Felipe Osório Costa

RETRACTED: Obesity-Induced Increase in Tumor Necrosis Factor-α Leads to Development of Colon Cancer in Mice

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and Deputy Editor-in-Chief following an investigation into the data that were presented in several figures within the article. A number of images used in this article are believed to be duplicated images. The authors stated that they inadvertently inserted images of the wrong blots in several of the figures, resulting in the duplications; however, they did not address all of the concerns raised. Because the editors were no longer confident in the conclusions of the article based on these incorrect data, a decision was made to retract the paper. All authors have been notified of this decision. The University of Campinas (UNICAMP) in São Paulo, Brazil was contacted regarding these concerns, but to date the journal has received no response.

SOLTI-0701: A Multinational Double-Blind, Randomized Phase 2b Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo When Administered in Combination with Capecitabine in Patients with Locally Advanced or Metastatic Breast Cancer (BC).

INTRODUCTION: Sorafenib (SOR) is a potent multikinase inhibitor with anti-angiogenic and anti-proliferation activity. It is indicated for the treatment of advanced renal cell carcinoma and unresectable hepatocellular carcinoma. As a single agent, SOR has shown modest activity in patients with advanced BC. Here, we report results from one (SOLTI-0701) of four Phase 2b trials of sorafenib in combination with chemotherapy for advanced breast cancer.METHODS: SOLTI-0701 is a multinational, double-blind, randomized, placebo-controlled phase 2b study in patients with locally advanced or metastatic BC. Eligibility criteria included HER-2 negative tumors and Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 45.

Sodium Intake Is Associated with Carotid Artery Structure Alterations and Plasma Matrix Metalloproteinase-9 Upregulation in Hypertensive Adults

The mechanisms by which dietary sodium modulates cardiovascular risk are not fully understood. This study investigated whether sodium intake is related to carotid structure and hemodynamics and to plasma matrix metalloproteinase (MMP) activity in hypertensive adults. One hundred thirty-four participants were cross-sectionally evaluated by clinical history, anthropometry, carotid ultrasound, and analysis of hemodynamic, inflammatory, and metabolic variables. Daily sodium intake (DSI) was estimated by 24-h recall, discretionary sodium, and a FFQ. In 42 patients, plasma MMP-2 and MMP-9 activities were also analyzed. The mean DSI was 5.52 ± 0.29 g/d. Univariate analysis showed that DSI correlated with common carotid artery systolic and diastolic diameter (r = 0.36 and 0.34; both P < 0.001), peak and mean circumferential tension (r = 0.44 and 0.39; both P < 0.001), Youngs Elastic Modulus (r = 0.40; P < 0.001), intima-media thickness (r = 0.19; P < 0.05), and internal carotid artery resistive index (r = 0.20; P < 0.05). Multivariate analyses revealed that only artery diameter, circumferential wall tension, and Youngs Elastic Modulus were independently associated with DSI. Conversely, plasma MMP-9 activity was associated with DSI (r = 0.53; P < 0.001) as well as with common carotid systolic diameter (r = 0.33; P < 0.05) and Youngs Elastic Modulus (r = 0.38; P < 0.01). In conclusion, sodium intake is associated with carotid alterations in hypertensive adults independently of systemic hemodynamic variables. The present findings also suggest that increased MMP-9 activity might play a role in sodium-induced vascular remodeling.

Molecular and neuroendocrine mechanisms of cancer cachexia

Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment.

Abstract P2-16-01: Overall Survival Data from SOLTI-0701: A Multinational, Double-Blind, Placebo-Controlled, Randomized Phase 2b Study Evaluating the Oral Combination of Sorafenib and Capecitabine in Patients with Locally Advanced or Metastatic HER2-Negative Breast Cancer

Background: Sorafenib (SOR) is an oral multikinase inhibitor with antiangiogenic and antiproliferative activity. We previously reported data from the primary analysis of SOLTI-0701 demonstrating a progressionfree survival (PFS) benefit with the oral regimen of SOR + capecitabine (CAP) vs placebo (PL)+CAP in patients with advanced breast cancer (BC). Here we describe overall survival (OS), a secondary endpoint of SOLTI-0701. Methods: SOLTI-0701 is a multinational (Brazil, France, Spain) phase 2b study in HER2-negative patients with locally advanced or metastatic BC and ≥1 prior chemo regimen for advanced BC. Patients were randomized (1:1) to receive CAP (1000 mg/m2 po, twice daily [BID], 14 of every 21 days) with PL or SOR (400 mg po, BID). The primary endpoint was PFS. The sample size was estimated at 220 patients based on patient accrual projections and the estimated rate of PFS events. OS analysis was planned after 120 events. Results: A total of 229 patients were enrolled (115 SOR+CAP and 114 PL+CAP) from August 2007 to December 2008. Treatment arms were balanced for age (mean 55.2 y), ECOG status 0 (68%) and 1 (30%), stage IV disease (91%), and visceral metastases (75%). In the primary analysis, median PFS was 6.4 mo for the SOR arm vs 4.1 mo for the PL arm (hazard ratio 0.58; 95% CI, 0.41-0.81; 1-sided P=0.0006); the most common Grade 3/4 toxicity was hand-foot skin reaction/syndrome (45% vs 13%, respectively); discontinuation of treatment due to adverse events was infrequent (15% vs 7%, respectively). OS data are expected by the 3rd quarter of this year and will be presented, as well as updated safety data. Conclusions: The oral combination of SOR+CAP significantly improved PFS in patients with advanced BC. The regimen was tolerable with a manageable toxicity profile. An ongoing phase 3 registration trial is evaluating the combination of SOR+CAP for advanced BC. The secondary endpoint of OS will better characterize the potential role of SOR in advanced BC as randomized controlled trials thus far have yet to demonstrate any survival benefit with antiangiogenic agents. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-01.

CYBA C242T polymorphism is associated with obesity and diabetes mellitus in Brazilian hypertensive patients

Diabet. Med. 29, e55–e61 (2012)