tbuckley/cabot-search huggingface dataset:
Self‐Assembling Peptide Hydrogel Matrices Improve the Neurotrophic Potential of Human Adipose‐Derived Stem Cells
Authors: Alessandro Faroni, Victoria L. Workman, Alberto Saiani, Adam J. Reid
Journal: Advanced Healthcare Materials (2019)

Abstract Despite advances in microsurgical techniques, treatment options to restore prior function following peripheral nerve injury remain unavailable, and autologous nerve grafting remains the therapy of choice. Recent experimental work has focused on the development of artificial constructs incorporating smart biomaterials and stem cells, aspiring to match/improve the outcomes of nerve autografting. Chemically stimulated human adipose‐derived stem cells (dhASC) can improve nerve regeneration outcomes; however, these properties are lost when chemical stimulation is withdrawn, and survival rate upon transplantation is low. It is hypothesized that interactions with synthetic hydrogel matrices could maintain and improve neurotrophic characteristics of dhASC. dhASC are cultured on PeptiGel‐Alpha 1 and PeptiGel‐Alpha 2 self‐assembling peptide hydrogels, showing comparable viability to collagen I control gels. Culturing dhASC on Alpha 1 and Alpha 2 substrates allow the maintenance of neurotrophic features, such as the expression of growth factors and neuroglial markers. Both Alpha 1 and Alpha 2 substrates are suitable for the culture of peripheral sensory neurons, permitting sprouting of neuronal extensions without the need of biological extracellular matrices, and preserving neuronal function. PeptiGel substrates loaded with hdASC are proposed as promising candidates for the development of tissue engineering therapies for the repair of peripheral nerve injuries.
Screening of nasopharyngeal carcinoma by serology and nasopharyngoscopy and treatment outcome in endemic region
Authors: D. T. Chua, M. Ji, Y. Zong, K. Chan, M. Ng
Journal: Journal of Clinical Oncology (2009)

6029 Background: To study the incidence and treatment outcome of nasopharyngeal carcinoma (NPC) detected by serology and nasopharyngoscopy in endemic region. Methods: A prospective screening program for NPC using Epstein-Barr virus-specific viral capsid antigen IgA antibody level and nasopharyngoscopy was carried out in Southern China from 1996 to 2002. Subjects without NPC at the time of enrollment were followed-up annually by serology and clinical examination irrespective of their serology status. Subjects diagnosed to have NPC at the time of enrollment or during follow-up received conventional radiotherapy using megavoltage photon. Results: A total of 42,048 adults in Zhongshan city of China were enrolled into the screening program. About 7.4% had elevated IgA titre at the time of enrollment. NPC was diagnosed at first screening in 40 subjects and during follow-up in 131 subjects. Among the 171 NPC patients, 74 were asymptomatic and the disease was detected by the screening procedures, whereas the disease was detected in 97 following onset of symptoms. Stage distribution in those diagnosed by screening program was 59.5% stage I, 8.1% stage II, 21.6% stage III, and 10.8% stage IV. The corresponding stage distribution in subjects diagnosed after onset of symptoms was 7.2%, 12.4%, 39.2%, and 41.2%. In all NPC patients the IgA titre was found elevated and there was a serologic window in which the raised titre preceded the diagnosis of NPC for a period of up to 10 years. The median interval of this serologic window was 29 months in patients with stage I NPC and 39 months in those with stage II-IV disease. The 5-year disease-specific survival rate was 90% for stage I disease, 56% for stage II, 48% for stage III, and 52% for stage IV. Conclusions: Screening by serology and nasopharyngoscopy leads to the early diagnosis of NPC in endemic region with a high survival rate after treatment for stage I disease. In view of the rapid transition of disease from stage I to more advanced stage, a screening interval shorter than 10 months is recommended for subjects entering the serologic window. No significant financial relationships to disclose.
Prognostic implication of KIT mutations in melanoma.
Authors: Katherine G. Roth, Emily C. Zabor, Marta N. Colgan, Jedd D. Wolchok, Paul B. Chapman, Gary K. Schwartz, Katherine S. Panageas, Richard D. Carvajal
Journal: Journal of Clinical Oncology (2013)

9049 Background: The natural history of BRAF and NRAS mutant (mut) melanoma (mel) has been described, but prognostic implications of KIT mut mel have not. Methods: We performed a single-center retrospective review of 180 patients (pts) enriched for mucosal, acral or chronic sun-damaged skin (CSD) mel and screened for KIT, BRAF, and NRAS mut from 4/07 - 4/10 as a part of a phase II imatinib study. Pt/disease characteristics were compared using the Kruskal-Wallis or Chi-square tests. Factors associated with outcomes were assessed by Kaplan-Meier methods and multivariable Cox regression. Results: Median age, 63.7 years; 54.4% male. Primary site: 40% mucosal, 29% acral, 22% CSD, 9% others. Mut rate: 18% KIT, 16% BRAF, 14% NRAS, 52% wild-type (wt). Pathologic subtype differed by genetic subgroup (p&lt;.001) while age, gender, and stage did not (all p&gt;0.05). 18/26 (69%) KIT mut pts received imatinib in the metastatic (met) setting; 6/18 received &gt; 1 other KIT inhibitor. 3/25 (12%) BRAF mut pts received vemurafenib. 8/27 (30%) KIT mut, 4/27 (15%) BRAF mut, 6/20 (30%) NRAS mut, and 6/20 (30%) wt pts received ipilimumab. 149/180 (83%) pts developed mets at a median of 2.15 years (95% CI: 1.72, 2.72). Median follow-up (FU) of pts not developing mets was 3.91 yrs (range: 0.25, 14.34). Older age (HR: 1.02, 95% CI: 1.00, 1.03) and pathologic subtype (mucosal vs CSD HR: 1.70, 95% CI: 1.02, 2.84; non-CSD/unknown vs CSD HR: 2.05, 95% CI: 1.00, 4.21) were associated with increased risk of mets but not with time from mets to death. Of 149 pts who progressed, 123 (83%) died during FU. Median time from met to death was 1.21 years (95% CI: 0.91, 1.67). Median FU from time of mets among those alive at last FU was 2.53 yrs (range: 0.06, 6.85). Mut status including KIT mut was not associated with time to first met or time from met to death. Pts who received ipilimumab from time of first distant met had reduced risk of death (HR: 0.55, 95% CI: 0.36, 0.87) independent of mut status. No impact was observed with KIT inhibition. Conclusions: KIT mut status is not an independent predictor of time to mets or survival in pts with mets. Ipilimumab improved pt outcomes regardless of mut status. The lack of impact of KIT inhibitors is likely due to the heterogeneity of KIT mut in mel but does not preclude efficacy in appropriately selected pts.
Effect of miR-506 on pirarubicin sensitivity and on mesenchymal to epithelial transition and DNA damage homologous recombination repair process in leiomyosarcoma.
Authors: Jilong Yang, Ting Li, Feng Li
Journal: Journal of Clinical Oncology (2019)

e22503 Background: MicroRNAs has been shown to be involved in many processes of tumorigenesis. Furthermore, miR-506 has been confirmed to be related to the occurrence of epithelial to mesenchymal transition (EMT) and tumor chemoresistance. However, the role of miR-506 in leiomyosarcoma has not yet been reported. Methods: A retrospective review of the 61 Chinese patients diagnosed with soft tissue leiomyosarcoma from January 2000 to December 2012 was investigated. Patient survival trends were examined by Kaplan-Meier analysis and log-rank tests. In vitro experiments were used to determine the biological function and physiological mechanism of drug sensitivity of miR-506. Results: In Chinese leiomyosarcoma patient cohort, we detected a decreased expression of miR-506 in the tumor tissues than that in marginal normal tissues. Tissue microarray analysis detected and confirmed a novel mesenchymal to epithelial transition (MET) in soft tissue leiomyosarcoma, also this MET phenomena was correlated with survival. In vitro, miR-506 inhibited the proliferation, migration, and invasion of leiomyosarcoma cells by promoting the occurrence of MET. Furthermore, RAD51, RAD52, ATM and ATR, which are defined as DNA damage homologous recombination repair related proteins, were highly expressed and associated with worse overall survival of leiomyosarcoma patients. Through targeting MET and DNA damage homologous recombination repair related proteins, miR-506 promoted the sensitivity of leiomyosarcoma cells to Pirarubicin. Conclusions: The current study reveals a novel mechanism that miR-506 increases the drug sensitivity of tumor cells, which are probably in association with the MET and DNA damage homologous recombination repair process.
Abstract 18804: Interleukin-18 Binding Protein Improves Cardiac Function in a Mouse Model of Western-diet Induced Cardiomyopathy
Authors: Pratyush Narayan, Salvatore Carbone, Adolfo G Mauro, Eleonora Mezzaroma, Donatas Kraskauskas, William P Adams, Priyanka Kundur, Krishna Ravindra, Benjamin W Van Tassell, Antonio Abbate, Stefano Toldo
Journal: Circulation (2017)

Introduction: Western Diet (WD) is a risk factor for metabolic and cardiovascular diseases, and induces cardiac dysfunction in mice, through an interleukin(IL)-18 mediated mechanism. However, wheth...
Relationship of alterations in the expression of nontargeted genes and suppression of bcl-2 by antisense oligonucleotides.
Authors: Marvin Rubenstein, Courtney M.P. Hollowell, Patrick Guinan
Journal: Journal of Clinical Oncology (2012)

e13513 Background: Antisense oligos have been employed against prostate cancer models targeting proteins associated with growth/apoptosis. However gene therapy may not be totally specific. Oligos against bcl-2 are in clinical trials and it was of interest: 1) To see whether therapy produces non-specific effects compromising efficacy; 2) To identify genes whose activity may have to be maintained/replaced. Methods: In LNCaP cells we evaluated monospecific (directed against bcl-2) and bispecific (directed against bcl-2 &amp; epidermal growth factor receptor) oligos which comparably suppressed bcl-2. Cells were evaluated by PCR for expression of non-targeted genes associated with apoptosis (caspase-3, clusterin); androgen regulation (androgen receptor [AR], p300, creb binding protein [CBP]); cytokines (interleukins 2 [IL-2], 4 [IL-4], interferon [IFN]); antigen expression (prostate specific antigen [PSA], prostate membrane antigen [PSMA], prostatic acid phosphatase [PAP]); and autocrine growth (insulin like growth factor [IGF1]). Results: Most non-targeted genes were unaffected. However following suppression of bcl-2 activity by mono- and bispecific oligos, cells compensated by suppressing caspase-3 (apoptosis promoter) and enhancing AR and coactivator p300 expression. This suggests an ability to reverse bcl-2 suppression of apoptosis through decreased expression of a promoter and increased androgen sensitivity. It identifies caspase-3 as an essential gene whose expression must be either maintained/replaced when bcl-2 is therapeutically suppressed. Among the differentiation antigens, cell surface PSMA expression was increased by bispecific oligos; secretory PSA and PAP were not. Increased PSMA may to be due to induced IFN expression produced by bispecific oligos, attributed to a 2X intrastrand conformation not seen in the monospecific oligo. Increased PSMA expression could make prostate cancer cells more recognizable to cytotoxic T cells and potentiate prostate cancer vaccines. Conclusions: If gene therapy is to be effective, the mechanisms for compensatory changes which contribute to tumor resistance must be further identified/controlled.
Tumor necrosis factor alpha (TNF-α) activates androgen receptor (AR) in LNCaP prostate cancer cells
Authors: Soo Ok Lee, Jae Yeon Chun, Wei Lou, Allen Gao
Journal: Cancer Research (2007)

313  TNF-α induces a range of biological responses associated with apoptosis/survival in many cells. TNF-α stimulates death receptor mediated signaling pathway that activates a downstream protease cascade leading to cell death. On the other hand, TNF-α induces a receptor mediated survival pathway involving activation of a series of protein kinases and NFκB. TNF-α has been shown to be associated with cancer progression. In prostate cancer patients, especially in recurrent tumor patients, the serum level of TNF-α is elevated and is closely correlated with the extent of disease state. Such result suggests that TNF-α is associated with the progression of prostate cancer. Nevertheless, very limited number of studies has been done regarding the effect of TNF-α on AR signaling in prostate cancer cells.  We tried to examine whether TNF-α affects AR signaling pathway in LNCaP prostate cells. We found that TNF-α stimulates nuclear translocation of AR. TNF-α increases transcriptional activity of AR significantly in androgen depleted condition. The mRNA and protein level of AR regulated PSA was increased upon TNF-α treatment. The effect of TNF-α on acetylation level of AR was examined by immunoprecipitation study using antibody against acetylated lys. We found that AR acetylation is increased by TNF-α treatment in the absence of androgen. In addition, TNF-α treatment increased CBP/p300 expression in LNCaP cells in the absence of androgen.  Taken together our results suggest that TNF-α acts as a non-steroidal activator of AR signaling in LNCaP cells, especially in the absence of androgen. The acetylation of AR signaling by TNF-α may be mediated through activation of CBP/p300.
Stress and microbiota: Between biology and psychology
Authors: Rasmus Hoffmann Birk
Journal: Behavioral and Brain Sciences (2019)

Abstract This comment expands on Hooks et al.’s criticism of the problematic and overly general uses of “stress” within the microbiota-gut-brain field. The comment concludes that, for the microbiota-gut-brain field (as for other fields drawing on “stress”), much work is yet to be done in terms of how we explore and understand biology vis-à-vis psychology.
Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations
Authors: Juncheng Dai, Jun Lv, Meng Zhu, Yuzhuo Wang, Na Qin, Hongxia Ma, Yong-Qiao He, Ruoxin Zhang, Wen Tan, Jingyi Fan, Tianpei Wang, Hong Zheng, Qi Sun, Lijuan Wang, Mingtao Huang, Zijun Ge, Canqing Yu, Yu Guo, Tong-Min Wang, Jie Wang, Lin Xu, Weibing Wu, Liang Chen, Zheng Bian, Robin Walters, Iona Y Millwood, Xi-Zhao Li, Xin Wang, Rayjean J Hung, David C Christiani, Haiquan Chen, Mengyun Wang, Cheng Wang, Yue Jiang, Kexin Chen, Zhengming Chen, Guangfu Jin, Tangchun Wu, Dongxin Lin, Zhibin Hu, Christopher I Amos, Chen Wu, Qingyi Wei, Wei-Hua Jia, Liming Li, Hongbing Shen
Journal: The Lancet Respiratory Medicine (2019)
A phase I trial combining plinabulin and nivolumab for metastatic NSCLC: Trial in progress.
Authors: Nicolas Villanueva, Klarissa Son, Shihfan Yeh, Sonia Jain, Elaine Eng, Ken Lloyd, Lan Huang, Ramon W. Mohanlal, Lyudmila Bazhenova
Journal: Journal of Clinical Oncology (2019)

TPS128 Background: Plinabulin (Plin) is a microtubule-destabilizing agent (MDA) that inhibits the polymerization of tubulin monomers and leads to disruption of the tumor vasculature. It has been shown in clinical studies of advanced NSCLC to produce a significantly longer duration of response when combined with docetaxel versus docetaxel alone (NCT00630110). MDAs were also shown to trigger the maturation of dendritic cells and the production of pro-inflammatory cytokines, thereby enhancing T-cell proliferation. Pre-clinical studies have shown that MDAs in combination with immune checkpoint inhibitors (ICI) demonstrated a superior response rate and survival when compared to ICI alone. Nivolumab is an anti-PD-1 antibody that is FDA approved for previously treated metastatic NSCLC regardless of PD-L1 expression. We hypothesized that the combination of Plin and Nivolumab will enhance the immune response, resulting in a higher response rate and longer overall survival. Methods: This is an open label single center phase I trial. The Dose Escalation Portion (Part 1) employs a 3+3 design with dose escalation of Plin starting at 13.5mg/m 2 (biologically effective dose as single agent), combined with the FDA approved dose of Nivolumab 240mg. Plin is given on days 1,8, and 15 of 28- day cycles and Nivolumab is given on days 1 and 15. The dose of Plin will be escalated to 20mg/m 2 , 30 mg/m 2 , and 40mg/m 2 until the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) is determined. The Expansion Cohort (Part 2) will enroll 20 patients with NSCLC to be treated at the RP2D, including the patients who will have received this dose in Part 1. Treatment will continue until disease progression, development of unacceptable toxicity, or a protocol-defined reason for discontinuation. Eligible patients include metastatic NSCLC who have failed platinum-based doublet and regardless of prior anti-PD-1/PD-L1 antibody treatment. Part 1 is enrolling in an expanded cohort 2 due to one dose-limiting toxicity (DLT) in this group. Clinical trial information: NCT02812667.
Sixty seconds on . . . Dr Alexa
Authors: Abi Rimmer
Journal: BMJ (2019)

This is the news that the NHS has partnered with Amazon to provide health information from the NHS website through the technology company’s smart speaker, Amazon Alexa.

You know—so that you can now shout things like, “Alexa, how do I treat a migraine?” from the comfort of your sofa. Although, if you do have a migraine, maybe don’t shout. …
Risk, Benefit, and Fairness in a Big Data World
Authors: Christine Cassel, Andrew Bindman
Journal: JAMA (2019)

humans, while societal, environmental, and ethical implications of such activity are discussed among scientific and governmental organizations."The organizing committee of the International Summit on Human Gene Editing followed suit with the conclusion that until there is resolution of relevant safety and efficacy issues and "broad societal consensus about the appropriateness of the proposed application," proceeding with any clinical use of germline editing would be irresponsible.Viewed collectively, earlier statements on heritable genome editing may have said it all without invoking the word moratorium.The battle lines over heritable genome editing currently pit those who choose to ask "whether" to proceed against those who ask "how" to press on.The latter hold that the collective ethical good is best served by a "responsible path" toward the prevention of crippling monogenic disorders; they are willing to trust that regulatory agencies such as the US Food and Drug Administration will hold applications for heritable genome editing to rigorous demonstrations of safety and efficacy before they garner agency approval.Those committed to asking whether to move forward with heritable genome editing espouse the primacy of a "broad societal consensus" as a precondition but have not articulated precisely how such societal accord may be attained.With few precedents or a process to draw upon, public education, discussion, and approval remain a work in progress.These and related challenges must be resolved in a timely fashion to ensure that the prevention of otherwise untreatable genetic maladies is not being held up.Such cures mustn't wait.
Germline Variants in Highly Selected Patients With Prostate Cancer
Authors: Patrick R. Benusiglio, Clément Korenbaum, Florence Coulet
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
18F-Fluciclovine Uptake in Celiac Ganglia
Authors: Sean Wo, Manuela Cristina Matesan
Journal: Clinical Nuclear Medicine (2019)

Abstract We present 4 cases of patients who underwent 18 F-fluciclovine PET for prostate cancer demonstrating physiologic uptake in the celiac ganglia, which could be mistaken for metastatic lymphadenopathy if the celiac ganglia have a nodular configuration and uptake higher than bone marrow. Uptake in celiac, cervical, and sacral ganglia has been reported previously as an important pitfall in 68 Ga-PSMA-HBED-CC PET for prostate cancer. In our patients, only celiac ganglion uptake was visualized. Advances in PET scanner technology may cause physiologic uptake of 18 F-fluciclovine in celiac ganglia to become more visually distinguishable from muscular uptake in adjacent diaphragmatic crura.
Potential of nintedanib in treatment of progressive fibrosing interstitial lung diseases
Authors: Lutz Wollin, Jörg H.W. Distler, Elizabeth F. Redente, David W.H. Riches, Susanne Stowasser, Rozsa Schlenker-Herceg, Toby M. Maher, Martin Kolb
Journal: European Respiratory Journal (2019)

A proportion of patients with fibrosing interstitial lung diseases (ILDs) develop a progressive phenotype characterised by decline in lung function, worsening quality of life and early mortality. Other than idiopathic pulmonary fibrosis (IPF), there are no approved drugs for fibrosing ILDs and a poor evidence base to support current treatments. Fibrosing ILDs with a progressive phenotype show commonalities in clinical behaviour and in the pathogenic mechanisms that drive disease worsening. Nintedanib is an intracellular inhibitor of tyrosine kinases that has been approved for treatment of IPF and has recently been shown to reduce the rate of lung function decline in patients with ILD associated with systemic sclerosis (SSc-ILD). In vitro data demonstrate that nintedanib inhibits several steps in the initiation and progression of lung fibrosis, including the release of pro-inflammatory and pro-fibrotic mediators, migration and differentiation of fibrocytes and fibroblasts, and deposition of extracellular matrix. Nintedanib also inhibits the proliferation of vascular cells. Studies in animal models with features of fibrosing ILDs such as IPF, SSc-ILD, rheumatoid arthritis-ILD, hypersensitivity pneumonitis and silicosis demonstrate that nintedanib has anti-fibrotic activity irrespective of the trigger for the lung pathology. This suggests that nintedanib inhibits fundamental processes in the pathogenesis of fibrosis. A trial of nintedanib in patients with progressive fibrosing ILDs other than IPF (INBUILD) will report results in 2019.
Intermittent preventive treatment with dihydroartemisinin–piperaquine and risk of malaria following cessation in young Ugandan children: a double-blind, randomised, controlled trial
Authors: Mary K Muhindo, Prasanna Jagannathan, Abel Kakuru, Bishop Opira, Peter Olwoch, Jaffer Okiring, Noeline Nalugo, Tamara D Clark, Theodore Ruel, Edwin Charlebois, Margaret E Feeney, Diane V Havlir, Grant Dorsey, Moses R Kamya
Journal: The Lancet Infectious Diseases (2019)