tbuckley/cabot-search huggingface dataset:
Progression of Aortic Dilatation and the Benefit of Long-Term β-Adrenergic Blockade in Marfan's Syndrome
Authors: Jennifer Shores, Kenneth R. Berger, Edmond A. Murphy, Reed E. Pyeritz
Journal: New England Journal of Medicine (1994)

The aortic root enlarges progressively in Marfan's syndrome, and this enlargement is associated with aortic regurgitation and dissection. Long-term treatment with beta-adrenergic blockade, by reducing the impulse (i.e., the rate of pressure change in the aortic root) of left ventricular ejection and the heart rate, may protect the aortic root.We conducted an open-label, randomized trial of propranolol in adolescent and adult patients with classic Marfan's syndrome (32 treated and 38 untreated [control] patients). Aortic-root dimensions and clinical end points (aortic regurgitation, aortic dissection, cardiovascular surgery, congestive heart failure, and death) were monitored for an average of 9.3 years in the control group and 10.7 years in the treatment group. All 70 patients were included in the analysis according to the intention-to-treat principle.The dose of propranolol was individualized; the mean (+/- SE) dose was 212 +/- 68 mg per day. The mean slope of the regression line for the aortic-root dimensions, which reflect the rate of dilatation, was significantly lower in the treatment group than in the control group (0.023 vs. 0.084 per year, P < 0.001). Clinical end points were reached in five patients in the treatment group and nine in the control group. The Kaplan-Meier survival curve for the treatment group differed significantly from that for the control group during the middle years of the trial and remained better for the treatment group throughout the study.Prophylactic beta-adrenergic blockade is effective in slowing the rate of aortic dilatation and reducing the development of aortic complications in some patients with Marfan's syndrome.
Abstract 585: PTEN is a critical determinant in sensitizing cells to γ-secretase inhibitors
Authors: Jayasree S. Nair, Tahir N. Sheikh, Yueming Li, Gary K. Schwartz
Journal: Cancer Research (2011)

Abstract Phase I studies of gamma secretase inhibitors (GSIs) that block Notch signaling have indicated clinical activity, especially in patients with sarcomas and melanoma. None of these patients had activating mutations, yet they showed intrinsic sensitivity to the drug. Therefore, an understanding of the mechanisms for de novo sensitivity and resistance to this class of drugs would be critical for drug development. Towards this end, we treated a panel of human melanoma and sarcoma cells lines with JC-34, a potent inhibitor of gamma secretase. Even though all the cell lines showed inhibition of cleaved Notch 1 and suppression of Hes1 luciferase, only some of the cell lines showed inhibition of growth or induction of apoptosis. The sensitive cell lines also underwent G1 cell cycle arrest. In addition, all the sensitive cell lines were characterized by induction of PTEN and suppression of p-AKT (473) after the administration of JC-34. Melanoma cell lines with wild type PTEN were sensitive (SKMEL 32 and SKMEL 267) while PTEN mutant/ null cells were insensitive (SKMEL 39 and 133). In order to further assess the impact of PTEN status upon drug susceptibility, we compared the impact of JC-34 upon isogenic breast cancer cell lines that differ only in PTEN status. In the breast cancer cell line MDAMB468, proliferation inhibition was approximately 50% in the presence of PTEN expression compared to 10% in MDAB468 cells without PTEN expression. In this system, induction of apoptosis was a significant contributor to inhibition of proliferation. Taken together, these data suggest that the status of PTEN before and/or after drug treatment may play a critical role in determining tumor susceptibility to Notch pathway inhibition. As PTEN is negatively regulated by Notch, modulation of PTEN status by GSIs may provide a rationale means to explain sensitivity of this class of drugs to particular subsets of tumor. This hypothesis will be validated in planned clinical trials with GSIs in patients with these diseases. 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 585. doi:10.1158/1538-7445.AM2011-585
Abstract 5177: SIRT2 deacetylates and activates glucose-6-phosphate dehydrogenase (G6PD) to protect cells against oxidative stress.
Authors: Yiping Wang, Lisha Zhou, Yuzheng Zhao, Shiwen Wang, Yi Yang, Dan Ye, Yue Xiong, Kun-Liang Guan
Journal: Cancer Research (2013)

Abstract Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first committed step in the pentose phosphate pathway (PPP), which converts β-D-glucose-6-phosphate into D-glucono-1,5-lactone-6-phosphate, while concomitantly producing reducing equivalents in the form of NADPH. NADPH is a required cofactor in reductive biosynthesis,and is also required for the generation of reduced glutathione, the major antioxidant responsible for preventing reactive oxygen species (ROS) damage. Lysine acetylation is an evolutionarily conserved post-translational modification in the regulation of a wide range of cellular processes. Several recent acetylome proteomic studies have identified more than 2000 potential acetylation substrates. Among these identified acetylated proteins is G6PD, implicating a novel modulation of G6PD at the post-translational level. However, our knowledge of how acetylation regulates G6PD activity is limited. This study is directed toward to understand the molecular mechanism by which acetylation regulates G6PD function to regulate cellular redox state in response to oxidative stress. Here, we found that G6PD activity is negatively modulated by acetylation, and the major regulated site of acetylation in G6PD was mapped to K403, an evolutionarily conserved lysine residue. Site-specific genetic incorporation of Nε-acetyl-lysine into the position 403 of G6PD revealed that K403 acetylated G6PD is incapable to form active dimers and displays a complete loss in activity. Moreover, we found that the reversible acetylation of K403 is critical to modulate G6PD activity in response to different physiologic conditions, such as high glucose and oxidizing agents. Cytosolic SIRT2 deacetylated G6PD at K403, and greatly restored G6PD activity by inducing the formation of active dimers. Knockdown of endogenous G6PD led to higher cellular susceptibility to oxidant-induced cell death. Re-expression of wild-type G6PD, but not the acetylated mimic G6PDK403Q, could rescue cells from oxidative injury. Together these results uncover a previously unknown mechanism by which SIRT2 deacetylates and activates G6PD and thus protects cells against ROS damage. Citation Format: Yiping Wang, Lisha Zhou, Yuzheng Zhao, Shiwen Wang, Yi Yang, Dan Ye, Yue Xiong, Kun-Liang Guan. SIRT2 deacetylates and activates glucose-6-phosphate dehydrogenase (G6PD) to protect cells against oxidative stress. [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 5177. doi:10.1158/1538-7445.AM2013-5177 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Endpiece: Good advice
Authors: T. Plume
Journal: BMJ (1998)

Dr Harvy (sic) enjoined him two things—to renew his cheerful conversation, and take moderate walks for exercise, assuring him that in his practice of physic since these times, he observed more people died of grief of mind than of any other disease, and that his studious and sedentary life would contract him frequent sickness, unless he used seasonable exercise.
Explaining symptoms after negative tests: towards a rational explanation
Authors: Christopher Burton, Peter Lucassen, Aase Aamland, Tim Olde Hartman
Journal: Journal of the Royal Society of Medicine (2014)

Many patients undergo diagnostic tests which are normal.In this essay, we consider how clinicians can provide acceptable explanations for symptoms which persist after ruling out known physical disease.We begin by examining explanations from the perspectives of patients and clinicians and consider the different ways of explaining symptoms following negative tests.We then propose the characteristics of an ideal, or rational, explanation.This rational explanation is a pragmatic approach which, while imperfect, makes sense to both doctor and patient and promotes appropriate action.
Unprecedented case of duodenal papillary disinsertion after endoscopic papillectomy for a neuroendocrine tumor
Authors: José Ardengh, Michele Lemos de Bonotto, Rodrigo Surjan, Julio Pereira Lima, Marcel Machado
Journal: Endoscopy (2015)

Disinsertion of the ampulla of Vater is a serious but rare event during gastric resection. Injury to this area is possible during any operation on the duodenum, but occurs most frequently in the presence of scarring or inflammation that causes secondary shortening of the duodenal bulb [1] [2] [3] [4]. Endoscopic papillectomy is a "high risk" procedure: the reported complication rate varying from 8 % to 35 %, with acute pancreatitis the most common complication (5 % – 15 %) [5] [6]; however, disinsertion of the ampulla of Vater has not been reported in the literature after endoscopic papillectomy.
Abstract A48: Effect of constitutive IGF2 overexpression on tumorigenicity of human ovarian carcinoma cells
Authors: Jurriaan Brouwer-Visser, Suzan K. Chao, Gloria S. Huang
Journal: Cancer Research (2011)

Abstract Introduction: We previously described the association of high tumoral IGF2 expression with reduced disease-free survival in epithelial ovarian tumors. The purpose of this study was to determine the effect of IGF2 overexpression on the tumorigenicity of human ovarian cancer cells. Methods: Expression constructs containing the full-length coding sequence of IGF2 or no insert (empty vector; EV) were made. HEY cells were stably transfected. Quantitative real-time PCR (of CDNA made from cell and xenograft RNA) and ELISA (of conditioned media) were performed to measure the IGF2 mRNA and protein expression levels, respectively. The relative IGF2 mRNA expression level was calculated by the 2−δδCt method with internal normalization to the cyclophilin B mRNA level. Tumorigenicity was evaluated in athymic nude mice by subcutaneous injection of 1×106 cells, with or without matrigel, followed by serial monitoring of in vivo tumor growth by digital caliper measurements. The two-tailed t-test was used to evaluate the significance of comparisons. Results: The IGF2 mRNA level was 5604 ±617 fold-change higher in HEY-IGF2 cells relative to HEY-EV cells (P&amp;lt;0.05). The IGF2 secreted protein level was 1852 ng/ml per 100,000 HEY-IGF2 cells, and was not detectable in the conditioned media of HEY-EV cells. After 4 weeks, the mean tumor volume of subcutaneous xenografts following cell injection without matrigel was 181 ±53 mm3 versus 52 ±15 mm3 for HEY-IGF2 and HEY-EV, respectively (P&amp;lt;0.05, N=10 per group); and for cells injected with matrigel, the mean tumor volume was 1608 ±330 mm3 versus 705 ±95 mm3 for HEY-IGF2 and HEY-EV xenografts, respectively (P&amp;lt;0.05, N=6 per group). The tumor growth rate differed significantly between the HEY-IGF2 and HEY-EV xenografts (P&amp;lt;0.01). In the HEY-IGF2 xenografts, overexpression of IGF2 relative to HEY-EV xenografts was maintained. Conclusions: Stable overexpression of IGF2 in HEY ovarian cancer cells and xenografts was achieved, and resulted in an increase in IGF2 protein secretion. IGF2 overexpression enhanced in vivo tumorigenicity of HEY ovarian cells, accompanied by an increased xenograft growth rate. Further evaluation is underway to fully characterize the mechanisms by which IGF2 overexpression promotes tumor growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A48.
Phase II Trial of Neoadjuvant Pegylated Liposomal Doxorubicin with Paclitaxel and Trastuzumab in Patients with Operable Her2-Positive Breast Cancer.
Authors: D. Hyams, G. Leichman, P. Klein, P. Rietchsel, E. Levine, V. Gebski, M. Kelley
Journal: Cancer Research (2009)

Abstract Background: Doxorubicin, paclitaxel and trastuzumab are among the most active agents used in the treatment of Her2-positive invasive breast cancer. However, trastuzumab is associated with cardiotoxicity that is significantly amplified in the presence of doxorubicin. Pegylated liposomal doxorubicin (PLD) has been reported to have greatly reduced cardiotoxicity when compared to native doxorubicin. This pilot study was designed to assess safety and efficacy of concurrent PLD, paclitaxel (TAX), and trastuzumab in the preoperative setting.Methods: Eligible patients included women with T1c-T4, N0-1, M0, Her2-positive invasive breast cancer who had received no prior treatment. The treatment regimen consisted of concomitant PLD 24 mg/m2 or 20 mg/m2 (14pts/10pts) q 3 weeks, TAX 80 mg/m2 weekly, and trastuzumab 2mg/m2 weekly after an initial 4 mg/m2 loading dose, for a total of 18 weeks. MUGA scans were obtained at baseline, after 9 weeks, and after 18 weeks prior to surgery. The primary endpoint was pathologic complete response (pCR).Results: Twenty-four patients were entered on study. The median age was 55 (range 30-72). One subject had AJCC Stage I disease, 14 subjects had Stage II disease, 9 subjects had Stage III disease, and the median pre-treatment tumor size was 4.5 cm (1.2 cm-10.0 cm). Twelve subjects required dose reductions of PLD, 9 required dose reduction of TAX, and 5 discontinued therapy early. One subject withdrew during the 1st cycle, and 1 patient died due to an event unrelated to the investigational treatment. Thirteen of the 22 evaluable subjects had pCR (59%), 9 subjects had PR (41%). The principal treatment-related toxicity was Grade II or III skin toxicity in 18 of 24 subjects (75%). No overt cardiotoxicity was noted, with the mean change between pre-treatment and pre-surgical MUGA of -.25% (range -12-7%).Discussion: The combination of PLD, TAX, and trastuzumab given every 3 weeks, appears to be a highly effective regimen, without evidence of increased cardiotoxicity. However skin toxicity is prominent and may be exacerbated by a previously reported effect of TAX on PLD pharmacokinetics. Further investigation of this highly effective regimen should focus on reducing skin toxicity, while maintaining efficacy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1098.
Abstract IA8: Natural killer cells in host defense against cancer
Authors: Lewis L. Lanier
Journal: Cancer Research (2011)

Abstract Natural killer (NK) cells provide host defense against cancer and infections with pathogens. NK cells express a sophisticated repertoire of activating and inhibitory receptors that regulate their ability to discriminate between healthy cells and cells that have become transformed as a consequence of genomic aberration or infected by pathogens. NKG2D is an activating receptor on NK cells and T cells that detects host-encoded cell surface glycoproteins preferentially displayed by “stressed” cells. In humans these include the MICA, MICB, and ULBP molecules that are frequently over-expressed by many types of human cancers. Despite expression of these ligands, tumors nonetheless can continue to grow and evade elimination by the immune system. We will present and discuss new mechanisms by which tumors can evade the NKG2D system of immunosurveillance and allow tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA8.
ANTI-HYPERGLYCEMIC MEDICATION USE AMONG MEDICARE BENEFICIARIES WITH HEART FAILURE, DIABETES, AND CHRONIC KIDNEY DISEASE
Authors: Priyesh Ashok Patel, Li Liang, Prateeti Khazanie, Bradley Hammill, Gregg Fonarow, Paul Heidenreich, Clyde Yancy, Deepak Bhatt, Lesley Curtis, Adrian Hernandez
Journal: Journal of the American College of Cardiology (2015)
Abstract B33: Dissecting the role of Nrf3 (NF-E2-related factor 3) in chemical carcinogenesis using knock-out mice
Authors: Grégory Chevillard, Zaynab Nouhi, Anna Derjuga, Marilene Paquet, Volker Blank
Journal: Cancer Research (2009)

Abstract In this study, we investigated the role of the transcription factor Nrf3 in chemical carcinogenesis induced by benzo[a]pyrene, a common carcinogen found in cigarette smoke, car exhaust and charcoal-grilled meats. Wild type and Nrf3-deficient mice were treated weekly for 4 consecutive weeks with benzo[a]pyrene and then sacrificed 30 weeks after the first administration of carcinogen. Here, we report that mice exposed to benzo[a]pyrene rapidly exhibit labored breathing further accompanied with different signs of morbidity. Kaplan-Meyer survival rate analyses indicate that mice deficient for Nrf3 die earlier that wild type mice following benzo[a]pyrene exposure. Upon necropsy, gross morphology analyses showed the presence of an increased number of lung and thymus lesions in Nrf3-deficient mice compared to wild type mice whereas the number of stomach lesions is identical in both genotypes. Pathology analysis strongly suggests that observed lesions in lung and thymus are from lymphoma origin. Overall, our study reveals that mice deficient for Nrf3 are highly sensitive to chemicalinduced carcinogenesis suggesting a protective role of the transcription factor Nrf3 in this process. This provides new important insights into the molecular mechanisms involved in the development of lymphomas induced by chemical agents. We also propose the Nrf3-deficient mice as a new in vivo model to study tumor formation and response to chemoprotective agents. Citation Information: Cancer Res 2009;69(23 Suppl):B33.
Consortium Cancer Center Formed By Drew, Meharry, Morehouse
Authors: M. Hampton
Journal: JNCI Journal of the National Cancer Institute (1988)

Consortium Cancer Center Formed By Drew, Meharry, Morehouse Get access Maree Hampton Maree Hampton Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 19, 7 December 1988, Pages 1522–1523, https://doi.org/10.1093/jnci/80.19.1522 Published: 07 December 1988
HEALTHCARE RESOURCE UTILIZATION AND IMPACT ON COST WITH USE OF REMOTE MONITORING STRATEGY COMPARED TO CONVENTIONAL FOLLOW-UP FOR IMPLANTABLE CARDIOVERTER DEFIBRILLATORS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Saurabh Aggarwal, Navdeep Gupta, rohit loomba, Anushree Agarwal, Imtiaz Ismail, Nawfal Al-Khafaji, Venkata Alla, Hussam Abuissa, Rohit Arora, Aryan Mooss
Journal: Journal of the American College of Cardiology (2015)
Peripheral Arterial Disease in Sub-Saharan Africa
Authors: Lily E. Johnston, Barclay T. Stewart, Herve Yangni-Angate, Martin Veller, Gilbert R. Upchurch, Adam Gyedu, Adam L. Kushner
Journal: JAMA Surgery (2016)

Peripheral arterial disease (PAD) causes significant morbidity and is an important risk factor for cardiovascular disease-related mortality. However, the burden of PAD in sub-Saharan Africa is poorly understood.To assess epidemiological and clinical reports regarding PAD from sub-Saharan Africa such that the regional epidemiology and management of PAD could be described and recommendations offered.A systematic search in PubMed, Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Google Scholar for reports pertaining to the epidemiology and/or management of PAD in sub-Saharan Africa was performed. Reports that met inclusion criteria were sorted into 3 categories: population epidemiology, clinical epidemiology, and surgical case series. Findings were extracted and described.The search returned 724 records; of these, 16 reports met inclusion criteria. Peripheral arterial disease epidemiology and/or management was reported from 10 of the 48 sub-Saharan African countries. Peripheral arterial disease prevalence ranged from 3.1% to 24% of adults aged 50 years and older and 39% to 52% of individuals with known risk factors (eg, diabetes). Medical management was only described by 2 reports; both documented significant undertreatment of PAD as a cardiovascular disease risk factor. Five surgical case series reported that trauma and diabetes-related complications were the most common indications for vascular surgery.The prevalence of PAD in sub-Saharan Africa may be equal to or higher than that in high-income countries, exceeding 50% in some high-risk populations. In addition to population-based studies that better define the PAD burden in sub-Saharan Africa, health systems should consider studies and action regarding risk factor mitigation, targeted screening, medical management of PAD, and defining essential vascular care.
Haemoptysis: a frequent diagnostic challenge
Authors: Michele Mondoni, Giuseppe Francesco Sferrazza Papa, Giovanni Sotgiu, Paolo Carlucci, Giulia Michela Pellegrino, Stefano Centanni
Journal: European Respiratory Journal (2015)

Haemoptysis is a frequent symptom, and the definition of aetiologies and a diagnostic pathway are often challenginghttp://ow.ly/U0f2X