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Nova Londrina, Brazil

Panis C.,Instituto Nacional do Cancer | Panis C.,State University Londrina | Pizzatti L.,Instituto Nacional do Cancer | Herrera A.C.,State University Londrina | And 3 more authors.
Cancer Letters | Year: 2013

This study evaluated the plasmatic proteomic profile of breast cancer patients in the early (ED) and advanced (AD) stages, employing high-throughput proteomics. We identified 92 differentially expressed proteins in ED and 73 proteins in AD patients. Gelsolin, lumican, clusterin, SALL4 and PMS2, as well hTERT, TNF-α and GRHL3 were chosen for further investigation. ED presented augmented expression of GRHL3 and reduced circulating TNF-α with high expression of GRHL3 in tumors. AD displayed high TNF-α and a significant expression of PMS2 in tumors. These findings suggest processes enrolling stem cell division in ED, with TNF-α signaling and DNA mismatch repair in the advanced stage. © 2012. Source


Panis C.,Instituto Nacional do Cancer | Panis C.,West Parana State University | Pizzatti L.,Instituto Nacional do Cancer | Pizzatti L.,Federal University of Rio de Janeiro | And 7 more authors.
Cancer Letters | Year: 2015

Overexpression of human epithelial growth factor receptor 2 (HER2) is a poor prognostic factor in breast cancer. HER2 is a transmembrane receptor comprising an extracellular domain (ECD), a single transmembrane domain, and an intracellular domain (ICD) with tyrosine-kinase activity. Receptor dimerization triggers pivotal effector pathways in cancer, such as phosphatidylinositol 3-kinase (PI3K) signaling. Currently, screening of HER2 in breast tumors for prognostic and therapeutic purposes involves immunohistochemical (IHC) phenotyping for the ECD, in which tumors with IHC scores below 2+ are reported as HER2-negative. We used a label-free liquid chromatography-mass spectrometry (LC-MS) proteomic approach to compare plasma samples from patients with HER2-positive breast tumors and patients with HER2-negative tumors. Patients with HER2-negative tumors expressed higher circulating levels of calpain-10 than patients with HER2-positive tumors. Calpains cleave HER2, releasing its ECD and transforming phenotypically positive tumors into phenotypically negative tumors. Therefore, we investigated the expression of the ICD in HER2-negative samples that overexpressed calpain-10. We found that 16% of HER2-negative tumors were positive for HER2-ICD, which was associated with circulating HER2-ECD. HER2 gene amplification was also observed in some HER2-negative tumors. Positive staining for the PI3K pathway was observed in the HER2-negative, ICD-positive tumors, similar to the HER2-positive cohort. Microarray analysis revealed that HER2-negative, ICD-positive samples clustered between HER2-positive tumors and triple-negative tumors. Survival analysis revealed that outcome in women with HER2-negative, ICD-positive tumors was better than in women bearing HER2-negative, ICD-negative (triple negative) tumors but was quite similar to HER2-positive tumors and worse than women with luminal A tumors. Moreover, in vitro analyses revealed that MDA-MB 231, a triple negative cell line, possesses calpain-10 and HER2-p-ICD up-regulation and blockage of calpain-10 activity promoted an increase in HER2-p-ICD and p-AKT levels, suggesting an increase in these pathways signaling. These data indicate that HER2-negative tumors with HER2-ICD positivity exhibit clinical behavior closer to that of HER2-positive tumors. This indicates a need for HER2-ICD screening when determining the molecular profile of breast tumors. These findings further indicate that lapatinib should be investigated as a target therapy for HER2-ICD-positive breast tumors. © 2014 Elsevier Ireland Ltd. Source


Pagliarini-e-Silva S.,State University of Maringa | Santos B.C.,State University of Maringa | Pereira E.M.F.,State University of Maringa | Ferreira M.E.,Hospital do Cancer de Maringa | And 3 more authors.
Clinics | Year: 2013

Objective: The JAK2 46/1 haplotype has recently been described as a major contributing factor to the development of myeloproliferative neoplasm, whether positive or negative for the JAK2 V617F mutation. The G allele, identified by a single-nucleotide polymorphism known as JAK2 rs10974944, is part of the JAK2 46/1 haplotype. The aim of this study was to verify the association between the presence of the G allele and the development of BCR-ABL-negative chronic myeloproliferative neoplasms in our population. Methods: Blood and oral mucosa swab samples were obtained from 56 patients of two local Brazilian hospitals who had previously been diagnosed with BCR-ABL-negative chronic myeloproliferative neoplasms. Blood samples from 90 local blood donors were used as controls. The presence of the G allele was assessed using a PCR-RFLP assay after extracting DNA from the samples. Results: The presence of the G allele was strongly associated with the presence of BCR-ABL-negative chronic myeloproliferative neoplasms (p=0.0001; OR= 2.674; 95% CI = 1.63024.385) in the studied population. Conclusion: In agreement with previous reports, the JAK2 46/1 haplotype, represented in this study by the presence of the G allele, is an important predisposing factor in the oncogenetic development of these neoplasms in our population. © 2013 CLINICS. Source


Castro-Gomez R.H.,State University Londrina | Aoki M.N.,Instituto Do Cancer Of Londrina
Experimental and Therapeutic Medicine | Year: 2010

Carboxymethyl-glucan (CM-G) is a water-soluble derivative of β(1-3)(1-6) glucan that is well known for its immunostimulant and hematopoiesis-enhancing activities. In this clinical trial, we assessed the effects of oral CM-G administration on the peripheral blood cells of patients with advanced prostate cancer, and examined its ability to alter hepatic and renal function. After CM-G administration, the total leukocyte count increased significantly (p≤0.02), with no associated changes in the lifestyle habits of the patients. A significant increase (p≤0.001) was also observed for red blood cell, hematocrit, hemoglobin and platelet counts. No changes were observed in hepatic or renal function after CM-G administration, and no side effects associated with its use were recorded. These results suggest that using CM-G as an adjuvant to cancer treatment may improve the health parameters of prostate cancer patients. Source


Macedo L.C.,State University of Maringa | Santos B.C.,State University of Maringa | Pagliarini-e-Silva S.,State University of Maringa | Pagnano K.B.B.,University of Campinas | And 7 more authors.
International Journal of Laboratory Hematology | Year: 2015

Introduction: This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR-ABL-negative chronic myeloproliferative neoplasms (cMPNs) in our population. Methods: The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR-RFLP assay. Results: The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F positive, than in the control population. We also compared the 46/1 haplotype status in each MPN disease entity, polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and MPNu with controls. The G allele frequency relative to controls was significantly enriched in patients with PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all of whom had the JAK2 V617F mutation, showed significant excess of the G allele. The frequency of JAK2 V617F mutation was associated with elevated hematological parameters, but when we analyze the occurrence of the mutation and the presence of the G allele, just the high hemoglobin was significantly. Conclusion: In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients. © 2015 John Wiley & Sons Ltd. Source

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