tbuckley/cabot-search huggingface dataset:
Dancing Dorsal Quadrilaterals—Organic or Functional?
Authors: Anjali Chouksey, Sanjay Pandey, Mark Hallett
Journal: JAMA Neurology (2019)

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Centralization of High-Risk Cancer Surgery Within Existing Hospital Systems
Authors: Kyle H. Sheetz, Justin B. Dimick, Hari Nathan
Journal: Journal of Clinical Oncology (2019)

Centralization is often proposed as a strategy to improve the quality of certain high-risk health care services. We evaluated the extent to which existing hospital systems centralize high-risk cancer surgery and whether centralization is associated with short-term clinical outcomes.We merged data from the American Hospital Association's annual survey on hospital system affiliation with Medicare claims to identify patients undergoing surgery for pancreatic, esophageal, colon, lung, or rectal cancer between 2005 and 2014. We calculated the degree to which systems centralized each procedure by calculating the annual proportion of surgeries performed at the highest-volume hospital within each system. We then estimated the independent effect of centralization on the incidence of postoperative complications, death, and readmissions after accounting for patient, hospital, and system characteristics.The average degree of centralization varied from 25.2% (range, 6.6% to 100%) for colectomy to 71.2% (range, 8.3% to 100%) for pancreatectomy. Greater centralization was associated with lower rates of postoperative complications and death for lung resection, esophagectomy, and pancreatectomy. For example, there was a 1.1% (95% CI, 0.8% to 1.4%) absolute reduction in 30-day mortality after pancreatectomy for each 20% increase in the degree of centralization within systems. Independent of volume and hospital quality, postoperative mortality for pancreatectomy was two times higher in the least centralized systems than in the most centralized systems (8.9% v 3.7%, P < .01). Centralization was not associated with better outcomes for colectomy or proctectomy.Greater centralization of complex cancer surgery within existing hospital systems was associated with better outcomes. As hospitals affiliate in response to broader financial and organization pressures, these systems may also present unique opportunities to improve the quality of high-risk cancer care.
GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism
Authors: Stephen G. Young, Loren G. Fong, Anne P. Beigneux, Christopher M. Allan, Cuiwen He, Haibo Jiang, Katsuyuki Nakajima, Muthuraman Meiyappan, Gabriel Birrane, Michael Ploug
Journal: Cell Metabolism (2019)
TCT-805 Impact of Pulmonary Hypertension on Outcome after Transcatheter Aortic Valve Implantation
Authors: Alexander Lauten, Ralf Zahn, Axel Linke, Sack Stefan, Markus Ferrari, Horst Sievert, Eberhard Grube, Ulrich Gerckens, Jochen Senges, Hans Figulla
Journal: Journal of the American College of Cardiology (2012)
Abstract 775: MicroRNA-1205 regulation of FRYL in neuroendocrine prostate cancer
Authors: Michelle K. Naidoo, Olorunseun Ogunwobi
Journal: Cancer Research (2019)

Abstract High mortality rates of prostate cancer (PCa) are associated with metastatic castration-resistant prostate cancer (mCRPC) due to the maintenance of androgen receptor (AR) signaling despite androgen deprivation therapies (ADTs). Resistance to second generation ADTs further leads to progression to neuroendocrine PCa (NEPC), which is observed in nearly 1 in 5 men with mCRPC and is associated with low survival rates. The molecular mechanisms of progression to NEPC are, however, still unclear. Further understanding of molecular mechanisms of NEPC is critical to improving patient outcomes. The 8q24 chromosomal locus is a highly susceptible PCa region that carries high risk genetic variants associated with PCa incidence. This region also carries frequent amplifications of the PVT1 gene, a non-protein coding gene that encodes microRNA-1205 (miR-1205). We have previously reported that miR-1205 is underexpressed in PCa tissues in comparison to normal prostate tissue, and is also underexpressed in vitro in CRPC cells in comparison to non-CRPC cells. We also demonstrated that exogenous miR-1205 significantly inhibited tumor volume in CRPC tumor xenografts in mice, and that miR-1205 directly targets the putative oncogene, Fry-like (FRYL). FRYL is predicted to regulate dendritic branching leading to the hypothesis that FRYL plays a role in NEPC. To test this hypothesis, we first examined miR-1205 expression levels in PCa tissues with Gleason scores ≥8 and &amp;lt;8, using a cohort of histologically confirmed tissues. We observed that miR-1205 was underexpressed in tumors with Gleason scores ≥8 when compared to those with Gleason scores &amp;lt;8, suggesting that miR-1205 underexpression is characteristic of high grade PCa. To examine miR-1205 regulation of FRYL specifically in NEPC, we analyzed RNA sequencing data from a cohort of histologically confirmed NEPC tissues and prostate adenocarcinoma tissues obtained from TCGA via cBioPortal. We observed increased FRYL mRNA expression in NEPC tissues when compared to prostate adenocarcinoma tissues, indicating a putative oncogenic role of FRYL in NEPC. In vitro data revealed that FRYL mRNA was overexpressed and miR-1205 was significantly underexpressed after fourteen days of induced NEPC differentiation using LNCaP cells when compared to undifferentiated LNCaP cells. In conclusion, these data suggest that miR-1205 regulation of FRYL may be a critical mechanism in NEPC. Further understanding this mechanism may provide novel insights into effective therapeutic strategies for NEPC. Citation Format: Michelle K. Naidoo, Olorunseun Ogunwobi. MicroRNA-1205 regulation of FRYL in neuroendocrine prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 775.
Abstract 18349: Long-term Results Comparing Recurrent Neurological Event Rates of Three Different Devices for Percutaneous PFO-Closure
Authors: Marius Hornung, Jennifer Franke, Stefan Bertog, Margaret Taaffe, Horst Sievert
Journal: Circulation (2012)

Background: Percutaneous patent foramen ovale (PFO)-closure for secondary stroke prevention is discussed controversially, and long-term data comparing different closure devices are very limited. Methods: This is a prospective trial comparing procedural complications and long-term results after PFO closure in 660 patients with cryptogenic stroke randomized to three different closure devices (Amplatzer, CardioSEAL-STARflex and Helex occluder, 220 patients per group). The primary endpoint was defined as recurrent cerebral ischemia (stroke, TIA or Amaurosis fugax) or death from neurological cause during 5 year follow-up (including periprocedural events). Results: The primary endpoint occured in 25 patients (3.8%; 10 TIAs, 12 strokes and 3 cases of cerebral death). Compared with the Amplatzer (1.4%; 2 strokes, 1 cerebral death), significantly more events (p=0.02) occurred in the CardioSEAL-STARflex group (6%; 6 TIAs, 6 strokes, 1 cerebral death). The event rate in the Helex group was 4% (4 TIAs, 4 stroke, 1 cerebral death). The procedure was complicated by pericardial tamponade requiring surgery in 1 patient (Amplatzer device) and device embolization in 3 patients (all Helex devices). Device-associated thrombus formation was detected in 12 cases (11 CardioSEAL-STARflex, 1 Helex, 0 Amplatzer; p&lt;0.0001), of which 2 required surgery. Complete closure after single device implantation was more common with the Amplatzer device than with the CardioSEAL-STARflex or Helex occluders. Conclusions: The periprocedural and long-term neurological event rates are low regardless of the device used. The recurrent neurological event rate was significantly higher after CardioSEAL-STARflex than after Amplatzer or Helex implantation. This has important implications regarding the interpretation of trials comparing PFO closure to medical management.
Sequentially responsive biomimetic nanoparticles with optimal size in combination with checkpoint blockade for cascade synergetic treatment of breast cancer and lung metastasis
Authors: Wenqi Yu, Xueqin He, Zhihang Yang, Xiaotong Yang, Wei Xiao, Rui Liu, Rou Xie, Lin Qin, Huile Gao
Journal: Biomaterials (2019)
Abstract 616: Literature review and meta-analyses of the prevalence of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) for colorectal (CRC), gastric (GC), endometrial (EC) and ovarian cancers (OC) in Chinese population
Authors: Xiaoqiao Liu, Jiaqi Fan, Kai-Li Liaw, Mo Xu, Yu Zhou, Mayur Amonkar, Gefei Zeng
Journal: Cancer Research (2019)

Abstract Purpose Given the high prevalence of MSI-H/dMMR in gastrointestinal and gynecologic cancers we systematically collected published studies and investigated its’ prevalence for Chinese CRC, GC, EC, OC subjects to better understand the size of potential target population available for pembrolizumab treatment in China. Experimental Design Both Chinese and English literature were searched in WanFang and PubMed database respectively. Studies were included if they assessed prevalence of MSI-H by PCR based method investigating 5 markers from NCI or Promega panel, and/or dMMR by immunohistochemistry (IHC) for all 4 MMR proteins. Studies focusing only on hereditary or sporadic cancer were filtered out. Among eligible studies, meta-analyses (DerSimonian Laird random effect model) were performed on the proportion of MSI-H/dMMR for each tumor type by R metafor package. Prevalence for advanced stage (III/IV) were also extracted if the data were available. Results For CRC, the prevalence of MSI-H estimated from 11 studies (13.7% [10.2-17.6%]) was similar as that of dMMR from 22 studies (14.6% [12.3-17.1%]). Pooled prevalence of MSI-H/dMMR from 32 studies (12,341 subjects) was estimated at 14.1% (12.2-16.1%), and 9.7% (7.2-12.5%) from 17 studies (3,933 subjects) for advanced stage CRC. The prevalence estimation for GC, EC and OC were 18.5%, 26% and 12.9% respectively. Further, the prevalence in advanced stage cancer, regardless of the cancer type, tended to be numerically lower than the all-stage combined prevalence. Conclusions This was the first study comprehensively integrating published studies to estimate prevalence of MSI-H/dMMR across 4 main tumor types for Chinese subjects. The meta-analysis indicated the prevalence of MSI-H/dMMR for all or advanced stage Chinese cancer patients might be similar as that for western population. Citation Format: Xiaoqiao Liu, Jiaqi Fan, Kai-Li Liaw, Mo Xu, Yu Zhou, Mayur Amonkar, Gefei Zeng. Literature review and meta-analyses of the prevalence of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) for colorectal (CRC), gastric (GC), endometrial (EC) and ovarian cancers (OC) in Chinese population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 616.
Abstract 4387: hnRNP Q1 promotes cell proliferation and tumorigenesis by translationally up-regulating cell cycle-related genes through the EGF pathway
Authors: Liang-Yi Hung
Journal: Cancer Research (2019)

Abstract Heterogeneous nuclear ribonucleoprotein (hnRNP) Q1, an RNA-binding protein, has been reported as overexpressing in cancer cells. However, the role of hnRNP Q1 in tumorigenesis remains unclear. By using RNA-immunoprecipitation (IP) assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnNRP Q1 can up-regulate Aurora-A and many spindle assembly checkpoint (SAC) proteins, but not alter their mRNA levels, through enhancing translational efficiency by interacting with the mRNA 5’-UTR. Ribosomal S6-IP and ribosomal profiling assay further confirmed the translational regulation of these mRNAs by hnRNP Q1. Stimulation with epidermal growth factor (EGF) enhances both binding between hnRNP Q1 and these mRNAs as well as the efficacy of the hnRNP Q1-induced translation of these mRNAs. EGF/hnRNP Q1-induced translation is mediated by the mTOR and ERK pathways. In addition, hnRNP Q1 overexpression is positively correlated with the levels of Aurora-A and these SAC genes in human colorectal cancer tissues. Taken together, our data suggest that hnRNP Q1 plays an important role in translationally regulating the expression of Aurora-A and a group of cell cycle-related genes, which increases cell proliferation and contributes to tumorigenesis in colorectal cancer. It may thereby contribute to tumorigenesis by translationally up-regulating these genes in colorectal cancer. Citation Format: Liang-Yi Hung. hnRNP Q1 promotes cell proliferation and tumorigenesis by translationally up-regulating cell cycle-related genes through the EGF pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4387.
Abstract 16844: Increased Circulating Levels of MiRNA-21 Mirrors Disease Activity in Rats With Monocrotaline-Induced Pulmonary Arterial Hypertension
Authors: Kenny Schlosser, Yupu Deng, Duncan J Stewart
Journal: Circulation (2013)

BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNA molecules that control gene expression by guiding the degradation or translational inhibition of cognate mRNA targets. To date, a small numbe...
Caveolin-1 selectively regulates microRNA sorting into microvesicles after noxious stimuli
Authors: Heedoo Lee, Chunhua Li, Yang Zhang, Duo Zhang, Leo E. Otterbein, Yang Jin
Journal: The Journal of Experimental Medicine (2019)

Emerging evidence suggests that extracellular vesicle (EV)–containing miRNAs mediate intercellular communications in response to noxious stimuli. It remains unclear how a cell selectively sorts the cellular miRNAs into EVs. We report that caveolin-1 (cav-1) is essential for sorting of selected miRNAs into microvesicles (MVs), a main type of EVs generated by outward budding of the plasma membrane. We found that cav-1 tyrosine 14 (Y14)–phosphorylation leads to interactions between cav-1 and hnRNPA2B1, an RNA-binding protein. The cav-1/hnRNPA2B1 complex subsequently traffics together into MVs. Oxidative stress induces O-GlcNAcylation of hnRNPA2B1, resulting in a robustly altered hnRNPA2B1-bound miRNA repertoire. Notably, cav-1 pY14 also promotes hnRNPA2B1 O-GlcNAcylation. Functionally, macrophages serve as the principal recipient of epithelial MVs in the lung. MV-containing cav-1/hnRNPA2B1 complex-bound miR-17/93 activate tissue macrophages. Collectively, cav-1 is the first identified membranous protein that directly guides RNA-binding protein into EVs. Our work delineates a novel mechanism by which oxidative stress compels epithelial cells to package and secrete specific miRNAs and elicits an innate immune response.
Abstract 3842: Co-targeting BET and MEK as salvage therapy for MAPKi and checkpoint inhibitor resistant melanoma
Authors: Jessie Villanueva, Ileabett M. Echevarria-Vargas, Patricia I. Reyes-Uribe, Adam Guterres, Amruta Ronghe, Delaine M. Zayas-Bazan Burgos, Qin Liu, Xiaowei Xu, David W. Speicher
Journal: Cancer Research (2019)

Abstract Despite novel therapies for melanoma, drug resistance remains a significant hurdle to achieving optimal responses. NRAS mutant melanoma is an archetype of therapeutic challenges in the field, which we used to test drug combinations to avert drug resistance. We show that the BET family member BRD4 is expressed at high levels in NRAS-mutant melanoma, and that high levels of BRD4 are associated with poor patient survival. Combining BET and MEK inhibitors synergistically curbed the growth of NRAS mutant melanoma and prolonged the survival of mice bearing tumors refractory to MAPK inhibitors and immunotherapy. Transcriptomic analysis revealed that combining BET and MEK inhibitors mitigated a MAPK- and checkpoint-inhibitor resistance transcriptional signature, downregulated the transcription factor TCF19, and induced apoptosis. Notably, TCF19 levels were downregulated in post-treatment biopsies from patients that responded to targeted or immunotherapies. In contrast, TCF19 levels were upregulated in tumor samples from non-responder patients. Furthermore, global proteomic analysis of PDX derived from patients resistant to immune checkpoint inhibitor indicate that the major downstream effects of concurrent BET and MEK inhibition is lipid metabolism. We are investigating the impact and mechanism whereby lipids modulate therapy response. Together our studies demonstrate that co-targeting MEK and BET can offset therapy resistance, offering a potential salvage strategy for melanomas with no other therapeutic options, and possibly other treatment-resistant tumor types. Citation Format: Jessie Villanueva, Ileabett M. Echevarria-Vargas, Patricia I. Reyes-Uribe, Adam Guterres, Amruta Ronghe, Delaine M. Zayas-Bazan Burgos, Qin Liu, Xiaowei Xu, David W. Speicher. Co-targeting BET and MEK as salvage therapy for MAPKi and checkpoint inhibitor resistant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3842.
New colorectal endoscopic submucosal dissection technique using a single tunnel: the “gateway” method
Authors: Akiko Ohno, Atsushi Kato, Mitsunori Kusuhara, Naohiko Miyamoto, Kensuke Arai, Yosuke Tsuji, Tadakazu Hisamatsu
Journal: Endoscopy (2019)

Recently, a single-tunnel endoscopic submucosal dissection (ESD) technique has been reported to be effective for large colorectal tumors [1] [2] [3]. However, even with this technique, ESD for a large colorectal tumor is sometimes difficult when working against gravity. We report a novel method that makes it possible to apply sufficient traction in the single-tunnel technique even when working against gravity ([Video 1]).
Abstract 1460: Generation of a novel, allogeneic cell-based, Gp96-Ig/OX40L cancer vaccine, improves anti-tumor immunity and long-term memory T-cell generation
Authors: Vikas Tahiliani, Jayalakshmi Miriyala, Patrick Dillon, Jason Rose, Louise Giffin, Jeff Hutchins, Matthew M. Seavey
Journal: Cancer Research (2019)

Abstract Our technology is focused on developing a next generation cellular vaccine platform – referred to as ComPACT (COMbination Pan-Antigen Cytotoxic Therapy), that incorporates a tumor antigen chaperone (gp96-Ig) with T-cell costimulation (OX40L-Ig), into a single tumor cell line that secretes both. Viagenpumatucel-L (HS-110; ImPACT), a human lung adenocarcinoma cell line, stably transfected to express gp96-Ig is being tested in a phase 1/2 clinical trial (NCT#02439450) with checkpoint inhibition for NSCLC. A similar line is being generated that will complement HS-110, providing costimulation in the form of secreted OX40-Ig (HS-130). To model how the addition of human HS-130 to HS-110 may impact anti-tumor immune responses, we generated mouse surrogates of these human lines and established an analogous system, that treats tumor-bearing animals with tissue-matched irradiated cancer cell lines (B16F10) expressing gp96-Ig (mHS-110) and OX40L-Ig (mHS-130) both expressing ovalbumin, as our model tumor-associated antigen. Single dose vaccination with mHS-110 identified that 1 to 10 million cells (290 ng to 2,900 ng of secreted gp96-Ig) provided sufficient anti-tumor CD8+ T-cell expansion, in vivo (*p&amp;lt;0.01; 1-way ANOVA), with the greatest expansion observed on day 7, post-immunization. To identify the best ratio of mHS-110 to mHS-130; a dose ratio study was performed. Fixed numbers of mHS-110 (1 million cells, 290 ng of secreted gp96-Ig) were matched with different ratios of mHS-130. Similar to our single dose vaccination study, our results demonstrated that the peak CD8+ T-cell expansion occurred on day 7 post-immunization, and that the addition of mHS-130 further boosted anti-tumor CD8+ T-cell expansion by 3-fold when the ratios of mHS-110 to mHS-130 were at a 1-to-1 ratio (290 ng of secreted gp96-Ig to 290 ng of secreted OX40L-Ig) (*p&amp;lt;0.05, Mann-Whitney). These animals were subsequently boosted 14-days post-immunization, and we similarly found that the 1-to-1 ratio of mHS-110 to mHS-130 gave the maximum expansion of CD8+ T cell responses, peaking on day 21 and contracting thereafter (*p&amp;lt;0.05; Mann-Whitney). Importantly, these ratios led to high frequencies of IFNγ+ antigen-specific CD8+ T cells at both priming and boosting, which enhanced rejection of established B16F10 tumors and increased overall survival. Citation Format: Vikas Tahiliani, Jayalakshmi Miriyala, Patrick Dillon, Jason Rose, Louise Giffin, Jeff Hutchins, Matthew M. Seavey. Generation of a novel, allogeneic cell-based, Gp96-Ig/OX40L cancer vaccine, improves anti-tumor immunity and long-term memory T-cell generation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1460.