tbuckley/cabot-search huggingface dataset:
Biologic meshes in cancer patients: A double-edged sword—Differences in production of IL6 and IL12 caused by acellular dermal matrices in human immune cells.
Authors: Maria Margarete Guenthner-Biller, Sabine Enders, Julia Knabl, Verena Engelstaedter, Peter Duewell, Brigitte Kathrin Rack, Doris Mayr, Udo Jeschke, Darius Dian
Journal: Journal of Clinical Oncology (2013)

3064 Background: Acellular dermal matrices (ADM) have been used in different fields of surgery for almost 20 years. In 2005 Breuing et al first described its use in breast cancer patients. It is assumed that it is safe to use in an oncologic setting, but data from controlled studies are still missing. Because of its lack of cells ADM are considered not to cause an immune reaction. With increasing knowledge about the importance of immunology in breast cancer more information about ADM on different immune cell populations is needed. IL6 and IL12 are two central cytokines and key regulators of immune supression and activation. Methods: Strattice (ST; LifeCell) CollaMend (CM; Bard Davol), Biodesign (BD; Cook Biotec) as well as TiLoop a synthetic mesh (TL; pfm medical) were used in this study. We isolated myeloid dendritic cells (MDC), untouched plasmacytoid dendritic cells (PDC), naïve B-cells and CD8+ T-cells using the MACS System and co-cultered them with the biologic meshes or TL. For positive controls, we used CpG ODN 2216 3 µg/ml and LPS in a concentration of 100 ng/ml. Cytokine concentration of IL12p70 and IL6 were determined after seven days by using sandwich Elisa sets. Statistical significance was determined by the nonparametric Friedman-Test. The single hypothesis was calculated with a paired Wilcoxon Test. Results: There was a highly significant difference between the different ADM and TL in the immunologic response. The statistical difference for IL 6 was p= 0.0006131 for B cells and p= 0.00418 for T cells between TL and ADM. ST also caused significantly more IL6 than CM and BD. We found similar differences in IL 12 with p= 0.00194 for B cells and p= 0.003636 in T cells in regard to the difference between TL and ADM. For IL 12 there was no statistical difference between the ADM. We didn´t see any significant differences in the cytokine profile between the various ADM/TL in the MDC and PDC subpopulations. Conclusions: Despite the assumed lack of immune answer to ADM, immune cells reacted in our study with significantly different cytokine profiles. These findings can have implications regarding the activation or suppression of effector cells in a cancer patient.
Identification of functional DNA methylation aberrations associated with outcome in melanoma patients with brain metastasis.
Authors: Diego M Marzese, Jamie L Huynh, Sharon Huang, Hajime Hirose, Eiji Kiyohara, Donald L. Morton, Daniel F. Kelly, Dave S. B. Hoon
Journal: Journal of Clinical Oncology (2013)

9095 Background: Brain metastasis (MBM) represents one of the most significant causes of death in melanoma patients. Identification of clinically relevant markers is necessary to recognize patients with high risk of MBM development. Alterations in DNA methylation patterns have been recognized as a major epigenetic hallmark of metastasis initiation and progression. Methods: To generate a comprehensive genomic DNA methylation landscape of MBM, we performed genome-wide data integrative analyses examining the DNA methylation (Illumina HumanMethylation 450K), gene expression (Affymetrix HumanExon 1.0), and genotype (Affymetrix SNP 6.0) of specimens related to melanoma progression from normal to MBM (n=65). Results: We observed significant genome-wide hypomethylation and CpG island hypermethylation according to melanoma progression to the brain. To identify significant differentially methylated CpG sites between lymph node metastasis and MBM, we applied a strict statistical threshold (β-value difference &gt;0.3 and FDR-corrected p &lt;0.005). We identified the homeobox D (HOXD) gene family members amongst the most significantly affected genes. The influence on gene expression and the frequency of HOXD hypermethylation were verified using integrative analysis of publicly available data generated from 168 melanoma specimens. In a cohort of clinically annotated melanoma patients (n = 159), we demonstrated that hypermethylation of a genomic region in the HOXD gene cluster was significantly associated with shorter disease-free survival (p = 0.004) and overall survival (p = 0.002).Multivariate analysis confirmed the association with poorer survival (p = 0.01 and HR = 2.8; CI95%: 1.3-6.1). Conclusions: The use of genome-wide DNA methylation, gene expression, and genotyping integrative analyses allowed the identification of novel markers with functional and clinical implications for melanoma patients with brain metastasis.
Multiply clustered gold-based nanoparticles complexed with exogenous pDNA achieve prolonged gene expression in stem cells
Authors: Se Won Yi, Ji Sun Park, Hye Jin Kim, Jung Sun Lee, Dae Gyun Woo, Keun-Hong Park
Journal: Theranostics (2019)

Development of a stable and prolonged gene delivery system is a key goal in the gene therapy field. To this end, we designed and fabricated a gene delivery system based on multiply-clustered gold particles that could achieve prolonged gene delivery in stem cells, leading to improved induction of differentiation. Methods: Inorganic gold nanoparticles (AuNPs) underwent three rounds of complexation with catechol-functionalized polyethyleneimine (CPEI) and plasmid DNAs (pDNAs), in that order, with addition of heparin (HP) between rounds, yielding multiply-clustered gold-based nanoparticles (mCGNPs). Via metal-catechol group interactions, the AuNP surface was easily coordinated with positively charged CPEIs, which in turn allowed binding of pDNAs. Results: Negatively charged HP was encapsulated with the positive charge of CPEIs via electrostatic interactions, making the NPs more compact. Repeating the complexation process yielded mCGNPs with improved transfection efficiency in human mesenchymal stem cells (hMSCs); moreover, these particles exhibited lower cytotoxicity and longer expression of pDNAs than conventional NPs. This design was applied to induction of chondrogenesis in hMSCs using pDNA harboring SOX9, an important chondrogenic transcription factor. Prolonged expression of SOX9 induced by mCGNPs triggered expression of chondrocyte extracellular matrix (ECM) protein after 14 days, leading to more efficient chondrogenic differentiation in vitro and in vivo.
Abstract 16027: Impact of Ancillary Ablation Strategies on One Year Outcomes of AF Intervention
Authors: Zhen Jiao, Niloufar Tabatabaei, Paul A Friedman, Samuel J Asirvatham, Yong-Mei Cha, Brain D Powell, Janis Haroldson, Kristi H Monahan, David O Hodge, Thomas M Munger, Douglas L Packer
Journal: Circulation (2012)

Background: Despite attempts at issue clarification, there remains considerable controversy over the need for ancillary interventions beyond pulmonary vein isolation (PVI) in patients with atrial f...
ALDH1-positive cells in primary tumor and axillary lymph node metastases after chemotherapy as a prognostic factor in breast cancer patients.
Authors: Masahiro Sakakibara, Takeshi Nagashima, Takafumi Sangai, Hiroshi Fujimoto, Tiberu-Hiroshi Suzuki, Masaru Miyazaki
Journal: Journal of Clinical Oncology (2013)

1097 Background: The cancer stem cell theory that was established for hematopoietic neoplasms has significantly changed the concept of cancer therapy. Aldehyde dehydrogenase 1 (ALDH1)-positive cells show stem-like or progenitor ability, and have been considered as a clinically important diagnostic and therapeutic target in breast cancer patients. However, responsiveness of ALDH1-positive cells to chemotherapy in primary and metastatic lesions remains unclear, along with relationships to prognosis in patients with breast cancer. This study evaluated responsiveness to chemotherapy in the ALDH1-positive cells for primary and metastatic lesions and relationships to prognosis in patients with node-positive breast cancer. Methods: We evaluated 115 breast cancer patients with cytologically confirmed lymph node metastases who had undergone surgery after neoadjuvant chemotherapy (NAC). Using ALDH1 immunohistochemistry of core needle biopsy for the primary tumor and cytology samples for axillary lymph nodes before NAC and pathological samples of each after NAC, we evaluated the clinical significance of ALDH1-positive cell status in primary and metastatic lesions before and after NAC. Results: Presence of ALDH1-positive cancer cells, not ALDH1-negative cancer cells, in primary and metastatic lesions after NAC was associated with worse prognosis. In multivariate analysis, only ALDH1-positive cells in metastatic lesions after NAC correlated with overall survival. Responsiveness of ALDH1-positive cells to chemotherapy differed between primary and metastatic lesions, and ALDH1-positive cells in metastatic lesions after NAC might clinically precede those in the primary lesion. Conclusions: Responsiveness of the ALDH1-positive cells to chemotherapy in primary and metastatic lesions, and the prognostic significance, were clarified in breast cancer patients. ALDH1-positive status might offer a surrogate marker as a new concept in patients with node-positive breast cancer.
ApoStream, a novel device for antibody-independent capture of circulating cancercells (CCCs) from blood of patients with various types of cancer.
Authors: Vishal Gupta, Insiya Jafferji, Miguel Garza, Sujita Sukumaran, Jacky Woo, Dave Hasegawa, Vladislava O. Melnikova, Darren W. Davis
Journal: Journal of Clinical Oncology (2012)

e13500 Background: The detection of circulating tumor cells (CTCs) using immunomagnetic EpCAM-based capture methods has been conceptually accepted as a “liquid tumor biopsy”. However, these methods have limited the recovery of CTCs for molecular profiling applications. We developed a novel continuous flow dielectrophoresis field-flow fractionation (DEP-FFF) device, ApoStream for antibody-independent capture of circulating cancer cells (CCCs), with improved recovery across multiple cancer types and preserved viability of CCCs for downstream characterization. Methods: The performance of ApoStream was demonstrated using a low EpCAM expressing cell line, SKOV3. ApoStream was further used to enrich CCCs from various cancer patient blood. Prostate, breast and NSCLC CCCs were stained for cytokeratin (CK), CD45, and DAPI; melanoma CCCs were stained with S100, CD45 and DAPI. CCC enumeration was performed using laser scanning cytometry. Results: In system precision performance studies, average inter-day recovery on the ApoStream was 80.3 ± 3.5%, CV = 4.3% when cancer cells were spiked into buffer, and 78.5 ± 3.0%, CV = 3.3% when cancer cells spiked into ~10 million healthy peripheral blood mononuclear cells (PBMCs). Linearity performance was demonstrated with spiking 5-2600 SKOV3 cells into 10 million PBMCs (R 2 =1). Cell viability was not affected by processing through ApoStream device. High CCC recovery from metastatic cancer patient blood samples was obtained with counts ranging from 0 - 2630 (NSCLC, n=66), 0 - 3490 (prostate, n=29), 10 - 968 (breast, n=11), and 3 - 3120 (melanoma, n=13) CCCs per 7.5 mL blood. Positive CCC counts were obtained in 90% of NSCLC samples, 93% of prostate cancer samples, 100% breast cancer and melanoma specimens. There were no CK+ cells detected in healthy donor blood controls. Conclusions: Improved CCC recovery from various cancer types was demonstrated with the ApoStream device. ApoStream provides an antibody-independent method for capture of viable CCCs that enables further downstream molecular characterization of rare cells for use in clinical applications. Acknowledgements: Funded by NCI Contract No. HHSN261200800001E.
Lumen-apposing metal stent for the creation of an endoscopic duodenojejunostomy to facilitate bile duct clearance following Roux-en-Y hepaticojejunostomy
Authors: Olaya I. Brewer Gutierrez, Thomas Runge, Yervant Ichkhanian, Kia Vosoughi, Mouen A. Khashab
Journal: Endoscopy (2019)

A 52-year-old woman with history of bile duct injury following cholecystectomy and previous Roux-en-Y hepaticojejunostomy was admitted because of cholangitis. Her work-up revealed a 7-mm stone in the right intrahepatic duct on magnetic resonance cholangiopancreatography (MRCP). An initial single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) revealed independent right and left hepaticojejunostomies and bilateral strictures. A large right intrahepatic filling defect was identified on an occlusion cholangiogram ([Fig. 1]). Bilateral dilation of the anastomosis was performed with an 8-mm hydrostatic balloon, but the stone could not be removed and two plastic biliary stents (7 F × 5 cm) were placed.
AB1065 Needle versus forceps technique in ultrasound-guided synovial biopsy of the knee joint
Authors: T Hügle, P Urbaniak, M Müller-Gerbl, C Marx, G Tamborrini
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Ultrasound-guided synovial biopsy is increasingly applied in rheumatology. Usually forceps- or needle-based techniques are used. So far there has been no direct comparison of different devices regarding their suitability in high resolution musculoskeletal ultrasound (hrMSUS)-guided synovial biopsy. <h3>Objectives</h3> To compare different forceps and needle-based instruments in hrMSUS-guided synovial biopsy in a cadaver study. <h3>Methods</h3> A core needle biopsy (A, Quickcore, Cook Medical, Bloomington, IN, USA), a retrograde forceps (B, Retroforce, Karl-Storz GmbH Tuttlingen, Germany), an anterograde arthroscopy forceps (C, Karl Storz GmbH, Tuttlingen, Germany) and an convexly shaped integrated core needle system (D, Synovex, Hipp Medical, Kolbingen, Germany) were tested for ultrasound-guided synovial biopsy of the suprapatellar recess in cadaver knee joints. Four senior rheumatologists scored each intervention from 0–5 regarding the following characteristics: visualization, handiness, accuracy, synovial tissue yield, invasiveness and overall suitability. Each intervention was recorded as static images and video clips. <h3>Results</h3> In all devices, enough representative synovial tissue was obtained and the instruments were all well visualized by hrMSUS. Core needle biopsy and the integrated needle system were best visualized due to their horizontally shaped closing mechanism. The core needle obtained a high yield of superficial synovial tissue and was the least invasive procedure. Despite handiness and accuracy were higher in the forceps instruments, overall suitability for hrMSUS-guided synovial biopsy was rated highest for the core biopsy needle. <h3>Conclusions</h3> Technically, all of the tested devices can be used for hrMSUS-guided synovial biopsy. Core needle biopsy seems to be most suitable for this intervention due to a low invasiveness, good visualisation and optimal yield of superficial synovial tissue. <h3>References</h3> Hügle T et al. Retrograde synovial biopsy of the knee joint using a novel biopsy forceps. Arthrosc Tech. 2014;3(3):e317–9. Hügle T et al. Development of a New Device for Synovial Biopsies. Surg Innov. 2015;22(5):496–9. <h3>Disclosure of Interest</h3> T. Hügle Shareholder of: Prof. Hügle contributed to the development of the Retroforce and Synovex instruments and receives royalties from Karl-Storz GmbH and Hipp Medical AG., P. Urbaniak: None declared, M. Müller-Gerbl: None declared, C. Marx: None declared, G. Tamborrini: None declared
Value of Collaboration among Multi-Domain Experts in Analysis of High-Throughput Genomics Data
Authors: Daoud Meerzaman, Barbara K. Dunn
Journal: Cancer Research (2019)

The recent explosion and ease of access to large-scale genomics data is intriguing. However, serious obstacles exist to the optimal management of the entire spectrum from data production in the laboratory through bioinformatic analysis to statistical evaluation and ultimately clinical interpretation. Beyond the multitude of technical issues, what stands out the most is the absence of adequate communication among the specialists in these domains. Successful interdisciplinary collaborations along the genomics pipeline extending from laboratory experiments to bioinformatic analyses to clinical application are notable in large scale, well managed projects such as The Cancer Genome Atlas. However, in certain settings in which the various experts perform their specialized research activities in isolation, the siloed approach to their research contributes to the generation of questionable genomic interpretations. Such situations are particularly concerning when the ultimate endpoint involves genetic/genomic interpretations that are intended for clinical applications. In spite of the fact that clinicians express interest in gaining a better understanding of clinical genomic applications, the lack of communication from upstream experts leaves them with a serious level of discomfort in applying such genomic knowledge to patient care. This discomfort is especially evident among healthcare providers who are not trained as geneticists, in particular primary care physicians. We offer some initiatives that have potential to address this problem, with emphasis on improved and ongoing communication among all the experts in these fields, constituting a comprehensive genomic "pipeline" from laboratory to patient.
The detection rate of human papillomavirus in well‐differentiated squamous cell carcinoma and keratoacanthoma: is there new evidence for a viral pathogenesis of keratoacanthoma?
Authors: C. Conforti, F. Paolini, A. Venuti, C. Dianzani, I. Zalaudek
Journal: British Journal of Dermatology (2019)

Linked Articles:Taibjee et al.Br J Dermatol 2019; 181:1343–1345; Conforti et al.Br J Dermatol 2019; 181:1345–1346.
Effect of Filgotinib vs Placebo on Clinical Response in Patients With Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy
Authors: Mark C. Genovese, Kenneth Kalunian, Jacques-Eric Gottenberg, Neelufar Mozaffarian, Beatrix Bartok, Franziska Matzkies, Jie Gao, Ying Guo, Chantal Tasset, John S. Sundy, Kurt de Vlam, David Walker, Tsutomu Takeuchi
Journal: JAMA (2019)

Patients with active rheumatoid arthritis (RA) despite treatment with biologic disease-modifying antirheumatic drug (bDMARD) therapy need treatment options.To evaluate the effects of filgotinib vs placebo on the signs and symptoms of RA in a treatment-refractory population.A 24-week, randomized, placebo-controlled, multinational phase 3 trial conducted from July 2016 to June 2018 at 114 sites internationally, randomizing 449 adult patients (and treating 448) with moderately to severely active RA and inadequate response/intolerance to 1 or more prior bDMARDs.Filgotinib, 200 mg (n = 148); filgotinib, 100 mg (n = 153); or placebo (n = 148) once daily; patients continued concomitant stable conventional synthetic DMARDs (csDMARDs).The primary end point was the proportion of patients who achieved 20% improvement in the American College of Rheumatology criteria (ACR20) at week 12. Secondary outcomes included week 12 assessments of low disease activity (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] ≤3.2) and change in Health Assessment Questionnaire-Disability Index, 36-Item Short-Form Health Survey Physical Component, and Functional Assessment of Chronic Illness Therapy-Fatigue scores, as well as week 24 assessment of remission (DAS28-CRP <2.6) and adverse events.Among 448 patients who were treated (mean [SD] age, 56 [12] years; 360 women [80.4%]; mean [SD] DAS28-CRP score, 5.9 [0.96]; 105 [23.4%] with ≥3 prior bDMARDs), 381 (85%) completed the study. At week 12, more patients receiving filgotinib, 200 mg (66.0%) or 100 mg (57.5%), achieved ACR20 response (placebo, 31.1%; difference vs placebo: 34.9% [95% CI, 23.5%-46.3%] and 26.4% [95% CI, 15.0%-37.9%], respectively; both P < .001), including among patients with prior exposure to 3 or more bDMARDs (70.3%, 58.8%, and 17.6%, respectively; difference vs placebo: 52.6% [95% CI, 30.3%-75.0%] for filgotinib, 200 mg, and 41.2% [95% CI, 17.3%-65.0%] for filgotinib, 100 mg; both P < .001). The most common adverse events were nasopharyngitis (10.2%) for filgotinib, 200 mg; headache, nasopharyngitis, and upper respiratory infection (5.9% each) for filgotinib, 100 mg; and RA (6.1%) for placebo. Four uncomplicated herpes zoster cases and 1 retinal vein occlusion were reported with filgotinib; there were no opportunistic infections, active tuberculosis, malignancies, gastrointestinal perforations, or deaths.Among patients with active RA who had an inadequate response or intolerance to 1 or more bDMARDs, filgotinib, 100 mg daily or 200 mg daily, compared with placebo resulted in a significantly greater proportion achieving a clinical response at week 12. However, further research is needed to assess longer-term efficacy and safety.ClinicalTrials.gov Identifier: NCT02873936.
Zwitterionic Polymer-Gated Au@TiO<sub>2</sub> Core-Shell Nanoparticles for Imaging-Guided Combined Cancer Therapy
Authors: Tao Zheng, Wentao Wang, Fan Wu, Ming Zhang, Jian Shen, Yi Sun
Journal: Theranostics (2019)

With advances in nanoparticle (NP) synthesis and engineering, nanoscale agents with both therapeutic and diagnostic functions have been increasingly exploited for cancer management.Herein, we synthesized a new type of zwitterionic polymer-gated Au@TiO 2 core-shell nanoparticles, which showed that they could selectively target and efficiently eliminate cancer cells via photothermal therapy (PTT), photodynamic therapy (PDT), pH/NIR-induced drug release, and cationic therapy.Methods: In the present study, the multifunctional therapeutic agent [Mn@P(CitAPDMAEMA) @Au@TiO 2 @DOX] was prepared to treat cancer with imaging-guided combination method.Firstly, Au@TiO 2 core-shell nanoparticles (NPs) were synthesized.Taking advantage of broad and strong photoabsorption and reactive oxygen species (ROS) generation, Au@TiO 2 core-shell NPs facilitated the single light-induced PTT and PDT.Next, a chemotherapy drug doxorubicin (DOX) was loaded into Au@TiO 2 core-shell NPs.Then, a biocompatible zwitterionic polymer P(CitAPDMAEMA) was grafted to improve the hemocompatibility of NPs and prolong the circulation time.The polymer also served as a capping or switching material for pH-triggered drug release.In addition, the cationic nature of P(CitAPDMAEMA) eased the binding to human cervical cancer (HeLa) cells and effectively inhibited their growth in acidic environments (termed cationic therapy).Moreover, with Mn 2+ ions immanently chelated, Mn@P(CitAPDMAEMA)@Au@TiO 2 @ DOX NPs were able to provide enhanced contrast under T 1 -or T 2 -weighted magnetic resonance imaging (MRI). Results:The in vitro and in vivo anticancer experiments demonstrated the tumor was effectively inhibited with minimal side effects by the multifunctional NPs.Conclusions: As far as we know, this is the first presentation of four therapeutic methods into one nanomaterial, which will open up a new dimension for the design of combined treatment.
The need for an ethics of responsibility in biodiversity
Authors: Michael E van Beinum
Journal: BMJ (2019)

Bernstein draws much needed attention to the catastrophic loss of biodiversity.1 I agree we need to think hard about medicine’s environmental impact, but we should go further than just reducing medicine’s ecological footprint. Bernstein argues we need to conserve biodiversity because we might benefit from possible future medical developments using other living organisms. This is a mindset where human beings …