tbuckley/cabot-search huggingface dataset:
Abstract 497: Engagement of activatory Fc γ receptors by immunoregulatory receptor-targeting antibodies mediates antitumor activity.
Authors: Yannick Bulliard, Rose Jolicoeur, Maurice Windman, Sarah Rue, Deborah Knee, Nick Wilson, Glenn Dranoff, Jennifer Brogdon
Journal: Cancer Research (2013)

Abstract Inhibitory FcγRIIB receptors are required for the therapeutic effects of agonistic antibodies targeting several tumor necrosis factor receptor (TNFR) superfamily members, including CD40, DR5, and Fas. However, it remains unclear how general this requirement is and whether activating FcγRs may be required for antibodies targeting other immunoregulatory receptors. Here we have explored the involvement of FcγRs for the antitumor effects of antibodies targeted to costimulatory TNFRs expressed on T cells. Surprisingly, FcγRIIB was completely dispensable for antibody-mediated anti-tumor effects. In contrast, activating FcγRs were required for maximal in vivo activity. A similar dependence on activating FcγRs was observed for antibodies targeted to the T cell surface antigen CTLA-4. Important changes in the tumor microenvironment and draining lymph nodes correlated with the in vivo efficacy of these antibodies. Our findings uncover a previously unknown requirement for activating FcγRs in the anti-tumor effects of immunomodulatory antibodies and raise important questions about the role of receptor signaling for therapeutic activity. A greater understanding of this activatory FcγR-based mechanism may improve the design and activity of immune-modulatory antibodies in clinical development, and those already approved for the clinic. Citation Format: Yannick Bulliard, Rose Jolicoeur, Maurice Windman, Sarah Rue, Deborah Knee, Nick Wilson, Glenn Dranoff, Jennifer Brogdon. Engagement of activatory Fc γ receptors by immunoregulatory receptor-targeting antibodies mediates antitumor activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 497. doi:10.1158/1538-7445.AM2013-497
Abstract 1536: UVB-irradiation regulates VLA-4-mediated melanoma cell adhesion to endothelial VCAM-1 under flow conditions
Authors: Wei Liu, Lei Wang, Venktesh S. Shirure, Monica M. Burdick, Shiyong Wu
Journal: Cancer Research (2011)

Abstract The major aspect contributing to the mortality of melanoma is its ability to spread, or metastasize. Ultraviolet B light (UVB) is considered an indirect cause of melanoma formation. However, little is known about the potential effects of UVB to melanoma metastasis. Integrins, a large family of cell adhesion molecules expressed on the melanoma cell surface, are important for cell signaling, growth, and migration during metastasis. Most critically, tumor cell tissue invasion is dependent on the initial interaction of tumor cells with vascular endothelium at the target organ, and there is increasing evidence for a prominent role of melanoma very late antigen-4 integrin (VLA-4, α4β1 integrin) binding to its endothelial ligand vascular cell adhesion molecule-1 (VCAM-1) in this process. This research focuses on the quantitative modulation of VLA-4 integrin expression and function on melanoma cells after UVB irradiation. The present data show that at 3, 12, and 18 hours post-UVB irradiation, VLA-4 expression was unchanged relative to untreated cells, but adhesion to VCAM-1 decreased significantly. Immunofluorescence studies implied that the spatial organization of α4 integrin on the melanoma cell surface contributed to the changes in avidity for VCAM-1 upon UVB irradiation. Further analysis suggested that the surface level of α4 integrin was maintained by Akt activity after UVB irradiation. The level of cell surface α4 integrin was significantly increased after UVB-irradiation when Akt was inhibited. Inhibition of Akt also reversed the reduction of avidity of cells after the irradiation. Our data also show that UVB reduces the level of Akt. The inhibition of Akt activity correlated with a reduced amount of coupled cNOS and reduced amount of iNOS after UVB-irradiation. However the effect of NOSs on melanoma cell adhesion appears due to their roles in regulation of apoptosis after UVB-irradiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1536. doi:10.1158/1538-7445.AM2011-1536
The Good Merger
Authors: Leemore S. Dafny, Thomas H. Lee
Journal: New England Journal of Medicine (2015)

Interview with Prof. Leemore Dafny on ways of producing health care mergers that are good for both patients and providers. (07:24)Download A good health care merger increases the value of care by reducing costs, improving outcomes, or both, enabling providers to generate and respond to competition. Such mergers generate "cognizable efficiencies" offsetting the potential harm of increased prices.
Pioglitazone ameliorates the phenotype of a novel Parkinson’s disease mouse model by reducing neuroinflammation
Authors: Milena Pinto, Nadee Nissanka, Susana Peralta, Roberta Brambilla, Francisca Diaz, Carlos T. Moraes
Journal: Molecular Neurodegeneration (2016)

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The cause of the motor symptoms is the loss of dopaminergic neurons in the substantia nigra with consequent depletion of dopamine in the striatum. Although the etiology of PD is unknown, mitochondrial dysfunctions, including cytochrome c oxidase (Complex IV) impairment in dopaminergic neurons, have been associated with the disease's pathophysiology. In order to analyze the role of Complex IV in PD, we knocked out Cox10 (essential for the maturation of COXI, a catalytic subunit of Complex IV) in dopaminergic neurons. We also tested whether the resulting phenotype was improved by stimulating the PPAR-γ pathway.Cox10/DAT-cre mice showed decreased numbers of TH+ and DAT+ cells in the substantia nigra, early striatal dopamine depletion, motor defects reversible with L-DOPA treatment and hypersensitivity to L-DOPA with hyperkinetic behavior. We found that chronic pioglitazone (PPAR-γ agonist) treatment ameliorated the motor phenotype in Cox10/DAT-cre mice. Although neither mitochondrial function nor the number of dopaminergic neurons was improved, neuroinflammation in the midbrain and the striatum was decreased.By triggering a mitochondrial Complex IV defect in dopaminergic neurons, we created a new mouse model resembling the late stages of PD with massive degeneration of dopaminergic neurons and striatal dopamine depletion. The motor phenotypes were improved by Pioglitazone treatment, suggesting that targetable secondary pathways can influence the development of certain forms of PD.
Development and evaluation of a cancer risk educational tool (CREdIT) for women with a family history of breast and ovarian cancer.
Authors: C Wilcox, R Lee, M Beattie, J Luce, G Joseph, K Lamvik, B Crawford, J Ziegler, D Braithwaite
Journal: Cancer Research (2009)

Abstract Abstract #2101 Introduction: In underserved, lower literacy and multiethnic women at risk of Hereditary Breast and Ovarian Cancer (HBOC), there is a need for culturally appropriate educational tools. The purpose of this Phase I study is to evaluate the use of a Cancer Risk Educational Intervention Tool (CREdIT) as an adjunct to genetic counseling for HBOC for underserved women at San Francisco General Hospital (SFGH).&amp;#x2028; Methods: CREdIT is a 15 minute audio-visual powerpoint story presentation (available in English and Spanish) which employs non-scientific images and language specifically designed for use by our target population. Participant questionnaires, administered before and after the intervention, evaluate patient satisfaction, risk perception, knowledge of cancer genetics, and anxiety. Genetic counselor questionnaires address counselor satisfaction and time-flow.&amp;#x2028; Results: To date, we have recruited 23 women of diverse backgrounds (mean age of 46, range: 26 to 63). Of these, seven (30%) are first-generation immigrants and four (17%) have less than a high school diploma. Eight (35%) have had cancer, and eighteen (78%) reported that cancer runs in their families. We have found an increase in knowledge following the CREdIT presentation, specifically vis-à-vis BRCA inheritance, BRCA-associated cancer risk, and risk-reducing options (all p &amp;lt; 0.05). These improvements occur without an increase in patient anxiety (p &amp;gt; 0.05). All participants believed that the presentation helped them learn more about cancer risk, and genetic counselors reported increased patient preparedness and counselor satisfaction as a result of CREdIT use (p &amp;lt; 0.05). Mean genetic counselor consultation time decreased by 5.5 minutes after CREdIT use.&amp;#x2028; Conclusions: CREdIT appears to increase knowledge and improve understanding of BRCA-associated risks without raising anxiety in underserved women at risk of HBOC. Genetic counselors report increased satisfaction and patient preparedness, and decreased counseling time with CREdIT. Future work will involve examining long-term outcomes of CREdIT use; subgroup analyses to identify patient populations most likely to benefit from CREdIT; further evaluation using clinical trial methodology; and strategies for its dissemination to other settings working with underserved, multiethnic populations. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2101.
Breast Augmentation: A Risk Factor for Breast Cancer?
Authors: Hans Berkel, Dale C. Birdsell, Heather Jenkins
Journal: New England Journal of Medicine (1992)

A relation between breast augmentation and the subsequent risk of breast cancer has been postulated. Since an estimated 2 million women in the United States alone have received breast implants, even a small increase in the risk of breast cancer could have considerable public health consequences.We performed a population-based nonconcurrent cohort-linkage study. All women in Alberta, Canada, who underwent cosmetic breast augmentation from 1973 through 1986 were included in the implant cohort (n = 11,676). This cohort was compared with the cohort of all women in Alberta in whom a first primary breast cancer was diagnosed (n = 13,557). The expected number of breast-cancer cases in the implant cohort was estimated by applying age-specific and calendar year--specific incidence rates of breast cancer (obtained from the Alberta Cancer Registry) to the implant cohort. Standardized incidence ratios were calculated by dividing the observed by the expected number of breast-cancer cases in the implant cohort.Forty-one patients with implants were subsequently found to have breast cancer. The expected number was 86.2. The standardized incidence ratio was thus 47.6 percent, significantly lower than expected (P less than 0.01). The average length of follow-up in the implant cohort was 10.2 years, and the average length of time from breast augmentation to the diagnosis of breast cancer was 7.5 years.Women who undergo breast augmentation with silicone implants have a lower risk of breast cancer than the general population. This finding suggests that these women are drawn from a population already at low risk and that the implants do not substantially increase the risk.
Acquired Hemoglobin H Disease
Authors: Robert W. Hamilton, Elias Schwartz, Jean Atwater, Allan J. Erslev
Journal: New England Journal of Medicine (1971)

Although hemoglobin H disease is usually inherited, similar syndromes may be acquired. In a 73-year-old woman of British descent with a myeloproliferative syndrome characterized by striking megakaryocytic hyperplasia and thrombocytosis, we also found hemolytic anemia with hypochromia, microcytosis, marked poikilocytosis and 20 per cent hemoglobin H (beta4). Incubation with brilliant cresyl blue produced inclusions in 60 per cent of the red cells. Hematologic studies before the onset of this illness gave normal results. In vitro studies of globinchain synthesis revealed a marked decrease of alpha-chain production similar to that found in hereditary hemoglobin H disease. The alpha/beta ratio of radioactivities was 0.13, demonstrating a severe imbalance of globin synthesis. Studies of the patient's two children gave normal results. Hematologic and globin synthesis in this acquired disorder is similar to those of its hereditary counterpart.
Comparison of Ventricular Ectopic Activity during 24-Hour Monitoring and Exercise Testing in Patients with Coronary Heart Disease
Authors: Michael Ryan, Bernard Lown, Howard Horn
Journal: New England Journal of Medicine (1975)

The exposure of ventricular ectopic activity (VEA) by maximal exercise testing and 24-hour ambulatory monitoring was compared in 100 unselected patients with coronary heart disease. The arrhythmia was noted with exercise in 56 patients and with monitoring in 88. Repetitive forms such as couplets and ventricular tachycardia were found to be twice as frequent (40 vs. 20) with monitoring than with exercise. Patients with prior myocardial infarction had more frequent ventricular ectopic activity of a more advanced grade with both exercise and monitoring than patients with angina pectoris. Exercise exposed the grades of ectopic activity that recurred during two or more hours of the monitoring session. Of seven patients with ventricular tachycardia on exercise only four exhibited this grade with monitoring. It may be that these two methods divulge different information regarding the electrophysiologic state of the myocardium. (N Engl J Med 292:224–229 1975)
Abstract 549: Interleukin-11 induces survivin expression in brain endothelial cells
Authors: Zhi Liu, Robin Yuan, Don Armstrong, Stan Louie, Axel H. Schönthal, Thomas C. Chen, Florence Hofman
Journal: Cancer Research (2010)

Abstract The tumor vasculature, which provides nutrients and oxygen to cancer cells, is particularly relevant in the highly vascular primary brain tumor, glioblastoma multiforme (glioma). The tumor-associated blood vessels within gliomas have been shown to be abnormal in their structure and function as compared to the normal vasculature. Previous studies from this laboratory have shown that these tumor-associated brain endothelial cells are resistant to chemotherapy; and this resistance is a result, in part, of the overexpression of survivin in these cells. Survivin, a member of the inhibitor of apoptosis gene family, is responsible for drug resistance in cancer cells, yet little is known about its role and regulation in the endothelial cells of the tumor vasculature. The mechanism of this survivin overexpression in the brain vasculature is the focus of this report. Here we present data showing that Interleukin (IL)-11, a cytokine known to stimulate survivin, is produced by human gliomas and is responsible for the increase in survivin in the brain endothelial cells. To demonstrate this, we examined glioma cell lines for IL-11 production. Our studies showed that the glioma cell lines, U87 and U251, secrete high levels of IL-11, as compared to normal cells. Furthermore, when brain endothelial cells are treated with exogenous IL-11, they exhibit increased levels of survivin, similar to the elevated basal level of tumor-associated endothelial cells. These studies suggest that tumor-derived IL-11 may play an important role in the overexpression of survivin in endothelial cells. Since survivin is important in chemoresistance, IL-11 or its receptor may be a relevant target for regulating survivin in the glioma vasculature, and thereby mediating an effective chemosensitizing mechanism and anti-vascular therapy for brain tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 549.
Peter Charles Collinson
Authors: C. Collinson
Journal: BMJ (2012)

Peter Charles Collinson was born in Rotherham and educated at Sheffield University and Saint Bartholomew’s Hospital. After house jobs he joined the Royal Navy and spent the next year embroiled in the battle of the Atlantic serving as ship’s surgeon on HMS Hurricane , escorting convoys to keep the British war effort supplied. His ship rescued more than 1100 mariners and passengers. In September 1940, the evacuee ship City …
P81 Long-term effect of combined anterior and posterior spinal fusion on pulmonary function and quality of life in young people with adolescent idiopathic scoliosis
Authors: DS Urquhart, S Gallela, E Brady, S Blacklock, AT Tsirikos
Journal: Thorax (2013)

<h3>Background</h3> The deleterious effects of progressive adolescent idiopathic scoliosis (AIS) on lung function and quality of life are cause for concern. Although surgical correction of AIS aims to halt progression of restrictive lung disease, evidence from current literature is conflicting with minor improvement, no change, or minor decline in lung function all reported in case series 2–5 years post-operatively. The longer term follow-up of lung function and quality of life of those who underwent surgery for AIS in adolescence are not well documented with only one study extending beyond 2 years. <h3>Aim</h3> To evaluate the long-term change in pulmonary function and quality of life in children with adolescent idiopathic scoliosis (AIS) following anterior and posterior spinal fusion (APSF). <h3>Methods</h3> Subjects who underwent APSF for AIS in the period 2005–2007 at RHSC Edinburgh were prospectively studied during 2011/2012. Data were collected for lung function by forced spirometry (Jaeger Masterscreen), and measurement of quality of life using the SRS-22 questionnaire. Paired t-test was used to compare data pre- and post-APSF. <h3>Results</h3> Paired pre- and post-operative data were available for 12 patients who underwent scoliosis correction at mean 13.8(11.8–15) years. 9/12(75%) were female. Follow-up occurred 5.8(4.1–6.7) years after surgery. Patients’ height increased from mean (sd) 169(9) cm pre-operatively to 175(5)cm at follow-up (p &lt; 0.01). Scoliosis corrected from 100(15) to 29(11) degrees (p &lt; 0.001). FEV<sub>1</sub> was 60(19)%predicted pre-operatively versus 62(19) post-operatively (p = 0.32); FVC was 62(19)%predicted before and 64(13) after surgery (p = 0.67). Overall SRS-22 scores improved from mean (sd) 3.6(0.3) before surgery to 4.6(0.4) at follow-up (p &lt; 0.001). Improvements in individual SRS-22 domains for function [3.9(0.2) vs. 4.9(0.2), p &lt; 0.001], pain [3.5(0.4) vs. 4.5(0.5), p &lt; 0.001], self-image [3.3(0.3) vs. 4.4(0.5), p &lt; 0.001] and mental health [3.7(0.5) vs. 4.4(0.6), p &lt; 0.001] were also noted. High rates of patient satisfaction [4.8(0.3)] were recorded. No correlation was noted between changes in FEV<sub>1</sub> (r = 0.08, p = 0.8) or FVC (r = 0.01, p = 0.97) with change in SRS-22 score. <h3>Conclusion</h3> Long-term follow-up of a single surgeon’s cohort of AIS patients suggests no deficit in pulmonary function, whilst quality of life and patient satisfaction are high 6 years after combined A/PSF.
Abstract 4096: Diffused intrinsic pontine glioma: An analysis of coding and non-coding RNA species
Authors: Annie Sandza, Tobey J. MacDonald, D. Ashley Hill, Javad Nazarian
Journal: Cancer Research (2010)

Abstract Diffused intrinsic pontine glioma (DIPG) is one of the most difficult pediatric cancers to treat. To date, there is only scant information on the molecular characteristics of this tumor because of the paucity of adequate tissue for investigation due to its inoperable location within the brainstem. In an attempt to uncover the pathogenesis of DIPG, we have generated comprehensive molecular profiles of coding and non-coding RNA species obtained from pediatric DIPG autopsy specimens. Coding and non-coding RNA species play an important role in oncogenesis. Micro RNAs (miRNAs or miRs) are the more recent non-coding RNA species that have been shown to play an essential role in cancer development and cancer biology. Our aim was to gain insight into the molecular underpinnings of DIPG by generating the complete miRNA and mRNA profiles of the tumor. Three frozen autopsy DIPG specimens were analyzed. Adjacent non-tumor areas were identified by a neuropathologist and used as controls. Total RNA was extracted and coding and non-coding small RNA were profiled using the Affymetrix platform. Human and viral non coding RNAs (n=13) were shown to be differentially expressed in DIPG tumors compared to the adjacent normal tissues. RNA species that showed to be dysregulated were further validated by RT-PCR (ABI platform). Furthermore, correlation analyses were done to assess expression levels of mRNAs and their corresponding miRs. Our preliminary data indicates specific dysregulation of micro RNA and RNA species that control cellular proliferation and tumorigenesis. Although preliminary, this is to our best knowledge, the first report of comprehensive RNA profiling of DIPG. Correlation of coding and non-coding RNA species observed here will require further validation. Understanding the molecular makeup of DIPG will provide insight into its pathogenesis and perhaps lead to the development of targeted therapeutics for this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4096.
Case 9-2011
Authors: Mandakolathur R. Murali, Mariana C. Castells, James Y. Song, David M. Dudzinski, Robert P. Hasserjian
Journal: New England Journal of Medicine (2011)

A 37-year-old man was admitted to the hospital because of flushing and hypotension with near-syncope. Similar episodes had occurred with increasing frequency during the past 12 years. A test result was received.
Abstract 4992: A Sox2-EGFR positive feedback loop contributes to oncogenesis of lung cancer
Authors: Yu-Ting Chou, Chih-Chan Lee, Sheng-Chieh Lin, Cheng-Wen Wu
Journal: Cancer Research (2011)

Abstract Sox2, a core transcription factor regulating self-renewal of stem cells, is highly expressed in a subset of lung cancer. Nonetheless, how Sox2 contributes to lung tumorigenesis is still elusive. In this study, we report the discovery and mechanistic characterization of the Sox2 as an oncogene in lung cancer cells and its role as a key mediator of EGFR expression. Ectopic expression of Sox2 promoted cell proliferation and anchorage-independent cell growth. Knockdown of Sox2 induced autophagic death and attenuated oncogenic properties of lung cancer. A cDNA microarray analysis and immunoblotting revealed that Sox2 induced expression of EGFR, which contributed to tumorigenesis of lung cancer. In support of this notion, Sox2 bound to the EGFR promoter and enhanced its activity. In addition, EGFR activation or ectopic expression of c-Myc induced Sox2 expression in lung cancer, suggesting that Sox2-EGFR positive feedback loop promotes oncogenesis of lung cancer via a c-Myc dependent pathway. Indeed, c-Myc bond to Sox2 promoter and enhanced its expression under EGFR stimulation. Overexpression of Sox2 promoted tumor growth with increased EGFR expression in xenograft mouse model, and knockdown of Sox2 inhibited tumor growth with attenuated EGFR expression. Our findings suggest that Sox2 could induce EGFR mediated oncogene addiction in lung cancer, with potential applications as a novel therapeutic target for lung cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4992. doi:10.1158/1538-7445.AM2011-4992