PubMed Health⌕ Search

Biomedical subjects

G Perilongo

Publications and source records attributed to G Perilongo.

At least 19 recordsLinked to original sources
PubMed2000

Activation of beta-catenin in epithelial and mesenchymal hepatoblastomas.

Wnt/beta-catenin signaling is frequently activated in cancer cells by stabilizing mutations of beta-catenin or loss-of-function mutations of the APC tumor suppressor gene. We have analysed the role of beta-catenin in the pathogenesis of hepatoblastoma (HB), an embryonic liver tumor occurring mainly in children under 2 years of age. Sequence analysis of the beta-catenin NH2-terminal domain in 18 epithelial and mixed HBs revealed missense mutations in the GSK3beta phosphorylation motif or interstitial deletions in 12 tumors (67%). In the remaining cases, no truncating mutation of APC could be evidenced. Immunohistochemical analysis of beta-catenin in 11 HBs demonstrated nuclear/cytoplasmic accumulation of the protein in all tumors analysed, with predominant nuclear beta-catenin immunostaining in undifferentiated cells. Membranous beta-catenin localization was preserved only in fetal-type tumoral hepatocytes and was associated with E-cadherin expression. Moreover, we show that beta-catenin is aberrantly overexpressed in a large spectrum of tumor components, including hepatocyte-like cells at various differentiation stages and heterologous elements such as squamous, osteoid and chrondroid tissues, and in occasional other mesenchymally-derived cells. These data strongly suggest that activation of beta-catenin signaling is an obligatory step in HB pathogenesis, and raise the possibility that it interferes with developmental signals that specify different tissue types at early stages of hepatic differentiation.

Biological Transport↗
PubMed2000

Somatic mosaicism in von Hippel-Lindau Disease.

von Hippel-Lindau (VHL) disease is an autosomal dominant familial cancer syndrome predisposing to the development of retinal and central nervous system haemangioblastomas, pheochromocytomas, renal and pancreatic cancer. In the course of a molecular analysis conducted to detect germline mutations of this gene in von Hippel-Lindau patients and individuals affected by sporadic tumors, we have identified a case of somatic mosaicism in the asymptomatic mother of a VHL patient who was subsequently diagnosed with pheochromocytoma. This is the first report providing molecular evidence of somatic mosaicism in von Hippel-Lindau disease. Mosaicism could provide some genetic explanation for the clinical heterogeneity and variable severity of the VHL phenotype, and should be considered, as a possible event when evaluating sporadic cases of VHL or patients with isolated VHL-related tumors. Hum Mutat 15:114, 2000.

Adult↗
PubMed1999

Chemotherapy for brain stem gliomas.

Approximately 80% of tumors arising in the brain stem are diffuse intrinsic lesions. Patients typically present with a short duration of symptoms and signs with significant neurological impairment. Imaging findings are typical, and biopsy is not usually necessary to make a diagnosis. Standard treatment consists of radiotherapy alone. Although the majority of patients will show a significant improvement in neurological status following such treatment, the prognosis is very poor. The median time to disease progression is of the order of 5-6 months, the median survival time less than 1 year, and survival at 2 years and beyond, less than 10%. Over the last 10-15 years, numerous studies have been undertaken in an attempt to develop more effective treatment for children with diffuse intrinsic brain stem tumors. Using a hyperfractionated (twice-daily) schedule, doses of radiotherapy as high as 78 Gy have been given without success. Other approaches use chemotherapy combined with radiotherapy in a variety of different ways, including up-front, concurrent, and adjuvant chemotherapy, and high-dose chemotherapy with rescue. The results of these studies using chemotherapy, as well as other approaches using other systemic agents, are reviewed in detail.

Antineoplastic Agents↗
PubMed1999

Liver tumours.

Primary hepatic tumours in children represent an heterogeneous group of neoplasms. Malignant tumours are more common (60% of primary liver tumours), but account for only 1.2-5% of all paediatric neoplasms. There are two main types of malignant tumour, those of epithelial origin, hepatoblastoma (HB) and hepatocellular carcinoma (HCC), and the rarer mesenchymal tumours, e.g. rhabdomyosarcoma and undifferentiated sarcoma, (Weinberg AG, Finegold, MJ. Primary hepatic tumours of childhood. Hum Pathol 1983, 14, 512-532). Vascular tumours e.g. haemangioendotheliomas are the most common of the benign tumours followed by mesenchymal hamartoma and the rare hepatic adenoma and focal nodular hyperplasia. This article will concentrate on the malignant epithelial tumours.

Carcinoma, Hepatocellular↗
PubMed1999

Spontaneous partial regression of low-grade glioma in children with neurofibromatosis-1: a real possibility.

At the age of 41 and 31 months, respectively, a boy and a girl affected by neurofibromatosis-1 were diagnosed with a visual pathway glioma during surveillance contrast-enhanced head magnetic resonance imaging (MRI). In the first child, the initial MRI showed that the entire optic chiasm, the intracranial tract of the left optic nerve, and hypothalamus were grossly enlarged and enhanced in the post-gadolinium T1-weighted images. Ten months later, the hypothalamic component of the lesion had regressed markedly and there were no more areas of contrast enhancement. In the second child, the initial MRI showed that the optic chiasm, the right optic tract, and geniculate body were enlarged and enhanced after gadolinium injection. At 6-month follow-up, the MRI showed that the right optic tract and the anterior aspect of the optic chiasm decreased in size and the contrast enhancement of the entire lesion was reduced dramatically. These findings, as indicated by other similar reports, confirm that spontaneous regression of visual pathway glioma is a rare but real possibility in children with neurofibromatosis-1. Therefore, clinicians need to be aware of visual pathway glioma's erratic behavior in children with neurofibromatosis-1 with special attention given to the importance of a very conservative attitude toward any type of treatment for such patients.

Child, Preschool↗
PubMed1999

Medulloblastoma with extensive nodularity: a variant with favorable prognosis.

OBJECT: Some medulloblastomas (MBs) are characterized by extreme nodularity and intranodular nuclear uniformity in a fine fibrillary background. These lesions have also been designated as "cerebellar neuroblastoma." Although numerous reports have been published in which their morphological features have been investigated, only a few studies have been focused on their neuroradiological appearance, biological behavior, and response to therapy. The goal of this study was to gather more information about these lesions. METHODS: The authors present 11 cases of MB with extensive nodularity. Five patients were boys and six were girls; all but one were 24 months of age or younger at diagnosis. Magnetic resonance imaging disclosed a peculiar grapelike architecture in eight cases. Surgical tumor removal was complete in nine cases and partial in one. In the other case a biopsy sample of the tumor was obtained after a preoperative course of chemotherapy. After surgery, two children were treated with radiotherapy alone and one with craniospinal irradiation followed by systemic chemotherapy. Eight patients were treated with chemotherapy only. All the patients in the study are presently alive with a median follow up of 66 months. Eight patients (73%) are in complete remission at 35 to 156 months. Three patients treated with chemotherapy alone postsurgery relapsed; however, all underwent successful retreatment (two with craniospinal irradiation and one with further surgery plus high-dose chemotherapy) and are in complete remission. A review of the literature revealed that patients in 11 of 12 reported cases were younger than 3 years of age and that seven of eight in whom follow-up information was available were alive and well, with survival times ranging from 6 to 84 months. CONCLUSIONS: Medulloblastomas with extensive nodularity represent a variant that is characterized by: 1) occurrence in very young children; 2) a peculiar grapelike appearance on neuroimaging; and 3) an apparently favorable outcome.

Cerebellar Neoplasms↗
PubMed1998

Cytogenetic analysis of hepatoblastoma: hypothesis of cytogenetic evolution in such tumors and results of a multicentric study.

Hepatoblastoma is a rare pediatric malignant tumor of the liver. Previous cytogenetic reports are sporadic. We karyotyped nine consecutive hepatoblastomas from the Italian centers participating in a multicentric study on hepatic tumors (SIOPEL 1). Six cases showed abnormal karyotypes. The most common abnormalities were trisomies of chromosomes 2 and 20. Four cases showed abnormalities of chromosome 1. On the basis of findings, we speculate the possibility of a cytogenetic evolutive pattern of hepatoblastomas.

Child, Preschool↗
PubMed1998

Intracranial ependymomas in children: a critical review of prognostic factors and a plea for cooperation.

BACKGROUND: Current controversies in pediatric intracranial ependymoma include histologic categorization and management. Most of our knowledge of this disease comes from single-institution reports. METHODS: A literature search was done, covering the period 1976-1996. The aim of this review is to analyze the prognostic factors reported in the literature over the last 20 years. RESULTS: Forty-five series were reviewed, including more than 1,400 children. The largest series reported on 92 patients, and the accrual rate ranged from 0.32-12 patients per year. None of the prognostic factors reported achieved a consensus throughout the different series. Histology remains a major issue, and the range in the incidence of anaplastic ependymo mas (7-89%) highlights the difficulty in agreeing on a histological grading system. The role of surgery on the outcome seems to be determinant. Recent series based on homogeneous imaging-documented extents of resection strongly support the benefit of postoperative radiotherapy. The lack of a proven, effective chemotherapy regimen precludes its use except in prospective pilot studies. CONCLUSIONS: Limited information is available from single-institution reports in ependymoma. Only large national or international studies can provide enough information to allow a multivariate analysis of the prognostic factors, and thus lead to new therapeutic proposals.

Brain Neoplasms↗
PubMed1998

The guanine triphosphatase (GTPase) activating protein (GAP)-related domain of the neurofibromatosis type 1 gene is not mutated in neural crest-derived sporadic tumours.

We conducted a mutation analysis of the most conserved region of the neurofibromatosis type 1 (NF1) gene, the guanine triphosphatase (GTPase) activating protein (GAP)-related domain (NF1 GRD), to which the function of tumour suppressor is attributed. Sixty primary neuroectodermal tumours were analysed. The rationale for the study was based on the likelihood of finding structural alterations resulting in loss of function of this region in tumours of neuroepithelial tissues, where the activity of neurofibromin seems to be crucial in regulating the mechanisms of signal transduction and cell transformation mediated by p21 ras. Following analysis of the whole NF1 GRD sequence, no mutations were identified in the tumours analysed. We conclude that the loss of NF1 gene tumour suppressor function, that might lead or contribute to the development of malignancies in neuroectodermal tissues, is not due to structural abnormalities of the region of the gene which interacts with p21 ras.

Base Sequence↗
PubMed1998

Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology.

Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and both its biological features and its prognostic behavior are still under investigation. DNA content and proliferative activity of the tumor have been considered as biological parameters related to the tumor's aggressiveness. The present study attempts to investigate the possible association between histologic subtype, DNA content, and proliferative indices in HB. DNA content and the proportion of cells in the S-phase were assessed by flow cytometry in 34 cases of HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin-fixed, paraffin-embedded archival samples. The proliferative cell nuclear antigen (PCNA) labeling index was also evaluated by immunohistochemistry, and both the flow cytometry (FC) and the immunohistochemical data were correlated with tumor pathology. A significant association was found between histological type, DNA content and the percentage of cells in the S-phase, with aneuploidy and the highest proportions of S-phase cells significantly associated with embryonal tumors. The PCNA labeling index was found to be significantly higher in embryonal than in fetal phenotype. The biological heterogeneity of HB is Confirmed by the different nuclear content of the fetal (diploid) and embryonal (aneuploid) epithelial components of the tumor, also ruling out the likelihood of fetal (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since the highly proliferative neoplastic clones (i.e., embryonal) are thought to be more sensitive to antimitotic drugs, further studies are indicated to determine the relationship between ploidy, proliferative indices and chemoresponsiveness.

Child↗
PubMed1997

Diencephalic syndrome and disseminated juvenile pilocytic astrocytomas of the hypothalamic-optic chiasm region.

BACKGROUND: Diencephalic syndrome (DS) is a complex of signs and symptoms related to hypothalamic dysfunction; its main features are emaciation, despite a normal or slightly diminished caloric intake, and an alert appearance. DS has been almost exclusively described in association with space-occupying lesions of the hypothalamic-optic chiasm region, mainly juvenile pilocytic astrocytoma (JPA). A systematic diagnostic approach, including contrast-enhanced magnetic resonance imaging (MRI) of the child's head, is rapidly expanding our knowledge of this syndrome. METHODS: The MRI findings for three children affected by DS associated with biopsy-proven JPA, consecutively referred to the Pediatric Neuro-Oncology Program of the Department of Pediatrics at the University of Padua between September 1991 and January 1996, are presented in this article. The children were boys, ages 6, 7, and 18 months, respectively. RESULTS: In all three patients, the initial contrast-enhancing MRIs of the head showed evidence of tumor dissemination. This finding prompted a study of the spine, which in turn showed tumor deposits in all three subjects. Among the 43 patients younger than 16 years with low grade astroctyoma who consecutively entered the Neuro-Oncology Program during the study period, these 3 patients were the only ones who had disseminated tumors. CONCLUSIONS: In this study, the hypothesis was formulated that DS and disseminated hypothalamic-optic chiasm JPA tend to be more commonly associated than previously stated. This study suggests that the initial contrast-enhanced MRI of the head of a child affected by DS and hypothalamic JPA must be looked at carefully for evidence of tumor dissemination, and that the spine must also be examined if the findings are positive.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Analyses of prognostic factors in a retrospective review of 92 children with ependymoma: Italian Pediatric Neuro-oncology Group.

The principal aim of this report is to present the results of multivariate analyses conducted to identify clinical prognostic factors in 92 children aged < 16 years with ependymoma (EPD) retrospectively collected in seven Italian centres. They were treated over a 16-year period (1977-1993). Treatment modalities varied. Surgery and radiotherapy (RT) was the "gold standard" management method for the majority of these children. Only in the late 1980s did some of them receive chemotherapy (CT), mainly with vincristine, lomustine (CCNU) and prednisone. The median follow-up of the entire study population is 36 months (average 43 months; range 12 to 214 months). The 10-year overall (OS) and the progression-free survival (PFS) of the study population were 55.5% (CI 41.4-69.4%) and 34.7% (CI 21.4-47.8%), respectively. Age (< 5 years; > 5 years), sex, site (infratentorial vs. supratentorial), histology (anaplastic/malignant vs. non-anaplastic/non-malignant), type of resection (complete vs. incomplete); use and fields of RT, and of CT employed were entered in a multivariate regression model to test their impact on OS and PFS. On univariate analysis, radical surgery, the use of RT and age more than 5 years at the time of diagnosis achieved statistically significant values for predicting long-term OS and PFS. Histology reached marginal statistical significance but only for PFS. When those variables were entered in a multivariate analysis only radical resection (P = 0.00142 and 0.0001) resulted a significant factor for predicting long-term OS and PFS, while the use of RT reached a marginal statistical significance, but only for PFS (P = 0.05). Children who had the tumour completely resected did significantly better than all the others who had less than a complete resection, with a 10-year OS and PFS for the two groups of patients of 69.8% (CI 53-86.5%) and 57.2% (CI 40.3-75%) and of 32.5% (CI 8.5-57.6%) and 11.1% (0-24.4%), respectively. These findings suggest that, for childhood EPD, radical resection should be pursued as much as reasonably possible. Thus, it seems justified proposing for future trials, patient stratification by entity of surgical resection.

Adolescent↗
PubMed1996

Cytogenetics of pediatric central nervous system tumors.

A cytogenetic analysis was performed on short-term cultures of 43 previously untreated childhood central nervous system neoplasms of various histology. The cells were obtained from pediatric patients, none of whom had received therapy before karyotypic evaluation. Successful chromosome studies were performed on 24 tumors. The most commonly detected structural abnormalities involved chromosomes 1 and 17. Other structural chromosome abnormalities involved chromosomes 3, 6, 8, 9, 11, 12, and 20.

Adolescent↗
PubMed1996

Nodular regenerative hyperplasia of the liver: description of two cases.

Nodular regenerative hyperplasia (NRH) of the liver is a condition of unknown origin, rarely occurring in children, usually accidentally discovered, described in association with a variety of clinical conditions and drugs. Confusion with other types of hepatic masses may pose a problem and for this reason NRH is considered a "tumor-like lesion." Histologically it consists of single or multiple regenerative foci. Hepatic failure and rupture of the liver have been rarely described as complications in adults, and not in children, and malignant transformation has not been demonstrated. Neither surgical removal nor other treatment is needed. These features are described as they were found in two patients we encountered.

Biopsy↗
PubMed1996

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors.

Primitive neuroectodermal tumors (PNETs) of the central nervous system, including medulloblastomas (PNET/MB), are the most common malignant brain tumor of childhood. These tumors often express proteins characteristic of glial differentiation (glial fibrillary acidic protein, GFAP), neuronal differentiation (neurofilament proteins, NFPs), and/or photoreceptor differentiation (retinal-S antigen). To identify biological factors of prognostic significance in PNETs, the expression of glial, neuronal, or photoreceptor antigens was evaluated in the tumor specimens of 86 patients with PNETs by immunohistochemistry after microwave antigen enhancement. Patterns of differentiation were then compared with patient relapse-free survival. Multivariate analysis of PNET immunohistochemistry and clinical variables indicated GFAP expression conferred a 6.7-fold greater risk of relapse than tumors that did not express GFAP or NFPs. Increased risk of relapse was directly related to the amount of GFAP expression. Tumors exhibiting clumps or sheets of GFAP-staining cells were associated with a 3.0-fold increased risk of relapse compared with tumors that did not express GFAP, irrespective of immunohistochemical evidence of other differentiation, while scattered GFAP staining was not associated with increased risk of relapse. These findings indicate that expression of GFAP in PNETs has prognostic power comparable with the most significant clinical factors currently used to predict clinical outcome.

Adolescent↗
PubMed1996

Neurofibromatosis type 1 and type I Chiari malformation: an unusual association.

We report an 11-year-old boy with neurofibromatosis type 1 (NF1) and asymptomatic type I Chiari malformation. This association may be considered a pure coincidence, due to the relative frequency of the two conditions, but recent reports describing the same association suggest that type I Chiari malformation probably should be added to the list of abnormalities of the central nervous system reported in patients affected by NF1.

Arnold-Chiari Malformation↗