tbuckley/cabot-search huggingface dataset:
Hyperglycemia Acutely Increases Cytosolic Reactive Oxygen Species via <i>O</i> -linked GlcNAcylation and CaMKII Activation in Mouse Ventricular Myocytes
Authors: Shan Lu, Zhandi Liao, Xiyuan Lu, Dörthe M. Katschinski, Mark Mercola, Ju Chen, Joan Heller Brown, Jeffery D. Molkentin, Julie Bossuyt, Donald M. Bers
Journal: Circulation Research (2020)

Rationale: Diabetes mellitus is a complex, multisystem disease, affecting large populations worldwide. Chronic CaMKII (Ca 2+ /calmodulin-dependent kinase II) activation may occur in diabetes mellitus and be arrhythmogenic. Diabetic hyperglycemia was shown to activate CaMKII by (1) O -linked attachment of N-acetylglucosamine ( O -GlcNAc) at S280 leading to arrhythmia and (2) a reactive oxygen species (ROS)–mediated oxidation of CaMKII that can increase postinfarction mortality. Objective: To test whether high extracellular glucose (Hi-Glu) promotes ventricular myocyte ROS generation and the role played by CaMKII. Methods and Results: We tested how extracellular Hi-Glu influences ROS production in adult ventricular myocytes, using DCF (2′,7′-dichlorodihydrofluorescein diacetate) and genetically targeted Grx-roGFP2 redox sensors. Hi-Glu (30 mmol/L) significantly increased the rate of ROS generation—an effect prevented in myocytes pretreated with CaMKII inhibitor KN-93 or from either global or cardiac-specific CaMKIIδ KO (knockout) mice. CaMKII KO or inhibition also prevented Hi-Glu–induced sarcoplasmic reticulum Ca 2+ release events (Ca 2+ sparks). Thus, CaMKII activation is required for Hi-Glu–induced ROS generation and sarcoplasmic reticulum Ca 2+ leak in cardiomyocytes. To test the involvement of O -GlcNAc–CaMKII pathway, we inhibited GlcNAcylation removal by Thiamet G (ThmG), which mimicked the Hi-Glu–induced ROS production. Conversely, inhibition of GlcNAcylation (OSMI-1 [(αR)-α-[[(1,2-dihydro-2-oxo-6-quinolinyl)sulfonyl]amino]-N-(2-furanylmethyl)-2-methoxy-N-(2-thienylmethyl)-benzeneacetamide]) prevented ROS induction in response to either Hi-Glu or ThmG. Moreover, in a CRSPR-based knock-in mouse in which the functional GlcNAcylation site on CaMKIIδ was ablated (S280A), neither Hi-Glu nor ThmG induced myocyte ROS generation. So CaMKIIδ-S280 is required for the Hi-Glu–induced (and GlcNAc dependent) ROS production. To identify the ROS source(s), we used different inhibitors of NOX (NADPH oxidase) 2 (Gp91ds-tat peptide), NOX4 (GKT137831), mitochondrial ROS (MitoTempo), and NOS (NO synthase) pathway inhibitors (L-NAME, L-NIO, and L-NPA). Only NOX2 inhibition or KO prevented Hi-Glu/ThmG–induced ROS generation. Conclusions: Diabetic hyperglycemia induces acute cardiac myocyte ROS production by NOX2 that requires O -GlcNAcylation of CaMKIIδ at S280. This novel ROS induction may exacerbate pathological consequences of diabetic hyperglycemia.
COMPARISON OF OUTCOMES BETWEEN INTRAVASCULAR ULTRASOUND-GUIDED VS. ANGIOGRAPHY-ALONE APPROACH IN STENTING OF UNPROTECTED LEFT MAIN CORONARY ARTERY: A META-ANALYSIS
Authors: Yazan Alkawaleet, Muhammad Yasin, Majd Kanaa, Ali Farooq, Elise Anderson, Mark C. Bates
Journal: Journal of the American College of Cardiology (2020)
COSTS OF SURGICAL AND TRANSCATHETER AORTIC VALVE REPLACEMENT AND MEDICAL THERAPY
Authors: Andrew M. Goldsweig, Hyo Jung Tak, Li-Wu Chen, Herbert D. Aronow, Binita Shah, Dhaval Kolte, Nihar R. Desai, Molly Szerlip, Poonam Velagapudi, J. Abbott
Journal: Journal of the American College of Cardiology (2020)
Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction
Authors: Michelle C. Williams, Jacek Kwiecinski, Mhairi Doris, Priscilla McElhinney, Michelle S. D’Souza, Sebastien Cadet, Philip D. Adamson, Alastair J. Moss, Shirjel Alam, Amanda Hunter, Anoop S.V. Shah, Nicholas L. Mills, Tania Pawade, Chengjia Wang, Jonathan Weir McCall, Michael Bonnici-Mallia, Christopher Murrills, Giles Roditi, Edwin J.R. van Beek, Leslee J. Shaw, Edward D. Nicol, Daniel S. Berman, Piotr J. Slomka, David E. Newby, Marc R. Dweck, Damini Dey
Journal: Circulation (2020)

The future risk of myocardial infarction is commonly assessed using cardiovascular risk scores, coronary artery calcium score, or coronary artery stenosis severity. We assessed whether noncalcified low-attenuation plaque burden on coronary CT angiography (CCTA) might be a better predictor of the future risk of myocardial infarction.
The impact of renal function on therapeutic options for advanced non-small cell lung cancer (NSCLC).
Authors: Bercin Kutluk Cenik, Drew Warren Rasco, Han Sun, David E. Gerber
Journal: Journal of Clinical Oncology (2012)

e18076 Background: Certain commonly used chemotherapeutic agents for advanced NSCLC require minimum threshold renal function for administration. To determine how such requirements affect treatment options, we evaluated renal function patterns in a real-world cohort of patients. Methods: Retrospective analysis of consecutive patients treated for stage IV NSCLC from 2000 to 2007 at the UT Southwestern Medical Center. Clinical data obtained from tumor registries and medical records. Creatinine clearance (CrCl) was determined using the Cockcroft-Gault formula. Mixed model analysis was used to evaluate associations between patient clinical factors and longitudinal renal function. Results: 296 patients (3,930 Cr measurements) were included in the analysis. Mean age was 63 years, 43% were women, and 47% were white. Patients had a median of 5 (IQR 4-18) Cr measurements. The median overall CrCl was 92 (IQR 68-124) mL/min; the median pre-treatment CrCl was 96 (IQR 74-123) mL/min; and the median nadir CrCl was 78 (IQR 56-100) mL/min, occurring a median of 35 (IQR 1-235) d after diagnosis. Renal function was significantly associated with age (P&lt;0.001), race (P=0.009), and gender (P=0.001). 22% of patients had a recorded CrCl &lt; 60 mL/min (a commonly used threshold for cisplatin administration), with median onset of 89 d after diagnosis and median time to recover to ≥ 60 mL of 20 (IQR 3-85) d. The incidence and median duration of CrCl &lt; 60 mL/min varied by age (&lt;65 y: 8%, 17 d; ≥65 y: 30%, 43 d), gender (male: 9%, 15 d; female: 28%, 36 d), and race (white: 30%, 42 d; non-white: 13%, 21 d). 10% of patients had a recorded CrCl &lt; 45 mL/min (threshold for pemetrexed), with median onset 228 d after diagnosis and median time to recover to ≥ 45 mL/min of 33 (IQR 3-73) d. The incidence and median duration of CrCl &lt; 45 mL/min also varied by age (&lt;65 y: 6%, 6 d; ≥65 y: 8%, 72 d), gender (male: 4%, 5 d; females: 9%, 68 d), and race (white: 4%, 68 d; non-white 8%, 8 d). Conclusions: In a real-world cohort of patients treated for stage IV NSCLC, renal function falls below commonly used thresholds for cisplatin and pemetrexed in fewer than a quarter of patients. When such declines in renal function do occur, their duration may preclude administration of these drugs for prolonged periods.
NKP-1339: Maximum tolerated dose defined for first-in-human GRP78 targeted agent.
Authors: Dana Shelton Thompson, Glen J. Weiss, Suzanne Fields Jones, Howard A. Burris, Ramesh K. Ramanathan, Jeffrey R. Infante, Johanna C. Bendell, Angela Ogden, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2012)

3033 Background: NKP-1339 is a first-in-class small molecule anti-cancer compound that down-regulates GRP78, a key regulator of misfolded protein processing and tumor survival/anti-apoptosis. GRP78 up-regulation occurs in many tumors, and is associated with intrinsic and chemotherapy-induced resistance. Preclinically, single agent NKP-1339 demonstrates activity against multiple tumor types, including chemoresistant lines. This phase I trial evaluates the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics (PD) of NKP-1339. Methods: Patients (pts) with advanced solid tumors, adequate organ function, ECOG 0-1 are enrolled. NKP-1339 is infused on day 1, 8, and 15 of 28 day cycles. Single pt cohorts are enrolled until grade 2 toxicity, then adjusted to standard 3+3 design. Doses from 20-780 mg/m 2 are evaluated. PD samples for plasma GRP78 are collected. At MTD, an expanded cohort of 25 pts is enrolled. Results: 34 pts are enrolled for dose escalation: 30 evaluable for dose determination; 4 replaced due to tumor progression in cycle 1. Demographics: 19M/15F; median age 62 yrs (range 28 to 79). Tumor types: colorectal (CRC, 10), non-small cell lung (NSCLC, 8); neuroendocrine (NET, 5); head and neck (H&amp;N, 3); and other cancer (8). Dose limiting toxicity of grade (gr) 2-3 nausea, with gr 2 creatinine in 1 pt, occurred at 780 mg/m 2 ; MTD is 625 mg/m 2 . Gr 1 fever/chills is observed above 420 mg/m 2 , but is prevented by steroid premedication. The most common drug-related events are gr 1 nausea, gr 1-2 vomiting, and gr 1-2 fatigue. No lab abnormalities were noted except reversible creatinine elevation in 4 pts: 3 pt with gr 1; 1 pt with gr 2 secondary to DLT. Partial response was in 1 pt (NET); stable disease in 7 pts, including NET (2), NSCLC (2), CRC (1), sarcoma (1), and unknown primary (1). Therapy duration 14+-88+ weeks. Soluble GRP78 is detected in the plasma of patients at baseline. Conclusions: NKP-1339is well tolerated with manageable side effects. Single agent activity is noted in multiple tumors including NET. Results from the expanded cohort and pre/post-therapy PD will be presented. Phase II single agent NKP-1339 and phase I NKP-1339 combination trials are planned.
AORTIC COREVALVE PROSTHESIS, A SAFEGUARD TO PREVENT LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION IN TRANSCATHETER MITRAL VALVE REPLACEMENT
Authors: Abdur Rehman, Archana Kodali, Nathaniel Dittoe, Harvey Hahn, Raja Nazir, Brian Schwartz
Journal: Journal of the American College of Cardiology (2020)
Activation of Akt and mTOR in mouse keratinocytes by skin tumor promoters
Authors: Okkyung Rho, Jerry Lu, Guiyu Jiang, John DiGiovanni
Journal: Cancer Research (2007)

2621  Akt is a serine/threonine kinase involved in a variety of cellular responses including cell proliferation and survival. Tumor promoters including TPA, okadaic acid (OA), and chrysarobin (CHRY) activate epidermal Akt early after tumor promoter treatment. Activation of Akt during tumor promoter treatment leads to enhanced downstream signaling. In the present studies, we demonstrated that phosphorylation of Akt was elevated in cultured primary keratinocytes exposed to TPA. TPA-induced activation of Akt was mediated by the PI3K and PDK-1-dependent pathways, not by MAPK pathways. TPA-induced PKC activation in cultured mouse keratinocytes results in increased HB-EGF production, followed by phosphorylation of the EGFr. The pan PKC inhibitor, bisindolylmaleimide I abrogates HB-EGF production and EGFr phosphorylation. However, PKC inhibition by bisindolylmaleimide I before or after TPA treatment stabilizes Akt phosphorylation even in the presence of reduced EGFr activation. The potent inhibitors of EGFr/erbB2 (GW2974) and EGFr (PD153035) reduced TPA-stimulated Akt activation as well as EGFr tyrosine phosphorylation in a dose dependent manner. Furthermore, phosphorylation of mTOR, an Akt downstream component was induced by TPA in a biphasic way; early activation of mTOR appeared to be PKC-mediated and then later phosphorylated through activation of Akt. The current results support the hypothesis that elevated Akt activity and subsequent activation of downstream signaling pathways is a common event in mouse keratinocyts following treatment with diverse skin tumor promoters. In addition, signaling through the EGFr via PI3K and PDK-1 dependent pathways may be the primary event leading to Akt activation during tumor promotion in mouse skin. Finally, activation of mTOR may also be critical for mouse skin tumor promotion. Together with data showing that overexpression of Akt in epidermis of transgenic mice enhances susceptibility to skin tumor promotion, the current results further demonstrate the importance of Akt signaling in epithelial carcinogenesis.
Limited Clinical Application and Concerns of Bias in Long-term Risk of Epilepsy, Psychiatric Disorders, and Mortality Following Febrile Seizures—Reply
Authors: Julie Werenberg Dreier, Yuelian Sun, Jakob Christensen
Journal: JAMA Pediatrics (2020)

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OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTION AMONG PATIENTS WITH CONNECTIVE TISSUE DISEASE; PROPENSITY MATCH ANALYSIS
Authors: Samson Eneyufuo Alliu, Justin Ugwu, Omotooke Babalola, Chukwudi Obiagwu, Norbert Moskovits, Sergey Ayzenberg, Gerald Hollander, Robert Frankel, Jacob Shani
Journal: Journal of the American College of Cardiology (2020)
Phylogenetics Identifies Two Eumetazoan TRPM Clades and an Eighth TRP Family, TRP Soromelastatin (TRPS)
Authors: Nathaniel J Himmel, Thomas R Gray, Daniel N Cox
Journal: Molecular Biology and Evolution (2020)

Abstract Transient receptor potential melastatins (TRPMs) are most well known as cold and menthol sensors, but are in fact broadly critical for life, from ion homeostasis to reproduction. Yet, the evolutionary relationship between TRPM channels remains largely unresolved, particularly with respect to the placement of several highly divergent members. To characterize the evolution of TRPM and like channels, we performed a large-scale phylogenetic analysis of &amp;gt;1,300 TRPM-like sequences from 14 phyla (Annelida, Arthropoda, Brachiopoda, Chordata, Cnidaria, Echinodermata, Hemichordata, Mollusca, Nematoda, Nemertea, Phoronida, Priapulida, Tardigrada, and Xenacoelomorpha), including sequences from a variety of recently sequenced genomes that fill what would otherwise be substantial taxonomic gaps. These findings suggest: 1) the previously recognized TRPM family is in fact two distinct families, including canonical TRPM channels and an eighth major previously undescribed family of animal TRP channel, TRP soromelastatin; 2) two TRPM clades predate the last bilaterian–cnidarian ancestor; and 3) the vertebrate–centric trend of categorizing TRPM channels as 1–8 is inappropriate for most phyla, including other chordates.
FASTING THERAPY WITH L-CARNITINE INCREASES ENDOTHELIAL FUNCTION AND REDUCES TRIMETHYLAMINE N-OXIDE AND LEPTIN IN PERSONS WITH HIGH BMI
Authors: Jiapan Sun, Tingying Zhang, Jiang He, Jianning Zhang, Yumin Qiu, Yuanya Liu, Jian Qin, Jun Tao
Journal: Journal of the American College of Cardiology (2020)
USE OF A NOVEL, VENDOR AGNOSTIC PATIENT MONITORING AND RISK STRATIFICATION SYSTEM TO IMPROVE OFF-SITE CENTRAL MONITORING FOR NON-ICU HOSPITALIZED PATIENTS: THE ENHANCED CENTRAL MONITORING UNIT (E-CMU)
Authors: Daniel Cantillon, Alicia Burkle, Molly Loy, Desiree Kirkwood, Kyrian Willis, Bud Collmar, John Tote, Zoe Zelazny, Laura Idzior, Marc Petre, Shannon Pengel
Journal: Journal of the American College of Cardiology (2020)
Exuberant Plasmocytosis in Bronchoalveolar Lavage Specimen of the First Patient Requiring Extracorporeal Membrane Oxygenation for SARS-CoV-2 in Europe
Authors: Marco Giani, Davide Seminati, Alberto Lucchini, Giuseppe Foti, Fabio Pagni
Journal: Journal of Thoracic Oncology (2020)
UTILITY OF LEFT ATRIAL STRAIN MECHANICS FOR PREDICTING EXERCISE INTOLERANCE IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY
Authors: Yoshihito Saijo, Erik Van Iterson, Milind Y. Desai, Harry Lever, Maran Thamilarasan, Zoran Popovic, Richard A. Grimm, Brian P. Griffin, Bo Xu
Journal: Journal of the American College of Cardiology (2020)
Reversal of the Warburg effect in breast cancer cells by a novel agent.
Authors: Ritu Arora, David Schmitt, Steven McClellan, Ming Tan, Eddie Reed, Laurie Owen, Windy Marie Dean-Colomb
Journal: Journal of Clinical Oncology (2013)

e13566 Background: It is well known that most cancer cells display a Warburg effect, a state of active glycolysis with lactate production under aerobic conditions. NF-κB has been shown to play a role in modulating cancer metabolism and control the balance between glycolysis and mitochondrial respiration. We have previously shown that panepoxydone (PP), a compound isolated from an edible mushroom, interferes with NF-κB mediated signal transduction. Additionally, we have shown that PP decreases cell viability and proliferation in breast cancer cells. To further characterize the antitumor effect of PP, here we have evaluated it ability to modulate cancer metabolism. Methods: The metabolic action of PP was evaluated in estrogen receptor positive (MCF-7) and triple negative (MDAMB-231) breast cancer cell lines. Cytotoxicity was determined by the cell titer glow assay and expressed as IC 50 . Metabolic activity, expressed as basal oxygen consumption rate (OCR, an indicator of oxidative phosphorylation) and extracellular acidification rate (ECAR, an indicator of lactate acid production), was measured in real-time using the XF24 Extracellular Flux Analyzer. Mitochondrial membrane potential (MMP) alteration was determined through flow cytometry and LDH-A expression was analyzed via western blot. Results: Significant antitumor activity with PP was seen in both MCF-7 (IC 50 5 µM) and MDAMB-231 cells (IC 50 15 µM). This correlated to a significant dose-dependent reduction in OCAR in MCF-7 (2-fold, p&lt;0.05) and MDAMB-231 cells (3.5-fold, p&lt;0.01). However, while a decrease in ECAR (1.5-fold, p&lt;0.05), along with decreased LDHA expression was noted in the 231 cells (3.5-fold, p&lt;0.01), this was not seen with the MCF-7 cells. A similar trend was noted with increased damaged mitochondria noted in 231-cells, but again no significant difference in MCF-7 cells. Conclusions: Taken together, these results indicate that PP has the potential to modulate metabolism in breast cancer cells, especially triple negative cells, as noted by its ability to inhibit glycolysis. The inhibition of glycolysis has become an important strategy in treating cancer and development of novel glycolytic inhibitors, such as PP, warrants its further investigation in breast cancer treatment.
Patient segmentation assay for MAPK pathway mutations.
Authors: Matthew John Marton, Ken Chang, Stefan Galuska, Ahmed Samatar, Ling Zhang, Russell Weiner
Journal: Journal of Clinical Oncology (2013)

11059 Background: Mutational status of solid tumors is increasingly important for identifying the best treatment options. Tumors harboring activating mutations in RAS and RAF result in constitutive activation of the RAS/MAPK signal transduction pathway and do not respond well to MAPK pathway inhibitors. Scientific attention is mostly focused on the major mutational hotspots in these genes (e.g., KRAS codons 12, 13 and 61, BRAF codon 600). However, there is increasing evidence that other mutations can be tumorigenic. Thus, there is a need for highly sensitive and specific assays to detect these mutations. To address this need, we developed and analytically validated an assay that detects 33 mutations that activate the MAPK pathway. Methods: We constructed a set of multiplexed single nucleotide primer extension (SNPE) assays that detect 33 activating mutations in KRAS, NRAS, or BRAF. The assays were analytically validated using a set of 60 formalin fixed paraffin embedded (FFPE) tissue samples from various tumor types, cell lines, and oligos with specific mutations. Performance was compared to dideoxy sequencing. Discordant calls were resolved with next generation sequencing (NGS). The limit of detection was determined by serial dilution of mutant DNA into wildtype DNA. Results: The developed multiplexed assay requires only 15 ng genomic DNA, relies on established technology, is cost effective, is amenable to high throughput, and can yield a patient eligibility decision in a CLIA lab in 4 days, making it a practical alternative to a NGS-based assay. Since low allele frequency mutations may be critical to patient survival, we devised a replicate strategy to increase the specificity and sensitivity of the assay. We showed that analysis of technical triplicates relative to no replicates increased the sensitivity from 97 to 100% and the specificity from 91 to 100%. Limit of detection varied from 2 -12%, depending on the mutation. Conclusions: We developed a selective and sensitive SNPE assay capable of detecting 33 hotspots in the MAPK pathway. Our approach reduced false positive and false negative calls of low allele frequency samples. The assay has clinical applicability for the selection of patients for early phase clinical studies.
THE ASSOCIATION OF SEVERITY OF SLEEP APNEA WITH ECHOCARDIOGRAPHIC MEASURES OF DIASTOLIC DYSFUNCTION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Farzane Saeidifard, Mohammed Al-Sadawi, Adekunle Kiladejo, Patricia Erwin, Louis F. Salciccioli, Adam Budzikowski
Journal: Journal of the American College of Cardiology (2020)
NON-ISCHEMIC CARDIOMYOPATHY AND ELECTRICAL DYSFUNCTION IMPORTANT CAUSE OF SUDDEN CARDIAC DEATH IN REPAIRED COARCTATION OF THE AORTA
Authors: Marc Lee, Lauren Terry Lastinger, Omer Cavus, Lauren J. Hassen, Saurabh Rajpal, May Ling Mah, Elisa Bradley
Journal: Journal of the American College of Cardiology (2020)
OM-RCA-01, an FGFR1 specific humanized antibody for the treatment of renal cell carcinoma (RCC).
Authors: Ilya Tsimafeyeu, Elina Zaveleva, Walter Low
Journal: Journal of Clinical Oncology (2012)

3070 Background: Fibroblast growth factor (FGF) receptor 1 (FGFR1) is a potential therapeutic target for the treatment of metastatic RCC. We investigated the preclinical activity of OM-RCA-01, a novel therapeutic humanized anti-FGFR1 antibody with high affinity (Kd of 1.59 nM), in RCC. Methods: To assess the effect of anti-FGFR1 antibody on FGF-mediated signaling, the human renal carcinoma Caki-1 FGFR1-expressing cells were dosed with OM-RCA-01 at 100, 10, and 1 mcg/ml. Control wells were left untreated. Three hours after dosing, bFGF was added at a concentration of 50 ng/ml. Additional control wells were treated with OM-RCA-01 without FGF-stimulation. Cell growth inhibition was determined using Promega’s Cell Titer-Glo assay. CR female NCr nu/nu mice were set up with 1 mm3 Caki-1 tumor fragments sc in flank. Tumor sizes were measured in a blind fashion twice a week with a vernier caliper. Mice with established tumors were randomly divided into vehicle, non-specific IgG or OM-RCA-01 groups per 10 animals in group. Endpoint was significant differences in tumor growth delay. Results: In vitro study showed that bFGF increased proliferation of the human FGFR1-expressing renal carcinoma cells (p=0.011). OM-RCA-01 antibody significantly inhibits FGF-triggered cell proliferation in comparison with control. In vivo, the tumors in untreated mice or mice treated with non-specific IgG continued their aggressive growth to reach the size of 2000 cm3, at which point the mice were killed. In contrast, treatment with OM-RCA-01 not only significant arrested further growth of the tumors (p=0.006) but also demonstrated differences in tumor volume compared with vehicle already on Day 13. A similar anti-tumor activity of OM-RCA-01 was observed when the antibody was given in low (1 mg/kg) or high (10 mg/kg) doses (p=0.917). Administration of 10 mg/kg antibody for up to 35 days resulted in minimal body weight loss and no observations of gross toxicity were made. Conclusions: Targeting FGFR1 blocks FGF/FGFR1 pathway in RCC. Monoclonal antibody OM-RCA-01 has significant early anti-tumor efficacy in Caki-1 xenograft model. Isolated blocking of FGFR1 by low-dose antibody could be safe and effective.