tbuckley/cabot-search huggingface dataset:
Clinical Sequelae from Arterial Needle Puncture, Cannulation, and Incision
Authors: Jdmortensen
Journal: Circulation (1967)

A study of 3,193 arterial entries of various types disclosed 66 major complications and 321 minor complications for a total complication rate of 13%. The Seldinger technique of percutaneous arterial catheterization was followed by the highest incidence of complications, the percutaneous needle puncture method was associated with an intermediate complication rate, and the cutdown arteriotomy with suture repair resulted in the lowest complication rate. Utilizing the brachial artery as the entry site resulted in a significantly higher complication rate than utilizing other sites for entering the arterial tree did. Factors significantly increasing the risk of arterial entry include the existence of aortic valvular incompetence in the patient, systemic anticoagulation at the time of the arterial entry, and the presence of arteriosclerosis or hypertension in the patient.
Early Potent Antithrombotic Effect With Combined Aspirin and a Loading Dose of Clopidogrel on Experimental Arterial Thrombogenesis in Humans
Authors: YvesCadroy, Jean-PierreBossavy, ClaireThalamas, LucSagnard, KjellSakariassen, BernardBoneu
Journal: Circulation (2000)

Background—We conducted a double-blind, randomized, crossover study to assess the antithrombotic effects of the combination of aspirin (acetylsalicylic acid, ASA) and clopidogrel, with or without a loading dose, versus ASA alone in a model of arterial thrombosis in humans. Methods and Results—Eighteen male volunteers received the following 3 regimens for 10 days separated by a 1-month period: (1) 325 mg ASA daily, (2) 325 mg ASA+75 mg clopidogrel daily, (3) 325 mg ASA daily+300-mg clopidogrel loading dose on day 1 and +75 mg clopidogrel per day on days 2 to 10. The antithrombotic effect was measured 1.5, 6, and 24 hours after drug intake on day 1 and 6 hours after drug intake on day 10. Arterial thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel-plate perfusion chamber to native blood for 3 minutes at an arterial wall shear rate. Without a loading dose, clopidogrel+ASA developed an antithrombotic effect within 6 hours after the first intake. It was superior to tha...
Abstract 5422: TMPRSS2-ERG fusions confers efficacy of enzalutamide in an <i>in vivo</i> bone tumor growth model
Authors: Sreenivasa R. Chinni, Louie Semaan, Michael Cher
Journal: Cancer Research (2018)

Abstract Castrate Resistant Prostate Cancer (CRPC) is an advanced disease resistant to systemic anti-androgen therapies and resistance is primarily attributed to reactivation of AR through multiple mechanisms. TMPRSS2-ERG fusions have been shown to regulate AR signaling, interfere with pro-differentiation functions, and mediate oncogenic signaling. In fact, cooperation between AR and ERG drives invasive adenocarcinoma even in the castrate environment. We have recently shown that ERG regulates intra-tumoral androgen synthesis thereby facilitates AR function in CRPC disease. We hypothesize that enzalutamide treatment will be more effective in cells/tumors with TMPRSS2-ERG translocations because these tumors have increased AR signaling. In other words, AR blockade is likely to induce a greater treatment response in tumors with ERG gene fusions than in tumors without such fusions. ERG knockdown was performed with VCaP cells using lentiviral infections to generate VCaP ERGshRNA cells and control VCaP scr cells with scrambled shRNA. Cell-growth analysis was performed to determine the effect of enzalutamide. Luciferase tagged VCaP scr and shRNA infected cells were used in intra-tibial animal model for bone tumor growth analysis and enzalutamide treatment used to inhibit AR signaling in bone tumors. Reverse transcription, quantitative real-time PCR (RT-qPCR) was used to determine the expression of AR responsive genes and androgen biosynthetic enzyme genes; Western blotting (WB) samples, for ERG, AR and AKR1C3 in VCaP bone tumors. Enzalutamide inhibited VCaP scr more effectively than shERG cells. Analysis of AR responsive genes show that Enzalutamide treatment at 5 micro molar concentration inhibited 85-90% in VCaP Scr cells whereas these genes inhibited to lesser extent in VCaP shERG cells. In bone tumor growth experiment, VCaP ERG shRNA cells grown at slower than VCaP scr shRNA cells. Enzalutamide treatment resulted in a sever growth inhibition in VCaP scr shRNA cells compared to VCaP shERG cells. Androgen biosynthetic enzyme expression is lower VCaP shERG bone tumors compared to VCaP scr shRNA bone tumors and enzalutamide inhibited the enzyme expression in both types of tumors. These data suggest that ERG transcription factor regulates androgen biosynthetic enzyme expression and enzalutamide treatment is effective against VCaP bone tumors with an intact ERG expression, and knocking down ERG in VCaP cells leads lesser response for enzalutamide therapy. Citation Format: Sreenivasa R. Chinni, Louie Semaan, Michael Cher. TMPRSS2-ERG fusions confers efficacy of enzalutamide in an in vivo bone tumor growth model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5422.
MicroRNA-15a and MicroRNA-16 Impair Human Circulating Proangiogenic Cell Functions and Are Increased in the Proangiogenic Cells and Serum of Patients With Critical Limb Ischemia
Authors: GaiaSpinetti, OrazioFortunato, AndreaCaporali, SaranShantikumar, MicolMarchetti, MarcoMeloni, BettyDescamps, IlariaFloris, ElenaSangalli, RosaVono, EzioFaglia, ClaudiaSpecchia, GianfrancoPintus, PaoloMadeddu, CostanzaEmanueli
Journal: Circulation Research (2013)

Rationale:Circulating proangiogenic cells (PACs) support postischemic neovascularization. Cardiovascular disease and diabetes mellitus impair PAC regenerative capacities via molecular mechanisms that are not fully known. We hypothesize a role for microRNAs (miRs). Circulating miRs are currently investigated as potential diagnostic and prognostic biomarkers. Objective:The objectives were the following: (1) to profile miR expression in PACs from critical limb ischemia (CLI) patients; (2) to demonstrate that miR-15a and miR-16 regulate PAC functions; and (3) to characterize circulating miR-15a and miR-16 and to investigate their potential biomarker value. Methods and Results:Twenty-eight miRs potentially able to modulate angiogenesis were measured in PACs from CLI patients with and without diabetes mellitus and controls. miR-15a and miR-16 were further analyzed. CLI-PACs expressed higher level of mature miR-15a and miR-16 and of the primary transcript pri–miR-15a/16-1. miR-15a/16 overexpression impaired heal...
Abstract 1132: PAX6 drives cancer cells toward a stem like state via GLI-SOX2 signaling axis in lung adenocarcinoma
Authors: Akira Oki, Mohammad O. Hoque
Journal: Cancer Research (2018)

Abstract PAX6 is an essential transcription factor for embryonic stem cell maintenance, but its contribution to lung cancer stem cells (CSCs) remains unexplored. We demonstrate that PAX6 acts as an oncogene responsible for induction of cancer stemness properties and plays a biological role in tumor initiation and CSC expansion in lung adenocarcinoma (LUAD). Mechanistically, PAX6 activates Hedgehog-GLI signaling in a SMO-independent noncanonical manner, resulting in SOX2 upregulation directly by the binding of GLI to the proximal promoter region of the SOX2 gene. The overexpressed SOX2 enhances the expression of key pluripotent factors (OCT4 and NANOG) and suppresses differentiation lineage factors (HOPX and NKX2-1). Thus, PAX6 drives cancer cells toward a stem-like state via the GLI-SOX2 signaling axis in LUAD. In contrast, in the differentiated non-CSCs that represent most of the tumor cell population, PAX6 is transcriptionally silenced by its promoter methylation. In human lung cancer tissues, the positive linear correlations of PAX6 expression with GLI and SOX2 expression and its negative correlations with HOPX and NKX2-1 expression were observed. Therapeutically, the blockade of the PAX6-GLI-SOX2 signaling axis elicits a long-lasting therapeutic efficacy by limiting CSC expansion following chemotherapy. Our findings provide a rationale for targeting the PAX6-GLI-SOX2 signaling axis with chemotherapy as an effective therapeutic strategy. Citation Format: Akira Oki, Mohammad O. Hoque. PAX6 drives cancer cells toward a stem like state via GLI-SOX2 signaling axis in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1132.
Dupilumab does not affect correlates of vaccine-induced immunity: A randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis
Authors: Andrew Blauvelt, Eric L. Simpson, Stephen K. Tyring, Lisa A. Purcell, Brad Shumel, Christopher D. Petro, Bolanle Akinlade, Abhijit Gadkari, Laurent Eckert, Neil M.H. Graham, Gianluca Pirozzi, Robert Evans
Journal: Journal of the American Academy of Dermatology (2018)

The impact of dupilumab, an anti-interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown.To assess T-cell-dependent and T-cell-independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety.In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16.In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3% and 83.7%, respectively) and meningococcal polysaccharide (86.7% and 87.0%, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2% dupilumab and 34.8% placebo). Dupilumab improved key AD efficacy endpoints (P < .001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo.Patients' prior vaccination status was not available before enrollment.Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile.
译后评论：肥胖——影响健康的流行病
Authors: 王王姮
Journal: BMJ (2005)

随着我国城乡经济快速发展，人民生活水平明显提高，膳食结构中脂肪量增加，日常生活中运动量显著减少，使超重或肥胖人群比例日趋增高。随之，超重或肥胖使糖尿病、高脂血症、高血压、冠心病及脑卒中等患病率升高。在卫生部、科技部和国家统计局的领导下，2002年开展的“中国居民营养与健康状况调查”结果显示18岁及18岁以上人群中超重率为22．8％，肥胖率为7．1％。与10年前相比，超重率增加38．6％，肥胖率增加80．6％。糖尿病患病率2．60％，20岁以上大城市居民糖尿病患病率6．37％，中、小城市为3．89％，
Beyond the brain: do peripheral mechanisms develop impaired awareness of hypoglycemia?
Authors: Elizabeth R. Seaquist
Journal: Journal of Clinical Investigation (2018)

The mechanisms responsible for the development of the impaired awareness of hypoglycemia often seen in insulin-treated patients with diabetes remain uncertain, but cerebral adaptations to recurrent hypoglycemia are frequently hypothesized. In this issue of the JCI, Ma et al. demonstrate that neuropeptide Y (NPY) secretion from adrenal chromaffin cells persists during exposure to recurrent hypoglycemia and activation of the sympathetic nerves at the same time that epinephrine secretion is reduced. This results in the inhibition of tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis. These observations suggest that a peripheral mechanism downstream from the brain contributes to the development of impaired awareness of hypoglycemia.
Abstract 1059: EpCAM differentially expressed on circulating and disseminated tumor cells promotes tumor metastasis in breast cancer patients
Authors: Peter P. Lin, Junjian Li, Daisy Wang, Olivier Gires, Hongxia Wang
Journal: Cancer Research (2018)

Abstract To investigate the role of EpCAM expressed on both circulating tumor cells (CTCs) in peripheral blood and disseminated tumor cells (DTCs) in bone marrow with respect to tumor metastases, the integrated subtraction enrichment and immunostaining-FISH (SE-iFISH) was performed to quantify, phenotypically and karyotypically characterize cytogenetically abnormal CTCs and DTCs expressing EpCAM in breast cancer patients. In a cohort of 34 recruited late stage patients, consisting of 32 metastatic and 2 non-metastatic subjects, the average number of detected CTCs in metastatic vs non-metastatic patients was 25 and 18 cells, respectively. Among those CTCs in metastatic subjects, 23.4% of them showed EpCAM+, whereas none of EpCAM+ CTCs was detected in non-metastatic patients. There were total of 49 CTC clusters detected in metastatic patients, and 33% of those clusters were EpCAM+, however, only 3 CTC clusters were found in non-metastatic patients, and none of them was EpCAM+. In the case of DTCs, the average number of 2224 and 364 DTCs per subject was detected in metastatic vs non-metastatic subjects, with EpCAM+ ratio of 66.53% in metastatic and 8% in non-metastatic patients. Analysis of DTC clusters indicated that the average of 226 and 21 DTC clusters/subject were identified in metastatic and non-metastatic patients, respectively, and metastatic subjects showed 62% of DTC clusters EpCAM+, whereas 37% of clusters were EpCAM+ in non-metastatic patients. Comparing to the breast cancer serum biomarker CA15-3 detected in 32 metastatic cancer patients, showing positivity (≥28 ng/ml) of only 41% (13 out of 32), both CTCs (≥5) and DTCs (≥5) had a positivity rate of 81 (26 out of 32) and 97% (31 out of 32), respectively. Obtained results indicated that EpCAM+ CTCs and DTCs are reliable markers in terms of evaluating therapeutic efficacy and predicting cancer patients' prognosis. Citation Format: Peter P. Lin, Junjian Li, Daisy Wang, Olivier Gires, Hongxia Wang. EpCAM differentially expressed on circulating and disseminated tumor cells promotes tumor metastasis in breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1059.
Abstract 5572: Circulating tumor cells: The tumor trail left in the blood
Authors: Arutha Kulasinghe, Chris Perry, Liz Kenny, Tony Blick, Majid Warkiani, Ian Vela, Ken O'Byrne, Jean-Paul Thiery, Erik Thompson, Colleen Nelson, Chamindie Punyadeera
Journal: Cancer Research (2018)

Abstract Background: Metastasis in HNC patients is reflected by measurable levels of circulating tumor cells (CTCs) in the peripheral blood of cancer patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an individual patient. For patients without CTCs at presentation, the detection of CTCs in the blood and analysis of biomarkers within them provide an opportunity to identify patients "at risk" of developing overt metastasis, accelerating targeted treatment in addition to routing care with the clear aim of improving cure. Methods: Our study aimed to assess whether CTCs from the blood of HNC patients attending the Princess Alexandra Hospital and Royal Brisbane and Women's Hospital provided early cues of distant metastases (n=250). Results: With significant advances in CTC isolation technologies, we could demonstrate a higher CTC capture efficiency using epitope-independent platforms. By assessment of single and clustered CTCs, our data showed that HNC patients can be identified 4-6 months prior to developing clinical/radiographically evident metastasis. In these patients, a window for treatment escalation could become a possibility. In a proof-of-principle study, using novel culture formulations and hypoxic conditions (1-2% O2), we were able to demonstrate, for the first time, short-term patient-derived CTC cultures ex vivo from 7/18 HNC samples (4/7 HPV-positive, oropharyngeal) in a clinically relevant time period. Recent advancements have shown that PD-1 immune checkpoint therapies have durable responses in metastatic HNC patients that fail 1st- and 2nd-line therapy. Our preliminary data suggest PD-L1 is frequently expressed on HNC CTCs, and an immunoscore may be able to stratify patients likely to respond to immunotherapy. Conclusion: Expanding CTCs outside the patient's body allows for the recapitulation of the molecular diversity present within the tumor, understanding the disease progression and testing of therapies. Patients with a high percentage of PD-L1+ CTCs could be potential candidates for anti-PD-L1 therapy, a promising new immunotherapy. Citation Format: Arutha Kulasinghe, Chris Perry, Liz Kenny, Tony Blick, Majid Warkiani, Ian Vela, Ken O'Byrne, Jean-Paul Thiery, Erik Thompson, Colleen Nelson, Chamindie Punyadeera. Circulating tumor cells: The tumor trail left in the blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5572.
Study of Luminal Coronary Collateral Circulation in the Beating Canine Heart
Authors: Ottohauswirth
Journal: Circulation Research (1969)

The action of halothane on sinoatrial, ventricular, and Purkinje fibers was studied by means of intracellular microelectrodes. Rabbit atrial fibers were not very sensitive to even high (2%) concentrations of halothane. Sheep Purkinje fibers showed a significant hyperpolarization from 82 mv to 87 mv, a marked shortening of the duration of the action potential from 370 msec to 233 msec, and a diminution of the overshoot from 30 mv to 21 mv under the influence of 1% halothane. The rate of rise was now significantly rchanged with this concentration. In the presence of 2% halothane the resting potential did not differ significantly from the value obtained with 1% halothane. The duration of the action potential and of the refractory period were further diminished to 165 msec and to 109 msec, respectively. The rate of rise was now significantly reduced to 245 v/sec and the overshoot further decreased to 17 mv. Conduction time was increased by about 20% with 1% halothane and more than twofold with 2% halothane. V...
Abstract LB-314: The good drug, the bad barrier and the handy peptide: Improved treatment of experimental melanoma brain metastases using a synthetic peptide
Authors: Synnøve Nymark Aasen, Heidi Espedal, Christopher Florian Holte, Olivier Keunen, Tine Veronica Karlsen, Olav Tenstad, Habib Baghirov, Dag Erlend Olberg, Rolf Bjerkvig, Gobinda Sarkar, Frits Thorsen
Journal: Cancer Research (2018)

Abstract Patients with brain metastases usually have a poor prognosis. Regardless of the constant progress in novel drug establishments, a crucial obstacle is the delivery of drugs across the blood brain barrier (BBB) and into the metastatic neoplasms. Different study designs to achieve temporary BBB opening have previously been studied. Here, we describe a synthetic peptide termed K16ApoE, which is able to transiently open the BBB for drug-delivery into experimental brain metastases.We conducted a systemic study of the ability of the peptide to open the BBB by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in nonobese diabetic/severe combined (nod/scid) mice. Further, we studied the mechanisms of the peptide using flow cytometry, electron microscopy and dynamic positron emission tomography (PET). The biodistribution of the peptide was studied in blood plasma and organs using I-125 labeled K16ApoE. Finally, a treatment study using the peptide in combination with the B-RAF inhibitor dabrafenib was conducted.An opening of the BBB for up to 60 mins was clearly demonstrated by DCE-MRI. Microscopy showed that the peptide disrupted brain endothelial cell monolayers by reducing the barrier properties of the cells. The treatment study demonstrated that the group of animals receiving K16ApoE followed by dabrafenib had smaller tumor volumes than the other two animal groups.In conclusion, the synthetic K16ApoE peptide in combination with dabrafenib decreased the number of experimental brain metastases. Thus, the current strategy could have the potential to improve the treatment of patients with brain metastatic disease. &amp;lt;!–EndFragment–&amp;gt; Citation Format: Synnøve Nymark Aasen, Heidi Espedal, Christopher Florian Holte, Olivier Keunen, Tine Veronica Karlsen, Olav Tenstad, Habib Baghirov, Dag Erlend Olberg, Rolf Bjerkvig, Gobinda Sarkar, Frits Thorsen. The good drug, the bad barrier and the handy peptide: Improved treatment of experimental melanoma brain metastases using a synthetic peptide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-314.
Molecular Mechanisms of Endothelin-1–Induced Cell-Cycle Progression
Authors: EtsuSuzuki, DaisukeNagata, MasaoKakoki, HiroshiHayakawa, AtsuroGoto, MasaoOmata, YasunobuHirata
Journal: Circulation Research (1999)

Abstract—Although it is well established that endothelin-1 (ET-1) has not only vasoconstrictive effects but also mitogenic effects, which seem to be implicated in vascular remodeling, little is known about the molecular mechanisms by which ET-1 induces cell-cycle progression. In this study, we examined the effects of ET-1 on the cell-cycle regulatory machinery, including cyclins, cyclin-dependent kinase (cdk), and cdk inhibitors in NIH3T3 cells. ET-1 increased cyclin D1 protein (5.1±1.9-fold increase, 8 hours after stimulation, P<0.05), cdk4 kinase activity (2.8±0. 5-fold increase, 12 hours after stimulation, P<0.01), and cdk2 kinase activity (2.1±0.4-fold increase, 16 hours after stimulation, P<0.05) in a time- and dose-dependent manner. ET-1–induced increase in cyclin D1 protein, and cdk4 kinase activity was not significantly inhibited by an inhibitor of the mitogen-activated protein kinase kinase 1/2, PD98059, nor by the protein kinase C inhibitor calphostin C, whereas ET-1–induced upregulation of cycl...