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This study investigated the effect of furosemide-forced diuresis and intravenous saline infusion matched with urine output, using a novel dedicated device designed for contrast-induced nephropathy (CIN) prevention.CIN is a frequent cause of acute kidney injury associated with increased morbidity and mortality.A total of 170 consecutive patients with chronic kidney disease (CKD) undergoing coronary procedures were randomized to either furosemide with matched hydration (FMH group, n = 87) or to standard intravenous isotonic saline hydration (control group; n = 83). The FMH group received an initial 250-ml intravenous bolus of normal saline over 30 min followed by an intravenous bolus (0.5 mg/kg) of furosemide. Hydration infusion rate was automatically adjusted to precisely replace the patient's urine output. When a urine output rate300 ml/h was obtained, patients underwent the coronary procedure. Matched fluid replacement was maintained during the procedure and for 4 h post-treatment. The definition of CIN was a ≥25% or ≥0.5 mg/dl rise in serum creatinine over baseline.In the FMH group, no device- or therapy-related complications were observed. Four (4.6%) patients in the FMH group developed CIN versus 15 (18%) controls (p = 0.005). A lower incidence of cumulative in-hospital clinical complications was also observed in FMH-treated patients than in controls (8% vs. 18%; p = 0.052).In patients with CKD undergoing coronary procedures, furosemide-induced high urine output with matched hydration significantly reduces the risk of CIN and may be associated with improved in-hospital outcome. (Induced Diuresis With Matched Hydration Compared to Standard Hydration for Contrast Induced Nephropathy Prevention [MYTHOS]; NCT00702728).

Acutely ruptured brain arteriovenous malformations (AVMs) are a known etiology of hemorrhagic stroke during pregnancy. The aim of this paper is to report two cases of patients which presented with ruptured AVMs during pregnancy and were successfully treated with endovascular techniques. Peculiar issues related to the application of this treatment strategy in this category of patients will be discussed as well. To the best of our knowledge, this therapeutic approach in cerebral AVMs ruptured during pregnancy has not been described yet.

BACKGROUND: Periosteal osteosarcoma is a rare variant of osteosarcoma. Wide surgical removal is the mainstay of treatment, but controversy remains about the role of chemotherapy. The objective of this study was to review and analyze the clinical and treatment-related factors that influence the survival of patients with periosteal osteosarcoma who received treatment in a single institution. METHODS: Thirty-three patients with periosteal osteosarcoma (19 males and 14 females) with a median age of 16 years (range, ages 6-32 years) underwent surgery (32 patients) and received radiotherapy (1 patient). Chemotherapy was received according to different regimens for high-grade osteosarcoma by 14 patients who had grade 3 tumors. RESULTS: The 10-year overall survival rate was 84%. The only patient who did not undergo surgery died of disease after 9 months; for the remaining 32 patients the 10-year disease-free survival rate was 65%. Survival was not influenced by the receipt of chemotherapy. The patients who received chemotherapy had a 10-year overall survival rate of 86%, and those who received only local treatment had an overall survival rate of 83% (P ¼ .73). CONCLUSIONS: The authors’ experience indicated that the treatment of periosteal osteosarcoma requires only wide surgical removal of the tumor and that adjuvant chemotherapy does not improve survival. Cancer 2010;000:000–000. V C 2010 American Cancer Society.

Made available in DSpace on 2014-06-11T19:24:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-05-20Bitstream added on 2014-06-13T19:52:47Z : No. of bitstreams: 1 gasparotto_gcf_me_rcla.pdf: 4690303 bytes, checksum: 26b7d79c22f2e9c743aa764e0ff54160 (MD5) O objetivo deste trabalho é analisar a questão da Alfabetização Matemática na série final do ensino fundamental. Entre os problemas educacionais enfrentados pelos professores de todo o país, está o da Não-Alfabetização Matemática de vários alunos, entre eles os da série final. A pesquisa tem uma abordagem qualitativa e entrevistas realizadas com os estudantes que possuem dificuldades de Alfabetização Matemática, e também pais seus pais ou responsáveis têm a intenção de analisar a vivência de cada um dentro e fora da escola. Para isso, opta-se pelo uso da cartografia, através dos mapas narrativos, que está presente neste trabalho com o objetivo de mostrar as linhas de forças que cercam tais alunos, por meio da descrição de sua fala a partir de seu próprio mapa, do seu traçado. E de um mapa a outro, sobrepondo-os, podese encontrar os pontos de conexão que existem a partir do mesmo problema que compartilham: a Alfabetização Matemática This study's purpose is to analyze the question about the Mathematical Literacy of students from Elementary School – final grade. Among the brazilian teacher's educational problems, there is the Non-Mathematical Literacy, specifically of final grade's students. It is done a qualitative research in this study and also interviews made with these students and their parents or responsible for them try to analyze their experience inside and outside school. For this, the cartography is the best option through narrative maps which objective is show the force lines around the students. Their speech is described by themselves through maps and traces. All the maps are able to show the connexion points from the same common problem: the Mathematical Literacy

Purpose: The germ-line polymorphisms TP53 Arg72Pro and MDM2 SNP309 T>G are risk factors for tumor development and affect response to chemotherapy and survival in several cancers, but their prognostic and predictive value in patients with high-grade osteosarcomas is not yet defined. The purpose of this study was to investigate the effect of the TP53 Arg72Pro and the MDM2 SNP309 on the risk of osteosarcoma development and survival. Experimental Design: The relative risk to develop osteosarcomas and the overall survival associated to TP53 Arg72Pro and MDM2 SNP309 polymorphisms were investigated in 201 patients. Correlations with event-free survival (EFS) were analyzed in a homogeneous subgroup of 130 patients with high-grade osteosarcomas of the limbs, nonmetastatic at diagnosis, which underwent neoadjuvant chemotherapy. Results: Multivariate analysis showed that the MDM2 polymorphism T309G was associated with an increased risk of developing osteosarcomas [GG versus TT; odds ratio, 2.09; 95% confidence interval (95% CI), 1.15-3.78]. A case/control gender approach evidenced a significant increased risk only for female osteosarcoma patients (GG versus TT; odds ratio, 4.26; 95% CI, 1.61-11.25). Subjects carrying the TP53 Arg72Pro polymorphism were found to have a significantly increased death risk (Pro/Pro versus Arg/Arg; hazard ratio, 2.90; 95% CI, 1.28-6.66). In the subgroup of 130 high-grade osteosarcomas, the TP53 Arg72Pro was an independent marker of EFS (Pro/Pro versus Arg/Arg; hazard ratio, 2.67; 95% CI, 1.17-6.11). Conclusion: The study provides evidence supporting the association of MDM2 SNP309 with high-grade osteosarcoma risk in females and shows that TP53 Arg72Pro has a prognostic value for overall survival and EFS in osteosarcoma patients.

BACKGROUND: The optimal treatment for synovial sarcoma remains controversial. Treatment, outcome, and prognostic factors in patients treated in a single institution were examined. METHODS: Synovial sarcoma patients who underwent surgery at the Rizzoli Institute between 1976 and 2006 were identified and analyzed. RESULTS: Characteristics of the 250 patients (128 female; 122 male) included: median age, 37 years (range, 7-83 years); 177 (71%) with tumors in the lower extremity, 40 (16%) with tumors in the upper extremity, and 33 with tumors in the trunk (13%); primary lesion size >5 cm in 121 patients (55%); and 204 (82%) patients with localized disease and 46 (18%) with metastatic disease at the time of presentation. All patients with localized disease underwent surgery. Twenty-four percent of patients underwent amputation. Adequate surgical margins were achieved in 88% patients. In patients with localized disease, radiotherapy was administered to 103 (50%) patients, and chemotherapy to 98 (48%). With a median follow-up of 5.5 years (range, 1-30 years), the 5-year overall survival rate was 10% for patients with metastatic disease and 76% for patients with localized disease (P = .0001). The 5-year event-free survival was 58% in patients with localized disease. Multivariate analysis indicated that size, age, histologic subtype, and the use of radiotherapy were independent factors for event-free survival. CONCLUSIONS: In those patients with localized disease, a good rate of cure can be achieved. Age, size, histology, and use of radiotherapy influence prognosis, whereas to the authors' knowledge, the role of adjuvant chemotherapy remains unproven. © 2009 American Cancer Society.

Purpose We reviewed the outcome of osteosarcoma patients older than 65 years, an age group usually excluded from protocols, to determine the different clinical features and prognostic factors in this age group compared with younger patients. Patients and Methods Patients treated at our institute who had high-grade osteosarcoma and were older than 65 years were observed. Results Forty-three patients were eligible to be enrolled onto this study; of these, 22 were male and 21 were female. The median age of this group was 69 years (range, 65 to 80 years). Of the 43 patients, 29 patients had localized disease, and 14 patients had metastatic disease. Localizations were appendicular in 33 patients, and axial in 10 patients. Twenty-nine patients had a primary osteosarcoma, 13 patients (30%) had a sarcoma in Paget's disease, and one patient had postradiotherapy (RT) osteosarcoma. The median interval from onset of symptoms to diagnosis was 4 months (range, 0 to 73 months).Thirty-two of 43 patients received surgery for a primary tumor. Of these, 18 patients had limb salvage, 13 patients had an amputation, and one patient had palliative surgery; the remaining 11 patients received palliative RT. Fourteen patients received chemotherapy; two deaths related to chemotherapy were observed. Median overall survival (OS) for all 43 patients was 19 months (range, 3 to 229 months); 5-year OS was 22% (SE = 3%) for the whole group, and 45% OS for those patients with localized primary osteosarcoma. Multivariate analysis demonstrated that stage, volume, and surgery were significant prognostic factors. Insignificant prognostic factors were sex, type of surgery, chemotherapy, and Paget's disease. Conclusion Patients older than 65 years with osteosarcoma have a worse prognosis compared with younger patients. This older age group is characterized by a longer time lapse from the onset of symptoms to diagnosis, more metastatic cases at diagnosis, less use of limb salvage, fewer patients receiving chemotherapy, and more patients excluded from clinical trials than a younger age group.

10526 Background: Extra Skeletal Osteosarcoma (ESO) account 1% among soft tissue sarcomas. There is no agreement on the best strategy of treatment. Methods: An EMSOS collaborative study was perform...

The purpose of the report was to evaluate the role of fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging gastric cancer comparing it with contrast enhancement computed tomography (CECT). This retrospective study included 45 patients who underwent performed whole body CECT and 18F-FDG PET/CT before any treatment. We calculated CECT and 18F-FDG PET/CT sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) for gastric, lymphnode, and distant localizations; furthermore, we compared the 2 techniques by McNemar test. The role of 18F-FDG PET/CT semiquantitative parameters in relation to histotype, grading, and site of gastric lesions were evaluated by ANOVA test. Sensitivity, specificity, accuracy, PPV and NPV of CECT, and 18F-FDG PET/CT for gastric lesion were, respectively, 92.11%, 57.14%, 86.66%, 92.11%, 57.14% and 81.58%, 85.71%, 82.22%, 96.88%, 46.15%. No differences were identified between the 2 techniques about sensitivity and specificity. No statistical differences were observed between PET parameters and histotype, grading, and site of gastric lesion. The results of CECT and 18F-FDG PET/CT about lymphnode involvement were 70.83%, 61.90%, 66.66%, 68%, 65% and 58.33%, 95.24%, 75.55%, 93.33%, 66.67%. The results of CECT and 18F-FDG PET/CT about distant metastases were 80%, 62.86%, 66.66%, 38.10%, 91.67% and 60%, 88.57%, 82.22%, 60%, 88.57%. 18FDG PET/CT specificity was significantly higher both for lymphnode and distant metastases. The 18F-FDG PET/CT is a useful tool for the evaluation of gastric carcinoma to detect primary lesion, lymphnode, and distant metastases using 1 single image whole-body technique. Integration of CECT with 18F-FDG PET/CT permits a more valid staging in these patients.

We evaluated the rate of second malignancies in 1205 patients with osteosarcoma of the extremity treated at our Institution with different protocols of adjuvant and neoadjuvant chemotherapy. Twenty-six patients (2.15%) developed a second malignant neoplasm at a median of 7.6 years (1 to 25 y) after primary osteosarcoma treatment. Of these, 2 developed a third cancer which were not considered in the series. Second neoplasms were leukemia (10), breast (7), lung (2), kidney (2), central nervous system cancer (2), soft tissue (1), parotid (1), and colon (1). The rate of second neoplasms was significantly higher in female patients, and the latent period shorter in hematologic tumors compared with solid tumors. Ten of these 26 patients are disease free at a median of 7.7 years (range 1 to 15 y) after the last treatment. The rate of second malignancies observed in the osteosarcoma group was significantly higher than that observed in the control group of 1160 patients with benign tumors treated in the same period at our Institute (2.2% vs. 0.8%, P

O presente trabalho teve como objetivo definir o rearranjo espacial da capacidade estática de armazenamento de soja no estado do Mato Grosso a partir de um modelo matemático de localização, visando à minimização dos custos logísticos envolvidos no escoamento da produção do grão aos armazéns e desses aos principais portos brasileiros. O instrumental utilizado para tanto foi a programação inteira-mista, considerando que o mercado em questão atua em concorrência perfeita, com oferta (produção) e demanda (exportação) fixas e ausência de diferença tecnológica e de economia de escala nas atividades de armazenamento e transporte. Foi adotado como premissa básica que o transporte dos locais armazenadores aos portos se dará apenas pela logística intermodal (rodo-ferro/hidroviário). Foram elaborados quatro cenários para tal análise, que incorporaram alterações na demanda, na economia de escala dos custos de construção dos armazéns graneleiros e mudanças na seleção dos armazéns para atendimento às exportações. Para todas essas simulações foi considerada a ausência de armazéns graneleiros no Mato Grosso, para comparação dos resultados com a situação da rede armazenadora existente. Os resultados obtidos sinalizaram que há uma tendência para ampliação da capacidade estática de armazenamento, principalmente nas mesorregiões Norte e Nordeste mato-grossenses, em torno de 1,4 milhões de toneladas. As microrregiões de Alto Paraguai (Centro-Sul), Alto Araguaia (Sudeste), Nova Lacerda e Tangará da Serra (Sudoeste) possuem uma defasagem na capacidade de estocagem atual, mostrando-se assim como locais potenciais para receber investimentos na ampliação. Portanto, pode-se concluir que o modelo desenvolvido atendeu ao objetivo do problema que foi de identificar os locais e dimensionar a capacidade de armazenamento para o Mato Grosso, mostrando assim, quais são as regiões que necessitam ampliar seu sistema armazenador. Dessa forma, a expansão planejada do sistema de armazenamento pode contribuir para minimizar as perdas no escoamento da produção, uma vez que o estado está muito distante dos portos. Assim, uma logística intermodal (mais competitiva) integrada com um sistema de armazenamento planejado pode diminuir o custo total envolvido para escoar a produção de soja mato-grossense até os portos. The current study aimed to define the spatial rearrangement of the static capacity of soybean storage in the state of Mato Grosso, making use of a mathematical model of location, seeking for the reduction of logistic costs involved in transporting the grains production to warehouses and from there to the mains harbors in Brazil. The method used for that purpose was the mixed-integer programming, considering that the market under study is under perfect competition, with fixed supply (production) and demand (exportation) and the absence of a technological difference and of economies of scale in the activities of stocking and transporting. It was adopted as basic premise that the transporting from warehouses to harbors will be done through inter modal logistics (road-railway / waterway). Four scenarios were developed for such analysis, which incorporate changes in demand, economies of scale on costs of building grain warehouses and a change in the choice of the warehouses to meet the demand for exportation. In all of these simulations it was considered the absence of warehouses in Mato Grosso for comparing the results to the system of the existing network of storage. The results obtained signal that there is a tendency to expand the static capacity of storage, specially in the regions of the North or Northeast of Mato Grosso, to 1.4 million tons roughly. The regions of Alto Paraguai (Center-South), Alto Araguaia (Southeast), Nova Lacerda and Tangará da Serra (Southwest) have a current gap in the capacity of storage, showing that they are potential places to receive investments for expansion. Therefore, it can be concluded that the model developed reached the objective of the problem, which was to identify places and to delineate the capacity of storage for the state of Mato Grosso, presenting this way the regions to expand their stocking system. The planned expansion of the system can contribute to minimizing the losses in transporting the production, once the state is located far from the harbors. Thus, an inter modal logistic (more competitive) integrated to a planned system of storage can reduce the total cost involved to transport the soybean production to the harbors.

Formyl-peptide receptors (FPRs) belong to the family A of the G-protein coupled receptor superfamily and include three subtypes: FPR, FPR-like-1 and FPR-like-2. They have been involved in the control of many inflammatory processes promoting the recruitment and infiltration of leukocytes in regions of inflammation through the molecular recognition of chemotactic factors. A large number of structurally diverse chemotypes modulate the activity of FPRs. Newly identified antagonists include bile acids deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The molecular recognition of these compounds at FPR receptor was computationally investigated using both ligand- and structure-based approaches. Our findings suggest that all antagonists bind at the first third of the seven helical bundles. A closer inspection of bile acid interaction reveals a number of unexploited anchor points in the binding site that may be used to aid the design of new potent and selective bile acids derivatives at FPR.

We have updated the results of an adjuvant chemotherapy study of 106 patients with osteosarcoma of the extremities published 17 years ago 1, treated by surgery followed by adjuvant chemotherapy with vincristine (VCR), methotrexate (MTX) and doxorubicin (ADM), between 1980-1983, and followed-up for at least 20 years (20-23 years). In comparison with the results reported 17 years ago with a median fol-low-up of 38 months (range: 27-66), this updated study showed 24 more deaths, 9 more relapses and 3 second malignancies. Consequently, event-free survival (EFS) and overall survival (OS) are significantly lower compared to the previous study with a 3-year follow up (EFS 38% vs 53%; OS 43.8% vs 67%).We conclude that osteosarcoma patients treated with chemotherapy are at risk of late adverse events. Protracted medical follow-up and long-term updated results are useful to identify, at an early stage, late relapses and late treatment-related complications.

A combined target-based and ligand-based drug design approach has been carried out to define a novel pharmacophore model of the human A(3) receptor antagonists. High throughput molecular docking and comparative molecular field analysis (CoMFA) have been used in tandem to assemble a new target based pharmacophore model. In parallel, to provide more accurate information about the putative binding site of these A(3) inhibitors, a rhodopsin-based model of the human A(3) receptor was built and a novel Y-shape binding motif has been proposed. Docking-based structure superimposition has been used to perform a quantitative study of the structure-activity relationships for binding of these pyrazolo-triazolo-pyrimidines to adenosine A(3) receptor using CoMFA. Both steric and the electrostatic contour plots obtained from the CoMFA analysis nicely fit on the hypothetical binding site obtained by molecular docking. On the basis of the combined hypothesis, we have designed, synthesized, and tested 17 new derivatives. Consistently, the predicted K(i) values were very close to the experimental values.

Pterygium recurrence is a common problem encountered by ophthalmic surgeons. Several methods have been suggested to avoid these recurrences. We studied the recurrence rate of pterygium after administration of a single intraoperative dosage of topical mitomycin C 0.05%.A retrospective analysis of fifty eyes in forty-nine patients who underwent pterygium excision by the same surgeon using intraoperative topical mitomycin C during the years 2002--2003. Mitomycin concentration was 0.05% applied to pterygium and adjacent areas after undermining and separation from sclera but prior to excision for three minutes. Postoperative follow up time was 12 months.The pterygium recurred in 4 (8%) eyes. Another four eyes (8%) had a cosmetically acceptable recurrence of2.0 mm. The only complication was a corneal dellen in one eye.Intraoperative administration of mitomycin C at 0.05% is safe and effective in preventing pterygium recurrences.

The addition of chemotherapy and radiotherapy to local treatment for Ewing's sarcoma of bone (ES) significantly bettered its prognosis. Nonetheless, although with no signs of local recurrence some patients still relapse with lung metastases. These patients are generally treated with non-surgical procedures. The few reports in literature on surgical resection of metachronous pulmonary metastases do not allow any conclusions. This study aims to report the results achieved in 24 Ewing's sarcoma patients who relapsed only with lung metastases, and no local recurrence, treated with surgery at the authors' institution.

Giant cell tumor of bone (GCT) is a neoplasm characterized by the presence of large numbers of multinucleated osteoclast-like giant cells, together with mononuclear spindle-shaped cells. Although GCT can be considered a benign lesion, it may exhibit a high biological aggressiveness, which is often associated with enhanced osteolytic properties and development of lung metastasis. By selecting different groups of GCT patients, including patients without evidence of relapse after a median follow-up of 114 months and patients who recurred with lung metastasis, this study focused on the analysis of the expression at clinical onset and in the metastasis of a series of markers involved either in bone resorption modulation or in the metastatic process. By using immunohistochemistry, we analyzed the expression of interleukin-6 (IL-6), a cytokine stimulating bone resorption that has been demonstrated to be released by GCT cells. The expression of factors of the urokinase-type plasminogen activation system, including the urokinase-type plasminogen activator (u-PA) and the plasminogen activator inhibitor type 1 (PAI-1), which have been described to be frequently implicated in the process of degradation of the extracellular matrix during the metastatic process, were also analyzed. Finally, since the action of plasminogen activators is facilitated by the presence of specific receptors on cell surfaces, the analysis included also the u-PA receptor (u-PAR). Our results showed that all these proteins were variably either expressed or overexpressed both in primary tumors and lung metastasis. However, both the level of expression and the incidence of overexpression were higher in primary GCT that relapsed and in lung metastasis compared to primary tumors from disease-free patients, suggesting a possible association of these proteins with a higher biologic aggressiveness of GCT cells. The parallel analysis of a group of primary tumors and of their respective lung metastasis demonstrated that the enhanced expression of one or more of these proteins may confer a selective advantage to GCT cells in terms of systemic invasiveness. Therefore, the evaluation of the expression levels of these proteins at the time of diagnosis may be taken into consideration for a classification of GCT into categories characterized by a different risk to relapse.

The region q13-15 of chromosome 12 frequently is altered in human sarcomas, and several genes, such as SAS, CDK4, and MDM2, have been found to be amplified in bone and soft tissue sarcomas. These genes and their products were studied by quantitative polymerase chain reaction and immunohistochemical analysis in 25 parosteal osteosarcoma samples (22 Grades I or II, three dedifferentiated) to evaluate if the possible alterations detected of the genes on chromosome 12 could have a role in the development of this rare bone tumor. Immunohistochemical analysis was performed on formalin fixed, paraffin embedded tumor sections to evaluate CDK4 and MDM2 protein expression. To measure the degree of SAS and CDK4 gene amplification, quantitative polymerase chain reaction was done on deoxyribonucleic acid derived from the same samples. The results showed that CDK4 protein was expressed in 92% of the cases. Strong and uniform CDK4 and MDM2 immunoreactivity was found respectively in three of three and two of three dedifferentiated parosteal osteosarcomas. SAS and CDK4 genes were found to be amplified fourfold in two Grade II tumors and in one dedifferentiated tumor. These findings, which should be investigated further, might suggest a possible role of the chromosome 12 genes in the pathogenesis of parosteal osteosarcoma.

New oncologic treatments have improved survival in osteosarcoma and Ewing's sarcoma. However, these treatments may cause secondary malignancies after radiotherapy. This study evaluated the incidence of secondary malignancies after neoadjuvant chemotherapy. Between April 1972 and December 1990, 518 osteosarcoma and 299 Ewing's sarcoma patients entered neoadjuvant chemotherapy protocols. Follow-up records of all patients were analyzed and malignant tumors were reported. Nine patients developed another malignancy, including 5 leukemias, 1 astrocytoma, 1 liposarcoma, 1 parotid, and 1 breast carcinoma. Four leukemias were found in patients treated for osteosarcoma with chemotherapy, but not radiotherapy. Only one leukemia developed after Ewing's sarcoma treated with chemotherapy and radiotherapy. The incidence of leukemias is high, while the other tumors can be explained as unrelated cases. Incidence densities for leukemia were calculated for both groups of patients. Treated osteosarcoma patients seem to have a predisposition to develop leukemias, but whether this is chemotherapy induced needs to be investigated.

Cyclins and cyclin-dependent kinases (cdks) form complexes that govern transitions during cell cycle phases. In this study we characterized a human osteosarcoma cell line, MG-63, for the expression level of cyclin D1, cyclin E, cdk4, cdk2, and cell cycle inhibitors pRb and p21. To investigate the role of these proteins we treated MG-63 cells with tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Cell proliferation analysis demonstrated an increased proliferation of MG-63 cells with IL-6, while TNF-alpha acted as an anti-proliferative agent. Immunoblotting revealed an increased expression of p21 with TNF-alpha and its complex with cdk2. TNF-alpha reduced the expression of the cyclin E-cdk2 complex. TNF-alpha did not affect the amount of cyclin D1, cyclin E, cdk4, cdk2, and of cyclin D1-cdk4 complex. IL-6 decreased p21 expression and its complex with cdk2, while it increased the cyclin E-cdk2 complex. Cyclin D1 and cdk4 expression and their complex did not change after IL-6 treatment, nor did cyclin E and cdk2 protein expression. Hyperphosphorylated/dephosphorylated Rb protein ratio was reduced with TNF-alpha whereas it increased with IL-6. These results may suggest an important role of p21 and of cyclin E-cdk2 complex in the G1 phase regulation through pRb phosphorylation in MG-63 cells.

The region q13-15 of chromosome 12 contains SAS, CDK4, and MDM2 genes that are rearranged or amplified in a variety of human sarcomas. This study evaluated SAS gene amplification, and MDM2 and CDK4 protein expression in 20 tumor samples of central low-grade osteosarcoma (16 primary, 3 recurrences, 1 lung metastasis). SAS amplification was analyzed by quantitative polymerase chain reaction (PCR), while from the same paraffin-embedded samples, MDM2 and CDK4 protein expression was evaluated by immunohistochemistry. MDM2 and CDK4 proteins were found strongly expressed in 35% and 65%, respectively, of the samples. SAS was found amplified in 15% of the samples. These findings indicate that these genes may be involved in tumorigenesis and progression of low-grade osteosarcoma.

To evaluate the distribution of cyclin protein expression, in relation to cell proliferation rate and clinical behavior, an immunohistochemical study was performed on 92 tumor samples of patients with high grade osteosarcoma (OS). A large cyclin A- and cyclin E-positive fraction was found respectively in 59% and 47% of the osteosarcomas, while immunostaining for cyclin D1 was weak or absent in most tumor samples. A positive, statistically significant correlation was found between A and E cyclins and Ki67 expression (p0.001). Disease-free survival (DFS) analysis included 69 of the 92 patients. A significantly higher probability of metastasis was seen in patients lacking cyclin D1 compared to those in which cyclin D1 was positive (p0.01). Conversely, patients with40% of cyclin A-positive cells relapsed more frequently than those with40% of cyclin A-positive cells (p0.05). The multivariate analysis demonstrated that cyclin A had a lower predective risk in terms of disease-free survival as opposed to the loss of cyclin D1 that is considered a powerful prognostic factor.

This paperwork discusses the main results of the Health Psychology Master Degree Dissertation of Universidade Catolica Dom Bosco (UCDB) concluded in 2012, which aimed to assess the health quality of life of cancer patients under palliative care. This is a quantitative, descriptive and cross-sectional study, approved by the Ethics Research Department of (UCDB) in Campo Grande, Mato Grosso do Sul. The sample consisted of 70 participants who underwent palliative monitoring care at the Cancer Hospital in Dourados/MS. Two instruments were applied to collect data: a Social Demographic Occupational Questionnaire and a specific instrument to assess the health quality of life in Oncology the EORTC QLQ – C30. The results showed that a target identification of domains, when related to Social Demographic Occupational variability, may favor the assistance interventions that the multidisciplinary team offers to cope with the disease and side effects of cancer treatment in order to improve those individuals health quality of life.

The CDC25Mm gene codes for Ras—guanine nucleotide exchange factors. Four different full-length cDNA clones derived from the same gene and coding for proteins of different sizes that have in common the last 661 amino acids have been isolated from mouse brain. In order to investigate the expression of the products of this gene in different tissues we have prepared two polyclonal antibodies directed toward two different regions of the protein comprised in the last C-terminal 472 amino acids. While in most of the tested tissues we have been unable to definitely identify CDC25Mm products, in NIH3T3 fibroblasts we have found a poorly expressed 120-kDa protein. In the mouse brain we have identified two proteins of 140 and 58 kDa. While the former is expressed in the adult mouse, the latter is present in the embryo and persists for few days after birth. This finding suggests that differential expression of various forms of CDC25Mm may be involved in brain development.

e19666 Background: Osteosarcoma and Ewing’s sarcoma are bone sarcomas that primarily affect children and young adults. The advent of chemotherapy greatly improved long term survival rates, however,...

By using a cotransfection assay with a ras-responsive fos-luciferase reporter gene, we present evidence that the catalytic domain of CDC25Mm constitutively activates p21ras in mammalian cells in vivo. Using immunopurified CDC25Mm-specific antibodies we show that different protein species are recognized in mouse tissues.

9551 Background: We report data of long term follow up of 883 patients with localized osteosarcoma of the extremity and 493 patients with localized Ewing's sarcoma treated with neoadjuvant chemotherapy from 1983 to 2007 to find out late side effects (second malignancies, cardiomyopathy, sterility). Methods: We reviewed our database and we interviewed by phone the missing patients. Data are updated to Dec 2009. Results: Osteosarcoma patients: 883 patients are evaluable. Median overall survival (OS) is 108 months (range 1-306), female/male: 370/403, alive 563, dead 320. 28 second malignant neoplasms (SMN) were reported for a cumulative risk at 10 yrs of 3.02 ±1.0 (SE): 9 hematologic malignancies (7 leukemia and 2 myelodysplastic syndrome) after a median of 36 ms and 19 solid tumor (6 breast ca, 3 parotid ca, 2 CNS tumor, 2 skin cancers, 2 soft tissue sarcomas, 1 Ewing's sarcoma, 1 kidney cancer, 1 colon cancer, 1 ovarian cancer) 2 patients had 2 SMN. 18 patients had adriamycin–cardiomyopathy. 46 male did sp...

10515 Background: After the introduction of pre-operative chemotherapy in the early 1980s, treatment of osteosarcoma had not advantages from new drugs/modalities. Aim of this work is to analyze improvements in overall survival for patients treated over 21 years (1982–2002), with a 5-year minimum follow-up, in the largest series from a single institute ever reported, including all high grade osteosarcomas, despite histology varieties, age, site, and stage. Data are also analyzed in subgroups to define patients who benefited most. Methods: All diagnoses of high grade osteosarcoma were included. Of the 1,656 consecutive cases observed, 198 patients were excluded (41 consultation only, 129 low-grade varieties and 28 lost to follow-up). Within 1,456 included patients, 1,032 had characteristics to be enrolled in conventional clinical trials (classic histology, age < 41, localized and extremity disease). Results: Considering all patients, with a median follow-up of 12 years (5–25 yrs), 754 (51.7%) are alive, 613 continuously disease-free. Survival at 5, 10, and 15 years is 57%, 52%, and 51% respectively. Patients candidates for clinical trials have a survival rate of 68%, 64%, and 61% respectively. Survival for the other patients is 30%, 25%, and 24% respectively. Jointpoint Statistical Analysis at real 5-year follow-up shows a yearly statistically significant improvement in survival of 1.31% (95% CI 0.5–2.1), from 51% for patients treated in 1982 to 68% for those treated in 2002. Within the subgroups, survival statistically improved in patients candidates to protocols, those who relapsed, or presented with metastatic disease at diagnosis, or had axial tumors. Surgery was also analyzed, with a statistical significant increase in the percentage of limb salvage procedures without an increased rate of local recurrences. Conclusions: Despite the lack of new drugs for osteosarcoma, survival has statistically improved, especially for those patients with the worst outcome. Aggressive treatments are therefore recommended for all patients including those with poor prognosis. No significant financial relationships to disclose.

10578 Background: The best adjuvant treatment for soft tissue sarcomas is still unclear. Soft tissue sarcomas is an eterogenous group of several different hystotypes. The aim of this retrospective study is to evaluate prognostic factors and treatments. Methods: All liposarcoma cases evaluated in our Pathology from Jan 1985 to December 2005 were reviewed: 299 cases of liposarcoma were found of these only 155 were treated at Rizzoli since their first diagnosis. Metastatic since diagnosis and pediatric cases were excluded. Of these 155 pts only 122 had localized liposarcoma of soft tissue and adequate informations and follow up. Results: Male were 71 and female 51, Median age 47 (15–85). Histology was as follows: mixoid 62, round cell 33, pleomorphic 27. Grading according to FNCCL was G1=18, G2=51, G3=53. Median tumor volume was 183 cm3 (8–3,800), mean 401. Surgical margins were adequate in 84 patients (66.4%) unadequate in 34 (27.9%), 4 missing. Treatment received were: 18 no treatment besides surgery, pres...

10506 Background: The optimal treatment for synovial sarcoma (SS) is controversial. The present study examines treatment, outcome and prognostic factors in patients treated in a single institution....

10037 Background: Few data are available in literature about osteosarcoma in patients older than 65.We reviewed the incidence and outcome of osteosarcoma in elderly over 65 in our casistic. Materials and Methods: Patients with high grade osteosarcoma treated in our Institute from 1961 to 2006 aged >65. End point was overall survival (OS). Results: 43 patients aged more than 65 treated for high grade osteosarcoma at our Institute were found: 22 male and 21 females, median age was 69 (range 65–80), 29 had localized disease and 13 were metastatic, 33 had extremity localization and 10 axial, 29 patients had a primitive osteosarcoma and 13 (30%) had a sarcoma in Paget's disease, 1 pt ha post-RT osteosarcoma. Median interval from symptoms to diagnosis was 4 months (0–73) 32 out of 43 received surgery for primitive tumour: 18 had a resection with endoprosthesis, 13 had amputation, 1 pt had palliative surgery, the others received palliative RT, 14 patients received chemotherapy (anthracycline, cisplatin, ifosfamide).2 major complication related to chemotherapy were observed: one toxic death and one septic shock. Twenty-one patients reached a disease free status after surgery. Median OS for all 43 pts was 19 months (SE 3),mean 35 mos (range 3–229), 3 years OS for the all group was 25%. Three years OS (Kaplan-Meyer) for pts with localized disease was 41,5% vs 0% for metastatic pts, 3 yrs OS for pts who had surgery was 30% compared to 0% for those without surgical treatment.Significant prognostic factors (Breslow statistic) were: localized vs metastatic (P No significant financial relationships to disclose.

9508 Background: Good cure rate has been reached in osteosarcoma treatment with chemotherapy, but there are late side effects. Methods: We reviewed charts of 755 patients (pts) with localized osteosarcoma of the extremity treated in 6 subsequent protocols (1983–2000) with Doxorubicin (300–480 mg/m2), Cisplatin (300–600 mg/m2), Methotrexate (3.7–75 g/m2), Ifosfamide (30–75 g/m2). Etoposide was employed only in 47 pts. Results: With a median follow up of 8 yrs (5–20), the median 10-yrs EFS was 58%. 13 patients (1.7%), 9 females and 4 males, had a symptomatic cardiopathy with two cardiopathy-related deaths, and 3 patients needed a heart transplant. The median age of these pts was 13 yrs (4–28). Median Doxorubicine dose = 480 mg/m2. Median interval from chemotherapy completion to cardiopathy onset was 3 months; 7 patients are alive, and 6 died: 4 for cardiopathy, 2 for metastatic disease. 17 second malignant neoplasms (SMN) occurred in 16 pts (2.1%) after a median interval of 7 yrs. One patient had both a breast and ovarian cancer. SMN were: 2 AML, 3 ALL, 1 CML, 3 breast cancer, 1 CNS tumor, 1 lung tumor, 1 parotid tumor, 2 soft tissue sarcoma, 1 skin cancer, 1 ovary cancer, 1 Ewing sarcoma. Eight of these 16 pts died of the second tumor. Infertility related to chemotherapy affected mostly males. Amenorrhea affected 69% of postpubertal females during chemotherapy but only two pts had permanent amenorrhea (39 and 43 yrs). No delay in pubertal maturation was seen in both gender. The incidence of infertility in male was related to Ifosfamide and was dose-dependent. Permanent azoospermia was 100% in males who received 60–75g/m2 Ifosfamide. No congenital defects were observed in the offsprings of both gender. The incidence of chronic renal failure was negligible in pts who received 2 Ifosfamide; in those who received >60 g/m2 a subclinical tubular impairment was observed in 48%, but only 1pt required dialysis. In the last protocol, a mild hearing impairment due to Cisplatin was evident in 40% of pts. Conclusions: Late toxicities are relevant and prolonged follow-ups are recommended as well as less toxic protocols. No significant financial relationships to disclose.

Aims and Background Forty-four bone hemangioendotheliomas (HEs) of different histological grades were studied to evaluate the expression and distribution of laminin, type IV collagen, cathepsin G and cathepsin D in cell differentiation and malignancy. Results In poorly-differentiated HEs the discontinuous distribution of laminin and type IV collagen around angioblastic cords, tubes and cavities revealed an irregular and disorganized basement membrane (BM) architecture corresponding to an increased cell proliferation and secretion of cathepsin D and cathepsin G by tumor cells. Conclusions The mean nucleolar organizer region (NOR) area, as a measure of cell proliferation, was significantly higher in grade 4 malignancies than in lower grades, revealing novel prognostic parameters.

In the yeast Saccharomyces cerevisiae genetic and biochemical evidence indicates that the product of the CDC25 gene activates the RAS/adenylyl cyclase/protein kinase A pathway by acting as a guanine nucleotide protein. Here we report the isolation of a mouse brain cDNA homologous to CDC25. The mouse cDNA, called CDC25Mm, complements specifically point mutations and deletion/disruptions of the CDC25 gene. In addition, it restores the cAMP levels and CDC25-dependent glucose-induced cAMP signalling in a yeast strain bearing a disruption of the CDC25 gene. The CDC25Mm-encoded protein is 34% identical with the catalytic carboxy terminal part of the CDC25 protein and shares significant homology with other proteins belonging to the same family. The protein encoded by CDC25Mm, prepared as a glutathione S-transferase fusion in Escherichia coli cells, activates adenylyl cyclase in yeast membranes in a RAS2-dependent manner. Northern blot analysis of mouse brain poly(A)+ RNA reveals two major transcripts of approximately 1700 and 5200 nucleotides. Transcripts were found also in mouse heart and at a lower level in liver and spleen.

Aims and Background Ewing's sarcoma is a highly malignant musculoskeletal tumor composed of small round cells. Although important results have been achieved with surgery associated with chemotherapy, recurrent disease is still a major problem. In order to define new prognostic factors useful for therapeutic decision-making, we conducted a study on 38 Ewing's sarcoma samples in which c-myc oncogene expression and Ki67 proliferation index were correlated with clinical outcome. Methods and Study Design Nineteen patients developed metastases during follow-up and 10 of these patients died. C-myc and Ki67 protein expression was evaluated by immunohistochemistry performed on 5 μm formalin-fixed and paraffin-embedded sections, while the c-myc mRNA transcript was localized using in situ hybridization. Results A statistically positive correlation was found between c-myc protein and Ki67 (P = 0.001) and c-myc mRNA and Ki67 expression (P = 0.047). The 38 patients were divided into two groups using as the cutoff 50% of Ki67-positive cells. The disease-free survival and overall survival estimates were 68% and 90%, respectively, in the group of patients with a percentage of Ki67-positive cells Conclusion These results suggest a possible role of the c-myc oncogene and Ki67 antigen in the malignant progression of Ewing's sarcoma.