tbuckley/cabot-search huggingface dataset:
Should we use small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC)-based therapy for the treatment of large cell neuroendocrine cancer (LCNEC) of the lung?
Authors: Nagla Fawzy Abdel Karim, Tariq Namad, Jung Ying, Jiang Wang, Ananta Bhatt, Mohamed Sakkal, John Charles Morris
Journal: Journal of Clinical Oncology (2014)

e18502 Background: LCNEC of the lung exhibits morphological and immunohistochemical characteristics of both neuroendocrine and large cell carcinoma. Optimal treatment for LCNEC remains unclear. Patients with LCNEC demonstrate shorter overall survival (OS) compared to patients with other types of NSCLC, and have a poorer prognosis even when cadidates for surgical resection. Whether these tumors should be treated as a NSCLC as recommended by NCCN guidelines or similar to SCLC is uncertain. We reviewed the outcome of LNCEC treated as SCLC versus NSCLC. Methods: A retrospective review of patients identified with a pathological diagnosis of LCNEC of the lung at the University of Cincinnati Medical Center between 2002 and 2012. OS was estimated using Kaplan-Meier and log-rank test. The hazard ratio (HR) for cancer-specific survival between groups was estimated using a Cox proportional hazard model. Results: Twenty-two patients were diagnosed with LCNEC of the lung, median age 58 years (range, 42-77 years) 11 men, 11 women, 11 Caucasians and 11 African-Americans. Five patients (23%) were never-smokers, 5 were light smokers (23%), and 12 (54%) were heavy smokers with >20 pack-years.. Eleven patients (50%) underwent resection (lobectomy or pneumonectomy) and 9 (43%) patients received radiation therapy. Thirteen patients recieved chemotherapy. Eight (36.4%) were treated with a SCLC-based chemotherapy (cisplatin/etoposide), and 5 patients (22.7%) received a NSCLC regimens. 9 patients (40.9%) did not receive chemotherapy. Median overall survival for all patients was 16 months (range, 11 to 42 months). OS of patients treated with either SCLC or NSCLC chemotherapy was found to be not statistically different from those who did not receive any chemotherapy (HR 0.43, and 0.79 ; p=0.23 and 0.71). However, patients who underwent surgery showed higher risk of death compared to no surgery (HR of 3.66 ; p=0.04). Conclusions: LCNECs of the lung behave aggressively and have poorer outcomes than other types of NSCLC when treated with surgery and chemotherapy. Patients with surgery had higher risk of death. The OS did not differ by specific chemotherapy regimen.
A Randomized Phase II study of Reolysin in Patients with Previously Treated Advanced or Metatstatic Non Small Cell Lung Cancer (NSCLC) receiving Standard Salvage Chemotherapy – Canadian Cancer Trials Group IND 211.
Authors: Donald Morris, Dongsheng Tu, Mustapha Ali Tehfe, Garth Andrew Nicholas, John R. Goffin, Richard William Gregg, Frances A. Shepherd, Nevin Murray, Rafal Wierzbicki, Christopher W. Lee, Sara Kuruvilla, Bruce Keith, A Ahmed, Normand Blais, Glenwood D. Goss, Grzegorz Korpanty, Joana Sederias, Scott Andrew Laurie, Lesley Seymour, Penelope Ann Bradbury
Journal: Journal of Clinical Oncology (2016)

e20512 Background: Despite advances associated with the use of targeted therapy, cytotoxic chemotherapy and immunotherapy the treatment of advanced NSCLC remains challenging. In this study we evaluated the effect of the oncolytic type 3 Dearing virus, Reolysin, in combination with standard salvage chemotherapy. Methods: This multicenter non-blinded phase II clinical trial randomized advanced stage refractory platinum doublet NSCLC patients to either docetaxel (squamous histology or pemetrexed pretreated) or to pemetrexed (non-squamous) plus or minus Reolysin. Results: No dose related toxicities were seen in a safety lead in group of patients in Arm A (N = 8) and Arm C (N = 6) allowing a total of 152 patients to be randomized as follows: Arm A: Pem (500mg/m2) IV plus Reo 4.5x1010 Day1-3 every 3 weeks; Arm B: Pem alone every 3 weeks; Arm C Doc (75mg/m2) IV plus Reo 4.5x1010Day1-3 every 3 weeks and Arm D: Doc alone every 3 weeks between January 2013 and August 2015. The arms were well balanced and at a median follow up of 16.5 months the median PFS was 2.96 (95% c.i. 2.56-4.17) and 2.83 (95% c.i. 2.50-3.98) months for Arms A/C and B/D, respectively. Response rate for all randomized patients was 14.3% (95% c.i. 7.4–24.1%) and 14.7 (95% c.i 7.6-24.7%) for Arms A/C and B/D, respectively (p = 0.96). The hazard ratio for survival of Arms A/C to B/D was 0.92 (0.63- 1.35, p = 0.9). Female gender PFS favoured Arms A/C vs B/D with a hazard ratio of 0.59 (95% c.i. 0.36-0.98). Further, post hoc analysis of PFS in selected EGFR/ERBB2/ERBB4/KRAS/NRAS/BRAF/PI3CA/PTEN/TP53 mutated patients was evaluated with only EGFR mut and p53 mutated pts trending to favoring the A/C arms HR 0.54 (95% c.i. 0.13-2.22) and HR 0.58 (95% c.i. 0.31-1.09). Conclusions:Reolysin was reasonably well tolerated at the dose and schedule administered with pemetrexed or docetaxel. No new safety signals were seen. It is of interest that females in the Reolysin containing arms did better than in the standard treatment arms and that in the post hoc subgroup analysis that EGFR mut and p53mut status was associated with a trend to improved PFS. Clinical trial information: NCT01708993.
Interleukin-6 is not involved in the interleukin-1-induced production of colony-stimulating factors by human bone marrow stromal cells and fibroblasts
Authors: MR Schaafsma, WE Fibbe, J Van Damme, N Duinkerken, P Ralph, K Kaushansky, BW Altrock, R Willemze, JH Falkenburg
Journal: Blood (1989)
AMECM/DCB足場はウサギ全半月切除モデルにおける成功した全半月板再生を促進する【Powered by NICT】
Authors: Yuan Zhiguo, Liu Shuyun, Hao Chunxiang, Guo Weimin, Gao Shuang, Wang Mingjie, Chen Mingxue, Sun Zhen, Xu Yichi, Wang Yu, Peng Jiang, Yuan Mei, Guo Quan-Yi
Journal: Biomaterials (2016)
Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study
Authors: Guillaume Joguet, Jean-Michel Mansuy, Giulia Matusali, Safouane Hamdi, Marie Walschaerts, Lynda Pavili, Stefanie Guyomard, Nadia Prisant, Pierre Lamarre, Nathalie Dejucq-Rainsford, Christophe Pasquier, Louis Bujan
Journal: The Lancet Infectious Diseases (2017)
Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials
Authors: Dirk Schadendorf, Jedd D. Wolchok, F. Stephen Hodi, Vanna Chiarion-Sileni, Rene Gonzalez, Piotr Rutkowski, Jean-Jacques Grob, C. Lance Cowey, Christopher D. Lao, Jason Chesney, Caroline Robert, Kenneth Grossmann, David McDermott, Dana Walker, Rafia Bhore, James Larkin, Michael A. Postow
Journal: Journal of Clinical Oncology (2017)

Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231). Results At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs ( P = .97). Median overall survival had not been reached in either group ( P = .23). The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy.
High-density lipoproteins suppress Aβ-induced PBMC adhesion to human endothelial cells in bioengineered vessels and in monoculture
Authors: Jérôme Robert, Emily B. Button, Sophie Stukas, Guilaine K. Boyce, Ebrima Gibbs, Catherine M. Cowan, Megan Gilmour, Wai Hang Cheng, Sonja K. Soo, Brian Yuen, Arvin Bahrabadi, Kevin Kang, Iva Kulic, Gordon Francis, Neil Cashman, Cheryl L. Wellington
Journal: Molecular Neurodegeneration (2017)

Alzheimer's Disease (AD), characterized by accumulation of beta-amyloid (Aβ) plaques in the brain, can be caused by age-related failures to clear Aβ from the brain through pathways that involve the cerebrovasculature. Vascular risk factors are known to increase AD risk, but less is known about potential protective factors. We hypothesize that high-density lipoproteins (HDL) may protect against AD, as HDL have vasoprotective properties that are well described for peripheral vessels. Epidemiological studies suggest that HDL is associated with reduced AD risk, and animal model studies support a beneficial role for HDL in selectively reducing cerebrovascular amyloid deposition and neuroinflammation. However, the mechanism by which HDL may protect the cerebrovascular endothelium in the context of AD is not understood.We used peripheral blood mononuclear cell adhesion assays in both a highly novel three dimensional (3D) biomimetic model of the human vasculature composed of primary human endothelial cells (EC) and smooth muscle cells cultured under flow conditions, as well as in monolayer cultures of ECs, to study how HDL protects ECs from the detrimental effects of Aβ.Following Aβ addition to the abluminal (brain) side of the vessel, we demonstrate that HDL circulated within the lumen attenuates monocyte adhesion to ECs in this biofidelic vascular model. The mechanism by which HDL suppresses Aβ-mediated monocyte adhesion to ECs was investigated using monotypic EC cultures. We show that HDL reduces Aβ-induced PBMC adhesion to ECs independent of nitric oxide (NO) production, miR-233 and changes in adhesion molecule expression. Rather, HDL acts through scavenger receptor (SR)-BI to block Aβ uptake into ECs and, in cell-free assays, can maintain Aβ in a soluble state. We confirm the role of SR-BI in our bioengineered human vessel.Our results define a novel activity of HDL that suppresses Aβ-mediated monocyte adhesion to the cerebrovascular endothelium.
Prenatal Antidepressant Use and Autism Spectrum Disorder
Authors: Deepa Singal, Dan Chateau, Marni Brownell
Journal: JAMA (2017)

To the Editor The study by Dr Brown and colleagues1 concluded that in utero serotonergic antidepressant exposure was not associated with the development of autism spectrum disorder in children. However, we conclude that the opposite may be true.
Multiple Tissue Carrier For Histologic Techniques&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Albert M. Kessel
Journal: JNCI Journal of the National Cancer Institute (1944)

Multiple Tissue Carrier For Histologic Techniques Get access Albert M. Kessel Albert M. Kessel senior medical technician National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 4, February 1944, Pages 361–362, https://doi.org/10.1093/jnci/4.4.361 Published: 01 February 1944
p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy
Authors: Myrthala Moreno-Smith, Anna Lakoma, Zaowen Chen, Ling Tao, Kathleen A. Scorsone, Linda Schild, Kevin Aviles-Padilla, Rana Nikzad, Yankai Zhang, Rikhia Chakraborty, Jan J. Molenaar, Sanjeev A. Vasudevan, Vivien Sheehan, Eugene S. Kim, Silke Paust, Jason M. Shohet, Eveline Barbieri
Journal: Clinical Cancer Research (2017)

Abstract Purpose: mTORC1 inhibitors are promising agents for neuroblastoma therapy; however, they have shown limited clinical activity as monotherapy, thus rational drug combinations need to be explored to improve efficacy. Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR signaling. Experimental Design: Using an orthotopic xenograft model and modulating p53 levels, we investigated the antitumor effects of the mTORC1 inhibitor temsirolimus in neuroblastoma expressing normal, decreased, or mutant p53, both as single agent and in combination with first- and second-generation MDM2 inhibitors to reactivate p53. Results: Nongenotoxic p53 activation suppresses mTOR activity. Moreover, p53 reactivation via RG7388, a second-generation MDM2 inhibitor, strongly enhances the in vivo antitumor activity of temsirolimus. Single-agent temsirolimus does not elicit apoptosis, and tumors rapidly regrow after treatment suspension. In contrast, our combination therapy triggers a potent apoptotic response in wild-type p53 xenografts and efficiently blocks tumor regrowth after treatment completion. We also found that this combination uniquely led to p53-dependent suppression of survivin whose ectopic expression is sufficient to rescue the apoptosis induced by our combination. Conclusions: Our study supports a novel highly effective strategy that combines RG7388 and temsirolimus in wild-type p53 neuroblastoma, which warrants testing in early-phase clinical trials. Clin Cancer Res; 23(21); 6629–39. ©2017 AACR.
Differential analysis between somatic mutation and germline variation profiles reveals cancer-related genes
Authors: Pawel F. Przytycki, Mona Singh
Journal: Genome Medicine (2017)

A major aim of cancer genomics is to pinpoint which somatically mutated genes are involved in tumor initiation and progression. We introduce a new framework for uncovering cancer genes, differential mutation analysis, which compares the mutational profiles of genes across cancer genomes with their natural germline variation across healthy individuals. We present DiffMut, a fast and simple approach for differential mutational analysis, and demonstrate that it is more effective in discovering cancer genes than considerably more sophisticated approaches. We conclude that germline variation across healthy human genomes provides a powerful means for characterizing somatic mutation frequency and identifying cancer driver genes. DiffMut is available at https://github.com/Singh-Lab/Differential-Mutation-Analysis .
Infographic: we need minimum reporting standards for biologics
Authors: Iain R Murray, Andrew D Murray, Andrew G Geeslin, Ewan B Goudie, Timothy O White, Frank A Petrigliano, Robert F LaPrade
Journal: British Journal of Sports Medicine (2017)

Biologic therapies, including platelet rich plasma (PRP) and mesenchymal stem cells, are now widely used to treat a spectrum of sports injuries without robust clinical evidence of efficacy.1 2 Physicians have a duty to use biologic therapies responsibly, using the best available research evidence to guide treatment decisions for patients. A large number of variables, including processing details, …
Multi-target chimaeric VLP as a therapeutic vaccine in a model of colorectal cancer
Authors: Braeden Donaldson, Farah Al-Barwani, Simon J. Pelham, Katie Young, Vernon K. Ward, Sarah L. Young
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> Colorectal cancer is responsible for almost 700,000 deaths annually worldwide. Therapeutic vaccination is a promising alternative to conventional treatment for colorectal cancer, using vaccines to induce targeted immune responses against tumour-associated antigens. In this study, we have developed chimaeric virus-like particles (VLP), a form of non-infectious non-replicative subunit vaccine consisting of rabbit haemorrhagic disease virus (RHDV) VP60 capsid proteins containing recombinantly inserted epitopes from murine topoisomerase IIα and survivin. These vaccines were developed in mono- (T.VP60, S.VP60) and multi-target (TS.VP60) forms, aiming to elucidate the potential benefits from multi-target vaccination. <h3>Methods</h3> Chimaeric RHDV VLP were developed by recombinantly inserting immune epitopes at the N-terminus of VP60. Vaccines were tested against a murine model of colorectal cancer by establishing MC38-OVA tumours subcutaneously. Unmethylated CpG DNA oligonucleotides (CpGs) were used as a vaccine adjuvant. Statistical tests employed included the Mantel-Cox log-rank test, ANOVA and unpaired t-tests depending on the data analysed, with a post hoc Bonferroni adjustment for multiple measures. <h3>Results</h3> Chimaeric RHDV VLP were found to form a composite particle in the presence of CpGs. Overall survival was significantly improved amongst mice bearing MC38-OVA tumours following vaccination with T.VP60 (60%, 9/15), S.VP60 (60%, 9/15) or TS.VP60 (73%, 11/15). TS.VP60 significantly prolonged the vaccine-induced remission period in comparison to each mono-therapy. <h3>Conclusions</h3> Chimaeric VLP containing multiple epitopes were found to confer an advantage for therapeutic vaccination in a model of colorectal cancer based on the prolongation of remission prior to tumour escape.
US declares opioid epidemic a “national emergency”
Authors: Michael McCarthy
Journal: BMJ (2017)

US president Donald Trump has declared the nation’s epidemic of opioid use a national emergency, directing his administration to use “all appropriate emergency and other authorities to respond to the crisis.”

Trump announced his decision on 10 August in response to reporters’ questions outside of a security briefing at the Trump National Golf Club, where the president is on vacation.

“The opioid crisis is an emergency, and I’m saying officially right now it is an emergency. It’s a national emergency. We’re going to spend a lot of time, …
Europium-doped mesoporous silica nanosphere as an immune-modulating osteogenesis/angiogenesis agent
Authors: Mengchao Shi, Lunguo Xia, Zetao Chen, Fang Lv, Huiying Zhu, Fei Wei, Shengwei Han, Jiang Chang, Yin Xiao, Chengtie Wu
Journal: Biomaterials (2017)
Optical transfer diagnosis differentiating benign and malignant pigmented lesions in a simulated primary care practice
Authors: D.L. Swanson, R.V. Venneugues, S.Q. Vicencio, J. Garioch, M. Biryulina, G. Ryzhikov, B. Hamre, L. Zhao, F.S. Castellana, K. Stamnes, J.J. Stamnes
Journal: British Journal of Dermatology (2017)

The detection of melanoma poses a substantial challenge, particularly for primary care providers (PCPs) who may have limited training in discriminating between suspicious and benign melanocytic lesions. The noninvasive optical transfer diagnosis (OTD) method was designed to be used by PCPs in their decision‐making process. To assess the potential of the OTD method by developing, training and validating an OTD indication algorithm for automated discrimination between benign melanocytic lesions and malignant lesions, based on a set of 712 lesions. The authors performed in vivoOTD capture and subsequent analysis of 712 pigmented lesions. Of the lesions, 415 were clinically and dermoscopically benign and 297 were dermoscopically suspicious or equivocal. After image capture, all suspicious or equivocal lesions were biopsied and examined histopathologically. Of the 297 suspicious or equivocal lesions, histopathological findings revealed 80 to be malignant (64 melanomas, 13 basal cell carcinomas and 3 squamous cell carcinomas). OTD misdiagnosed one of the 80 malignant lesions as benign (sensitivity, 99%). OTD specificity was 93% for the dermoscopically benign lesions, 73% for all lesions included in the study and 36% for the clinically suspicious but histopathologically benign lesions. High sensitivity and specificity, as provided by OTD in this preliminary study, would help PCPs reduce the number of referrals for dermatology consultation, excision or biopsy. Further studies are planned for screening patients in a primary care setting, with comparisons of OTD results with biopsy or dermoscopy results.
Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series
Authors: Sang Taek Kim, Jean Tayar, Van Anh Trinh, Maria Suarez-Almazor, Salvador Garcia, Patrick Hwu, Daniel Hartman Johnson, Marc Uemura, Adi Diab
Journal: Annals of the Rheumatic Diseases (2017)

Background Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with numerous cancers. However, these therapies are associated with immune-related adverse events (irAEs), which are inflammatory side effects potentially affecting any organ. Cases of ICI-induced inflammatory arthritis have also been reported. In general, mild irAEs are treated with corticosteroids, while tumour necrosis factor-α (TNFα) inhibitors are reserved for refractory cases. However, prolonged use of TNFα inhibitor (TNFαi) can induce widespread, significant immunosuppression, which can negatively impact the antitumour efficacy of ICI therapy. Therefore, in clinical scenarios where patients develop severe immunotherapy-induced irAEs, an unmet need exists for alternative therapeutic strategies that are effective and without immune dampening effects. Case reports The anti-interleukin (IL)−6 receptor antibody, tocilizumab, is a biological agent Food and Drug Administration approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Here, we report on three patients who developed severe polyarthritis while receiving ICI therapy and were treated with tocilizumab. All three patients demonstrated significant clinical improvement; one patient maintained a durable antitumour response derived from checkpoint inhibition. Conclusions These three cases suggest that anti-IL-6 receptor antibody may be an effective alternative to corticosteroids or TNFαi for the treatment of arthritis irAEs.
National Cancer Database Report on Pneumonectomy Versus Lung-Sparing Surgery for Malignant Pleural Mesothelioma
Authors: Vivek Verma, Christopher A. Ahern, Christopher G. Berlind, William D. Lindsay, Sonam Sharma, Jacob Shabason, Melissa J. Culligan, Surbhi Grover, Joseph S. Friedberg, Charles B. Simone
Journal: Journal of Thoracic Oncology (2017)