10 resultados para Second primary tumors

em Biblioteca Digital da Produção Intelectual da Universidade de São Paulo


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Background. Previous knowledge of cervical lymph node compromise may be crucial to choose the best treatment strategy in oral squamous cell carcinoma (OSCC). Here we propose a set four genes, whose mRNA expression in the primary tumor predicts nodal status in OSCC, excluding tongue. Material and methods. We identified differentially expressed genes in OSCC with and without compromised lymph nodes using Differential Display RT-PCR. Known genes were chosen to be validated by means of Northern blotting or real time RT-PCR (qRT-PCR). Thereafter we constructed a Nodal Index (NI) using discriminant analysis in a learning set of 35 patients, which was further validated in a second independent group of 20 patients. Results. Of the 63 differentially expressed known genes identified comparing three lymph node positive (pN+) and three negative (pN0) primary tumors, 23 were analyzed by Northern analysis or RT-PCR in 49 primary tumors. Six genes confirmed as differentially expressed were used to construct a NI, as the best set predictive of lymph nodal status, with the final result including four genes. The NI was able to correctly classify 32 of 35 patients comprising the learning group (88.6%; p = 0.009). Casein kinase 1alpha1 and scavenger receptor class B, member 2 were found to be up regulated in pN + group in contrast to small proline-rich protein 2B and Ras-GTPase activating protein SH3 domain-binding protein 2 which were upregulated in the pN0 group. We validated further our NI in an independent set of 20 primary tumors, 11 of them pN0 and nine pN+ with an accuracy of 80.0% (p = 0.012). Conclusions. The NI was an independent predictor of compromised lymph nodes, taking into the consideration tumor size and histological grade. The genes identified here that integrate our "Nodal Index" model are predictive of lymph node metastasis in OSCC.

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Purpose: The purpose of this study was to evaluate mouth-breathing and nasal-breathing children prior to surgical intervention and 28 months postoperatively, comparing the occlusal features obtained pre- and postoperatively through orthodontic study costs. Methods: The mouth-breathing (MB) group consists of 33 MB children who underwent surgery and presented a nasal-breathing (NB) pattern after surgery The control group comprised 22 NB children. The orthodontic examinations were accomplished prior to surgery (77) and an average of 28 months postoperatively (T2). Results: At T1, the MB and NB children presented no statistically significant difference in any analyzed occlusal features and measurements. At T2, the MB presented larger overjet comparing to NB children (P<.05). MB and NB groups presented statistically similar results (P>.05) concerning intercanine and intermolor distances, second primary molar terminal plane and canine relationship, overbite, crossbite, and open bite. From T1 to T2, the MB and NB groups showed a statistically significant difference in the molar terminal plane. Conclusion: Neither the breathing pattern nor the surgery had any effect on occlusal features in 3- to 6-year-olds. (Pediatr Dent 2012;34:10842) Received May 14, 2010 vertical bar Last Revision April 11, 2010 vertical bar Accepted April 12, 2010

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As a part of the AMAZE-08 campaign during the wet season in the rainforest of central Amazonia, an ultraviolet aerodynamic particle sizer (UV-APS) was operated for continuous measurements of fluorescent biological aerosol particles (FBAP). In the coarse particle size range (> 1 mu m) the campaign median and quartiles of FBAP number and mass concentration were 7.3x10(4) m(-3) (4.0-13.2x10(4) m(-3)) and 0.72 mu g m(-3) (0.42-1.19 mu g m(-3)), respectively, accounting for 24% (11-41%) of total particle number and 47% (25-65%) of total particle mass. During the five-week campaign in February-March 2008 the concentration of coarse-mode Saharan dust particles was highly variable. In contrast, FBAP concentrations remained fairly constant over the course of weeks and had a consistent daily pattern, peaking several hours before sunrise, suggesting observed FBAP was dominated by nocturnal spore emission. This conclusion was supported by the consistent FBAP number size distribution peaking at 2.3 mu m, also attributed to fungal spores and mixed biological particles by scanning electron microscopy (SEM), light microscopy and biochemical staining. A second primary biological aerosol particle (PBAP) mode between 0.5 and 1.0 mu m was also observed by SEM, but exhibited little fluorescence and no true fungal staining. This mode may have consisted of single bacterial cells, brochosomes, various fragments of biological material, and small Chromalveolata (Chromista) spores. Particles liquid-coated with mixed organic-inorganic material constituted a large fraction of observations, and these coatings contained salts likely from primary biological origin. We provide key support for the suggestion that real-time laser-induce fluorescence (LIF) techniques using 355 nm excitation provide size-resolved concentrations of FBAP as a lower limit for the atmospheric abundance of biological particles in a pristine environment. We also show some limitations of using the instrument for ambient monitoring of weakly fluorescent particles < 2 mu m. Our measurements confirm that primary biological particles, fungal spores in particular, are an important fraction of supermicron aerosol in the Amazon and that may contribute significantly to hydrological cycling, especially when coated by mixed inorganic material.

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CONTEXT: Liver metastases are a common event in the clinical outcome of patients with colorectal cancer and account for 2/3 of deaths from this disease. There is considerable controversy among the data in the literature regarding the results of surgical treatment and prognostic factors of survival, and no analysis have been done in a large cohort of patients in Brazil. OBJECTIVES: To characterize the results of surgical treatment of patients with colorectal liver metastases, and to establish prognostic factors of survival in a Brazilian population. METHOD: This was a retrospective study of patients undergoing liver resection for colorectal metastases in a tertiary cancer hospital from 1998 to 2009. We analyzed epidemiologic variables and the clinical characteristics of primary tumors, metastatic disease and its treatment, surgical procedures and follow-up, and survival results. Survival analyzes were done by the Kaplan-Meier method and the log-rank test was applied to determine the influence of variables on overall and disease-free survival. All variables associated with survival with P<0.20 in univariate analysis, were included in multivariate analysis using a Cox proportional hazard regression model. RESULTS: During the period analyzed, 209 procedures were performed on 170 patients. Postope-rative mortality in 90 days was 2.9% and 5-year overall survival was 64.9%. Its independent prognostic factors were the presence of extrahepatic disease at diagnosis of liver metastases, bilateral nodules and the occurrence of major complications after liver surgery. The estimated 5-year disease-free survival was 39.1% and its prognostic factors included R1 resection, extrahepatic disease, bilateral nodules, lymph node involvement in the primary tumor and primary tumors located in the rectum. CONCLUSION: Liver resection for colorectal metastases is safe and effective and the analysis of prognostic factors of survival in a large cohort of Brazilian patients showed similar results to those pointed in international series. The occurrence of major postoperative complications appears to be able to compromise overall survival and further investigation in needed in this topic.

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Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. Patients and Methods Patients were randomly assigned to first-or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand-foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.

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The aim of this in vitro study was to compare the degradation of resin-dentin bonds of an etch-and-rinse adhesive system to primary and permanent teeth. Flat superficial coronal dentin surfaces from 5 primary second molars and 5 permanent third molars were etched with phosphoric acid and bonded with an adhesive system (Adper Single Bond 2, 3M ESPE). Blocks of resin composite (Z250, 3M ESPE) were built up and the teeth sectioned to produce bonded sticks with a 0.8 mm(2) cross-sectional area. The sticks of each tooth were randomly divided and assigned to be subjected to microtensile testing immediately (24 h) or after aging by water storage (6 months). Data were analyzed by two-way repeated measures ANOVA and Tukey post hoc test (alpha = 0.05). Failure mode was evaluated using a stereomicroscope (400x). Microtensile values significantly decreased after the 6 months aging, independent of the dentin substrate. In 24 h, the values obtained to primary dentin were lower compared with permanent dentin. This difference was not maintained after aging. Adhesive/mixed failure was predominant in all experimental groups. In conclusion, degradation of resin-dentin bonds of the etch-and-rinse adhesive system occurred after 6 months of water storage; however, the reduction in bond strength values was higher for permanent teeth.

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Purpose: Two-millimeter punch biopsy is a swift and practical diagnostic tool in the outpatient setting. However, few studies have evaluated the efficacy of the method for diagnosis of malignant eyelid tumors. Methods: This was an observational study of patients with suspicion of malignant eyelid tumor attending the Ocular Plastic Surgery Center at Hospital das Clinicas, University of Sao Paulo School of Medicine. Following standard procedures, preoperative biopsies were taken with a 2-mm trephine and surgical excision was performed with safety margins, followed by reconstruction. Anatomopathologic analysis of the surgical specimen was used as gold standard to evaluate the accuracy of diagnosis by punch biopsy. Results: The study included 50 periocular tumors with suspicion of malignancy. The indicators of efficacy in the identification of malignancy by 2-mm punch biopsy were: sensitivity 88%, specificity 100%, positive predictive value 100%, and negative predictive value 64%. Accuracy was 90% for malignancy and 80% for histologic type. The. index of agreement between the diagnostic methods was 0.722 (p < 0.001). Conclusion: A positive result with 2-mm punch biopsy is a safe indication for surgical excision of the tumor, whereas a negative result does not necessarily imply benignity. In cases of high clinical suspicion, a second biopsy should be taken from a different part of the tumor to rule out malignancy. (Ophthal Plast Reconstr Surg 2012;28:282-285)

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Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that risperidone treatment can have negative skeletal consequences by direct activation of osteoclast activity and by indirect non-cell autonomous mechanisms. Our findings further support the tenet that the negative side effects of SGAs on bone mass should be considered when weighing potential risks and benefits, especially in children and adolescents who have not yet reached peak bone mass. This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism. (C) 2011 Elsevier Inc. All rights reserved.

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Abstract Introduction The natural history of patients with spontaneous parathyroid necrosis is unknown. In this case report we describe the clinical course, laboratory, radiographic, bone densitometry tests, parathyroid ultrasonography and scintigraphy examinations of a patient performed over a period of eight years after she first presented with a sudden episode of spontaneous resolution of primary hyperparathyroidism (PHPT). Case presentation A 24-year-old woman with a clinical history and laboratory and radiographic tests compatible with PHPT suffered a sudden episode of cervical pain and presented with clinical evidence of hypocalcemia. Biopsy of a cervical nodule revealed necrotic material compatible with ischemia of the parathyroid. The follow-up of the patient presented four distinct phases: the first, which lasted two years, was compatible with a period of bone hunger during which it was necessary to introduce calcitriol and calcium carbonate. During this period, the patient showed bone mass gain. The second phase was characterized by normalization of calcium and parathyroid hormone levels and its end was difficult to define. During the third phase there was a recurrence of hypercalcemia associated with elevated parathyroid hormone (PTH) levels and loss of bone mass. The last phase corresponded to the interval after parathyroidectomy, which was characterized by normalization of serum levels of calcium and PTH, as well as bone mass gain. Conclusion This case report indicates that spontaneous resolution of PHPT by adenoma necrosis is potentially temporary. Thus, in cases in which a conservative approach is chosen, clinical and laboratory follow-up is indispensable. Bone mass measurement is a useful tool in the follow-up of these cases. However, this option exposes the patient to a potential roller-coaster ride of bone mass gain and loss, whose long term consequences are still unknown.

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Abstract Background ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS-1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS-1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines. Results In a series of primary breast tumors, we observed variable levels of ADAMTS-1 mRNA expression but lower levels of ADAMTS-1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS-1 knockdown in breast cancer cells in vitro. MDA-MB-231 cells with depleted ADAMTS-1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS-1 may be related to VEGF, a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS-1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells (HUVEC) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS-1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS-1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels. Conclusions ADAMTS-1 expression was decreased in human breast tumors, and ADAMTS-1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro. Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS-1 in breast cancer cells.