ventricular ependyma in the hypothalamus. On the same grounds, a dual origin of FMRFamide-ir neurons is inferred in the sturgeon, an ancestral bony fish: prior to the observation of ir cells in the nasal area and in the telencephalon stained neurons were noted in circumventricular hypothalamic regions.

Age Factors↗
PubMed2000

Helicobacter pylori seroprevalence in hepatitis C virus positive patients with cirrhosis.

BACKGROUND/AIMS: Liver cirrhosis is a significant cause of death in Italy and one of the most frequent causes of hospitalization. Acute peptic ulcer and upper gastrointestinal bleeding reportedly occur in over one-third of cirrhotic patients. Since Helicobacter pylori (H. pylori) infection strongly correlates with peptic ulcer, we sought to ascertain the prevalence of H. pylori infection in cirrhotic patients. METHODS: In a case-control study, we examined 254 consecutive patients (127 male and 127 female, age range 30-82 years) suffering from hepatitis C virus (HCV)-related cirrhosis and 463 sex- and age-matched patients admitted to the Department of Emergency Care of our hospital (254 male, 209 female, age range 30-79 years) resident in the same area. RESULTS: Antibodies to H. pylori were present in 226/254 (89%) cirrhotic patients and in 275/463 (59%) controls (p<0.0001). The difference was significant both in males and in females. CONCLUSIONS: The very high prevalence of H. pylori infection may explain the frequent occurrence of gastroduodenal ulcer in cirrhotic patients and may possibly determine the prognosis of those who are also infected with HCV.

Adult↗
PubMed2000

Role and new perspectives of transforming growth factor-alpha (TGF-alpha) in adenocarcinoma of the gastro-oesophageal junction.

The incidence of gastro-oesophageal junction (GEJ) adenocarcinoma is increasing in Western countries and prognosis is poor since metastasis is most often present at diagnosis. We examined samples from 87 resected type II GEJ adenocarcinomas, 30 of these with endoscopic diagnostic biopsy material, to evaluate transforming growth factor alpha (TGF-a) expression and p53 overexpression by immunohistochemistry and in situ hybridization (for TGF-alpha), in relation to biological and clinical behaviour. TGF-alpha messenger RNA (mRNA) and protein were detectable in neoplastic cells in 56% and 64% cases respectively. TGF-alpha mRNA was detected in intra- and peritumoral lymphocytes and those of metastatic lymph nodes. TGF-alpha protein expression was significantly associated with tumour progression (P= 0.025) and lymph node metastasis (P < 0.05). The strong TGF-alpha expression found in neoplastic cells inside blood and lymphatic vessels and in metastatic localizations suggests that TGF-a-positive GEJ adenocarcinomas could have a more aggressive biological phenotype. The expression of TGF-alpha mRNA and protein in both inflammatory and neoplastic cells indicates that TGF-alpha is directly synthesized by both cell compartments. Finally, since TGF-alpha expression was associated with lymph node metastasis, its detection in preoperative perendoscopic biopsies might identify patients with more aggressive tumours who may need additional therapy, including neo-adjuvant treatment.

Adenocarcinoma↗
PubMed2000

Hepatocellular carcinoma in a non-cirrhotic liver. Two case reports and literature review.

Hepatocellular carcinoma (HCC) is closely associated with cirrhosis, but it also develops, although much less frequently, in a non-cirrhotic liver. It is suspected that hepatocellular carcinoma has a different etiology when associated and not associated with chronic liver disease. We report two cases of patients with hepatocellular carcinoma that developed in a non-cirrhotic liver. In the first case we describe an incidental liver nodular lesion containing multiple foci of HCC including pseudogland or trabecular formation and areas of sclerosis. The non-cancerous parenchyma of the liver was histologically unremarkable except for mild fatty changes of hepatocytes and minimal dysplasia. The second case describes a combined hepatocellular carcinoma and cholangiocellular carcinoma (CCC) (mixed carcinoma) in a patient who was serologically negative for both hepatitis B and C viruses. The adjacent liver parenchyma showed mild piecemeal necrosis and mild lobular activity compatible with chronic viral hepatitis, but cirrhosis was not established. This case appears to indicate that mixed type carcinoma can develop in a non-cirrhotic liver, with CCC being far more dominant than HCC; such a finding is extremely unusual, based on previously published reports.

Aged↗
PubMed2000

Acquired expression of p27 is a favorable prognostic indicator in patients with hepatocellular carcinoma.

The p27 cyclin-dependent kinase inhibitor is a negative regulator of cell-cycle progression. In many human epithelial malignancies, decreased expression of p27 correlates with high grade, early recurrence, and poor prognosis. To evaluate the prognostic significance of p27 in hepatocellular carcinoma (HCC), we studied 54 HCCs along with corresponding nontumoral tissue. Immunohistochemistry (IHC) and Western blot (WB) analysis before and after immunoprecipitation with Cdk2 were performed on paraffin-embedded tissues and protein homogenates, respectively, to compare localization and expression of the p27 protein and to determine the total and active (Cdk2-bound) fractions of p27. Correlations were analyzed between IHC-assessed levels of p27, survival, and major clinical and pathological variables. IHC revealed no p27 expression in the majority of hepatocytes from normal and cirrhotic liver, whereas 14 HCCs (26%) were high p27 expressers (>50% positive cells), 26 (48%) low expressers (<50% positive cells), and 14 (26%) negative. High IHC signals of p27 correlated with Cdk2-bound p27 as assessed by immunoprecipitation-WB; by contrast, WB alone displayed similar levels of p27 protein in all normal and tumoral samples. High IHC p27 expression correlated with prolonged survival (P = 0.027), whereas the presence of cirrhosis was associated with poor outcome (P = 0.029). We conclude that with respect to their nonneoplastic counterparts, a subset of HCCs acquire significant p27 expression and that high expression of p27 is a favorable independent prognostic parameter for HCC.

Aged↗