Involvement of the long arm of chromosome 9 in medulloblastoma in an adult.

Abstract Medulloblastoma is the most common primitive neuroectodermal tumor (PNET) in children, but is very rare in adults. An isochromosome for the long arms of 17, i(17q), is found in about 30% of pediatric cases. Cytogenetic studies in adults are very scarce; only six cases have been described cytogenetically: three cases had normal karyotype, two were studied partially, and another presented only two clonal structural anomalies: del(9)(q12) and del(11)(q22). We studied the chromosomes from medulloblastoma in a 27-year-old woman and found one hypotetraploid stemline with clonal alterations. In the structural anomalies, chromosomes 3, 9, 12, and i(17q) were involved. Chromosome 9 presente…

Anti-Inflammatory Triterpenes from Pistacia terebinthus Galls

From the galls of Pistacia terebinthus we obtained an extract that proved to be effective against chronic and acute inflammation. Now we report on the isolation and identification of three triterpenes: two tirucallane-type lanostanoids and one oleanane, which we have identified as masticadienonic acid (1), masticadienolic acid (2), and morolic acid (3), respectively. All of them showed effectiveness on the mouse ear inflammation induced by repeated applications of 12-O-tetradecanoylphorbol 13-acetate and on the phospholipase A2-induced foot paw edema. The pharmacological activity of the compounds was ratified by a histological study of the ear samples. In addition, they inhibited leukotrien…

Epigenetic changes underlie the aggressiveness of histologically benign meningiomas that recur

Meningiomas are the most frequent primary brain tumor. Usually, they are curable by surgery, but even after seemingly complete resection, some low-grade lesions recur. Despite recent improvements, signatures having prognostic value in grade I tumors remain poorly characterized. The frequency and delicate location of these tumors suggest that the risk of recurrence might be more accurately predicted. Herein, we show an easy way to evaluate the methylation status of meningiomas and its correlation with the prognosis of the disease. A series of 120 meningiomas, including primary tumors and recurrences, were analyzed histopathologically, and 24 tumor suppressor genes (TSGs) were studied by meth…

Metastasizing anaplastic ependymoma in an adult. Chromosomal imbalances, metabolic and gene expression profiles

Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.

Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…

Oligoastrocitoma con diferenciación en células en anillo de sello. Estudio morfológico, ultraestructural e inmunohistoquímico

Resumen Presentamos un caso de tumor glial mixto (oligoastrocitoma) con celulas en anillo de sello. Esta diferenciacion celular es rara en tumores gliales del sistema nervioso central. En este estudio analizamos las caracteristicas morfologicas, ultraestructurales e inmunohistoquimicas del tumor. Las celulas neoplasicas con caracteristicas morfologicas en anillo de sello mostraban expresion de GFAP, S-100 y vimentina. En la discusion consideramos el diagnostico diferencial con otros tumores primarios del sistema nervioso central, asi como con metastasis cerebrales de neoplasias con diferenciacion en celulas en anillo de sello.

Identification of a Novel BRCA1 Alteration in Recurrent Melanocytoma Resulting in Increased Proliferation

Abstract Primary meningeal melanocytomas are rare tumors of the central nervous system. Although they are considered benign neoplasms, some reports describe recurrent rates up to 45%. Little is known about their genetic and epigenetic landscape because of their infrequency. Even less has been described about markers with prognostic value. Here we describe a patient who developed a primary meningeal melanocytoma, suffered 3 recurrences in a period of 6 years and died of the tumor. The genetic and epigenetic changes explored confirmed GNAQ mutation as an initiating event. We found an epigenetic alteration of GSTP1, a feature that has recently been described in meningiomas, from the beginning …

Metabolic aggressiveness in benign meningiomas with chromosomal instabilities.

Abstract Meningiomas are often considered benign tumors curable by surgery, but most recurrent meningiomas correspond to histologic benign tumors. Because alterations in chromosome 14 among others have suggested clinical aggressiveness and recurrence, determining both the molecular phenotype and the genetic profile may help distinguish tumors with aggressive metabolism. The aim of this study was to achieve higher specificity in the detection of meningioma subgroups by measuring chromosomal instabilities by fluorescence in situ hybridization and cytogenetics and metabolic phenotypes by high-resolution magic angle spinning spectroscopy. We studied 46 meningioma biopsies with these methodologi…

New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile

Gene amplification is a process that is characterized by an increase in the copy number of a restricted region in a chromosome arm, and is frequently associated with an overexpression of the corresponding amplified gene. Amplified DNA can be organized either as extrachromosomal elements, repeated units at a single locus or scattered throughout the genome. The amplification of the gene for epidermal growth factor receptor (EGFR) is a common finding in glioblastomas and the amplified gene copies appears as double minutes. The aim of this study was to investigate the different patterns of EGFR amplification in 40 cases of glioblastoma using FISH analysis in metaphases and paraffin sections, an…

Complex rearrangement of chromosomes 6 and 11 as the sole anomaly in atypical teratoid/rhabdoid tumors of the central nervous system.

Atypical teratoid/rhabdoid tumor of the central nervous system is a rare childhood tumor with a distinct histologic appearance and an aggressive clinical course. Few tumors have been analyzed cytogenetically. The only consistent chromosomal abnormality identified in some of these tumors has been monosomy or deletions of chromosome 22; in others, a normal chromosome 22 was present. The authors report an atypical teratoid/rhabdoid neoplasm of the central nervous system with a novel complex rearrangement affecting chromosomes 6 and 11 as the sole anomaly. The involvement of region 11p15 could be important in the pathogenesis of this entity.

In vivo anti-inflammatory activity of saponins from Bupleurum rotundifolium

Seven oleanane-type triterpene saponins were isolated from the methanolic extract of the aerial parts of Bupleurum rotundifolium. They were identified on the basis of their spectral data as 3-O-[alpha-L-rhamnopyranosyl (1--2)-beta-D-glucopyranosyl (1--2)-beta-D-glucopyranosyl]-28-O-[beta-D-glucopyranosyl (1--2)-beta-D-glucopyranosyl] echinocystic acid (saponin 1), 3-O-[alpha-L-rhamnopyranosyl (1--2)-beta-D-glucopyranosyl (1--2)-beta-D-fucopyranosyl] 11-methoxy-primulagenin A (saponin 2), rotundioside E (saponin 3), rotundioside F (saponin 4), 3beta-sulfate, 28-O-[beta-D-glucopyranosyl (1--6)-beta-D-glucopyranosyl (1--2)-beta-D-glucopyranosyl (1--2)-beta-D-glucopyranosyl] ester of primulagen…

Angiotensin II-Induced Mononuclear Leukocyte Interactions with Arteriolar and Venular Endothelium Are Mediated by the Release of Different CC Chemokines

Abstract Angiotensin II (Ang-II) is associated with atherogenesis and arterial subendothelial mononuclear leukocyte infiltration. We have demonstrated that Ang-II causes the initial attachment of mononuclear cells to the arteriolar endothelium. We now report on the contribution of CC chemokines to this response. Intraperitoneal administration of 1 nM Ang-II induced MCP-1, RANTES, and MIP-1α generation, maximal at 4 h, followed by mononuclear leukocyte recruitment at 8 and 24 h. Using intravital microscopy within the rat mesenteric microcirculation 4 h after exposure to 1 nM Ang-II, arteriolar mononuclear cell adhesion was 80–90% inhibited by pretreatment with Met-RANTES, a CCR1 and CCR5 ant…

L-NAME induces direct arteriolar leukocyte adhesion, which is mainly mediated by angiotensin-II.

Acute inhibition (1 h) of nitric oxide synthase (NOS) with L-NAME causes leukocyte recruitment in the rat mesenteric postcapillary venules that is angiotensin-II (Ang-II) dependent. Since 4-h exposure to Ang-II provokes arteriolar leukocyte adhesion, this study was designed to investigate whether subacute (4-h) NOS inhibition also causes this effect.Rats were intraperitoneally injected with saline, L-NAME, or 1H-[1,2,4]-oxidazolol-[4,3-a]-quinoxalin-1-one (ODQ). Leukocyte accumulation in the mesenteric microcirculation was examined 4 h later via intravital microscopy. Some groups were pretreated with losartan, an AT(1) Ang-II receptor antagonist.At 4-h, L-NAME caused a significant increase …

Erythromycin exertsin vivoanti-inflammatory activity downregulating cell adhesion molecule expression

1. Macrolides have long been used as anti-bacterial agents; however, there is some evidence that may exert anti-inflammatory activity. Therefore, erythromycin was used to characterize the mechanisms involved in their in vivo anti-inflammatory activity. 2. Erythromycin pretreatment (30 mg kg(-1) day(-1) for 1 week) reduced the lipopolysaccharide (LPS; intratracheal, 0.4 mg kg(-1))-induced increase in neutrophil count and elastase activity in the bronchoalveolar lavage fluid (BALF) and lung tissue myeloperoxidase activity, but failed to decrease tumor necrosis factor-alpha and macrophage-inflammatory protein-2 augmented levels in BALF. Erythromycin pretreatment also prevented lung P-selectin,…

Inhibition of Delayed-Type Hypersensitivity by Cucurbitacin R through the Curbing of Lymphocyte Proliferation and Cytokine Expression by Means of Nuclear Factor AT Translocation to the Nucleus

Cucurbitacin R is known to exhibit an anti-inflammatory effect in different experimental models of inflammation. In this article, we outline the effect of cucurbitacin R on T lymphocyte proliferation, cytokine production, and nuclear factor activation, as well as its influence on various experimental models of delayed-type hypersensitivity (DTH) in mice. Cucurbitacin R reduced the proliferation of phytohemagglutinin A-stimulated human T lymphocytes (IC(50), 18 microM), modifying the cell cycle, as well as the production of cytokines [interleukin (IL)-2, IL-4, IL-10, and especially interferon-gamma] and the induction of the principal cyclins implicated in the cell cycle (A(1), B(1), D(2), an…

Association of loss of 1p and alterations of chromosome 14 in meningioma progression

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…

Loss of 1p in recurrent meningiomas

Deletion of 1p is associated with histological progression to meningiomas. Detection of this alteration may be a predicting factor for recurrences in this tumor. We present 8 meningiomas from four patients: the original tumor and the first recurrence in one patient, and the first and second recurrences in the other three were studied. We compared results of monosomy 22 and deletion of chromosome 1p with cytogenetic methods and fluorescence in situ hybridization (FISH) analysis obtained from slides of direct preparations, of cultured cells and slides of touch preparations. The cytogenetic study showed normal chromosome 22 and deletion on 1p32 in both samples of one patient; only monosomy 22 …

Dihydrocucurbitacin B Inhibits Delayed Type Hypersensitivity Reactions by Suppressing Lymphocyte Proliferation

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. Dihydrocucurbita…

Assessment of the anti-inflammatory activity and free radical scavenger activity of tiliroside

Three flavonoids, gnaphaliin, pinocembrin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their antioxidant and/or scavenger properties and in vivo in different models of inflammation. In vitro tests included lipid peroxidation in rat liver microsomes, superoxide radical generation in the xanthine/xanthine oxidase system and the reduction of the stable radical 1,1-diphenyl-2-pycryl-hydrazyl (DPPH). Acute inflammation was induced by application of 12-O-tetradecanoylphorbol 13-acetate (TPA) to the mouse ear or by subcutaneous injection of phospholipase A(2) or serotonin in the mouse paw. Eczema provoked on the mouse ear by repeated administration of TPA was selec…

Molecular Progression in Unusual Recurrent Non-Pediatric Intracranial Clear Cell Meningioma

We report a case of a recurrent clear cell meningioma (CCM) in the frontal lobe of the brain of a 67-year-old man. The patient developed three recurrences: at 3, 10, and 12 years after his initial surgery. Histopathology observations revealed a grade 2 CCM with positivity for vimentin and epithelial membrane antigen. Expression of E-cadherin was positive only in the primary tumour and in the first available recurrence. Fluorescence in situ hybridization analyses demonstrated 1p and 14q deletions within the last recurrence. Multiplex ligation-dependent probe amplification studies revealed a heterozygous partial NF2 gene deletion, which progressed to total loss in the last recurrence. The las…

Anti-inflammatory glycoterpenoids from Scrophularia auriculata.

The activity of the four glycoterpenoids: two saponins, verbascosaponin A and verbascosaponin, and two iridoids, scropolioside A and scrovalentinoside, isolated from Scrophularia auriculata ssp. pseudoauriculata, were studied in different models of acute and chronic inflammation. Both saponins significantly inhibited the mouse paw edema induced by carrageenan and ear edema induced by single and multiple doses of 12-O-tetradecanoylphorbol 13-acetate (TPA). Verbascosaponin A showed a potency twice as high as that of indomethacin in the acute TPA model. Verbascosaponin A and scropolioside A were active after a long latency period against ethyl phenylpropiolate edema, as are glucocorticoids. Wh…

BRAF V600E Mutation in Two Distinct Meningeal Melanocytomas Associated With a Nevus of Ota

Magnetic Resonance Microscopy at 14 Tesla and Correlative Histopathology of Human Brain Tumor Tissue

Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 µm spatial resolution. The use of …

Meningioma: Un modelo de evolución citogenética en la iniciación y progresión tumoral

Resumen Los meningiomas son tumores del sistema nervioso central con amplia heterogeneidad morfologica. Aunque son generalmente benignos, tienen la capacidad de evolucionar a un grado histologico mayor (atipico y anaplasico) que esta relacionado con un incremento de su agresividad biologica y/o la capacidad de recidivar. Esta evolucion se caracteriza a nivel citogenetico por la monosomia total o parcial del cromosoma 22 en la etapa mas temprana, seguida de cambios cromosomicos secundarios tanto numericos como estructurales durante la progresion tumoral. En este trabajo presentamos una revision sobre 85 casos de meningiomas, 43 benignos, 28 atipicos y 14 malignos, estudiando sus caracteristi…

Histologically benign metastatic meningioma: morphological and cytogenetic study. Case report.

✓ The authors report on a 75-year-old man with histologically benign fibroblastic meningioma metastasizing to the lung, liver, spleen, and kidney. The original tumor exhibited a complex karyotype involving different structural and numerical anomalies associated with monosomy of chromosome 22. The implication of chromosome 1p36 was confirmed by fluorescence in situ hybridization in most interphase nuclei. Metastases occurred 4 months after incomplete resection with prior therapeutic embolization. The recurrent tumor in turn displayed anaplastic features and an increased Ki-67 labeling index. Genetic alterations in such morphologically benign meningiomas have been implicated in the malignant …

Gene expression profiles of metabolic aggressiveness and tumor recurrence in benign meningioma.

Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after s…

Cucurbitacin R Reduces the Inflammation and Bone Damage Associated with Adjuvant Arthritis in Lewis Rats by Suppression of Tumor Necrosis Factor-α in T Lymphocytes and Macrophages

The aim of this study was to investigate the effects of cucurbitacin R on an experimental model of adjuvant-induced arthritis in rats. The treatment of arthritic rats with cucurbitacin R (1 mg/kg p.o. daily) modified the evolution of the clinical symptoms, whereas the histopathology of paws demonstrated a reduction in the signs of arthritis. Compared with the control group, radiography of the tibiotarsal joints of cucurbitacin R-treated rats showed a decrease in joint damage and soft tissue swelling of the footpad. The in vivo study of the expression of proinflammatory enzymes (nitric-oxide synthase-2 and cyclooxygenase-2) with the aid of the Western blot technique, and that of tumor necros…

Primary glioblastomas with and without EGFR amplification: Relationship to genetic alterations and clinicopathological features

Glioblastomas express a notable heterogeneity in both the histological and cell patterns with glial astrocytic differentiation. Primary glioblastoma, which is the most frequent presentation (90-95%), occurs mainly in older patients and arises de novo, without any clinical or histological evidence of a less malignant precursor lesion. EGFR amplification has been identified as a genetic hallmark of primary glioblastomas and occurs in 40-60% of cases. However, there exist primary glioblastomas without EGFR amplification/overexpression. The purpose of this study was to stabilize the association between cases with and without EGFR gene amplification with clinical and genetic parameters in 45 cas…

Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin-induced lung injury

Mandarin translation of abstract Background and purpose:  The effects of a phosphodiesterase 4 (PDE4) inhibitor, roflumilast, on bleomycin-induced lung injury were explored in ‘preventive’ and ‘therapeutic’ protocols and compared with glucocorticoids. Experimental approach:  Roflumilast (1 and 5 mg·kg−1·d−1, p.o.) or dexamethasone (2.5 mg·kg−1·d−1, p.o.) was given to C57Bl/6J mice from day 1 to 14 (preventive) or day 7 to 21 (therapeutic) after intratracheal bleomycin (3.75 U·kg−1). In Wistar rats, roflumilast (1 mg·kg−1·d−1, p.o.) was compared with methylprednisolone (10 mg·kg−1·d−1, p.o.) from day 1 to 21 (preventive) or from day 10 to 21 (therapeutic), following intratracheal instillatio…

Anti-inflammatory activity of erycristagallin, a pterocarpene from Erythrina mildbraedii.

Erycristagallin, a pterocarpene isolated from Erythrina mildbraedii, was tested in vitro for its antioxidant properties on the stable 2,2-diphenyl-1-pycryl-hydrazyl (DPPH) free radical and on the arachidonic acid metabolism. In addition, erycristagallin was tested on different experimental models of inflammation, such as the acute and chronic inflammation induced by the application of 12-O-tetradecanoylphorbol 13-acetate (TPA) on mice and the phospholipase A(2)-induced mouse paw oedema test. In the carrageenan-induced mouse paw oedema test, the ethyl acetate extract obtained from E. mildbraedii showed anti-inflammatory activity, and erycristagallin was isolated as the active principle. In v…

Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity.

One of the best known bioactive triterpenoids is oleanolic acid, a widespread 3-hydroxy-17-carboxy oleanane-type compound. In order to determine whether further oxidation of carbon 3 affects anti-inflammatory activity in mice, different tests were carried out on oleanolic acid and its 3-oxo-analogue oleanonic acid, which was obtained from Pistacia terebinthus galls. The last one showed activity on the ear oedema induced by 12-deoxyphorbol-13-phenylacetate (DPP), the dermatitis induced by multiple applications of 12-O-tetradecanoyl-13-acetate (TPA) and the paw oedemas induced by bradykinin and phospholipase A2. The production of leukotriene B4 from rat peritoneal leukocytes was reduced by ol…

Expression of chemokine receptor CXCR3, CXCR4, and CXCR7 and their respective ligands in rhabdomyosarcoma

In Vivo Studies on the Anti-Inflammatory Activity of Pachymic and Dehydrotumulosic Acids

Pachymic and dehydrotumulosic acids were studied in different models of acute and chronic inflammation. They proved to be active in most of the methods applied. None of them were active against arachidonic acid-induced ear edema. Dehydrotumulosic acid significantly diminished the mouse ear edema induced by ethyl phenylpropiolate, while pachymic acid was ineffective. When the putative corticoid-like mechanism of both compounds was explored, pachymic acid activity was partially abolished by the glucocorticoid receptor antagonist progesterone, but dehydrotumulosic acid activity was not affected. In vivo experiments demonstrated the inhibition by both principles of the phospholipase A2 (PLA2)-i…

Isolation of two triterpenoids and a biflavanone with anti-Inflammatory activity from Schinus molle fruits.

Three compounds with anti-inflammatory activity were isolated from Schinus molle fruits. Two of the compounds were identified as 3- epi-isomasticadienolalic acid ( 1), isomasticadienonalic acid ( 2) and chamaejasmin ( 3). Triterpenes 1 and 2, and biflavanone 3 were tested on two models of mice paw inflammation: one of acute inflammation, induced by subcutaneous injection of either phospholipase A (2) (PLA (2)) or carrageenan in the paws of mice, and one of chronic inflammation in the form of eczema, provoked by repeated administration of TPA to the ears of mice. On the PLA (2)-induced mouse paw oedema, only 2 was active (30 mg/kg, 66 % inhibition at 60 min), whereas all compounds reduced th…

Hipofisitis granulomatosa idiopática. Estudio morfológico e inmunohistoquímico de una observación

Resumen Los procesos inflamatorios de la glandula hipofisaria constituyen un grupo de interes por su escasa frecuencia. Con frecuencia se presentan como lesiones ocupantes de espacio y cursan con cuadros de panhipopituitarismo. Ello platea problemas de diagnostico diferencial con implicaciones terapeuticas importantes En este trabajo presentamos un caso de hipofisitis granulomatosa idiopatica, en una paciente de 55 anos con crisis diarias de cefalea y panhipopituitarismo y un aumento de tamano de la glandula hipofisaria. La morfologia destaca una lesion inflamatoria granulomatosa no necrotizante, con celulas multinu-cleadas gigantes y un infiltrado linfoplasmocitario. El estudio inmunohisto…

Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced neutrophil recruitment in vivo.

AbstractAngiotensin-II (Ang-II) has inflammatory activity and is involved in different diseases associated with the cardiovascular system. This study has evaluated the effect of boldine (B), and two phenanthrene alkaloids semisynthesized by us, secoboldine (SB) and boldine methine (BM), on Ang-II-induced neutrophil recruitment. Intraperitoneal administration of 1 nM Ang-II induced significant neutrophil accumulation, which was maximal at 4–8 h. BM inhibited neutrophil infiltration into the peritoneal cavity at 4 h and 8 h by 73% and 77%, respectively, SB at 8 h by 55%, and B had no effect on this response. Although BM inhibited the release of cytokine-inducible neutrophil chemoattractant/ke…

The activation of ERK1/2 MAP kinases in glioblastoma pathobiology and its relationship with EGFR amplification.

The ERK1/2 activated protein kinase (MAPK) pathway is a critical signaling system that mediates ligand-stimulated signals for the induction of cell proliferation, differentiation and survival, involved in malignant transformation. The purpose of this study was to determine the activation of ERK1/2 in this tumor, and to determine the relationship of ERK1/2 activation with the amplification/overexpression of EGFR as well as with 9p21 locus gene alterations, both of which are genetic factors frequently associated with glioblastoma. We used immunohistochemistry and Western blot analysis to analyze the activation of ERK1/2 in 22 patients with glioblastoma, and we studied the amplification/overex…

Roflumilast inhibits leukocyte-endothelial cell interactions, expression of adhesion molecules and microvascular permeability

Background and purpose: The present study addressed the effects of the investigational PDE4 inhibitor roflumilast on leukocyte-endothelial cell interactions and endothelial permeability in vivo and in vitro. Experimental approach: In vivo, intravital video-microscopy was used to determine effects of roflumilast p.o. on leukocyte-endothelial cell interactions and microvascular permeability in rat mesenteric venules. In vitro, the effects of roflumilast N-oxide, the active metabolite of roflumilast in humans, and other PDE4 inhibitors on neutrophil adhesion to tumour necrosis factor α (TNFα)-activated human umbilical vein endothelial cells (HUVEC), E-selectin expression and thrombin-induced e…

Identification of New Genetic Clusters in Glioblastoma Multiforme: EGFR Status and ADD3 Losses Influence Prognosis

Glioblastoma multiforme (GB) is one of the most aggressive tumors. Despite continuous efforts to improve its clinical management, there is still no strategy to avoid a rapid and fatal outcome. EGFR amplification is the most characteristic alteration of these tumors. Although effective therapy against it has not yet been found in GB, it may be central to classifying patients. We investigated somatic-copy number alterations (SCNA) by multiplex ligation-dependent probe amplification in a series of 137 GB, together with the detection of EGFRvIII and FISH analysis for EGFR amplification. Publicly available data from 604 patients were used as a validation cohort. We found statistical associations…

Study of the activation of TLR receptors in neurospheres from glioblastoma cells in vitro

Melanoma primario sobre quiste epidermoide. Una rara asociación tumoral. Estudio clínico-patológico

Resumen Presentamos una observacion de un quiste epidermoide de localizacion frontal parasagital, en un paciente de 69 anos de edad con crisis comiciales de 40 anos de evolucion, ictus cerebrales. El paciente desarrollo sobre la pared del quiste una neoformacion maligna identificada morfologica e inmunohistoquimicamente con la HMb45, como un melanoma maligno. La falta de antecedentes, el estudio radiologico sistemico, conducen a considerar el diagnostico de melanoma maligno primario sobre un quiste epidermoide, siendo discutida la histogenie de esta posible asociacion.

Effect of two phenanthrene alkaloids on angiotensin II-induced leukocyte-endothelial cell interactionsin vivo

The present study has evaluated the effect of two phenanthrene alkaloids, uvariopsine and stephenanthrine, on angiotensin II (Ang-II)-induced leukocyte–endothelial cell interactions in vivo and the mechanisms involved in their activity. Intravital microscopy within the rat mesenteric microcirculation was used. A 60 min superfusion with 1 nM Ang-II induced a significant increase in the leukocyte–endothelial cell interactions that were completely inhibited by 1 μM uvariopsine cosuperfusion. A lower dose of 0.1 μM significantly reduced Ang-II-induced leukocyte adhesion by 75%. When Ang-II was cosuperfused with 1 and 0.1 μM stephenanthrine, Ang-II-induced leukocyte responses were significantly …

Benign and Atypical Meningioma Metabolic Signatures by High-Resolution Magic-Angle Spinning Molecular Profiling

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 meningioma…

Monosomía 1p y fosfatasa alcalina en meningiomas. Estudio clinicopatológico, histoquímico y genético en 10 tumores

Fundamento Los estudios citogeneticos en meningiomas indican que la monosomia 1p es unimportante factor en su progresion. En este cromosoma, en 1p34-p36.1, aparecen localizadoslos genes que codifican la fosfatasa alcalina inespecifica (FA-in), enzima de amplia distribucionen el organismo, que se localiza tambien en los meningiomas. La perdida de expresion deesta enzima en los meningiomas ha sido asociada con la monosomia 1p en estas neoplasias. Pacientes y metodo En este trabajo estudiamos 10 meningiomas correspondientes a 8 pacientesque tienen como caracteristica comun la monosomia 1p, tres de ellos con patron morfologicobenigno, dos atipicos y 5 malignos. Se realiza un estudio citogenetic…

Alteration of major vault protein in human glioblastoma and its relation with EGFR and PTEN status.

Glioblastoma (GBM) is the most frequent and malignant primary brain tumor. Conventional therapy of surgical removal, radiation and chemotherapy is largely palliative. Major vault protein (MVP), the main component of the vault organelle has been associated with multidrug resistance by reducing cellular accumulation of chemotherapeutic agents. With regard to cancer, MVP has been shown to be overexpressed in drug resistance development and malignant progression. The aim of the present study was to evaluate the MVP gene dosage levels in 113 archival samples from GBM and its correlation with patients' survival and epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog (PTEN) …

Dihydrocucurbitacin B, isolated from Cayaponia tayuya, reduces damage in adjuvant-induced arthritis

23,24-Dihydrocucurbitacin B, from the anti-rheumatic plant Cayaponia tayuya, was tested on arthritis induced by adjuvant to corroborate the anti-inflammatory properties of this plant. Arthritis was induced in Lewis rats; the resulting arthritic rats were then treated with dihydrocucurbitacin B (1 mg/kg orally, daily, 1 week). The effect of dihydrocucurbitacin B on the synthesis, release, and activity of pro-inflammatory enzymes (elastase, cyclooxygenase-2, and nitric oxide synthase-2) as well as its effect on different mediators (tumor necrosis factor-alpha and interleukin-1beta) were determined. Dihydrocucurbitacin B modified the evolution of the clinical symptoms, reducing the swelling an…

Anti-inflammatory activity of two cucurbitacins isolated from Cayaponia tayuya roots.

Fractionation of an anti-inflammatory extract from Cayaponia tayuya roots yielded two active compounds, identified as 23,24-dihydrocucurbitacin B (1) and cucurbitacin R (2). Both were evaluated for their anti-inflammatory activity on several experimental models of pain and inflammation. In addition, their cytotoxicity and effects on leukotriene B 4 (LTB 4 ) formation were evaluated in rat polymorphonuclear leukocytes. Both compounds showed activity in the following models: carrageenan-induced mouse paw oedema (1, 4 mg/kg p.o., 46% inhibition at 3 h), phospholipase A 2 -induced mouse paw oedema (2, 3 mg/kg i.p., 61% inhibition at 60 min), serotonin-induced mouse paw oedema (1 and 2, 0.5 mg/k…

Recombinations of chromosomal bands 10q24, 12q14-q15, and 14q24 in two cases of pulmonary chondroid hamartoma studied by fluorescence in situ hybridization.

Abstract Pulmonary chondroid hamartomas (PCH) are benign mesenchymal tumors consisting of at least two cytogenetic subgroups. These subgroups are defined by chromosomal alterations at either 12q14∼q15 or 6p21. Cytogenetic analysis of short-term cultures from two PCHs revealed two different rearrangements with 12q14∼q15. One of these had a unique translocation t(12;14)(q14∼15;q24) with presence of two normal chromosomes 12 and a der(14), but missing the der(12). The other showed a complex rearrangement between chromosomes 10 and 12 with two different derivatives. Our data have been confirmed with fluorescence in situ hybridization analysis. These cases represent variant forms of the standard…

Correlation between EGFR Amplification and the Expression of MicroRNA-200c in Primary Glioblastoma Multiforme

Extensive infiltration of the surrounding healthy brain tissue is a critical feature in glioblastoma. Several miRNAs have been related to gliomagenesis, some of them related with the EGFR pathway. We have evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns, studied by fluorescence in situ hybridization in tissue microarrays, of 30 cases of primary glioblastoma multiforme, whose clinicopathological and immunohistochemical features have also been analyzed. MicroRNA-200c showed a very significant difference between tumors having or not EGFR amplification. This microRNA plays an important role in epithelial-mesenchymal transition, but its impl…

Inhibition of the pro-inflammatory mediators' production and anti-inflammatory effect of the iridoid scrovalentinoside.

We have studied scrovalentinoside, an iridoid with anti-inflammatory properties isolated from Scrophularia auriculata ssp. pseudoauriculata, as an anti-inflammatory agent in different experimental models of delayed-type hypersensitivity. We found that scrovalentinoside reduced the edema induced by oxazolone at 0.5 mg/ear and sheep red blood cells at 10 mg/kg. The observed effect occurred during the last phase or inflammatory response; during the earlier phase or induction of the delayed-type hypersensitivity reaction, no significant activity was noted. Thus, scrovalentinoside reduced both the edema and cell infiltration in vivo and reduced lymphocyte proliferation in vitro, affecting the cy…

Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganum.

We have studied the effect of 5- O-demethylnobiletin ( 1) on both the inflammation of mouse ears induced by repeated application of 12- O-tetradecanoylphorbol 13-acetate (TPA) and the acute mouse paw oedemas induced by carrageenan and phospholipase A (2) (PLA (2)), and determined its activity on 5-lipoxygenase (5-LOX) and elastase release/activity. Compound 1 reduced the oedema formation, cell infiltration, and tissue damage in the inflammation induced by TPA in mouse ears, along with the acute oedema induced by carrageenan in mouse paws and the acute PLA (2)-induced oedema in mouse paws. The flavone inhibited leukotriene B (4) formation in rat neutrophils and elastase release in human neut…

Chromosomal and genetic changes produced in tumoral progression of embryonal rhabdomyosarcoma

The Status of EGFR Modulates the Effect of miRNA-200c on ZEB1 Expression and Cell Migration in Glioblastoma Cells

Migration of glioblastoma cells into surrounding tissue is one of the main features that makes this tumor incurable. We evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns in 30 cases of primary glioblastoma. From the 64 miRNAs that showed differential expression between tumors with a high level of EGFR amplification and tumors without EGFR amplification, 40% were related with cell migration, being miR-200c the most differentially expressed between these two groups. We investigated the effect of miR-200c on ZEB1 expression and cell migration in an in vitro transfection model with a miR-200c mimic, a miR-200c inhibitor and siRNA targeting E…

Cytogenetic analysis and metabolic profiling reveal a subgroup of benign meningiomas with chromosomal instabilities and aggressive metabolism

Meningiomas add up to 30% of Central Nervous System (CNS) tumours. Atypical meningiomas show a high index of recurrence 5 years after complete resection. Sometimes, meningiomas with histological diagnosis of benign meningioma show genetics characteristics of atypical meningioma. Aberrations of chromosomes 1, 14, and 22 are the most frequently reported abnormalities in meningiomas. In this communication we used cytogenetic, FISH, and NMR metabolic profiling for a molecular characterization of a series of 46 meningiomas. Tumor samples were obtained from 46 patients with meningioma (36 benign and 12 atypical) from the Clinic Hospital of Valencia. Cytogenetic analyses were performed by short-te…

Anti-inflammatory and antiallergic activity in vivo of lipophilic Isatis tinctoria extracts and tryptanthrin.

The effects of a supercritical CO2 (SFE) extract, a dichloromethane (DCM) extract from Isatis tinctoria leaf and the alkaloidal constituent tryptanthrin were studied in acute and subchronic experimental models of inflammation. The SFE and DCM extracts showed anti-inflammatory activity in the carrageenan-induced acute mouse paw oedema (ED50 values of 78 mg/kg and 165 mg/kg P. O., respectively) and in the acute tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema in oral (62% and 32% oedema reduction at 100 and 125 mg/kg, respectively) and topical application (37% and 33% reduction of oedema at 0.5 mg/ear). In contrast, tryptanthrin showed no significant anti-inflammatory effect. The D…

Direct evidence of leukocyte adhesion in arterioles by angiotensin II

AbstractAlthough leukocytes adhere in arteries in various vascular diseases, to date no endogenous proinflammatory molecule has been identified to initiate leukocyte adhesion in the arterial vasculature. This study was undertaken to assess angiotensin II (Ang II)-induced leukocyte adhesion in arterioles in vivo. Rats received intraperitoneal injections of Ang II; 4 hours later, leukocyte recruitment in mesenteric microcirculation was examined using intravital microscopy. Ang II (1 nM) produced significant arteriolar leukocyte adhesion of mononuclear cells. Using function-blocking monoclonal antibodies (mAbs) against different rat cell adhesion molecules (CAMs), we discovered that this effec…

Anti-arthritic activity of a lipophilic woad (Isatis tinctoria) extract

A dichloromethane extract of Isatis tinctoria was tested in the adjuvant-induced arthritis model in rats. The extract (150 mg/kg p. o.) leads to a significant reduction of paw oedema. Radiographic, histological and clinical assessment confirmed reduced damage of cartilage and signs of inflammatory response in comparison to untreated control. No significant differences were observed in the tissular levels of cyclooxygenases 1 and -2, and of inducible nitric oxide synthase in Isatis treated and untreated animals. High dose treatment with Isatis extract for two weeks did not result in macroscopic lesions of the gastric mucosa.