tbuckley/cabot-search huggingface dataset:
Future Eye Implants Focus on Neurotransmitters
Authors: Brian Vastag
Journal: JAMA (2002)

WASHINGTON—Superman had it, and in a decade many others could have supervision, according to scientists who are developing eye implants that translate digital camera images into a flow of neurotransmitters that mimic natural vision. “The possibilities are limitless if you continue this [research] to its logical conclusion,” said Harvey Fishman, MD, PhD, director of the Ophthalmic Tissue Engineering Laboratory at Stanford University School of Medicine. “You could have any kind of vision you want, you could see infrared, you could see the stars.” Before that sky-high vision materializes, though, research being conducted by Fishman and others offers hope to more than 4 million blind people in the United States. Because the implants would act as artificial retinas, they could help those whose blindness is caused by age-related macular degeneration or hereditary retinitis pigmentosa, the two most common retinadestroying diseases.
Abstract 1919: Profiling of cancer cell lines demonstrates a dynamic relationship between epithelial, mesenchymal and cancer stem states
Authors: James R. Hernandez, Steven M. Mooney, Takumi Shiraishi, James E. Verdone, Calvin A. Harberg, Donald Vindivich, Kenneth J. Pienta
Journal: Cancer Research (2014)

Abstract Our previous work has demonstrated that exposure of M2 - Tumor Associated Macrophages M2-TAMs) to epithelial cancer cells can induce an Epithelial to Mesenchymal Transition (EMT). The resulting mesenchymal cancer cells exhibit a more aggressive phenotype, which places patients at a higher risk of relapse and death. Although most patients are cured by radical prostatectomy or radiation, it has been demonstrated that the majority of patients have disseminated tumor cells in their bone marrow at the time of primary treatment and approximately 10-15% of these men will eventually suffer a relapse after a period of dormancy. Further characterization of these disseminated cells both at the time of primary treatment and over time, is needed. It is unclear if these cells, especially those destined to eventually proliferate, are “mesenchymal”, “epithelial”, or “cancer stem” cells (CSCs). In this work, we investigate the CSC molecular and gene expression profile across multiple cancer cell lines and cell phenotypes. In part, this was done by utilizing various culturing conditions, such as 3D growth in stem cell media in order to generate sphere-like cultures known as tumorspheres. Flow cytometric analysis was performed based on ALDH, CD44 variant and CD133 expression. This was followed by gene expression analysis and characterization of the resulting tumorspheres and standard 2D cultures. The results demonstrate that there may be a level of plasticity that allows these cancer cells to alter gene expression and shift towards a CSC state and/or that there is a common CSC progenitor that exists within the population which can give rise to both epithelial and mesenchymal cell types. Therefore, furthering our understanding of the dynamic relationship between CSCs, EMT, and the converse mesenchymal to epithelial transition, is critical in developing novel therapeutics and prognostic tools in the field of cancer medicine. Citation Format: James R. Hernandez, Steven M. Mooney, Takumi Shiraishi, James E. Verdone, Calvin A. Harberg, Donald Vindivich, Kenneth J. Pienta. Profiling of cancer cell lines demonstrates a dynamic relationship between epithelial, mesenchymal and cancer stem states. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1919. doi:10.1158/1538-7445.AM2014-1919
Development and preclinical modeling of a topoisomerase I pharmacodynamic immunoassay for use in clinical trials
Authors: Thomas Pfister, Sonny Khin, Melinda Hollingshead, Ralph Parchment, Joseph Tomaszewski, James Doroshow, Robert Kinders
Journal: Clinical Cancer Research (2008)

B23   Topoisomerase I (TopI) is a proven target for cancer therapeutics. Recent data from the Fluorouracil, Oxaliplatin,  CPT-11: Use and Sequencing (FOCUS) trial demonstrates that nuclear staining of TopI correlates with chemotherapy efficacy [J Clin Oncol (2008) 26, 2690-8]. We have developed and validated a two-site enzyme chemiluminescent immunoassay for TopI; commercially obtained TopI antibodies and purified-recombinant protein were used as standards and assay controls were derived from A375 cell extracts. The LLQ of the assay was 0.8 ng/mL and the LOD (3 SD above the zero) was 0.22 ng/mL. The assay dynamic range was 0.2 to 12.5 ng/mL and the standard curve was linear (R 2 > 0.98). Recovery of recombinant TopI spiked into mouse xenograft extracts ranged from 81% to 105%. Preclinical pharmacodynamic (PD) modeling of topotecan time- and dose-effect was performed in either topotecan-responsive or -nonresponsive xenografts in an athymic nude mouse model [NCr(nu/nu)]. Topotecan-responsive A375 and HCT-116 xenografts showed decreased TopI levels in response to topotecan, with a maximal decrease occurring by 4 to 7 hours post-dose. These results should qualify this TopI assay for use in clinical trials of TopI inhibitors. In addition, this assay could potentially be used to monitor clinical response during therapy and to identify patients most likely to benefit from treatment with TopI inhibitors.  Funded by NCI Contract N01-CO-12400  NCI-Frederick is accredited by AAALAC International and follows the Public Health Service Policy for the Care and Use of Laboratory Animals. Animal care was provided in accordance with the procedures outlined in the Guide for Care and Use of Laboratory Animals (National Research Council; 1996; National Academy Press; Washington, D.C.)
microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma
Authors: Zong-Tao Chai, Xiao-Dong Zhu, Jian-Yang Ao, Wen-Quan Wang, Dong-Mei Gao, Jian Kong, Ning Zhang, Yuan-Yuan Zhang, Bo-Gen Ye, De-Ning Ma, Hao Cai, Hui-Chuan Sun
Journal: Journal of Hematology & Oncology (2015)

microRNAs (miRNAs) have been reported to modulate macrophage colony-stimulating factor (M-CSF) and macrophages. The aim of this study was to find whether miR-26a can suppress M-CSF expression and the recruitment of macrophages. Hepatocellular carcinoma (HCC) cell lines with decreased or increased expression of miR-26a were established in a previous study. M-CSF expression by tumor cells was measured by enzyme-linked immunosorbent assay, and cell migration assays were used to explore the effect of HCC cell lines on macrophage recruitment in vitro. Real-time PCR measured a panel of mRNAs expressed by macrophages. Xenograft models were used to observe tumor growth. Immunohistochemistry was conducted to study the relation between miR-26a expression and M-CSF expression and macrophage recruitment in patients with HCC. Ectopic expression of miR-26a reduced expression of M-CSF. The conditioned medium (CM) from HepG2 cells that overexpressed miR-26a reduced the migration ability of THP-1 cells stimulated by phorbol myristate acetate (PMA) increased expression of interleukin (IL)-12b or IL-23 mRNA and decreased expression of chemokine (C-C motif) ligand (CCL)22, CCL17, and IL-10 mRNA, in comparison to the medium from the parental HepG2 cells. These effects could be interrupted by the PI3K/Akt pathway inhibitor LY294002. Ectopic expression of miR-26a in HCC cells suppressed tumor growth, M-CSF expression, and infiltration of macrophages in tumors. Similar results were also found when using HCCLM3 cells. Furthermore, the expression of miR-26a was inversely correlated with M-CSF expression and macrophage infiltration in tumor tissues from patients with HCC. miR-26a expression reduced M-CSF expression and recruitment of macrophages in HCC.
Addressing Consent Issues in Donation After Circulatory Determination of Death
Authors: Kim J. Overby, Michael S. Weinstein, Autumn Fiester
Journal: The American Journal of Bioethics (2015)

Given the widening gap between the number of individuals on transplant waiting lists and the availability of donated organs, as well as the recent plateau in donations based on neurological criteria (i.e., brain death), there has been a growing interest in expanding donation after circulatory determination of death. While the prevalence of this form of organ donation continues to increase, many thorny ethical issues remain, often creating moral distress in both clinicians and families. In this article, we address one of these issues, namely, the challenges surrounding patient and surrogate informed consent for donation after circulatory determination of death. First we discuss several general concerns regarding consent related to this form of organ donation, and then we address additional issues that are unique to three different patient categories: adult patients with medical decision-making capacity or potential capacity, adult patients who lack capacity, and pediatric patients.
Abstract 4228: 6,7,4-Trihydroxyisoflavone, a daidzein metabolites, regulated glycogen synthase kinase 3β/β-catenin signaling and inhibited cell proliferation in MCF10DCIS.com human breast cancer cells
Authors: Hyun-Chang Park, Cheng Bao, Jiwon Ko, Jaehoo Lee, Hong Jin Lee
Journal: Cancer Research (2014)

Abstract Recent studies have demonstrated that hepatic daidzein metabolites exerted significant activities in regulating different types of cancer including skin and colon. However, the role of daidzein metabolites on breast cancer has not been extensively studied. In this study, we found that 6,7,4′-trihydroxyisoflavone exerted the strongest inhibitory effect on the proliferation of MCF10DCIS.com human breast cancer cells among the daidzein metabolites we tested. Cell cycle at S and G2/M phase were arrested by 6,7,4-trihydroxyisoflavone, which were derived from regulating cyclins and cyclin dependent kinases (CDKs) including cyclin B, CDK1 and CDK2, as well as CDK inhibitor, p27 in a dose dependent manner. Furthermore, 6,7,4′-trihydroxyisoflavone increased the GSK3β activity through inhibiting the phosphorylation at Ser9, which was caused by the enhancement of phosphatase activity. These effects of 6,7,4′-trihydroxyisoflavone led to inhibition of the nuclear translocation of β-catenin, and regulation of cell cycle related proteins, cyclinB and CDK2. Taken together, 6,7,4′-trihydroxyisoflavone regulated GSK3β/β-catenin signaling, and arrested at S and G2/M phase in MCF10DCIS.com human breast cancer cells, and it suggests that the hepatic metabolite of daidzein, 6,7,4′-trihydroxyisoflavone, may be a potent agent in inhibiting MCF10DCIS.com human breast cancer growth. Citation Format: Hyun-Chang Park, Cheng Bao, Jiwon Ko, Jaehoo Lee, Hong Jin Lee. 6,7,4-Trihydroxyisoflavone, a daidzein metabolites, regulated glycogen synthase kinase 3β/β-catenin signaling and inhibited cell proliferation in MCF10DCIS.com human breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4228. doi:10.1158/1538-7445.AM2014-4228
Mammography no better than physical breast examination, study shows
Authors: Deborah Josefson
Journal: BMJ (2000)

Careful physical breast examination is as effective as screening mammography in reducing mortality from breast cancer in women aged over 50, according to a controversial new study ( Journal of the National Cancer Institute 2000:92:1490-9).

The second Canadian national breast screening study found that mammography detected breast cancers earlier than physical breast examination, but surprisingly, earlier detection did not translate into a survival advantage.

The Canadian study, led by Dr Anthony Miller and colleagues at the University of Toronto, followed 39 405 women aged 50-59. Only women who were not pregnant, had no history of breast cancer, and had not had mammography within the previous 12 months were eligible for enrolment.

The women were recruited from six provinces and 15 medical centres between 1980 and 1985 and were randomised into two arms: 19 711 women received both mammography and physical breast examinations by nurses or doctors, and 19 694 women received physical breast examinations alone.

All the women were taught to examine their breasts and were followed via record linkage with the Canadian national cancer registry and the national …
Abstract 18343: Antisynthetase Syndrome-Associated Myocarditis
Authors: Kavita Sharma, Ana-Maria Orbai, Dipan Desai, Oscar H Cingolani, Marc K Halushka, Lisa Christopher-Stine, Andrew L Mammen, Katherine C Wu, Sammy Zakaria
Journal: Circulation (2014)

Background: The antisynthetase (AS) syndrome is characterized by fever, non-erosive arthritis, inflammatory myopathy, interstitial lung disease, cutaneous involvement, and antibody specificity. Cardiac involvement is extremely rare; we present one of two cases of AS syndrome-associated myocarditis from our institution. Clinical Case: A 51 year old woman with history of inflammatory arthritis and hypothyroidism presented with 6 months of increasing fatigue, bilateral proximal muscle weakness, leg edema, dyspnea, and orthopnea. Physical examination revealed a Caucasian woman, markedly dyspneic while speaking, with signs of acute decompensated heart failure (HF) including elevated jugular venous pulse, bilateral rales, S3 gallop, and massive peripheral edema with bilateral proximal upper and lower extremity weakness. Diagnostic Testing: Her muscle weakness was concerning for myopathy along with new HF symptoms. Laboratory studies revealed elevations of serum creatine kinase, aldolase, and cardiac troponin I. Thyroid stimulating hormone and free T4 were consistent with subclinical hypothyroidism. MRI and electromyography of the lower extremities and skeletal muscle biopsy were consistent with myositis. Anti-Jo1 antibody was positive, confirming the diagnosis of AS syndrome. Electrocardiogram showed sinus rhythm and low-voltages in all leads. Echocardiography showed severely depressed biventricular function, left ventricular (LV) ejection fraction of 10-15%, normal LV cavity size and wall thickness. Cardiac MRI and endomyocardial biopsy revealed active myocarditis. She received pulse dose corticosteroid therapy, intravenous furosemide, inotropic therapy, and hemofiltration therapy for renal failure. She was discharged home on intravenous dobutamine palliative therapy. Two months later, she presented in cardiogenic shock, failed intensive medical therapy, and died after a cardiac arrest. Conclusions: AS syndrome is a rare entity not typically associated with cardiac involvement. We report one of only two known cases of AS syndrome-associated myocarditis, to our knowledge. Based on these observations, we suggest that myocarditis be considered and evaluated for in patients with AS syndrome presenting with HF.
Abstract 14646: Internal Medicine Housestaff Perceptions of Statins and ACC/AHA Blood Cholesterol Guidelines
Authors: Peter Flueckiger, Stephen Juraschek, Micah Eades, Amit Khera, Michael Blaha, Laurence Sperling
Journal: Circulation (2014)

Background: Statins are integral in the prevention of atherosclerotic cardiovascular disease (ASCVD). Provider perceptions and prescribing practices of statins vary. Internal medicine housestaff (HS) perceptions of statins and new ACC/AHA cholesterol guidelines have not previously been assessed. Methods: We examined internal medicine HS perceptions of statins and ACC/AHA cholesterol guidelines through a 48-question survey. We surveyed HS at three academic training programs. Anonymous responses were collected via a secure website. Results: 99 respondents’ results (84% categorical residents) were examined from Emory, Johns Hopkins, and UTSW. HS report observing low rates of statin side effects: 64% and 91% reported rates of &lt;3% and &lt;10%. Majority of side effects were myalgias (69%), transaminitis (23%), and gastrointestinal symptoms (5%). Over half (54%) of respondents check transaminases prior to statin therapy. If transaminitis &gt;1-2x upper limit of normal (ULN) develop only 6% of residents stop statin therapy, though 62% stop therapy if transaminitis &gt;3x ULN. In stable liver disease, 13% use non-statin therapy. Most residents (73%) agree that patients understand why they are prescribed statins and feel compliance is influenced by experienced/perceived risk of side effects (44%), cost (30%), and medical benefit (13%). However, HS do not discuss side effects in 25% of patients and only 44% agree patients frequently ask about side effects. Additionally, only 51% of HS discuss ASCVD risk with a majority of patients. HS perceive high rates of statin adherence (87% state &gt;50% adherence at one year). Of 61 HS, 72% learned of new lipid guidelines through residency training. Nearly all (89%) read a portion of the guidelines and are likely to implement them (97%). However, only 57% agree the guidelines are clear or straightforward to apply in clinical practice and 66% agreed the guidelines will improve/reduce ASCVD risk. Only 48% agree new guidelines will improve quality of patient care. Conclusion: Practice patterns of statin therapy vary among medicine HS. Side effects and ASCVD risk are not frequently discussed with patients. Though HS are aware of new cholesterol guidelines, a gap exists between implementation and perceived benefits/ASCVD risk reduction.
Abstract 3675: Extracellular ATP Protects Human Endothelial Cells From Apoptotic Death During Ischemia by Activating a P2Y2-receptor Mediated MEK/ERK- and PI3K/Akt-signaling
Authors: Daniel Urban, Frauke Hartel, Krishnaveni Gadiraju, Hans M Piper, Thomas Noll
Journal: Circulation (2009)

Background: Apoptotic death of endothelial cells (EC) plays a crucial role in the development and progression of cardiovascular disease. Recently it was shown that endothelial apoptosis initiated d...
Abstract 4080: Smad and NFAT pathways cooperate to regulate CD103 expression in human CD8 T lymphocytes and TCR-mediated epithelial tumor cell killing
Authors: Fathia Mami-Chouaib, M'barka Mokrani, Georges Bismuth
Journal: Cancer Research (2014)

Abstract The interaction of integrin αE(CD103)β7, often expressed on tumor-infiltrating lymphocytes (TIL), with epithelial cell marker E-cadherin on tumor cell surface plays a major role in antitumor cytotoxic T lymphocyte (CTL) responses. CD103 is encoded by ITGAE gene and is induced in CD8 T cells upon T-cell receptor (TCR) engagement and exposure to transforming growth factor (TGF)-β1, abundant within the tumor microenvironment. However, the transcriptional mechanisms underlying the cooperative role of these two signaling pathways in inducing CD103 expression in CD8 T cells remain unknown. Using a model system based on a CD8+/CD103- T-cell clone, we demonstrated that the transcription factors Smad2/3 and NFAT-1 are required for CD103 induction on T lymphocytes activated with a combination of TGF-β1 and anti-CD3 monoclonal antibodies. We also identified the promotor and enhancer elements of human ITGAE gene, and showed that Smad2/3 and NFAT-1 are necessary for the activity of the ITGAE enhancer, and thus for CD103 expression. Overall, our results explain how TGF-β1 induces CD103 expression on locally activated CD8 T cells, thus contributing to antitumor CTL responses and malignant cell killing. Citation Format: Fathia Mami-Chouaib, M'barka Mokrani, Georges Bismuth. Smad and NFAT pathways cooperate to regulate CD103 expression in human CD8 T lymphocytes and TCR-mediated epithelial tumor cell killing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4080. doi:10.1158/1538-7445.AM2014-4080
High throughput multiplexing phosphor retinoblastoma tumor suppressor protein (Rb) and cell cycle analysis using acuman technology.
Authors: Xi Lin, Lawrence Gelbert, Shaoyou Chu, Diego Medina, Cristina Garcia-Paredes, Alfonso De Dios
Journal: Cancer Research (2007)

4372   The mammalian cell cycle consists of 4 phases- G1, S, G2 and M, and is responsible for the regulation of cellular replication. Sensing extracellular signals, the transition from G1 to S phase is controlled by cyclin dependent kinases 4 and 6 (CDK4/6). These kinases phosphorylate the retinoblastoma gene product (Rb) releasing E2F/DP transcription factors resulting in the expression of genes required for transition into S phase and DNA replication. Inhibition of CDK4/CDK6 results in hypo-phosphorylation of Rb and arrest cells in G1 phase. The CDK4/CDK6/Rb pathway is dysregulated in many tumors and the development of selective small molecule CDK4/CDK6 inhibitors for the treatment of cancer has been the focus of numerous efforts.  Selective and effective CDK4/6 inhibitors will have two properties, decreasing the amount of phosphorylated Rb (pRb ser780) and arresting cells in the G1 phase. The development of small molecule CDK4/6 inhibitors requires require assay that effectively monitor the both the level of pRb in the cells and cell cycle status. Several assays exist that measure these two properties including Western blot, ELISA, and enzymatic assays for pRb (S780), and flow cytometry to measure cell cycle status. However, none of these assays allow for the simultaneous measurement of pRb and cell cycle status, and these assays formats either time-consuming, have low throughput and/or low sensitivity, and lack the ability to monitor activity on individual cells.  Here we describe a high throughput multiplexed acumen assay for pRb (S780) and DNA content (cell cycle status). The assay can easily generate EC50s for 8 to 10 different CDK4/6 inhibitors in one 96-well plate, and indirectly can identify cytotoxicity and off-target activities for G2/M kinases.
Abstract 15626: Physical Activity Tracking Studies: The Effect of an Entirely Mobile (mHealth) Platform for Data Capture
Authors: David I Feldman, Seth S Martin, Michael J Blaha
Journal: Circulation (2014)

Background: In most prior activity tracking pedometer trials, physical activity had to be manually recorded by participating subjects. As a result, these trials have reported missing pedometer data in up to 45% of subjects. Mobile health (mHealth) real-time activity tracking interventions offer a possible solution for increasing participant engagement, streamlining study coordination, and increasing adherence. Methods: The mActive trial (NCT01917812), a 5-week blinded, randomized mHealth trial of digital activity tracking and “smart” text messaging, enrolled 48 adult cardiology patients at a single academic medical center. Eligible participants were smartphone users who reported a low amount of leisure time physical activity. Low energy Bluetooth capable pedometers were paired to participants’ smartphones, and digital activity data was continuously uploaded in real-time. Subjects received an automated weekly email reminding them to wear their pedometer, and targeted emails if data upload was incomplete fo...
Abstract 1425: Prevention of Major Cardiovascular Events With Rosuvastatin Among Patients With Impaired Fasting Glucose: The JUPITER Trial
Authors: Aruna Pradhan, Robert J Glynn, Paul M Ridker
Journal: Circulation (2009)

Few randomized data are available regarding primary prevention of cardiovascular disease (CVD) among patients with impaired fasting glucose (IFG), an important clinical issue as several major trial...