For an isolated adrenal metastasis from NSCLC, patients with a synchronous metastasis who underwent adrenalectomy had a shorter median overall survival than those with a metachronous metastasis. However, a durable long-term survival is achieved in approximately 25% in both groups.

During the early part of the past century, hundreds of clinical studies involving more than 37,000 patients were conducted that showed radiotherapy (RT) to be a successful and safe alternative to drug therapy for the treatment of many diverse inflammatory conditions and diseases (e.g. tendonitis, bursitis, arthritis, and serious inflammatory lung conditions). Data from these studies were collected and analyzed with the intent of estimating an optimal dosing range for RT that would induce an efficacious treatment response. RT was reported to be frequently effective after only a single treatment, with a rapid (within 24 h) and often long-lasting (from months to years) relief from symptoms. Over a two-decade span from the 1920s to the 1940s, the therapeutic responses to a single RT treatment consistently improved as the dosing for multiple ailments decreased over time to between 30 roentgen (r) and 100 r. These findings are significant and in agreement with a number of contemporary reports from Germany where RT has been commonly and successfully employed in treating ailments with an inflammatory origin. A proposed mechanism by which RT mitigates inflammation and facilitates healing is via the polarization of macrophages to an anti-inflammatory or M2 phenotype.

No abstract

In NHL patients, hyperglycemia correlates with NHemT, and a similar although less clear pattern is suggested in PC patients. Prospective studies are needed to assess whether a better glycemic control during chemotherapy can improve toxicity and outcomes.

This paper provides a broad overview of hormesis, a specific type of biphasic dose response, its historical and scientific foundations as well as its biomedical applications, especially with respect to aging. Hormesis is a fundamental component of adaptability, neutralizing many endogenous and environmental challenges by toxic agents, thereby enhancing survival. Hormesis is highly conserved, broadly generalizable, and pleiotrophic, being independent of biological model, endpoint measured, inducing agent, level of biological organization and mechanism. The low dose stimulatory hormetic response has specific characteristics which defines both the quantitative features of biological plasticity and the potential for maximum biological performance, thereby estimating the limits to which numerous medical and pharmacological interventions may affect humans. The substantial degrading of some hormetic processes in the aged may profoundly reduce the capacity to respond effectively to numerous environmental/ischemic and other stressors leading to compromised health, disease and, ultimately, defining the bounds of longevity.

No abstract

Objectives-The objective of this study was to investigate survival of ovarian cancer patients with BRCA1 and BRCA2 mutations compared to those without mutations in a population-based sample of incident epithelial ovarian cancer cases. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript the two analyses were similar, thus data involving the 209 invasive epithelial cancer cases are presented, as this was judged to be more clinically relevant. NIH Public AccessResults-In the multivariate analysis, BRCA status and stage were statistically significant, and were adjusted for in the survival analysis model. The Kaplan-Meier method estimated expected survival at 4 years of 83% of BRCA2 carriers compared to 37% of BRCA1 carriers and 12% of non-carriers. There was a statistically significant difference between BRCA2 carriers and noncarriers (p = 0.013). No statistically significant survival differences were seen for BRCA1 carriers when compared with either BRCA2 carriers or non-carriers.Conclusion-These data suggest that BRCA2 mutation carriers with ovarian cancer may have better survival than BRCA1 carriers and non-carriers. The etiology of this possible survival advantage is currently unknown. Larger studies are needed to confirm these results and to clarify their etiology and clinical significance.

Purpose: Endothelins and their cell membrane receptors (ET A R and ET B R) are implicated in neoplastic pathogenesis. Atrasentan, a potent, selective ET A R antagonist, has a direct effect on tumor proliferation, apoptosis, and angiogenesis.This study was designed to assess the influence of atrasentan on paclitaxel pharmacokinetics and to determine the safety and efficacy of atrasentan in combination with paclitaxel-carboplatin. Experimental Design: Chemonaive patients with stage IIIB (malignant pleural effusion) and IV non^small cell lung cancer were enrolled. Toxicity and response were determined using the National Cancer Institute CommonToxicity Criteria version 2.0 and Response Evaluation Criteria in Solid Tumors criteria, respectively. Treatment consisted of paclitaxel (225 mg/m 2 ) and carboplatin (area under the curve, 6) administered on day 1every 3 weeks. A fixed 10 mg daily oral dose of atrasentan was administered continuously, starting on day 4 of cycle 1. Paclitaxel clearance was calculated during the first two cycles (pre-and post-atrasentan) in the first 10 patients. Results: All 44 patients were evaluable for survival, toxicity, and response. No significant change in mean paclitaxel clearance was detected (mean F SD, 21.2 F 4.5 L/h versus 21.3 F 4.9 L/h) for pre-and post-atrasentan values, respectively (P = 0.434). Grade 3/4 toxicities z10% were lymphopenia (22.7%), neutropenia (20.5%), dyspnea (11.4%), and hyperglycemia (11.4%). Response rate was 18.2%, with progression-free survival of 4.2 months, median survival of 10.6 months, and 1-year survival of 43%. Conclusion: Atrasentan plus paclitaxel-carboplatin was safe and well tolerated, with no apparent paclitaxel-atrasentan pharmacokinetic interaction. Efficacy and survival in advanced non^small cell lung cancer were comparable with studies of chemotherapy alone.In 2006, lung cancer remains the most frequent cause of cancer mortality in the United States (1). More than 80% of patients have non -small cell lung cancer (NSCLC) and half of them have advanced disease at diagnosis (2). In these cases, treatment mostly consists of chemotherapy with a platinumbased doublet (3). Chemotherapy, however, has reached an efficacy plateau, and newer therapies are needed (4,5). Improved understanding of the molecular biology of NSCLC (signaling pathways, etc.) has opened a whole new field of therapeutic options, where development of many new agents targets these pathways (6, 7), such as the endothelin axis pathway (8).The endothelins include three 21 -amino acid isopeptides (ET-1, ET-2, and ET-3) characterized by a single a-helix and two disulfide bridges. They exert their effects by binding to two cell surface receptors (ET A R and ET B R), which belong to the G protein -linked family of receptors (8,9). The binding of ET-1 to ET A R exerts pleiotropic biological effects that influence cell survival and proliferation (through activation of various kinases, namely, protein kinase C, epidermal growth factor, and insulin-like growth factor), apoptosis (b...