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Centuori S.M.,Arizona Cancer Center
Digestive diseases and sciences | Year: 2014

A high-fat diet coincides with increased levels of bile acids. This increase in bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway. Source

Gerner E.W.,Arizona Cancer Center
Cancer Prevention Research | Year: 2010

Ornithine decarboxylase has a relatively long history as a target for cancer chemoprevention and chemotherapy. Plym Forshell et al. report new evidence (beginning on p. 140 in this issue of the journal) indicating that spermidine synthase, a fellow enzyme of ornithine decarboxylase in polyamine metabolism, is transactivated in part by the MYC gene and is a potential target for chemoprevention of B-cell lymphomas. ©2010 AACR. Source

Rana S.,Arizona Cancer Center
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2014

The Radiation Therapy Oncology Group (RTOG) 0813 protocol requires the use of dose calculation algorithms with tissue heterogeneity corrections to compute dose on stereotactic body radiation therapy (SBRT) non-small cell lung cancer (NSCLC) plans. A new photon dose calculation algorithm called Acuros XB (AXB) has recently been implemented in the Eclipse treatment planning system (TPS). The main purpose of this study was to compare the dosimetric results of AXB with that of anisotropic analytical algorithm (AAA) for RTOG 0813 parameters. Additionally, phantom study was done to evaluate the dose prediction accuracy of AXB and AAA beyond low-density medium of different thicknesses by comparing the calculated results with the measurements. For the RTOG dosimetric study, 14 clinically approved SBRT NSCLC cases were included. The planning target volume (PTV) ranged from 3.2-43.0 cc. RapidArc treatment plans were generated in the Eclipse TPS following RTOG 0813 dosimetric criteria, and treatment plans were calculated using AAA with heterogeneity correction (AAA plans). All the AAA plans were then recalculated using AXB with heterogeneity correction (AXB plans) for identical beam parameters and same number of monitor units. The AAA and AXB plans were compared for following RTOG 0813 parameters: ratio of prescription isodose volume to PTV (R100%), ratio of 50% prescription isodose volume to PTV (R50%), maximal dose 2 cm from the PTV in any direction as a percentage of prescription dose (D2cm), and the percentage of ipsilateral lung receiving dose equal to or larger than 20 Gy (V20). The phantom study showed that the results of AXB had better agreement with the measurements, and the difference ranged from -1.7% to 2.8%. The AAA results showed larger disagreement with the measurements, with differences from 4.1% to 12.5% for field size 5 × 5cm2 and from 1.4% to 6.8% for field size 10 × 10 cm2. The results from the RTOG SBRT lung cases showed that, on average, the AXB plans produced lower values for R100%, R50%, and D2cm by 4.96%, 1.15%, and 1.60%, respectively, but higher V20 of ipsilateral lung by 1.09% when compared with AAA plans. In the set of AAA plans, minor deviation was seen for R100% (six cases), R50% (nine cases), D2cm (four cases), and V20 (one case). Similarly, the AXB plans also showed minor deviation for R100% (one case), R50% (eight cases), D2cm (three cases), and V20 (one case). The dosimetric results presented in the current study show that both the AXB and AAA can meet the RTOG 0813 dosimetric criteria. Source

New anticancer agents that target a single cell surface receptor, up-regulated or amplified gene product, or mutated gene, have met with some success in treating advanced cancers. However, patients' tumors still eventually progress on these therapies. If it were possible to identify a larger number of targetable vulnerabilities in an individual's tumor, multiple targets could be exploited with the use of specific therapeutic agents, thus possibly giving the patient viable therapeutic alternatives. In this exploratory study, we used next-generation sequencing technologies (NGS) including whole genome sequencing (WGS), and where feasible, whole transcriptome sequencing (WTS) to identify genomic events and associated expression changes in advanced cancer patients. WGS on paired tumor and normal samples from nine advanced cancer patients and WTS on six of these patients' tumors was completed. One patient's treatment was based on targets and pathways identified by NGS and the patient had a short-lived PET/CT response with a significant reduction in his tumor-related pain. To design treatment plans based on information garnered from NGS, several challenges were encountered: NGS reporting delays, communication of results to out-of-state participants and their treating oncologists, and chain of custody handling for fresh biopsy samples for Clinical Laboratory Improvement Amendments (CLIA) target validation. While the initial effort was a slower process than anticipated due to a variety of issues, we demonstrate the feasibility of using NGS in advanced cancer patients so that treatments for patients with progressing tumors may be improved. Source

Bookman M.A.,Arizona Cancer Center
Annals of Oncology | Year: 2010

Advanced-stage epithelial ovarian cancer is generally managed with cytoreductive surgery and chemotherapy consisting of carboplatin and paclitaxel, achieving clinical complete remission in the majority of patients. However, most tumors recur, and are associated with progressive chemotherapy resistance. Techniques to optimize chemotherapy have included intraperitoneal administration and weekly scheduling of paclitaxel. Efforts to improve on the long-term results of primary therapy through addition of a third cytotoxic agent have not been successful, including extended maintenance, as well as strategies to overcome chemotherapy resistance. Limited data emerging from phase III trials using bevacizumab suggest some advantage in progression-free survival, particularly in the maintenance setting, and further data are awaited. At present, primary therapy with carboplatin and paclitaxel remains a well-tolerated standard regimen, including the option of weekly paclitaxel dosing, intraperitoneal delivery and neoadjuvant therapy in selected patients. Emerging biological paradigms will hopefully contribute to individualized treatment options in the future. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

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