tbuckley/cabot-search huggingface dataset:
OS8.7 Targeting Pi3k-Akt-mTOR and MAPKinase pathways in aggressive meningiomas: in vitro study
Authors: G Mondielli, F Darriet, C Roche, C Lisbonis, A Querdray, D Figarella-Branger, H Dufour, A Barlier, T Graillon
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Recurrent and aggressive meningiomas remain an unmet medical need in neuro-oncology. In our preclinical model on meningioma primary cell culture, the combination of the mTOR inhibitor, everolimus and the somatostatin analog, octreotide decreased cell viability and proliferation without inducing apoptosis. The interest of the combined treatment everolimus plus octreotide were clinically validated by the CEVOREM clinical trial demonstrating a decrease in growth rate of meningiomas in most treated patients. Nevertheless, everolimus induced an increase in Akt activity in vitro, which probably limited everolimus efficiency. We hypothesized that targeting Pi3K could prevent this positive feedback on Akt phosphorylation, induced by mTOR inhibition. The involvement of MAPKinase pathway in meningioma tumorigenesis was recently demonstrated. Our aim was to decipher the effect of the Pi3k α inhibitor Alpelisib (BYL719) and the specific inhibitor of MEK1,2 Mekinist (Trametinib) alone or in combination, in comparison to the mTor inhibitor everolimus on human meningioma primary cell cultures. MATERIAL AND METHODS The impact of the drugs was studied on 40 meningiomas, well characterized at clinical, histological and molecular level. The cell viability, cell proliferation and apoptosis were analyzed under drugs. RESULTS BYL719 induced a dose dependent decrease in cell viability (maximal effect -90%, IC50 10-6M) in all tested meningiomas (n=30). This effect was stronger than those of everolimus (maximal effect -50%, n=24, IC50 10-8M). 22 tumors were sensitive to Trametinib (maximal effect &lt;-50%, IC50 10–5 M), 14 were partially sensitive (maximal effect between -20 and -40% IC50 10–5 M) and 3 were resistant. An apoptotic effect was observed under BYL719 in 6/18 tested tumors whereas no apoptosis was observed under Trametinib and Everolimus. Combination of BYL719 and Trametinib induced a significant stronger decrease in cell viability than each drug alone. Correlation analysis between these functional results, the tumor genomic profile and the activation of ERK/MEK kinase pathway is ongoing. CONCLUSION PI3K-Akt-mTOR and ERK/MEK kinase pathways constitute relevant targets in aggressive meningioma therapy. In our preclinical model, previously validated by CEVOREM clinical trial, co-targeting Pi3k-Akt-mTOR and MAPkinase pathways improved cell proliferation inhibition in comparison to the target of each pathway alone. BYL719 induced apoptosis which was not achieved by everolimus. These results support the ongoing clinical trial ALTREM combining Alpelisib and Trametinib on patients harboring aggressive recurrent meningiomas.
Non-coding RNA in endothelial-to-mesenchymal transition
Authors: Melanie S Hulshoff, Gonzalo del Monte-Nieto, Jason Kovacic, Guido Krenning
Journal: Cardiovascular Research (2019)

Abstract Endothelial-to-mesenchymal transition (EndMT) is the process wherein endothelial cells lose their typical endothelial cell markers and functions and adopt a mesenchymal-like phenotype. EndMT is required for development of the cardiac valves, the pulmonary and dorsal aorta, and arterial maturation, but activation of the EndMT programme during adulthood is believed to contribute to several pathologies including organ fibrosis, cardiovascular disease, and cancer. Non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, modulate EndMT during development and disease. Here, we review the mechanisms by which non-coding RNAs facilitate or inhibit EndMT during development and disease and provide a perspective on the therapeutic application of non-coding RNAs to treat fibroproliferative cardiovascular disease.
Development or Exacerbation of Head and Neck Dermatitis in Patients Treated for Atopic Dermatitis With Dupilumab
Authors: Angèle Soria, Aurélie Du-Thanh, Julien Seneschal, Marie Jachiet, Delphine Staumont-Sallé, Sébastien Barbarot
Journal: JAMA Dermatology (2019)

Development or Exacerbation of Head and Neck Dermatitis in Patients Treated for Atopic Dermatitis With DupilumabThe efficacy and safety of dupilumab, a humanized monoclonal antibody targeting the α subunit of the interleukin (IL)-4 and IL-13 receptors, has been assessed in adults with moderateto-severe atopic dermatitis (AD). 1,2 Injection site reactions, nasopharyngitis, conjunctivitis, and transient increases in eosinophil counts from baseline were higher in the dupilumab groups than in the placebo groups in pivotal studies. 1,2A recent study by Zhu et al 3 reported new regional dermatoses in 17 patients with AD treated with dupilumab, with facial area involvement in 14 cases, whereas Blauvelt et al 4 reported an equal improvement of AD with dupilumab on different anatomic regions in a post hoc analysis of data extracted from 4 phase 3 clinical trials.
Pertinence of sequential use of gemcitabine and irinotecan following docetaxel and cisplatin for non operable non small cell lung cancer
Authors: P. Nouyrigat, A. Madroszyk, C. Audigier-Valette, B. Escarguel, D. Andreotti, D. D’Amore, L. Marqueste, X. Tchiknavorian, L. Cals
Journal: Journal of Clinical Oncology (2006)

17138 Background: The objective of the study is to determine if the switch to a gemcitabin (G) and irinotecan (I) is efficient after low efficacy of a docetaxel (D) and cisplatin (C) regimen for advenced non small cells carcinoma (NSCLC). Methods: Eligible patients were above 18 years old and under 75, with stage IIIb or IV NSCLC. No previously chemotherapy, WHO = 0, 1, 2 under 60 and WHO = 0, 1 under 60. mesurable target. Treatment D and C = 75 mg/m 2 were given wekks 1, 4 and 7. After evaluation on week 10: in case of objective response 3 more cycles of DC were administred, if not a switch was performed with G 1000 mg/m 2 and I 100 mg/m 2 given as 90 minutes infusion J1-J8 every 3 weeks before a new evaluation after 3 cycles. Results: 21 patients entered the study, median age 57 (37–74). Stage IIIb = 8, IV = 13. Efficacy: we observed 8 patients with objective response (38%). Among 13 patients without an objective response after 3 DC only 4 patients received the switch treatment of GI. We found no new objective respons among them. Conclusions: For non responsive NSCLC patients to docetaxel-cisplatin regimen the treatment by gemcitabin-irinotecan does not seem relevant. No significant financial relationships to disclose.
The Diagnostic Value of Kappa/Lambda Ratios Determined By Flow Cytometric Analysis of Peripheral Blood and Bone Marrow Specimens in B-Cell Chronic Proliferative Disease
Authors: Aldair Sousa Paiva, Alessandra Suelen Jardim, Victor lima Soares, Hugo Diogenes De Oliveira Paiva, Frank Bahia, Valéria SF Sales, Marcos Dias Leão, Antonia Eduarda Martins Oliveira Elói Silva, João Pedro Andrade Lima, Geraldo Barroso Cavalcanti
Journal: Blood (2018)
Uptake of 18F-FDG in Adrenal Adenomas Is Associated With Unenhanced CT Value and Constituent Cells
Authors: Ryo Murayama, Akihiro Nishie, Tomoyuki Hida, Shingo Baba, Junichi Inokuchi, Yoshinao Oda, Hiroshi Honda
Journal: Clinical Nuclear Medicine (2019)

Purpose The purposes of this study were to investigate the correlation between unenhanced CT attenuation values and 18 F-FDG uptake in adrenal adenomas, and to clarify the mechanism of FDG uptake in adrenal adenomas based on immunohistochemical findings. Materials and Methods In 57 adrenal adenomas, the correlation between SUV max on 18 F-FDG PET and unenhanced CT attenuation was retrospectively investigated. In the 11 surgically resected nodules, the clear cell ratio (CCR) and expression levels of glucose transporters (GLUTs) 1 to 4 were pathologically evaluated. The GLUT expression levels were scored at 0 to 3 points for each transporter, and the sum of these expression levels was defined as the GLUT score. The relationships between CCR and either the CT attenuation number or SUV max , and between the GLUT score and each of the CT attenutation value, SUV max , or CCR were evaluated. Results There was a significant positive correlation between SUV max and the CT attenuation value for the group of 57 adenomas ( R = 0.44, P = 0.0007). For the 11 surgically resected cases, there was a nonsignificant trend of negative correlation between SUV max and CCR ( R = 0.57, P = 0.06). There was a significant positive correlation between GLUT score and CT attenuation value ( R = 0.68, P = 0.02), and a significant negative correlation between GLUT score and CCR ( R = 0.60, P = 0.003). Conclusions Adrenal adenomas composed of many compact cells or having high attenuation on unenhanced CT showed high FDG uptake. FDG uptake of adrenal adenomas may depend on the constituent cells.
P11.32 Combined effects of niclosamide and temozolomide against human glioblastoma tumorspheres
Authors: E Kim, H Oh, J Shim, S Kang
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma (GBM) is the most aggressive type of brain tumor and has poor survival outcomes, even after a combination of surgery, radiotherapy, and chemotherapy. Temozolomide is the only agent that has been shown to be effective against GBM, suggesting that combination of temozolomide with other agents may be more effective. Niclosamide, an FDA approved anthelmintic agent, has shown anti-cancer effects against human colon, breast, prostate cancers as well as GBM. However, the efficacy of the combination of niclosamide with temozolomide against GBM tumorspheres (TSs) has not been determined. We hypothesized that the combined treatment could effectively suppress GBM TSs. MATERIAL AND METHODS Effects of niclosamide and/or temozolomide on GBM TSs were evaluated. Viability, stemness, and invasive properties of GBM TSs were examined. In vivo anticancer efficacy was tested in a mouse orthotopic xenograft model. RESULTS The combination of niclsoamide and temozolomide significantly inhibited the viability, sphere formation, expression of stemness-related proteins, and invasive properties of GBM TSs. This combination significantly down-regulated the expression of epithelial mesenchymal transition-related proteins. Bioluminescence imaging further showed that compared with either agent alone, combination of niclosamide and temozolomide significantly reduced the tumor burden in orthotopic xenograft models. CONCLUSION The combination of niclosamide and temozolomide effectively decreased the stemness and invasive properties of GBM TSs, suggesting that this regimen may be therapeutically effective in treating patients with GBM.
Adopting the STITCH Trial
Authors: Christopher Yheulon, S. Scott Davis
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Measles, Mumps, Rubella Vaccination and Autism
Authors: Jake Crosby
Journal: Annals of Internal Medicine (2019)

Letters3 September 2019Measles, Mumps, Rubella Vaccination and AutismJake Crosby, MPHJake Crosby, MPHSt. Johns County, Florida (J.C.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0381 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Hviid and colleagues' (1) results contradict their conclusion, a circumstance that also occurred with a study that Hviid coauthored in 2002 (2). The value that stands out in Figure 3 of Hviid and colleagues' 2019 article is the hazard ratio of autism of 2.69 among children who received the MMR vaccine who have siblings with autism. Although the magnitude of this value is far greater than that of any other reported hazard ratio in this figure, it is not significant because of the small sample size of this group. A preferable alternative would have been to report ...References1. Hviid A, Hansen JV, Frisch M, et al. Measles, mumps, rubella vaccination and autism. A nationwide cohort study. Ann Intern Med. 2019. [PMID: 30831578] doi:10.7326/M18-2101 LinkGoogle Scholar2. Madsen KM, Hviid A, Vestergaard M, et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med. 2002;347:1477-82. [PMID: 12421889] CrossrefMedlineGoogle Scholar3. Stott C, Blaxill M, Wakefield AJ. MMR and autism in perspective: the Denmark story. Journal of American Physicians and Surgeons. 2004;9:89-91. Google Scholar Author, Article, and Disclosure InformationAffiliations: St. Johns County, Florida (J.C.)Note: Mr. Crosby has previously received funding from Autism Media Channel and Children's Medical Safety Research Institute.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0381. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeasles, Mumps, Rubella Vaccination and Autism Anders Hviid , Jørgen Vinsløv Hansen , Morten Frisch , and Mads Melbye Measles, Mumps, Rubella Vaccination and Autism Anthony R. Mawson Measles, Mumps, Rubella Vaccination and Autism Anders Hviid , Jørgen Vinsløv Hansen , Morten Frisch , and Mads Melbye Metrics 3 September 2019Volume 171, Issue 5Page: 387-388KeywordsAutismChildrenDisclosureEpidemiologyHazard ratioMMR vaccineRisk managementSafetyVaccines ePublished: 3 September 2019 Issue Published: 3 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
P08.04 Glioblastoma and Alzheimer pathology: lessons from a single case with practical implications and need for further research
Authors: J Gállego Pérez-Larraya, I Esparragosa, M Puigdelloses, M Idoate, M Alonso
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma (GBM) and Alzheimer’s disease (AD) are frequent among the elderly: about 50% of all GBM patients are 65 years or older, and 5–10% of people above this age threshold suffer from AD. MATERIAL AND METHODS We describe the case of an elderly patient with newly diagnosed GBM who developed a rapidly progressive severe dementia immediately following concomitant radio-chemotherapy. A purposed retrospective analysis of the surgical sample revealed Alzheimer pathology. RESULTS A 69-year old woman with no relevant past-medical history was diagnosed with a right temporo-parietal GBM on May 2017, with wild-type IDH1R132H gene and methylated MGMTP. After complete resection she received radiotherapy (60 Gy in 30 fractions) and concomitant chemotherapy with Temozolomide 75 mg/m2/day. During the last weeks of concomitant radio-chemotherapy and further on the patient developed a progressive neurological worsening with severe cognitive dysfunction, gait impairment and sphincter incontinence, becoming severely disabled and requiring continuous assistance. Brain MRI exams showed no signs of tumor recurrence, with focal white matter changes consisting on T2/FLAIR hyperintensities within the radiation field, enlarged sulci and ventriculomegaly. Underlying infectious and metabolic disorders, non-convulsive epileptic status and normal-pressure hydrocephalus were ruled out. Facing this situation the patient relatives were purposely asked for previous cognitive symptoms, and described very mild complaints of short-term memory loss during the previous year. Aiming at investigating the possibility of an underlying AD, focused examination of the surgical sample revealed the presence of frequent neuritic plaques, a neuropathological hallmark of AD. The patient developed a severe dementia with akinetic mutism by September 2017. Without evidence of tumor recurrence despite lack of adjuvant chemotherapy, she died of aspiration pneumonia on January 2019. CONCLUSION A unique retrospective study including elderly GBM patients treated only with surgery revealed that Alzheimer disease pathology was present in 42% of them. This case illustrates the need for actively addressing the previous cognitive status of elderly patients with GBM. Histopathological assessment of Alzheimer pathology might also be considered in this specific population. In positive cases, particularly in those with methylated MGMTP, radiotherapy should be avoided and treatment alone with Temozolomide might be considered.
Challenges of Suicide Outcomes Ascertainment in Administrative Claims Databases
Authors: Dinci D. Pennap, Andrew D. Mosholder, Richard S. Swain
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
JS1.3 Autoimmune encephalitis as immune related adverse event (irAE) of check point inhibitors (CPI) not so rare as we thought
Authors: A Taliansky, M Gadot, D Urban, J Bar, R Shapira-Frumer, B Kaufman, N Asher, R Leibowitz-Amit, A Itay
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION CPI has significant efficacy and toxicities. We describe our experience with CPI treated patients diagnosed with irAE encephalitis. METHODS Patients treated with CPI during 2017–2018 were identified from institute’s EMR. Patients treated for irAE encephalitis were identified from the database of the Neuro-Oncology Unit of the Institute. Results: Eleven patients were diagnosed with irAE encephalitis out of 1500 treated with CPI at the Institute (0.73%). Four patients had NSCLC, 3 had melanoma, the one patient had each of SCLC, uterine carcinoma, RCC and breast cancer. Median age was 69 years (49–87). Four of 11 were treated with chemo-CPI, 3-with CPI combinations. Median onset of symptoms was at 19 days (5–180) following initial treatment. All events were high grade severity. Eight patients fully recovered after immunotherapy discontinuation and steroid treatment, of these, 2 melanoma patients underwent uncomplicated CPI re-challenge. Three patients, all non-melanoma, had severe neurological sequelae. Two of them were treated with steroids, PLEX and cyclophosphamide: one improved neurologically although died 6 months later from cancer. One patient was oncologically stable but died from neurological deterioration 7 months later. The additional patient was treated with steroids only because his advanced age and decease in hospice 2 months later. CONCLUSION Encephalitis, as an irAE of CPI, seems to be more common and severe than previously thought, predominantly in non melanoma patients. Nevertheless, in the majority of cases it is reversible and in some melanoma patients immunotherapy re-challenge is safe. Future studies will have to define risk factors and severity prediction.
P04.16 TP53 mutations in codon 273 is predictive of overall survival in astrocytoma patients
Authors: H Noor, R Rapkins, K McDonald
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Tumour Protein 53 (TP53) is a tumour suppressor gene that is mutated in at least 50% of human malignancies. The prevalence of TP53 mutation is much higher in astrocytomas with reports of up to 75% TP53 mutant cases. Rare cases of TP53 mutation also exist in oligodendroglial tumours (10–13%). P53 pathway is therefore an important factor in low-grade glioma tumorigenesis. Although the prognostic impact of TP53 mutations has been studied previously, no concrete concordance were reached between the studies. In this study, we investigated the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. MATERIAL AND METHODS A cohort of 65 matched primary and recurrent fresh frozen tumours were sequenced to identify hotspot exons of TP53 mutation. Exons 1 to 10 were sequenced and pathogenic mutations were mostly predominant between Exons 4 and 8. The cohort was further expanded with 78 low grade glioma fresh frozen tissues and hotspot exons were sequenced. Selecting only the primary tumour from 65 matched tumours, a total of 50 Astrocytoma cases and 51 oligodendroglioma cases were analysed for prognostic effects of TP53. Only pathogenic TP53 mutations confirmed through COSMIC and NCBI databases were included in the over survival and progression-free survival analysis. RESULTS 62% (31/50) of astrocytomas and 16% (8/51) of oligodendrogliomas harboured pathogenic TP53 mutations. Pathogenic hotspot mutations in codon 273 (c.817 C&gt;T and c.818 G&gt;A) was prevalent in astrocytoma with 58% (18/31) of tumours with these mutations. TP53 mutation status was maintained between primary and recurrent tumours in 93% of cases. In astrocytoma, overall survival of TP53 mutant patients was longer compared to TP53 wild-type patients (p&lt;0.01) but was not significant after adjusting for age, gender, grade and IDH1 mutation status. In contrast, astrocytoma patients with specific TP53 mutation in codon 273 showed significantly better survival compared to other TP53 mutant and TP53 wild-type patients combined (p&lt;0.01) in our multivariate analysis. Time to first recurrence (progression-free survival) of TP53 mutant patients was significantly longer than TP53 wild-type patients (p&lt;0.01) after adjustments were made, while TP53 mutation in codon 273 was not prognostic for progression-free survival. In oligodendroglioma patients, TP53 mutations did not significantly affect overall survival and progression-free survival. CONCLUSION In agreement with others, TP53 mutation is more prevalent in Astrocytoma and mutations in codon 273 are significantly associated with longer survival.