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Telepak L.C.,University of Florida | Jensen S.E.,Northwestern University | Dodd S.M.,Palo Alto Health Care System | Morgan L.S.,University of Florida | Pereira D.B.,University of Florida
British Journal of Health Psychology | Year: 2014

Objectives Psychosocial factors have previously been linked with survival and mortality in cancer populations. Little evidence is available about the relationship between these factors and outcomes in gynaecologic cancer populations, particularly endometrial cancer, the fourth most common cancer among women. This study examined the relationship between several psychosocial factors prior to surgical resection and risk of all-cause mortality in women with endometrial cancer.Design The study utilized a non-experimental, longitudinal design.Methods Participants were 87 women (Mage = 60.69 years, SDage = 9.12 years) who were diagnosed with T1N0-T3N2 endometrial cancer and subsequently underwent surgery. Participants provided psychosocial data immediately prior to surgery. Survival statuses 4-5 years post-diagnoses were abstracted via medical record review. Cox regression was employed for the survival analysis.Results Of the 87 women in this sample, 21 women died during the 4- to 5-year follow-up. Adjusting for age, presence of regional disease and medical comorbidity severity (known biomedical prognostic factors), greater use of an active coping style prior to surgery was significantly associated with a lower probability of all-cause mortality, hazard ratio (HR) = 0.78, p =.04. Life stress, depressive symptoms, use of self-distraction coping, receipt of emotional support and endometrial cancer quality of life prior to surgery were not significantly associated with all-cause mortality 4-5 years following diagnosis.Conclusions Greater use of active coping prior to surgery for suspected endometrial cancer is associated with lower probability of all-cause mortality 4-5 years post-surgery. Future research should attempt to replicate these relationships in a larger and more representative sample and examine potential behavioural and neuroendocrine/immune mediators of this relationship. Statement of contribution What is already known on this subject? Psychosocial factors have previously been linked with clinical outcomes in a variety of cancer populations. With regards to gynecologic cancer, the majority of the research has been conducted in ovarian cancer and examines the protective role of social support in mortality outcomes. What does this study add? Demonstrates association between active coping during perioperative period and 5 year survival. Demonstrates psychosocial-survival relationship exists independent of biobehavioral factors. © 2013 The British Psychological Society. Source


Ilgen M.A.,Serious Mental Illness Treatment Research and Evaluation Center | Ilgen M.A.,University of Michigan | Perron B.,Serious Mental Illness Treatment Research and Evaluation Center | Perron B.,University of Michigan | And 4 more authors.
American Journal on Addictions | Year: 2010

Using data from the National Comorbidity Survey - Replication, this study examined the timing of onset of self-report comorbid chronic nonarthritis pain and substance use disorders (SUDs) and characteristics associated with different onset patterns. Most individuals (58.2%; N = 351632) report that the SUD preceded the onset of pain. Relative to those with SUDs prior to the onset of chronic pain, those experiencing pain first were less likely to have a drug use disorder, more likely to have head pain, to be younger at the onset of the first condition, and to have a shorter duration between condition onsets. © 2010 American Academy of Addiction Psychiatry. Source


Li H.,Palo Alto Health Care System | Liu J.,Palo Alto Health Care System
Biochemical Journal | Year: 2012

PCSK9 (proprotein convertase subtilisin/kexin type 9) plays an important role in control of plasma LDL (low-density lipoprotein) cholesterol metabolism by modulating the degradation of hepatic LDL receptor. Previous studies demonstrated that PCSK9 is a target gene of the SREBP2 [SRE (sterol-regulatory element)- binding protein 2] that activates PCSK9 gene transcription through an SRE motif of the promoter. In addition to SREBP2, HNF1α(hepatic nuclear factor 1α) positively regulates PCSK9 gene transcription in hepatic cells through a binding site located 28 bp upstream from SRE. In the present study, we have identified a novel HINFP (histone nuclear factor P) recognitionmotif residing between the HNF1 motif and SRE that is essential for basal and sterol-regulated transcriptions of the PCSK9 promoter. Mutation of this motif lowers the basal promoter activity and abolishes the sterol-mediated repression as well as the SREBP2-induced activation of the PCSK9 promoter. We show further that the activity of SREBP2 in stimulating PCSK9 promoter activity is greatly enhanced by HINFP. Additional experiments suggest that HINFP and its cofactor NPAT (nuclear protein of the ataxia telangectasia mutated locus) form a functional complex, and NPAT may subsequently recruit the HAT (histone acetyltransferase) cofactor TRRAP (transformation/transactivation domain-associated protein) to facilitate the histone H4 acetylation of the PCSK9 promoter. Knockdown of HINFP, NPAT or TRRAP each markedly reduces the amount of acetylated histone H4 on the PCSK9 promoter region and lowers PCSK9 protein levels. Importantly, by utilizing co-immunoprecipitation assays, we have demonstrated a direct interaction between SREBP2 and HINFP and its cofactorsNPAT/TRRAP. Taken together, these new findings identify HINFP as a co-activator in SREBP-mediated transactivation of PCSK9 gene expression. ©The Authors Journal compilation © 2012 Biochemical Society. Source


Li H.,Palo Alto Health Care System | Liu J.,Palo Alto Health Care System
Journal of Biological Chemistry | Year: 2010

hnRNP K, a member of the family of heterogeneous ribonucleoproteins, is known to exert various functional roles in the nucleus, cytoplasm, and mitochondria to affect different cellular processes including chromatin remodeling, transcription, splicing, and translation. Here we report, for the first time, that hnRNPK is specifically involved in human LDL receptor (LDLR) gene transcription in HepG2 cells. We show that depletion of hnRNPK by siRNA transfection reduces the expression of LDLR mRNA and protein by more than 50% as measured by quantitative real-time PCR and Western blot analysis. Importantly, we show that the decay rate of LDLR mRNA is not affected by hnRNP K siRNA transfection, whereas the LDLR promoter activity is significantly decreased. Furthermore, overexpression of hnRNP K increased the LDLR promoter activity by the luciferase reporter assay. By utilizing a series of mutational and deletional constructs of LDLR promoter luciferase reporters, we mapped the K-responsive element to the repeat 3 (R3) sequence of the LDLR promoter. Electrophoretic mobility shift assays show that the K protein binds to a single-stranded DNA probe containing the CT-rich element of R3, which is in contrast to the requirement of double-stranded DNA for Sp1 to bind to R3. Finally, chromatin immunoprecipitation assays reveal a direct interaction of hnRNP K with the LDLR promoter in intact HepG2 cells. These new findings provide strong evidence demonstrating that hnRNP K is an important transactivator for human LDLR gene transcription. This work sheds new light on our current understanding of how LDLR gene expression is controlled at the transcriptional level. Source


Dong B.,Palo Alto Health Care System | Wu M.,Palo Alto Health Care System | Li H.,Palo Alto Health Care System | Kraemer F.B.,Palo Alto Health Care System | And 4 more authors.
Journal of Lipid Research | Year: 2010

We investigated the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the resistance of dyslipidemic hamsters to statin-induced LDL-cholesterol (LDL-C) reduction and the molecular mechanism by which statins modulated PCSK9 gene expression in vivo. We utilized the fructose diet-induced dyslipidemic hamsters as an in vivo model and rosuvastatin to examine its effects on liver PCSK9 and LDL receptor (LDLR) expression and serum lipid levels. We showed that rosuvastatin induced PCSK9 mRNA to a greater extent than LDLR mRNA in the hamster liver. The net result was that hepatic LDLR protein level was reduced. This correlated closely with an increase in serum LDL-C with statin treatment. More importantly, we demonstrated that in addition to an increase in sterol response element binding protein 2 (SREBP2) expression, rosuvastatin treatment increased the liver expression of hepatocyte nuclear factor 1 α (HNF1α), the newly identified key transactivator for PCSK9 gene expression. Our study suggests that the inducing effect of rosuvastatin on HNF1α is likely a underlying mechanism accounting for the higher induction of PCSK9 than LDLR because of the utilization of two transactivators (HNF1α and SREBP2) in PCSK9 transcription versus one (SREBP2) in LDLR transcription. Thus, the net balance is in favor of PCSK9-induced degradation of LDLR in the hamster liver, abrogating the effect of rosuvastatin on LDL-C lowering. Source

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