tbuckley/cabot-search huggingface dataset:
PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline
Authors: William P. Tew, Christina Lacchetti, Annie Ellis, Kathleen Maxian, Susana Banerjee, Michael Bookman, Monica Brown Jones, Jung-Min Lee, Stéphanie Lheureux, Joyce F. Liu, Kathleen N. Moore, Carolyn Muller, Patricia Rodriguez, Christine Walsh, Shannon N. Westin, Elise C. Kohn
Journal: Journal of Clinical Oncology (2020)

To provide recommendations on the use of poly(ADP-ribose) polymerase inhibitors (PARPis) for management of epithelial ovarian, tubal, or primary peritoneal cancer (EOC).Randomized, controlled, and open-labeled trials published from 2011 through 2020 were identified in a literature search. Guideline recommendations were based on the review of the evidence, US Food and Drug Administration approvals, and consensus when evidence was lacking.The systematic review identified 17 eligible trials.The guideline pertains to patients who are PARPi naïve. All patients with newly diagnosed, stage III-IV EOC whose disease is in complete or partial response to first-line, platinum-based chemotherapy with high-grade serous or endometrioid EOC should be offered PARPi maintenance therapy with niraparib. For patients with germline or somatic pathogenic or likely pathogenic variants in BRCA1 (g/sBRCA1) or BRCA2 (g/sBRCA2) genes should be treated with olaparib. The addition of olaparib to bevacizumab may be offered to patients with stage III-IV EOC with g/sBRCA1/2 and/or genomic instability and a partial or complete response to chemotherapy plus bevacizumab combination. Maintenance therapy (second line or more) with single-agent PARPi may be offered for patients with EOC who have not received a PARPi and have responded to platinum-based therapy regardless of BRCA mutation status. Treatment with a PARPi should be offered to patients with recurrent EOC that has not recurred within 6 months of platinum-based therapy, who have not received a PARPi and have a g/sBRCA1/2, or whose tumor demonstrates genomic instability. PARPis are not recommended for use in combination with chemotherapy, other targeted agents, or immune-oncology agents in the recurrent setting outside the context of a clinical trial. Recommendations for managing specific adverse events are presented. Data to support reuse of PARPis in any setting are needed.Additional information is available at www.asco.org/gynecologic-cancer-guidelines.
GSK-3β activation accelerates early-stage consumption of Hippocampal Neurogenesis in senescent mice
Authors: Fei Liu, Na Tian, Hua-Qiu Zhang, Shi-Hong Li, Qiu-Zhi Zhou, Ying Yang, Jie Zheng, Jian-Zhi Wang
Journal: Theranostics (2020)

Adult hippocampal neurogenesis (AHN) deficits contribute to the progression of cognitive impairments during accelerated senescence, with the mechanistic causes poorly understood. Glycogen synthase kinase-3β (GSK-3β) is a critical regulator in prenatal neurodevelopment. The present study aims to study whether and how GSK-3β regulates AHN during the accelerated senescence. Methods: AHN and AHN-dependent cognition and GSK-3β were evaluated in 3- and 6-month senescence-accelerated mice prone 8 (SAM-P8) and senescence resistant 1 (SAM-R1) mice, respectively. GSK-3β was selectively overexpressed in wild-type mice using adeno-associated virus, or knocked-out by crossbreeding with GSK-3β floxed mice in the neural stem cells (NSCs) of Nestin-Cre mice, or pharmacologically inhibited with SB216763 in SAM-P8 mice. AHN was evaluated by BrdU-, DCX-staining and retrovirus-labeling. Results: AHN transiently increased at 3-month, but dramatically dropped at 6-month of age in SAM-P8 mice with a simultaneous activation of GSK-3β at 3-month. Selective overexpression of GSK-3β in hippocampal NSCs of wildtype mice induced long-term AHN deficits due to an accelerated depletion of NSC pool, although it transiently increased the proliferation and survival of the newborn neurons. Pharmacologically inhibiting GSK-3β by SB216763 efficiently preserved AHN and improved contextual memory in 6-month SAM-P8 mice, while conditional knock-out of GSK-3β in NSCs impaired AHN. Conclusion: Early-stage activation of GSK-3β in NSCs impairs AHN by accelerating the depletion of NSC pool, and pharmacological inhibition of GSK-3β is efficient to preserve AHN during the accelerated aging. These results reveal novel mechanisms underlying the AHN impairments during accelerated senescence and provide new targets for pro-neurogenic therapies for related diseases.
Characteristics of Marijuana Use During Pregnancy — Eight States, Pregnancy Risk Assessment Monitoring System, 2017
Authors: Jean Y. Ko, Kelsey C. Coy, Sarah C. Haight, Tamara M. Haegerich, Letitia Williams, Shanna Cox, Rashid Njai, Althea M. Grant
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Marijuana is the most commonly used illicit substance under federal law in the United States (1); however, many states have legalized medical and adult nonmedical use. Evidence regarding the safety and health effects of cannabis use during pregnancy is largely inconclusive (2). Potential adverse health effects to exposed infants (e.g., lower birthweight) have been documented (2). To provide population-based estimates of use surrounding pregnancy, identify reasons for and mode of use, and understand characteristics of women who continue versus cease marijuana use during pregnancy, CDC analyzed data from eight states participating in the 2017 Pregnancy Risk Assessment Monitoring System (PRAMS) marijuana supplement. Overall, 9.8% of women self-reported marijuana use before pregnancy, 4.2% during pregnancy, and 5.5% after pregnancy. The most common reasons for use during pregnancy were to relieve stress or anxiety, nausea or vomiting, and pain. Smoking was the most common mode of use. In multivariable models that included age, race/ethnicity, marital status, education, insurance status, parity, trimester of entry into prenatal care, and cigarette and e-cigarette use during pregnancy, women who continued versus ceased marijuana use during pregnancy were more likely to be non-Hispanic white or other race/ethnicity than non-Hispanic black, be unmarried, have ≤12 years of education, and use cigarettes during pregnancy. The American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) recommend refraining from marijuana use during pregnancy and lactation (3,4). Given the increasing number of states legalizing medical and adult nonmedical marijuana use, surveillance of perinatal marijuana use can inform clinical guidance, provider and patient education, and public health programs to support evidence-based approaches to addressing substance use.
Abstract 10705: Recurrent Atrial Fibrillation/flutter Detection After Ablation or Cardioversion Using the Alivecor® Kardiamobile Device: Iheart Results
Authors: Isaac L Goldenthal, Robert R Sciacca, Teresa Riga, Suzanne Bakken, Maurita Baumeister, Angelo B Biviano, Jose M Dizon, Daniel Wang, Ketty C Wang, William Whang, Kathleen T Hickey, Hasan Garan
Journal: Circulation (2019)

Introduction: This study evaluated the impact of daily ECG self-recordings to on time to documented recurrent atrial fibrillation (AF) or atrial flutter (AFL) and time to treatment of recurrent arr...
Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans
Authors: Douglas Vormstein-Schneider, Jessica D. Lin, Kenneth A. Pelkey, Ramesh Chittajallu, Baolin Guo, Mario A. Arias-Garcia, Kathryn Allaway, Sofia Sakopoulos, Gates Schneider, Olivia Stevenson, Josselyn Vergara, Jitendra Sharma, Qiangge Zhang, Tom P. Franken, Jared Smith, Leena A. Ibrahim, Kevin J. Mastro, Ehsan Sabri, Shuhan Huang, Emilia Favuzzi, Timothy Burbridge, Qing Xu, Lihua Guo, Ian Vogel, Vanessa Sanchez, Giuseppe A. Saldi, Bram L. Gorissen, Xiaoqing Yuan, Kareem A. Zaghloul, Orrin Devinsky, Bernardo L. Sabatini, Renata Batista-Brito, John Reynolds, Guoping Feng, Zhanyan Fu, Chris J. McBain, Gord Fishell, Jordane Dimidschstein
Journal: Nature Neuroscience (2020)
Abstract 1751: BPI-23314: A novel orally bioavailable small molecular BET inhibitor with target protein degradation activity
Authors: Jing Guo, Yan Xu, Dan Yan, Bo Yu, Weiwei Yu, Haibo Chen, Xiaofeng Xu, Xiangyong Liu, Hong Lan, Lieming Ding, Jiabing Wang
Journal: Cancer Research (2020)

Abstract The Bromo- and Extra-Terminal (BET) proteins, BRD2, BRD3, and especially BRD4, play important roles in transcriptional regulation of many oncogenes like MYC or BCL2, thus makes it an attractive drug target in multiple pathological settings, particularly in cancer. Earlier BET inhibitors, while effectively bind and inhibit the activity of BRD4, adversely induce compensatory accumulation of the target protein, that may account for their limited preclinical and clinical efficacy. Herein, we report BPI-23314, a potent, selective, and orally available small molecular BET bromodomain inhibitor, which possesses potent target inhibition activity as well as target protein degradation property. In vitro, BPI-23314 induced dose-dependent growth inhibition in a wide range of cancer cell lines, including those from AML, MM, DLBCL, NSCLC, TNBC, and CRPC, etc. Quantitative RT-PCR revealed that BPI-23314 markedly affected the transcription of genes encoding MYC, BCL2, and HEXIM1, thus induced G1 cell cycle arrest and apoptosis in MV-4-11 AML cell line. In vivo, oral administration of BPI-23314 led to tumor growth suppression or regression in multiple xenograft models of AML and MM. Transcriptional modulation of MYC, BCL2 and HEXIM1 were confirmed in BPI-23314-treated xenografts and in normal monkey, supporting their potential as pharmacodynamic biomarkers in clinical trials. Unlike previously described BET inhibitors that induced BRD4 accumulation, BPI-23314 serendipitously decreased BRD4 protein in MV-4-11 cells and in tumors from MV-4-11 xenografts. The feature of target-protein degradation differentiates BPI-23314 from the other BET inhibitors, renders it good in vivo efficacy, and suggests a lower risk of drug resistance in future clinical development. In conclusion, our study establishes BPI-23314 as a novel small molecular BET inhibitor with target BRD4 protein degradation property. BPI-23314 has obtained IND approval from Chinese regulatory authority and is planned to enter Phase 1 clinical development in hematologic malignancies in early 2020. Citation Format: Jing Guo, Yan Xu, Dan Yan, Bo Yu, Weiwei Yu, Haibo Chen, Xiaofeng Xu, Xiangyong Liu, Hong Lan, Lieming Ding, Jiabing Wang. BPI-23314: A novel orally bioavailable small molecular BET inhibitor with target protein degradation activity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1751.
Fabrication of a hydroxyapatite-PDMS microfluidic chip for bone-related cell culture and drug screening
Authors: Qiangqiang Tang, Xiaoyu Li, Chen Lai, Lei Li, Hongkai Wu, Yingjun Wang, Xuetao Shi
Journal: Bioactive Materials (2020)

Bone is an important part of the human body structure and plays a vital role in human health. A microfluidic chip that can simulate the structure and function of bone will provide a platform for bone-related biomedical research. Hydroxyapatite (HA), a bioactive ceramic material, has a similar structure and composition to bone mineralization products. In this study, we used HA as a microfluidic chip component to provide a highly bionic bone environment. HA substrates with different microchannel structures were printed by using ceramic stereolithography (SLA) technology, and the minimum trench width was 50 μm. The HA substrate with microchannels was sealed by a thin polydimethylsiloxane (PDMS) layer to make a HA-PDMS microfluidic chip. Cell culture experiments demonstrated that compared with PDMS, HA was more conducive to the proliferation and osteogenic differentiation of the human foetal osteoblast cell line (hFOB). In addition, the concentration gradient of the model drug doxorubicin hydrochloride (DOX) was successfully generated on a Christmas tree structure HA-PDMS chip, and the half maximal inhibitory concentration (IC50) of DOX was determined. The findings of this study indicate that the HA-PDMS microfluidic chip has great potential in the field of high-throughput bone-related drug screening and bone-related research.
A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber with reduced kidney function
Authors: Weng Kit Lye, Euan Paterson, Christopher C. Patterson, Alexander P. Maxwell, Riswana Banu Binte Mohammed Abdul, E. Shyong Tai, Ching Yu Cheng, Takamasa Kayama, Hidetoshi Yamashita, Mark Sarnak, Michael Shlipak, Kunihiro Matsushita, Unal Mutlu, Mohammad A. Ikram, Caroline Klaver, Annette Kifley, Paul Mitchell, Chelsea Myers, Barbara E. Klein, Ronald Klein, Tien Y. Wong, Charumathi Sabanayagam, Gareth J. McKay
Journal: Kidney International (2020)
Abstract 6384: TEAD inhibition reduces tumor proliferation in Merlin null meningioma and schwannoma
Authors: Liyam Laraba, Julio Grimm de Guibert, Tracy T. Tang, Leonard Post, David B. Parkinson
Journal: Cancer Research (2020)

Abstract Introduction: Meningiomas are the most common intracranial tumor and arise from the arachnoidal cell layer of the meninges. Schwannomas develop from Schwann cells which provide myelin and trophic support in the peripheral nerves. The tumor suppressor Merlin is deleted in approximately 50-60% of meningiomas and 70% of schwannomas. Loss of Merlin results in dysregulation of the Hippo pathway and consequent aberrant activation of the transcriptional coactivators YAP and TAZ. Nuclear localisation of YAP and TAZ has been shown to drive tumor phenotypes in many cancers. The TEAD family of transcription factors are major targets of YAP and TAZ-dependent signaling. TEAD family members undergo autopalmitoylation and this modification is required for transcriptional activation by YAP or TAZ. Vivace therapeutics have identified small molecule inhibitors of autopalmitoylation that block the interaction of TEAD family members with YAP and TAZ. This study seeks to establish the efficacy of small molecule inhibitors of TEAD activity in meningioma and schwannoma tumor cells. Experimental Procedures: Meningioma cell lines, primary human meningioma and schwannoma cells, as well as a schwannoma mouse model (PerisotinCRE /NF2 fl/fl) were treated with Vivace inhibitors to assess their effects upon tumor cell proliferation and TEAD driven transcription. Results: TEAD inhibition significantly reduced the proliferation of the BenMen-1 meningioma cell line, as well as in primary human meningioma cells. In schwannoma, inhibitors reduced proliferation and also reduced the expression of CTGF, a target of TEAD activation in both primary human meningioma and schwannoma cells. These novel inhibitors are also currently being tested in the Periostin CRE-NF2fl/fl schwannoma mouse model to evaluate their efficacy in vivo. Conclusions: The use of these novel compounds to inhibit TEAD function shows great potential as an effective treatment for reducing the rate of cell proliferation in meningioma and schwannoma, two clinically important tumor types. Citation Format: Liyam Laraba, Julio Grimm de Guibert, Tracy T. Tang, Leonard Post, David B. Parkinson. TEAD inhibition reduces tumor proliferation in Merlin null meningioma and schwannoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6384.
Reply to Yaroshetskiy <i>et al.</i>: Acute Respiratory Distress Syndrome in COVID-19: Do All These Patients Definitely Require Intubation and Mechanical Ventilation?
Authors: David R. Ziehr, Jehan Alladina, Camille R. Petri, Jason H. Maley, Ari Moskowitz, Benjamin D. Medoff, Kathryn A. Hibbert, B. Taylor Thompson, C. Corey Hardin
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
HP0033 Development of a system of networks and continuing education for physical therapists regarding the treatment of patients with rheumatic diseases: the fyranet project
Authors: J Verhoef, R Hoekman, M Bakker, HM de Vries-van der Zwan, FGJ Oosterveld, TPM Vliet Vlieland
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Objectives</h3> It has been observed by physical therapists and patients that treatment of patients with rheumatic diseases by physical therapists is hampered by a lack of specific knowledge and technical and communicative skills. Moreover, co-ordination between different health professionals involved in the treatment has been perceived as not optimal. Aim of the study was to set up a system of continuous improvement of specific knowledge and skills regarding the physiotherapeutic treatment of patients with rheumatic diseases and to start networks of physical therapists working in primary care, hospitals and rehabilitation centres. <h3>Methods</h3> In November 1999 all physical therapists working within the catchment area of two rheumatological centres (Leiden, Enschede) were invited to participate. Education programmes were organised in parallel in both regions and consisted of a 5-day postgraduate training programme, followed by 2-monthly seminars. The programme focussed on examination and treatment of patients with rheumatic diseases and on communication with patients with a chronic disease. Communication among health professionals was enhanced by teaching practices within the rheumatological centres and by developing a draft guideline on communication among health professionals. Outcome measurements included questionnaires on the organisation, didactics and contents of the training programme (6-point scales, range 1; very bad to 6; very good), knowledge, interdisciplinary communication and patient satisfaction. <h3>Results</h3> 63 of the 64 physical therapists (98.4%) finished the education programme and were formally registered. Evaluation of the training programme measured directly after each part of it showed positive scores with respect to contents, didactics and organisation (all medians 5, ranges 2–6). Knowledge scores increased significantly directly following the training programme (p &lt; 0.001; Mann Whitney U). Measurements regarding the effectiveness on quality of care (interdisciplinary communication and patient satisfaction) will be completed in 2001. <h3>Conclusions</h3> The preliminary results indicate that setting up a system of networks and continuing education for physical therapists with respect to the treatment of patients with rheumatic diseases is feasible. The complete set of results will be available by the end of 2001. Further research will focus on the implementation of the system on a larger scale. Funded by The Health Research and Development Council of The Netherlands; ZON.
Combination of 5-Fluorouracil and N1, N11-diethylnorspermine markedly activates spermidine/spermine N1-acetyltransferase expression, depletes polyamines, and synergistically induces apoptosis in colon carcinoma cells
Authors: Woonyoung Choi, Eugene W. Gerner, Jheri Dupart, Latha Ramdas, Jennifer Carew, Lynsey Proctor, Peng Huang, Wei Zhang, Stanley R. Hamilton
Journal: Cancer Research (2005)

4951  Onconase (ONC), a new family of proteins isolated from the eggs and early embryos of the leopard frog, Rana pipiens, significantly improved tumor blood flow, tumor interstitial fluid pressure, and tumor oxygen level of MCaIV tumors (J. Surg. Oncol. 73: 164-171, 2000). This led us to consider the therapeutic effectiveness of ONC alone and ONC plus cisplatin (or carboplatin) on A549 human non-small cell lung cancer cells (NSCLC). Using a clonogenic assay, ONC alone significantly inhibited the tumor growth of A549 tumors (IC50 = 1 μg/ml). When cisplatin was simultaneously treated with ONC for 24 h, an enhanced efficacy of cisplatin was observed (SER=1.3). Similar efficacy was observed when cisplatin was added after ONC. However, when ONC was added after cisplatin, the enhanced efficacy of cisplatin was diminished. A similar tendency was also observed in combined treatments of ONC and carboplatin (SER=1.35). Using a growth delay assay, ONC alone (10 mg/ml) significantly retarded the A549 tumor growth by 15 days. Cisplatin alone (5 mg/kg) delayed tumor growth by 7 days. When two drugs were combined, the tumor growth delay was 25 days. Although body weight was decreased to 10-15% by either ONC or cisplatin (or carboplatin), it recovered to the control levels within 7 days post-treatment. By a dynamic contrast enhanced MRI using a diffusible MRI contrast agent (Gd-DPTA), we monitored the effect of ONC on perfusion of both the kidney and tumor. Changes in T1-relaxation time in the medulla and cortex of the kidney, and tumors were non-invasively monitored by MRI 1H-perfusion and 1H-density methods for 8 days post-treatment of ONC. T1-relaxation time in both medulla and cortex of the kidney was decreased at 1-2 days, but it returned to the original level at 4-8 days post-treatment of ONC. Currently, we are estimating the kinetic parameters from dynamic contrast-enhanced T1-weighted MRI data, including the volume transfer constant (Ktrans map & histogram) and the volume of extravascular space per unit volume of tissue (Ve map & histogram) from both the kidney and tumors. This investigation suggests important potential clinical uses for ONC.
Abstract 6442: Investigation of custom biomarkers on circulating tumor cells from clinical samples using RarePlex® Developer Kits
Authors: Edward Lo, Daniel Campton, Arturo Ramirez, Lillian Costandy, Brady Gardner, Ryan Houston, Heather Itamoto, Jeffery L. Werbin, VK Gadi, Tanisha Mojica, Alisa Clein, Celestia Higano, Daniel E. Sabath, Eric P. Kaldjian, Tad George
Journal: Cancer Research (2020)

Abstract Enumeration and phenotypic profiling of circulating tumor cells (CTCs) can give important information about tumor progression, presence of therapeutic targets, and metastatic potential. New and informative cancer-specific biomarkers are being discovered at a rapid pace, so there is a strong need for tools that enable investigator driven assays to best study and utilize these biomarkers. Through the RareCyte platform, we provide sensitive and specific assays that are optimized and validated for CTC enumeration and biomarker expression. RarePlex Developer Kits enable the addition of user-selected antibodies against biomarkers of interest to a CTC detection assay. Here we demonstrate the application of RarePlex Developer Kits to study the presence of a variety of cancer related biomarkers. Using the Developer strategy, we present results for several biomarkers, including HER2, ER, PR, EGFR, Ki67, AR, ARv7, PDL1, and PSMA. We also characterized clinical samples from prostate (AR and ARv7) and breast (HER2 and ER) cancer patients. The biomarkers demonstrated proper localization on or within model CTC control cells when using default antigen retrieval and fixation conditions. For each biomarker, fluorescence intensity cut-offs that segregated negative and positive cell lines were statistically defined to maximize classification accuracy. For clinical samples, breast and prostate cancer sample staining showed expected localization based on available clinical information. In conclusion, RarePlex Developer Kits provide a flexible tool for custom CTC assay development that enables researchers to develop assays in their own lab for characterization of phenotypic heterogeneity. Citation Format: Edward Lo, Daniel Campton, Arturo Ramirez, Lillian Costandy, Brady Gardner, Ryan Houston, Heather Itamoto, Jeffery L. Werbin, VK Gadi, Tanisha Mojica, Alisa Clein, Celestia Higano, Daniel E. Sabath, Eric P. Kaldjian, Tad George. Investigation of custom biomarkers on circulating tumor cells from clinical samples using RarePlex® Developer Kits [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6442.