Biomedical subjects

P Cavalla

Publications and source records attributed to P Cavalla.

33 records · Page 2Linked to original sources

PubMed1996

Bcl-2 distribution in neuroepithelial tumors: an immunohistochemical study.

Bcl-2 proto-oncogene prevents apoptosis in many conditions. First detected in lymphomas, it has been also described in non-lymphoid tissues. The immunohistochemical distribution of bcl-2 protein in 100 neuroepithelial tumors is presented. Bcl-2 was positive in some neurons of normal nervous tissue, in reactive astrocytes and variably in all neuroepithelial tumor. The reaction product was either diffuse or granular, due to bcl-21 protein localization on cytoplasmic, nuclear and mitochondrial membranes. The positivity was high in medulloblastomas and in astrocytic tumors. In the latter, the strongest staining was found in cells retaining the astrocytic aspect. Oligodendroglial cells were minimally stained. No correlation of bcl-2 staining with survival was found in each tumor type. The interpretation of the results is based on the one side on the constitutive role played by bcl-2 in the nervous tissue and its neoplastic derivatives. On the other side, in tumors bcl-2 acts by preventing tumor cells from undergoing apoptosis. BCl-2 expression in brain tumors, therefore, receives a dual interpretation. For this reason and for the lacking of correlation with survival, bcl-2 expression cannot be regarded as a prognostic factor.

Astrocytoma↗

PubMed1996

Reactive astrogliosis of the spinal cord in amyotrophic lateral sclerosis.

Many observations have been carried out on astrogliosis in the cerebral cortex in amyotrophic lateral sclerosis (ALS), whereas little attention has been paid to astrogliosis in the spinal cord. Twenty autopsy cases of sporadic, common form of ALS have been studied. Spinal cords have been examined at the cervical, thoracic and lumbar levels by histological methods and immunohistochemistry for GFAP, Vimentin, Tau-protein, Neurofilaments, PCNA. A gliosis was found in the ventral horns, in dorsal horns and at the transition between gray matter and anterior and lateral funiculi, especially close to laminae VII, VI and V as being due to secondary gliosis. The findings cannot be interpreted on the only basis of the substitutive role of reacting glia. The proposed pathogenetic mechanisms of ALS are evaluated as possible responsible stimuli; the coincidence of the distribution of reactive astrocytes with the entering points of the corticospinal tracts into the gray matter is considered of primary importance. Of special interest are reactive astrocytes at the transition between laminae VII, VI and V and the lateral funiculus, where dystrophic neurites are known to concentrate.

Adult↗

PubMed1995

Apoptosis and cell proliferation in human neuroepithelial tumors.

Apoptosis and cell proliferation were studied in 180 human neuroepithelial tumors (30 medulloblastomas, 30 intracranial ependymomas, 30 oligodendrogliomas and 90 astrocytic tumors, including 30 astrocytomas, 30 anaplastic astrocytomas and 30 glioblastomas). Apoptotic nuclei were detected by morphology and in situ end-labeling (ISEL) of DNA breaks. The frequency of apoptotic nuclei varied from oncotype to oncotype and their distribution in each oncotype was uneven. An apoptotic index (AI) was calculated; this was high in malignant tumors and in tumors of embryonal origin and lower in tumors of the glial series. The AI/mitotic index (MI) ratio was lower in malignant tumors and higher in benign tumors, suggesting a relationship between apoptosis and cell proliferation. There was no significant correlation of either AI or AI/MI ratio with either labeling index (LI) of Ki-67 clone MIB-1 or with survival. A trends towards low AI/MI ratio in tumors with high LI and short survival was observed. Apoptosis expresses cell loss in tumors, but it did not appear to be a prognostic factor.

Apoptosis↗

PubMed1995

Mutations and immunohistochemistry of p53 and proliferation markers in astrocytic tumors of childhood.

Thirty cases of hemispheric astrocytic tumors of childhood, consisting of 11 pilocytic astrocytomas, 2 fibrillary astrocytomas, 9 anaplastic astrocytomas, and 8 glioblastomas, were studied for the presence of p53 mutations and for immunohistochemical demonstrations of p53 and proliferation markers PCNA and Ki-67 MIB-1. The study was performed using polymerase chain reaction (PCR)-assisted single-strand conformation polymorphism analysis of exons 5-8 and direct sequence analysis of PCR products. For immunohistochemistry, DO1 and PAb 1801 were used. No mutation and no positivity for p53 protein were found in pilocytic astrocytomas. Mutations (at codons 144, 202, and 245) were found in 2 out of 8 glioblastomas and in 1 out of 9 anaplastic astrocytomas, whereas positive staining was found in 11 out of 17 malignant gliomas. Cases with mutations showed the highest p53 labeling index and also PCNA and MIB-1 labeling indices. The negative results in pilocytic astrocytomas are in line with the benign course of these tumors, whereas for malignant gliomas no difference seems to exist in comparison with adult cases.

Adolescent↗

PubMed1994

bcl-2 protein expression in aged brain and neurodegenerative diseases.

The proto-oncogene bcl-2 is involved in the regulation of cell death and is able to block apoptosis in neurones through reduced generation of reactive oxygen species (ROS). We have studied the immunohistochemical expression of bcl-2 protein in the aged brain and in various human neurodegenerative diseases. In all cases, bcl-2 was strongly enriched within lipofuscin and autophagic vacuoles of neurones, glial and vascular cells. Our data show that accumulation of bcl-2 is not disease-specific and represents a general cellular response which accompanies the increased formation of lipofuscin. Since oxidative stress is directly involved in lipofuscinogenesis, accumulation of bcl-2 may reflect a mechanism for counterbalancing ROS-mediated damage, or it might represent the impairment of bcl-2-dependent protection from ROS.

Aging↗

PubMed1994

Tumor cell proliferation and apoptosis in medulloblastoma.

The distribution of proliferating cell nuclear antigen (PCNA)-(clone PC 10)- and Ki-67-(clone MIB-1)-positive nuclei was investigated in 60 medulloblastomas of childhood. Although the labeling index of the two markers did not coincide, both showed a wide range of parallel variations. The percentage of positive nuclei was similar in both classic and desmoplastic tumors. A variable proliferation capacity was found in the different tumor structures. Areas with neuronal and glial differentiation showed very few positive nuclei; these were very abundant in the infiltration areas, and along penetrating vessels from subarachnoidal growths. Pale islands were negative or positive only in their peripheral part. Large-cell areas were richer in positive nuclei than classic ones, accounting for their more malignant character. Hyperchromatic round nuclei, not belonging to necrotic foci and called lymphocyte-like nuclei, differently interpreted in the past, were variably found in every case. They are known, from previous experience, to stain orange with Acridine Orange fluorochroming, like single-stranded DNA. They were not easily distinguishable from mitoses and were stained by in situ end-labeling of DNA strand breaks, as demonstrated by incorporation of labeled nucleotides. They were regarded as possible apoptotic nuclei, representing either a peculiar type of cell death or the preservation of the cell deletion capacity, typical of the embryonal tissue of origin.

Adolescent↗

PubMed1994

Intracranial dissemination of pituitary adenoma. Case report and review of the literature.

Leptomeningeal dissemination of pituitary adenoma is a very rare occurrence. The present report describes the case of a 28 year old man with a nonfunctioning pituitary adenoma which was operated on and irradiated. Eight years later, the patient developed Cushing's syndrome and multiple leptomeningeal masses were revealed by brain CT and MNR. The diagnosis was ACTH-cell adenoma, without malignant histological signs. The growth fraction of the tumor, detected by means of the immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA), was 5.45% of cells; this figure is higher than that reported for non-recurrent pituitary adenomas. From a review of the reported cases, the possibility of predicting late malignant behaviour is discussed. The microscopic aspect has no prognostic value, since metastasizing cases are not overtly malignant in a histological or cytological sense. The application of methods aimed at detecting the growth fraction of the tumor may prove useful in the early identification of aggressive pituitary tumors.

Adenoma, Chromophobe↗

PubMed1994

A study of apoptosis in normal and pathologic nervous tissue after in situ end-labeling of DNA strand breaks.

Programmed cell death (PCD) via apoptosis is characterized by nuclear pyknosis and fragmentation, and biochemically by oligonucleosomal cleavage of DNA. Apoptosis occurs in the developing nervous system, whereas its role in neurodegenerative diseases is still debated. Recognition of apoptotic cells has recently been facilitated by in situ end-labeling (ISEL) techniques which identify DNA strand breaks through incorporation of labeled nucleotides. We have applied two ISEL assays to physiological and pathological conditions affecting the nervous system in which PCD is likely to occur. Terminal transferase assay was more sensitive than DNA polymerase assay and allowed the recognition of a larger number of cells than conventional histology. Apoptotic cells were readily found in the developing spinal cord and dorsal root ganglia. Medulloblastomas, gliomas, brain lymphomas and metastases showed abundant apoptotic cells either isolated or grouped in small foci. Labeling was also found in cells without a clearcut apoptotic morphology. Apoptotic cells were not found in Alzheimer's disease, amyotrophic lateral sclerosis and human and mouse prionic encephalopathies. Our results show that ISEL is a useful technique for demonstrating apoptotic cells in nervous tissue during development and in brain tumors. Lack of staining in neurodegenerative diseases suggests that other types of PCD might be involved.

Animals↗

PubMed1994

Reactive cell proliferation and microglia following injury to the rat brain.

The non-astrocytic cells which proliferate in the rat brain after the induction of an area of necrosis have been characterized and counted by means of combined in vivo bromodeoxyuridine (BrdU) administration and immunohistochemical demonstration of glial fibrillary acid protein (GFAP), vimentin, Ricinus communis agglutinin 120 (RCA-1), Griffonia simplicifolia B4 isolectin (GSI-B4), keratan sulphate (KS), carbonic anhydrase C (CA.C), transferrin (TF) and ferritin. Two days after the injury, 7.5% of the proliferating cells were GFAP-positive reactive astrocytes, 5.7% were RCA-1-positive cells and 17.4% were GSI-B4-positive cells. Lectin-binding cells had the microscopic and ultrastructural aspects of microglia; they proliferated around the needle track and in the corpus callosum. Microglia represented a large fraction of the proliferating cells. Evidence is presented for the origin of at least a proportion of perilesional astrocytes and microglia from the periventricular matrix, and of microglia from blood precursors. Other non-proliferating microglia cells transiently appeared in the normal brain around the wound, in agreement with the existence of two different microglia cell populations reacting with different modalities to an area of necrosis.

Animals↗

PubMed1993

Immunohistochemistry of glial reaction after injury in the rat: double stainings and markers of cell proliferation.

The astrocytic reaction in the rat after brain injury has been studied immunohistochemically for intermediate filaments (GFAP and vimentin), also with double staining procedures, and for markers of proliferation (BrdU and PCNA). GFAP-positive reactive astrocytes appeared around the lesion, where they were vimentin-positive and at a distance. BrdU and PCNA showed a high labelling index around the wound at day 2 and scattered positive nuclei were also found at a distance in the ipsilateral side. BrdU-positive astrocytes represented a minor fraction of GFAP- and vimentin-positive astrocytes. The expression of vimentin persisted at least 15 days after the lesion. Our results could suggest that distant reactive astrocytes originate through hypertrophy while those close to lesion arise by hyperplasia from mature or immature glial cells. The hypothesis is formulated that cells of the periventricular matrix contribute to the post-traumatic proliferative activity.

Animals↗

PubMed1991

Relationship between glial reaction to a stab wound and tumor development after receiving transplacental ethylnitrosourea in the rat.

Fisher 344 rats born from mothers treated with ethylnitrosourea (ENU) 50 mg/kg intravenously were injured at the 1st and 2nd month of extrauterine life by a transcranial stab. The wound affected cerebral cortex, white matter and basal ganglia. The animals were killed 15 and 45 days and 5 months after injury and cell reaction was studied histologically and immunohistochemically. Bromodeoxyuridine (BrdUrd) was administered 1 h before sacrifice and the labeled cells were evaluated. In ENU-treated rats injured at 1 month of age only minor differences were found in comparison with injured controls. In ENU rats injured at 2 months of age and killed 15 days later, a higher number of BrdUrd-labeled cells was found in comparison with controls; 45 days after injury the cell reaction acquired the aspect of a microtumor, however, no microtumor unrelated with the needle track was present. In ENU rats killed 5 months after the injury, there was no difference between injured and not injured ENU-treated rats, as far as the aspect and the number of tumors were concerned. The tumor phenotype was, thus, anticipated by the cell response to trauma in ENU rats. The interpretation is that the additional cell division, in response to trauma, anticipate not only the phenotypic, but also the cell kinetics changes, as indicated by BrdUrd labeling.

Animals↗

PubMedDate not supplied

Prognostic factors in adult medulloblastoma. A clinico-pathologic study.

AIMS AND BACKGROUND: Medulloblastoma in adults is a rare tumor. The small number of cases in the reported series has not permitted a definite assessment of the prognostic role of clinical, pathologic and cell kinetics factors. The largest series of medulloblastoma in adults treated in a single institution is herein reported. METHODS: The clinical, therapeutic, pathologic and proliferation features of medulloblastoma in 44 adult patients (> 18 years) were analyzed retrospectively with regard to postoperative survival. The proliferation potential of each tumor was evaluated by the immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) and Ki-67, clone MIB-1, in paraffin sections. RESULTS: The overall 5- and 10-year survival rates were 40% and 35.6%, respectively. Significant factors in predicting a longer postoperative survival were: age < 37 years, decade of management (1977-1990), radiotherapy (50-55 Gy on the posterior fossa and 30-35 Gy on the spinal cord) and nuclear isomorphism. When corrected for adequacy of radiotreatment, desmoplastic type and differentiation were significantly correlated with a shorter survival. The PCNA-labelling index (LI) ranged from 34.5 to 82.2%, the MIB-1-LI ranged from 9.6 to 64.7%. No association was found between PCNA- or MIB-1-LI values and microscopic features, or between LI values and prognosis. CONCLUSIONS: Contrary to a general assumption, desmoplastic medulloblastoma and differentiated medulloblastoma are negative prognostic factors in adequately radiotreated adult patients. This may possibly be referred to lower radiosensitivity of these tumor variants. The LI with PCNA or Ki-67 is of no help in identifying aggressive tumors.

Adult↗

PubMedDate not supplied

Heterogeneity of apoptotic pathways and c.Jun/JNK expression in malignant gliomas.

In brain tumors, the prognostic value of apoptosis is still debated, even though recent observations are rather negative. In 50 astrocytic gliomas, apoptotic nuclei were recognized by TUNEL technique and morphology and apoptotic index (AI), mitotic index (MI) and the MI/AI ratio were calculated in proliferative areas and in areas containing perinecrotic palisadings and hypercellular centres. In proliferative areas, a positive linear correlation between MI and AI and a MI/AI ratio > I were found. The latter was < I in perinecrotic palisadings and hypercellular centres. This suggests the possibility that apoptosis is triggered respectively by cell proliferation and hypoxia. A small number of apoptotic nuclei was positive for c-Jun and JNKI, suggesting the involvement of this pathway in apoptosis as well as that of sphingomyelinase/ceramide. No relationship was found between AI and labeling indices of Bcl-2, Bcl-x, Bax, p53, APO.I/Fas. The rationale for a prognostic value of apoptosis in gliomas is thus poor.

Apoptosis↗

PubMedDate not supplied

Cell proliferation and invasion in malignant gliomas.

Cell proliferation and invasion were studied in sixty biopsies of malignant gliomas selected to reproduce the spreading modalities identified in ninety autopsy cases of glioblastoma. Cell proliferation was studied by the immunohistochemical demonstration of PCNA and MIB-1 and by the calculation of their labeling indexes (LI). The main finding was that cell proliferation and cell invasion are not necessarily associated. The interface between the solid tumor and the adjacent brain was represented either by a gradient of tumor cell density or by a clearcut demarcation of the tumor. In the first case the LI either did not change in the infiltration area in comparison with solid tumor or it was much lower, whereas in the second case there was a ring with a high density of labeled nuclei at the tumor periphery. Perineuronal satellites were usually positive for proliferation markers. Cells accumulated in the outer cortical layers, from a deeply located tumor, were almost negative, whereas those originating from subarachnoidal or subpial invasion showed a high LI. High LIs were also found in subarachnoidal and subpial growths, and in a cell population descending into the brain parenchyma around meningeal penetrating vessels. The relationship between cell proliferation and invasion from in vivo studies is not a direct and a simple one.

Brain Neoplasms↗

PubMedDate not supplied

Cell cycle and proliferation markers in neuroepithelial tumors.

Cell proliferation is characteristic, though non specific, of tumors. The cell cycle is regarded as a clock with ordered activation of protein complexes triggering initiation and advancement through checkpoints. The cell cycle and its control mechanisms are briefly described herein focusing on neuroepithelial tumors. The assessment of cell proliferation in brain tumors is a very important tool in diagnosis and especially in prognosis. It can be performed by different methods: counting mitoses, calculating the labeling index (Ll) of [3H] Thymidine, BrdU, Ki-67, MIB.1, PCNA, cytometry and AgNORs. Each method has its advantages and disadvantages. The main obstacles to the usefulness of different Lls in establishing prognosis in individual cases are sampling error, heterogeneity of the proliferation potential of brains tumors and the wide overlapping of Ll ranges between classic and anaplatic variants. The principal findings are critically described and commented upon.

Biomarkers↗