tbuckley/cabot-search huggingface dataset:
Are epigenetic therapies modifying sensitivity to conventional chemotherapy?
Authors: A. Bizot, P. Romano-Martin, C. Baldini, S. Champiat, A. Varga, A. Gazzah, R. Bahleda, P. Vuagnat, A. Hollebecque, J.-M. Michot, V. Ribrag, C. Massard, S Postel Vinay
Journal: Annals of Oncology (2019)
Gelatin Hydrogel Microspheres Enable Pinpoint Delivery of Basic Fibroblast Growth Factor for the Development of Functional Collateral Vessels
Authors: AkihiroHosaka, HiroyukiKoyama, ToshihiroKushibiki, YasuhikoTabata, NobuhiroNishiyama, TetsuroMiyata, HiroshiShigematsu, TsuyoshiTakato, HirokazuNagawa
Journal: Circulation (2004)

Background— Various growth factors promote collateral vessel development and are regarded as promising for the treatment of vascular occlusive diseases. However, an efficacious delivery system for them has yet to be established. We devised a strategy to augment functional collateral vessels by using acidic gelatin hydrogel microspheres (AGHMs) incorporating basic fibroblast growth factor (bFGF). The aim of the present study was to investigate the hypothesis that by intra-arterial (IA) administration of bFGF-impregnated AGHMs, bFGF could be delivered from AGHMs trapped in distal small-diameter vessels and thereby induce functional collateral vessels with an assured blood supply through the process of arteriogenesis. Methods and Results— Various sizes of AGHMs (3 mg) incorporating 125I-labeled bFGF were injected into the left internal iliac artery of a rabbit model of hindlimb ischemia. Less than 50% of radioactivity accumulated in the ischemic hindlimb after injection of AGHMs that were 10 μm in diameter, ...
FPA150 (B7-H4 antibody) phase I update in advanced solid tumours: Monotherapy and in combination with pembrolizumab
Authors: Z.A. Wainberg, J.C. Sachdev, T. Bauer, S. Pant, S. Chawla, N. Marina, H. Xiang, W. Deng, M. Schmidt, A. Patnaik, P. LoRusso
Journal: Annals of Oncology (2019)
Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumour DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global phase III study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations
Authors: K. Nishio, K. Sakai, T. Seto, M. Nishio, M. Reck, E.B. Garon, C.M. Visseren-Grul, R.R. Hozak, S.R. Wijayawardana, S. Enatsu, K. Nakagawa
Journal: Annals of Oncology (2019)
High dose neo-adjuvant chemotherapy in triple-negative breast cancer with evidence of homologous recombination deficiency (HRD)
Authors: S.B. Vliek, E. Van Werkhoven, I. Mandjes, T. Westphal, E.H. Lips, L. Mulder, C. Loo, N. Russel, M. Holtkamp, M. Schot, J. Baars, M. Karger, A.H. Honkoop, M E M M Bos, A.L.T. Imholz, S. Vrijaldenhoven, V. Dezentje, P.M. Nederlof, S.C. Linn
Journal: Annals of Oncology (2019)
Phone triage &amp; acute review clinics: The emerging role of the oncology specialist nurse
Authors: F.E. Barrett, F. Keane, D. O’Doherty, W. Connolly, C. Matassa, B. Ryan, T. Doyle, K. Dempsey, L. Grogan, P.G. Morris, B.T. Hennessy, O.S. Breathnach, C. O’Shea, A. Christie
Journal: Annals of Oncology (2019)
POLAF study: Efficacy and safety of FOLFIRI/aflibercept in a phase II trial in patients with metastatic colorectal cancer: Results of plasmatic prognostic and predictive markers
Authors: M E Elez Fernandez, M.A. Gómez-España, C. Grávalos, P. García-Alfonso, B. Rodríguez, F. Losa, I.C. Ales-Diaz, B Graña Suarez, M. Toledano, M. Valladares-Ayerbes, E Polo Marques, M Salgado Fernandez, E Martínez de Castro, M Gil Raga, M A Salud Salvia, A. Ruiz-Casado, A. Rodríguez-Ariza, E Aranda Aguilar
Journal: Annals of Oncology (2019)
Abstract 1082: Cytoskeletal Protein 4.1R Affects Repolarisation And Regulates Calcium Handling In The Heart
Authors: Cesare M Terracciano, Nadia Sohrabi, Urszula Siedlecka, Mark A Stagg, Gopal K Soppa, Joon Lee, Paul J Barton, Pauline Bennett, Jennifer C Pinder, Magdi H Yacoub
Journal: Circulation (2007)

The 4.1 proteins are a family of multifunctional adaptor proteins that organise signalling/transport/cell adhesion molecules. They are capable of interaction with the spectrin-actin network thereby conferring mechanical stability to the cell membrane, with several ion transporters associated to this macromolecular complex. Protein 4.1R is expressed in the heart and upregulated in deteriorating human heart failure. However, no data exists on the roles of protein 4.1R in myocardial regulation and function. In particular, it is unknown whether this protein can influence cardiac contractility and/or electrophysiology. 4.1R-deficient mice (KO) were studied using echocardiography and ECG monitoring with radiotelemetry. Left ventricular dimensions were increased in KO mice (LV diameter - Dia (cm): WT = 0.43 ± 0.01 [6] (mean ± SEM [n]); KO = 0.49 ± 0.01 [6]; p &lt; 0.01) - Sys cm): WT = 0.29 ± 0.01 [6]; KO = 0.34 ± 0.02 [6]; p &lt; 0.05) with no changes in ejection fraction and fractional shortening. ECG analysis revealed reduced heart rate (RR interval (ms): WT = 113±5 [6]; KO = 139 ± 601 [6]; p &lt; 0.01) accompanied by prolonged QT interval (corrected (ms): WT = 46 ± 2 [6]; KO = 52 ± 1 [6]; p &lt; 0.05). The action potential duration (APD) measured in isolated ventricular myocytes was prolonged in KO (APD 90% at 1Hz (ms) WT = 146 ± 20 [21]; KO = 231 ± 29 [28]; p &lt; 0.05). Ca transients, elicited by 1Hz field-stimulation and measured using the fluorescent indicator indo-1, were larger (amplitude (ratio units r.u.): WT = 0.07 ± 0.006 [22]; KO = 0.1 ± 0.006 [33]; p&lt;0.05) and slower to decay in the KO group (time to 50% decline (ms): WT = 78 ± 3 [22]; KO = 91 ± 3 [33]; p &lt; 0.05). This was associated with increased SR Ca content, (20 mM caffeine-induced indo-1 transient amplitude (r.u.): WT = 0.09 ± 0.01 [7]; KO = 0.13 ± 0.01 [16]; p &lt; 0.05) and increased frequency of Ca sparks, measured by confocal microscopy using Fluo-4 (sparks/100μm/s. WT = 0.52 ± 0.08 [111]; KO = 1.21 ± 0.14 [124]; p &lt; 0.001). We conclude that protein 4.1 R affects repolarisation of cardiac myocytes. This may have a role in bringing about QT prolongation in KO mice. The prolonged APD, together with effects on Ca handling proteins, may alter Ca regulation and cell contractility. The specific mechanisms controlling these effects are under investigation.
Publisher Correction: A repeated molecular architecture across thalamic pathways
Authors: James W. Phillips, Anton Schulmann, Erina Hara, Johan Winnubst, Chenghao Liu, Vera Valakh, Lihua Wang, Brenda C. Shields, Wyatt Korff, Jayaram Chandrashekar, Andrew L. Lemire, Brett Mensh, Joshua T. Dudman, Sacha B. Nelson, Adam W. Hantman
Journal: Nature Neuroscience (2019)
Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC)
Authors: G. Kaval, M. Altun, K. Ibis, K. Ozkaya, R. Meral, A.N. Karadeniz, M. Sarı, M. Ekenel, M. Basaran, S. Bavbek
Journal: Annals of Oncology (2019)
Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gastric cancer with peritoneal dissemination refractory to first-line therapy: WJOG10617G/P-SELECT
Authors: K. Hirata, Y. Hamamoto, K. Tsuchihashi, C. Kondoh, K. Yamazaki, S. Hironaka, M. Ando, C.K. Imamura, K. Yoshimura, K. Muro
Journal: Annals of Oncology (2019)
A randomized phase II study of maintenance therapy with multiepitope vaccine tedopi (OSE2101) ± nivolumab or FOLFIRI after induction chemotherapy (CT) with FOLFIRINOX in patients (Pts) with advanced pancreatic ductal adenocarcinoma (aPDAC) (TEDOPaM – PRODIGE 63 GERCOR study)
Authors: C. Neuzillet, V. Hautefeuille, A. Lambert, M.-L. Garcia-Larnicol, D. Vernerey
Journal: Annals of Oncology (2019)
Prospective, multicenter registry trial to evaluate the clinical feasibility of targeted axillary dissection (TAD) in patients (pts) with breast cancer (BC) and core biopsy proven axillary involvement (cN+)
Authors: M. Reinisch, J. Heil, A. Rüland, C. Seiberling, H. Harrach, D. Schindowski, J. Lubitz, C. Ankel, S.-T. Graßhoff, P. Deuschle, V. Hanf, J. Holtschmidt, E. Traut, T. Kuehn, S. Kuemmel
Journal: Annals of Oncology (2019)
Phase I/II study of 9-ING-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor, as a single agent and combined with chemotherapy, in patients with refractory haematological malignancies or solid tumours
Authors: B. Carneiro, L. Cavalcante, P. Munster, A. de Souza, H.P. Safran, F. Giles
Journal: Annals of Oncology (2019)
Effective treatment with T-VEC monotherapy in stage IIIB/C-IVM1a melanoma of the head &amp; neck region
Authors: V. Franke, E.H.A. Stahlie, D.M.S. Berger, W.M.C. Klop, L. Zuur, B. van der Hiel, B.A. van de Wiel, M W J M Wouters, W.J. van Houdt, A.C.J. van Akkooi
Journal: Annals of Oncology (2019)
Development of a living organoid biobank derived from colorectal cancer patients: Towards personalized medicine
Authors: F. Papaccio, M.F. Gutierrez-Bravo, M. Cabeza-Segura, V. Gambardella, M. Huerta, C Martinez Ciarpaglini, S Rosello Keranen, F. Gimeno-Valiente, T. Fleitas, N Tarazona Llavero, D. Roda, A. Cervantes, J. Castillo
Journal: Annals of Oncology (2019)
PSA is an autocrine survival factor in prostate cancer LNCaP cells
Authors: Thomas M. Nicotera, David S. Schuster, Kailish C. Chadha
Journal: Cancer Research (2005)

793  Serum prostate specific antigen (PSA) levels are elevated in prostate cancer patients and serve as a diagnostic marker for the disease. Prostate cancer is generally responsive to androgen ablation therapy and produces a drop in PSA levels. In time, hormone-refractory disease often develops and PSA levels once again rise. Under normal circumstances PSA is deposited in the lumen of prostatic ducts, whereas PSA secreted from malignant cells gains access to the circulation. The underlying biochemical mechanisms for the aberrant control of PSA secretion in prostate tumors are not well-known. Regulation of peptide secretion by iPLA2-β has recently been reported in non-prostatic tissue. In prostate tissue, both iPLA2-β and PSA expression are reportedly under androgen regulation. We therefore investigated whether iPLA2-β plays a role in PSA secretion in normal prostate epithelial RWPE-1 cells and in LNCaP prostate cancer cells. We observed an increase in iPLA2 activity in LNCaP cells that corresponded with an increase in expression of the two active isoforms, LH-iPLA2 and SH-iPLA2, as well as a decrease in the inhibitory ankyrin-iPLA2 isoform. We further demonstrated that treatment with the iPLA2-specfic inhibitor, BEL, inhibited PSA secretion from LNCaP cells and subsequently resulted in cell death. While BEL treatment triggered an apoptotic response in LNCaP cells, normal prostate RWPE-1epithelial cells were not vulnerable to BEL-induced cell death. Addition of exogenous PSA to LNCaP cultures suppressed BEL-induced cell death and addition of anti-PSA antibody reversed the survival effect of PSA. These data demonstrate that iPLA2 plays a role in regulating PSA secretion from cells and the release of PSA provides an autocrine survival function for LNCaP cells. The mechanism by which PSA imparts its survival effect is not currently understood.
Ror1 Targeting Monoclonal Antibodies Induced Apoptosis of Chronic Lymphocytic Leukemia Cells– A Potential Novel Therapeutic Approach
Authors: Hodjattallah Rabbani, Amir Hossein Daneshmanesh, Abdul Salam Khan, Mohammad Hojjat-Farsangi, Mahmood Jeddi-Tehrani, Mohammad Mehdi Akhondi, Anders Österborg, Fazel Shokri, Håakan Mellstedt
Journal: Blood (2010)
Non-immunogenic utrophin gene therapy for the treatment of muscular dystrophy animal models
Authors: Yafeng Song, Leon Morales, Alock S. Malik, Andrew F. Mead, Christopher D. Greer, Marilyn A. Mitchell, Mihail T. Petrov, Leonard T. Su, Margaret E. Choi, Shira T. Rosenblum, Xiangping Lu, Daniel J. VanBelzen, Ranjith K. Krishnankutty, Frederick J. Balzer, Emanuele Loro, Robert French, Kathleen J. Propert, Shangzhen Zhou, Benjamin W. Kozyak, Peter P. Nghiem, Tejvir S. Khurana, Joe N. Kornegay, Hansell H. Stedman
Journal: Nature Medicine (2019)
The efficacy and safety of lenvatinib in patients who did not meet the inclusion criteria of the phase III trial (REFLECT trial) and those with BCLC Stage B hepatocellular carcinoma: A nationwide multicenter study in Japan
Authors: A. Sakamoto, M. Kurosaki, K. Tsuchiya, T. Abe, C. Ogawa, T. Soda, H. Kimura, M. Kondo, K. Tsuji, F. Koichiro, M. Shigeno, K. Jyoko, R. Narita, Y. Uchida, H. Yoshida, T. Akahane, H. Kobashi, A. Mitsuda, H. Marusawa, N. Izumi
Journal: Annals of Oncology (2019)
Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells
Authors: Yan Zhang, Jia Xu, Siying Liu, Meikuang Lim, Shuang Zhao, Kaige Cui, Kaiyue Zhang, Lingling Wang, Qian Ji, Zhongchao Han, Deling Kong, Zongjin Li, Na Liu
Journal: Theranostics (2019)

Background: Embryonic stem cells (ES) have a great potential for cell-based therapies in a regenerative medicine. However, the ethical and safety issues limit its clinical application. ES-derived extracellular vesicles (ES-EVs) have been reported suppress cellular senescence. Mesenchymal stem cells (MSCs) are widely used for clinical cell therapy. In this study, we investigated the beneficial effects of ES-EVs on aging MSCs to further enhancing their therapeutic effects. Methods:In vitro, we explored the rejuvenating effects of ES-EVs on senescent MSCs by senescence-associated β-gal (SA-β-gal) staining, immunostaining, and DNA damage foci analysis. The therapeutic effect of senescent MSC pre-treated with ES-EVs was also evaluated by using mouse cutaneous wound model. Results: We found that ES-EVs significantly rejuvenated the senescent MSCs in vitro and improve the therapeutic effects of MSCs in a mouse cutaneous wound model. In addition, we also identified that the IGF1/PI3K/AKT pathway mediated the antisenescence effects of ES-EVs on MSCs. Conclusions: Our results suggested that ES cells derived-extracellular vesicles possess the antisenescence properties, which significantly rejuvenate the senescent MSCs and enhance the therapeutic effects of MSCs. This strategy might emerge as a novel therapeutic strategy for MSCs clinical application.
Single-cell immune landscape of human atherosclerotic plaques
Authors: Dawn M. Fernandez, Adeeb H. Rahman, Nicolas F. Fernandez, Aleksey Chudnovskiy, El-ad David Amir, Letizia Amadori, Nayaab S. Khan, Christine K. Wong, Roza Shamailova, Christopher A. Hill, Zichen Wang, Romain Remark, Jennifer R. Li, Christian Pina, Christopher Faries, Ahmed J. Awad, Noah Moss, Johan L. M. Bjorkegren, Seunghee Kim-Schulze, Sacha Gnjatic, Avi Ma’ayan, J Mocco, Peter Faries, Miriam Merad, Chiara Giannarelli
Journal: Nature Medicine (2019)
Donor cell engineering with GSK3 inhibitor–loaded nanoparticles enhances engraftment after in utero transplantation
Authors: Stavros P. Loukogeorgakis, Camila G. Fachin, Andre I. B. S. Dias, Haiying Li, Li Tang, Aimee G. Kim, Jesse D. Vrecenak, John D. Stratigis, Nicholas J. Ahn, Ilana Nissim, Izhtak Nissim, Antonio F. Moron, Jose L. Martins, William H. Peranteau, Paolo De Coppi, Darrell J. Irvine, Alan W. Flake
Journal: Blood (2019)
Validation of a clinicopathological and gene expression profile (CP-GEP) model for sentinel lymph node metastasis in primary cutaneous melanoma
Authors: E E A P Mulder, J.T. Dwarkasing, L.M. Hollestein, D. Tempel, L. Bosman, D. Verver, A.L. Mooyaart, A.A.M. Van der Veldt, C. Verhoef, T.E.C. Nijsten, D.J. Grünhagen
Journal: Annals of Oncology (2019)
Association of Socioeconomic Status (SES) with Outcomes of Autologous Hematopoietic Cell Transplantation (ASCT) for Lymphoma
Authors: Sanghee Hong, Lisa A. Rybicki, Donna M Abounader, Brian J. Bolwell, Robert M. Dean, Aaron T. Gerds, Betty K. Hamilton, Brian T. Hill, Deepa Jagadeesh, Matt Kalaycio, Hien K. Liu, Brad Pohlman, Ronald Sobecks, Navneet S. Majhail
Journal: Blood (2015)
Analytical validation of a thyroid cancer diagnostic method based on the relative quantification of CLDN10, HMGA2 and LAMB3 expression
Authors: M.C. Barrosfilho, J.B.H. Mello, V.P. de Andrade, M.A. Saieg, C.A.L. Pinto, L.P. Kowalski, S.R. Rogatto
Journal: Annals of Oncology (2019)
Gem-(R)CHOP Versus (R)CHOP: A Randomized Phase II Study of Gemcitabine Combined with (R)CHOP in Untreated Aggressive Non- Hodgkin’s Lymphoma - EORTC Lymphoma Group Protocol 20021
Authors: Igor Aurer, Houchingue Eghbali, John M. Raemaekers, Hussein M Khaled, Martine Van Glabbeke, Liliana Baila, Richard van der Maazen
Journal: Blood (2008)
Taste and smell alterations (TSAs) in patients (pts) with stage II-III colon cancer (CC): A pilot within the PROTECT study
Authors: J.W.G. Derksen, M. Koopman, D. ten Bokkel Huinink, D.W. Sommeijer, B. Dorresteijn, M. Jourdan, A.M. May
Journal: Annals of Oncology (2019)
Outcomes of advanced melanoma patients who discontinued pembrolizumab (pembro) after complete response (CR) in the French early access program (EAP)
Authors: P. Saiag, L. Mortier, C. Dutriaux, L. Benmahammed, O. Morsli, C. Train, A. Spampinato, M.T. Leccia, N. Meyer, J.J. Grob
Journal: Annals of Oncology (2019)
Radiation-related lymphopenia after pelvic nodal irradiation for prostate cancer.
Authors: Sunil W Dutta, Michael D Schad, Donald A Muller, Krishni Wijesooriya, Timothy N Showalter
Journal: Journal of Clinical Oncology (2019)

26 Background: Given uncertainty regarding the effectiveness of pelvic nodal irradiation (PNI) for prostate cancer, we aimed to determine whether prostate cancer patients treated with PNI are at a higher risk of developing radiation-related lymphopenia (RRL) and whether RRL is predictive for worse treatment outcomes. Methods: The electronic charts of 886 consecutive patients treated with radiation therapy (RT) for prostate cancer from 2006 to 2018 at our institution were retrospectively analyzed. Qualifying patients were those with total lymphocyte counts (TLCs) within one year prior to and 3–24 months after the start of RT. Lymphopenia was the primary outcome; overall survival (OS) and biochemical progression-free survival (bPFS) were secondary outcomes. Results: Thirty-six patients with PNI and ninety-five patients without PNI qualified. In the PNI cohort, 61.1% of patients developed RRL (median follow-up TLC &lt; 1000 cells/µL), versus 26.3% of non-PNI patients. On univariate analysis, initial prostate specific antigen (iPSA), baseline lymphopenia, treatment modality, PNI status, increased planned target volume, and androgen deprivation therapy administration were all significant predictors of RRL ( p &lt; 0.05). On multivariate analysis, PNI status was a significant predictor of RRL ( p &lt; 0.001; HR 3.42; 95% CI 1.22–9.61) as well as iPSA ( p = 0.006; HR 1.05; 95% CI 1.00–1.11) and baseline lymphopenia ( p = 0.007; HR 8.32; 95% CI 2.19–31.6). RRL was not predictive for bPFS, distant metastasis, or OS on multivariate analysis, though the numbers of events were likely insufficient for these analyses. Conclusions: The higher risk of RRL among PNI patients comports with other papers that show increased treatment volumes are associated with higher rates of RRL. Mounting evidence for the adverse effects of RRL on clinical outcomes supports the significance of our findings and suggests further studies are needed on RRL as a potential harm of PNI that may affect interpretation of results from clinical trials of PNI.
Abstract 1031: First Human Experiments: Aggressive Statin Therapy Reduced Key Inflammatory Factors including c-Jun N-terminal kinase (JNK) and Dendritic Cell and Matrix Metalloproteinase Expression in Human Abdominal Aortic Aneurysmal Wall
Authors: Kan Kajimoto, Katsumi Miyauchi, Kazunori Shimada, Takatoshi Kasai, Yuko Kojima, Akie Shimada, Katsuhiko Sumiyoshi, Hiroshi Niinami, Atsushi Amano, Hiroyuki Daida
Journal: Circulation (2007)

Abdominal aortic aneurysms (AAA) accumulate feature of a chronic inflammatory disorder and irreversible destruction connective tissue. Recent experimental study demonstrated that c-Jun N terminal kinase (JNK) was a proximal signaling molecule in the pathogenesis of AAA and vascular dendritic cells (DC) were the key molecular in inflammatory reaction and the degradation of the extracellular matrix. Statins can inhibit cell proliferation and vascular inflammation, which might contribute to prevent AAA progrssion. But supporting clinical data from human studies are lacking. We hypothesized that atorvastatin might inhibit JNK and DC, resulting in suppression of inflammatory cells and matrix metalloproteinase (MMPs) in human tissue of AAA. Methods : Patients with AAA were randomized to the atorvastatin (20 mg/day, 10 patients) group or control (10 patients) group. After treatment of 4 weeks, patients underwent abdominal aorta replacement, tissue specimens were obtained, and the tissue composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Results :Atorvastatin significantly reduced JNK and DC expression (46% and 72%) compared to control. T cells, macrophages (60%, 72%, P&lt; 0.05), and MMP-2 and MMP-9 immunoreactivity (47%, 43%, P&lt; 0.05) were also suppressed in atorvastatin group. However, tissue expression of metalloproteinase 1 (TIMP-1) immunoreactivity and a collagen content by sirius red staining were similar in both groups. In atorvastatin group, serum LDL-C level was significantly decreased by 40%. Conclusion: Atorvastatin treatment reduced the JNK expression and DE, resulting in inflammatory cells content and the expression of MMPs in human abdominal aortic aneurysm wall.
FOXN1 compound heterozygous mutations cause selective thymic hypoplasia in humans
Authors: Qiumei Du, Larry K. Huynh, Fatma Coskun, Erika Molina, Matthew A. King, Prithvi Raj, Shaheen Khan, Igor Dozmorov, Christine M. Seroogy, Christian A. Wysocki, Grace T. Padron, Tyler R. Yates, M. Louise Markert, M. Teresa de la Morena, Nicolai S.C. van Oers
Journal: Journal of Clinical Investigation (2019)

We report on 2 patients with compound heterozygous mutations in forkhead box N1 (FOXN1), a transcription factor essential for thymic epithelial cell (TEC) differentiation. TECs are critical for T cell development. Both patients had a presentation consistent with T–/loB+NK+ SCID, with normal hair and nails, distinct from the classic nude/SCID phenotype in individuals with autosomal-recessive FOXN1 mutations. To understand the basis of this phenotype and the effects of the mutations on FOXN1, we generated mice using CRISPR-Cas9 technology to genocopy mutations in 1 of the patients. The mice with the Foxn1 compound heterozygous mutations had thymic hypoplasia, causing a T–B+NK+ SCID phenotype, whereas the hair and nails of these mice were normal. Characterization of the functional changes due to the Foxn1 mutations revealed a 5–amino acid segment at the end of the DNA-binding domain essential for the development of TECs but not keratinocytes. The transcriptional activity of this Foxn1 mutant was partly retained, indicating a region that specifies TEC functions. Analysis of an additional 9 FOXN1 mutations identified in multiple unrelated patients revealed distinct functional consequences contingent on the impact of the mutation on the DNA-binding and transactivation domains of FOXN1.
临床证据（九）：急性心肌梗死
Authors: ShamirMehta
Journal: BMJ (2002)

背景知识定义 急性心肌梗死 (ＡＭＩ)是指引起心肌缺血坏死的冠状动脉的突然闭塞。发病率和患病率 无论在发达国家还是在发展中国家 ,ＡＭＩ都是最常见的死亡原因之一。 1990年全世界约 6 30万人死于缺血性心脏病 ,是导致死亡的首要原因。其年龄标准化发病率在不同国家之间和同一国家的不同地区之间是不同的1 。在美国 ,每年有大约 90万人发生一次ＡＭＩ,其中 2 2 5万人死亡。死亡者中约 1 2死于症状出现 1小时内和到达医院急诊室前2 。男性与女性的发病率均随年龄的增高而增高 ,男性高于女性 ,而且在任何年龄段 ,穷人高于富人。近2 0年 ,在许多西方国家ＡＭＩ死亡率已经下降。病因学和
Paclitaxel in combination with cisplatin and 5-fluorouracil (TPF) induction chemotherapy for locally advanced borderline-resectable esophageal squamous cell carcinoma: A phase II clinical trial
Authors: Y. Li, Z. Wang, H. Yang, Q. Li, H. Liu, D.S. Wang, S.Y. Xi, M.Z. Qiu, C. Ren
Journal: Annals of Oncology (2019)
Randomized phase III trial of avelumab + axitinib vs sunitinib as first-line treatment for advanced renal cell carcinoma: JAVELIN renal 101 Japanese subgroup analysis
Authors: M. Uemura, Y. Tomita, H. Miyake, S. Hatakeyama, H.-O. Kanayama, K. Numakura, T. Takagi, T. Kato, M. Eto, W. Obara, H. Uemura, R.J. Motzer, Y. Fujii, Y. Kamei, M. Oya
Journal: Annals of Oncology (2019)