Expression of ck-19, galectin-3 and hbme-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis

Background: To distinguish between malignant and benign lesions of the thyroid gland histological demonstration is often required since the fine-needle aspiration biopsy method applied pre-operatively has some limitations. in an attempt to improve diagnostic accuracy, markers using immunocytochemistry and immunohistochemistry techniques have been studied, mainly cytokeratin-19 (CK-19), galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1). However, current results remain controversial. the aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions.Methods: A systematic review of published articles on MEDLINE and the Cochrane Library was performed. After establishing inclusion and exclusion criteria, 66 articles were selected. the technique of meta-analysis of diagnostic accuracy was employed and global values of sensitivity, specificity, area under the summary ROC curve, and diagnostic odds ratio (dOR) were calculated.Results: for the immunohistochemistry technique, the positivity of CK-19 for the diagnosis of malignant thyroid lesions demonstrated global sensitivity of 81% and specificity of 73%; for Gal-3, sensitivity of 82% and specificity of 81%; and for HBME-1, sensitivity of 77% and specificity of 83%. the association of the three markers determined sensitivity of 85%, specificity of 97%, and diagnostic odds ratio of 95.1. Similar results were also found for the immunocytochemistry assay.Conclusion: This meta-analysis demonstrated that the three immunomarkers studied are accurate in pre- and postoperative diagnosis of benign and malignant thyroid lesions. Nevertheless, the search for other molecular markers must continue in order to enhance this diagnostic accuracy since the results found still show a persistency of false-negative and false-positive tests.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fac Med ABC, Dept Biochem, Santo Andre, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFac Med ABC, Dept Head & Neck Surg, Santo Andre, BrazilFac Med ABC, Med Sch Students, Santo Andre, BrazilFac Med ABC, Dept Hematol & Oncol, Santo Andre, BrazilAlbert Einstein Jewish Hosp, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilWeb of Scienc

XM02, the First Biosimilar G-CSF, is Safe and Effective in Reducing the Duration of Severe Neutropenia and Incidence of Febrile Neutropenia in Patients with Small Cell or Non-small Cell Lung Cancer Receiving Platinum-Based Chemotherapy

BackgroundRecombinant granulocyte colony-stimulating factors such as Neupogen are used to treat chemotherapy-induced neutropenia. The aim of the study was to show that a new granulocyte colony-stimulating factor, XM02, is as safe and effective as Neupogen in the treatment of chemotherapy-induced neutropenia in patients with small cell or non-small cell lung cancer.Patients and methodsA total of 240 patients receiving platinum-based chemotherapy were randomized in cycle 1 to treatment with daily injections (subcutaneous 5 µg/kg/d) of XM02 (n = 160) or Filgrastim Neupogen (n = 80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received XM02.ResultsThe mean duration of severe neutropenia was 0.5 and 0.3 days in cycle 1 for XM02 and Filgrastim, respectively. In the analysis of covariance for duration of severe neutropenia in cycle 1, the estimated treatment difference “XM02 minus Filgrastim” was 0.157 days, with 95% confidence level (−0.114 days, 0.428 days), which was included in the prespecified equivalence range (−1, 1). There was no statistically significant difference of the end point incidence of febrile neutropenia in cycle 1 between XM02 and Filgrastim (p = 0.2347). The adverse event profile was similar between XM02 and Filgrastim.ConclusionXM02 demonstrated similar efficacy and safety profile as the reference medication Filgrastim in cycle 1. In conclusion, treatment with XM02 is beneficial in ameliorating severe neutropenia and febrile neutropenia in lung cancer patients receiving myelosuppressive chemotherapy. XM02 is safe and well tolerated in the doses applied in this study

Bisphosphonate-associated jaws osteonecrosis: an important complication of oncology treatment

Os bisfosfonatos são um grupo de medicamentos utilizados no tratamento de doenças malignas metastáticas e em outras doenças ósseas como osteoporose e doença de Paget. A despeito dos seus benefícios, uma importante complicação denominada de osteonecrose dos maxilares vem sendo observada nos pacientes usuários crônicos dos bisfosfonatos que se caracteriza clinicamente por exposições ósseas na região maxilofacial persistente, acompanhadas de osteomielite, geralmente sintomáticas e cujo tratamento é complexo. Este estudo tem por objetivo revisar a literatura sobre a osteonecrose associada ao uso dos bisfosfonatos, em especial, em oncologia, no período de 2003 a 2008. Serão apresentados e discutidos os fatores de risco, aspectos etiopatogênicos, clínicos, imagenológicos, terapêuticos e preventivos desta doença. Devido à dificuldade de tratamento da osteonecrose associada aos bisfosfonatos, o foco deve ser a prevenção, sendo o ideal a eliminação de quadros infecciosos orais antes da terapia com os bisfosfonatos ter sido iniciada e minimizar traumas em boca após o uso destes medicamentos.Bisphosphonates are drugs used in the treatment of malignant metastatic diseases and in other bone lesions such as osteoporosis and Paget´s disease. Besides their benefits, jaw osteonecrosis, an important side effect, has been observed in long-term users of these drugs. Jaw osteonecrosis is clinically characterized by prolonged maxillary and mandible bone exposure accompanied by osteomyelitis. These lesions are usually symptomatic and difficult to treat. This study has the objective of reviewing publications from 2003 to 2008 about bisphosphonate-associated jaw osteonecrosis, in particular in relation to oncology. Risk factors, and etiopathological, clinical, radiographic, therapeutic, and preventive aspects of this condition are presented and discussed. Due to the difficulty to treat this disease, the focus must be prevention, with the ideal therapy being the elimination of oral infections before treatment with bisphosphonates is initiated thereby attempting to minimize possible traumas to the mouth with the use of these medications

Heparan sulfate mediates trastuzumab effect in breast cancer cells

Background: Trastuzumab is an antibody widely used in the treatment of breast cancer cases that test positive for the human epidermal growth factor receptor 2 (HER2). Many patients, however, become resistant to this antibody, whose resistance has become a major focus in breast cancer research. But despite this interest, there are still no reliable markers that can be used to identify resistant patients. A possible role of several extracellular matrix (ECM) components-heparan sulfate (HS), Syn-1(Syndecan-1) and heparanase (HPSE1)-in light of the influence of ECM alterations on the action of several compounds on the cells and cancer development, was therefore investigated in breast cancer cell resistance to trastuzumab.Methods: the cDNA of the enzyme responsible for cleaving HS chains from proteoglycans, HPSE1, was cloned in the pEGFP-N1 plasmid and transfected into a breast cancer cell lineage. We evaluated cell viability after trastuzumab treatment using different breast cancer cell lines. Trastuzumab and HS interaction was investigated by confocal microscopy and Fluorescence Resonance Energy Transfer (FRET). the profile of sulfated glycosaminoglycans was also investigated by [S-35]-sulfate incorporation. Quantitative RT-PCR and immunofluorescence were used to evaluate HPSE1, HER2 and Syn-1 mRNA expression. HPSE1 enzymatic activity was performed using biotinylated heparan sulfate.Results: Breast cancer cell lines responsive to trastuzumab present higher amounts of HER2, Syn-1 and HS on the cell surface, but lower levels of secreted HS. Trastuzumab and HS interaction was proven by FRET analysis. the addition of anti-HS to the cells or heparin to the culture medium induced resistance to trastuzumab in breast cancer cells previously sensitive to this monoclonal antibody. Breast cancer cells transfected with HPSE1 became resistant to trastuzumab, showing lower levels of HER2, Syn-1 and HS on the cell surface. in addition, HS shedding was increased significantly in these resistant cells.Conclusion: Trastuzumab action is dependent on the availability of heparan sulfate on the surface of breast cancer cells. Furthermore, our data suggest that high levels of heparan sulfate shed to the medium are able to capture trastuzumab, blocking the antibody action mediated by HER2. in addition to HER2 levels, heparan sulfate synthesis and shedding determine breast cancer cell susceptibility to trastuzumab.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Biochem, BR-04044020 São Paulo, BrazilFac Med ABC, Dept Biochem, BR-09060650 Santo Andre, SP, BrazilFac Med ABC, Dept Oncol, BR-09060650 Santo Andre, SP, BrazilUniversidade Federal de São Paulo, Dept Biochem, BR-04044020 São Paulo, BrazilWeb of Scienc

Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients

INTRODUCTION: Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients. METHODS: We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group). RESULTS: In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019). CONCLUSION: We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment

Mutação do Gene p53 induzindo predisposição hereditária ao câncer: relato de um caso da síndrome de Li-Fraumeni

Li-Fraumeni syndrome is a familiar cancer predisposition syndrome characterized by the appearance of various types of tumors, such as sarcomas, breast carcinomas, brain tumors and leukemia. We present the case of a 37-year-old female who had a strong family history of cancer and herself had a history of six different primary tumors (one colon, one displasic nevus, one ovary and three breast tumors). P53 gene sequencing of her peripheral blood lymphocytes revealed an amino acid change of tryptofan (TGG) to a stop-codon (TAG) in the nucleotide 437 of codon 146 of exon 5 of this gene. Clinical, preventive and ethical implications of this molecular finding are also discussed.A Síndrome de Li-Fraumeni é uma síndrome de predisposição familiar ao câncer, caracterizada pela presença de múltiplos tumores, tais como sarcomas, carcinomas de mama, tumores cerebrais e leucemia. O caso relatado é de uma paciente feminina de 37 anos, que apresenta uma significativa história familiar de câncer, bem como história pessoal de seis diferentes tumores primários (um de cólon, um nevus displásico, um de ovário e três de mama). O seqüenciamento do gene supressor de tumor p53 em seus linfócitos presentes no sangue periférico revelou uma mutação do aminoácido triptofano (TGG) para um códon de parada prematuro (TAG), no nucleotídeo 437 do códon 146 do exon 5 deste gene. As implicações clínicas, preventivas e éticas deste caso são também abordadas

Experience with The ABC Foundation School of Medicine Undergraduate Meeting

OBJECTIVE: To quantify the number of studies that were presented during oral sessions, selected for awards and published from 2002 to 2007 at the Undergraduate Medical Congress of ABC at the ABC Foundation School of Medicine. METHODS: A retrospective systematic survey of papers selected for oral presentation and award at these undergraduate meeting from 2002 to 2007 was carried out by searching Medline and Lilacs databases and the annals of other medical meetings in order to ascertain which papers would eventually be published. RESULTS: From 2002 to 2007, 408 papers were selected for oral presentation and 71 (17.4%) received at least one award. The total number of papers published was 138 (33.8%), of which 33 (8.1%) were in Medline, 57 (14%) in Lilacs and 48 (11.7%) in the annals of other scientific meetings. Receiving an award by the scientific committee was an independent variable for publication (OR: 2.05 95% CI 1.22-3.46, p = 0.006) as well as for publication in Medline (OR: 2.62 95% CI 1.21 - 5.69, p = 0.01). CONCLUSION: The institutional scientific production of undergraduate medical students presented in Undergraduate Medical Meetings is relevant and should continue to be stimulated.OBJETIVO: Quantificar e descrever o número de trabalhos premiados e não premiados em apresentação oral no Congresso Médico Universitário do ABC no período de 2002 a 2007, que obtiveram posterior publicação em revistas científicas, a fim de avaliar se o trabalho premiado teria maior potencial para publicação. Mapear áreas por produtividade científica na instituição. MÉTODOS: Busca retrospectiva dos trabalhos inscritos no período de 2002 a 2007 que obtiveram publicação em periódicos indexados nas bases de dados Medline (Pubmed) e Lilacs ou em anais de congressos científicos de especialidades nacionais ou internacionais. RESULTADOS: Entre 2002 e 2007, foram inscritos 408 trabalhos e 71 foram premiados. O total de trabalhos publicados foi de 138 (33,8%), sendo 8,1% na base Medline, 14% na base Lilacs e 11,7% encontrados a partir da plataforma Lattes. Premiação pela banca examinadora foi variável independente para publicação (OR: 2,05 IC95% 1,22-3,46; p=0,006) assim como para publicação na base Medline (OR: 2,62 IC95% 1,21- 5,69; p=0,01). CONCLUSÃO: O papel de alunos de graduação na produção científica institucional refletido na produção de um Congresso Médico Universitário é relevante e deve continuar a ser estimulado