News Article | February 16, 2017
BIRMINGHAM, Ala.--(BUSINESS WIRE)--Proton International and the University of Alabama at Birmingham (UAB) announced today they are securing necessary approvals to begin construction this year of a proton therapy center that will provide cancer patients with an effective treatment option that is an alternative to traditional radiation therapy. Proton therapy is a highly precise treatment for treating cancer and some non-cancerous tumors without many of the side effects that often accompany traditional radiation therapy. This will be the 4th of 7 centers Proton International has been involved with as one of the world’s leading developers of facilities offering this advanced therapy. The UAB center, which will be the first in the State, has been approved by an Administrative Law Judge appointed by the Alabama State Health Planning and Development Agency. The two-year construction process is expected to begin this year with an opening planned for 2019. Proton International will build and own the center with UAB physicians providing clinical services and providing the leadership for education and research within the facility. “This is a significant step forward in cancer treatment for residents of Alabama and surrounding areas,” said Will Ferniany, PhD, and CEO of the UAB Health System. “Proton therapy is an extremely advanced cancer-fighting technology. Coupled with the skill, experience and resources of the UAB Comprehensive Cancer Center, the UAB Proton Therapy Center will be a life-changing resource for thousands of cancer patients throughout our region.” The Comprehensive Cancer Center is the only National Cancer Institute Designated Cancer Center in Alabama. “UAB is joining a stellar group of 25 of the nation’s top hospitals and cancer treatment centers providing proton therapy to patients,” said Chris Chandler, CEO, who founded Proton International after developing, opening and overseeing the operation of some of the first proton centers in the U.S. and Europe. “This center will have advanced proton therapy technology – a fully featured system with dynamic peak pencil beam scanning, developed by Varian Medical Systems an important technology leader.” “Recent advances in imaging have made proton therapy much more viable,” said John Fiveash, M.D., professor in the UAB Department of Radiation Oncology. “It uses sophisticated imaging to create a 3D image of the tumor. It then delivers a focused beam of radiation, custom-sized and shaped, so that it paints the tumor site while leaving surrounding tissue generally untouched, reducing collateral damage.” It is conservatively estimated that some 250,000 cancer patients in the U.S. alone could benefit from proton therapy, which is mainly being used to treat solid cancer tumors, including tumors of the brain and central nervous system, spine, head and neck, lung, prostate, liver, gastrointestinal tract and colon, and some breast tumors. While it primarily treats single-site tumors, it can in some cases be used for treating cancer that has spread (metastasized) to surrounding tissue because of its focused dose capabilities. Protons are widely used to treat children, who are particularly sensitive to the effects of radiation therapy. Because of its precision in targeting tumors, proton therapy greatly reduces damage to nearby healthy tissue, which is the cause of most short- and long-term side-effects, including cancer recurrence later in life. The three-story UAB Proton Center will be built on the Campus of UAB. Planning and pre-treatment will continue to be done at UAB’s Hazelrig-Salter Radiation Oncology Center and medical staff will be exclusively from UAB. The center will enroll its patients in national proton therapy registries and will participate in clinical research studies to advance the application of proton therapy and determine best practices. In partnering with Proton International UAB has a team of proven providers. Proton International is currently participating in the development of 7 centers two of which are under construction; another set to break ground in March, and a memorandum of understanding approved for 4 others. PI’s turnkey development model significantly lowers project risk and provides access to long-term funding. For this project UAB and PI have selected Varian Medical Systems, an innovator in proton therapy systems Varian has been a longtime partner with UAB in the delivery of radiation therapy, and this new proton system will integrate UAB’s existing network of Varian products, including TrueBeam linear accelerators, Eclipse treatment planning, and ARIA information system. UAB Medicine comprises the School of Medicine and the $3 billion UAB Health System that includes all of the University of Alabama at Birmingham’s patient-care activities and 2,300 licensed beds in six hospitals, one of which is UAB Hospital — the third-largest public hospital in the United States, winner of the Women's Choice award, and one of U.S. News and World Report's Best Hospitals. UAB is the state of Alabama’s largest single employer and an internationally renowned research university and academic health center; its professional schools and specialty patient-care programs are consistently ranked among the nation’s top 50. UAB is the largest academic medical center in Alabama and one of the top four largest academic medical centers in the United States. UAB’s Center for Clinical and Translational Science is advancing innovative discoveries for better health as a two-time recipient of the prestigious Center for Translational Science Award. Find more information at www.uab.edu and www.uabmedicine.org. Proton International (PI) www.protonintl.com has an experienced team dedicated to bringing proton therapy to patients. The company works with hospitals and physician groups to develop one- and two-room proton therapy facilities, as well as larger facilities, on a turnkey basis. The PI team has developed and operated large centers and as well as the smaller alternatives. PI has centers under construction with Beaumont Hospital, Royal Oak, Mich., and the University Medical Center in Groningen, The Netherlands; as well as an upcoming project with Delray Medical Center, Delray Beach, Fla. PI’s business model ensures that projects are completed on time, on budget, and within the scope and needs of the Institution. Services include business planning, organizational structure, financing, building design and construction, installation and commissioning, equipment, staff training and more.
Tang Z.,University of Alabama at Birmingham |
Araysi L.M.,University of Alabama at Birmingham |
Fathallah-Shaykh H.M.,University of Alabama at Birmingham |
Fathallah-Shaykh H.M.,Comprehensive NeuroScience |
Fathallah-Shaykh H.M.,The Comprehensive Cancer Center
PLoS ONE | Year: 2013
Malignant gliomas remain associated with poor prognosis and high morbidity because of their ability to invade the brain; furthermore, human gliomas exhibit a phenotype of accelerated brain invasion in response to anti-angiogenic drugs. Here, we study 8 human glioblastoma cell lines; U251, U87, D54 and LN229 show accelerated motility in low ambient oxygen. Src inhibition by Dasatinib abrogates this phenotype. Molecular discovery and validation studies evaluate 46 molecules related to motility or the src pathway in U251 cells. Demanding that the molecular changes induced by low ambient oxygen are reversed by Dasatinib in U251 cells, identifies neural Wiskott-Aldrich syndrome protein (NWASP), Focal adhesion Kinase (FAK), β-Catenin, and Cofilin. However, only Src-mediated NWASP phosphorylation distinguishes the four cell lines that exhibit enhanced motility in low ambient oxygen. Downregulating c-Src or NWASP by RNA interference abrogates the low-oxygen-induced enhancement in motility by in vitro assays and in organotypic brain slice cultures. The findings support the idea that c-Src and NWASP play key roles in mediating the molecular pathogenesis of low oxygen-induced accelerated brain invasion by gliomas. © 2013 Tang et al.
Virk-Baker M.K.,University of Alabama at Birmingham |
Barnes S.,University of Alabama at Birmingham |
Barnes S.,The Comprehensive Cancer Center |
Krontiras H.,The Comprehensive Cancer Center |
And 3 more authors.
Nutrition Research | Year: 2014
Soy foods are the richest sources of isoflavones, mainly daidzein and genistein. Soy isoflavones are structurally similar to the steroid hormone 17. β-estradiol and may protect against breast cancer. S-(-)equol, a metabolite of the soy isoflavone daidzein, has a higher bioavailability and greater affinity for estrogen receptor β than daidzein. Approximately one-third of the Western population is able to produce S-(-)equol, and the ability is linked to certain gut microbes. We hypothesized that the prevalence of breast cancer, ductal hyperplasia, and overall breast pathology will be lower among S-(-)equol producing, as compared with nonproducing, postmenopausal women undergoing a breast biopsy. We tested our hypothesis using a cross-sectional study design. Usual diets of the participants were supplemented with 1 soy bar per day for 3 consecutive days. Liquid chromatography-multiple reaction ion monitoring mass spectrometry analysis of urine from 143 subjects revealed 25 (17.5%) as S-(-)equol producers. We found no statistically significant associations between S-(-)equol producing status and overall breast pathology (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.23-1.89), ductal hyperplasia (OR, 0.84; 95% CI, 0.20-3.41), or breast cancer (OR, 0.56; 95% CI, 0.16-1.87). However, the mean dietary isoflavone intake was much lower (0.3 mg/d) than in previous reports. Given that the amount of S-(-)equol produced in the gut depends on the amount of daidzein exposure, the low soy intake coupled with lower prevalence of S-(-)equol producing status in the study population favors toward null associations. Findings from our study could be used for further investigations on S-(-)equol producing status and disease risk. © 2014.
Chaffee B.R.,Miami University Ohio |
Hoang T.V.,Miami University Ohio |
Leonard M.R.,Miami University Ohio |
Bruney D.G.,Miami University Ohio |
And 5 more authors.
Developmental Biology | Year: 2016
Lens epithelial cells express many receptor tyrosine kinases (RTKs) that stimulate PI3K-AKT and RAS-RAF-MEK-ERK intracellular signaling pathways. These pathways ultimately activate the phosphorylation of key cellular transcription factors and other proteins that control proliferation, survival, metabolism, and differentiation in virtually all cells. Among RTKs in the lens, only stimulation of fibroblast growth factor receptors (FGFRs) elicits a lens epithelial cell to fiber cell differentiation response in mammals. Moreover, although the lens expresses three different Fgfr genes, the isolated removal of Fgfr2 at the lens placode stage inhibits both lens cell survival and fiber cell differentiation. Phosphatase and tensin homolog (PTEN), commonly known as a tumor suppressor, inhibits ERK and AKT activation and initiates both apoptotic pathways, and cell cycle arrest. Here, we show that the combined deletion of Fgfr2 and Pten rescues the cell death phenotype associated with Fgfr2 loss alone. Additionally, Pten removal increased AKT and ERK activation, above the levels of controls, in the presence or absence of Fgfr2. However, isolated deletion of Pten failed to stimulate ectopic fiber cell differentiation, and the combined deletion of Pten and Fgfr2 failed to restore differentiation-specific Aquaporin0 and DnaseIIβ expression in the lens fiber cells. © 2016 Elsevier Inc.
PubMed | King Fahad Medical City, King Saud University and The Comprehensive Cancer Center
Type: | Journal: Disease markers | Year: 2015
The aim of this study was to investigate the role of APE1 Asp148Glu polymorphism in breast cancer progression in Saudi population.We examined the genetic variations (rs1130409) in the DNA base excision repair gene APE1 at codon 148 (Asp148Glu) and its association with breast cancer risk using genotypic assays and in silico structural as well as functional predictions. In silico structural analysis was performed with Asp148Glu allele and compared with the predicted native protein structure. The wild and mutant 3D structures of APE1 were compared and analyzed using solvent accessibility models for protein stability confirmation.Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. The in silico analysis results indicated that the nsSNP Asp148Glu may cause changes in the protein structure and is associated with breast cancer risk.Taken together, this is the first report that established that Asp148Glu variant has structural and functional effect on the APE1 and may play an important role in breast cancer progression in Saudi population.
PubMed | The Comprehensive Cancer Center
Type: Journal Article | Journal: Diagnostic molecular pathology : the American journal of surgical pathology, part B | Year: 2010
Infection by the human papillomavirus (HPV) is a cause of cervical intraepithelial neoplasia (CIN) and cancer. microRNA (miRNA) in situ analysis of the transformation zone epithelia, the site of initial cervical HPV infection, showed that miRNAs let-7c, -99a, 26a, and 125b were the most abundantly expressed. In situ testing of CIN 1 showed a dramatic reduction in miR-125b expression in the koilocytes, the cytologic marker of productive HPV infection. A marked reduction in miR-125b was likewise observed in the HPV-infected cells of the condyloma acuminatum, verruca vulgaris, and epidermodysplasia verruciformis. Reverse transcriptase in situ polymerase chain reaction (PCR) showed that the pre-miRNA 125b was present in the koilocyte, suggesting direct inactivation of the mature miRNA. HEK cells transfected with only the antimiR-125b showed perinuclear halos equivalent to HPV-infected koilocytes. NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b showed a marked reduction in viral DNA and protein synthesis by quantitative PCR and in situ-based analyses, respectively (P=0.002). Alternatively, cotransfection with anti-miR-125b and HPV 16 markedly increased HPV DNA (P=0.002). Sequence analyses showed strong homology between L2 of different HPV genotypes and miR-125b. Transfection with HPV 16 L2 resulted in a marked reduction in miR-125b levels in the NIH 3T3 cells. HPV L2-induced inactivation of miR-125b is associated with the classic cytologic changes of the koilocyte, and the exogenous application of mimetic miR-125b markedly inhibits HPV DNA synthesis.