Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

Background: Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs). Methods: Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients’ clinical-pathological parameters. Results: MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival. Conclusions: The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients’ prognosis, while nuclear expression is associated with better prognosis.The authors thank Dr. Pierre Aman, from the Lundberg Laboratory for Cancer Research, Department of Pathology, Sahlgrenska Academy at Goteborg University, Goteborg, Sweden, for providing the myxoid liposarcoma cell line MLS-1765. CP received a post-doctoral fellowship from FCT (Portuguese Foundation for Science and Technology, SFRH/BPD/69479/2010). FMS received a doctoral fellowship from FCT (SFRH/BD/87139/2012)

What is the impact of local control in Ewing sarcoma : analysis of the first Brazilian collaborative study group – EWING1

Background: Relapse in localized Ewing sarcoma patients has been a matter of concern regarding poor prognosis. Therefore, we investigated the impact of local control modality (surgery, surgery plus radiotherapy, and radiotherapy) on clinical outcomes such as survival and recurrence in patients with non-metastatic Ewing sarcoma treated on the first Brazilian Collaborative Group Trial of the Ewing Family of Tumors (EWING1). Methods: Seventy-three patients with localized Ewing sarcoma of bone aged < 30 years were included. The treating physicians defined the modality of local control based on the recommendations of the coordinating center and the patient and tumor characteristics. Possible associations of local control modality with local failure (LF), disease-free survival (DFS), event-free survival (EFS), overall survival (OS), and clinical characteristics were analyzed. Results: Mean patient age was 12.8 years (range, 2 to 25 years) and median follow-up time was 4.5 years (range, 2. 3 to 6.7 years). Forty-seven patients underwent surgery, 13 received radiotherapy, and 13 received both. The 5-year EFS, OS, and DFS for all patients was 62.1%, 63.3%, and 73.1%, respectively. The 5-year cumulative incidence (CI) of LF was 7.6% for surgery, 11.1% for radiotherapy, and 0% for postoperative radiotherapy (PORT) (p = 0.61). The 5-year EFS was 71.7% for surgery, 30.8% for radiotherapy, and 64.1% for PORT (p = 0.009). Conclusions: There was a significant effect of local control modality on EFS and OS in the study. Surgery and PORT modalities yielded very close results. The group treated with radiotherapy alone had considerably worse outcomes. This may be confounded by greater risk factors in these patients. There was no significant effect of local control modality on the CI of LF and DFS

Centrosome amplification in chondrosarcomas: A primary cell culture and cryopreserved tumor sample study

The genetics background underlying the aggressiveness of chondrosarcoma (CS) is poorly understood. One possible cause of malignant transformation is chromosomal instability, which involves an error in mitotic segregation due to numerical and/or functional abnormalities of centrosomes. The present study aimed to evaluate centrosome amplification in cryopreserved samples of tumor tissue from patients with CS. An analysis was performed on 3 primary cultures of tumors from patients who underwent surgery between January 2012 and December 2012 at the Department of Orthopedics at the Barretos Cancer Hospital (Barretos, Brazil). Additionally, cryopreserved tumor specimens were analyzed from 10 patients. The data were assessed using immunocytochemistry and immunohistochemistry staining techniques with monoclonal antibody anti-gamma-tubulin. A total of 4 samples of CS cultured cells were obtained from 3 patients. A recurrence of a histological grade III tumor was detected in a female patient with Ollier's syndrome. The other 2 cases were grade I and III. The incidence of centrosome amplification in the primary cultures ranged from 15-64% of the cells. Whereas control cultured fibroblasts showed baseline levels of 4% amplified cells. For the cryopreserved specimens, two independent observers analyzed each sample and counted the cells stained with.-tubulin, verifying the percentage of affected cells to be a mean of 14%, with the number of clusters ranging between 0-6 per slide. In conclusion, centrosome amplification was found to be a consistent biological feature of CS and may underlie chromosomal instability in this tumor.info:eu-repo/semantics/publishedVersio

What is the impact of local control in Ewing sarcoma: analysis of the first Brazilian collaborative study group-EWING1

Background: Relapse in localized Ewing sarcoma patients has been a matter of concern regarding poor prognosis. Therefore, we investigated the impact of local control modality (surgery, surgery plus radiotherapy, and radiotherapy) on clinical outcomes such as survival and recurrence in patients with non-metastatic Ewing sarcoma treated on the first Brazilian Collaborative Group Trial of the Ewing Family of Tumors (EWING1). Methods: Seventy-three patients with localized Ewing sarcoma of bone aged < 30 years were included. The treating physicians defined the modality of local control based on the recommendations of the coordinating center and the patient and tumor characteristics. Possible associations of local control modality with local failure (LF), disease-free survival (DFS), event-free survival (EFS), overall survival (OS), and clinical characteristics were analyzed. Results: Mean patient age was 12.8 years (range, 2 to 25 years) and median follow-up time was 4.5 years (range, 2. 3 to 6.7 years). Forty-seven patients underwent surgery, 13 received radiotherapy, and 13 received both. The 5-year EFS, OS, and DFS for all patients was 62.1%, 63.3%, and 73.1%, respectively. The 5-year cumulative incidence (CI) of LF was 7.6% for surgery, 11.1% for radiotherapy, and 0% for postoperative radiotherapy (PORT) (p = 0.61). The 5-year EFS was 71.7% for surgery, 30.8% for radiotherapy, and 64.1% for PORT (p = 0.009). Conclusions: There was a significant effect of local control modality on EFS and OS in the study. Surgery and PORT modalities yielded very close results. The group treated with radiotherapy alone had considerably worse outcomes. This may be confounded by greater risk factors in these patients. There was no significant effect of local control modality on the CI of LF and DFS.Children's Cancer InstituteRafael Accordi Foundation, Porto Alegre, RS, BrazilHCPA, Serv Orthoped & Traumatol, Rua Ramiro Barcelos 2350, BR-90035903 Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, HCPA, Dept Pediat, Porto Alegre, RS, BrazilPontificia Univ Catolica Rio Grande Sul PUCRS, Dept Pediat, Hosp Sao Lucas, Porto Alegre, RS, BrazilHCPA, Serv Orthoped & Traumatol, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Support Grp Children & Adolescents Canc GRAACC, Sao Paulo, SP, BrazilHosp Canc Infantojuvenil, Fundacao Pio 12, Barretos, SP, BrazilCtr Hosp Pereira Rossell, Montevideo, UruguayHosp AC Camargo Canc Ctr, Orthoped Serv, Sao Paulo, SP, BrazilSanta Casa Misericordia Porto Alegre, Serv Orthoped & Traumatol, Porto Alegre, RS, BrazilUniv Sao Paulo, Orthoped Trauma Inst, Hosp Clin Sao Paulo, Sch Med, Sao Paulo, SP, BrazilSanta Casa Misericordia Sao Paulo HSCSP, Dept Orthoped & Traumatol, Sao Paulo, SP, BrazilPontificia Univ Catolica Rio Grande Sul PUCRS, Hosp Sao Lucas, Serv Orthoped & Traumatol, Porto Alegre, RS, BrazilUniv Estadual Paulista UNESP, Hosp Clin Botucatu, Sch Med, Botucatu, SP, BrazilInst Canc Infantil, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Support Grp Children & Adolescents Canc GRAACC, Sao Paulo, SP, BrazilChildren's Cancer InstituteRafael Accordi Foundation, Porto Alegre, RS, BrazilWeb of Scienc

Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively

Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during diagnosis and the development of effective clinical parameters is crucial for correct management of the disease. The use of biological markers in cancer is a useful tool to determine patient prognosis. Ki-67 is a protein marker for proliferation of somatic cells and is widely used in prognostic studies of various types of tumor, including STSs. Cluster of differentiation 100 (CD100) is a member of the semaphorin family. The family was initially described as axon guidance molecules important for angiogenesis, organogenesis, apoptosis and neoplasia. CD100 was previously utilized as a prognostic factor in tumors and also in STSs. In the present study, protein expression of Ki-67 and CD100 was analyzed by immunohistochemistry in samples of STS patients of the Barretos Cancer Hospital (Barretos, Brazil) to establish prognostic criteria of the disease. Results demonstrate a correlation between CD100 expression and poor prognosis, consistent with a previous study. Moreover, the expression of Ki-67 was identified to correlate with presence of local or locoregional recurrence. To the best of our knowledge, no large casuistic study has revealed this correlation between Ki-67 and local recurrence in STSs. The use of Ki-67 and CD100 as markers in clinical pathological analysis may be suitable as a prognostic criterion in disease progression

In vivo antimalarial activity and mechanisms of action of 4-nerolidylcatechol derivatives

4-Nerolidylcatechol (1) is an abundant antiplasmodial metabolite that is isolated from Piper peltatum roots. O-Acylation or O-alkylation of compound 1 provides derivatives exhibiting improved stability and significant in vitro antiplasmodial activity. The aim of this work was to study the in vitro inhibition of hemozoin formation, inhibition of isoprenoid biosynthesis in Plasmodium falciparum cultures, and in vivo antimalarial activity of several 4-nerolidylcatechol derivatives. 1,2-O,O-Diacetyl-4-nerolidylcatechol (2) inhibited in vitro hemozoin formation by up to 50%. In metabolic labeling studies using [1-(n)-3H]geranylgeranyl pyrophosphate, diester 2 significantly inhibited the biosynthesis of isoprenoid metabolites ubiquinone 8, menaquinone 4, and dolichol 12 in cultures of P. falciparum 3D7. Similarly, 2-O-benzyl-4-nerolidylcatechol (3) significantly inhibited the biosynthesis of dolichol 12. P. falciparum in vitro protein synthesis was not affected by compounds 2 or 3. At oral doses of 50 mg per kg of body weight per day, compound 2 suppressed Plasmodium berghei NK65 in infected BALB/c mice by 44%. This in vivo result for derivative 2 represents marked improvement over that obtained previously for natural product 1. Compound 2 was not detected in mouse blood 1 h after oral ingestion or in mixtures with mouse blood/blood plasma in vitro. However, it was detected after in vitro contact with human blood or blood plasma. Derivatives of 4-nerolidylcatechol exhibit parasite-specific modes of action, such as inhibition of isoprenoid biosynthesis and inhibition of hemozoin formation, and they therefore merit further investigation for their antimalarial potential. Copyright © 2015, American Society for Microbiology. All Rights Reserved

Uma nova abordagem para as endopróteses parciais de joelho em sarcomas primários ósseos

OBJETIVO: As endopróteses parciais de joelho para as ressecções em sarcomas ósseos demonstram serem boa solução para o tratamento de pacientes com imaturidade esquelética. O objetivo deste estudo é avaliar o escore funcional, as vantagens, as desvantagens e indicações para esta técnica cirúrgica em quatorze pacientes em um protocolo brasileiro de osteossarcoma e sarcoma de Ewing. MÉTODOS: Análise retrospectiva realizada para identificar a evolução funcional e as possíveis complicações do procedimento. 14 pacientes com idade entre 10 e 22 anos avaliados funcionalmente pelos critérios de Enneking/ISOLS (International Society of Limb Salvage), sendo todos operados na mesma Instituição e pelo mesmo cirurgião. Foram utilizadas endopróteses parciais das extremidades distal do fêmur e proximal da tíbia com reconstrução ligamentar. ReSULTADOS: A análise do escore funcional de Enneking/ISOLS demonstrou 78,6 % de excelentes resultados e 21,4% de bons. Dos 14 pacientes, todos portadores de tumores primitivos ósseos em protocolo de quimioterapia, nove não apresentaram nenhum tipo de complicação e cinco indivíduos evoluíram com complicações relacionadas ao procedimento, sendo que houve relação estatística positiva entre os maus resultados e a presença de complicações (p=0,027). CONCLUSÃO: As endopróteses parciais de joelhos são menos prejudiciais ao estoque ósseo de pacientes com esqueleto imaturo. As críticas sobre os maus resultados funcionais estão sendo suplantadas pelas novas técnicas de reconstrução, corretos protocolos de reabilitação, qualidade e tecnologia dos implantes, e o aumento da curva de aprendizado. Essa opção de tratamento per-mite a preservação do estoque ósseo e a possibilidade de revisão da artroplastia não convencional de modo menos agressivo

The AMERIGO Lander and the Automatic Benthic Chamber (CBA): Two New Instruments to Measure Benthic Fluxes of Dissolved Chemical Species

Marine environments are currently subject to strong ecological pressure due to local and global anthropic stressors, such as pollutants and atmospheric inputs, which also cause ocean acidification and warming. These strains can result in biogeochemical cycle variations, environmental pollution, and changes in benthic-pelagic coupling processes. Two new devices, the Amerigo Lander and the Automatic Benthic Chamber (CBA), have been developed to measure the fluxes of dissolved chemical species between sediment and the water column, to assess the biogeochemical cycle and benthic-pelagic coupling alterations due to human activities. The Amerigo Lander can operate in shallow as well as deep water (up to 6000 m), whereas the CBA has been developed for the continental shelf (up to 200 m). The lander can also be used to deploy a range of instruments on the seafloor, to study the benthic ecosystems. The two devices have successfully been tested in a variety of research tasks and environmental impact assessments in shallow and deep waters. Their measured flux data show good agreement and are also consistent with previous data

Hemipelvectomias: tratamento, avaliação funcional e prognóstica dos tumores pélvicos

OBJETIVO: Demonstrar a experiência de uma única instituição em hemipelvectomias internas sem reconstrução. Avaliar as cirurgias pélvicas preservadoras e as amputações interílio-abdominais e seu prognóstico. MÉTODOS: 21 pacientes com tumores primitivos pélvicos submetidos à hemipelvectomia com ou sem preservação de membro. Sete foram tratados com hemipelvectomias externas (amputação) e 14 com internas, entre junho de 2004 e julho de 2009. A classificação cirúrgica utilizada foi a de Enneking para tumores pélvicos. O método de avaliação funcional foi o escore de ISOLS/MSTS. RESULTADOS: A sobrevida dos pacientes em dois anos foi de 63,9%. A média de sobrevida do grupo todo foi de 43 meses. A avaliação funcional demonstrou que as hemipelvectomias preservadoras com ressecção do osso inominado obtiveram 12,5%, 62,5% e 25% de resultados ruins, bons e excelentes, respectivamente. Nos casos em que o osso inominado foi preservado, os resultados foram 16,7% e 83,3% bons e excelentes, respectivamente. CONCLUSÕES: A hemipelvectomia é procedimento pouco usual e causador de importante limitação funcional e comorbidades. A alternativa de ressecar a hemipelve sem reconstrução tem demonstrado resultados tão bons quanto a não-reconstrução. Os elevados custos médicos, além das possíveis complicações com uso de enxerto e próteses justificam a técnica empregada neste artigo. Nível de Evidência IV, Estudo de caso-controle