tbuckley/cabot-search huggingface dataset:
Abstract 2758: Cancer risk in relatives of nasopharyngeal carcinoma - A register-based cohort study in Sweden
Authors: Zhiwei Liu, Fang Fang, Ellen T. Chang, Weimin Ye
Journal: Cancer Research (2015)

Abstract Background: Little is known about the cancer susceptibility among relatives of patients with nasopharyngeal carcinoma (NPC) in non-endemic areas. We conducted a register-based cohort study to assess the relative risks (RRs) of cancer in families (including both first- and second-degree relatives) of NPC patients, compared with other individuals of the general population in Sweden, a low-incidence area for NPC. Method: The present study included 11,602,616 individuals that were identified from the Swedish Censuses in 1960, 1970, 1980, and 1990, and were born in Sweden (defined as “general population”). Cross-linking this population to the Swedish Cancer Register and the Swedish Multi-Generation Register, we identified 9,157 relatives (3,645 first-degree and 5,512 second-degree) of 1,211 NPC probands that were diagnosed between 1958 and 2009 and were the first NPC cases in their families. The occurrence of incident cancers in these relatives and other individuals of the general population during 1961-2009 was ascertained through the Swedish Cancer Register. RRs of cancer in the relatives of NPC probands, compared with other individuals from the general population were calculated from Poisson regression models. Results: The RR of all cancers combined among the first- or second-degree relatives of NPC probands was 1.03 (95% confidence interval [CI] = 0.95 to 1.11, P = 0.50), compared with other individuals of the general population. First-degree relatives of NPC probands had higher risks of NPC (N = 2, RR = 4.29, 95% CI = 1.07 to 17.17), and cancers of the larynx (N = 5, RR = 2.53, 95% CI = 1.05 to 6.09), prostate (N = 76, RR = 1.35, 95% CI = 1.07 to 1.68), and thyroid (N = 10, RR = 2.44, 95% CI = 1.31 to 4.53). In addition, a higher risk of cancer of the salivary glands was observed among the first-degree relatives of NPC probands with undifferentiated carcinoma (N = 2, RR = 6.64, 95% CI = 1.66 to 26.57). In contrast, a decreased risk of colorectal cancer incidence among relatives of NPC probands has been observed (N = 43, RR = 0.71, 95% CI = 0.53 to 0.96). Conclusion: The increased risk of NPC and some other cancers among the first-degree relatives of NPC patients may potentially be explained by shared genetic and environmental risk factors, the latter including Epstein-Barr virus infection and tobacco smoking. However, interpretation of these findings should be cautious given the small number of cancer cases observed among the relatives of NPC patients. Citation Format: Zhiwei Liu, Fang Fang, Ellen T. Chang, Weimin Ye. Cancer risk in relatives of nasopharyngeal carcinoma - A register-based cohort study in Sweden. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2758. doi:10.1158/1538-7445.AM2015-2758
577. Empower Multiplex CRISPR-Mediated Gene Manipulation with Self-Cleaving Ribozymes and tRNA
Authors: Li Xu, Mona El Refaey, Lixia Zhao, Jing Xu, Yandi Gao, Renzhi Han
Journal: Molecular Therapy (2016)

Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) has been recently introduced as an efficient tool to edit the genome. Moreover, it can be targeted to specific gene loci by using single guide RNA (sgRNAs) for genetic manipulation and potential therapy. However, its targeting capability is often restricted by (gRNA) and generation of large deletions in genome by CRISPR requires expression of two distinct guide RNAs simultaneously. Here we report an innovative modification to increase the CRISPR/cas9 editing efficiency in the form of Ribozyme-flanked guide RNA/CRISPR system, which expresses two gRNA in equal molar amount. Our results show that this approach can be used to generate large DNA deletion with transfection of only one plasmid in human and mouse cells. Furthermore, we also used this system to target multiple transcriptional activators to a single promoter and the results showed that RNA level of targeting gene was statistically significantly up-regulated via Ribozyme gRNA/hCas9. Taken together our data, we prove that this strategy can be used in gene editing study broadly to enhance the targeting and the editing efficiency of CRISPR system.
Coronary heart disease (CHD) and stroke risk associated with breast cancer (CA) irradiation (RT) based on patient baseline cardiac risk profile
Authors: R. C. Chen, S. E. Hankinson, J. R. Harris, W. Y. Chen
Journal: Journal of Clinical Oncology (2009)

606 Background: Although population-based studies showed increased fatal and non-fatal CHD risk associated with left-sided breast RT, presumably from “bystander” cardiac dose, how RT interacts with underlying cardiac risk factors to influence these outcomes is unclear. We used data from the Nurses’ Health Study (NHS) to examine the effect of RT on fatal and non-fatal CHD, stratified by baseline CHD risk factors. Methods: 121,700 female registered nurses enrolled in 1976. Ongoing biennial medical information collected includes CHD risk factors, cardiac events, CA diagnosis, treatment, and cause of death. Medical record review confirms CA diagnoses and cardiac events. Numerous publications establishing the causes of CHD and cardiac mortality have resulted. 3863 women have developed stage 0-III breast CA and received RT. Proportional hazards models were used to assess the association between left-sided RT and CHD development, after adjusting for age and CHD risk factors. Results: During 38,538 person-years follow-up after breast CA diagnosis, 126 CHD events developed. In age- adjusted univariate models, left-sided RT (vs. right-sided), diabetes, parental CHD before age 60, and smoking were significantly associated with fatal and non-fatal CHD; aspirin and postmenopausal hormone use were protective. Crude incidence of CHD after left-sided RT was 396 per 100,000 person-years, compared to 259 after right-sided RT. A multivariable model that accounted for the above plus other risk factors (hypertension, hyperlipidemia, physical activity, alcohol use) and stage showed that left-sided RT was independently associated with CHD development (rate ratio, RR 1.5, 95% CI 1.1–2.2). Stratified analyses by the presence of hypertension, hyperlipidemia, and smoking showed similar RR from left-sided RT in all subgroups. In contrast, left-sided RT did not affect risk of stroke in multivariable analysis (RR 0.7, 95% CI 0.4–1.2). Conclusions: Left-sided RT is an independent CHD risk factor, and indicates a similar RR to patients in all subgroups of baseline CHD risk, though absolute risk increase was larger in women who had additional risk factors. Breast CA survivors after left-sided RT may need long-term cardiac follow-up and management. No significant financial relationships to disclose.
Total Therapy 3 Successor (TT3-S) Protocol (2006-66)–Confirming Results Reported for Initial TT3 (TT3-I) Protocol (2003-33) for Newly Diagnosed Multiple Myeloma (MM).
Authors: Bijay Nair, Yazan Alsayed, Sarah Waheed, Elias Anaissie, Frits van Rhee, Jackie Szymonifka, Antje Hoering, John Crowley, Bart Barlogie
Journal: Blood (2009)
Abstract 355: A monoclonal antibody against laminin alpha 4 inhibits both MCAM and integrin-a6b1 binding, blocks tumor cell adhesion in vitro and slows melanoma tumor growth in vivo
Authors: Stephen J. Tam, Lauri E. Li, Carlos Lorenzana, Yue Liu, Ken Flanagan, Philip J. Dolan, Lana Alexander, Josh Salmans, Robin M. Barbour, Jeffrey N. Higaki, Tarlochan Nijjar, Wagner Zago, Ted A. Yednock, Gene Kinney
Journal: Cancer Research (2015)

Abstract Laminin is an extracellular matrix molecule that is secreted as a trimeric protein composed of an α, β and γ chain. There are five distinct laminin α chains that impart distinct binding and signaling activities for cell adhesion, migration, and differentiation in a tissue-specific fashion. Laminin a4 (LAMA4) is expressed by vascular endothelial cells throughout the body, but is also overexpressed by cells within tumors of different origin compared to healthy human tissue. LAMA4 serves as a ligand for the cell adhesion receptors MCAM and a6b1 integrin, as well as for cell surface heparin sulfate proteoglycans. In order to probe how the MCAM/Laminin interaction contributes to tumor growth, we screened for LAMA4-specific monoclonal antibodies that block MCAM binding. We identified several such antibodies, and found that a subset also inhibits LAMA4 binding to a6b1 integrin, indicating that MCAM and a6b1 integrin recognize a similar region of LAMA4. Examining cells from multiple types of tumors, we found that these antibodies were potent inhibitors of tumor cell adhesion to LAMA4 in vitro. Finally, with in vivo administration, we demonstrated dose-dependent inhibition of human melanoma tumor growth in a mouse xenograft model, accompanied by morphologic changes in LAMA4 tumor distribution. These findings suggest that the MCAM/a6b1 integrin binding activity of LAMA4 contributes to both tumor adhesion and growth and that LAMA4 may provide a therapeutic drug target for several different oncology indications. Citation Format: Stephen J. Tam, Lauri E. Li, Carlos Lorenzana, Yue Liu, Ken Flanagan, Philip J. Dolan, Lana Alexander, Josh Salmans, Robin M. Barbour, Jeffrey N. Higaki, Tarlochan Nijjar, Wagner Zago, Ted A. Yednock, Gene Kinney. A monoclonal antibody against laminin alpha 4 inhibits both MCAM and integrin-a6b1 binding, blocks tumor cell adhesion in vitro and slows melanoma tumor growth in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 355. doi:10.1158/1538-7445.AM2015-355
Adult Utilization of Psychiatric Drugs and Differences by Sex, Age, and Race
Authors: Thomas J. Moore, Donald R. Mattison
Journal: JAMA Internal Medicine (2016)

Among adults reporting taking psychiatric drugs, more than 8 of 10 reported long-term use.Prescribing information for the leading antidepressants includes limited information about appropriate duration of treatment.However, benzodiazepines have warnings about drug dependence, tolerance, withdrawal, and rebound symptoms. 4In a previous study, 5 we found most patients were long-term users of the hypnotic zopidem tartrate despite recommendations for short-term use, and many were combining it with other central nervous system depressants despite warnings.Safe use of psychiatric drugs could be improved by increasing emphasis on prescribing these agents at the lowest effective dose and systematically reassessing the need for continued use.
Salvage Therapy with Intravenous Liposomal Adryamicin (A), Bortezomib (B), Cyclophosphamide (C), and Dexamethasone (D) (ABCD) in Previously Treated Myeloma Patients
Authors: Francesco Di Raimondo, Alessandra Romano, Ausilia Gorgone, Annalisa Chiarenza, Maide Cavalli, Salvatore Berretta, Paolo Fiumara, Giovanna Motta, Giuseppe A. Palumbo
Journal: Blood (2008)
Effect of metabolic syndrome and its components on survival in patients with early-stage non-small cell lung cancer.
Authors: Y. Yang, P. Mauldin, M. Ebeling, T. Hulsey, E. R. Camp, B. Liu, M. B. Thomas, C. Reed, N. F. Esnaola
Journal: Journal of Clinical Oncology (2011)

e17510 Background: Epidemiologic studies suggest that MetS increases the risk of lung cancer, yet its effect on cancer mortality remains controversial. We analyzed the effect of MetS/its various components on cancer mortality in large, national cohort of patients with early stage NSCLC, controlling for patient/tumor characteristics and treatment. Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 11,190 patients aged 66 and older with stage I-II NSCLC diagnosed between 1999-2004. Patient/tumor characteristics were obtained from the SEER dataset; data on MetS/its components and cancer treatment was ascertained from Medicare claims. Relationships between the various patient/tumor characteristics and survival were analyzed using chi square tests and logistic regression. Survival in patients with/without MetS/its components was compared using multivariate Cox models. Results: A significant proportion of patients had MetS (19.0%), diabetes (26.6%), hypertension (74.0%) and dyslipidemia (55.7%). Patients with MetS were more likely to be younger, non-white, less educated, and have greater comorbidity (all P<0.001). There was no association between tumor stage, histology, or grade and metabolic syndrome. MetS had no apparent effect on survival. When the effect of its individual components was analyzed, however, diabetes and hypertension were found to be independently associated with worse outcomes (adjusted hazard ratios [aHR] 1.18 [95% confidence internal {CI} 1.11-1.25] and 1.15 [95% CI 1.09-1.22], respectively) after adjusting for other patient/tumor/treatment factors. In contrast, dyslipidemia was associated with significantly improved survival on both univariate (5-year survival: 41% v 29%, P<0.001) and multivariate analyses (aHR 0.82 [95% CI 0.78-0.86]). Conclusions: Diabetes and hypertension have independent adverse effects on survival in patients with early stage NSCLC, whereas dyslipidemia appears to have a protective effect. Trials are needed to determine if use of metformin (in diabetic patients) and/or statins in the adjuvant setting improves long term outcomes in this patient population.
543. Efficient Neuronal But Limited Glia Transduction by AAVshH10 in Dorsal Root Ganglion and Spinal Cord of Adult Rats
Authors: Quinn H. Hogan, Gregory Fischer, Dean Caron, Hongwei Yu
Journal: Molecular Therapy (2015)

Recombinant adeno-associated viral (AAV)-mediated therapeutic gene transfer is an effective and safe tool for the treatment of chronic pain. Activated glial cells play important roles in pain pathophysiology and are promising targets for the therapeutic intervention. However, the natural tropism of AAV vectors leads to gene transfer predominantly to neurons while glial cells are refractory to AAV transduction in both the central and peripheral nervous system (CNS and PNS). AAVshH10 is a recently engineered novel AAV6-like variant that demonstrates efficient and selective Muller glia transduction in the retina. The present study was designed to evaluate whether in vivo glia transduction in the dorsal root ganglion (DRG) and the spinal cord (SC) could be enhanced using AAVshH10. Titer-matched AAVshH10 and original AAV6, both encoding the enhanced green fluorescent protein (EGFP) reporter driven by the ubiquitous cell-potent CMV promoter, were injected into DRGs and spinal cords (SCs) of adult rats. Neurotropism of gene transfer by AAVshH10 in comparison to AAV6 was determined by immunohistochemistry. Results showed that injection of AAVshH10 into DRGs and SCs resulted in a similar profile to its parent AAV6, both showing efficient transduction of all sub-populations of sensory neurons in DRGs or the neurons in SCs, without significant transduction of glial cell populations in both sites. Together, this study demonstrates an efficient neuronal but limited glia transduction of AAVshH10, which can be used as a viable alternative to AAV6 for efficient neuronal transduction in DRGs and SCs.
Phase I-II Trial of Adoptive Immunotherapy with Haploidentical KIR Ligand-Mismatched Natural Killer Cells in High Risk Acute Myeloblastic Leukemia Patients.
Authors: Antonio Curti, Loredana Ruggeri, Alessandra D’Addio, Elena Urbani, Andrea Bontadini, Fiorenza Fruet, Valeria Giudice, Elisa Dan, Maria Rosa Motta, Simona Rizzi, Stefania Paolini, Gabriele Gugliotta, Roberto Conte, Giovanni Martinelli, Andrea Velardi, Michele Baccarani, Roberto M. Lemoli
Journal: Blood (2007)
Maximun Standard Uptake Value At the Biopsy Site During 18f-Fluorodeoxyglucose Positron Emission Tomography Does Not Predict the Proliferation Potential of Tumor Cells in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type
Authors: Yoshimi Yamamoto, Naoto Tomita, Seiji Sakata, Kengo Takeuchi, Ukihide Tateishi, Reina Watanabe, Rika Sakai, Yoshiaki Ishigatsubo
Journal: Blood (2011)
Mobile Intramural Gastroesophageal Junction Mass
Authors: Jacob Kanter, Farah Khan, Ankit Bharat
Journal: JAMA Surgery (2016)

A healthy 43-year-old woman presented with weight loss, heartburn, and progressively worsening dysphagia to solid food. Intriguingly, the heartburn was most severe while she was sitting up but lying supine relieved the symptoms. What is your diagnosis?
Main Plenary Sessions
Journal: British Journal of Dermatology (2016)

Medication adherence is a major barrier to optimizing the effectiveness of available therapies; however, few high-quality studies have examined adherence to systemic therapies used for psoriasis. We assessed whether patients with psoriasis can be categorized into groups with similar medication beliefs,and examined the relationship between belief group member-ship with adherence to systemic therapy and psychological distress. Cross-sectional data from 565 patients with moderate-to-severe psoriasis using a systemic therapy for ≤ 2 years were collected from 35 dermatology clinics across England:685% prescribed a biologic and 315% prescribed a conventional systemic therapy. A questionnaire assessed patients’medication beliefs (Beliefs about Medicines Questionnaire),psychological distress (Hospital Anxiety and Depression Scale)and medication adherence [Medication Adherence Report Scale(MARS)], with a score ≤ 38 on the MARS indicating non adherence. The optimal number of medication belief groups was identiﬁed using latent proﬁle analysis (LPA). In total, 215%were classiﬁed as non adherent to systemic therapy, with a higher proportion of patients using a conventional systemic classiﬁed as non adherent (313%) compared with those usinga biologic (168%). The LPA model-ﬁt statistics supported athree-group model; each group reported strong and positivebeliefs in the necessity of their systemic therapy and perceivedtreatment controllability, but differed in their level of concernabout systemic therapies and medicines in general; group 1(220%) reported the strongest concerns, followed by group 2(640%), with group 3 (140%) reporting the weakest con-cerns. The proportion of patients classiﬁed as nonadherent sig-niﬁcantly differed by belief group (v2= 94, P = 001), with non adherence highest in group 1 (287%), followed by group 2 (213%) and lowest in group 3 (104%). There were significant differences in level of anxiety (H = 771, P = 002) and depression (H = 191, P < 001) between the three belief groups, with group 1 reporting the highest level of anxiety[median 75, interquartile range (IQR) 325–110] and depression (median 600, IQR 200–975), compared with group 2 (median 600, IQR 325–900, and median 400,IQR 100–700, respectively) and group 3 (median 600, IQR200–900, and median 300, IQR 100–700, respectively).Signiﬁcant proportions of patients with psoriasis using sys-temic therapies reported nonadherence. Patients can be catego-rized into groups with similar medication beliefs. Patients with conﬂicting medication beliefs, holding strong beliefs in medication necessity and strong medication concerns, reported higher non adherence and higher levels of psychological dis-tress. Assessing medication beliefs may help identify those most likely to experience self-management difﬁculties and have poorer medication outcomes.
Abstract POSTER-THER-1427: Epidermal growth factor receptor mediated alterations in DNA methylation associated with the development of platinum resistance in ovarian cancer cells
Authors: Sabrina L. Samudio-Ruiz, Michaela L. Granados, Laurie G. Hudson
Journal: Clinical Cancer Research (2015)

Abstract Acquisition of platinum resistance following first line platinum-taxane therapy occurs in a large portion of ovarian cancer patients and continues to be a major challenge in clinical effectiveness. To date, there are limited interventions available to prevent or reverse platinum resistance; however, there has been some advances in the use of demethylating agents in the resensitization of patients to platinum based therapy. This highlights epigenetic alterations, in particular DNA methylation, as critical contributors to the acquisition of drug resistance in ovarian cancer. The Epidermal Growth Factor Receptor (EGFR) has also been linked to chemoresistance and is known to be activated by cisplatin treatment. We previously published that activation of the EGFR can increase DNA methyltransferase (DMNT) activity and, over extended activation, can significantly increase global DNA methylation in ovarian cancer cells. We hypothesized that cisplatin induced activation of the EGFR could mediate changes in DNA methylation associated with the development of platinum resistance. To investigate this, we used an in vitro model of platinum resistance and evaluated EGFR signaling and DNMT activity after acute cisplatin and in platinum resistant cells. We found that cisplatin treatment activates the EGFR and downstream signaling pathways JAK and AKT. Cisplatin also increased DNMT activity and this increase was dependent on EGFR activation. Over repeated sequential treatments of cisplatin, we successfully developed platinum resistant cells that possessed significant increases in DNMT activity and had moderate, but significant, increases in global DNA methylation. Preliminary data using the EGFR inhibitor Erlotinib during the development of platinum resistant cells suggest that the EGFR plays an integral role in the acquisition of platinum resistance. This work implicates EGFR driven alterations to DNMT activity and DNA methylation as a novel mechanism for development of platinum resistance. Further studies are currently being done to evaluate potential alterations in activation of downstream signaling pathways, levels of DNA methyltransferases and other changes in expression associated with platinum resistance. Citation Format: Sabrina L. Samudio-Ruiz, Michaela L. Granados, Laurie G. Hudson. Epidermal growth factor receptor mediated alterations in DNA methylation associated with the development of platinum resistance in ovarian cancer cells [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1427.