The Authors, after briefly reviewing the literature on chemotherapy of malignant gliomas, present their own experience on forty-four patients with such tumors. All of them had been previously operated and irradiated. The clinical course was controlled by various parameters which are described. Results obtained in glioblastomas, anaplastic astrocytomas and malignant oligodendrogliomas are discussed. BCNU and CCNU seem to be beneficial not only in prolonging survival time but also in improving its quality: the average survival time of treated patients is 9.2 +/- 9.8 against 6.7 +/- 3.4 of controls. These values however are not statistically significant. In 15 out of 31 patients, who died at varying intervals after chemoterapy, an autopsy was performed. The morphology of the tumors was compared with that of previous biopsies. No specific alterations to be referred to chemotherapy were found. The side effects are described in detail and particular attention is focused on toxicity (blood and liver) whose main effect is the lowering of platelets and white cells. However, this and the epatic alterations did not reach values requiring interruption of chemotherapy. Other drugs have been used such as MeCCNU, VM 26 and Procarbazine. The number of patients, treated with each of them, is low for a definite conclusion; even if VM 26 and Procarbazine seem to offer the best effects.

Adult↗

PubMedDate not supplied

A cytomorphological scheme of differentiating neuronal phenotypes in cerebellar medulloblastomas based on immunolocalization of class III beta-tubulin isotype (beta III) and proliferating cell nuclear antigen (PCNA)/cyclin.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III) to that of the proliferating cell nuclear antigen (PCNA)/cyclin in 46 cerebellar neuroblastic tumors (medulloblastomas). Both class III beta-tubulin (beta III) and PCNA/cyclin reactivities were present in all tumors, but the topographic distribution and cytomorphologic features of stained cells varied considerably between classic and desmoplastic medulloblastomas. Four neoplastic phenotypes, representing gradations of neuronal differentiation, were identified: [Allegranza 1991] apolar, blast-like PCNA/cyclin(+) cells devoid of beta III reactivity (Nb1); [Bravo et al. 1987] apolar, often binucleated and/or fusiform, PCNA/cyclin (+) cells with pronounced beta III staining in their protoperikarya and their growth cones (Nb2); [Burger et al. 1987] beta III-immunoreactive immature polar neurons with varying degrees of neuritic development, reading to significant neuritogenesis in the "pale islands" of desmoplastic medulloblastomas (Nb3). The majority of Nb3 phenotypes were PCNA/cyclin (-), although subpopulations of such polar tumor cells exhibiting PCNA staining were also identified; and [Burger et al. 1991] beta III-immunoreactive, PCNA/cyclin (-) mature ganglion-like cells (Nb4). A high PCNA/cyclin labeling index (> 80%) was obtained in 20 poorly differentiated classic medulloblastomas while, significant intratumoral staining heterogeneity was observed in 23 cases of desmoplastic medulloblastomas and 3 cases of "medulloblastomas with ganglion cells": A high labeling index (LI)(> 80%) in the reticulin-impregnated poorly differentiated areas of tumor contrasted with sharp decline of PCNA staining and a very low LI (< 10%) in areas of overt neoplastic neuritogenesis ("pale islands") displaying strong beta III reactivity. Neoplastic ganglion cells were beta III (+)/PCNA (-). Our findings indicate that the majority of differentiating neuronal phenotypes undergoing cytomorphological changes of neuritic development (Nb3), and all neoplastic ganglion cells (Nb4 phenotypes) are PCNA (-), in contrast to actively proliferating, poorly differentiated, tumor cells that are PCNA (+). Although PCNA staining corresponded in part, to beta III (-) blast-like elements (Nb1), a co-expressive pattern of staining for beta III and PCNA/cyclin also was observed in subpopulations of poorly differentiated tumor cells (Nb2), indicating that transformed neuroblasts are capable of expressing differentiation-associated neuronal cytoskeletal proteins while still remaining in the proliferative compartment of the cell cycle. Our observations suggest that only neuritogenesis and acquisition of ganglionic phenotype are significant maturational events in medulloblastomas (indicating entry into the quiescent phase of the cell cycle) and provide further support for the neuronal lineage and differentiation potential of these cerebellar embryonal tumors.

Adolescent↗

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↗

PubMedDate not supplied

[Chemotherapeutic effects of nitrosourea derivatives in ENU-induced experimental tumors in the rat].

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Animals↗