tbuckley/cabot-search huggingface dataset:
Efficacité des prothèses coliques métalliques expansives dans les obstructions néoplasiques colorectales
Authors: JB Ngomirakiza, N Pichon, JF Vincensini, F Cessot, B Pillegand, D Sautereau
Journal: Endoscopy (2004)

Objectif: Evaluer l’efficacité, la durée de fonctionnement et les complications des prothèses coliques métalliques expansives en traitement palliatif ou pré-opératoire chez les patients admis pour obstruction colique sur néoplasie. Patients et Méthodes: Entre janvier 2001 et septembre 2003, 25 patients ont nécessité la mise en place d’une prothèse colique sur obstruction colique néoplasique. Il s’agissait de 8 femmes et 17 hommes d’âge moyen 77 ans (extrêmes: 41–91). La mise en place des prothèses a été possible chez 22 patients (88%), 1 patient ayant bénéficié de la pose de deux prothèses. Trois échecs (12%) sont à noter. La pose était réalisée en urgence sur occlusion aiguë pour 6 patients et différée pour 16 patients. Le délai moyen entre la découverte de la néoplasie et la pose de la prothèse était de 19 jours (extrêmes: 0–150). Le largage de la prothèse était contrôlé par endoscopie seule dans 8 cas ou associée à la radiologie dans 15 cas. Les prothèses utilisées étaient des Wallstent (14) et Ultraflex (9) Microvasive® (Boston Scientific). Dix examens étaient réalisés sous sédation et 15 sans sédation. Résultats: Le siège de la néoplasie était recto sigmoïdien dans 21 cas (84%), colique gauche dans 1 cas (4%), colique transverse dans 2 cas (8%) et colique droit dans 1 cas (4%). Il s’agissait de 22 adénocarcinomes étendus (88%), 1 carcinome neuro-endocrine (4%) et 2 adénomes tubulo villeux avec dysplasie sévère et foyers de carcinome in situ. La levée de l’obstruction était constatée dans 100% des cas. L’abdomen sans préparation réalisé 24 heures après la pose montrait une expansion complète de la prothèse dans tous les cas. Les complications précoces étaient la migration de la prothèse dans 1 cas (4,4%) et la perforation du colon par la prothèse dans un cas (4,4%). Sept patients ont subi une colectomie secondaire programmée en un temps (délai moyen entre la pose de la prothèse et la chirurgie: 7 jours; extrêmes: 2–10) et 15 patients ont conservé leur prothèse à titre palliatif. Une amélioration de la qualité de vie était objectivée chez 13 des patients ayant bénéficié d’une prothèse à titre temporaire ou définitif (59%). Huit des patients ayant bénéficié de la pose d’une prothèse sont décédés à ce jour avec une durée moyenne de survie de 119 jours (extrêmes: 6–240). Conclusion: La mise en place d’une prothèse colique dans l’urgence devant un tableau d’occlusion aiguë sur néoplasie en vue de réaliser une chirurgie en un temps après levée de l’occlusion fait actuellement l’objet d’un protocole d’étude par la SFED mais localement le bénéfice semble indéniable. La mise en place d’une prothèse à visée palliative améliore la qualité de vie du patient. Le taux d’échec est de 12% et le taux de complications de 8,7%. La durée de fonctionnement sans complications est en moyenne supérieure à trois mois.
Hepatic Lipid Accumulation and Nrf2 Expression following Perinatal and Peripubertal Exposure to Bisphenol A in a Mouse Model of Nonalcoholic Liver Disease
Authors: Prajakta C. Shimpi, Vijay R. More, Maneesha Paranjpe, Ajay C. Donepudi, Jaclyn M. Goodrich, Dana C. Dolinoy, Beverly Rubin, Angela L. Slitt
Journal: Environmental Health Perspectives (2017)

Exposure to chemicals during critical windows of development may re-program liver for increased risk of nonalcoholic fatty liver disease (NAFLD). Bisphenol A (BPA), a plastics component, has been described to impart adverse effects during gestational and lactational exposure. Our work has pointed to nuclear factor E2-related factor 2 (Nrf2) being a modulator of hepatic lipid accumulation in models of NAFLD.To determine if chemical exposure can prime liver for steatosis via modulation of NRF2 and epigenetic mechanisms.Utilizing BPA as a model exposure, pregnant CD-1 mice were administered 25μg/kg/day BPA via osmotic minipumps from gestational day 8 through postnatal day (PND)16. The offspring were weaned on PND21 and exposed to same dose of BPA via their drinking water through PND35. Tissues were collected from pups at week 5 (W5), and their littermates at week 39 (W39).BPA increased hepatic lipid content concomitant with increased Nrf2 and pro-lipogenic enzyme expression at W5 and W39 in female offspring. BPA exposure increased Nrf2 binding to a putative antioxidant response element consensus sequence in the sterol regulatory-element binding protein-1c (Srebp-1c) promoter. Known Nrf2 activators increased SREBP-1C promoter reporter activity in HepG2 cells. Methylated DNA immunoprecipitation-PCR and pyrosequencing revealed that developmental BPA exposure induced hypomethylation of the Nrf2 and Srebp-1c promoters in livers of W5 mice, which was more prominent in W39 mice than in others.Exposure to a xenobiotic during early development induced persistent fat accumulation via hypomethylation of lipogenic genes. Moreover, increased Nrf2 recruitment to the Srebp-1c promoter in livers of BPA-exposed mice was observed. Overall, the underlying mechanisms described a broader impact beyond BPA exposure and can be applied to understand other models of NAFLD. https://doi.org/10.1289/EHP664.
FRI0356 Antisense long noncoding rnas are deregulated in skin tissue of ssc patients
Authors: T Messemaker, L Chadli, G Cai, V Goelela, M Boonstra, A Dorjee, S Andersen, H Mikkers, T Huizinga, Z Li, O Distler, M Whitfield, R Toes, J Aarbiou, J De Groot, J Vries-Bouwstra De, F Kurreeman
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and multiple organs of which pathogenesis is poorly understood. Here we studied differentially expressed coding and non-coding genes in relation to SSc pathogenesis with a specific focus on antisense non-coding RNAs. <h3>Objectives</h3> Here we studied differentially expressed coding and non-coding genes in relation to SSc pathogenesis with a specific focus on antisense non-coding RNAs. <h3>Methods</h3> Skin biopsy-derived RNAs from fourteen early SSc patients and six healthy individuals were sequenced with ion-torrent and analysed using DEseq2. Protein-coding and non-coding genes annotated in GENCODEV7 were analysed. Significant long non-coding RNAs were independently replicated in a Northern American dataset. <h3>Results</h3> 4901 genes with a fold change &gt;1.5 and a false discovery rate of less than 5% were detected in patients versus controls. Upregulated coding genes clustered in immunological, cell adhesion and keratin-related processes as previously found by microarray studies. Interestingly, 676 deregulated non-coding genes were detected, 257 of which were classified as antisense genes. 42% of these antisense genes had a concurrent deregulated sense gene. The majority of the sense-antisense genes had a similar effect sizes in an independent North American dataset with three genes (OTUD6B-AS1, CTBP1-AS2 and HMGN3-AS1) exceeding the study-wide Bonferroni-corrected ρ-value (P<sub>Bonf</sub>&lt;0.0024, P<sub>combined</sub>=1.6x10<sup>-9</sup>, 1.7x10<sup>-6</sup>, 2.6xx10<sup>-6</sup>, respectively). Intriguingly, the correlation of sense-antisense gene pairs deregulated in SSc is stronger than sense-antisense gene pairs not deregulated in SSc (p&lt;0.001). <h3>Conclusions</h3> For the first time we highlight that together with coding genes, (antisense) long noncoding RNAs are deregulated in skin tissue of SSc patients suggesting a novel class of genes involved in pathogenesis of SSc. <h3>Disclosure of Interest</h3> None declared
Small Change, Big Consequences — Partial Medicaid Expansions under the ACA
Authors: Adrianna McIntyre, Allan M. Joseph, Nicholas Bagley
Journal: New England Journal of Medicine (2017)

Interview with Prof. Nicholas Bagley on why partial Medicaid expansions could be harmful for patients and the federal budget. (10:23)Download The Trump administration may decide to permit states to partially expand their Medicaid programs to cover people with incomes up to 100% of the federal poverty level. Arkansas has requested a waiver to do so, and if it is granted, other states may follow suit.
高治療効率と低有害効果を達成するためのほう素中性子捕獲療法におけるROS除去能を有するほう素クラスターを含む酸化還元ナノ粒子の利用【Powered by NICT】
Authors: Gao Zhenyu, Horiguchi Yukichi, Nakai Kei, Matsumura Akira, Suzuki Minoru, Ono Koji, Nagasaki Yukio
Journal: Biomaterials (2016)
Administration of aldoxorubicin and 14 days continuous infusion of ifosfamide/mesna in metastatic or locally advanced sarcomas.
Authors: Frederick C. Eilber, Kamalesh Kumar Sankhala, Sant P. Chawla, Victoria S. Chua-Alcala, Erlinda Maria Gordon, Doris Quon, Katherine Kim, Shanta Chawla, Nancy Wu, Scott Wieland, Daniel J. Levitt
Journal: Journal of Clinical Oncology (2017)

11051 Background: Aldoxorubicin (A) has demonstrated superior anti-tumor efficacy and lack of cumulative cardiac toxicity in multiple studies. A is doxorubicin (D) with a linker which rapidly binds in vivo to albumin after iv. We studied the combination of A administered on Day 1 with continuous infusion (CI) of ifosfamide/Mesna (I-M) days 1-14, as first line therapy or second line therapy in patients with soft tissue sarcomas (STS) to evaluate efficacy and toxicity. Methods: 27 patients have entered the study at 250 mg/m2 ( 185 mg/m2 D equiv) administered on Day 1. I-M (1 g/m2 of each per day) was given up to 14 days as a CI via an out-patient portable pump. Chemotherapy cycles were repeated at 28 day interval. I-M was limited to a maximum of 6 cycles to avoid cumulative marrow toxicity, but A was continued per investigator decision in responding or SD patients for clinical benefit. Subjects were followed for tumor response (RECIST 1.1) by CT scans and echocardiogram/ECG for cardiac toxicity every 8 weeks along with standard labs. Enrollment continues up to 50 patients. Results: Demographics: Leiomyosarc. = 20%, liposarc. = 20%, synovial sarc. = 20%, rhabdosarc. = 8%, others = 32%. Caucasian, 11% Asian, 4% Black; 67% no prior tx, 26% 1 prior tx, 7% &gt; 1 prior tx; Median cum. A = 1000 mg/m 2 (740 mg/m 2 D eq.; 185-4070 mg/m 2 D eq.); I = 6.9 g/m 2 (2.1-12.6 g/m 2 ). Best response: 42% PR, 58% SD. Median PFS not reached. 10 subjects with either PR or SD had surgery to remove accesible tumors. Range of tumor necrosis = 70 to &gt; 95%. Grade 3/4 AEs: neutropenia = 78%, febrile neutropenia = 9%, thrombocytopenia = 22%, anemia = 65%, nausea = 4%. Related SAEs = 4 (febrile neutropenia (2), pyrexia, stomatitis). No tx related deaths. No clinically significant cardiac AEs, no decrease in LVEF &gt; 20% Conclusions: A can be administered for prolonged periods and safely with CI ifosfamide/mesna and achieves high ORR and SD with substantial tumor necrosis. Clinical trial information: NCT02235701.
EGFR tyrosine kinase inhibitors<i>versus</i>chemotherapy in<i>EGFR</i>wild-type pre-treated advanced nonsmall cell lung cancer in daily practice
Authors: Pascale Tomasini, Solenn Brosseau, Julien Mazières, Jean-Philippe Merlio, Michèle Beau-Faller, Jean Mosser, Marie Wislez, L'Houcine Ouafik, Benjamin Besse, Isabelle Rouquette, Didier Debieuvre, Fabienne Escande, Virginie Westeel, Clarisse Audigier-Valette, Pascale Missy, Alexandra Langlais, Frank Morin, Denis Moro-Sibilot, Gérard Zalcman, Fabrice Barlesi
Journal: European Respiratory Journal (2017)

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are approved for second-line treatment of EGFR wild-type ( EGFR -wt) nonsmall cell lung cancer (NSCLC). However, results from randomised trials performed to compare EGFR-TKIs with chemotherapy in this population did not show any survival benefit. In the era of immunotherapy, many drugs are approved for second-line treatment of EGFR- wt NSCLC and there is a need to reassess the role of EGFR-TKIs in this setting. The Biomarkers France study is a large nationwide cohort of NSCLC patients tested for EGFR mutations. We used this database to collect clinical, biological, treatment and outcome data on EGFR- wt patients who received second-line treatment with either EGFR-TKIs or chemotherapy. Among 1278 patients, 868 received chemotherapy and 410 received an EGFR-TKI. Median overall survival and progression-free survival were longer with chemotherapy than with an EGFR-TKI. Overall survival was 8.38 versus 4.99 months, respectively (hazard ratio 0.70, 95% CI 0.59–0.83; p&lt;0.0001) and progression-free survival was 4.30 versus 2.83 months, respectively (hazard ratio 0.66, 95% CI 0.57–0.77; p&lt;0.0001). This study is helpful to guide a multiline treatment strategy for EGFR- wt NSCLC patients. Immunotherapy is approved for second-line treatment. For third-line treatment, chemotherapy results in longer overall survival and progression-free survival, and should be preferred to EGFR-TKIs.
Observational study of treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in activating EGFR-mutation–positive (EGFRm+) advanced or recurrent non-small cell lung cancer (NSCLC) after radiologic progression to first-line therapy with EGFR-TKI.
Authors: Yukio Hosomi, Chiharu Tanai, Kiyotaka Yoh, Yasushi Goto, Yasuo Ohashi, Hideo Kunitoh
Journal: Journal of Clinical Oncology (2014)

8071 Background: NSCLC with activating EGFR mutation is generally sensitive to EGFR-TKIs, but resistance is inevitable. The clinical course after radiological (RECIST-based) “progressive disease” (PD) judgment is variable and yet to be fully elucidated. Methods: Thirty-one institutions in Japan participated in the survey of patients with EGFRm+ advanced or recurrent NSCLC who received first-line EGFR-TKIs between 2009 and 2011. The primary endpoint was the time from RECIST-based radiological PD (R-PD) to clinical PD (C-PD) in patients who continuously received TKI beyond R-PD. C-PD was defined as one or more of the following: 1) symptomatic PD; 2) worsening performance status due to PD; 3) threat to major vital organ(s); or 4) multi-organ unequivocal PD. Durations of TKI administration, reasons for discontinuation, therapies concomitantly given with TKI, “flare” phenomenon after TKI stoppage, and overall survival were also recorded. Results: At the time of submission, 578 cases were registered; 412 were analyzed, of whom 38 were still on TKI without R-PD (Group E). The remaining 374 were sub-classified into the following groups: Group A, TKI stopped at R-PD concurrently occurring with C-PD (n=140); Group B, TKI stopped at R-PD without C-PD (n=104); Group C, TKI continued beyond R-PD (n=63); and Group D, TKI stopped due to other reasons (n=67). Therefore, 63/167 patients (38%) continued to receive TKI beyond clinically stable R-PD. Median time from R-PD to C-PD or TKI discontinuation in Group C was 4.2 months. Median survival time for Groups A, B, C and D were 20.6, 23.3, 27.4 and 13.6 months, respectively, whereas median periods on TKIs were 8.8, 9.9, 18.3 and 2.7 months, respectively. Disease flare was observed in 6 cases. Conclusions: Clinical courses and pattern of care after resistance to EGFR-TKI varied. Some 38% of the patients without clinical deterioration at R-PD were continued on TKI, for a median period to C-PD of 4.2 months. Supported by the Public Health Research Center Foundation, with fund from AstraZeneca.
Use of microarray analysis of differentially expressed genes in luminal B subtype of breast cancers to evaluate NHERF1 as a marker of endocrine resistance
Authors: A. Rody, T. Karn, C. Solbach, E. Ruckhaeberle, L. Hanker, A. Ahr, R. Gaetje, U. Holtrich, M. Kaufmann
Journal: Journal of Clinical Oncology (2009)

11015 Background: In vitro and in vivo data demonstrate that the expression of estrogen receptor (ER) in breast cancer is mainly associated with low proliferation. Gene expression profiling has recently been used to identify a group of high proliferating estrogen receptor positive breast cancers (the luminal B subtype), which are associated with a prognosis that is even worse than that of high proliferating estrogen receptor negative tumors. The analysis of those tumors might provide valuable information about breast cancer biology and could be helpful for adjuvant or neoadjuvant treatment decisions.Methods and Results: We analyzed microarray data from breast cancer specimens to gain insight into genes which play a role in estrogen receptor signalling. Genes were identified showing strong expression in high proliferating ER-positive tumors but no expression in either Ki67-/ER+ or Ki67+/ER- samples. Among these genes the Na+/H+ exchanger regulatory factor NHERF1 was found. We assessed the clinical relevance of NHERF1 transcript levels using a total of 2469 breast cancers. Analysis indicates that enhanced NHERF1 expression is associated with metastatic progression and poor prognosis of breast cancer patients. We found no correlation between NHERF1 and the nodal status as well as age, but positive correlations for tumor size (P&lt;0.001), grade (P&lt;0.001) and erbb2 (P=0.033). Weak NHERF1 expression correlated with longer disease free survival (DFS) in grade 1 and 2 tumors, but not in grade 3 breast cancers. Since NHERF1 expression is strongly linked to the presence of ER, the predictive value for endocrine treatment was analyzed. For samples with weak or none NHERF1 expression a treatment benefit was observed (P=0.007). While untreated patients display a 10 yr DFS rate of 67.2 ± 3.8%, endocrine treatment resulted in 80.1 ± 4.0%. In contrast no differences in disease free survival were found for corresponding NHERF1 expressing breast cancers. Conclusions: Our data indicate that expression of NHERF1 defines a state of differentiation, where breast cancer cells are refractory to endocrine treatment. No significant financial relationships to disclose.
ヒトにおける免疫老化の特徴としてのT細胞移動におけるE CM橋かけの新たな役割【Powered by NICT】
Authors: Moreau Jean-Francois, Pradeu Thomas, Grignolio Andrea, Nardini Christine, Castiglione Filippo, Tieri Paolo, Capri Miriam, Salvioli Stefano, Taupin Jean-Luc, Garagnani Paolo, Franceschi Claudio
Journal: Ageing Research Reviews (2017)
Phase I study of the PD-L1 inhibitor, durvalumab (MEDI4736; D) in combination with a PARP inhibitor, olaparib (O) or a VEGFR inhibitor, cediranib (C) in women's cancers (NCT02484404).
Authors: Jung-min Lee, Alexandra Dos Santos Zimmer, Stan Lipkowitz, Christina M. Annunziata, Tony Weishiu Ho, Victoria L. Chiou, Lori M. Minasian, Nicole D. Houston, Irene Ekwede, Elise C. Kohn
Journal: Journal of Clinical Oncology (2016)

3015 Background: Immune checkpoint blockade has shown clinical activity in subsets of advanced solid tumors. O and C have single agent activity in recurrent ovarian cancer (OvCa). We hypothesize O and C will complement the antitumor activity of D by increasing DNA damage through repair inhibition and hypoxia induction. This phase I study evaluated the safety and preliminary activity of the combinations of D+O and D+C. Methods: Eligible pts with PS 0-1 and good end organ function received D+O or D+C in parallel dose escalations in a 3+3 design. D+O included O tablets (200 or 300 mg bid) with D 10 mg/kg IV every 14d (dose level [DL] 1, 2) and O 300 mg bid with D 1500 mg IV every 28d (DL3). D+C tested C 20 or 30 mg daily with D 10 mg/kg IV every 14d (DL1, 2). The DLT period was one 28d cycle. Safety was assessed by CTCAEv4.0 and response by RECISTv1.1. Results: 19 pts (median age 66 [39-70], median 4 prior therapies [2-7]) were treated. D+O includes 10 OvCa and 2 triple negative breast Ca pts. D+C had 4 OvCa, 2 cervical Ca and 1 uterine leiomyosarcoma pts. The MTD for D+O is DL3. Gr3/4 D+O adverse events (AEs) include lymphopenia (2/12) and anemia (1/12). D+C gr3/4 AEs include hypertension (2/7), diarrhea (2/7), pulmonary embolism (2/7), pulmonary hypertension (1/7), and lymphopenia (1/7). 2 D+C DL1 pts required early discontinuation of C for pulmonary embolism and 1 pt on DL1 had C dose reduction due to recurrent gr2 fatigue and abdominal pain on cycle 2. 4 D+C DL2 pts had dose reduction on cycles 2 or 3 due to recurrent gr2 fatigue, abdominal pain and/or dyspnea. 1 PR (6+ mo) and 5 SD ≥ 4 mo (56%; [4-6+]) were seen in 9 evaluable D+O pts, yielding a 67% disease control rate (DCR). All were BRCA wild type. 2 PR (5, 4+ mo) and 2 SD ≥ 4 mo (4+ mo) were seen in 7 evaluable D+C pts, for a 57% DCR. Archival tissue samples for PD endpoints including PD-L1 expression and blood for PK are under analysis. Conclusions: The RP2D for D+O (O tablets 300 mg bid with M 1500 mg q28d) is tolerable and active in OvCa and TNBC pts without germline BRCA mutation. New D+C DLs will examine an intermittent C schedule with D 1500 mg every 28d. Phase II expansion studies of D+O in OvCa, TNBC, lung, and prostate cancers are now open to accrual. Clinical trial information: NCT02484404.
Nuclear orphan receptor NR2F6 as a safeguard against experimental murine colitis
Authors: Victoria Klepsch, Romana R Gerner, Sebastian Klepsch, William J Olson, Herbert Tilg, Alexander R Moschen, Gottfried Baier, Natascha Hermann-Kleiter
Journal: Gut (2017)

Objective Nuclear receptors are known to regulate both immune and barrier functions in the GI tract. The nuclear orphan receptor NR2F6 has been shown to suppress the expression of proinflammatory cytokines in T lymphocytes. NR2F6 gene expression is reduced in patients with IBS or UC, but its functional role and tissue dependency in healthy and inflamed gut have not yet been investigated. Design Intestinal inflammation was induced in wild-type, Nr2f6 -deficient, Rag1 -deficient or bone marrow-reconstituted mice by administration of chemical (dextran sodium sulfate (DSS)) and immunogenic (T cell transfer) triggers. Disease phenotypes were investigated by survival, body weight, colon length and analysis of immune cell infiltrates. Additionally, histology, intestinal permeability, tight junction proteins, bacterial fluorescence in situ hybridisation, apoptosis, cell proliferation and mucus production were investigated. Results Nr2f6 -deficient mice were highly susceptible to DSS-induced colitis characterised by enhanced weight loss, increased colonic tissue destruction and immune cell infiltration together with enhanced intestinal permeability and reduced Muc2 expression. T cell transfer colitis and bone marrow reconstitution experiments demonstrated that disease susceptibility was not dependent on the expression of Nr2f6 in the immune compartment but on the protective role of NR2F6 in the intestinal epithelium. Mechanistically, we show that NR2F6 binds to a consensus sequence at −2 kb of the Muc2 promoter and transactivates Muc2 expression. Loss of NR2F6 alters intestinal permeability and results in spontaneous late-onset colitis in Nr2f6 -deficient mice. Conclusion We have for the first time identified a fundamental and non-redundant role of NR2F6 in protecting gut barrier homeostasis.
神経疾患:ヒトDCCの両対立遺伝子性変異は発生学的なsplit‐brain syndrome(分離脳症候群)を引き起こす
Authors: Jamuar Saumya S, Schmitz‐Abe Klaus, D’Gama Alissa M, Servattalab Sarah, Lam Anh‐Thu N, Markianos Kyriacos, Engle Elizabeth C, Walsh Christopher A, Chan Wai‐Man, Drottar Marie, Peeva Maya, Grant P Ellen, Delgado Mauricio R, Clegg Nancy J, Zayed Zayed Al, Dogar Mohammad Asif, Alorainy Ibrahim A, Jamea Abdullah Abu, Abu‐Amero Khaled, Griebel May, Ward Wendy, Lein Ed S, Barkovich A James, Robson Caroline D, Bosley Thomas M
Journal: Nature Genetics (2017)