tbuckley/cabot-search huggingface dataset:
In vivo efficacy of gimatecan, a Novartis new topoisomerase 1 inhibitor alone or combined with RAD001, bevacizumab or erlotinib in breast, lung and ovary human cancer xenografts.
Authors: mariefrance poupon, Franck Assayag, Ludmilla DePlater, Elisabetta Marangoni, Veronique Dieras
Journal: Cancer Research (2007)

783   Gimatecan, a novel oral lipophilic camptothecin with a favorable pharmacology profile, is a promising anticancer agent currently in clinical development. Current studies focused on evaluating the antitumor activities of gimatecan as a single agent and in combination with bevacizumab, erlotinib and the mTOR inhibitor RAD001 in seven breast cancer, three NSCLC and one ovarian cancer murine xenograft models. We used a new xenograft model where primary tumors from cancer patients were directly transplanted into female Swiss nude mice.  Drug effects were measured based on complete tumor regression with or without recurrence and in case of partial response, tumor growth inhibition (% TGI) and growth delay (TGD) leading to survival prolongation were measured. Gimatecan was orally administered via gavages at 0.32, 0.24, 0.16 and 0.12 mg/kg/day daily for 5 days per week for 4 weeks.  In breast BC146 tumor bearing-nude mice, single agent gimatecan was well tolerated showing no deaths or weight loss at gimatecan doses below 0.48 mg/kg. Complete tumor regressions were observed at a low 0.03 mg/kg (10% of the highest dosage), without recurrence 90 days after the start of treatment. Anti-tumor activity was not observed with single agent bevacizumab and RAD001, but anti-tumor activity was restored when either agent was combined with gimatecan in BC146 line.  In six other BC lines also showed high sensitivities to gimatecan, one being resistant to anthracycline and docetaxel based treatments. The squamous NSCLC IC1, resistant to platinum based therapy, and moderately sensitive to docetaxel, responded to gimatecan modestly and only at the highest dosage (72% of optimal TGI and TGD of 2-fold).  The lung adenocarcinoma IC14, poorly sensitive to platinum based therapy and sensitive to docetaxel, responded to the 0.12 mg dosage, with a TGD of 4-fold and tumor regressions at the higher dosages. Gimatecan efficacy was not increased by combination with erlotinib, which did not reduced tumor growth as a single agent. Combination with RAD001 and bevacizumab are in course of test. The lung adenocarcinoma IC8 regressed significantly under gimatecan treatment.  The ovarian model OVA2 displayed a high sensitivity to gimatecan, with complete regressions at the highest dosages and late recurrences at the two lowest dosages. Bevacizumab showed a modest efficacy and significantly reinforced the gimatecan antitumor effect with RAD001 giving similar results.  Our first series of studies confirmed the high efficacy of gimatecan in 7/7 HBC, 2/3 NSCLC, ovary, retinoblastoma, pancreas tumor models, irrespective of their sensitivity or resistance to standard treatment and was well tolerated with the dosages and the protocol used.
Transglutaminase 2 Is a Direct Target Gene of YAP-TAZ—Response
Authors: Matthew L. Fisher, Gautam Adhikary, Candace Kerr, Daniel Grun, Richard L. Eckert
Journal: Cancer Research (2017)

Transglutaminase 2 (TG2) is an important cancer stem cell survival protein (1–4). Our recent article described a novel transglutaminase 2 (TG2) signaling pathway whereby TG2 enhances cancer stem cell survival, spheroid formation, Matrigel invasion, and tumor formation in squamous cell carcinoma (5). We showed that TG2 triggers these events by activating an integrin, FAK, Src, PI3K signaling cascade that phosphorylates PDK1, causing it to dissociate from LATS1 to inhibit LATS1 activity. Inactivation of LATS1 leads to accumulation of nonphosphorylated YAP1, which then interacts with and stabilizes ΔNp63α, which drives the cancer stem cell phenotype (5). Hong and colleagues, in a letter to the editor, noted that our article did not describe regulation of TG2 by YAP1 in SCC-13 and HaCaT epidermis-derived cancer cells (5). In particular, we did not observe a change in TG2 level in squamous cell carcinoma cells expressing YAP(S127A), a constitutively active form of YAP1, or in cells treated with YAP1-siRNA. This is in contrast to their observation that YAP1 and TAZ interact with the TG2 promoter to regulate TG2 mRNA and protein level in MCF10A, HaCaT, and HCT116 cells (6). Although we have not studied the impact of YAP1 or TAZ on TG2 gene expression, we can confirm that TG2 is regulated by YAP1 and TAZ in some cell lines. For example, Fig. 1 shows a reduction in TG2 level in MCF-7 cells following treatment with YAP1 or TAZ-specific siRNA and confirms that this is associated with reduced spheroid formation. Thus, we conclude based on these findings that TG2 can be regulated by YAP1 and TAZ, but we further propose that this may depend upon the cell type and the cellular environment.See the original Letter to the Editor, p. 4734No potential conflicts of interest were disclosed.This work was supported by grants from the NIH (RLE - CA131074 and CA184027).
水環境における超微量酸化グラフェンはゼブラフィッシュ幼生におけるパーキンソン病様症状と代謝障害を誘発する【Powered by NICT】
Authors: Ren Chaoxiu, Hu Xiangang, Li Xueyan, Zhou Qixing
Journal: Biomaterials (2016)
OUP accepted manuscript
Authors: Kirsi J Granberg, Matti Annala, Birgitta Lehtinen, Juha Kesseli, Joonas Haapasalo, Pekka Ruusuvuori, Olli Yli-Harja, Tapio Visakorpi, Hannu Haapasalo, Matti Nykter, Wei Zhang
Journal: Neuro-Oncology (2017)

Inhibitors of fibroblast growth factor receptors (FGFRs) have recently arisen as a promising treatment option for patients with FGFR alterations. Gene fusions involving FGFR3 and transforming acidic coiled-coil protein 3 (TACC3) have been detected in diffuse gliomas and other malignancies, and fusion-positive cases have responded well to FGFR inhibition. As high FGFR3 expression has been detected in fusion-positive tumors, we sought to determine the clinical significance of FGFR3 protein expression level as well as its potential for indicating FGFR3 fusions.We performed FGFR3 immunohistochemistry on tissue microarrays containing 676 grades II-IV astrocytomas and 116 grades II-III oligodendroglial tumor specimens. Fifty-one cases were further analyzed using targeted sequencing.Moderate to strong FGFR3 staining was detected in gliomas of all grades, was more common in females, and was associated with poor survival in diffuse astrocytomas. Targeted sequencing identified FGFR3-TACC3 fusions and an FGFR3-CAMK2A fusion in 10 of 15 strongly stained cases, whereas no fusions were found in 36 negatively to moderately stained cases. Fusion-positive cases were predominantly female and negative for IDH and EGFR/PDGFRA/MET alterations. These and moderately stained cases show lower MIB-1 proliferation index than negatively to weakly stained cases. Furthermore, stronger FGFR3 expression was commonly observed in malignant tissue regions of lower cellularity in fusion-negative cases. Importantly, subregional negative FGFR3 staining was also observed in a few fusion-positive cases.Strong FGFR3 protein expression is indicative of FGFR3 fusions and may serve as a clinically applicable predictive marker for treatment regimens based on FGFR inhibitors.
Local allergic rhinitis is an independent rhinitis phenotype: The results of a 10‐year follow‐up study
Authors: C. Rondon, P. Campo, I. Eguiluz‐Gracia, C. Plaza, G. Bogas, P. Galindo, C. Mayorga, M. J. Torres
Journal: Allergy (2017)

Abstract Background The knowledge about the natural history of local allergic rhinitis ( LAR ) is limited. One unmet question is to demonstrate whether LAR should be considered the first step in the development of allergic rhinitis ( AR ) or an independent phenotype. The aim of this study was to prospectively evaluate the natural history of a population with LAR , the potential conversion to AR with systemic atopy and the development of asthma during 10 years. Methods This is the second phase of a 10‐year follow‐up study of a cohort of 176 patients with LAR of recent onset and 115 age‐ and sex‐matched healthy controls prospectively evaluated from 2005 to 2016. Clinical‐demographic questionnaire, spirometry, skin prick test and specific IgE were evaluated yearly. Nasal allergen provocation tests ( NAPT ) with Dermatophagoides pteronyssinus, Alternaria alternata , Olea europaea and grass pollen were performed at baseline, and after 5 and 10 years. Results After 10‐year LAR , patients experienced a significant and clinically relevant worsening of the rhinitis, with increase in emergency assistance, development of asthma, loss of allergen tolerance and impairment of the quality of life. This worsening became significant after 5 years and progressed throughout 10 years. A similar rate of development of AR with systemic atopy was detected in patients and controls (9.7% vs 7.8%, log‐rank P =.623). In 5 patients, conversion to systemic atopy occurred &gt;10 years (3%). Conclusions LAR is a well‐differentiated clinical entity with a low rate of development of systemic atopy, a natural evolution towards worsening and a risk factor for suffering asthma.
Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency
Authors: Carolyn D. Hurst, Olivia Alder, Fiona M. Platt, Alastair Droop, Lucy F. Stead, Julie E. Burns, George J. Burghel, Sunjay Jain, Leszek J. Klimczak, Helen Lindsay, Jo-An Roulson, Claire F. Taylor, Helene Thygesen, Angus J. Cameron, Anne J. Ridley, Helen R. Mott, Dmitry A. Gordenin, Margaret A. Knowles
Journal: Cancer Cell (2017)
The study of NKG2D ligand expression and NK cell cytotoxicity after HDAC inhibitors in lung cancer cell lines
Authors: Se-Hoon Lee, Soon Joo Lee, Tae Min Kim, Dae Seog Heo
Journal: Cancer Research (2008)

4646    Background:  Natural killer (NK) cell can directly kill tumor cells without the aid of other immune cells. The killing activity is determined by the balance of stimulatory signals and inhibitory signals. A signal through NKG2D receptor can overcome inhibitory signals such as major histocompatibility complex (MHC) class I, and activate NK cells. Induction of NKG2D ligand in tumor cells by some known drugs would lead to easier clinical application than genetic engineering in increasing the tumor cell’s susceptibility to NK cell killing.  Histone acetylation is one of epigenetic mechanism of gene expression control. Histone deacetylase (HDAC) inhibitor showed anti-tumor effect and has been approved in some cancers. The anti-tumor mechanism of HDAC inhibitor is not fully understood. There would be other mechanisms of anti-tumor effect besides epigenetic control of gene transcription. Immunomodulatory effect of HDAC inhibitor is a possible mechanism of action.   Methods:  We evaluated the ability of valproate (VPA) and vorinostat (SAHA) to induce NKG2D ligand in eight NSCLC cell lines (A549, NCI-H23, NCI-H157, NCI-H358, NCI-H522, NCI-H1975, PC9, SNU2292), and NK-cell cytotoxicity assay. We also investigated the ability of NKG2D ligand induction in vivo mouse model (C57BL/6 mouse with RMA cell lines).   Results:  1) We showed that NSCLC cell lines expressed NKG2D ligands with varying degree between cell lines. ULBP-2 and MICA expression was more prevalent than other NKG2D ligands at basal status. 2) VPA and SAHA increased NKG2D ligand surface expression in NSCLC cell lines. Among five NKG2D ligands, ULBP-2 and MICA were predominantly and universally induced in surface of NSCLC cell lines.  3) The surface expression of NKG2D ligands lead to increased NK cell cytotoxicity against tumor cell lines, and this increased cytotoxicity was abrogated by blocking NKG2D receptor, suggesting the increased cytotoxicity by NK cells is mediated by NKG2D signaling pathways. 4) NKG2D ligand induction was independent of apoptosis process. 5) We found that induction of NKG2D ligand occurs not only in vitro but also in vivo.   Conclusion:  We showed that HDAC inhibitor can kill tumor cells by inducing surface NKG2D ligand induction in NSCLC cell lines. The future research of anti-tumor effect by HDAC inhibitor should include this immune-facilitated mechanism, especially in clinical research.
A Song of Hope
Authors: Carol Snyder Halberstadt
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
In high-risk patients with arthritis and previous upper GI bleeding, celecoxib vs naproxen reduced recurrent bleeding
Authors: Noel Chan, Jeffrey Weitz
Journal: Annals of Internal Medicine (2017)

Source Citation Chan FK, Ching JY, Tse YK, et al. Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN): an industry-independent, double-blind, double-dummy, randomised trial. Lancet. 2017;389:2375-82. 28410791
General intelligence is an emerging property, not an evolutionary puzzle
Authors: Franck Ramus
Journal: Behavioral and Brain Sciences (2017)

Abstract Burkart et al. contend that general intelligence poses a major evolutionary puzzle. This assertion presupposes a reification of general intelligence – that is, assuming that it is one “thing” that must have been selected as such. However, viewing general intelligence as an emerging property of multiple cognitive abilities (each with their own selective advantage) requires no additional evolutionary explanation.
Survey of delivery of prophylactic immunoglobulins following exposure to a measles case
Authors: A Bernier, C Le Goaster, H Peigue-Lafeuille, D Floret
Journal: Eurosurveillance (2012)

In France, almost 23,000 cases of measles and 10 deaths have been reported between January 2008 and August 2012. French health authorities recommend delivery of human polyvalent immunoglobulins in the event of exposure to a measles case for some categories of unvaccinated persons (children under the age of 12 months, immunocompromised persons and pregnant women), within six days after exposure and following laboratory confirmation of the contact case. We carried out a postal survey among 368 French hospital pharmacies to evaluate the number of persons affected by this measure between 1 January 2010 and 31 August 2011, to describe the characteristics of these patients and to evaluate the application of the recommendations in terms of delay between exposure and immunoglobulin delivery, and confirmation of the contact case. The response rate to the survey was 73%. In total, 400 immunoglobulin deliveries were listed, most of them for children under the age of one year, and 84% of the 250 administrations with available information occurred within six days after exposure, as recommended. However, only 48% of the 209 treated contacts with available information were laboratory-confirmed when the immunoglobulins were delivered. This survey is the first evaluation of this recommendation since its introduction in 2005 and suggests that the recommendations may need to be updated.
Number of people using NHS stop smoking services continues to fall
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The number of people using NHS smoking cessation services to help them quit has fallen for the fifth year in a row.

Official figures from NHS Digital’s annual smoking cessation report showed that 307 507 people set a quit date through NHS services in 2016-17,1 down 15% from the previous year. And the number of people who self reported successfully quitting smoking after accessing NHS services fell by 16% to 155 875. NHS Digital said that the self reported quit rate therefore remained stable at 51%.

NHS Digital …
硫酸化ヒアルロン酸はスクレロスチンの結合と骨芽細胞機能を促進することにより糖尿病ラットの骨再生を改善する【Powered by NICT】
Authors: Picke Ann-Kristin, Salbach-Hirsch Juliane, Hintze Vera, Rother Sandra, Rauner Martina, Kascholke Christian, Moller Stephanie, Bernhardt Ricardo, Rammelt Stefan, Pisabarro M. Teresa, Ruiz-Gomez Gloria, Schnabelrauch Matthias, Schulz-Siegmund Michaela, C Hacker Michael, Scharnweber Dieter, Hofbauer Christine, C Hofbauer Lorenz
Journal: Biomaterials (2016)
Alveolar Recruitment Strategies After Cardiac Surgery—Reply
Authors: Marcelo B. P. Amato, Marcia S. Volpe, Ludhmila A. Hajjar
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 290: Haemogenic Endocardium Contribute To Definitive Hematopoiesis During Cardiogenesis
Authors: Haruko Nakano, Xiaoqian Liu, Armin Arshi, Ben van Handel, Rajkumar Sasidharan, Andrew W Harmon, Jae-Ho Shin, Robert J Schwartz, Simon J Conway, Richard P Harvey, Mohammad Pashmforoush, Hanna K Mikkola, Atsushi Nakano
Journal: Circulation Research (2013)

The circulatory system is the first functional organ system that develops during mammalian life. Accumulating evidences suggest that cardiac and endocardial cells can arise from a single common progenitor cell during mammalian cardiogenesis. Notably, these early cardiac progenitors express multiple hematopoietic transcription factors, consistent with previous reports. Indeed, a close relationship among cardiac, endocardial and hematopoietic lineages has been suggested in fly, zebrafish, and embryonic stem cell in vitro differentiation models. However, it is unclear when, where and how this hematopoietic gene program is in operation during in vivo mammalian cardiogenesis. Hematopoietic colony assay suggests that mouse heart explants generate myeloids and erythroids in the absence of circulation, suggesting that the heart tube is a de novo site for the definitive hematopoiesis. Lineage tracing revealed that putative cardiac-derived Nkx2-5+/Isl1+ endocardial cells give rise to CD41+ hematopoietic progenitors that contribute to definitive hematopoiesis in vivo and ex vivo during embryogenesis earlier than in the AGM region. Furthermore, Nkx2-5 and Isl1 are both required for the hemogenic activity of the endocardium. Together, identification of Nkx2-5/Isl1-dependent hemogenic endocardial cells (1) adds hematopoietic component in the cardiogenesis lineage tree, (2) changes the long-held dogma that AGM is the only major source of definitive hematopoiesis in the embryo proper, and (3) represents phylogenetically conserved fundamental mechanism of cardio-vasculo-hematopoietic differentiation pathway during the development of circulatory system.
Long-term outcomes and secondary prevention after acute coronary events in patients with rheumatoid arthritis
Authors: Ängla Mantel, Marie Holmqvist, Tomas Jernberg, Solveig Wållberg-Jonsson, Johan Askling
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Patients with rheumatoid arthritis (RA) are at increased risk of acute coronary syndrome (ACS) and suffer from poorer short-term outcomes after ACS. The aims of this study were to assess long-term outcomes in patients with RA with ACS compared with non-RA patients with ACS, and to investigate whether the use of secondary preventive drugs could explain any differences in ACS outcome. Methods We performed a cohort study based on 1135 patients with RA and 3184 non-RA patients who all developed an incident ACS between 2007 and 2010. We assessed 1-year and overall relative risks for ACS recurrence and mortality, as well as prescriptions of standard of care secondary preventive drugs. Results The risk of ACS recurrence, and of mortality, was increased in RA, both at 1 year after adjusting for baseline comorbidities (HR=1.30(95% CI 1.04 to 1.62) and 1.38(95% CI 1.20 to 1.59), respectively) and throughout the complete (mean 2 years) follow-up (HR=1.27(95% CI 1.06 to 1.52) and 1.50(95% CI 1.34 to 1.68), respectively). Among certain subgroups of ACS, there was a tendency of lower usage of statins, whereas there were no apparent differences in others. The increased rates of ACS recurrence and mortality remained in subgroup analyses of individuals whose prescription pattern indicated both adequate initiation and persistence to secondary preventive treatments. Conclusions Patients with RA suffer from an increased risk of ACS recurrence and of death following ACS compared with general population, which in the present study could not readily be explained by differences in usage of secondary preventive drugs.
EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis
Authors: Gopinath M. Sundaram, Hisyam M. Ismail, Mohsin Bashir, Manish Muhuri, Candida Vaz, Srikanth Nama, Ghim Siong Ow, Ivshina Anna Vladimirovna, Rajkumar Ramalingam, Brian Burke, Vivek Tanavde, Vladimir Kuznetsov, E. Birgitte Lane, Prabha Sampath
Journal: The Journal of Experimental Medicine (2017)

Epithelial carcinomas are well known to activate a prolonged wound-healing program that promotes malignant transformation. Wound closure requires the activation of keratinocyte migration via a dual-state molecular switch. This switch involves production of either the anti-migratory microRNA miR-198 or the pro-migratory follistatin-like 1 (FSTL1) protein from a single transcript; miR-198 expression in healthy skin is down-regulated in favor of FSTL1 upon wounding, which enhances keratinocyte migration and promotes re-epithelialization. Here, we reveal a defective molecular switch in head and neck squamous cell carcinoma (HNSCC). This defect shuts off miR-198 expression in favor of sustained FSTL1 translation, driving metastasis through dual parallel pathways involving DIAPH1 and FSTL1. DIAPH1, a miR-198 target, enhances directional migration through sequestration of Arpin, a competitive inhibitor of Arp2/3 complex. FSTL1 blocks Wnt7a-mediated repression of extracellular signal–regulated kinase phosphorylation, enabling production of MMP9, which degrades the extracellular matrix and facilitates metastasis. The prognostic significance of the FSTL1-DIAPH1 gene pair makes it an attractive target for therapeutic intervention.