First, we defined the TKI group as those who received TKIs before brain metastasis, meaning that in all cases brain metastasis represented progression after exposure to the agent. P .001) was associated with improved OS. Forty-four (13%) patients developed a brain metastasis, including 29 (15.8%) of the non-TKI group and 15 (9.7%) of the TKI group. The 5-12 months actuarial rate of brain metastasis was 40% versus 17%, respectively (P .001). TKI treatment was associated with lower incidence of brain metastasis in Cox multivariate analysis (HR, 0.39; Pexmetinib (ARRY-614) 95% CI, 0.21C0.73; P = .003). Lung metastasis increased the risk of brain metastasis (HR, 9.61; 95% CI, 2.97C31.1; P .001). CONCLUSIONS Treatment with TKI brokers reduces the incidence of brain metastasis in mRCC. Lung metastasis is usually a risk factor for brain metastasis Pexmetinib (ARRY-614) development. strong class=”kwd-title” Keywords: renal cell carcinoma, tyrosine kinase inhibitors, sunitinib, sorafenib, brain metastasis Cancers of the kidney and renal pelvis account for approximately 3.9% of all cancers in the United States, with an estimated 57,760 new cases and 12,980 deaths in 2009 2009.1 Most of these cancers arise in the kidney, and the most common histological type, renal cell carcinoma (RCC), presents with metastatic disease in up to 30% of cases.2 The most common sites of metastasis include lung, lymph nodes, and bone,2 with the brain involved in 10% to 20% of cases.3,4 Because metastatic RCC (mRCC) is generally resistant to chemotherapy, immunologic therapy with interferon or interleukin-2 (IL-2) has been the most commonly used treatment, despite substantial toxicity5 and disappointingly low response rates (5%C20%).2 The advent of tyrosine kinase inhibitors (TKIs) has drastically altered the management of mRCC. These brokers take action by inhibiting intracellular kinases in the vascular endothelial growth factor pathway, the up-regulation of which is usually central to the pathogenesis of RCC.6C8 During the past 5 years, 3 TKIs, sunitinib, sorafenib, and pazopanib, were approved by the US Food and Drug Administration for use in advanced RCC. Sunitinib was approved in 2006 for RCC after Rabbit Polyclonal to RBM26 phase 2 and 3 trials9 exhibited that sunitinib, given as first-line therapy, doubled the progression-free survival (PFS) time compared with that obtained with interferon. Sorafenib was approved for RCC in 2005 after phase 3 trials similarly showed that it improved PFS compared with placebo for patients with cytokine-refractory disease,10 and pazopanib was approved in 2009 2009 after another phase 3 trial showed that it led to improved PFS compared with placebo for both previously untreated and cytokine-refractory disease.11 The outcome for patients with RCC who develop brain metastasis is typically poor, with median survival times of only 4 to 11 months after diagnosis3,12 even after surgical resection, whole-brain radiotherapy, or stereotactic radiosurgery. The influence of TKIs around the development or progression of brain metastasis has not yet been clearly established. Several case reports have been published describing brain metastasis responding to treatment with sunitinib or sorafenib,13,14 raising the possibility that use of TKIs may improve the overall outcome for patients with RCC and brain metastasis. In addition, a recent review of patients enrolled in the TARGET trial found a lower incidence of brain metastasis in the group that received sorafenib,15 suggesting that these brokers may also help to prevent or delay the development of brain metastasis. In this retrospective analysis, we sought to evaluate the effect of treatment with 1 of 2 TKIs, sunitinib and sorafenib, on brain metastasis development in patients with mRCC. Given the timing of the approval and increasing use of these brokers in early 2006, we selected 2 groups of patients, 1 that offered to The University or college of Texas MD Anderson Malignancy Center in 2002 to 2003 and the other in 2006 to 2007 with the expectation that these periods would segregate patients by TKI exposure status. We extracted a wide array of clinicopathologic characteristics and used univariate and multivariate analyses to evaluate potential treatment effects on Pexmetinib (ARRY-614) the incidence of brain metastasis, time to the diagnosis of brain metastasis, and outcomes, including survival and local control, after systemic therapy or treatment of brain metastasis. MATERIALS AND METHODS Patient Selection The institutional review table of The University or college of Texas MD Anderson Malignancy Center approved this retrospective analysis. Patients were recognized by searching an institutional Pexmetinib (ARRY-614) tumor registry database for those with stage IV obvious cell RCC who offered for.
- Next These data support the 12F4 IHC analyses and demonstrate that aged 3xTg-ADxTNF-RI/RII KO mice have significantly higher A peptide/plaque burden compared with age-matched 3xTg-AD counterparts
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- In the malarial parasite, pyrimidine biosynthesis provides the only route to these essential metabolites, as the parasite is unable to scavenge preformed pyrimidines (11C13)
- Rats received either automobile (0
- Abbreviations: CON, control; CANA, canagliflozin; AMPK, AMP-activated proteins kinase; ACC, acetyl-CoA carboxylase
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- Results of ethnicities suggest that Dll1 enhances Ig secretion, while Jg1 has an inhibitory part(Santos recently demonstrated that Notch signaling protects germinal center (GC) B cells from apoptosis