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Meningiomas are neoplasms that arise from the leptomeningeal covering of the brain and spinal cord, accounting for 15%-20% of CNS tumors. The WHO classifies meningiomas into three histological grades: benign, atypical, and anaplasic in accordance with the clinical prognosis. Atypical and anaplasic meningiomas tend to recur. Sometimes, meningiomas with histological diagnosis of benign meningioma show clinical characteristics of atypical meningioma. In this context, high-resolution magic-angle spinning (HR-MAS) spectroscopy of intact tissue from brain tumor biopsies has shown great potential as a support diagnostic tool. In this work, we show differences between benign and atypical meningiomas in HR-MAS molecular profiles of meningioma biopsies. Metabolic differences between meningioma grades include changes in the levels of glutathione. Glutathione role in cancer is still unclear, as it may act both as protective and pathogenic factor. Glutamine and glutamate, which are related to glutathione metabolism and have been associated with tumor recurrence, are also increased in atypical meningiomas. Other metabolites associated with tumor malignancy that show statistically significant differences between benign and atypical meningiomas include phosphocholine and phosphoethanolamine. Overall, this work suggests that the additional information obtained by NMR metabolomics applied to biopsies of human meningiomas may be useful for assessing tumor grade and determining optimum treatment strategies.

Plant phenolic antioxidants, among them catechins and hydroxycinnamoyl conjugates, constitute a well defined class of inhibitors of reactive nitrogen species (RNS). To gain deeper insight in this field, we examined the effects of 3,5-di-O-caffeoylquinic acid (DCA), its methyl ester (DCE) and epigallocatechin gallate (EGCG) in nitrative and oxidative processes. These compounds were found to be strong inhibitors of the nitration of tyrosine residues induced by ONOO- in bovine seroalbumin, with their IC50 values (10-40 microM) notably decreasing in the presence of bicarbonate. When studied on the intracellular protein tyrosine nitration induced by ONOO- in cultured murine fibroblasts as well as that induced by phorbol ester (PMA) in nitrite-supplemented human neutrophils, all three phenolics were also effective (100% and over 75% inhibition for fibroblasts and neutrophils, respectively, at 25 microM). This ability seems to be due to a direct interaction with ONOO- or with the species generated by leukocytes. The possible interference with the production of NO was also studied: both DCA and EGCG inhibited nitrite production in LPS-stimulated macrophages by 24% and 40%, respectively, and the expression of nitric oxide synthase-2 (NOS-2), as well. DCA and EGCG reduced by 52% and 59%, respectively, the NF-kappaB transcriptional activity. In contrast, DCE did not show any effect. The assayed phenolics exert varying degrees of protection against the chemical modifications induced by RNS depending not only on the hydroxyl pattern, but also on the presence of bicarbonate.

Glioblastoma multiforme is the most common and most aggressive of the primary brain tumors. The mean survival of patients is 10-12 months. Conventional therapy of surgery, radiation and chemotherapy is largely palliative. Cytogenetically, karyotypes of glioblastomas are very complex with trisomy 7 and monosomy 10 as the most frequent abnormalities. A genetic alteration that is significantly more frequent in primary than in secondary glioblastomas, the latter arising from preceding low-grade gliomas, is epidermal growth factor receptor gene (EGFR) amplification, whereas TP-53 mutations are significantly more frequent in low-grade gliomas and secondary glioblastomas derived there- from. We report the histological and genetic study of two glioblastomas, one case arising de novo and the other case arising 3 years after a previously diagnosed anaplastic astrocytoma, with concurrent EGFR amplification and TP-53 mutation. These anomalies were initially deemed as mutually exclusive. However, a small percentage of cases have been found with both anomalies although at a significantly lower level than could be expected. We have analyzed these two cases cytogenetically and by molecular studies in order to detect additional alterations associated with this phenotype. Cytogenetically, both cases showed in common the monosomy of chromosomes 10 and 17. At the molecular level, a rare mutation of TP-53 was found in the secondary glioblastoma and hypermethylation of the promoter region of p16(INK4a) and p14(ARF) genes were observed in the primary and secondary glioblastoma, respectively.

We have studied the effects of dihydrocucurbitacin B, a triterpene isolated from Cayaponia tayuya roots, on different models of delayed type hypersensitivity (DTH) in mice, as well as on T-lymphocyte proliferation and the mediators involved. In experiments with mice, dihydrocucurbitacin B inhibited the inflammatory reactions induced by oxazolone, dinitrofluorobenzene, and sheep red blood cells, reducing both the edema and cell infiltration. Moreover, the analysis of inflamed tissues showed that dihydrocucurbitacin B reduced the presence of the most relevant cytokines implicated in these processes, including interleukin-1 beta, interleukin-4, and tumor necrosis factor-alpha. Dihydrocucurbitacin B was also found to inhibit the proliferation of phytohemagglutinin-stimulated human T lymphocytes (IC(50) = 1.48 microM), halting the cell cycle in the G(0) phase. In addition, the triterpene reduced the production of interleukin-2, interleukin-4, interleukin-10, and interferon-gamma in human T lymphocytes, and it hampered the induction of the principal cyclins involved in the cell cycle, including A(1), B(1), D(2), and E(1). Finally, dihydrocucurbitacin B was found to exert a selective inhibition on the nuclear factor of activated T cells (NFAT) in human lymphocytes without affecting the calcium influx. Taken together, these results suggest that dihydrocucurbitacin B curbs DTH reactions by inhibiting NFAT, which in turn suppresses the proliferation of the most relevant cells involved in DTH reactions, namely the T cells.

Solitary fibrous tumor (SFT), a benign neoplasm arising in mesenchymal structures, was initially described in the pleura but subsequently has also been documented in other locations. It is uncommon in the orbit, where it closely resembles other benign spindle-shaped mesenchymal tumors of this area such as schwannoma, meningioma or hemangiopericytoma. We present a case of orbital SFT in a 34-year-old woman. The radiological study showed the presence of an enhanced uptake lesion measuring 2 cm in major diameter. The histopathological evaluation revealed alternating cellular and hypocellular areas with spindle-shaped cells. The cellular organization displayed a broad variety of irregular morphological patterns. The neoplastic cells were intensely positive for CD34 and vimentin, while S100, epithelial membrane antigen (EMA), Caldesmon, Calretinin and WT-1 proved negative. The pericellular matrix exhibited strong positivity for CD44 and collagen IV. Scarce mitotic figures, a Ki-67 nuclear labeling index of <5%, and focal expression of p53 were also observed. Measurement of DNA content revealed a DNA index of 1, indicating a diploid peak in 95% of the tumor cells. A normal 46,XX karyotype was present. No TP53 (exons 5-8) mutations or MDM2 and CDK4 amplifications were observed. No p14(ARF), p15(INK4B) and p16(INK4A) deletions or hypermethylation were observed in this benign tumor. Following surgical resection and radiotherapy, the patient showed no tumor relapse after one year of follow-up.

Meningiomas are usually benign tumors; however, they can recur after surgical resection and occasionally show histologic progression to a higher grade II and III malignancy. The second most frequently reported genetic abnormality after 22q loss is deletion of 1p, although alterations in 9q, 10q, and 14q are also implicated in meningioma progression. Fourteen tumors comprising six benign, four atypical, and four malignant meningiomas were examined by means of cytogenetic and fluorescence in situ hybridization analysis. All tumors showed losses in different regions of 1p, with 1p11, 1p13, 1p21, 1p22, 1p32, and 1q21 breakpoints; eight tumors also presented alterations of chromosome 14. Five of the six cases with deletions on 1p and normal chromosome 14 were grade I, and two were recurrent. All but one of the eight cases with simultaneous 1p deletion and alterations of chromosome 14 were grade II (3 cases) and grade III (4 cases); all the grade III cases were recurrent. These results support the possible association between changes in 1p and chromosome 14 with the evolution of aggressive meningiomas through tumor progression.

Chondrosarcomas are malignant cartilage-forming tumors that represent the second most common malignant solid tumor of bone. These biologically poorly understood neoplasms vary considerably in clinical presentation and biologic behavior. Chemotherapy and radiation therapy are generally ineffective. Here we describe the establishment and characterization of a new human chondrosarcoma cell line named ch-2879, and we compare the cell line with its tumor of origin. The cell line was established from a recurrent grade 3 chondrosarcoma of the chest wall and characterized by growth kinetics and morphologic studies. Immunocytochemistry and RT-PCR were performed to examine the expression of cartilage-specific phenotypes. Genetic characterization was performed using cytogenetics, fluorescence in situ hybridization, flow cytometry, and molecular techniques for analysis of the genes implicated in cell cycle control, amplification of MDM2, CDK4, and Cyclin D1, and mutations in the p53 gene. ch-2879 cells were subcultured for more than 80 passages. They expressed vimentin, HNK-1, HBA-71, Ki-67, cyclin D1, Fli-1, S-100, p21, p27, and p53 and were negative for cytokeratin, EMA, p14, p16, MDM2, Rb, and c-erb-b2 antigens. Cytogenetically the recurrent tumor showed a hyperhaploid karyotype with clonal numerical and structural abnormalities. The sole structural abnormality was a chromosome derivative of a t(1;21) translocation. The cell line at passage 3 showed two populations: the hyperhaploid and an exactly duplicated, hypotriploid population. After the 18th passage, only the hypotriploid population was present. The cells expressed collagen 2. Molecular comparison of the primary and recurrent tumor evidenced an in vivo molecular change consisting of a deletion of 9p21 genes in the recurrence, probably caused by a selection process. Because of its gene expression profile, including expression of genes implicated in chondrogenesis in uncoated plastic dishes, this cell line may prove useful for cellular and molecular studies as well as studies of chondrosarcoma characterization and treatment.

A rat cell line-nominated CC-62 derived from a combined hepatocellular and cholangiocellular carcinoma obtained by administration of 2-acetylaminofluorene to male Wistar rats, has been established. Using light and electron microscopy it was determined that morphologically the tumor consisted of a mixed population of hepatocytes and cholangiolar neoplastic cells, intermingled with small, undifferentiated oval-like cells. The CC-62 line has been maintained through 90 passages in culture adopting a paving stone arrangement. Doubling time at the 12th passage was 23 h. Immunostaining with a panel of antisera was performed to identify the cytological profiles of the cell line. There was no k-ras or p53 expression by immunohistochemistry, and molecular biology failed to detect mutations. Molecular analysis by reverse transcriptase-polymerase chain reaction revealed transcripts for c-met but no expression of HGF messenger ribonucleic acid. Three cell lines cloned from CC-62 showed the same immunohistochemical and molecular pattern as the parental line. Cytogenetic analysis revealed a chromosome number ranging from 74 to 82 with a modal number of 79 but no clonal structural abnormalities were found. Deoxyribonucleic acid ploidy analysis showed an aneuploid peak. CC-62 caused tumors 1 mo after subcutaneous transplantation into nude mice, with morphological patterns of mucosecretory solid and spindle-shaped carcinoma. This cell line is the first established from a primary rat combined hepatocellular and cholangiocellular neoplasm. The resulting cells expressed biological and morphological markers of hepatocytes and cholangiolar cells. Therefore this cell line may contribute to a better understanding of the histogenesis of liver cancer.

Angiosarcoma of the breast is quite rare, and the development of cutaneous angiosarcoma after segmental mastectomy and radiation therapy is even less common. A cytogenetic analysis of a mammary angiosarcoma arising in a breast after previous irradiation and segmental mastectomy for infiltrating ductal carcinoma revealed multiple clonal rearrangements involving chromosomes X, 1, 2, 3, 4, 5, 6, 7, 8, 9, 15, 17, 20, and 22. No cytogenetically analyzed angiosarcomas of the breast have been reported before.

This study examines the behavior of glycogen-storing rat hepatoma (N13) in vitro using cytophotometric techniques. A significant increase in glycogen is observed in these cells after 30 min incubation in a buffered solution containing 0.1 mM glucose, that is 80 times lower than the physiological glucose concentration in rat blood. N13 hepatoma cells grow exponentially in culture using RPMI 1640 tissue culture medium supplemented with 10% fetal bovine serum. During the first day in culture these cells store a large amount of glycogen and this increase is also observed in serum-free cultures. In more prolonged cultures the amount of glycogen per cell gradually becomes lower, although the culturing conditions are maintained. Similar variations of protein are also observed during the initial period of culture. DNA distribution does not show significant changes, although in serum-free cultures an increase in the proportion of cells in S and G2/M phases is observed. The addition of glucagon, epinephrine and cyclic AMP derivatives to serum-free cultures does not impede the storage of glycogen. Nevertheless, addition of either 2 mM N6,O2'-dibutyryl cyclic AMP or 0.1 mM 8-(4-chlorophenylthio)-cyclic AMP blocks the cell cycle at G0/G1 and glycogen content does not decrease after the first day in culture. We believe that this cell line offers an appropriated model to study glycogen metabolism and its involvement in the neoplastic process.

A case of familial translocation t(3;22) (q21;q13) detected through a boy carrier with various functional and phenotypical alterations is described. The caryotype study (G bands) showed that the mother, one maternal aunt, two maternal uncles, and the brother of the proband were likewise carriers of the same translocation. We discuss the type of segregation and the high familial incidence of the translocation.

Cytogenetic studies on newborn infants show a high incidence in chromosomal abnormalities (0.5-1% of the population). Chromosomal study is carried out on 750 children from the University Hospital of Valencia over a two-year period, chosen at random and without any clinical pathology. Five gonosomopathies and three autosomopathies were found. In the former, three 47,XXY, one triple-X, and one isochromosome of long arms of chromosome X, were detected. In autosomal chromosomopathies, a Robertsonian translocation was seen between chromosomes 13 and 14, a reciprocal translocation between chromosomes 8 and 10, and an inversion of chromosome 3. Altogether eight cytogenetic anomalies appeared, a percentage slightly over one percent. Importance of early diagnosis of chromosomal abnormalities is discussed, with the aim of establishing adequate treatment when possible, and genetic counselling for the family.