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Richmond, VA, United States

Dinnel J.,Virginia Commonwealth University | Moore B.L.,Virginia Commonwealth University | Skiver B.M.,Virginia Commonwealth University | Bose P.,Virginia Commonwealth University | Bose P.,Massey Cancer Center
Core Evidence | Year: 2015

Tumor lysis syndrome (TLS) is a potentially life-threatening complication of cancer therapy characterized by two or more of the following laboratory abnormalities: hyperuricemia, hyperkalemia, hypocalcemia, and hyperphosphatemia, with resultant end-organ damage, eg, renal failure, seizures, or cardiac arrhythmias. High-risk patients include those with highly proliferative cancers and/or large tumor burdens, particularly in the setting of highly effective chemotherapy, among other risk factors. Before 2002, antihyperuricemic drug therapy was limited to allopurinol, a xanthine oxidase inhibitor. Rasburicase, a recombinant urate oxidase, was approved by the US Food and Drug Administration for children in 2002 and adults in 2009, ushering in a new era in TLS therapy. We attempted to critically appraise the available evidence supporting the perceived benefits of rasburicase in the management of TLS. A Medline search yielded 98 relevant articles, including 26 retrospective and 22 prospective studies of rasburicase for the treatment of TLS, which were then evaluated to determine the best available evidence for the effectiveness of rasburicase in terms of disease-oriented, patient-oriented, and economic outcomes. Rasburicase is now a standard of care for patients at high risk of TLS despite continuing debate on the correlation between its profound and rapid lowering of plasma uric acid levels with hard patient outcomes, eg, need for renal replacement therapy and mortality. Rasburicase is dramatically effective in lowering plasma uric acid levels. The mortality and cost-effectiveness benefits of this expensive drug remain to be conclusively proven, and well designed, randomized controlled trials are needed to answer these fundamentally important questions. © 2015 Dinnel et al. Copyright © 2011 Massachusetts Medical Society. Source

Matsuyama R.K.,Virginia Commonwealth University | Moghanaki D.,Virginia Commonwealth University | Vachhani H.,Massey Cancer Center | Paasche-Orlow M.,Boston University
Patient Education and Counseling | Year: 2011

Objective: Cancer patients receiving adjuvant therapy encounter increasingly complex situations and decisions with each new procedure and therapy. To make informed decisions about care, they need to be able to access, process, and understand information. Individuals with limited health literacy may not be able to obtain or understand important information about their cancer and treatment. The rate of low health literacy has been shown to be higher among African Americans than among non-Hispanic Whites. This study examined the associations between race, health literacy, and self-reported needs for information about disease, diagnostic tests, treatments, physical care, and psychosocial resources. Methods: Measures assessing information needs were administered to 138 newly diagnosed cancer patients. Demographics were assessed by survey and health literacy was assessed with two commonly used measures: the Rapid Estimate Adult Literacy in Medicine (REALM) and the Short Test of Health Literacy in Adults (STOFHLA). Results: Study findings indicate that educational attainment, rather than health literacy, is a significant predictor of information needs. Conclusion: Overcoming barriers to information needs may be less dependent on literacy considerations and more dependent on issues that divide across levels of educational attainment. Practice implications: Oncologists and hospital staff should be attentive to the fact that many patients require additional assistance to meet their information needs. © 2011 Elsevier Ireland Ltd. Source

Shultz J.C.,VCU | Goehe R.W.,VCU | Wijesinghe D.S.,VCU | Murudkar C.,VCU | And 5 more authors.
Cancer Research | Year: 2010

Increasing evidence points to the functional importance of alternative splice variations in cancer pathophysiology. Two splice variants are derived from the CASP9 gene via the inclusion (Casp9a) or exclusion (Casp9b) of a four-exon cassette. Here we show that alternative splicing of Casp9 is dysregulated in non-small cell lung cancers (NSCLC) regardless of their pathologic classification. Based on these findings we hypothesized that survival pathways activated by oncogenic mutation regulated this mechanism. In contrast to K-RasV12 expression, epidermal growth factor receptor (EGFR) overexpression or mutation dramatically lowered the Casp9a/9b splice isoform ratio. Moreover, Casp9b downregulation blocked the ability of EGFR mutations to induce anchorage-independent growth. Furthermore, Casp9b expression blocked inhibition of clonogenic colony formation by erlotinib. Interrogation of oncogenic signaling pathways showed that inhibition of phosphoinositide 3-kinase or Akt dramatically increased the Casp9a/9b ratio in NSCLC cells. Finally, Akt was found to mediate exclusion of the exon 3,4,5,6 cassette of Casp9 via the phosphorylation state of the RNA splicing factor SRp30a via serines 199, 201, 227, and 234. Taken together, our findings show that oncogenic factors activating the phosphoinositide 3-kinase/Akt pathway can regulate alternative splicing of Casp9 via a coordinated mechanism involving the phosphorylation of SRp30a. ©2010 AACR. Source

Bean M.K.,Virginia Commonwealth University | Wilson D.B.,Massey Cancer Center | Thornton L.M.,University of North Carolina at Chapel Hill | Kelly N.,Virginia Commonwealth University | Mazzeo S.E.,Virginia Commonwealth University
Preventive Medicine | Year: 2012

Objective: NOURISH is a community-based treatment program for parents of overweight and obese children (ages 6-11, BMI ≥ 85th percentile). This study examined the impact of Nourishing Our Understanding of Role modeling to Improve Support and Health on child and parent dietary intake, secondary trial outcomes. Methods: In Virginia from 2008 to 2009, this randomized controlled pilot was implemented and dietary assessment of parents and children conducted at baseline, post-test, and 6-month follow-up. Parents (85% female, 62% African American, mean BMI = 34.1 ± 9.1) were randomized into intervention (n=46) or control (n=50) groups. Children's (mean age = 8.6 ± 1.5) mean Body Mass Index percentile was 98.1 ± 2.6. Parents completed 24-hour dietary records for themselves and their child(ren). Repeated measures analyses assessed treatment effects over time. T-tests evaluated within-group changes from baseline to post-test and to follow-up, using a modified intent-to-treat approach. Results: Both groups reported significant dietary changes, with few treatment effects found. For parents in NOURISH, significant improvements were found in intakes of total kilocalories/day, grams/day of carbohydrates and sugar, and percent calories from protein (p<0.05). Among control group children, significant improvements in total kilocalories/day and grams/day of carbohydrates and sugar were found (p<0.05). Conclusions: Among parents who self-select into a childhood obesity program, minimal intervention can elicit short-term dietary changes comparable to those of a structured intervention. © 2012 Elsevier Inc. Source

Manjili M.H.,Massey Cancer Center | Najarian K.,Virginia Commonwealth University | Wang X.-Y.,Virginia Commonwealth University
Future Oncology | Year: 2012

Breast cancer mortality is usually due to distant recurrence of cancer at an advanced stage of the disease rather than from primary cancer. Therefore, prediction of breast cancer recurrence at the time of diagnosis could lead to advances in personalized treatment of cancer patients in order to prevent risk of recurrence. Two prognostic biomarkers that are currently being used in clinical practice are a 70-gene MammaPrint® signature and a 21-gene Oncotype DX® panel. These assays generate relative risks of recurrence, but they do not provide a 'yes or 'no answer about recurrence in a given patient. These tests include genes that are involved in the cell cycle, invasion, metastasis and angiogenesis related to breast cancer. Emerging evidence suggests that a signature of genes involved in tumor-immune interactions may provide a more accurate prognostic tool. This paper reviews recent advances in the discovery of prognostic biomarkers for breast cancer patients. © 2012 Future Medicine Ltd. Source

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