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Felice Giangaspero

Publications and source records attributed to Felice Giangaspero.

31 records · Page 2Linked to original sources
PubMed2004

REN(KCTD11) is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma.

Hedgehog signaling is suggested to be a major oncogenic pathway in medulloblastoma, which arises from aberrant development of cerebellar granule progenitors. Allelic loss of chromosome 17p has also been described as the most frequent genetic defect in this human neoplasia. This observation raises the question of a possible interplay between 17p deletion and the Hedgehog tumorigenic pathway. Here, we identify the human orthologue of mouse REN(KCTD11), previously reported to be expressed in differentiating and low proliferating neuroblasts. Human REN(KCTD11) maps to 17p13.2 and displays allelic deletion as well as significantly reduced expression in medulloblastoma. REN(KCTD11) inhibits medulloblastoma cell proliferation and colony formation in vitro and suppresses xenograft tumor growth in vivo. REN(KCTD11) seems to inhibit medulloblastoma growth by negatively regulating the Hedgehog pathway because it antagonizes the Gli-mediated transactivation of Hedgehog target genes, by affecting Gli1 nuclear transfer, and its growth inhibitory activity is impaired by Gli1 inactivation. Therefore, we identify REN(KCTD11) as a suppressor of Hedgehog signaling and suggest that its inactivation might lead to a deregulation of the tumor-promoting Hedgehog pathway in medulloblastoma.

Alleles↗
PubMed2004

Solitary fibrous tumors of the meninges: report of four cases and literature review.

Central nervous system solitary fibrous tumors are a new pathological entity. To our knowledge, only 60 meningeal solitary fibrous tumors both in the spinal cord and in the brain have been described in the literature. The 56 previously reported cases of meningeal solitary fibrous tumors are critically reviewed. In addition, we report four new cases of solitary fibrous tumors of the meninges. There is a slight male prepoderance. Meningeal solitary fibrous tumors show a tendency to arise in the posterior fossa (26%) and spine (25%). The treatment was mainly total surgical excision. Radiotherapy was given only to four patients with tumors involving the cerebral parenchyma. Sporadic cases of recurrence and distant metastasis have been reported. The prognosis of meningeal solitary fibrous tumors is still unknown because the follow-up of the reported cases is short. It is probable that cases of solitary fibrous tumors of the meninges have been misdiagnosed as other tumors in the past. The best management of these tumors seems to be total surgical excision whenever possible. It is important that every new case of meningeal SFT be reported to throw light on this particular tumor and to affirm its status as a clinicopathological entity.

Adult↗
PubMed2004

Hyperfractionated radiotherapy and chemotherapy for childhood ependymoma: final results of the first prospective AIEOP (Associazione Italiana di Ematologia-Oncologia Pediatrica) study.

PURPOSE: A postsurgical "stage-based" protocol for ependymoma was designed. METHODS AND MATERIALS: Children were given: (1) focal hyperfractionated radiotherapy (HFRT) if with no evidence of disease (NED), or (2) 4 courses with VEC followed by HFRT for residual disease (ED). HFRT dose was 70.4 Gy (1.1 Gy/fraction b.i.d.); VEC consisted of VCR 1.5 mg/m2 1/w, VP16 100 mg/m2/day x 3, CTX 3 g/m2 d 1. When feasible, second-look surgery was recommended. RESULTS: Sixty-three consecutive children were enrolled: 46 NED, 17 ED; the tumor was infratentorial in 47 and supratentorial in 16, with spinal metastasis in 1. Of NED patients, 35 of 46 have been treated with HFRT; 8 received conventionally fractionated radiotherapy, and 3 received no treatment. Of the 17 ED patients, 9 received VEC + HFRT; violations due to postsurgical morbidity were as follows: HFRT only (2), conventionally fractionated radiotherapy (3) + VEC (2), and no therapy (1). Objective responses to VEC were seen in 54%; objective responses to RT were seen in 75%. Overall survival and progression-free survival at 5 years for all 63 children were 75% and 56%, respectively; for the NED subgroup, 82% and 65%; and for the ED subgroup, 61% and 35%, respectively. All histologies were centrally reviewed. At multivariate analysis, grading, age, and site proved significant for prognosis. CONCLUSIONS: HFRT, despite the high total dose adopted, did not change the prognosis of childhood ependymoma as compared to historical series: New radiotherapeutic approaches are needed to improve local control. Future ependymoma strategies should consider grading when stratifying treatment indications.

Adolescent↗
PubMed2004

Emerging tumor entities and variants of CNS neoplasms.

Since the appearance in 2000 of the World Health Organization (WHO) classification for central nervous system (CNS) neoplasms, numerous descriptions of new entities or variants have appeared in the literature. In the group of neuronal and mixed glioneuronal neoplasms are lesions with distinctive morphological features that are still not included in a precise classification, including extraventricular neurocytoma, papillary glioneuronal tumor, rosette-forming glioneuronal of the fourth ventricle, glioneuronal with neuropil-like rosette, and DNT-like tumor of the septum pellucidum. The glioneuronal tumor with neuropil-like rosette and oligodendroglioma with neurocytic differentiation represent morphological variants of genetically proven diffuse gliomas. The lipoastrocytoma and the pilomixoid astrocytoma enlarge the group of astrocytic lesions. Rare, low-grade gliomas of the spinal cord with extensive leptomeningeal dissemination associated with unusual neuroimaging are described. The chordoid glioma of the third ventricle and the papillary tumor of the pineal region seem to be correlated by a common histogenesis from the specialized ependyma of the subcommissural organ. An embryonal tumor with neuropil and true rosettes combining features of neuroblastoma and ependymoblastoma is discussed. These new, recently described lesions indicate that the complex morphologic spectrum of CNS tumors is far from being completely delineated.

Central Nervous System Neoplasms↗
PubMed2004

Genetic and expression profiles of cerebellar liponeurocytomas.

Cerebellar liponeurocytoma, a rare, newly identified CNS neoplasm of adults, is characterized by advanced neuronal/neurocytic and focal lipomatous differentiation, low proliferative potential and a favorable clinical prognosis. Despite the different age distribution and benign biological behavior, the cerebellar liponeurocytoma shares several features with the cerebellar medulloblastoma, which may include an origin from the periventricular matrix of the fourth ventricle or the external granular layer of the cerebellum. To establish the genetic profile of cerebellar liponeurocytomas, we have formed an international consortium and collected tumor samples from 20 patients. DNA sequencing revealed TP53 missense mutations in 4 (20%) of 20 cerebellar liponeurocytomas, a frequency higher than in medulloblastomas. There was no case with PTCH, APC, or beta-catenin mutations, each of which may be present in subsets of medulloblastomas. Isochromosome 17q, a genetic hallmark of classic medulloblastomas, was not observed in any of the cases investigated by FISH analysis. cDNA array analyses were carried out on 4 cerebellar liponeurocytomas, 4 central neurocytomas, and 4 classic medulloblastomas. Cluster analysis of the cDNA expression data of 1176 genes grouped cerebellar liponeurocytomas close to central neurocytomas, but distinct from medulloblastomas. These results suggest cerebellar liponeurocytoma as a distinct tumor entity that is genetically different from medulloblastoma. Furthermore, the cDNA expression array data suggest a relationship to central neurocytomas, but the presence of TP53 mutations, which are absent in central neurocytomas, suggests that their genetic pathways are different.

Adult↗
PubMed2003

Familial gliomas. Analysis of six families with cerebral gliomas and without other inheritable syndromes.

Although a familial tendency to develop brain tumors in the absence of well-recognized hereditary disorders is an important issue, it has been rarely reported. Studies of the familial occurrence of gliomas have yielded conflicting results. This phenomenon may be imputable to chance or environmental or hereditary factors. Furthermore, epidemiological and genetic investigations are fundamental to evidence of whether hereditary factors are active in the development of these tumors. We describe a group of six families, in each of which more than one member had glioma, and discuss the probable mechanisms of oncogenesis in familial tumors in light of the pertinent literature.

Adolescent↗
PubMed2003

Low-grade gliomas and leptomeningeal dissemination: a poorly understood phenomenon.

DISCUSSION: The leptomeningeal dissemination (LMD) of low-grade gliomas (LGGs) is reported in clinical neuro-oncology practice more and more frequently. It is estimated that 5% of all childhood LGGs present LMD at diagnosis and 7-10% at the time of progression. LMD has been reported in association with almost all the known subtypes of LGGs. Furthermore, "unusual " LGGs can be encountered among slow-growing brain neoplasm capable of LMD, which cannot comfortably be included in the present WHO brain tumour classification. The biological, genetic and clinical characteristics that seem to favour LMD are far from being understood. Similarly, the clinical profile of those children with disseminated LGGs has not yet been firmly established. Young, non-neurofibromatosis type 1 boys with large hypothalamic-chiasmatic pilocytic astrocytomas seem to be at increased risk of LMD. The neuroradiological appearance of LMD in childhood LGGs is similar to that observed in malignant tumours, except for those cases characterised by multiple superficial non-enhancing cystic lesions, which seem to be almost exclusively associated with a type of slow-growing not yet fully identified brain stem or spinal tumour. No firm guidelines for the treatment of these diseases are yet available, mostly due to the rarity of this condition and the existing uncertainties regarding their natural clinical history. CONCLUSION: The evidence of LMD in children with LGGs does not seem to have a negative impact on patients' long-term outcome.

Brain Neoplasms↗
PubMed2003

Atypical teratoid/rhabdoid tumors and choroid plexus tumors: when genetics "surprise" pathology.

Atypical teratoid/rhabdoid tumor (ATRT) and choroid plexus tumors (CPT) represent, so far, 2 well defined types of CNS neoplasm on the basis of their histological features and clinical presentation (10). While CPTs are intraventricular epithelial tumors arising from choroid plexus epithelium, the cellular origin of ATRTs is still unknown. Inactivating mutations of the hSNF5/INI-1 gene located in the chromosomal region 22q11.2 are regarded as a crucial step in the molecular pathogenesis of ATRTs; the genetic changes associated with CPTs are largely unknown. However, the recent finding of inactivation of hSNF5/INI-1 in choroid plexus carcinomas and papillomas (9, 18) points to a closer relationship between these 2 entities. This is supported by the occurence of choroid plexus carcinomas (CPC) in the setting of families with rhabdoid predisposition syndrome (RPS), (19) caused by germ line inactivation of the INI1 gene.

Central Nervous System Neoplasms↗
PubMed2002

Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy.

Poly(A(+)) RNA was extracted from the temporal lobe (TL) of medically intractable epileptic patients which underwent surgical TL resection. Injection of this mRNA into Xenopus oocytes led to the expression of ionotropic receptors for gamma-aminobutyric acid (GABA), kainate (KAI) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Membrane currents elicited by GABA inverted polarity at -15 mV, close to the oocyte's chloride equilibrium potential, were inhibited by bicuculline, and were potentiated by pentobarbital and flunitrazepam. These basic characteristics were also displayed by GABA currents elicited in oocytes injected with mRNAs isolated from human TL glioma (TLG) or from mouse TL. However, the GABA receptors expressed by the epileptic TL mRNA exhibited some unusual properties, consisting in a rapid current run-down after repetitive GABA applications and a large EC(50) (125 microM). AMPA alone evoked very small or nil currents, whereas KAI induced larger currents. Nevertheless, upon cyclothiazide treatment, AMPA elicited substantial currents that, like the KAI currents, were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Furthermore, the glutamate receptor 5 (GluR5) agonist, ATPA, failed to evoke an obvious current although both RT-PCR and Western blot analyses showed GluR5 expression in the epileptic TL. Oocytes injected with mouse TL or human TLG mRNAs generated KAI and AMPA currents similar to those evoked in oocytes injected with epileptic TL mRNA but, in contrast to these, the mouse TL and human TLG oocytes were also responsive to ATPA. Our findings are in accord with the concept that both a depression of GABA inhibition and a dysfunction of the KAI-receptor system maintain a high neuronal excitability that results in epileptic seizures.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2002

Spinal low-grade neoplasms with extensive leptomeningeal dissemination in children.

OBJECTIVE: The aim of this study is to re-appraise paediatric leptomeningeal disseminated spinal low-grade neoplasms putting forward the hypothesis that these tumours may represent a possible distinctive clinico-pathological entity. CASE REPORT: Three children affected by these rare neoplasms are reported, 2 boys and 1 girl aged 40 months, 7 and 12 years respectively. RESULTS: Despite treatment, 2 died at 9 months and 9 years, while 1 has survived with stable disease at 24 months after diagnosis. Histologically, these tumours shared the generic histological appearance of low-grade neuroectodermal neoplasms, without any features that allowed them to be included in a specific classification niche. The magnetic resonance imaging of the leptomeningeal dissemination took the form of a thick, diffuse subarachnoidal enhancement involving the brain as well the spine in 2 patients; in 1 patient there was an extensive enhancement along the surface of the brain and of the spinal cord and multiple small cysts, creating the impression of a diffuse microcystic meningoencephalopathy. DISCUSSION: The patients described here and the similar ones found in the literature cannot be easily placed into the present WHO system of classification for central nervous system tumours.

Child↗
PubMedDate not supplied

Glioblastoma multiforme and breast cancer: report on 11 cases and clinico-pathological remarks.

The association between breast cancer and glioblastoma multiforme has not been amply analyzed in the literature. We describe 11 female patients with a diagnosis of glioblastoma multiforme who were treated when younger for breast cancer. We believe that this association is not due to chance but rather to genetic changes in hormone status and in particular to sex hormones. Another important point of view is represented by the chemotherapy treatment of breast cancer, which could have a carcinogenic effect and explain the growth of glioblastoma. This consideration, in our opinion, is important, because more effort should be made to understand the pathogenesis of glioblastoma multiforme and to improve the therapeutic approaches.

Adult↗
PubMedDate not supplied

Treatment of glioblastoma multiforme in elderly patients. Clinico-therapeutic remarks in 22 patients older than 80 years.

We report our remarks on 22 patients, 80 years of age and older, who were treated for glioblastoma multiforme. The 16 patients who underwent a multimodality treatment (surgery + radiotherapy + chemotherapy) had an average survival of 16.7 months versus the 5.8 months of the 8 patients treated with biopsy followed by radiotherapy and/or chemotherapy (log-rank test, P < 0.001). Moreover, we point out the importance of MGMT hypermethylation as a significant prognostic factor: the 9 patients with nonmethylated MGMT had a mean survival of 7.7 months vs. 17.9 months of the 13 patients with the MGMT promoter methylated (log-rank test, P = 0.0006). Several studies have pointed out age as an important negative factor for the outcome of elderly patients affected by glioblastoma multiforme. Elderly patients with a diagnosis of glioblastoma multiforme are thus generally excluded from clinical trials of treatment for the neoplasm, because it is a common opinion that the prognosis for such patients is particularly poor. On the contrary, according to our clinical and surgical experience, we firmly believe that patients older than 80 years with a histologically proven diagnosis of glioblastoma multiforme and in good health conditions (Karnofsky performance status >60) should be treated in the same way as younger patients.

Age Factors↗