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PubMed | University of Houston, Stephenson Cancer Center, Anderson University, South Carolina, Uniformed Services University of the Health Sciences and Rice University
Type: Journal Article | Journal: Health psychology : official journal of the Division of Health Psychology, American Psychological Association | Year: 2016

To examine whether initial orienting (IO) and inability to disengage (ITD) attention from negative affective stimuli moderate the association of negative affect with smoking abstinence during a quit attempt.Data were from a longitudinal cohort study of smoking cessation (N = 424). A negative affect modified Stroop task was administered 1 week before and on quit day to measure IO and ITD. Ecological Momentary Assessments were used to create negative affect intercepts and linear slopes for the week before quitting and on quit day. Quit day and long-term abstinence measures were collected.Continuation ratio logit model analyses found significant interactions for prequit negative affect slope with prequit ITD, odds ratio (OR) = 0.738 (0.57, 0.96), p = .02, and for quit day negative affect intercept with quit day ITD, OR = 0.62 (0.41, 950), p = .03, predicting abstinence. The Prequit Negative Affect Intercept Prequit IO interaction predicting quit day abstinence was significant, OR = 1.42 (1.06, 1.90), p = .02, as was the Quit Day Negative Affect Slope Quit Day IO interaction predicting long-term abstinence, OR = 1.45 (1.02, 2.08), p = .04.The hypothesis that the association of negative affect with smoking abstinence would be moderated by ITD was generally supported. Among individuals with high ITD, negative affect was inversely related to abstinence, but unrelated to abstinence among individuals with lower levels of ITD. Unexpectedly, among individuals with low IO, negative affect was inversely related to abstinence, but unrelated to abstinence among individuals with higher levels of ITD. (PsycINFO Database Record


News Article | December 5, 2016
Site: www.eurekalert.org

What if a smartphone app could help you avoid relapsing back to smoking even before you knew you were at risk? A researcher from the Oklahoma Tobacco Research Center at the Stephenson Cancer Center is developing smartphone-based technology to help people receive real-time tobacco cessation treatment when they are most at risk. Michael Businelle, Ph.D., Associate Professor of Family and Preventive Medicine, and Director of the Mobile Health core at the Oklahoma Tobacco Research Center, has published a paper in the Journal of Medical Internet Research that demonstrates that real-time estimation of risk for imminent smoking relapse is possible. Most tobacco cessation research in underserved communities has been conducted in clinical settings where patients are commonly asked to recall thoughts and emotions that triggered tobacco use days, or even weeks, after a smoking lapse. This data collection method can be vulnerable to errors in memory and subject to bias. Businelle enlisted socioeconomically disadvantaged smokers seeking smoking cessation treatment and asked them to use smartphones to answer questions multiple times each day. The aim was to determine whether the number of reported lapse-risk factors was greater when smoking lapse was imminent compared with moments when a lapse was not imminent. Results indicated that a lapse risk estimator that combined just six questions (i.e., urge to smoke, stress, recent alcohol consumption, interaction with someone smoking, cessation motivation, and cigarette availability) identified 80 percent of all smoking lapses within 4 hours of the first lapse. "This research may pave the way for development of smartphone-based smoking cessation treatments that automatically tailor treatment content in real-time based on presence of specific lapse triggers," said Businelle. "For instance, if a person indicates a higher than usual urge to smoke and slightly lower motivation to remain smoke free, an app could automatically address relapse risk by delivering a tailored message such as: Remember that the urge WILL pass! Even though it might seem like smoking would be pleasant right now, it will only make you feel worse later." "Interventions that identify risk for lapse and automatically deliver tailored messages or other treatment components in real-time could offer effective, low cost, and highly disseminable treatments to individuals who do not have access to other, more standard, cessation treatments," said Businelle. According to a survey by the Pew Research Center, smartphone ownership among American adults has nearly doubled since 2011, including among low-income Americans. A recent study of Businelle revealed that of 610 homeless adults in Oklahoma City 72 percent owned active mobile phones.


News Article | October 31, 2016
Site: www.eurekalert.org

Nearly 7 in 10 cigarette smokers are looking for a way to quit - and many smokers have turned to e-cigarettes for help. A researcher at the Oklahoma Tobacco Research Center at the Stephenson Cancer Center has received a 5-year, $3 million R01 grant from the National Cancer Institute to study the impact of e-cigarette usage on smoking rates. The grant was awarded to Theodore Wagener, PhD, assistant professor of pediatrics, associate director for training at the Oklahoma Tobacco Research Center, and an Oklahoma TSET Research Scholar. National Cancer Institute R01 grants are the oldest and most prestigious type of cancer research grants. Wagener's research will assess how effective different types of e-cigarettes are in helping smokers switch from cigarettes to these vaping products and what impact switching has on smokers' exposure to harmful carcinogens and cancer risk. "We know that traditional combustible cigarettes, when used as intended kill one out of three smokers and is the leading cause of preventable death," Wagener said. "There may be a potential benefit if smokers switch to e-cigarettes completely, but we need additional research to understand to what extent." Since e-cigarettes have emerged on the market, the design and nicotine delivery has evolved. The newest generation of high-powered e-cigarettes is able to deliver nicotine much more like a cigarette, but with much lower levels of cancer-causing agents and no carbon monoxide. Early research demonstrates that an e-cigarette user may see some health benefit if they switch completely to the newer generation of e-cigarettes and reduce their exposure to combustible cigarette smoke. "Missing from the current literature is a long-term randomized trial assessing differences between earlier, low-powered e-cigarette devices and newer, high-powered devices on affecting smoking behaviors, nicotine addiction, and users' exposure to harmful chemicals and the resulting changes in cancer risk," said Wagener. Wagener's study will monitor levels of chemicals and toxicants in an e-cigarette user's body and inform the developing research base about the health impacts of e-cigarettes. Through this improved understanding, the study hopes to better inform the Food and Drug Administration as it considers any product-specific regulations. Historically, the e-cigarette market has been unregulated. As a TSET Research Scholar, Wagener, a clinical psychologist, has used a grant from TSET to fund research into the evolving field of e-cigarette use for more than four years. These pilot studies allowed Wagener to gather the necessary data to apply for the National Cancer Institute grant. "[E-cigarettes are] a new and evolving field for tobacco addiction, and it's important that those working to end tobacco use, regulators and consumers have the best information needed to make informed decisions," said TSET Executive Director Tracey Strader. "While the science on e-cigarettes is developing, wedo know that nicotine is not good for the developing brains of youth and young adults, and that children, pregnant women, and nonsmokers should not be exposed to the secondhand aerosol from e-cigarettes. Dr. Wagener's research will certainly benefit Oklahomans, and should have relevance for the nation, and across the globe." According to the Centers for Disease Control and Prevention, cigarette smoking is responsible for more than 480,000 deaths each year in the United States alone. The e-cigarette research is funded by NCI grant R01 CA204891.


WALTHAM, Mass.--(BUSINESS WIRE)--ImmunoGen, Inc. (Nasdaq:IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, today announced that results from the Phase 1 expansion cohort evaluating mirvetuximab soravtansine (IMGN853) in patients with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer were published in the Journal of Clinical Oncology. The data demonstrate the potential clinical benefit of mirvetuximab soravtansine for the treatment of platinum-resistant ovarian cancer. “Standard single-agent therapy for patients with platinum-resistant ovarian cancer typically has a response rate below 20% and median progression-free survival below four months,” said Kathleen Moore, M.D., Associate Professor, Stephenson Cancer Center, University of Oklahoma, and lead author of the publication. “Mirvetuximab soravtansine generated encouraging efficacy and tolerability data in the Phase 1 trial that suggest the potential to improve clinical outcomes for this patient population.” The Phase 1 expansion cohort enrolled 46 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer whose tumors were positive for FRα. Patients were dosed with mirvetuximab soravtansine once every three weeks. Mirvetuximab soravtansine demonstrated single-agent activity in the 46-patient cohort with a 26% confirmed response rate and median progression free survival (PFS) of 4.8 months. In a subset of 23 patients with low, medium or high FRα, who had received three or fewer prior lines of therapy, there was a 39% objective response rate (ORR) and median PFS of 6.7 months. On the basis of the study findings and additional data demonstrating the importance of FRα expression levels with mirvetuximab soravtansine, the Company has designed the Phase 3 FORWARD I study to enroll patients with platinum-resistant ovarian cancer with one to three prior therapies and with medium or high FRα. This group of patients in the Phase 1 expansion cohort exhibited a 44% ORR and a median PFS of 6.7 months.1 Mirvetuximab soravtansine exhibited a manageable safety profile. Adverse events (AEs) were generally mild with the majority being grade 1 or grade 2 (least severe grades). The most commonly observed AEs were diarrhea, blurred vision, nausea, and fatigue. “These results demonstrate that mirvetuximab soravtansine is active in platinum-resistant ovarian cancer, with encouraging response rates and progression-free survival combined with a manageable safety profile,” said Anna Berkenblit, M.D., Vice President and Chief Medical Officer of ImmunoGen. “On the basis of these findings, we have moved confidently into a Phase 3 registration study evaluating this promising agent against the standard of care in the platinum-resistant setting. In addition, we are evaluating combination regimens to assess mirvetuximab soravtansine in expanded patient populations and will begin reporting data from these combinations in mid-2017.” The publication, “Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study,” is available on the Journal of Clinical Oncology website. Mirvetuximab soravtansine (IMGN853) is the first FRα-targeting ADC. It uses a FRα-binding antibody to target the ADC specifically to FRα-expressing cancer cells and a potent anti-tumor agent, DM4, to kill the targeted cancer cells. Mirvetuximab soravtansine is ImmunoGen’s lead program and is now in Phase 3 testing as a single agent for the treatment of platinum-resistant ovarian cancer. The candidate is also being assessed in combination regimens for both platinum-resistant and platinum-sensitive disease in Phase 1b/2 FORWARD II trial. In 2016, approximately 22,300 new cases of ovarian cancer will be diagnosed in the U.S. and more than 14,200 women will die from the disease.2 ImmunoGen estimates that 60% of ovarian cancer cases have medium or high FRα expression. Standard first-line therapy for ovarian cancer is a platinum-based regimen. Once the cancer becomes platinum-resistant, treatment options include single-agent cytotoxic therapies such as pegylated liposomal doxorubicin, paclitaxel, or topotecan. ImmunoGen is a clinical-stage biotechnology company that develops targeted cancer therapeutics using its proprietary ADC technology. ImmunoGen’s lead product candidate, mirvetuximab soravtansine, is in a Phase 3 trial for FRα-positive platinum-resistant ovarian cancer, and is in Phase 1b/2 testing in combination regimens for earlier-stage disease. ImmunoGen’s ADC technology is used in Roche's marketed product, Kadcyla®, in three other clinical-stage ImmunoGen product candidates, and in programs in development by partners Amgen, Bayer, Biotest, CytomX, Lilly, Novartis, Sanofi and Takeda. More information about the Company can be found at www.immunogen.com. Kadcyla® is a registered trademark of Genentech, a member of the Roche Group. 1Moore KN, Martin LP, Matulonis UA et al: IMGN853 (mirvetuximab soravtansine), a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC): single-agent activity in platinum-resistant epithelial ovarian cancer (EOC) patients, presented at American Society of Clinical Oncology, June 2016, abstract # 5567 This press release includes forward-looking statements. For these statements, ImmunoGen claims the protection of the safe harbor for forward-looking statements provided by the Private Securities Litigation Reform Act of 1995. It should be noted that there are risks and uncertainties related to the development of novel anticancer products, including mirvetuximab soravtansine, including risks related to preclinical and clinical studies, their timings and results. A review of these risks can be found in ImmunoGen’s Annual Report on Form 10-K for the fiscal year ended June 30, 2016 and other reports filed with the Securities and Exchange Commission.


Aravindan S.,The University of Oklahoma Health Sciences Center | Aravindan S.,Annamalai University | Aravindan S.,Stephenson Cancer Center | Natarajan M.,University of Texas Health Science Center at San Antonio | And 3 more authors.
PLoS ONE | Year: 2013

Recently, we demonstrated that radiation (IR) instigates the occurrence of a NFκB-TNFα feedback cycle which sustains persistent NFκB activation in neuroblastoma (NB) cells and favors survival advantage and clonal expansion. Further, we reported that curcumin targets IR-induced survival signaling and NFκB dependent hTERT mediated clonal expansion in human NB cells. Herein, we investigated the efficacy of a novel synthetic monoketone, EF24, a curcumin analog in inhibiting persistent NFκB activation by disrupting the IR-induced NFκB-TNFα-NFκB feedback signaling in NB and subsequent mitigation of survival advantage and clonal expansion. EF24 profoundly suppressed the IR-induced NFκB-DNA binding activity/promoter activation and, maintained the NFκB repression by deterring NFκB-dependent TNFα transactivation/intercellular secretion in genetically varied human NB (SH-SY5Y, IMR-32, SK-PN-DW, MC-IXC and SK-N-MC) cell types. Further, EF24 completely suppressed IR-induced NFκB-TNFα cross-signaling dependent transactivation/translation of pro-survival IAP1, IAP2 and Survivin and subsequent cell survival. In corroboration, EF24 treatment maximally blocked IR-induced NFκB dependent hTERT transactivation/promoter activation, telomerase activation and consequent clonal expansion. EF24 displayed significant regulation of IR-induced feedback dependent NFκB and NFκB mediated survival signaling and complete regression of NB xenograft. Together, the results demonstrate for the first time that, novel synthetic monoketone EF24 potentiates radiotherapy and mitigates NB progression by selectively targeting IR-triggered NFκB-dependent TNFα-NFκB cross-signaling maintained NFκB mediated survival advantage and clonal expansion. © 2013 Aravindan et al.


Ramraj S.K.,The University of Oklahoma Health Sciences Center | Aravindan S.,Stephenson Cancer Center | Somasundaram D.B.,The University of Oklahoma Health Sciences Center | Herman T.S.,The University of Oklahoma Health Sciences Center | And 3 more authors.
Oncotarget | Year: 2016

Background: Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Results: Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (> 10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. Conclusion: For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression.


Khan F.H.,University of Oklahoma | Pandian V.,University of Oklahoma | Ramraj S.,University of Oklahoma | Natarajan M.,University of Texas Health Science Center at San Antonio | And 4 more authors.
BMC Cancer | Year: 2015

Background: Determining the driving factors and molecular flow-through that define the switch from favorable to aggressive high-risk disease is critical to the betterment of neuroblastoma cure. Methods: In this study, we examined the cytogenetic and tumorigenic physiognomies of distinct population of metastatic site- derived aggressive cells (MSDACs) from high-risk tumors, and showed the influence of acquired genetic rearrangements on poor patient outcomes. Results: Karyotyping in SH-SY5Y and MSDACs revealed trisomy of 1q, with additional non-random chromosomal rearrangements on 1q32, 8p23, 9q34, 15q24, 22q13 (additions), and 7q32 (deletion). Array CGH analysis of individual clones of MSDACs revealed genetic alterations in chromosomes 1, 7, 8, and 22, corresponding to a gain in the copy numbers of LOC100288142, CD1C, CFHR3, FOXP2, MDFIC, RALYL, CSMD3, SAMD12-AS1, and MAL2, and a loss in ADAM5, LOC400927, APOBEC3B, RPL3, MGAT3, SLC25A17, EP300, L3MBTL2, SERHL, POLDIP3, A4GALT, and TTLL1. QPCR analysis and immunoblotting showed a definite association between DNA-copy number changes and matching transcriptional/translational expression in clones of MSDACs. Further, MSDACs exert a stem-like phenotype. Under serum-free conditions, MSDACs demonstrated profound tumorosphere formation ex vivo. Moreover, MSDACs exhibited high tumorigenic capacity in vivo and prompted aggressive metastatic disease. Tissue microarray analysis coupled with automated IHC revealed significant association of RALYL to the tumor grade in a cohort of 25 neuroblastoma patients. Clinical outcome association analysis showed a strong correlation between the expression of CFHR3, CSMD3, MDFIC, FOXP2, RALYL, POLDIP3, SLC25A17, SERHL, MGAT3, TTLL1, or LOC400927 and overall and relapse-free survival in patients with neuroblastoma. Conclusion: Together, these data highlight the ongoing acquired genetic rearrangements in undifferentiated tumor-forming neural crest cells, and suggest that these alterations could switch favorable neuroblastoma to high-risk aggressive disease, promoting poor clinical outcomes. © 2015 Khan et al.


PubMed | Stephenson Cancer Center, The University of Oklahoma Health Sciences Center and Annamalai University
Type: | Journal: Oncotarget | Year: 2016

Therapy-resistant pancreatic cancer (PC) cells play a crucial role in tumor relapse, recurrence, and metastasis. Recently, we showed the anti-PC potential of an array of seaweed polyphenols and identified efficient drug deliverables. Herein, we investigated the benefit of one such deliverable, Hormophysa triquerta polyphenol (HT-EA), in regulating the dissemination physiognomy of therapy-resistant PC cells in vitro,and residual PC in vivo. Human PC cells exposed to ionizing radiation (IR), with/without HT-EA pre-treatment were examined for the alterations in the tumor invasion/metastasis (TIM) transcriptome (93 genes, QPCR-profiling). Utilizing a mouse model of residual PC, we investigated the benefit of HT-EA in the translation regulation of crucial TIM targets (TMA-IHC). Radiation activated 30, 50, 15, and 38 TIM molecules in surviving Panc-1, Panc-3.27, BxPC3, and MiaPaCa-2 cells. Of these, 15, 44, 12, and 26 molecules were suppressed with HT-EA pre-treatment. CXCR4 and COX2 exhibited cell-line-independent increases after IR, and was completely suppressed with HT-EA, across all PC cells. HT-EA treatment resulted in translational repression of IR-induced CXCR4, COX2, -catenin, MMP9, Ki-67, BAPX, PhPT-1, MEGF10, and GRB10 in residual PC. Muting CXCR4 or COX2 regulated the migration/invasion potential of IR-surviving cells, while forced expression of CXCR4 or COX2 significantly increased migration/invasion capabilities of PC cells. Further, treatment with HT-EA significantly inhibited IR-induced and CXCR4/COX2 forced expression-induced PC cell migration/invasion. This study (i) documents the TIM blueprint in therapy-resistant PC cells, (ii) defines the role of CXCR4 and COX2 in induced metastatic potential, and (iii) recognizes the potential of HT-EA in deterring the CXCR4/COX2-dependent dissemination destiny of therapy-resistant residual PC cells.


Eifler J.B.,Vanderbilt University | Cookson M.S.,Stephenson Cancer Center
Nature Reviews Urology | Year: 2014

After biochemical recurrence following radical prostatectomy, external beam radiation therapy (EBRT) reduces the risk of prostate-cancer-specific mortality. However, many men with a detectable serum PSA level will never experience clinical progression. New definitions of biochemical recurrence could help to determine the most appropriate candidates and time points for salvage EBRT.


Khan F.H.,The University of Oklahoma Health Sciences Center | Pandian V.,The University of Oklahoma Health Sciences Center | Ramraj S.,The University of Oklahoma Health Sciences Center | Aravindan S.,Stephenson Cancer Center | And 3 more authors.
BMC Genomics | Year: 2015

Background: MetastamiRs have momentous clinical relevance and have been correlated with disease progression in many tumors. In this study, we identified neuroblastoma metastamiRs exploiting unique mouse models of favorable and high-risk metastatic human neuroblastoma. Further, we related their deregulation to the modulation of target proteins and established their association with clinical outcomes. Results: Whole genome miRNA microarray analysis identified 74 metastamiRs across the manifold of metastatic tumors. RT-qPCR on select miRNAs validated profile expression. Results from bio-informatics across the ingenuity pathway, miRCancer, and literature data-mining endorsed the expression of these miRNAs in multiple tumor systems and showed their role in metastasis, identifying them as metastamiRs. Immunoblotting and TMA-IHC analyses revealed alterations in the expression/phosphorylation of metastamiRs' targets, including ADAMTS-1, AKT1/2/3, ASK1, AURKβ, Birc1, Birc2, Bric5, β-CATENIN, CASP8, CD54, CDK4, CREB, CTGF, CXCR4, CYCLIN-D1, EGFR, ELK1, ESR1, CFOS, FOSB, FRA, GRB10, GSK3β, IL1aα, JUND, kRAS, KRTAP1, MCP1, MEGF10, MMP2, MMP3, MMP9, MMP10, MTA2, MYB, cMYC, NF2, NOS3, P21, pP38, PTPN3, CLEAVED PARP, PKC, SDF-1β, SEMA3D, SELE, STAT3, TLR3, TNFaα, TNFR1, and VEGF in aggressive cells ex vivo and in a manifold of metastatic tumors in vivo. miRNA mimic (hsa-miR-125b, hsa-miR-27b, hsa-miR-93, hsa-miR-20a) and inhibitor (hsa-miR-1224-3p, hsa-miR-1260) approach for select miRNAs revealed the direct influence of the altered metastamiRs in the regulation of identified protein targets. Clinical outcome association analysis with the validated metastamiRs' targets corresponded strongly with poor overall and relapse-free survival. Conclusions: For the first time, these results identified a comprehensive list of neuroblastoma metastamiRs, related their deregulation to altered expression of protein targets, and established their association with poor clinical outcomes. The identified set of distinctive neuroblastoma metastamiRs could serve as potential candidates for diagnostic markers for the switch from favorable to high-risk metastatic disease. © 2015 Khan et al.

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