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ABSTRACT: Several reports showed incomplete adoption of adjuvant radiotherapy (RT) for resectable gastric cancer since the publication of Intergroup 0116 trial results. The aims of this study were to identify demographic factors associated with omission of adjuvant RT and assess the impact of this omission on survival.
SEER database was queried for cases of resected gastric cancer. Multivariate analyses with logistic and Cox regressions were used to examine (a) likelihood of receiving adjuvant RT for different patient and county demographics and (b) effect of demographics on survival outcomes.
A total of 7,348 patients met the study criteria. Adjuvant RT was used in 33.1% of cases diagnosed in 1998-2001 and in 45.3% of cases in 2002-2007 (P < 0.001). Controlling for independent covariates, African Americans were 8.9% less likely to receive adjuvant RT than Caucasians or Asians (P < 0.001). Correspondingly, overall survival rates were significantly lower for African Americans than other races (HR = 1.38, P < 0.001). Furthermore, both the likelihood of receiving RT and the survival rates were significantly affected by county demographics: percent of population without high school education, percent of households below the poverty line, and median household income. Survival rates were highest among Asians, but this finding did not reflect more frequent use of RT.
Race and socioeconomic factors are significant predictors of treatment and survival outcomes for patients with resectable gastric cancer.
The findings of this and similar studies may aide the medical community in designing more effective strategies to ameliorate the standards of care nationwide.
Cancer Epidemiology Biomarkers & Prevention 03/2011; 20(2):223-33. · 4.12 Impact Factor
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ABSTRACT: Cancer of the exocrine pancreas is the fifth leading cause of cancer death in the United States. Neoadjuvant chemoradiation has been investigated in several trials as a strategy for downstaging locally advanced disease to resectability. The aim of the present study is to examine the effect of neoadjuvant radiation therapy (RT) vs. other treatments on long-term survival for patients with resectable pancreatic cancer in a large population-based sample group.
The Surveillance, Epidemiology, and End Results (SEER) registry database (1994-2003) was queried for cases of surgically resected pancreatic cancer. Retrospective analysis was performed. The endpoint of the study was overall survival.
Using Kaplan-Meier analysis we found that the median overall survival of patients receiving neoadjuvant RT was 23 months vs. 12 months with no RT and 17 months with adjuvant RT. Using Cox regression and controlling for independent covariates (age, sex, stage, grade, and year of diagnosis), we found that neoadjuvant RT results in significantly higher rates of survival than other treatments (hazard ratio [HR], 0.55; 95% confidence interval, 0.38-0.79; p = 0.001). Specifically comparing adjuvant with neoadjuvant RT, we found a significantly lower HR for death in patients receiving neoadjuvant RT rather than adjuvant RT (HR, 0.63; 95% confidence interval, 0.45-0.90; p = 0.03).
This analysis of SEER data showed a survival benefit for the use of neoadjuvant RT over surgery alone or surgery with adjuvant RT in treating pancreatic cancer. Therapeutic strategies that use neoadjuvant RT should be further explored for patients with resectable pancreatic cancer.
International journal of radiation oncology, biology, physics 07/2008; 72(4):1128-33. · 4.59 Impact Factor
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ABSTRACT: In a model for neuronal movement, PC12 cells undergo fast migration in response to nerve growth factor (NGF) and phorbol ester (PMA). We previously showed that NGF increases intracellular cAMP via activation of soluble adenylyl cyclase (sAC). In this report, we demonstrate that sAC activation is an essential component of NGF- + PMA-induced fast migration in PC12 cells. Interestingly, PMA also raises intracellular cAMP but does so by stimulating transmembrane adenylyl cyclases (tmAC); however, this tmAC-generated cAMP does not contribute to fast migration. Therefore, cells must possess independent pools of cAMP capable of modulating distinct functions.
Journal of Neuroscience Research 02/2008; 86(1):118-24. · 2.74 Impact Factor
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ABSTRACT: Nerve growth factor (NGF) and the ubiquitous second messenger cyclic AMP (cAMP) are both implicated in neuronal differentiation. Multiple studies indicate that NGF signals to at least a subset of its targets via cAMP, but the link between NGF and cAMP has remained elusive. Here, we have described the use of small molecule inhibitors to differentiate between the two known sources of cAMP in mammalian cells, bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC) and G protein-regulated transmembrane adenylyl cyclases. These inhibitors, along with sAC-specific small interfering RNA, reveal that sAC is uniquely responsible for the NGF-elicited rise in cAMP and is essential for the NGF-induced activation of the small G protein Rap1 in PC12 cells. In contrast and as expected, transmembrane adenylyl cyclase-generated cAMP is responsible for Rap1 activation by the G protein-coupled receptor ligand PACAP (pituitary adenylyl cyclase-activating peptide). These results identify sAC as a mediator of NGF signaling and reveal the existence of distinct pathways leading to cAMP-dependent signal transduction.
Journal of Biological Chemistry 07/2006; 281(25):17253-8. · 4.77 Impact Factor
