tbuckley/cabot-search huggingface dataset:
Mouse IP-10 Gene Delivered by Folate-modified Chitosan Nanoparticles and Dendritic/tumor Cells Fusion Vaccine Effectively Inhibit the Growth of Hepatocellular Carcinoma in Mice
Authors: Zixi Hu, Jiaojiao Chen, Sufang Zhou, Nuo Yang, Siliang Duan, Zhenghua Zhang, Jing Su, Jian He, Zhiyong Zhang, Xiaoling Lu, Yongxiang Zhao
Journal: Theranostics (2017)

Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy.However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment.In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors.FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells.The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice.The combination therapy significantly reduced myeloid-derived suppressor cells (MDSC) in mouse spleen, local tumor, and bone marrow while increasing tumor-specific IFN-γ responses.Furthermore, the combination therapy significantly inhibited tumor cell proliferation while promoting their apoptosis.Taken together, our data illustrate that the mIP-10 enhances the anti-tumor effect of DC/tumor cell fusion vaccine by alleviating the immunosuppressive tumor environment.
The<i> DICER1</i> syndrome: Genotype-phenotype correlation in PPB patients.
Authors: Leslie Ann Doros, Joyce Turner, Gretchen M Williams, Christopher Rossi, Kris Ann Pinekenstein Schultz, Douglas Stewart, Louis P Dehner, Yoav H. Messinger, D Ashley Hill
Journal: Journal of Clinical Oncology (2015)

10022 Background: Mutations in DICER1 were first described in 2009 from individuals diagnosed with pleuropulmonary blastoma (PPB). Since then, DICER1 mutations have been found in individuals with other tumor types. Collectively, mutations in this gene and associated tumors make up the DICER1 Syndrome. About 40% of PPB patients or first/second-degree relatives exhibit ≥ 1 feature of the syndrome. Through a multi-institutional study, we aim to better understand the DICER1syndrome disease spectrum and genotype-phenotype correlations. Methods: Informed consent was obtained from participants or legal guardians. Use of Sanger and Next-Gen sequencing, and targeted aCGH on blood, saliva and tumor tissue was performed. Phenotypes were abstracted from the International PPB Registry (IPPBR) records. Results: To date, 409 PPB patients have enrolled in the IPPBR. More than 150 individuals with PPB have undergone genetic testing; 111 have a deleterious mutation. About 43% of PPB mutation positive individuals were found to have additional related conditions: benign lung cysts (22%), cystic nephroma(CN)/renal cysts (16%), thyroid hyperplasia/cancer (20%), embryonal rhabdomyosarcoma (5%), nasal chondromesenchymal hamartoma (6%), ovarian Sertoli-Leydig cell tumor (4%), ciliary body medulloepithelioma (2%), and rarely Wilms tumor, Hodgkin’s lymphoma, neuroblastoma, and brain tumors. Twelve (30%) mutation negative PPB patients were found to have additional related conditions with the most common being CN and thyroid disease. Patients with mosaic RNase IIIb mutations had the greatest number of disease foci. Conclusions: The germline mutation detection rate among this cohort is ~67% via Sanger sequencing. Use of Next-Gen sequencing and targeted aCGH increased detection to 75%. Deletions and mosaicism have been identified through these means. DICER1 mutation positive PPB patients are at significant risk for other conditions. Sanger and Next-Gen sequencing mutation negative patients with multiple conditions require further molecular analysis. Understanding the DICER1 syndrome spectrum of conditions and specific genotype-phenotype correlations will improve surveillance recommendations.
HPV status to predict outcome for anal cancer treated with radiochemotherapy.
Authors: Sabine Kathrin Mai, Miriam Reuschenbach, Martine Ottstadt, Grit Welzel, Marcus Trunk, Nicolas Wentzensen, Frank Lohr, Magnus von Knebel Doeberitz, Frederik K. Wenz
Journal: Journal of Clinical Oncology (2013)

4065 Background: Evaluation of the HPV infection- and transformation-status as a predictor of the response to definitive radio-chemotherapy for anal cancer. Methods: 80 patients (54 fm, 26 m) with histologically confirmed anal cancer and known HPV-Infection- (determined by PCR) and p16-expression-status (determined by immunohistochemistry) were analyzed. All pts. were treated with definitive radio-chemotherapy (RCT) with 5-FU/MMC, median age 60ys (35–86), median follow up 54mo (4–180). 41 pts. were HPV+ and p16+ (group 1), 10 pts. were HPV-/p16+ (group 2), 9 pts. were HPV+/p16- (group 3) and 17 pts. were HPV+/p16- (group 4). Endpoints were local control (LC) at 5ys and overall survival (OS) at 5ys. In addition to HPV/p16 status, the influence of T-stage and tumor localization (canal vs. margin) was analyzed. Results: More women than men were HPV+ (fm 77% vs. m 33%) while gender was evenly distributed among HPV-pts. (fm 48% vs. m 53%). Upon univariate analysis, gender, HPV+ and p16+ were significant predictors of both LC and OS (p&lt;0.05) while T-Stage was predictive for LC (p&lt;0.05). Upon multivariate analysis, gender and T-Stage significantly influenced LC (w85.2% vs. m54.9%, p=0.028; &lt;T3 84.2% vs ≥ T3 48,1%, p=0,019). OS was significantly influenced by gender (w95% vs. m59.2%, p=0.005), while the influence of HPV/p16-status did not reach significance when all four groups were analyzed simultaneously in this moderately sized cohort. Upon direct univariate comparison of HPV+/p16+ und HPV-/p16-pts, both gender and combined HPV/p16-positivity had a significant influence on LC and OS. Upon multivariate analysis, combined HPV/p16-positivity resulted in better LC (HPV+/p16+: 85% vs. HPV-/p16-: 38.7%, p=0.003), while, as a consequence of moderate patient numbers, only gender significantly predicted OS (fm93.7% vs. m62.6%, p=0.015). Viral status, however, showed a trend for significance. Conclusions: The data from one of the largest monocentric series treated with a uniform treatment regimen suggest that HPV-status predicts response to RCT in pts. with anal cancer. Patients with tumors not associated with HPV whatsoever (HPV-/P16-) have both inferior LC and a clear trend for inferior OS and might require an intensified treatment regimen.
Functional Decline 5 Years After Blast Traumatic Brain Injury
Authors: Kristen Dams-O’Connor, Jack W. Tsao
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Payments to Physicians
Authors: Bernard Lo, Deborah Grady
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
Electronic Cross Matching System. Is Routine Pre-Operative Cross Matching of Blood for Colorectal Resections Required Anymore?
Authors: N Kulkarni, M Ali, PN Haray, A Joseph, A Masoud
Journal: Endoscopy (2006)

Aims: ACPGBI guidelines for colorectal cancer advocate routine blood cross matching for all colorectal resections apart from right hemicolectomies. As the electronic cross matching system in our DGH enables blood to be issued within minutes of request, we have reviewed the usage of blood in patients operated for colorectal cancer.
Assessing varicella vaccine effectiveness and its influencing factors using health insurance claims data, Germany, 2006 to 2015
Authors: Thorsten Rieck, Marcel Feig, Matthias an der Heiden, Anette Siedler, Ole Wichmann
Journal: Eurosurveillance (2017)

In Germany, routine childhood varicella vaccination was implemented in 2004 with two doses recommended since 2009. We used an immunisation information system based on countrywide health insurance claims data to analyse vaccine effectiveness (VE) and factors influencing VE. We applied proportional hazard models to estimate VE under various conditions and compared the risk of acquiring varicella among unvaccinated children in regions with high vs low vaccination coverage (VC). Among 1.4 million children we identified 29,404 varicella cases over a maximum follow-up of 8 years post-vaccination. One-dose VE was 81.9% (95% confidence interval (CI): 81.4-82.5), two-dose VE 94.4% (95% CI: 94.2-94.6). With dose one given 1-27 days after measles-containing vaccine (MCV), one-dose VE was 32.2% (95% CI: 10.4-48.6), two-dose VE 92.8% (95% CI: 84.8-96.6). VE was not associated with age at vaccination (11-14 vs ≥ 15 months), time since vaccination, or vaccine type. Unvaccinated children had a twofold higher risk of acquiring varicella in low VC regions. Our system generated valuable data, showing that two-dose varicella vaccination provides good protection for at least 8 years. Unvaccinated children benefit from herd effects. When the first varicella vaccine dose is given shortly after MCV, a second dose is essential.
Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia
Authors: Lifeng Feng, Jiaqiu Li, Lixian Yang, Libo Zhu, Xiufeng Huang, Shuzheng Zhang, Likang Luo, Zhinong Jiang, Tingting Jiang, Wenxia Xu, Xian Wang, Hongchuan Jin
Journal: Theranostics (2017)

Long-term application of Tamoxifen (TAM) is usually recommended for hormone receptor positive breast cancer patients.Unfortunately, TAM will inevitably increase the incidence of endometrial hyperplasia even endometrial cancer.Despite of substantial investigations, no effective approaches to prevent TAM-induced endometrial carcinogenesis have been acknowledged.In this study, we found that inhibition of Nrf2 could be valuable to prevent TAM-induced endometrial hyperplasia.Upon TAM treatment, the mRNA and protein expression of autophagy adaptor SQSTM1 was specifically increased in endometrial cells but not breast cancer cells.Knocking-down of SQSTM1 expression retarded TAM-promoted growth of endometrial cancer cells.TAM stimulated SQSTM1 transcription specifically in endometrial cells by enhancing phosphorylation and nuclear translocation of Nrf2.Indeed, the expression of Nrf2 and SQSTM1 were positively correlated in primary endometrial tissues.In rats with TAM-induced endometrial hyperplasia, both Nrf2 and SQSTM1 expression were increased.Nrf2 inhibitor brusatol effectively attenuated TAM-induced SQSTM1 upregulation and endometrial hyperplasia.The kinase of Nrf2, PRKCD, was activated by TAM.Once PRKCD was depleted, TAM failed to promote Nrf2 phosphorylation and SQSTM1 expression.In summary, TAM stimulated Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia by activating PRKCD.Therefore, blocking PRKCD-Nrf2-SQSTM1 signaling could be useful to prevent TAM-induced endometrial hyperplasia.
Antitumoral activity of EC70124, a novel multitarget kinase inhibitor, in triple-negative breast cancer.
Authors: Maria D. Cuenca-Lopez, Juan Carlos Montero, Gemma Serrano-Heras, Verónica Corrales-Sánchez, Jorge Morales, Francisco Moris, Atanasio Pandiella, Alberto Ocana Fernandez
Journal: Journal of Clinical Oncology (2014)

1116 Background: Receptor tyrosine kinases (RTK) and downstream signaling routes play a central role in the genesis and/or promotion of different breast cancer tumors including the triple negative subtype. Kinase inhibitors designed to neutralize their function are in clinical development. We describe the preclinical evaluation of EC-70124, a novel, unique profile, multi-target kinase inhibitor, in triple negative breast cancer. Methods: Cell proliferation and growth was measured by MTT uptake and matrigel in a representative panel of triple negative cell lines. Evaluation of apoptosis and cell cycle was performed by flow cytometry. Western-blot and phospho-array kits were used for evaluation of signaling intermediates. To evaluate if EC-70124 combined with other chemotherapy drugs was synergistic we used the CalcuSyn v2.0 software. Gene-set enrichment analyses were performed to identify relevant functions affected by the drug and the identified genes were confirmed by RT-PCR. In vivo anti-tumor effect was evaluated using xenografted animals. Results: EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine pathways and produced by fermentation. Doses of EC-70124 in the nanomolar ranged reduced proliferation in a panel of triple negative cell lines including HS578T, BT549, MDA-MB231 and HCC3153. Treatment with EC-70124 at 500 nM led to an induction of DNA damage measured by γH2AX. Cell cycle analyses showed an arrest at the G2/M phase in HS578T and BT549; that was confirmed by the biochemical evaluation of cell cycle mediators. Gene expression analyses showed different cellular functions induced by EC70124 being up regulation of DNA repair genes one of them. The up-regulation of these genes was confirmed by RT-PCR. EC70124 produced tumor regression of MDA-MD231 tumors in xenografted animals. No major toxicities were observed. Studies in combination with standard of care chemotherapy showed enhanced activity. Conclusions: EC-70124 is a novel multi-target kinase inhibitor with anti-tumoral activity in triple negative breast cancer. Its mechanism of action is mediated through an induction of DNA damage and cell cycle arrest at G2/M.
Asthma in reproductive-aged women with polycystic ovary syndrome and association with obesity
Authors: Thaw D. Htet, Helena J. Teede, Barbora de Courten, Deborah Loxton, Francisco G. Real, Lisa J. Moran, Anju E. Joham
Journal: European Respiratory Journal (2017)

Recent research suggests that women with polycystic ovary syndrome (PCOS) may have a higher prevalence of asthma. However, there are no epidemiological studies aimed primarily at exploring the relationship between PCOS and asthma, and the effect of body mass index (BMI) on this association. This study is a cross-sectional analyses of data from the Australian Longitudinal Study on Women's Health, a large, community-based, prospective study to examine the association between PCOS and asthma in women aged 28–33 years (n=478 PCOS and n=8134 controls). The prevalence of asthma was 15.2% in women with PCOS and 10.6% in women without PCOS (p=0.004). Women with PCOS who had asthma had a trend for a higher BMI compared with women without asthma (29.9±0.9 versus 27.7±0.4 kg·m −2 ; p=0.054). Women without PCOS who had asthma had a higher BMI compared with women without asthma (26.4±0.2 versus 24.9±0.1 kg·m −2 ; p&lt;0.001). After adjusting for age, BMI and smoking status, PCOS was associated with increased odds of asthma (odds ratio 1.34, 95% CI 1.004–1.79; p=0.047). This study showed both PCOS status and overweight/obese status were independently associated with asthma. Further prospective studies are required to explore the possible mechanisms underpinning the association between asthma and PCOS.
Skilled Movements Require Non-apoptotic Bax/Bak Pathway-Mediated Corticospinal Circuit Reorganization
Authors: Zirong Gu, Najet Serradj, Masaki Ueno, Mishi Liang, Jie Li, Mark L. Baccei, John H. Martin, Yutaka Yoshida
Journal: Neuron (2017)
A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric Antigen Receptors by Affinity Optimization
Authors: Esther Drent, Maria Themeli, Renée Poels, Regina de Jong-Korlaar, Huipin Yuan, Joost de Bruijn, Anton C.M. Martens, Sonja Zweegman, Niels W.C.J. van de Donk, Richard W.J. Groen, Henk M. Lokhorst, Tuna Mutis
Journal: Molecular Therapy (2017)
Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells
Authors: M K Hasan, J Yu, L Chen, Bing Cui, G F Widhopf II, L Rassenti, Z Shen, S P Briggs, T J Kipps
Journal: Leukemia (2017)

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration.
Analysis of the AAVrh. 10 Capsid Structure and Its Antigenic and Receptor Interactions
Authors: Mario Mietzsch, Kim van Vliet, Bridget Lins-Austin, Chun Yu, Mandy E Janssen, Felix Bröcker, Paulina Kaplonek, Giovanni Cardone, Robert McKenna, Ronald Crystal, James Wilson, Timothy Baker, Peter H. Seeberger, Regine Heilbronn, Mavis Agbandje-McKenna
Journal: Molecular Therapy (2017)
Genomic Profiling Identifies Novel Mutations and Fusion Genes in Newly Diagnosed and Relapsed Pediatric FLT3-ITD-Positive AML
Authors: Daelynn R Buelow, Stanley Pounds, Yong-Dong Wang, Lei Shi, Yongjin Li, David Finkelstein, Sheila A Shurtleff, Geoffrey A. Neale, Hiroto Inaba, Raul C. Ribeiro, Dominique Garrison, Shelley Orwick, James S. Blachly, John C. Byrd, Karl Kroll, Tanja A. Gruber, Jeffrey E Rubnitz, Sharyn D Baker
Journal: Blood (2016)
Bystander Efforts and 1-Year Outcomes in Out-of-Hospital Cardiac Arrest
Authors: Kristian Kragholm, Mads Wissenberg, Rikke N. Mortensen, Steen M. Hansen, Carolina Malta Hansen, Kristinn Thorsteinsson, Shahzleen Rajan, Freddy Lippert, Fredrik Folke, Gunnar Gislason, Lars Køber, Kirsten Fonager, Svend E. Jensen, Thomas A. Gerds, Christian Torp-Pedersen, Bodil S. Rasmussen
Journal: New England Journal of Medicine (2017)

The effect of bystander interventions on long-term functional outcomes among survivors of out-of-hospital cardiac arrest has not been extensively studied.We linked nationwide data on out-of-hospital cardiac arrests in Denmark to functional outcome data and reported the 1-year risks of anoxic brain damage or nursing home admission and of death from any cause among patients who survived to day 30 after an out-of-hospital cardiac arrest. We analyzed risks according to whether bystander cardiopulmonary resuscitation (CPR) or defibrillation was performed and evaluated temporal changes in bystander interventions and outcomes.Among the 2855 patients who were 30-day survivors of an out-of-hospital cardiac arrest during the period from 2001 through 2012, a total of 10.5% had brain damage or were admitted to a nursing home and 9.7% died during the 1-year follow-up period. During the study period, among the 2084 patients who had cardiac arrests that were not witnessed by emergency medical services (EMS) personnel, the rate of bystander CPR increased from 66.7% to 80.6% (P<0.001), the rate of bystander defibrillation increased from 2.1% to 16.8% (P<0.001), the rate of brain damage or nursing home admission decreased from 10.0% to 7.6% (P<0.001), and all-cause mortality decreased from 18.0% to 7.9% (P=0.002). In adjusted analyses, bystander CPR was associated with a risk of brain damage or nursing home admission that was significantly lower than that associated with no bystander resuscitation (hazard ratio, 0.62; 95% confidence interval [CI], 0.47 to 0.82), as well as a lower risk of death from any cause (hazard ratio, 0.70; 95% CI, 0.50 to 0.99) and a lower risk of the composite end point of brain damage, nursing home admission, or death (hazard ratio, 0.67; 95% CI, 0.53 to 0.84). The risks of these outcomes were even lower among patients who received bystander defibrillation as compared with no bystander resuscitation.In our study, we found that bystander CPR and defibrillation were associated with risks of brain damage or nursing home admission and of death from any cause that were significantly lower than those associated with no bystander resuscitation. (Funded by TrygFonden and the Danish Heart Foundation.).