Biomedical subjects

M Fiorentino

Publications and source records attributed to M Fiorentino.

At least 55 records · Page 3Linked to original sources

PubMed1996

Neuropeptide Y: localization in the brain and pituitary of the developing frog (Rana esculenta).

The immunohistochemical localization of neuropeptide Y (NPY)-like peptide has been investigated in the peripheral terminal nerve, brain and pituitary of the frog, Rana esculenta, during development. Soon after hatching, a rather simple NPY-immunoreactive (-ir) neuronal system is present, with elements located mainly in the diencephalon. When hind limbs appear and develop, the NPY-neuronal system undergoes considerable elaboration and NPY-ir perikarya appear in several regions of the telencephalon (dorsal, medial, and lateral pallium; medial septum; medioventral telencephalon; anterior preoptic area), diencephalon (ventromedial, central and posterior thalamic nuclei; suprachiasmatic nucleus; infundibulum), mesencephalon (anteroventral mesencephalic tegmentum), and rhombencephalon (central grey; area of the cerebellar and vestibular nuclei). The frequency of NPY-ir neurons increases during larval development, and then decreases in the anterior preoptic area during the metamorphic climax. Dense plexuses of NPY-ir fibers are formed in several brain areas. NPY-ir fibers are found in the peripheral terminal nerve, and ir-neurons through its course along the ventromedial surface of the olfactory bulbs. NPY-ir fiber projections to the median eminence and pars intermedia derive mainly from the ventral infundibular group of NPY-ir neurons, with a contribution from the suprachiasmatic group of NPY neurons. NPY and carboxyl terminal flanking peptide of proneuropeptide Y coexist in the same neurons throughout the brain. The ontogenetic pattern of NPY-ir neuronal system in the brain of Rana esculenta is remarkably different than that reported for Xenopus laevis.

Animals↗

PubMed1996

Histogenesis of primary liver carcinomas: strengths and weaknesses of cytokeratin profile and albumin mRNA detection.

To assess the utility of cytokeratin (CK) profile and albumin mRNA detection (as revealed by in situ hybridization) in the differential diagnosis of primary liver carcinomas (PLCs) we evaluated a series of surgically resected PLCs, comprising 20 "pure" hepatocellular carcinomas (HCCs) (10 well-differentiated, 10 poorly differentiated), 15 cholangiocarcinomas (CCs) (6 peripheral, 5 hilar, and 4 major duct ones) and 10 hepatocholangio-carcinomas (HCC-CCs). 11 of 20 (55%) of the pure HCCs expressed CKs of pure hepatocytic lineage (CK 8 and CK 18); 2 of 10 (20%) of the HCC-CCs displayed only hepatocytic profile, whereas 12 of 15 (80%) of the CCs evidenced mature bile duct cell phenotype (CK 8, CK 18, CK 7, CK 19). All HCCs expressed varying distributions of albumin mRNA, whereas 4 of 6 (67%) peripheral CCs showed cells with focal positivity for albumin mRNA. This suggests that the phenotypic expression of PLC cells are often not fixed, and in particular: (1) peripheral CCs have a different phenotype from hilar and large duct ones; (2) the CK profile and albumin mRNA expression in peripheral CCs show many similarities with those of some HCCs. Furthermore, the results show that a mixed biological phenotype (ie, CK 8, CK 18 and CK 7 and/or CK 19) can be found both among morphologically pure HCCs and peripheral CCs, suggesting that these two forms could share a common histogenesis. We think that special attention should be given to cases in which CK profile and albumin mRNA reveal mixed phenotype, as these tumors could have different biological behavior and respond differently to therapy.

Aged↗

PubMed1996

Expression of cadherins and alpha-catenin in primary epithelial tumors of the liver.

BACKGROUND & AIMS: Cadherins and their associated molecules, such as alpha-catenin, have been shown recently to play a pivotal role in epithelial carcinogenesis. METHODS: The expression of E-cadherin, N-cadherin, and alpha-catenin in 10 normal samples, 28 focal nodular hyperplasias, 9 liver cell adenomas, 65 hepatocellular carcinomas, and 9 cholangiocarcinomas was studied by immunohistochemistry and Western blotting. RESULTS: In the normal liver, hepatocytes expressed E-cadherin and a 129-kilodalton cadherin identified by the anti-N-cadherin antibody GC4. The expression level of alpha-catenin was low. Bile duct cells expressed only E-cadherin and showed high levels of alpha-catenin. The expression of cadherins and alpha-catenin was preserved in focal nodular hyperplasia. In liver cell adenomas, cadherins and alpha-catenin were heterogeneously expressed. In hepatocellular carcinomas, cadherin and alpha-catenin expression was frequently reduced or absent. Alterations in cadherin expression correlated with large tumor size, low grade of histological differentiation, and occurrence of capsular and vascular invasion. In cholangiocarcinomas, neoplastic cells inconstantly expressed E-cadherin and alpha-catenin. CONCLUSIONS: Alterations of cadherin and alpha-catenin expression are frequent in liver cell adenomas and primary liver carcinomas. Their incidence in hepatocellular carcinomas is of prognostic significance.

Adenoma, Liver Cell↗

PubMed1996

Hepatitis C virus reinfection in orthotopic liver transplant patients with or without concomitant hepatitis B infection.

Although recurrence of hepatitis C virus (HCV) in orthotopic liver transplant (OLT) patients is frequent, the relationship between HCV recurrence and graft pathology, particularly in patients who also have a history of hepatitis B virus (HBV), is unclear. The recurrence of HCV after OLT was determined by reverse transcriptase-nested polymerase chain reaction (RT-PCR) in the sera and livers of 41 patients with OLT, 32 of whom underwent transplants for HCV or HBV-related disease. Results were compared with liver function tests, liver histology (including HBV immunohistochemistry), and antibody status. HCV PCR was more frequently positive in OLT patients with a history of HCV only (59%) than in those with a history of both HCV and HBV (41%) or no history of viral infection (2%). Recurrent HCV (60% overall) was associated with mild elevation of liver function tests and mild to moderate hepatitis. In patients who underwent transplants for both HCV and HBV disease, hepatitis on biopsy was more frequently associated with recurrent HBV than with recurrent HCV. We conclude that graft reinfection with HCV, which is frequent in OLT patients with or without HBV recurrence, is usually associated with only mild to moderate hepatitic changes compatible with graft survival.

Base Sequence↗

PubMed1996

Surgical therapy for undifferentiated (embryonal) sarcomas of the liver in adults.

Undifferentiated (embryonal) sarcoma of the liver is a rare malignant mesenchymal tumor with a poor prognosis. Thirty cases worldwide have been reported over the last 40 years. The absence of specific symptoms, the rapid tumor growth, the normality of the common tumoral markers and the consequential delay in the diagnosis, often allow a significant enlargement of the hepatic mass. Three patients ages 15, 25, and 60 were admitted to our department with such a tumor. In spite of the large dimensions of the neoplasms, all underwent a right hepatectomy without any major surgical complications. Two of them died due to tumor recurrence after 10 and 67 months, respectively. The one case remaining is alive and disease free 62 months postoperatively. The latter one was the only case where a complete tumoral capsule was found in the resected specimen. Surgery is strongly recommended for every case with evidence of a liver-confined tumor even if it is large.

Adolescent↗

PubMed1995

Focal nodular hyperplasia of the liver: composition of the extracellular matrix and expression of cell-cell and cell-matrix adhesion molecules.

We studied by immunohistochemistry 25 cases of focal nodular hyperplasia (FNH) to evaluate the composition of the extracellular matrix and the expression and distribution of endothelial cell-cell adhesion molecules and integrin receptors. The extracellular matrix of FNH retained the overall organization of that of normal liver. The matrix of central scars resembled that of portal tracts. The main difference was the presence of large vitronectin deposits, which might indicate the existence of local hemodynamic disturbances. The matrix lining the sinusoid-like vessels running in the hyperplastic parenchyma retained characteristic features of the normal perisinusoidal matrix, such as the presence of tenascin. In the zone surrounding the central scars, it contained large amounts of laminin, von Willebrand factor, and thrombospondin, suggesting the development of perisinusoidal fibrosis. Laminin deposition was accompanied by the induction of cell-cell adhesion molecules on adjacent endothelial cells and by the up-regulation of specific integrin receptors on both hepatocytes and sinusoidal endothelial cells. In conclusion, our study: (1) reinforces the hypothesis that FNH is merely a hyperplastic response of liver parenchyma to local vascular abnormalities, and (2) shows that the lesions of perisinusoidal fibrosis associated with FNH are accompanied by the induction of integrin receptors on hepatocytes and sinusoidal endothelial cells.

Adult↗

PubMed1995

Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer.

PURPOSE: In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval. PATIENTS AND METHODS: Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis. RESULTS: Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068). CONCLUSION: FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.

Adenocarcinoma↗

PubMed1995

Overexpression of c-met protooncogene product and raised Ki67 index in hepatocellular carcinomas with respect to benign liver conditions.

The c-met protooncogene encodes a 190-kd transmembrane tyrosine kinase. This molecule is the receptor for the hepatocyte growth factor (HGF), which is an important mitogen for hepatocytes both in vitro and in vivo. In experimental models, the c-met transcripts appeared strongly expressed by actively proliferating oval cells (OCs). We evaluated the phenotypic modulation of the c-met protooncogene product (c-met pp), in 10 hepatocellular carcinomas (HCCs), 5 focal nodular hyperplasias (FNHs), 4 cases of fulminant hepatitis (FH), and 1 regenerated liver, selected to include the different biological states of hepatocyte (mature normal hepatocytes, transformed ones, and OCs). The supposed mitogenic effect of HGF was analyzed by comparing c-met pp overexpression with the Ki67 index, whereas anti-OV-6 antibody was used for comparison with the presence of OCs. The anti-c-met pp showed a typical plasma membrane-specific staining in all cases. The signal was much stronger in the HCCs than in the benign conditions. The anti-OV-6 monoclonal antibody showed positive immunostaining in many of the cells expressing c-met pp. The percentage of Ki67+ nuclei in high-grade HCCs paralleled c-met protooncogene overexpression. The c-met pp in OV-6+ cells suggests that the paracrine mechanism postulated in experimental models could also apply to human liver.

Biomarkers, Tumor↗

PubMed1994

Immunocytochemical localization of POMC-derived peptides (adrenocorticotropic hormone, alpha-melanocyte-stimulating hormone and beta-endorphin) in the pituitary, brain and olfactory epithelium of the frog, Rana esculenta, during development.

Developmental stages of Rana esculenta, starting with the posterior limb-bud stage (stage 26) up to a few days after metamorphosis, were examined immunohistochemically to localize cells and fibers producing some POMC-derived peptides, namely, alpha-MSH, ACTH and beta-END. Anti ACTH and anti alpha-MSH revealed a positive reaction in the pars intermedia during all stages of development included in this study, whereas no immunoreactivity in this pituitary zone was ever evidenced with anti beta-END. In the pars distalis strongly positive cells were seen with anti ACTH and anti beta-END, while anti alpha-MSH yielded weakly positive cells. Interestingly, these peptides were colocalized in the same cells. Immunoreactivity for alpha-MSH was no longer present in the pars distalis during metamorphic climax and postmetamorphosis. In the brain of premetamorphic tadpoles, belonging to stages 26 to 30, a few neurons in the posterior telencephalon showed a positive reaction only with anti alpha-MSH, but from stage 31 (prometamorphosis) onwards, ACTH and beta-endorphin-like peptide producing cells, together with alpha-MSH-immunoreactive cells, were seen in this region and in the anterior preoptic area and infundibulum. This situation persisted in the subsequent stages of development. Anti alpha-MSH also revealed weakly positive cells in the olfactory epithelium in premetamorphic tadpoles; strong immunoreactivity with anti alpha-MSH was seen in olfactory epithelium cells in animals during prometamorphosis, metamorphic climax and postmetamorphosis. The possible significance of these findings is briefly discussed.

Adrenocorticotropic Hormone↗

PubMed1994

Different in situ expression of insulin-like growth factor type II in hepatocellular carcinoma. An in situ hybridization and immunohistochemical study.

Reexpression of the insulin-like growth factor type II (IGF-II) gene has recently been described in hepatocellular carcinoma (HCC). In this study, we used a nonisotopic in situ hybridization method to analyze the expression of IGF-II mRNA in a series of 28 HCCs arising on cirrhotic and noncirrhotic livers. An immunohistochemical method was used to detect IGF-II peptide. Hepatitis B virus (HBV) status and the histological differentiation degree were also evaluated. Increased expression of IGF-II mRNA was found in 4 of 28 HCCs, and 7 of 17 cirrhotic patients showed IGF-II mRNA in the cirrhotic nodules surrounding the HCC. A slightly higher rate of positivity for IGF-II mRNA was found in the HBV-negative patients than in HBV-positive ones. Positive immunostaining for the IGF-II peptide in the HCC and/or in surrounding cirrhotic nodules was found in 10 of 28 cases. The normal hepatocytes of the noncirrhotic patients were always negative for IGF-II peptide and mRNA. The similarities between our results and those from experimental models in woodchucks seem to support the concept that heterogeneous phenotypic groups could exist in human HCCs.

Carcinoma, Hepatocellular↗

PubMed1994

Gelatinase A (MMP-2) and its mRNA detected in both neoplastic and stromal cells of tumors with different invasive and metastatic properties.

Simultaneous presence of gelatinase A (MMP-2) and MMP-2 messenger RNA (mRNA) in 30 malignant tumors with various degrees of differentiation and biological behavior was evaluated by immunohistochemistry and in situ hybridization. The series consisted of 10 gastric carcinomas, 10 colorectal carcinomas, five squamous skin carcinomas, and five basal cell skin tumors. MMP-2 was detected in all cases. MMP-2 mRNA was expressed in the stromal cells in all cases and was more marked in the less-differentiated gastric and colonic carcinomas; it was also detected in the neoplastic cells of poorly differentiated tumors, particularly in those of the signet-ring cell type, both in the colon and stomach. The study confirmed that stromal cells have a specific role in tumor invasion and suggests a direct relationship between neoplastic epithelium and stromal cells in the most aggressive varieties.

Adenocarcinoma↗

PubMed1994

Expression of insulin-like growth factor II (IGF-II) in human hepatocellular carcinomas: an immunohistochemical study.

Recent results obtained using molecular biology techniques have suggested a possible role for insulin-like growth factor II (IGF-II) in the pathogenesis of hepatocellular carcinoma (HCC). To investigate this phenomenon, a monoclonal antibody was used against IGF-II to study 54 patients with HCC. The presence of HBsAg was also tested both in serum and liver tissue. A positive immunoreaction was found in 9/15 (60%) of the HCC arising in cirrhotic livers of patients who had serum markers for HBV (HBV + positive patients). These results provide further evidence that HBV might play a role in the expression of IGF-II. In HCC of patients without any markers of HBV infection (HBV- negative patients), IGF-II was detected in 10/39 (25.6%) of the tumors, and in some benign neoplastic lesions. It was found not only in neoplastic cells but also in some dysplastic nodules. The speculation arises that IGF-II expression may play a role in some steps of hepato-carcinogenesis.

Adult↗

PubMed1994

Overexpression of p53 protein and Ki67 proliferative index in hepatocellular carcinoma: an immunohistochemical study on 109 Italian patients.

The overexpression of p53 protein and the Ki67 proliferative index was evaluated in 96 hepatocellular carcinomas (HCC), 67 in cirrhotic livers and 29 in non-cirrhotic ones, and in 13 non-carcinomatous lesions, all surgically resected from Italian patients. Overexpression of p53 was detected only in carcinomatous lesions, and was significantly related to the grade of HCC (P < 0.001). In fact, p53 was observed in 7/7 (100%) cases of grade IV, 13/43 (30.3%) of grade III, and 10/46 (21.7%) of grade II. The relationship between p53 and Ki67 scores was determined in serial sections from corresponding areas of both diffuse and patchy immunoreactivity. In the overall population, p53-positive tumors showed a significantly higher Ki67 score (15.9 +/- 5.5% vs 9.2 +/- 4.3% [P < 0.001]). This observation was evident in all grades of HCC.

Carcinoma, Hepatocellular↗

PubMed1994

Antiphospholipid antibody syndrome associated with ovarian cancer. A new paraneoplastic syndrome?

We describe a 41-year-old woman, in whom antiphospholipid antibody syndrome (APS) occurred at presentation, before the detection of an ovarian endometrial adenocarcinoma. This syndrome was characterized by widespread and worsening thromboembolism and it did not respond to conventional anticoagulant treatment. The paraneoplastic nature of this APS was strongly suggested by the disappearance of both thromboembolism and antiphospholipid antibodies only after surgical removal of the cancer.

Adenocarcinoma↗

PubMed1994

Prognosis of gastric carcinoma revealed by interactions between tumor cells and basement membrane.

The extra-cellular matrix (ECM) related antigens, type IV collagen, laminin, M(r) 68,000 laminin receptor (LR), M(r) 72,000 type IV collagenase (MMP-2), its inhibitor TIMP-2, and alpha 2-macroglobulin expression have been immunohistochemically investigated in 100 cases of human gastric carcinoma with a 5-yr follow up. Basement membranes were inversely related to tumoral differentiation. At the early intramucosal stage of both intestinal and diffuse histological types, TIMP-2 was expressed by the majority of tumor cells (60/63%), whereas MMP-2+ and LR+ cells were in the minority (24/19%, 23/0%, respectively). At the early submucosal stage, TIMP-2+ cells moderately decreased in both histological types (49/49%), whereas a consistently higher number of both MMP-2+ and LR+ cells were detected only in the diffuse carcinomas (72%). In the advanced stage, the expression of TIMP-2 further declined (22/24%), although the other two antigens increased or maintained high levels of expression. AMG+ cells never exceeded 10% in either histological type at any stage. In the liver metastases, both MMP-2+ and LR+ cells were more numerous than in the primary tumor (P < 0.002 and P < 0.01). Patients who died from their primary tumor had higher percentages of LR+, MMP-2+, and AMG+ cells and lower percentages of TIMP-2+ cells with respect to survivors. We believe evaluation of ECM-related antigens, and especially TIMP-2, may help determine a confident prognosis for gastric cancer.

Antineoplastic Agents↗

PubMed1993

Secondary leukemia following treatment for Hodgkin's disease.

AIMS AND BACKGROUND: Patients treated for Hodgkin's disease with chemotherapy or with the association of chemotherapy and radiotherapy have an increased risk of secondary leukemia. The aim of this study was to evaluate the leukemogenic risk due to these treatment modalities. METHODS: We performed a case-control study on a population of 1410 patients treated for Hodgkin's disease from 1970 to 1990 in our Institute. Among these patients, we identified 25 cases of secondary leukemia and 3 cases of myelodysplasia, all occurring more than one year after the diagnosis of Hodgkin's disease. Three cases occurred among the patients treated with radiotherapy alone. When we analyzed the risk in relation to the type of treatment (radiotherapy, chemotherapy, or both), the comparisons were relative to patients treated with radiotherapy alone. RESULTS: We found that chemotherapy alone is associated with a fivefold increased risk (odds ratio = 5.4) compared with radiotherapy alone. When both treatments are used, the risk is not further increased (odds ratio = 4.4). Patients receiving more than 6 courses of chemotherapy have an excess risk (relative risk = 2.5) compared with those treated with 6 courses or less. No increased risk was observed after splenectomy. CONCLUSIONS: This study confirms an increased incidence of secondary leukemia occurring in patients treated for Hodgkin's disease. The increased risk seems to be correlated with the number of courses of alkylating agent therapy, whereas it is unaffected by the addition of radiotherapy.

Adolescent↗

PubMed1993

Bone marrow myeloid cell kinetics during treatment of small cell carcinoma of the lung with chemotherapy not associated and associated with granulocyte-macrophage colony-stimulating factor.

Information on the kinetics of bone marrow (BM) myeloid precursors (BMMP) is required for integrating cancer chemotherapy with granulocyte-macrophage colony-stimulating factor (rhGM-CSF), with the aim of reducing neutropenia. Using bivariate flow-cytometric analysis of the in vivo incorporation of bromode-oxyuridine (BUDR) vs DNA content we have studied the kinetics of BMMP in 21 patients with SCLC during the first of six chemotherapy courses (etoposide, epirubicin, and cis-platinum, days 1-3, every 21 days), given alone (eight patients) or followed by rhGM-CSF (10 micrograms/kg/day s.c., days 4-14) as BM rescue (eight patients) or both preceded (days -17 to -7, as BM priming) and followed by rhGM-CSF (five patients). At 11-14 days after the start of these therapies there was an increase in the baseline proliferative activity of proliferating BMMP and a shortening in the time needed by the metamyelocyte to mature and to leave the marrow. Both effects were greater and were maintained to a significantly greater degree a week later in patients who received chemotherapy plus rhGM-CSF rescue than in those who received chemotherapy alone or rhGM-CSF priming alone. At day 11-14 the pretreatment median cell production rate of pBMMP was increased by 340%, 150%, and 183% and the maturation time was reduced by 80%, 45%, and 57%, respectively, in the three groups. A week later, the corresponding figures were 206%, 111%, and 157% and 50%, 18%, and 45%. Hence, an identical rhGM-CSF schedule is more effective in increasing the neutrophil production by BMMP when given following chemotherapy as BM rescue than before it as BM priming. In both the rescue and the priming schedule, the increase in proliferative activity of BMMP just at the end of rhGM-CSF stimulation was linked to both an increase in the labeling index and a reduction in duration of S-phase (TS), while a week later it was linked solely to reduction in TS. This could actually reduce one of the two kinetic targets of subsequently administered cytostatics, i.e., a high LI and a long time spent in S phase. From this study, accurate kinetic data can be obtained with the in vivo BUDR technique that are useful in scheduling rhGM-CSF.

Aged↗

PubMed1993

Detection of anti-sense transcripts of the insulin-like growth factor-2 gene in Wilms' tumor.

The expression of the insulin-like growth factor-2 (IGF-2) gene was studied by means of both in situ hybridization and immunohistochemistry in eight cases of Wilms' tumor with different histological features. An anti-sense cRNA IGF-2 probe revealed the presence of abundant IGF-2 mRNAs in all eight tumors examined, localized in the most undifferentiated tumoral cells (blastemal cells); none of the tumors showed immunoreactivity for the anti-IGF-2 antibody. Using a sense cRNA IGF-2 probe, we also detected anti-sense transcripts of the IGF-2 gene in five of eight tumors. These transcripts were exclusively localized in the cells expressing the IGF-2 mRNAs. Although the function of these anti-sense transcripts is unknown, we think that their presence could explain the lack of IGF-2 peptides in Wilms' tumors despite increased expression of IGF-2 mRNAs.

Child↗