tbuckley/cabot-search huggingface dataset:
Do celebrity endorsements matter? Observational study of BRCA gene testing and mastectomy rates after Angelina Jolie’s New York Times editorial
Authors: Sunita Desai, Anupam B Jena
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To examine the effect on BRCA testing and mastectomy rates of a widely viewed 2013 <i>New York Times</i> editorial by public figure Angelina Jolie that endorsed BRCA testing and announced Jolie's decision to undergo preventive mastectomy. <b>Design</b>&nbsp;Observational study with difference-in-difference analysis. <b>Setting</b>&nbsp;Commercially insured US population. <b>Participants</b>&nbsp;Women aged 18-64 years with claims in the Truven MarketScan commercial claims database (n=9 532 836). <b>Main outcome measures</b>&nbsp;Changes in BRCA testing rates in the 15 business days before versus after 14 May 2013 (editorial date) compared with the change in the same period in 2012; mastectomy rates in the months before and after publication, both overall and within 60 days of BRCA testing among women who were tested; national estimates of incremental tests and expenditures associated with Jolie's article in the 15 days after publication. <b>Results</b>&nbsp;Daily BRCA test rates increased immediately after the 2013 editorial, from 0.71 tests/100 000 women in the 15 business days before to 1.13 tests/100 000 women in the 15 business days after publication. In comparison, daily test rates were similar in the same period in 2012 (0.58/100 000 women in the 15 business days before 14 May versus 0.55/100 000 women in the 15 business days after), implying a difference-in-difference absolute daily increase of 0.45 tests/100 000 women or a 64% relative increase (P&lt;0.001). The editorial was associated with an estimated increase of 4500 BRCA tests and $13.5m (£10.8m; €12.8) expenditure nationally among commercially insured adult women in those 15 days. Increased BRCA testing rates were sustained throughout 2013. Overall mastectomy rates remained unchanged in the months after publication, but 60 day mastectomy rates among women who had a BRCA test fell from 10% in the months before publication to 7% in the months after publication, suggesting that women who underwent tests as a result of to the editorial had a lower pre-test probability of having the BRCA mutation than women tested before the editorial. <b>Conclusions</b>&nbsp;Celebrity endorsements can have a large and immediate effect on use of health services. Such announcements can be a low cost means of reaching a broad audience quickly, but they may not effectively target the subpopulations that are most at risk for the relevant underlying condition.
Abstract 5462: Extracellular ATP promotes cancer cell drug resistance to tyrosine kinase inhibitors by competing for the ATP-binding site of tyrosine kinase
Authors: Xuan Wang, Yanrong Qian, Yunsheng Li, Xiaozhuo Chen
Journal: Cancer Research (2015)

Abstract ATP plays important roles in cellular processes in cancer cells, which are a heterogeneous population in tumors regarding their genetic background and oxygen and energy supplies. The fact that cancer cells undergo rapid proliferation suggests that they must possess mechanisms, which may not be present in normal cells, to meet their high energy needs. Studies by others revealed that extracellular ATP levels of various cancer types are 10^3 to 10^4 times higher than those in their corresponding normal tissues (1). We recently reported that extracellular ATP can be taken up directly by cancer cells by macropinocytosis (2). Based on these results, we hypothesized that the internalized extracellular ATP not only promotes cancer cell growth and survival, but also drug resistance. In this study, human lung cancer A549 and breast cancer MCF7 cells were used as cell models to determine the effects of extracellular ATP on drug resistance to tyrosine kinase inhibitors (TKIs) in cancer cells. Cancer cell viability and intracellular ATP measurement results showed that extracellular ATP substantially increased intracellular ATP levels and promoted cancer cell drug resistance to TKIs. Viability of TKI treated cancer cells was significantly increased in the presence of extracellular ATP, compared to cancer cells with TKI treatment alone. Administration of macropinocytosis inhibitors significantly reduced the drug resistance induced by extracellular ATP, suggesting that extracellular ATP promoted drug resistance by contributing to the intracellular ATP pool. Protein and protein phosphorylation analyses results suggested that the increased intracellular ATP reversed the inhibition of TKIs by competing with the inhibitor for the ATP-binding site of platelet-derived growth factor receptor (PDGFR) and enhancing Akt and MAPK signaling pathways. These findings identify, for the first time, new biological functions of extracellular ATP in tumors and may lead to novel anti-cancer strategies combating drug resistance in cancers. 1. Pellegatti P, et al. PLoS ONE 2008;3:e2599. 2. Qian Y, et al. Cancer Lett 2014;351:242-51. Citation Format: Xuan Wang, Yanrong Qian, Yunsheng Li, Xiaozhuo Chen. Extracellular ATP promotes cancer cell drug resistance to tyrosine kinase inhibitors by competing for the ATP-binding site of tyrosine kinase. [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 5462. doi:10.1158/1538-7445.AM2015-5462
Abstract 2565: Aryl hydrocarbon receptor agonist 5F 203 induces oxidative stress triggering DNA damage and cytoglobin up-regulation in human breast cancer cells
Authors: Leah K. Rowland, Lancelot S. McLean, Petreena Campbell, Cheri N. Watkins, Dain Zylstra, Louisa H. Amis, Maheswari Senthil, Eileen Brantley
Journal: Cancer Research (2015)

Abstract Breakthroughs are needed in breast cancer therapy to improve clinical outcomes. Emerging evidence suggests that tumorigenesis stems, in part, from epigenetically silenced tumor suppressor genes (TSGs) and restoring TSGs may represent a viable strategy to treat breast cancer. We previously found that aryl hydrocarbon receptor (AhR) agonist 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) exhibits potent cytotoxicity, increases reactive oxygen species (ROS), induces DNA damage and up-regulates the expression of putative tumor suppressor gene cytoglobin in breast cancer cells. In the current study, we seek to delineate the mechanism by which 5F 203 induces DNA damage and cytoglobin expression in susceptible breast cancer cells. We found that 5F 203 activated p38 mitogen activated protein kinase (p38) and c-Jun-N terminal kinase (JNK) signaling in breast cancer cells. Pretreatment with antioxidant N-acetyl-L-cysteine or AhR inhibitor α-naphthoflavone diminished 5F 203-mediated p38 or JNK activation in a cell context-dependent fashion. Pretreatment with pharmacological inhibitors of p38 or JNK suppressed 5F 203-mediated increases in intracellular ROS to suggest the presence of a positive feedback loop. 5F 203 induced oxidative DNA damage in breast cancer cells but not breast epithelial MCF-10A cells unlike AhR agonist benzo[a]pyrene which induced oxidative DNA damage more indiscriminately. Pretreatment with p38 or JNK inhibitors suppressed 5F 203-induced single strand break formation and cytoglobin mRNA expression in breast cancer cells. Our data show 5F 203 confers anticancer activity in breast cancer cells in part by increasing ROS via a positive feedback loop to sustain p38 and JNK activation resulting in DNA damage and cytoglobin restoration. Citation Format: Leah K. Rowland, Lancelot S. McLean, Petreena Campbell, Cheri N. Watkins, Dain Zylstra, Louisa H. Amis, Maheswari Senthil, Eileen Brantley. Aryl hydrocarbon receptor agonist 5F 203 induces oxidative stress triggering DNA damage and cytoglobin up-regulation in human breast cancer cells. [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 2565. doi:10.1158/1538-7445.AM2015-2565
Screening Efectiveness with SERUM Galactomannan in High and Low Risk Patients for Fungal Infection in the Post ALLO-HTC
Authors: Fabio Augusto Ruiz Gómez, Valentin García Gutierrez, Elia Gomez, Pilar Herrera Puente, Isabel Page Herráez, Gustavo Alberto Pinto Solano, Carlos Montalban, Javier Lopez
Journal: Blood (2015)
Severe Malaria in African Children — The Need for Continuing Investment
Authors: Kathryn Maitland
Journal: New England Journal of Medicine (2016)

Today, 57% of Africans live in areas with moderate-to-high rates of malaria transmission, with 10 countries accounting for 87% of people exposed to the highest-intensity transmission. About 1200 children die from malaria in sub-Saharan Africa every day.
Association of β-Blockers With Functional Outcomes, Death, and Rehospitalization in Older Nursing Home Residents After Acute Myocardial Infarction
Authors: Michael A. Steinman, Andrew R. Zullo, Yoojin Lee, Lori A. Daiello, W. John Boscardin, David D. Dore, Siqi Gan, Kathy Fung, Sei J. Lee, Kiya D. R. Komaiko, Vincent Mor
Journal: JAMA Internal Medicine (2016)

Although β-blockers are a mainstay of treatment after acute myocardial infarction (AMI), these medications are commonly not prescribed for older nursing home residents after AMI, in part owing to concerns about potential functional harms and uncertainty of benefit. To study the association of β-blockers after AMI with functional decline, mortality, and rehospitalization among long-stay nursing home residents 65 years or older. This cohort study of nursing home residents with AMI from May 1, 2007, to March 31, 2010, used national data from the Minimum Data Set, version 2.0, and Medicare Parts A and D. Individuals with β-blocker use before AMI were excluded. Propensity score-based methods were used to compare outcomes in people who did vs did not initiate β-blocker therapy after AMI hospitalization. Functional decline, death, and rehospitalization in the first 90 days after AMI. Functional status was measured using the Morris scale of independence in activities of daily living. The initial cohort of 15 720 patients (11 140 women [70.9%] and 4580 men [29.1%]; mean [SD] age, 83 [8] years) included 8953 new β-blocker users and 6767 nonusers. The propensity-matched cohort included 5496 new users of β-blockers and an equal number of nonusers for a total cohort of 10 992 participants (7788 women [70.9%]; 3204 men [29.1%]; mean [SD] age, 84 [8] years). Users of β-blockers were more likely than nonusers to experience functional decline (odds ratio [OR], 1.14; 95% CI, 1.02-1.28), with a number needed to harm of 52 (95% CI, 32-141). Conversely, β-blocker users were less likely than nonusers to die (hazard ratio [HR], 0.74; 95% CI, 0.67-0.83) and had similar rates of rehospitalization (HR, 1.06; 95% CI, 0.98-1.14). Nursing home residents with moderate or severe cognitive impairment or severe functional dependency were particularly likely to experience functional decline from β-blockers (OR, 1.34; 95% CI, 1.11-1.61 and OR, 1.32; 95% CI, 1.10-1.59, respectively). In contrast, little evidence of functional decline due to β-blockers was found in participants with intact cognition or mild dementia (OR, 1.03; 95% CI, 0.89-1.20; P = .03 for effect modification) or in those in the best (OR, 0.99; 95% CI, 0.77-1.26) and intermediate (OR, 1.05; 95% CI, 0.86-1.27) tertiles of functional independence (P = .06 for effect modification). Mortality benefits of β-blockers were similar across all subgroups. Use of β-blockers after AMI is associated with functional decline in older nursing home residents with substantial cognitive or functional impairment, but not in those with relatively preserved mental and functional abilities. Use of β-blockers yielded a considerable mortality benefit in all groups.
Mismatch repair protein loss and microsatellite instability in cholangiocarcinoma.
Authors: Lipika Goyal, Vikram Deshpande, Daniel C Chung, Ryan Thomas Groeschl, T. Clark Gamblin, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2014)

237 Background: Hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch Syndrome, is an autosomal dominant syndrome characterized by mutations in genes involved in DNA mismatch repair (MMR) and consequent microsatellite instability (MSI). These genetic aberrations lead to an increased incidence of multiple malignancies including colorectal and endometrial cancer, among others. While an association between biliary tumors and HNPCC has been proposed, no published studies have documented MMR protein loss and MSI in a series of biliary tumor samples. After diagnosing cholangiocarcinoma (CCA) in two clinic patients known to have HNPCC and incidentally noting MMR protein loss and MSI in their tumor, we conducted an exploratory study to evaluate the frequency of MMR protein loss and MSI in patients with CCA. Methods: Discarded tissue samples from patients with CCA treated at the Massachusetts General Hospital (n=44) were evaluated for the loss of MLH1, PMS2, MSH2, and MSH6 with immunohistochemical staining. The results were correlated with clinicopathologic features, and the MSI status was collected from the medical record. Results: Four (9.1%) of 44 patients were found to have loss of at least two MMR proteins: 2 pts had MSH2/MSH6 loss, 1 had MLH1/PMS2 loss, and 1 had loss of all 4 proteins. Two patients had previously been tested for microsatellite instability and both were MSI-high. The clinicopathologic features of the 4 patients included: median age 54.5 yo; M:F 1:3; diagnosed with ≥ 1 HNPCC-related malignancy 1/4; family history of ≥ 2 HNPCC-related tumors 2/4, intrahepatic:extrahepatic CCA 3:1; moderately-poorly:poorly differentiated 2:2; T1:T2 3:1; ≥1 positive lymph node 1/4; lymphovascular invasion 2/3; perineural invasion 2/4. Conclusions: MMR protein loss was discovered in 9.1% of patients with CCA in this initial cohort. A second validation cohort from a different institution is currently being tested, and the results will be presented at the meeting. CCA may be an underappreciated co-morbid neoplasm in the spectrum of tumors for HNPCC. MMR protein loss should be further explored as a mechanism of oncogenesis in CCA, and clinicians should be aware of this malignancy in surveillance of patients with HNPCC.
Is There a Risk in Allogeneic PBPC Donation for Autoimmune Diseases Due to Short-Term Treatment with rhG-CSF? Preliminary Results of a Prospective Study in 100 Unrelated Stem Cell Donors.
Authors: Frank Kroschinsky, Karsten Conrad, Kirsten Poppe-Thiede, Rainer Ordemann, Andrea Schlaupitz, Gabi Rall, Claudia Rutt, Gerhard Ehninger
Journal: Blood (2004)
436. Developing a Synthetic DNA Vaccine for an Emerging Pathogen - Middle East Respiratory Syndrome
Authors: Emma L. Reuschel, Karrupiah Muthumani, Kim Kraynyak, Colleen Tingey, Sagar B. Kudchodkar, Amir S. Khan, Niranjan Y. Sardesai, J. Joseph Kim, Joel Maslow, Young K. Park, Gary Kobinger, Darryl Falzarano, Heinrich Feldman, David B. Weiner
Journal: Molecular Therapy (2016)

Background: Middle East Respiratory Syndrome (MERS) was first reported in 2012 in Saudi Arabia when a patient died from severe respiratory disease caused by a novel betacorona virus, MERS-CoV. Through November 2015, there have been 1618 confirmed global cases of MERS-CoV infection and 579 deaths reported to the World Health Organization (WHO). Currently, no vaccine or specific treatment is available and patients are treated with supportive care based on their clinical condition. While most MERS cases occur in and around Saudi Arabia, the recent outbreak in Korea highlights the potential for this disease to spread beyond the immediate region. A vaccine is needed to prevent future disease caused by MERS-CoV. Methods: A synthetic DNA MERS vaccine was generated using a consensus sequence of the MERS spike protein. Mice, dromedary camels, and non-human primates (NHP) were immunized with MERS-vaccine by intramuscular injection followed by electroporation. Cellular immune responses were measured by flow cytometry and IFNγ ELISpot. Humoral immune responses were measured by ELISA and neutralizing antibody (nAb) assay. Following immunization, NHPs were challenged with infectious MERS-CoV (EMC/2012) and monitored for signs of infection by clinical scoring and examinations. Viral load was measured by qRT-PCR and tissue sections were stained with H&E. Results: Immunization of mice with MERS-vaccine induced strong humoral and cellular responses. Mice produced strong binding antibody (bAb) titers and nAb titers. A strong, polyfunctional, CD4 and CD8 T cell response was detected against multiple epitopes across the MERS spike protein. Immunization of dromedary camels induced the production of MERS spike specific antibodies and nAbs. Immunization of NHPs induced strong bAb titers and nAb titers and a strong CD4 and CD8 T cell response. NHPs immunized with multiple vaccination regimens were also protected from signs of disease upon challenge with infectious MERS-CoV and showed a greater than 3 log reduction in viral load after challenge compared to unvaccinated animals. Conclusions: A consensus DNA MERS-vaccine was able to generate both a strong T cell and neutralizing antibody response in multiple animal models, including camels, a natural host for MERS-CoV and a probable source of human infection. MERS-vaccine was also able to protect NHPs from an infectious MERS-CoV challenge. These results demonstrate the promise of this consensus DNA MERS-vaccine as a candidate for vaccine development.
Risk Associated With Surgery Within 12 Months After Coronary Drug-Eluting Stent Implantation
Authors: Gro Egholm, Steen Dalby Kristensen, Troels Thim, Kevin K.W. Olesen, Morten Madsen, Svend E. Jensen, Lisette O. Jensen, Henrik T. Sørensen, Hans E. Bøtker, Michael Maeng
Journal: Journal of the American College of Cardiology (2016)
Abstract 1439: RANK expression by osteosarcoma cells increases lung metastasis in Nude mouse while has no effect in immune-competent mouse
Authors: Benjamin Navet, Kosei Ando, Hideo Yagita, Christopher G. Mueller, Dominique Heymann, Frederic Lezot
Journal: Cancer Research (2015)

Abstract Abstract Background: Osteosarcoma, the most frequent malignant primary bone tumor, is characterized by an osteoid tumor tissue formation associated to a tumor-induced osteolysis. Lung metastasis occurs in some osteosarcomas with dramatic consequence for patient lifespan. Expression of RANK has been reported in some osteosarcoma cells and the question of the potential repercussion on tumor growth, tumor-induced osteolysis and lung metastasis was raised. Methods: Human HOS, human MG63 and mouse MOS-J osteosarcoma cell-lines were transfected to stably over-express RANK and injected in para-tibia muscle of Nude mice and syngeneic C57BL/6 mice for MOS-J cells. Tumor growth was follow and associated osteolysis analyzed by micro-CT and histology comparatively to injections of native cells. Lung metastases were numbered in each group. Results: In Nude mouse RANK over-expression, whatever the cell-line considered (human or mouse), induces a significant increase of the number of lung metastasis while the tumor growth and the induced osteolysis are not affected. Injections of a RANKL blocking antibody reverse the impact of RANK over-expression on lung metastasis. In the C57BL/6, RANK over-expression has no impact on the lung metastasis and tumor-induced osteolysis. The tumor growth was slightly reduced. Conclusions: Reported data evidence that RANK expression by osteosarcoma cells has no significant effect on the tumor growth and tumor-induced osteolysis but in immune-deficient Nude mouse induces an important increase of the lung metastases dependently of RANKL stimulation. Citation Format: Benjamin Navet, Kosei Ando, Hideo Yagita, Christopher G. Mueller, Dominique Heymann, Frederic Lezot. RANK expression by osteosarcoma cells increases lung metastasis in Nude mouse while has no effect in immune-competent mouse. [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 1439. doi:10.1158/1538-7445.AM2015-1439
Perioperative Major Adverse Cardiovascular and Cerebrovascular Events Associated With Noncardiac Surgery
Authors: Nathaniel R. Smilowitz, Navdeep Gupta, Harish Ramakrishna, Yu Guo, Jeffrey S. Berger, Sripal Bangalore
Journal: JAMA Cardiology (2016)

<h3>Importance</h3> Major adverse cardiovascular and cerebrovascular events (MACCE) are a significant source of perioperative morbidity and mortality following noncardiac surgery. <h3>Objective</h3> To evaluate national trends in perioperative cardiovascular outcomes and mortality after major noncardiac surgery and to identify surgical subtypes associated with cardiovascular events using a large administrative database of United States hospital admissions. <h3>Design, Setting, Participants</h3> Patients who underwent major noncardiac surgery from January 2004 to December 2013 were identified using the National Inpatient Sample. <h3>Main Outcomes and Measures</h3> Perioperative MACCE (primary outcome), defined as in-hospital, all-cause death, acute myocardial infarction (AMI), or acute ischemic stroke, were evaluated over time. <h3>Results</h3> Among 10 581 621 hospitalizations (mean [SD] patient age, 65.74 [12.32] years; 5 975 798 female patients 56.60%]) for major noncardiac surgery, perioperative MACCE occurred in 317 479 hospitalizations (3.0%), corresponding to an annual incidence of approximately 150 000 events after applying sample weights. Major adverse cardiovascular and cerebrovascular events occurred most frequently in patients undergoing vascular (7.7%), thoracic (6.5%), and transplant surgery (6.3%). Between 2004 and 2013, the frequency of MACCE declined from 3.1% to 2.6% (<i>P</i>for trend &lt;.001; adjusted odds ratio [aOR], 0.95; 95% CI, 0.94-0.97) driven by a decline in frequency of perioperative death (aOR, 0.79; 95% CI, 0.77-0.81) and AMI (aOR, 0.87; 95% CI, 0.84-0.89) but an increase in perioperative ischemic stroke from 0.52% in 2004 to 0.77% in 2013 (<i>P</i>for trend &lt;.001; aOR 1.79; CI 1.73-1.86). <h3>Conclusions and Relevance</h3> Perioperative MACCE occurs in 1 of every 33 hospitalizations for noncardiac surgery. Despite reductions in the rate of death and AMI among patients undergoing major noncardiac surgery in the United States, perioperative ischemic stroke increased over time. Additional efforts are necessary to improve cardiovascular care in the perioperative period of patients undergoing noncardiac surgery.
Transcriptome of Expressed Genes in CD34+ and CD66b+ Chronic Myeloid Leukemia Cells and Its Potential Role in the Transport of Kinase Inhibitors
Authors: Caroline Fátima Aquino Moreira-Nnes, Ana Cristina Simões Beltrão, Tereza Cristina Brito Azevedo, Larissa Tatiana Valente Martins Francês, Rodrigo Guarischi Mattos Amaral Sousa, Israel Tojal Silva, Artur Luiz Costa Silva, Wilson Araújo Silva-Jr, José Alexandre Rodrigues Lemos
Journal: Blood (2011)