tbuckley/cabot-search huggingface dataset:
P11.06 Non epigenetic effect of vorinostat in glioblastoma cells
Authors: T Perez, R Berges, H Maccario, D Braguer, S Honoré
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma multiform (GBM) is the most frequent primitive brain tumor. GBM has a high recurrence and mortality. Histone deacetylase (HDAC) inhibitors have evoked great interest because they are able to change transcriptomic profiles to promote tumor cell death but also show undesirable side effects due to the lack of selectivity.We show new properties of low dose vorinostat, which inhibits cytoplasmic HDAC6 and display interesting non-epigenetics effects, especially on the microtubular cytoskeleton. MATERIAL AND METHODS We used murine (GL261) and human (U87 and GBM6 stem cells) cellular models. The cell proliferation was assessed by MTT tests, the migration by the 24 hours Transwell technic and by wound/healing tests. The expression levels of proteins of interest were assessed by Western Blot. Microtubules dynamics were assessed by time-lapse videomicroscopy. The synergy between drugs was tested by Loewe model. RESULTS Vorinostat inhibited the proliferation and the migration of the three cell lines mentioned above at level below the EC50.Vorinostat induces tubulin acetylation and alpha-tubulin c-terminal detyrosination that signed microtubular stabilization and these effects are independent of histone acetylation (HADC3). Interestingly, vorinostat decreases EB1 expression (a bad prognostic factor in GBM) and decreases microtubule dynamics. Moreover, vorinostat decreases neural markers such as GFAP, beta3-tubulin and CNPase and increases mural markers expression such as SMA/EGFR and PDGFR. Finally, it showed a synergy combined with erlotinib. CONCLUSION Low dose vorinostat, which do not affect histone désacetylase, has antitumor effect on glioblastoma cells by a new mechanism involving microtubule cytoskeleton. Interestingly, combination of low doses vorinostatand erlotinibshowed a strong synergy. Low dose, vorinostat could therefore represent an interesting therapeutic option and fewer side effects and that could be used to increased GBM patient sensitivity to erlotinib.
Double CD19/CD22 Chimeric Antigen Receptor-Modified T Cells for the Treatment of Stage IV Relapsed and Refractory Follicular Lymphoma
Authors: Xun Lai, Xuezhong Gu, Shih-Ting Tsao, Qin Zhang, Yu-Chen Liu, Jiang Yaxian, Li Yan, Jun Chun, Rui Zhang, Yunyun Du, Xiaoli Gao, Yingyu Yang, Xiaolian Qiu, Mingjing Fang, Song Wei, Lung-Ji Chang
Journal: Blood (2017)
Distribution of Neisseria meningitidis serogroup b (NmB) vaccine antigens in meningococcal disease causing isolates in the United States during 2009–2014, prior to NmB vaccine licensure
Authors: How-Yi Chang, Jeni Vuong, Fang Hu, Paul Liberator, Alex Chen, Cecilia B. Kretz, Amy Blain, Li Hao, Adam C. Retchless, Melissa J. Whaley, Annaliesa S. Anderson, Xin Wang
Journal: Journal of Infection (2019)
Fibroblast Growth Factor 23 and Mortality in Patients With Type 2 Diabetes and Normal or Mildly Impaired Kidney Function
Authors: Stanley M.H. Yeung, S. Heleen Binnenmars, Christina M. Gant, Gerjan Navis, Ron T. Gansevoort, Stephan J.L. Bakker, Martin H. de Borst, Gozewijn D. Laverman
Journal: Diabetes Care (2019)

OBJECTIVE To study whether fibroblast growth factor 23 (FGF23) is associated with adverse outcomes in patients with type 2 diabetes and normal or mildly impaired kidney function. RESEARCH DESIGN AND METHODS We analyzed C-terminal FGF23 levels in 310 patients with type 2 diabetes and estimated glomerular filtration rate ≥60 mL/min/1.73 m2. Associations of FGF23 with all-cause mortality and major adverse cardiovascular events (MACE) were studied by Cox regression. RESULTS During a follow-up of 5.8 years (3.3–6.5), 47 patients developed MACE and 28 patients died. FGF23 was associated with an increased risk of all-cause mortality (age- and sex-adjusted hazard ratio 2.78 [95% CI 1.76–4.40]) and MACE (1.67 [1.12–2.49]). Results were similar after additional adjustment for other potential confounders and were consistent upon replication in an independent cohort. CONCLUSIONS In patients with type 2 diabetes and normal or mildly impaired kidney function, FGF23 is associated with an increased risk of cardiovascular events and mortality.
Subsequent mortality in survivors of Ebola virus disease in Guinea: a nationwide retrospective cohort study
Authors: Mory Keita, Boubacar Diallo, Samuel Mesfin, Abdourahmane Marega, Koumpingnin Yacouba Nebie, N'Faly Magassouba, Ahmadou Barry, Seydou Coulibaly, Boubacar Barry, Mamadou Oury Baldé, Raymond Pallawo, Sadou Sow, Alpha Oumar Bah, Mamadou Saliou Balde, Steven Van Gucht, Mandy Kader Kondé, Amadou Bailo Diallo, Mamoudou Harouna Djingarey, Ibrahima Socé Fall, Pierre Formenty, Judith R Glynn, Lorenzo Subissi
Journal: The Lancet Infectious Diseases (2019)
Annals Story Slam - While Trying to Save a Noncompliant Patient's Life, They Were Trying to Save Me
Authors: John M. Spandorfer
Journal: Annals of Internal Medicine (2019)

Web Exclusives3 September 2019Annals Story Slam - While Trying to Save a Noncompliant Patient's Life, They Were Trying to Save MeFREEJohn M. Spandorfer, MDJohn M. Spandorfer, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0019 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - While Trying to Save a Noncompliant Patient's Life, They Were Trying to Save Me "While Trying to Save a Noncompliant Patient's Life, They Were Trying to Save Me," by John M. Spandorfer, MD (Duration 5:55)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 September 2019Volume 171, Issue 5Page: SS1 ePublished: 3 September 2019 Issue Published: 3 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
LINC01123, a c-Myc-activated long non-coding RNA, promotes proliferation and aerobic glycolysis of non-small cell lung cancer through miR-199a-5p/c-Myc axis
Authors: Qian Hua, Mingming Jin, Baoming Mi, Fei Xu, Tian Li, Li Zhao, Jianjun Liu, Gang Huang
Journal: Journal of Hematology & Oncology (2019)

Abstract Background Long non-coding RNAs (lncRNAs) have been associated with non-small cell lung cancer (NSCLC), but the underlying molecular mechanisms of their specific roles in mediating aerobic glycolysis have been poorly explored. Methods Next-generation RNA sequencing assay was performed to identify the differentially expressed RNAs between NSCLC tissues with high 18 F-fluorodeoxyglucose (FDG) uptake and their adjacent normal lung tissues. LINC01123 expression in NSCLC tissues was measured by real-time PCR and in situ hybridization (ISH) assay. The biological role of LINC01123 in cell growth and aerobic glycolysis capability was determined by performing functional experiments in vitro and in vivo. Further, the transcription of LINC01123 was explored by bioinformatics analysis, dual-luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay. RNA immunoprecipitation (RIP) and luciferase analyses were used to confirm the predicted competitive endogenous RNA (ceRNA) mechanisms between LINC01123 and c-Myc. Results Three hundred sixty-four differentially expressed genes were identified in RNA-seq assay, and LINC01123 was one of the most overexpressed lncRNAs. Further validation in expanded NSCLC cohorts confirmed that LINC01123 was upregulated in 92 paired NSCLC tissues and associated with poor survival. Functional assays showed that LINC01123 promoted NSCLC cell proliferation and aerobic glycolysis. Mechanistic investigations revealed that LINC01123 was a direct transcriptional target of c-Myc. Meanwhile, LINC01123 increased c-Myc mRNA expression by sponging miR-199a-5p. In addition, rescue experiments showed that LINC01123 functioned as an oncogene depending on miR-199a-5p and c-Myc. Conclusion Since LINC01123 is upregulated in NSCLC, correlates with prognosis, and controls proliferation and aerobic glycolysis by a positive feedback loop with c-Myc, it is expected to be a potential biomarker and therapeutic target for NSCLC.
Who is the best haploidentical donor for acquired severe aplastic anemia? Experience from a multicenter study
Authors: Lan-Ping Xu, Shun-Qing Wang, Yan-Ru Ma, Su-Jun Gao, Yi-Fei Cheng, Yuan-Yuan Zhang, Wen-Jian Mo, Xiao-Dong Mo, Yu-Ping Zhang, Chen-Hua Yan, Yu-Hong Chen, Ming Zhou, Yu Wang, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang
Journal: Journal of Hematology & Oncology (2019)

Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0–1), or moderate graft mononuclear cell (MNC) counts (6–10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0–1). Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.
P04.08 The role of SCN1A in glioblastomas and mixed neuronal glial tumors of pediatric age
Authors: L Giunti, V Cetica, V De Gregorio, D Mei, C Barba, A Buccoliero, L Genitori, R Guerrini, S Giglio, I Sardi, M Guidi, M Censullo
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Low and high grade gliomas, are the most common pediatric central nervous system (CNS) tumors and they show an extremely broad range of clinical behavior. Pediatric glioma is distinct from its adult counterpart with different genetic/epigenetic profile and biological features. Recently, several studies have shown the involvement of voltage-gated Na+ channels (VGSC) in different types of cancer, including gliomas. VGSC are multimeric transmembrane complexes, responsible for membrane depolarization in excitable cells playing an important role also in cell proliferation, migration, apoptosis and differentiation. VGSC are therapeutic targets in cardiovascular and neurological disorders and, in cancers, they could be a novel target for the development of promising anticancer therapy MATERIAL AND METHODS Firstly, we explored the genetic background of 9 pediatric glioblastomas (1–9 pGBMs), through whole-exome sequencing (WES) using HiSeq1000 platform (Illumina) with paired-end approach. On the basis of our results, we extended our study in another group of 16 epileptogenic mixed neuronal-glial tumors of pediatric age, (WHO grade I and II), through an amplicon approach (TSCA) using MiniSeq System platform (Illumina) RESULTS We identified variants in SCN1A gene in 3/9 pGBMs: case 3 had c.5782C&gt;G in tumor and blood; case 5 showed c.2278G&gt;T and two mosaic variants (c.5933C&gt;T, 22% and c.4942C&gt;T, 14%); case 6 showed c.667G&gt;T variant only in tumor, and not in other non tumoral tissues (blood, urine and buccal swab). No variants in SCN1A were identified in a group of 16 pediatric mixed gliomas CONCLUSION In this study, we explore the genetic background of two groups of pediatric neuroepithelial brain tumors, through Next generation sequencing approach. We identified only in pGBMs variants in SCN1A gene that encoded for VGSCs and is involved in a spectrum of early-onset epileptic encephalopathies. None of our mutated patients showed history of epilepsy. Now, it is not clear the significance of these variants in pGBMs but interestingly, these variants are present in pGBM and not in mixed gliomas. Further studies on a big cohort of patients are needed to establish if they could play a role in pGBMs aggressiveness, migration and progression. Moreover, VGSCs could be a pharmacological target in pGBMs treatment
Germline <i>BRCA</i>-Associated Endometrial Carcinoma Is a Distinct Clinicopathologic Entity
Authors: Marthe M. de Jonge, Lauren L. Ritterhouse, Cornelis D. de Kroon, Maaike P.G. Vreeswijk, Jeremy P. Segal, Rutika Puranik, Harry Hollema, Matti A. Rookus, Christi J. van Asperen, Flora E. van Leeuwen, Vincent T.H.B.M. Smit, Brooke E. Howitt, Tjalling Bosse
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Whether endometrial carcinoma (EC) should be considered part of the gBRCA1/2-associated hereditary breast and ovarian cancer (HBOC) syndrome is topic of debate. We sought to assess whether ECs occurring in gBRCA carriers are enriched for clinicopathologic and molecular characteristics, thereby supporting a causal relationship. Experimental Design: Thirty-eight gBRCA carriers that developed EC were selected from the nationwide cohort study on hereditary breast and ovarian cancer in the Netherlands (HEBON), and these were supplemented with four institutional cases. Tumor tissue was retrieved via PALGA (Dutch Pathology Registry). Nineteen morphologic features were scored and histotype was determined by three expert gynecologic pathologists, blinded for molecular analyses (UCM-OncoPlus Assay including 1213 genes). ECs with LOH of the gBRCA-wild-type allele (gBRCA/LOHpos) were defined “gBRCA-associated,” those without LOH (gBRCA/LOHneg) were defined “sporadic.” Results: LOH could be assessed for 40 ECs (30 gBRCA1, 10 gBRCA2), of which 60% were gBRCA/LOHpos. gBRCA/LOHpos ECs were more frequently of nonendometrioid (58%, P = 0.001) and grade 3 histology (79%, P &amp;lt; 0.001). All but two were in the TP53-mutated TCGA-subgroup (91.7%, P &amp;lt; 0.001). In contrast, gBRCA/LOHneg ECs were mainly grade 1 endometrioid EC (94%) and showed a more heterogeneous distribution of TCGA-molecular subgroups: POLE-mutated (6.3%), MSI-high (25%), NSMP (62.5%), and TP53-mutated (6.3%). Conclusions: We provide novel evidence in favor of EC being part of the gBRCA-associated HBOC-syndrome. gBRCA-associated ECs are enriched for EC subtypes associated with unfavorable clinical outcome. These findings have profound therapeutic consequences as these patients may benefit from treatment strategies such as PARP inhibitors. In addition, it should influence counseling and surveillance of gBRCA carriers.
Teenager diagnosed with optic neuropathy resulting from poor diet despite normal BMI
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Clinicians should consider nutritional optic neuropathy in any patient with unexplained vision symptoms and poor diet, regardless of BMI, a case report from the Annals of Internal Medicine has recommended.1

The case involved a 17 year old described as a “fussy eater” who primarily ate chips, crisps, white bread, processed ham slices, and sausage. He was given a diagnosis of nutritional optic neuropathy after two years of progressive vision loss.

He first presented to his GP with tiredness at 14, when he was noted as a “fussy eater” but otherwise well and taking no medications. He was treated for low vitamin B12 concentrations and given dietary …
关于 AE 治疗研究注册核心数据集测量的共识
Authors: F.M. Vermeulen, L.A.A. Gerbens, A.L. Bosma, C.J. Apfelbacher, A.D. Irvine, B.W.M. Arents, S. Barbarot, M. Deleuran, L.F. Eichenfield, A. Manca, J. Schmitt, C. Vestergaard, D. Wall, S. Weidinger, M.A. Middelkamp‐Hup, P.I. Spuls, C. Flohr
Journal: British Journal of Dermatology (2019)

中重度特应性湿疹 (AE) 常通过光疗(光线治疗)或全身治疗(通过全身发挥作用的药物)来治疗。目前尚无关于这些治疗有效性和安全性的长期数据。为了解决这一问题,应在国家研究注册中收集正在现实生活环境中或曾经在此环境中使用这些治疗的儿童和成人患者的相关数据。理想情况下,这些国家注册应是可以相容的,从而可以合并尽可能多的患者数据,并加以分析(举例而言,这对于发现罕见副作用是必须的)。因此,所有国家都需要以相同方式收集相同的数据。为此,建立了国际特应性湿疹治疗 (TREAT) 注册任务组。它已经标准化了需要测量的项目(例如疾病严重程度、副作用)。这项研究解决了两个剩余问题:如何和何时测量这些项目。为了确定如何测量这些项目(即,使用何种测量工具),作者们使用了来自湿疹结局测量一致化 (HOME) 行动中的推荐意见、相关文献(已发表的科学研究)、德国已有的 AE 注册和专家意见。在多次会议上和通过电子邮件讨论了这些提案。这导致就如何测量已标准化的项目集达成了一致(共识)。通过在线调查解决了何时测量这些项目的问题(随访频率)。就开始治疗后 4 周,后续治疗中每 3 个月一次,停止治疗后每 6 个月一次的最低随访频率达成了共识。完整核心数据集线现已可用,将帮助标准化儿童和成人 AE 患者光疗和全身治疗数据的采集。这将有助于及时回答这些治疗长期有效性和安全性的问题,并改善中重度 AE 患者的治疗。
OS4.4 Hypofractionated stereotactic radiotherapy and anti-PDL1 Durvalumab combination in recurrent glioblastoma: Results of the phase I part of the phase I/II STERIMGLI trial
Authors: D Pouessel, A Mervoyer, D Larrieu-Ciron, B Cabarrou, M Robert, J Frenel, P Olivier, M Mounier, E Cohen-Jonathan Moyal
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma (GBM) remains a lethal disease with inevitable local relapse and no standard treatment. Re-irradiation by hypofractionated stereotactic radiotherapy (hFSRT) is an option of treatment with tolerable safety, but needs improvement in term of efficacy. Radiotherapy (RT) causes immunogenic tumor cell death but also induces PDL1 and PD1 expression on tumors and immune cells, potentially evoking resistance to RT. Pre-clinical studies combining hFSRT with an anti-PD-1 antibody in GBM have shown increased efficacy of the combination. Clinical studies also show encouraging results when checkpoint inhibitors have been combined with high dose RT. We hypothesized that combining the anti PD-L1 Durvalumab (Durva) with hFSRT will be an effective regimen for patients with recurrent GBM. We designed a phase I/II clinical trial studying the combination of hFSRT with Durva for recurrent GBM≤35 mm diameter. Results of the phase I are presented. MATERIAL AND METHODS Patients were included from February 2017 to October 2017. A standard 3 + 3 de-escalation design was used. Patients were treated by hFSRT 24 Gy, 8 Gy/fraction at 80% isodose, every other day, combined with Durva infusion 1500mg first dose (Level 1) or 750 mg (Level -1) delivered on the last hFSRT day followed by 1500 mg Durva infusion every four weeks until relapse. The schema was defined as safe if one patient or less among 6 presents a dose limiting toxicity (DLT). Brain MRI was performed before RT and then every 8 weeks until relapse. Tumor assessment was performed according to RANO criteria. RESULTS Among the 6 patients (3 methylated MGMT, 3 unmethylated MGMT; all wild type IDH) included at the level 1, all completed the hFSRT course, only one had a DLT which was an immune related grade 3 vestibular neuritis. At the time of analysis (24/01/19), all the patients had a local tumor progression, 4 were still alive. Local progression free interval (LPFI) ranges from 2.1 to 8.1 months. Interestingly the 2 patients who presented a pseudo-progression had a prolonged LPFI (5.7 and 8.1 months) compared to the other patients. All the patients except these 2 patients had a lymphopenia at inclusion. PDL-1 expression varied from 0 to 70% in the primary tumor. CONCLUSION Combining three 8 Gy fractions of hFSRT with 1500 mg Durvalumab on the 3rd fraction hFSRT and every 4 weeks for recurrent GBM is well tolerated justifying exploration of its efficacy in the phase II which is currently in interim analysis
Optimal Whole Blood Storage Conditions for Measuring BCR-ABL1 Accurately for Xpert® BCR-ABL Ultra
Authors: Gwo-Jen Day, Alba Levitas, Christophe Ferrand, Marina Deschamps, Krupa Shridhar, Sandy Huang, Brian Rhees, Michael P. Bates, Wendy Wong, Jerald P. Radich
Journal: Blood (2017)
Novel Immune Targets in Melanoma—Letter
Authors: Giuseppe Nocentini, Luigi Cari, Carlo Riccardi
Journal: Clinical Cancer Research (2019)

We have read with great interest the article by Edwards and colleagues, recently published in Clinical Cancer Research ([1][1]). However, we have concerns about the conclusions on GITR expression in tumor-infiltrating cells.

Figure 1D of the article depicts the expression of T-cell markers in the
Trends in chemotherapy (CT) utilization for colorectal cancer: A provincial population-based analysis
Authors: D. J. Renouf, H. Kennecke, S. Gill
Journal: Journal of Clinical Oncology (2007)

17014 Background: Significant advances have been made in the treatment of colorectal cancer in both the adjuvant and metastatic setting. The purpose of this study is to examine CT prescribing patterns for adjuvant therapy of colon cancer and metastatic colorectal cancer over the last 15 years in British Columbia, Canada. Methods: All patients (pts) with stage 2 or 3 colon cancer, or stage 4 colorectal cancer at presentation referred to the BC Cancer Agency during a one year period for three time cohorts: 1990, 2000 and 2004, were reviewed. A pt was considered to be treated with CT if they received a cycle of CT within 6 months of referral. Results: A total of 1421 pts were included: stage 2/3 n=915, stage 4 n=506. Chemotherapy utilization increased significantly from 1990 to 2004 for adjuvant CT (1990: 49 (29%), 2000: 129 (45%), 2004: 235 (52%), p&lt;0.001) and for palliative CT (1990: 41(35%), 2000: 100 (51%), 2004 120 (63%), p&lt;0.001). The proportion of pts with stage 2 disease treated with adjuvant CT dramatically increased (1990: 3(4%), 2000: 38 (26%), 2004: 50 (30%), p&lt;0.001). CT utilization was associated with a later time cohort and younger age of presentation ( Table 1 ). The use of palliative CT was significantly associated with male gender (p=0.025). This gender bias was not observed in the adjuvant setting. Among pts &gt;70y, only 25% (99/394) received adjuvant CT [1990: 5(8%), 2000:38 (28%), 2004: 57 (28%] and 31% (50/162) received palliative CT [1990:4 (15%), 2000:17 (24%), 2004:30 (45%)]. Conclusions: In this population-based cohort, adjuvant and palliative CT utilization has increased since 1990 however there is room for improvement. Despite the lack of conclusive evidence, the use of adjuvant CT for stage II disease has increased significantly. Female pts appear less likely to receive palliative CT. Despite evidence that the elderly can accrue similar proportional benefits, the majority of referred pts &gt;70y did not receive adjuvant or palliative CT. Such discrepancies in CT utilization require further investigation. [Table: see text] No significant financial relationships to disclose.