CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants

OBJECTIVES: We investigated four components of the Wnt signaling pathway in medulloblastomas. Medulloblastoma is the most common type of malignant pediatric brain tumor, and the Wnt signaling pathway has been shown to be activated in this type of tumor. METHODS: Sixty-one medulloblastoma cases were analyzed for β-catenin gene (CTNNB1) mutations, β-catenin protein expression via immunostaining and Wnt signaling pathway-related gene expression. All data were correlated with histological subtypes and patient clinical information. RESULTS: CTNNB1 sequencing analysis revealed that 11 out of 61 medulloblastomas harbored missense mutations in residues 32, 33, 34 and 37, which are located in exon 3. These mutations alter the glycogen synthase kinase-3β phosphorylation sites, which participate in β-catenin degradation. No significant differences were observed between mutation status and histological medulloblastoma type, patient age and overall or progression-free survival times. Nuclear β-catenin accumulation, which was observed in 27.9% of the cases, was not associated with the histological type, CTNNB1 mutation status or tumor cell dissemination. The relative expression levels of genes that code for proteins involved in the Wnt signaling pathway (CTNNB1, APC, AXIN1 and WNT1) were also analyzed, but no significant correlations were found. In addition, large-cell variant medulloblastomas presented lower relative CTNNB1 expression as compared to the other tumor variants. CONCLUSIONS: A small subset of medulloblastomas carry CTNNB1 mutations with consequent nuclear accumulation of β-catenin. The Wnt signaling pathway plays a role in classic, desmoplastic and extensive nodularity medulloblastoma variants but not in large-cell medulloblastomas

Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue

Factors associated with serum CA19-9 levels among healthy children: a cross-sectional study

Abstract\ud \ud \ud \ud Background\ud CA19-9 is a tumor marker mainly used for biliary tract, pancreas and colorectum. Since the marker applies usually for adults, the normal range of serum CA19-9 among children has been rarely reported. This is the first study reporting the distribution of serum CA19-9 levels among cancer-free children as well as their parents, taking into account the Lewis and secretor gene polymorphism and physical growth.\ud \ud \ud \ud Methods\ud Study subjects were 972 apparently healthy Japanese Brazilians including 476 children aged from 1 to 19 years.\ud \ud \ud \ud Results\ud The comparisons in five-year age groups demonstrated that the mean values of serum CA19-9 was lower in the boys than in the girls, and higher in younger age groups; 22.5 U/ml for 1–4 year-old (n=13), 17.4 U/ml for 5–9 year-old (n=36), 15.5 U/ml for 10–14 year-old (n=96) and 10.2 U/ml for 15–19 year-old (n=74) in boys, and 25.3 U/ml (n=11), 27.1 U/ml (n=50), 17.7 U/ml (n=105) and 13.5 U/ml (n=59) in girls, respectively. The difference in those geometric means was statistically significant among four age groups (p=0.006, ANOVA adjusted for sex). After Lewis and secretor genotypes, which are definitive factors of serum CA19-9, were taken into account, geometric mean of serum CA19-9 was associated with any of BMI (p<0.001), height (p<0.001) and weight (p<0.001) among children excluding those with le/le genotype. The associations were still significant when age was adjusted.\ud \ud \ud \ud Conclusions\ud Serum CA19-9 values were higher among children than among adults, and influenced by sex, height, weight, and BMI even after the adjustment for age as well as Le and Se genotypes.This study was supported in part by a Grant-in-Aid for Scientific Research on Special Priority Areas of Cancer from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. We are grateful to Ms. Yoko Mitsuda and Ms. Keiko Shibata for their technical assistance

IDH1 mutations in a Brazilian series of Glioblastoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Albert Einstein Jewish HospitalUniversidade de São Paulo Faculdade de Medicina Department of NeurologyUniversidade de São Paulo Faculdade de Medicina Department of PathologyCancer Institute of São PauloFundação Pio XII Barretos Cancer HospitalFederal University of São Paulo School of Medicine Department of NeurologyFederal University of São Paulo School of Medicine Department of PathologyNove de Julho HospitalAlbert Einstein Jewish HospitalUNIFESP, EPM, Department of NeurologyUNIFESP, EPM, Department of PathologyFAPESP: 04/12133-6SciEL

Balanced Subdivisions with Boundary Condition of Two Sets of Points in the Plane

Abstract Let R and B be two disjoint sets of red points and blue points in the plane, respectively, such that no three points of R ∪ B are collinear, and let a, b and g be positive integers. We show that if ag ≤ |R| &lt; (a + 1)g and bg ≤ |B| &lt; (b + 1)g, then we can subdivide the plane into g convex polygons so that every open convex polygon contains exactly a red points and b blue points and that the remaining points lie on the boundary of the subdivision. This is a generalization of equitable subdivision of ag red points and bg blue points in the plane

Factors associated with serum CA19-9 levels among healthy children: a cross-sectional study

BACKGROUND: CA19-9 is a tumor marker mainly used for biliary tract, pancreas and colorectum. Since the marker applies usually for adults, the normal range of serum CA19-9 among children has been rarely reported. This is the first study reporting the distribution of serum CA19-9 levels among cancer-free children as well as their parents, taking into account the Lewis and secretor gene polymorphism and physical growth. METHODS: Study subjects were 972 apparently healthy Japanese Brazilians including 476 children aged from 1 to 19 years. RESULTS: The comparisons in five-year age groups demonstrated that the mean values of serum CA19-9 was lower in the boys than in the girls, and higher in younger age groups; 22.5 U/ml for 1–4 year-old (n=13), 17.4 U/ml for 5–9 year-old (n=36), 15.5 U/ml for 10–14 year-old (n=96) and 10.2 U/ml for 15–19 year-old (n=74) in boys, and 25.3 U/ml (n=11), 27.1 U/ml (n=50), 17.7 U/ml (n=105) and 13.5 U/ml (n=59) in girls, respectively. The difference in those geometric means was statistically significant among four age groups (p=0.006, ANOVA adjusted for sex). After Lewis and secretor genotypes, which are definitive factors of serum CA19-9, were taken into account, geometric mean of serum CA19-9 was associated with any of BMI (p<0.001), height (p<0.001) and weight (p<0.001) among children excluding those with le/le genotype. The associations were still significant when age was adjusted. CONCLUSIONS: Serum CA19-9 values were higher among children than among adults, and influenced by sex, height, weight, and BMI even after the adjustment for age as well as Le and Se genotypes

Syntheses and Molecular Structures of Monomeric and Hydrogen-Bonded Dimeric Dawson-Type Trialuminum-Substituted Polyoxotungstates Derived under Acidic and Basic Conditions

The syntheses and molecular structures of the two types of α-Dawson-type trialuminum-substituted polyoxometalates, [B-α-H₃P₂W₁₅O₅₉{Al­(OH₂)}₃]^6– (<b>1</b>) and [B-α-H₃P₂W₁₅O₅₉{Al­(OH)}₂{Al­(OH₂)}]₂^16– (<b>2</b>), are described herein. The potassium and cesium salts of <b>1</b>, K₆[B-α-H₃P₂W₁₅O₅₉{Al­(OH₂)}₃]·14H₂O (<b>K-1</b>), and Cs₆[B-α-H₃P₂W₁₅O₅₉{Al­(OH₂)}₃]·13H₂O (<b>Cs-1</b>) were formed by a stoichiometric reaction in water of trilacunary α-Dawson polyoxotungstate with aluminum nitrate under acidic conditions (pH ∼3). The potassium/sodium and tetramethylammonium/sodium salts of <b>2</b>, K₁₄Na₂[B-α-H₃P₂W₁₅O₅₉{Al­(OH)}₂{Al­(OH₂)}]₂·30H₂O (<b>KNa-2</b>) and [(CH₃)₄N]₁₄Na₂[B-α-H₃P₂W₁₅O₅₉{Al­(OH)}₂{Al­(OH₂)}]₂·39H₂O (<b>TMANa-2</b>) were obtained under basic conditions (pH ∼9). These compounds were characterized by X-ray structure analyses, elemental analyses, thermogravimetric/differential thermal analyses, Fourier transform infrared, and solution ³¹P, ²⁷Al, and ¹⁸³W NMR spectroscopy. The polyoxoanion <b>1</b> is a monomeric, α-Dawson-type structure, resulting in an overall <i>C</i>_3<i>v</i> symmetry, while the polyoxoanion <b>2</b> is a hydrogen-bonded dimeric structure, resulting in an overall <i>S</i>₃ symmetry in the solid state. The pH dependence of polyoxoanions <b>1</b> and <b>2</b> in aqueous solution was also investigated by ³¹P NMR spectroscopy