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(2013) C2ORF40 suppresses breast cancer cell proliferation and invasion through modulating expression of M phase cell cycle genes, Epigenetics, 8:6,[571][572][573][574][575][576][577][578][579][580][581][582][583]

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The dopaminergic system can adapt to the different physiological or pathological situations to which the kidneys are subjected throughout life, maintaining homeostasis of natriuresis, extracellular volume, and blood pressure levels. The role of renal dopamine receptor dysfunction is clearly established in the pathogenesis of essential hypertension. Its associations with other pathological states such as insulin resistance and redox balance have also been associated with dysfunction of the dopaminergic system. The different dopamine receptors (D1–D5) show a protective effect against hypertension and kidney disorders. It is essential to take into account the various interactions of the dopaminergic system with other elements, such as adrenergic receptors. The approach to therapeutic strategies for essential hypertension must go through the blocking of those elements that lead to renal vasoconstriction or the restoration of the normal functioning of dopamine receptors. D1-like receptors are fundamental in this role, and new therapeutic efforts should be directed to the restoration of their functioning in many patients. More studies will be needed to allow the development of drugs that can be targeted to renal dopamine receptors in the treatment of hypertension.

6009 Background: Induction chemotherapy (IC) with TPF isa standard regimen for patients (pts) with locally advanced head and neck squamous cell carcinoma (N Engl J Med. 2007;357:1705–1715). However, CRT alone is standard treatment for unresectable LAHNC. We designed a trial to compare two different regimens of IC followed by CRT versus CRT alone in pts with unresectable LAHNC. Methods: Pts with unresectable, measurable LAHNC, adequate organ function, and ECOG 0–1 were enrolled and stratified according to primary tumor site. (IC) regimens (3 cycles): PF (cisplatin 100 mg/m2 day [d] 1, then 5-FU 1,000 mg/m2 continuous infusion [CI], d1–5, q21d); TPF (docetaxel 75 mg/m2 d1, cisplatin 75 mg/m2 d1, 5-FU 750 mg/m2 CI, d1–5, q21d plus G-CSF and ciprofloxacin). All pts were to receive CRT, consisting of conventional radiotherapy up to 70 Gy plus cisplatin 100 mg/m2 d 1, 22, 43. The primary end point was time to treatment failure (TTF) for (IC) vs. no (IC); secondary endpoints included locoregional control (LRC) rate and safety; 438 pts were needed to demonstrate a 15% difference in treatment failure (death, progression, surgery, other treatments) with α = 0.05, β = 0.2. Results: From December 2002 to June 2007, 439 pts were enrolled: IC 311 pts (TPF 155, PF 156) and CRT 128 pts. The majority of pts were: ECOG 1 (70%); oropharynx and oral cavity (63%); T4 (75%); N2-N3 (61%). In evaluable pts (at least 1 cycle), the median TTF was 12.5 months with IC/CRT vs. 4.9 months with CRT alone (p < 0.001; HR 0.57; 95%CI 0.44–0.74); LRC rate was 60.9% IC/CRT vs. 44.5% CRT (p = 0.003; OR = 0.52; 95%CI 0.3–0.81). Grade 3–4 adverse events (IC/CRT vs. CRT) occurred in 83% vs. 69% of pts and included febrile neutropenia (10% vs 1%), and stomatitis (43.7% vs 37%). Conclusions: This is the first phase III trial to demonstrate that (IC) followed by CRT significantly increases TTF and LRC compared with CRT alone in pts with unresectable LAHNC. IC/CRT should now be considered standard treatment for these pts. No significant financial relationships to disclose.