tbuckley/cabot-search huggingface dataset:
Is the blood–brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data
Authors: Jann N Sarkaria, Leland S Hu, Ian F Parney, Deanna H Pafundi, Debra H Brinkmann, Nadia N Laack, Caterina Giannini, Terence C Burns, Sani H Kizilbash, Janice K Laramy, Kristin R Swanson, Timothy J Kaufmann, Paul D Brown, Nathalie Y R Agar, Evanthia Galanis, Jan C Buckner, William F Elmquist
Journal: Neuro-Oncology (2017)

The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast material in essentially all GBM has popularized a belief that the BBB is uniformly disrupted in all GBM patients so that consideration of drug distribution across the BBB is not relevant in designing therapies for GBM. However, contrary to this view, overwhelming clinical evidence demonstrates that there is also a clinically significant tumor burden with an intact BBB in all GBM, and there is little doubt that drugs with poor BBB permeability do not provide therapeutically effective drug exposures to this fraction of tumor cells. This review provides an overview of the clinical literature to support a central hypothesis: that all GBM patients have tumor regions with an intact BBB, and cure for GBM will only be possible if these regions of tumor are adequately treated.
細胞外マトリックス蛋白質のN末端特異的共役2-ピリジンカルボキサルデヒド官能化ポリアクリルアミドヒドロゲル【Powered by NICT】
Authors: P Lee Jessica, Kassianidou Elena, I MacDonald James, B Francis Matthew, Kumar Sanjay
Journal: Biomaterials (2016)
Hidden heritability due to heterogeneity across seven populations
Authors: Felix C. Tropf, S. Hong Lee, Renske M. Verweij, Gert Stulp, Peter J. van der Most, Ronald de Vlaming, Andrew Bakshi, Daniel A. Briley, Charles Rahal, Robert Hellpap, Anastasia N. Iliadou, Tõnu Esko, Andres Metspalu, Sarah E. Medland, Nicholas G. Martin, Nicola Barban, Harold Snieder, Matthew R. Robinson, Melinda C. Mills
Journal: Nature Human Behaviour (2017)
A Phase II Study of Pomalidomide, Daily Low Dose Oral Cyclophosphamide, and Dexamethasone in Relapsed/Refractory Multiple Myeloma
Authors: Ajai Chari, Hearn Jay Cho, Samir Parekh, Kenneth Lau, Gillian Morgan, Donna Catamero, Melissa Cortes, Meredith Curtis, Juliet Escalon, Erika Florendo, Daniel Verina, Nadege Stevens, Elaine Chan, Katarzyna Garcia, Lisa La, Marisa Shields, Gina Strumolo, Sundar Jagannath
Journal: Blood (2016)
Abstract 12150: Molecular Network Analysis Identifies NEDD9 as a Critical Node Regulating Vascular Fibrosis in Pulmonary Arterial Hypertension
Authors: Thomas E Stephens, Rui-Sheng Wang, Andriy Samokhin, Minwei Cao, Elena Arons, Sara O Vargas, Joseph Loscalzo, Jane A Leopold, Bradley A Maron
Journal: Circulation (2016)

Vascular fibrosis in pulmonary arterial hypertension (PAH) is associated with increased morbidity. In PAH, elevated levels of aldosterone (ALDO) increase fibrillar collagen in pulmonary artery endothelial cells (PAECs). However, ALDO also promotes adaptive fibrosis in skin wound healing, suggesting that cell type-specific pathways regulated by ALDO distinguish fibrosis subtypes. To explore this concept further, published mRNA array data were used to model an interactome of fibrosis-related genes. Betweeness centrality analysis identified the Crk-associated protein NEDD9 as a critical ALDO-regulated node distinguishing vascular from dermal fibrosis (P=7.5x10 -7 vs. random network). To validate this observation, PAECs and dermal microvascular ECs were treated with ALDO (10 -7 mol/L) or vehicle control (V) for 24 hr and NEDD9 levels were analyzed by immunoblot. Compared to V-treated cells, ALDO increased NEDD9 expression in PAECs (46 ± 12 vs. 90 ± 7 a.u., P&lt;0.05) but not dermal microvascular ECs (P=NS). To determine the relevance of NEDD9 to fibrosis in PAH, anti-NEDD9 immunohistochemistry was performed on explanted lung tissue from patients. Compared to controls, PAH patients had increased pulmonary arteriole NEDD9 (32 ± 2.8 vs. 69 ± 12 a.u., P&lt;0.05), which correlated with collagen deposition levels assessed by Gomori trichrome stain (r=0.73, P&lt;0.02) and was confirmed by confocal microscopy imaging demonstrating increased overlap between collagen III and NEDD9 expression in PAH pulmonary arterioles. We next analyzed the functional effect of NEDD9 on ALDO-induced collagen III in PAECs in vitro . Compared to V-treated cells, ALDO increased collagen III expression (117 ± 16 vs. 225 ± 34 a.u., P&lt;0.01) and the number of Gomori stain positive PAECs (2.1 ± 0.8 vs. 8.1 ± 0.6 cells/h.p.f., P&lt;0.01). By contrast, si-NEDD9 decreased collagen III and fibrosis in ALDO-treated cells by 81% (P&lt;0.03) and 70.5% (P&lt;0.01), respectively. Overall, we used a systems approach to demonstrate NEDD9 targeting by ALDO as a key mechanism defining pathogenic fibrosis. Identifying fibrillar collagen regulation by NEDD9 in PAECs may have novel therapeutic implications for patients with PAH and other diseases characterized by pulmonary vascular fibrosis.
Poly(2-ethyl-2-oxazoline) conjugates with doxorubicin for cancer therapy: In vitro and in vivo evaluation and direct comparison to poly[N-(2-hydroxypropyl)methacrylamide] analogues
Authors: Ondrej Sedlacek, Bryn D. Monnery, Jana Mattova, Jan Kucka, Jiri Panek, Olga Janouskova, Anita Hocherl, Bart Verbraeken, Maarten Vergaelen, Marie Zadinova, Richard Hoogenboom, Martin Hruby
Journal: Biomaterials (2017)
Report of the NIH Panel To Define Principles of Therapy of HIV Infection*
Journal: Annals of Internal Medicine (1998)

Recent research advances have afforded substantially improved understanding of the biology of human immunodeficiency virus (HIV) infection and the pathogenesis of the acquired immunodeficiency syndrome (AIDS). With the advent of sensitive tools for monitoring HIV replication in infected persons, the risk of disease progression and death can be assessed accurately and the efficacy of anti-HIV therapies can be determined directly. Furthermore, when used appropriately, combinations of newly available, potent antiviral therapies can effect prolonged suppression of detectable levels of HIV replication and circumvent the inherent tendency of HIV to generate drug-resistant viral variants. However, as antiretroviral therapy for HIV infection has become increasingly effective, it has also become increasingly complex. Familiarity with recent research advances is needed to ensure that newly available therapies are used in ways that most effectively improve the health and prolong the lives of HIV-infected persons. To enable practitioners and HIV-infected persons to best use rapidly accumulating new information about HIV disease pathogenesis and treatment, the Office of AIDS Research of the National Institutes of Health sponsored the NIH Panel to Define Principles of Therapy of HIV Infection. This Panel was asked to define essential scientific principles that should be used to guide the most effective use of antiretroviral therapies and viral load testing in clinical practice. Based on detailed consideration of the most current data, the Panel delineated eleven principles that address issues of fundamental importance for the treatment of HIV infection. These principles provide the scientific basis for the specific treatment recommendations made by the Panel on Clinical Practices for the Treatment of HIV Infection sponsored by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation. The reports of both of these panels are provided in this publication. Together, they summarize new dta and provide both the scientific basis and specific guidelines for the treatment of HIV-infected persons. This information will be of interest to health-care providers, HIV-infected persons, HIV/AIDS educators, public health educators, public health authorities, and all organizations that fund medical care of HIV-infected persons.
Synergism Between Mycophenolate Mofetil and Cyclosporine in Preventing Graft-Versus-Host Disease Among Lethally Irradiated Dogs Given DLA-Nonidentical Unrelated Marrow Grafts
Authors: Cong Yu, Kristy Seidel, Richard A. Nash, H. Joachim Deeg, Brenda M. Sandmaier, Alexander Barsoukov, Erlinda Santos, Rainer Storb
Journal: Blood (1998)
Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium
Authors: L. Giraldi, E. Leoncini, R. Pastorino, V. Wünsch-Filho, M. de Carvalho, R. Lopez, G. Cadoni, D. Arzani, L. Petrelli, K. Matsuo, C. Bosetti, C. La Vecchia, W. Garavello, J. Polesel, D. Serraino, L. Simonato, C. Canova, L. Richiardi, P. Boffetta, M. Hashibe, Y.C.A. Lee, S. Boccia
Journal: Annals of Oncology (2017)

BackgroundThis study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC.Patients and methodsWe conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis.ResultsFive-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01–6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16–2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22–3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03–1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity.ConclusionsOS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.
Effect of abiraterone acetate and low-dose prednisone on PSA in patients with nonmetastatic castration-resistant prostate cancer: The results from IMAAGEN core study.
Authors: Charles J. Ryan, E. David Crawford, Neal D. Shore, Willie Underwood, Jim Wang, Jannell DePalantino, Anil Londhe, Zandong Yang, Tracy McGowan, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2014)

5086 Background: Abiraterone acetate (AA) is a prodrug of abiraterone, which is a selective, irreversible CYP17 inhibitor of androgen biosynthesis and significantly reduces testosterone production in the testes, adrenal glands and prostate cancer tissue. AA, 1000mg, in combination with prednisone (P), 10mg daily is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Patients with non-metastatic CRPC (nmCRPC) will eventually progress to mCRPC. Currently there is no approved therapy for nmCRPC. This phase II, multi-center study evaluated the ability of AA plus 5 mg of prednisone to decrease PSA levels in patients with nmCRPC and rising PSA. Methods: All patients had nmCRPC but with clinical features placing them at higher risk of developing mCRPC: PSA value ≥ 10ng/mL or PSA doubling time ≤ 10 months at screening. Patients received AA 1000mg with P 5mg (AA+P5) daily. The primary endpoint was PSA response rate at 6 months. Key secondary endpoints included change in testosterone levels, safety, time to PSA progression and time to radiographic disease progression. PSA assessment and imaging scans were conducted every 3 months. Results: From May 2011 to July 2013, 131 patients were enrolled at 38 sites in the US. Data cutoff for this analysis was December 31, 2013. Median age was 72 years (range 48-90). Median baseline PSA was 13.7ng/mL (range 1.6-167.8ng/mL). There were 122 patients evaluable for the analysis of PSA response. By the end of 6 cycles of treatment, 87% (106/122) of patients had ≥ 50% reduction in PSA and 60% (73/122) had ≥ 90% PSA reduction. To date, no patient has had his prednisone dose increased to greater than 5mg to manage symptoms of mineralocorticoid excess. Complete details of radiographic progression and other secondary endpoints including safety will be available by the time of the ASCO meeting. Conclusions: In men with high-risk nmCRPC, treatment using AA+P5 is very effective in lowering PSA. The rate and depth of PSA decline appear superior to men with mCRPC. Clinical trial information: NCT01314118.
Isocitrate Dehydrogenase 1 Mutant Cancers Are Metabolically Vulnerable to Inhibition of Acetyl CoA Carboxylase Via a 2-Hydroxyglutarate Independent Mechanism
Authors: Daniel Thomas, Subarna Sinha, Steven M. Chan, Manhong Wu, Damoun Torabi, Gary Peltz, Yang Gao, David L Dill, Ravi Majeti
Journal: Blood (2016)
A Human Mixture Risk Assessment for Neurodevelopmental Toxicity Associated with Polybrominated Diphenyl Ethers Used as Flame Retardants
Authors: Olwenn V. Martin, Richard M. Evans, Michael Faust, Andreas Kortenkamp
Journal: Environmental Health Perspectives (2017)

Background: The European Food Safety Authority recently concluded that the exposure of small children (1–3 y old) to brominated diphenyl ether (BDE)-99 may exceed acceptable levels defined in relation to neurodevelopmental toxicity in rodents. The flame retardant BDE-209 may release BDE-99 and other lower brominated BDEs through biotic and abiotic degradation, and all age groups are exposed not only to BDE-209 and -99 but also to a cocktail of BDE congeners with evidence of neurodevelopmental toxicity. The possible risks from combined exposures to these substances have not been evaluated. Objectives: We performed a congener-specific mixture risk assessment (MRA) of human exposure to combinations of BDE-209 and other BDEs based on estimated exposures via diet and dust intake and on measured levels in biologic samples. Methods: We employed the Hazard Index (HI) method by using BDE congener-specific reference doses for neurodevelopmental toxicity. Results: Our HI analysis suggests that combined exposures to polybrominated diphenyl ethers (PBDEs) may exceed acceptable levels in breastfeeding infants (0–3 mo old) and in small children (1–3 y old), even for moderate (vs. high) exposure scenarios. Our estimates also suggest that acceptable levels of combined PBDEs may be exceeded in adults whose diets are high in fish. Small children had the highest combined exposures, with some estimated body burdens that were similar to body burdens associated with developmental neurotoxicity in rodents. Conclusions: Our estimates corroborate reports from several recent epidemiological studies of associations between PBDE exposures and neurobehavioral outcomes, and they support the inclusion of BDE-209 in the persistent organic pollutant (POP) convention as well as the need for strategies to reduce exposures to PBDE mixtures, including maximum residue limits for PBDEs in food and measures for limiting the release of PBDEs from consumer waste. https://doi.org/10.1289/EHP826
Left Ventricular Free-Wall Rupture
Authors: Enrico Cerrato, Ferdinando Varbella
Journal: New England Journal of Medicine (2017)

A 67-year-old man presented 12 hours after the onset of chest pain. During emergency coronary angiography, his condition became hemodynamically unstable. Left ventriculography, shown in a video, revealed rupture of the left ventricular free wall.
Cre/loxPベースハイブリッドバキュロウイルスで加工されたASCによる増強された臨界サイズの頭蓋冠骨治癒【Powered by NICT】
Authors: Lo Shih-Chun, Li Kuei-Chang, Chang Yu-Han, Hsu Mu-Nung, Sung Li-Yu, Vu Truong Anh, Hu Yu-Chen
Journal: Biomaterials (2017)
ヒト組織工学は神経膠芽腫の攻撃性の活性miRNA調節因子の同定を可能にする【Powered by NICT】
Authors: E Cosset, T Petty, V Dutoit, D Tirefort, P Otten-Hernandez, L Farinelli, Dietrich P.-Y., O Preynat-Seauve
Journal: Biomaterials (2016)
赤血球マイクロキャリアを用いた低酸素腫瘍に対する直交近赤外周波数逓倍共調節部位特異的O_2デリバリーおよび光線力学療法【Powered by NICT】
Authors: Wang Peiyuan, Li Xiaomin, Yao Chi, Wang Wenxing, Zhao Mengyao, El-Toni Ahmed Mohamed, Zhang Fan
Journal: Biomaterials (2017)
A multifunctional nanocarrier for efficient TRAIL‐based gene therapy against hepatocellular carcinoma with desmoplasia in mice
Authors: Chun‐Hung Liu, Guann‐Jen Chern, Fu‐Fei Hsu, Kuan‐Wei Huang, Yun‐Chieh Sung, Hsi‐Chien Huang, Jiantai Timothy Qiu, Sheng‐Kai Wang, Chu‐Chi Lin, Chien‐Hsun Wu, Han‐Chung Wu, Jia‐Yu Liu, Yunching Chen
Journal: Hepatology (2017)

The anticancer efficacy of TNF‐related apoptosis‐inducing ligand (TRAIL)‐based therapy is limited because of systemic toxicity, poor bioavailability, and development of TRAIL resistance. We developed a tumor‐targeted LCPP (lipid/calcium/phosphate/protamine) nanoparticle (NP) to deliver TRAIL plasmid DNA (pDNA) into hepatocellular carcinoma (HCC) cells in a mouse model of HCC. TRAIL pDNA was encapsulated in a pH stimuli‐responsive calcium phosphate (CaP) core, and protamine was added to facilitate nuclear delivery of pDNA. In addition, intracellular release of Ca 2+ from the CaP core overcame TRAIL resistance by calcium influx‐dependent DR5 up‐regulation. TRAIL expression also attenuated fibrosis in liver tissues surrounding HCCs by reverting activated hepatic stellate cells (HSCs) to a quiescent state or by directly inducing apoptosis in activated HSCs. Conclusion: TRAIL pDNA delivered by HCC‐targeted LCPP NPs in combination with conventional sorafenib treatment attenuated HCC progression as well as liver fibrosis. Overall, our study presents an effective TRAIL‐based cancer therapy that could be developed for clinical applications. (H epatology 2018;67:899–913)
Endothelial to haematopoietic transition contributes to pulmonary arterial hypertension
Authors: Olin D. Liang, Eui-Young So, Pamela C. Egan, Laura R. Goldberg, Jason M. Aliotta, Keith Q. Wu, Patrycja M. Dubielecka, Corey E. Ventetuolo, Anthony M. Reginato, Peter J. Quesenberry, James R. Klinger
Journal: Cardiovascular Research (2017)

The pathogenic mechanisms of pulmonary arterial hypertension (PAH) remain unclear, but involve dysfunctional endothelial cells (ECs), dysregulated immunity and inflammation in the lung. We hypothesize that a developmental process called endothelial to haematopoietic transition (EHT) contributes to the pathogenesis of pulmonary hypertension (PH). We sought to determine the role of EHT in mouse models of PH, to characterize specific cell types involved in this process, and to identify potential therapeutic targets to prevent disease progression.
Treatment strategies for the right heart in pulmonary hypertension
Authors: Berend E. Westerhof, Nabil Saouti, Willem J. van der Laarse, Nico Westerhof, Anton Vonk Noordegraaf
Journal: Cardiovascular Research (2017)

The function of the right ventricle (RV) determines the prognosis of patients with pulmonary hypertension. While much progress has been made in the treatment of pulmonary hypertension, therapies for the RV are less well established. In this review of treatment strategies for the RV, first we focus on ways to reduce wall stress since this is the main determinant of changes to the ventricle. Secondly, we discuss treatment strategies targeting the detrimental consequences of increased RV wall stress. To reduce wall stress, afterload reduction is the essential. Additionally, preload to the ventricle can be reduced by diuretics, by atrial septostomy, and potentially by mechanical ventricular support. Secondary to ventricular wall stress, left-to-right asynchrony, altered myocardial energy metabolism, and neurohumoral activation will occur. These may be targeted by optimising RV contraction with pacing, by iron supplement, by angiogenesis and improving mitochondrial function, and by neurohumoral modulation, respectively. We conclude that several treatment strategies for the right heart are available; however, evidence is still limited and further research is needed before clinical application can be recommended.
Cutaneous melanoma in Birt-Hogg-Dubé syndrome: part of the clinical spectrum?
Authors: E.C. Sattler, B. Ertl-Wagner, C. Pellegrini, K. Peris, M. Reithmair, N. Schädle, T. Ruzicka, O.K. Steinlein
Journal: British Journal of Dermatology (2017)

Birt-Hogg-Dube syndrome (BHDS) is a rare genetic disorder caused by mutations in the FLCN gene. Clinically, BHDS is highly heterogeneous even within the same family. The most characteristic features of BHDS are fibrofolliculomas, lung cysts that confer the risk of pneumothorax, and benign or malignant renal tumours. Additionally, several other tumours are discussed to be possibly linked to BHDS including colon and breast cancer, thyroid tumors, and parathyroid adenomas.

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CBT is effective for treating patients with health anxiety, study shows
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Cognitive behavioural therapy (CBT) can help patients overcome health anxiety effectively and could avoid thousands of unnecessary NHS appointments if used more widely, a clinical trial has found.1

UK researchers estimated that one in five people attending general hospital clinics has abnormal health anxiety, exacerbated by researching symptoms online. Symptoms include chest pains or headaches that persist despite medical reassurance that the patient’s distress has no physical cause.

The CHAMP (cognitive behaviour therapy for health anxiety in medical patients) study examined the effectiveness of CBT-HA, a modified form of CBT targeted at people who worry excessively about their health and frequently seek reassurance and diagnosis from clinicians.

The …
Spinal Manipulative Therapy for Low Back Pain
Authors: Romy Lauche, Tobias Sundberg, Holger Cramer
Journal: JAMA (2017)

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