ABSTRACT
In pituitary tumors, P27(CDKN1B) is underexpressed. We aimed to clarify whether translational regulation underlies this phenomenon. This study evaluated the expression of P27/CDKN1B, its targets (CCNE1, CDK2) and translational regulators (DKC1, RPS13, miR221, miR222) and screened for DKC1 variants in sporadic pituitary adenomas. Samples were obtained during transsphenoidal surgery from 48 patients with pituitary adenomas: 10 ACTH-, 17 GH-secreting, and 21 nonfunctioning (NFPA). The control group comprised 7 normal pituitaries (NP) obtained during autopsies. Gene expression was assessed by RT-PCR and protein expression by immunohistochemistry. The 15 exons of DKC1 were sequenced. P27 protein underexpression was observed in all adenomas subtypes (p=0.001). CCNE1 mRNA (p=0.01) overexpression, but not protein, was observed in NFPA. No differential gene expression among groups was observed in CDKN1B regulators RPS13 (p=0.23) and DKC1 (p=0.34). The expression of miR221 and miR222 was similar among tumors and NP. Frequent DKC1 variants (SNPs) were found in exon 14 and in the 3'-UTR in similar frequency to NCBI-dsSNP databases. We also observed rare DKC1 variants in 11% of the studied tumor samples, indicating a high prevalence in pituitary adenomas, however, in silico studies failed to indicate deleterious effects. The high frequency of DKC1 variants may influence, in some extent, pituitary tumors development, without clear role in its tumorigenesis. Our data reinforce the P27 underexpression in pituitary adenomas and provide further evidence of the post-translational machinery involvement, although this phenomenon cannot be explained either by mis-expression of P27 translational regulators - DKC1, RPS13, miR221, miR222 - or directly by DKC1 mutations.
Subject(s)
Carcinogenesis/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Pituitary Neoplasms/metabolism , Protein Biosynthesis , Base Sequence , Carcinogenesis/pathology , Cell Cycle Proteins/metabolism , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Nuclear Proteins/metabolism , Pituitary Gland/metabolism , Pituitary Gland/pathology , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , Reference StandardsABSTRACT
PURPOSE: Telomere dysfunction and telomerase activation underlie cancer transformation. This study aims to investigate the contribution of telomere biology to pituitary tumor behavior. SUBJECTS AND METHODS: Samples from 50 patients with pituitary tumors (11 ACTH-secreting, 18 GH-secreting, and 21 non-secreting tumors) and 7 subjects without pituitary lesions were collected. The expressions of telomerase essential components TERT and TERC and tumor telomere content were measured by quantitative PCR techniques. RESULTS: Telomerase (TERT) expression was detected in 36% of tumors. No correlation was observed between TERT and TERC expression level and tumor size in any tumor type. There was no association between gene expression and clinical findings. Telomere content (T/S ratio) was similar between pituitary adenomas (0.39 ± 0.16) and normal pituitaries (0.47 ± 0.12; p = 0.24) and also was between the different adenoma types: ACTH-secreting (0.43 ± 0.08), GH-secreting (0.31 ± 0.12), and non-secreting (0.42 ± 0.20; p = 0.10) tumors. CONCLUSIONS: The telomere content and expression of telomerase components are comparable between normal pituitary glands and tumor tissues, suggesting that telomere biology does not play an important role in pituitary tumor development.
Subject(s)
Gene Expression/physiology , Pituitary Neoplasms/metabolism , Telomerase/metabolism , Telomere/metabolism , Adult , Humans , Middle Aged , Pituitary Neoplasms/enzymology , RNA/metabolismABSTRACT
OBJECTIVES: Pituitary stem cells play a role in the oncogenesis of human adamantinomatous craniopharyngiomas (aCPs). We hypothesized that crosstalk between the Wnt/ß-catenin and Sonic Hedgehog (SHH) pathways, both of which are important in normal pituitary development, would contribute to the pathogenesis of aCPs. DESIGN: To explore the mRNA and protein expression of components of the SHH signaling pathway in aCPs and their relationship with the identification of CTNNB1/ß-catenin mutations and patients outcomes. PATIENTS AND METHODS: In 18 aCP samples, CTNNB1 was sequenced, and the mRNA expression levels of SHH pathway members (SHH, PTCH1, SMO, GLI1, GLI2, GLI3, and SUFU) and SMO, GLI1, GLI3, SUFU, ß-catenin, and Ki67 proteins were evaluated by quantitative real-time PCR and immunohistochemistry respectively. Anterior normal pituitaries were used as controls. Associations between molecular findings and clinical data were analyzed. RESULTS: The aCPs presented higher mRNA expression of SHH (+400-fold change (FC); P<0.01), GLI1 (+102-FC; P<0.001), and GLI3 (+5.1-FC; P<0.01) than normal anterior pituitaries. Longer disease-free survival was associated with low SMO and SUFU mRNA expression (P<0.01 and P=0.02 respectively). CTNNB1/ß-catenin mutations were found in 47% of the samples. aCPs with identified mutations presented with higher mRNA expression of SMO and GLI1 (+4.3-FC; P=0.02 and +10.2-FC; P=0.03 respectively). SMO, GLI1, GLI3, and SUFU staining was found in 85, 67, 93, and 64% of the samples respectively. Strong GLI1 and GLI3 staining was detected in palisade cells, which also labeled Ki67, a marker of cell proliferation. CONCLUSIONS: The upregulation of SHH signaling occurs in aCPs. Thus, activation of Wnt/ß-catenin and SHH pathways, both of which are important in pituitary embryogenesis, appears to contribute to the pathogenesis of aCP.
Subject(s)
Craniopharyngioma/metabolism , Hedgehog Proteins/metabolism , Pituitary Neoplasms/metabolism , Adolescent , Adult , Child , Craniopharyngioma/genetics , Female , Hedgehog Proteins/genetics , Humans , Male , Mutation , Pituitary Neoplasms/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptor Cross-Talk , Signal Transduction/genetics , Up-Regulation , Young Adult , beta Catenin/metabolismABSTRACT
Glioblastoma (GBM) is one of the most aggressive central nervous system tumors with a patient's median survival of <1 year. Polo-like kinases (PLKs) are a family of serine/threonine kinases that have key roles in cell cycle control and DNA-damage response. We evaluated PLK1, 2, 3 and 4 gene expression in 8 GBM cell lines and 17 tumor samples, and analyzed the effect of the PLK1 inhibition on SF188 and T98G GBM cell lines and 13 primary cultures. Our data showed PLK1 overexpression and a variable altered expression of PLK2, 3 and 4 genes in GBM tumor samples and cell lines. Treatments with nanomolar concentrations of BI 2536, BI 6727, GW843682X or GSK461364 caused a significant decrease in GBM cells proliferation. Colony formation was also found to be inhibited (P<0.05), whereas apoptosis rate and mitotic index were significantly increased (P<0.05) after PLK1 inhibition in both GBM cell lines. Cell cycle analysis showed an arrest at G2 (P<0.05) and cell invasion was also decreased after PLK1 inhibition. Furthermore, simultaneous combinations of BI 2536 and temozolomide produced synergistic effects for both the cell lines after 48 h of treatment. Our findings suggest that PLK1 might be a promising target for the treatment of GBMs.
Subject(s)
Brain Neoplasms/metabolism , Cell Cycle Checkpoints , Cell Cycle Proteins/antagonists & inhibitors , Glioblastoma/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/pharmacology , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/genetics , Cell Cycle Proteins/genetics , Cell Death/drug effects , Cell Death/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Dacarbazine/pharmacology , Drug Synergism , Glioblastoma/drug therapy , Glioblastoma/genetics , Humans , Protein Kinase Inhibitors/administration & dosage , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics , Temozolomide , Tumor Stem Cell Assay , Polo-Like Kinase 1ABSTRACT
Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98 th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.
Subject(s)
Cerebellum/metabolism , Myosin Type V/metabolism , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Cadaver , Child , Child, Preschool , Electrophoresis, Agar Gel , Female , Humans , Immunoblotting , Immunohistochemistry , Infant , Infant, Newborn , Male , Young AdultABSTRACT
Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Young Adult , Cerebellum/metabolism , Myosin Type V/metabolism , Age Factors , Cadaver , Electrophoresis, Agar Gel , Immunoblotting , ImmunohistochemistryABSTRACT
Adrenocortical tumors (ACT) are rare neoplasms of the adrenal glands accounting for 0.2% of all pediatric cancers. However, the incidence of ACT in South Brazilian children is 10 to 15 times greater than the worldwide incidence. Comparative genomic hybridization studies have revealed the presence of a high degree of chromosomal instability in ACT. We evaluated 16 ACT, 8 of them carcinomas and 8 adenomas. The presence of changes in DNA copy numbers was determined by comparative genomic hybridization, and the findings were validated by real-time polymerase chain reaction on the basis of IGF-II gene expression. The adenomas showed a mean of 19.7 imbalances per case, with the most frequent gain and loss being 4p15.1-p15.3 and 20p11.2-p13.2, respectively. The carcinomas presented with a mean of 35.5 imbalances per case, with the more frequent gain being 2q14.1-q24.3 and the more frequent losses being 3q21-q26.2, 20q12-qter, and 22q11.2-q13.3. The most frequent imbalances in both adenomas and carcinomas were gains of 1p21-p31.2, 2p12-p21 and loss of 20p11.2-p12. The expression of IGF-II mRNA (11p15.5) was higher in samples that presented with a gain of this region. It has been established that great genomic instability exists in pediatric ACT.
Subject(s)
Adrenal Cortex Neoplasms/genetics , Adolescent , Adrenal Cortex Neoplasms/pathology , Child , Child, Preschool , Comparative Genomic Hybridization , DNA Copy Number Variations , Female , Gene Expression Regulation, Neoplastic , Humans , Infant , Insulin-Like Growth Factor II/genetics , MaleABSTRACT
Interference by autofluorescence is one of the major concerns of immunofluorescence analysis of in situ hybridization-based diagnostic assays. We present a useful technique that reduces autofluorescent background without affecting the tissue integrity or direct immunofluorescence signals in brain sections. Using six different protocols, such as ammonia/ethanol, Sudan Black B (SBB) in 70% ethanol, photobleaching with UV light and different combinations of them in both formalin-fixed paraffin-embedded and frozen human brain tissue sections, we have found that tissue treatment of SBB in a concentration of 0.1% in 70% ethanol is the best approach to reduce/eliminate tissue autofluorescence and background, while preserving the specific fluorescence hybridization signals. This strategy is a feasible, non-time consuming method that provides a reasonable compromise between total reduction of the tissue autofluorescence and maintenance of specific fluorescent labels.
Subject(s)
Coloring Agents/pharmacology , Histocytological Preparation Techniques/methods , Ammonia , Azo Compounds , Brain , Fluorescence , Fluorescent Antibody Technique , Fluorescent Antibody Technique, Direct , Formaldehyde , Frozen Sections , Histological Techniques , Humans , Indicators and Reagents , Naphthalenes , Nucleic Acid Hybridization , Paraffin Embedding , PhotobleachingABSTRACT
Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.
Subject(s)
Cadherins/genetics , Gene Expression Profiling , Neoplasms, Neuroepithelial/genetics , Adolescent , Adult , Brain/metabolism , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Neoplasms, Neuroepithelial/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.
Subject(s)
Humans , Adolescent , Adult , Middle Aged , Cadherins/genetics , Gene Expression Profiling , Neoplasms, Neuroepithelial/genetics , Cerebrum/metabolism , Gene Expression Regulation, Neoplastic , Neoplasms, Neuroepithelial/pathology , Reverse Transcriptase Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
OBJECTIVE: In children with and without infantile spasms, this study determined brain volumes and cell densities in epilepsy surgery patients with tuberous sclerosis complex (TSC) and cortical dysplasia with balloon cells (CD). METHODS: We compared TSC (n = 18) and CD (n = 17) patients with normal/autopsy controls (n = 20) for MRI gray and white matter volumes and neuronal nuclei (NeuN) cell densities. RESULTS: In patients without a history of infantile spasms, TSC cases showed decreased gray and white matter volumes (-16%). In cases with a history of infantile spasms, both CD (-25%) and TSC (-35%) patients showed microencephaly. This was confirmed in monozygotic twins with TSC, where the twin with a history of spasms had cerebral volumes less (-16%) than the twin without a history of seizures. Regardless of seizure history, TSC patients showed decreased NeuN cell densities in lower gray matter (-36%), whereas CD patients had increased densities in upper cortical (+52%) and white matter regions (+65%). For TSC patients, decreased lower gray matter NeuN densities correlated with reduced MRI volumes. CONCLUSIONS: Patients with tuberous sclerosis without spasms showed microencephaly associated with decreased cortical neuronal densities. In contrast, cortical dysplasia patients without spasms were normocephalic with increased cell densities. This supports the concept that tuberous sclerosis and cortical dysplasia have different pathogenetic mechanisms despite similarities in refractory epilepsy and postnatal histopathology. Furthermore, a history of infantile spasms was associated with reduced cerebral volumes in both cortical dysplasia and tuberous sclerosis patients, suggesting that spasms or their treatment may contribute to microencephaly independent of etiology.
Subject(s)
Cerebral Cortex/abnormalities , Cerebral Cortex/pathology , Microcephaly/pathology , Spasms, Infantile/complications , Spasms, Infantile/pathology , Tuberous Sclerosis/complications , Tuberous Sclerosis/pathology , Child , Cohort Studies , Female , Humans , Infant, Newborn , Male , Microcephaly/complicationsABSTRACT
We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79 percent). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25 percent (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6 percent), which declined to 11 of 31 (35.5 percent) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Epilepsy, Temporal Lobe/surgery , Hippocampus/pathology , Temporal Lobe/pathology , Atrophy , Electroencephalography/methods , Magnetic Resonance Imaging , Postoperative Period , Retrospective Studies , Treatment Outcome , Video RecordingABSTRACT
We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79%). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25% (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6%), which declined to 11 of 31 (35.5%) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.
Subject(s)
Epilepsy, Temporal Lobe/pathology , Hippocampus/pathology , Temporal Lobe/pathology , Atrophy , Child , Child, Preschool , Electroencephalography/methods , Epilepsy, Temporal Lobe/surgery , Female , Humans , Magnetic Resonance Imaging , Male , Postoperative Period , Retrospective Studies , Treatment Outcome , Video RecordingSubject(s)
Brain Neoplasms/pathology , Dura Mater/pathology , Lymphoma, B-Cell, Marginal Zone/pathology , Brain Neoplasms/therapy , Combined Modality Therapy , Diabetes Mellitus , Diagnosis, Differential , Female , Humans , Hypertension/complications , Lymphoma, B-Cell, Marginal Zone/therapy , Magnetic Resonance Imaging , Meningioma/pathology , Middle Aged , Neoplasm Recurrence, Local/pathology , Tomography, X-Ray ComputedABSTRACT
The objective of the present study was to assess the effectiveness of a combined protocol of muscle stretching and strengthening after immobilization of the hindlimb. Thirty female Wistar rats were divided into 6 groups: group immobilized for 14 days to cause full plantar flexion by cast (GI, n = 6); group immobilized/stretched (GIS, n = 6): submitted to the same immobilization and to 10 days of passive stretching; group immobilized/electrically stimulated (GIES, n = 6): similarly immobilized and submitted to 10 days of low frequency electrical stimulation (ES); group immobilized/stretched/electrically stimulated (GISES, n = 6): similarly immobilized, submitted to 10 days of stretching and ES application; group immobilized/free (GIF, n = 3): similarly immobilized and then left with free limbs for 10 days; control group (CG, n = 3). The middle portion of the soleus muscle was frozen and sections were stained with HE or mATPase. Morphological analysis revealed high cellular reactivity in the GISES, GIES and GIS groups. The lesser diameter and proportion of type I fibers (TIF) and type II fibers (TIIF) (at pH 9.4) and connective area (at HE stain) were measured with an image analyzer and the data obtained were analyzed statistically by the unpaired Student t-test (p < or = 0.05). The results indicated that: a) immobilization generated atrophy of both fiber types (p < 0.05); b) joint application of ES and stretching was not efficient in reestablishing the size of the two fiber types compared to CG (p < 0.05); c) the ES protocol reestablished only the size of TIIF, which showed values similar to those detected in CG (p < 0.05); d) the stretch increased the proliferation of the perimysium connective tissue (p < 0.05). Thus, we conclude that, in the model applied here to female rats, a stretching protocol may limit the volume protein gain of soleus muscle fibers and increase the connective interstitial tissue.
Subject(s)
Muscle, Skeletal/pathology , Animals , Cell Proliferation , Electric Stimulation , Female , Hydrogen-Ion Concentration , Image Processing, Computer-Assisted , Immobilization , Models, Statistical , Muscle Contraction , Muscle Fibers, Skeletal/pathology , Muscular Atrophy , Rats , Rats, WistarABSTRACT
Costicosteroides sistemicos em altas doses podem causar miopatia metabolica. O Objetivo deste estudo foi valiar, por meio de ensaios de tracao, os efeitos da miopatia induzida por corticosteroides nas propriedades mecanicas do musculo gastrocnemio medial de coelhos. Foram estudados dois grupos de 15 coelhas da raca Nova Zelandia: grupo experimental (GE), que recebeu injecoes subcutaneas de metil-prednisolona (2mg/kg/dia), e grupo-controle (GC), que recebeu solucao fisiologica por via subcutanea. Os grupos foram tratados por 21 dias. Foram feitos ensaios de tracao nos musculos gastrocnemios mediais esquerdos. Resultados: o peso final dos animais do GE foi 3,6+-0,1kg e do GC, 40+-0,1kg. O peso final do gastrocnemio do GE foi 5,6+-1,0g e do GC, 7,0+-1,3g. Os valores de area, largura e espessura do gastrocnemio...
Subject(s)
Adrenal Cortex Hormones , Biomechanical PhenomenaABSTRACT
BACKGROUND: Although neuroimage and surgical techniques have improved substantially, the prognosis of patients with astrocytic tumors remains unchanged. The purpose of this study was to evaluate the proliferative activity in astrocytic tumors in different grades of malignancy and correlate it to other clinical features. PATIENTS AND METHODS: From archival paraffin-embedded surgical specimens of 40 patients of the Ribeirão Preto Medical School with World Health Organization grade II (n = 10), grade III (n = 5) and grade IV astrocytomas (n = 25), the MIB-1 labeling index (LI) was determined using at least a half of the blocks per case. The results were correlated to the biological behavior of the tumors. The aims of this study were to determine the level of MIB-1 LI values (cut-off) that reflect differences in biological behavior of these tumors, the impact on survival of clinical features such as age, tumor location or extension of surgical removal as well as the adjuvant therapy. RESULTS AND CONCLUSIONS: As expected, a wide range of MIB-1 LI values was disclosed (mean of 2.35% in grade II astrocytomas to 12.28% in glioblastomas). A close relationship was found between MIB-1 LI and survival of patients with astrocytomas according to the histological grade. All but 1 recurrent tumor presented higher MIB-1 LI in the second biopsy, and the mean MIB-1 LI of the patients who died in the immediate postoperative period (n = 7) was higher in comparison to the MIB-1 LI of the respective grade. Postoperative radiation therapy was an important factor that affected the survival of patients with high-grade astrocytomas (p = 0.006). MIB-1 LI cut-off of 3% divided the astrocytomas in 2 groups with significantly different survival (p < 0.001): median survival time of 12 months (low-grade) versus 45 months (high-grade). On the other hand, univariate analysis did not show any correlation between survival and extension of surgical resection (radical versus partial), tumor's location or patient's age at surgery.
Subject(s)
Astrocytoma/metabolism , Biomarkers, Tumor/analysis , Brain Neoplasms/metabolism , Ki-67 Antigen/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Astrocytoma/mortality , Astrocytoma/pathology , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Child , Child, Preschool , Female , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Male , Middle Aged , Prognosis , Reference Values , Retrospective Studies , Survival AnalysisABSTRACT
Castleman's disease is an atypical lymphoproliferative disorder that may present as a localized or multicentric form. The involvement of the central nervous system is rare. We describe here a case of Castleman's disease with involvement of the hypothalamus and meninges, presenting as hypopituitarism. Radiological and clinical pathological features are emphasized and a review of the literature is presented.