tbuckley/cabot-search huggingface dataset:
Functional identity of hypothalamic melanocortin neurons depends on Tbx3
Authors: Carmelo Quarta, Alexandre Fisette, Yanjun Xu, Gustav Colldén, Beata Legutko, Yu-Ting Tseng, Alexander Reim, Michael Wierer, Maria Caterina De Rosa, Valentina Klaus, Rick Rausch, Vidhu V. Thaker, Elisabeth Graf, Tim M. Strom, Anne-Laure Poher, Tim Gruber, Ophélia Le Thuc, Alberto Cebrian-Serrano, Dhiraj Kabra, Luigi Bellocchio, Stephen C. Woods, Gert O. Pflugfelder, Rubén Nogueiras, Lori Zeltser, Ilona C. Grunwald Kadow, Anne Moon, Cristina García-Cáceres, Matthias Mann, Mathias Treier, Claudia A. Doege, Matthias H. Tschöp
Journal: Nature Metabolism (2019)
Finalists are announced for 11th BMJ Awards
Authors: Zosia Kmietowicz
Journal: BMJ (2019)

The hunt to find the best medical innovators and leaders of 2018 is nearly over, with this week’s announcement of the 78 teams shortlisted for the 11th BMJ Awards.

This year’s awards attracted 291 entries across 14 categories, which for the first time include care of the older person, diabetes, and digital innovation.

The awards reflect The BMJ ’s mission to improve patient outcomes and showcase the very best healthcare by recognising and celebrating the exceptional work done by doctors and their teams around the UK.

In the clinical leadership category, finalists include teams …
Abstract 13647: Different Prognosis Between Superficial Femoral and Coronary Arteries After Bare Metal Stent Implantation Can be Demonstrable by Comparative Histopathological Analysis
Authors: Katsumi Inoue, Masao Imai, Kenji Ando, Takeshi Kimura
Journal: Circulation (2017)

Background: Bare metal stent (BMS) implantation is far more commonly performed for superficial femoral artery (SFA) disease than for coronary artery (CA) disease; however, the prognosis after BMS i...
Sputum autoantibody-mediated macrophage dysfunction in severe eosinophilic asthmatics with recurrent infections
Authors: Manali Mukherjee, Joseph Chon, Mark Sorin, Katherine Radford, Terence N. Ho, Paige Lacy, Dawn M. Bowdish, Parameswaran K. Nair
Journal: Journal of Allergy and Clinical Immunology (2019)
Relation between the size of nonmetastatic and metastatic lymph nodes and outcomes in patients with stage III colon cancer.
Authors: Kazutake Okada, Sotaro Sadahiro, Yutaro Kamei, Takashi Ogimi, Hiroshi Miyakita, Gota Saito, Akira Tanaka, Toshiyuki Suzuki, Lin Fung Chan
Journal: Journal of Clinical Oncology (2019)

494 Background: In colon cancer, retrieval of less than 12 lymph nodes is a risk factor for recurrence. We previously reported that the long-axis diameter of the largest LNs (maximum LNs) is associated with a higher number of retrieved LNs and better outcomes in stage II disease (Int J Colorectal Dis 2015). Furthermore, the number of natural killer cells in the maximum LNs is associated with the number of retrieved LNs and lymph node size, and is an independent prognostic factor (Oncology 2018). We examined whether the long-axis diameter of maximum LNs with and without metastasis is a prognostic factor in stage III colon cancer. Methods: The study group comprised 190 patients with stage III colon cancer from 2005 to 2014. For each patient, one negative LN and one positive LN with the greatest long-axis diameter were selected, and the diameter was measured on H-E stained specimens. The endpoint of survival analysis was relapse free survival (RFS). The cut-off value (COV) was determined by using receiver operating characteristic curves. Results: The mean long-axis diameter of maximum negative and positive LNs were 8.5 ± 3.7 and 9.9 ± 4.9 mm, respectively. Factors related to the number of retrieved LNs were the tumor size (less than 4.3 cm, 13.5 ± 6.4; 4.3 cm or more, 16.6 ± 7.3; p = 0.004) and the long axis diameter of maximum negative LNs (&lt; 8.1 mm, 13.4 ± 6.9; ≥ 8.1 mm, 17.6 ± 6.6; p &lt; 0.001). Maximum negative LNs with a diameter of ≥ 8.1 mm was associated with significantly better RFS than maximum negative LNs with a diameter of &lt; 8.1 mm (p = 0.020). The diameter of maximum positive LNs was not a prognostic factor. On multivariate analysis, the tumor size (≥ 4.3 cm/&lt; 4.3 cm, HR 3.02; p &lt; 0.001), venous invasion (absent/present, HR 0.41; p = 0.017), the number of LNs (≥ 12/&lt; 12, HR 0.56; p = 0.043), and the diameter of maximum negative LNs (≥ 8.1 mm/&lt; 8.1 mm, HR 0.45; p = 0.008) were independent prognostic factors. Conclusions: In stage III colon cancer, the long-axis diameter of negative maximum LNs was a prognostic factor. Enlarged negative LNs are caused by hyperplasia of cell components in LNs. The size of negative maximum LNs might reflect the tumor immunity of the host.
Postlicensure Safety Surveillance of Recombinant Zoster Vaccine (Shingrix) — United States, October 2017–June 2018
Authors: Elisabeth M. Hesse, Tom T. Shimabukuro, John R. Su, Beth F. Hibbs, Kathleen L. Dooling, Ravi Goud, Paige Lewis, Carmen S. Ng, Maria V. Cano
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Recombinant zoster vaccine (RZV; Shingrix), an adjuvanted glycoprotein vaccine, was licensed by the Food and Drug Administration (FDA) and recommended by the Advisory Committee on Immunization Practices for adults aged ≥50 years in October 2017 (1).The previously licensed liveattenuated zoster vaccine (ZVL; Zostavax) is recommended for adults aged ≥60 years.RZV is administered intramuscularly as a 2-dose series, with an interval of 2-6 months between doses.In prelicensure clinical trials, 85% of 6,773 vaccinated study participants reported local or systemic reactions after receiving RZV, with approximately 17% experiencing a grade 3 reaction (erythema or induration >3.5 inches or systemic symptoms that interfere with normal activity).However, rates of serious adverse events (i.e., hospitalization, prolongation of existing hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death) were similar in the RZV and placebo groups (2).After licensure, CDC and FDA began safety monitoring of RZV in the Vaccine Adverse Event Reporting System (VAERS) (3).During the first 8 months of use, when approximately 3.2 million RZV doses were distributed (GlaxoSmithKline, personal communication, 2018), VAERS received a total of 4,381 reports of adverse events, 130 (3.0%) of which were classified as serious.Commonly reported signs and symptoms included pyrexia (fever) (1,034; 23.6%), injection site pain (985; 22.5%), and injection site erythema (880; 20.1%).No unexpected patterns were detected in reports of adverse events or serious adverse events.Findings from early monitoring of RZV are consistent with the safety profile observed in prelicensure clinical trials.VAERS is a national passive surveillance system for adverse events after administration of U.S.-licensed vaccines and is coadministered by CDC and FDA (3).VAERS accepts reports from health care providers, vaccine manufacturers, and the public.Signs and symptoms of each adverse event are coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology (3).A single VAERS report might be assigned more than one MedDRA Preferred Term*; these terms are not necessarily medically confirmed diagnoses.VAERS reports are classified as "serious" according to Code of Federal Regulations Title 21 Section 600.80.† Medical records are requested for * A distinct descriptor (e.g., for a symptom, sign, or disease diagnosis).https:// www.meddra.org/how-to-use/basics/hierarchy.
Role of Tumor-Associated Macrophages in the Clinical Course of Pancreatic Neuroendocrine Tumors (PanNETs)
Authors: Lei Cai, Theodoros Michelakos, Vikram Deshpande, Kshitij S. Arora, Teppei Yamada, David T. Ting, Marty S. Taylor, Carlos Fernandez-del Castillo, Andrew L. Warshaw, Keith D. Lillemoe, Soldano Ferrone, Cristina R. Ferrone
Journal: Clinical Cancer Research (2019)

This study evaluated the potential role of immune cells and molecules in the pathogenesis and clinical course of pancreatic neuroendocrine tumors (PanNET).Surgically resected PanNETs (N = 104) were immunohistochemically analyzed for Ki67 index, mitotic rate, macrophage, CD4+ cells, and CD8+ T-cell infiltration, as well as HLA class I, PD-L1, and B7-H3 expression. Results were correlated with clinicopathologic characteristics as well as with disease-free (DFS) and disease-specific (DSS) survival.The median age of the 57 WHO grade 1 and 47 WHO grade 2 patients was 55 years. High intratumoral CD8+ T-cell infiltration correlated with prolonged DFS (P = 0.05), especially when the number of tumor-associated macrophages (TAM) was low. In contrast, high peritumoral CD4+ cell and TAM infiltration was associated with a worse DFS and DSS. PD-L1 and B7-H3 were expressed in 53% and 78% PanNETs, respectively. HLA class I expression was defective in about 70% PanNETs. HLA-A expression correlated with favorable DSS in PD-L1-negative tumors (P = 0.02). TAM infiltration (P = 0.02), WHO grade (P = 0.04), T stage (P = 0.01), and lymph node positivity (P = 0.04) were independent predictors of DFS. TAM infiltration (P = 0.026) and T stage (P = 0.012) continued to be predictors of DFS in WHO grade 1 PanNET patients. TAM infiltration was the sole independent predictor of DSS for WHO grade 1 and 2 patients (P = 0.02). Therefore, this biomarker may contribute to identifying WHO grade 1 patients with poor prognosis.TAM infiltration appears to be the most informative prognostic biomarker in PanNET. It may represent a useful immunotherapeutic target in patients with PanNET.
Pruritic Rash in a Woman With Hodgkin Lymphoma
Authors: Clayton Jackson, Lindsey Strowd, Zanetta Lamar
Journal: JAMA Oncology (2019)

A 31-year-old woman with a history of Wolff-Parkinson-White disease and a recent stage II Hodgkin lymphoma diagnosis developed a pruritic rash within 24 hours of the first day of chemotherapy. What is your diagnosis?
Abstract 20918: Cytokines Involved in Arterial Wall Inflammation Are Transported by High Density Lipoprotein Particles
Authors: Kate Townsend Creasy, Eveline O Stock, Xiaoli Tian, Arun Prakash, Clive R Pullinger, Mary J Malloy, John P Kane
Journal: Circulation (2017)

Introduction: Inflammation plays an important role in the induction of CAD and the progression to deadly coronary syndromes. Cytokines are key mediators of inflammation, both in pro- and anti-inflammatory capacities. HDL has a vital role in the maintenance of cardiovascular health, and recent discoveries highlight the diversity of HDL functions to include the transport of lipid signaling molecules, microRNAs, and other effectors of metabolic regulation. Given the importance of HDL in transporting molecules involved in cardiovascular health, we questioned if HDL has a direct role in transporting cytokines and effecting inflammatory responses in CAD. Hypothesis: HDL plays an important role in the transport of cytokines involved in CAD. Methods: To explore the role of HDL in arterial inflammation, we profiled the abundance of 35 cytokines in plasma and HDL of men and women with and without CAD. We analyzed whole plasma and native HDL isolated using a selected-affinity immunosorption technique from patients who suffered myocardial infarction at an early age (&lt;60 years, male n=19; female n=20) and control patients (male n=10, female n=10). Samples were assayed by multiplex array technology for quantification of cytokines. Results: Of 35 cytokines analyzed, 25 appear to be significantly transported in HDL. Three cytokines (IL-12, MCP-1, and IL-RA) are excluded from HDL and are only detectable in plasma. IL-3 and IL-7 are predominately associated with HDL and are elevated in both males and females with MI. There are differences in several HDL-associated cytokines that appear to be sex-dependent. Conclusions: We have discovered that a number of cytokines are transported in HDL complexes. Significant elevations or decreases in a number of these cytokines are observed in patients with CAD, and vary in abundance between males and females.
Abstract 15627: Chronic Exposure to Traffic-related Air Pollution and Cancer Incidence Among 10,000 Israeli Patients Undergoing Percutaneous Coronary Interventions: A Follow-up Study
Authors: Gali Cohen, Ilan Levy, Yuval, Jeremy D Kark, Noam Levin, Guy Witberg, Zaza Iakobishvili, David M Broday, David M Steinberg, Ran Kornowski, Yariv Gerber
Journal: Circulation (2017)

Background: Exposure to traffic-related air pollution (TRAP) is considered to have a carcinogenic effect. The authors previously reported an association between TRAP and risk of cancer in a relatively small cohort of first myocardial infarction survivors. This study assessed the association in a much larger cohort of coronary patients. Methods: Consecutive patients undergoing percutaneous coronary interventions (PCI) between 2004 and 2014 at Rabin Medical Center in central Israel were followed for cancer incidence through the Israeli National Cancer Registry until 2015. Information regarding cancer risk factors at the index PCI was extracted from the patients’ electronic medical records. Using land use regression models, residential annual averages of nitrogen oxides (NOx), a proxy measure for TRAP exposure, during follow-up were estimated individually. Cox proportional hazards models were constructed to study relationships with cancer. Results: Among 12,784 candidate patients, 11,395 had no history of ca...
Real-world outcomes among patients (pts) treated with gemcitabine (GEM)-based therapy post-FOLFIRINOX (FFOX) failure in advanced pancreatic cancer (APC).
Authors: Erica S Tsang, Jennifer L. Spratlin, Winson Y. Cheung, Christina Kim, Shiying Kong, Yuan Xu, Sharlene Gill
Journal: Journal of Clinical Oncology (2019)

303 Background: Limited evidence exists for the selection of chemotherapy in APC after first-line (1 st L) FFOX. Gemcitabine/nab-paclitaxel (GEMNAB) is publicly funded for second-line (2 nd L) use in the provinces of Alberta (AB) and Manitoba (MB), but is not covered in British Columbia (BC). We compared population-based outcomes by region to examine the utility of 2 nd L GEMNAB versus GEM alone. Methods: We identified pts treated with 1 st L FFOX between 2013-2015 across BC, AB, and MB. Baseline characteristics and treatment regimens were compared between AB/MB and BC. Survival outcomes were assessed by the Kaplan-Meier, and compared with log-rank test. Results: 370 pts treated with 1 st L FFOX were identified (145 AB/MB, 225 BC), with a median age of 61y, 42% female, and 68% with metastatic disease (similar in both groups). Receipt of 2 nd L therapy was 49% AB/MB vs 44% BC ( p = 0.35), and time from diagnosis to 2 nd L therapy measured 7.6 mos AB/MB versus 9.4 mos BC ( p = 0.1). The distribution of 2 nd L gemcitabine use was: 72% GEMNAB, 23% GEM in AB/MB versus 27% GEMNAB, 66% GEM in BC ( p &lt; 0.001). Median overall survival (OS) from diagnosis was similar: 12.4 mos in AB/MB versus 10.9 mos in BC ( p = 0.75). On Cox regression analysis, region was not significant. A secondary survival analysis by 2 nd L regimen demonstrated a median OS of 18.0 mos with GEMNAB versus 14.3 mos GEM ( p &lt; 0.01). Conclusions: In our population-based comparison of APC pts treated with 1 st L FFOX, survival outcomes were comparable regardless of publicly funded access to 2 nd L GEMNAB versus GEM. OS by regimen favored 2 nd L GEMNAB, but patient selection may be largely responsible for this difference. Randomized trials are needed to demonstrate the benefit of GEMNAB post-FFOX in APC.
Telomere length and health outcomes: An umbrella review of systematic reviews and meta-analyses of observational studies
Authors: Lee Smith, Claudio Luchini, Jacopo Demurtas, Pinar Soysal, Brendon Stubbs, Mark Hamer, Alessia Nottegar, Rita T. Lawlor, Guillermo Felipe Lopez-Sanchez, Joseph Firth, Ai Koyanagi, Justin Roberts, Peter Willeit, Thomas Waldhoer, Mike Loosemore, Adam David Abbs, James Johnstone, Lin Yang, Nicola Veronese
Journal: Ageing Research Reviews (2019)
Permissive HLA-DPB1 Mismatch and Survival after Unrelated Donor Allogeneic Stem Cell Transplantation for Hematological Malignancies: A Comparative Analysis of Different Immunogenetic Models on 422 Patients from GITMO and IBMDR
Authors: Francesca Lorentino, Nicoletta Sacchi, Elena Oldani, Valeria Miotti, Alessandra Picardi, Anna Maria Gallina, Paolo Bernasconi, Riccardo Saccardi, Lucia Farina, Fabio Benedetti, Francesca Patriarca, Michela Cerno, Benedetto Bruno, Alessandro Rambaldi, Fabio Ciceri, Katharina Fleischhauer, Luca Vago, Francesca Bonifazi
Journal: Blood (2018)
A novel traction device (EndoTrac) for use during endoscopic submucosal dissection
Authors: Shinwa Tanaka, Takashi Toyonaga, Hidetoshi Kaku, Hiroya Sakaguchi, Shinichi Baba, Toshitatsu Takao, Yuzo Kodama
Journal: Endoscopy (2019)

Recently, various traction methods have been employed to ensure that endoscopic submucosal dissection (ESD) is performed safely and efficiently [1] [2] [3]. These methods provide good exposure of the submucosal layer and facilitate ESD. We developed a novel traction device (the EndoTrac) to facilitate line tying and change in the direction of traction.
Genotypic Representation of Myelodysplastic/Myeloproliferative Neoplasms in Nrg, Nrg-3GS and Srg-W41 Mice with Transgenic Expression of Human Cytokines
Authors: Hein Than, Naoto Nakamichi, Anthony D. Pomicter, John O'Shea, Orlando Antelope, Thomas O'Hare, Connie J. Eaves, Michael W. Deininger
Journal: Blood (2018)
MAPK pathway proteins expression and correlation with clinicopathological indices and long-term outcome according to the etiology of underlying chronic liver disease in hepatocellular carcinoma.
Authors: Paulo Henrique Costa Diniz, Serena Dafne do Carmo Silva, Caio Cesar Lobo Sampaio, Paula Vieira Teixeira Vidigal, Marcelo Antonio Pascoal Xavier, Luciana Costa Faria, Teresa Cristina de Abreu Ferrari
Journal: Journal of Clinical Oncology (2019)

286 Background: Different etiologies of chronic liver disease (CLD) potentially lead to hepatocellular carcinoma (HCC) by multiple mechanisms that can be translated into clinicopathological and prognostic differences. We evaluated the expression of some proteins of MAPK pathway, an important signalling cascade in HCC, and correlated them to clinical and histopathological parameters, and long-term outcome, according to the etiology of the CLD. Methods: 80 patients (pts) who underwent orthotoptic liver transplantation (OLT) for HCC at Universidade Federal de Minas Gerais, a referral center in Brazil, were randomly selected: 41 viral (V) (HBV or HCV infection), 39 nonviral (NV) (alcohol abuse and cryptogenic) etiology. Clinical pre-OLT and histological data were retrospectively collected. Event (E) was defined as death and/or HCC-recurrence since OLT. In explanted liver, tumor and adjacent cirrhosis were subjected to immunohistochemistry, using antibodies against K-RAS, B-RAF and MEK, analysed by two pathologists. Results: V and NV groups were well balanced regarding clinicopathologic indices, but alcohol was the main etiology in men (95%) and HCV in women (38.7%). Median E-free survival (EFS) was 74.5 months (range, 8.5-105), without difference between groups. Microvascular invasion (MIV) (p &lt; 0.01) and age (p = 0.04) were independently associated with E. 11 pts (26.8%) of the V group had strong expression (SE) of K-RAS in tumor comparing to 0 (0%) in cirrhosis (p = 0.008) and to three (7.7%) in NV group HCC (p = 0.024). SE of B-RAF was seen in seven pts (17.0%) in V versus 11 (28.2%) in NV (p = 0.257), without difference from cirrhosis (p = 0.755). SE of MEK was not seen. Weak KRAS expression was more common in older pts (p = 0.04). The proteins expression was not related to E or EFS. Conclusions: SE of K-RAS, but not of BRAF and MEK, were more frequent in V group HCC than in cirrhosis and NV group tumors. It suggests that HBV and HCV can lead to HCC by different mechanisms comparing to NV etiology and KRAS could have a role on carcinogenesis. As there were no differences in clinical outcomes, prognostic, and therapeutic implications need to be stablished.
Alternative chemoradiotherapy to treat locally advanced (LA) anal carcinoma (AC) in patients (pts) with mutations in thymidylate synthase (<i>TYMS</i>) and dihydropyrimidine dehydrogenase (<i>DPYD</i>) genes: A case series.
Authors: Wasif M. Saif, Ruchi Hamal, Nauman Saleem Siddiqui, Antonia Maloney, Lilian Chen, Kathryn Huber
Journal: Journal of Clinical Oncology (2019)

605 Background: 5-FU and mitomycin-C (MMC) with radiotherapy (RT) remain an established treatment for pts with LA (T2-4, N0-1, M0 or T1-4, N2-3, M0) AC. Genetic mutations in 2 major metabolizing enzymes for 5-FU; DPYD and TYMS have been associated with clinical response and toxicity. However their place in treatment of AC remains undetermined. Methods: We retrospectively reviewed 21 pts with LA AC treated between 2012 - 2018. All pts were treated with 5-FU 1,000mg/m 2 /day continuous IV infusion 1–4 and 29–32, MMC 10mg/m 2 IV bolus Days 1 and 29 plus RT. Acute toxicity was recorded and discussed during weekly multidisciplinary meetings. The worst grade was scored from start of treatment until 30 days after the last fraction of radiotherapy according to the NCI-CTCAE, v4.03. Tumor response was evaluated by DRE and palpation of inguinal nodes during treatment, at the end of treatment, and radiological imaging 4–6 weeks after completion of treatment. Pts who developed ≥3 toxicities were tested for DPYD and TYMS genes (2 major polymorphisms has been associated with altered TYMS: polymorphic 28bp tandem repeat polymorphism in 5’-untranslated region (5’UTR) into TYMS sequence enhancer region (TSER) and TYMS 1494del, is a 6-base pair (bp) deletion polymorphism in 3’-UTR. Results: 6/21 ptsdeveloped severe toxicities (Caucasians; 5 females, 1 male; age range: 42 -68 yrs) consisting of grade ≥3 pancytopenia, neutropenia, thrombocytopenia, mucositis, nausea, rash and nephritis. The most common genetic mutations found in these pts included TYMS 2RG/3RC (2), 3RG/3RC (1), 2R/2R (2), TYMS 3 ' UTR del/Ins (2) and DPYD c.2864A&gt;T heterozygous (1). Treatment was changed in 2 pts to MMC 10 mg/m 2 Day 1 and 29 with cisplatin 25 mg/m 2 /week plus RT. These 2 pts reached pCR at 70 days and other 4 pts at 140 days. Conclusions: Molecular testing for DPYD and TYMS genes can allow us to identify pts who are most likely to respond or face severe toxicity to 5-FU. Combining radiation with MMC and cisplatin in pts with LA AC is feasible and EORTC is currently comparing this combination with MMC/5-FU in a large phase III trial.
Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin β1
Authors: Gaoxiang Zhao, Liyan Gong, Dan Su, Yujuan Jin, Chenchen Guo, Meiting Yue, Shun Yao, Zhen Qin, Yi Ye, Ying Tang, Qibiao Wu, Jian Zhang, Binghai Cui, Qiurong Ding, Hsinyi Huang, Liang Hu, Yuting Chen, Peiyuan Zhang, Guohong Hu, Luonan Chen, Kwok-Kin Wong, Daming Gao, Hongbin Ji
Journal: Journal of Clinical Investigation (2019)

Metastasis is the dominant cause of patient death in small-cell lung cancer (SCLC), and a better understanding of the molecular mechanisms underlying SCLC metastasis may potentially improve clinical treatment. Through genome-scale screening for key regulators of mouse Rb1-/- Trp53-/- SCLC metastasis using the pooled CRISPR/Cas9 library, we identified Cullin5 (CUL5) and suppressor of cytokine signaling 3 (SOCS3), two components of the Cullin-RING E3 ubiquitin ligase complex, as top candidates. Mechanistically, the deficiency of CUL5 or SOCS3 disrupted the functional formation of the E3 ligase complex and prevented the degradation of integrin β1, which stabilized integrin β1 and activated downstream focal adhesion kinase/SRC (FAK/SRC) signaling and eventually drove SCLC metastasis. Low expression levels of CUL5 and SOCS3 were significantly associated with high integrin β1 levels and poor prognosis in a large cohort of 128 clinical patients with SCLC. Moreover, the CUL5-deficient SCLCs were vulnerable to the treatment of the FDA-approved SRC inhibitor dasatinib. Collectively, this work identifies the essential role of CUL5- and SOCS3-mediated integrin β1 turnover in controlling SCLC metastasis, which might have therapeutic implications.