tbuckley/cabot-search huggingface dataset:
GENE-38. IDH1MUT INDUCES N6-METHYLADENOSINE (m6A) RNA HYPERMETHYLATION VIA D-2-HG IN GLIOMA
Authors: Sean Pianka, Tie Li, Matthew Ji, Albert Lai
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION IDH1 MUT confers slower tumor growth rates and improved prognoses for glioma patients, but the precise mechanisms underlying these clinically relevant benefits remain largely unknown. IDH1MUT gliomas produce high levels of D-2-HG, a putative oncometabolite that inhibits a range of α-ketoglutarate-dependent dioxygenases. D-2-HG-mediated inhibition of TET-family proteins involved in DNA demethylation is known to be a key driver leading to the oncogenic DNA hypermethylation phenotype (known as G-CIMP) seen in IDH1MUT gliomas. Recent evidence indicates that D-2-HG also functionally inhibits FTO and AlkBH5, two dioxygenases responsible for demethylation of RNA N6-methyladenosine (m6A) sites. This study sought to determine if D-2-HG mediates an increase in m6A content in IDH1MUT gliomas. METHODS Total RNA was isolated from patient tumor samples, patient-derived gliomaspheres, human embryonic kidney cell (HEK293T), normal human astrocyte (NHA), and U87 glioma model systems expressing either IDH1MUT or IDH1WT. Relative abundance of m6A modifications was determined both quantitatively and qualitatively using colorimetric ELISA-like assays and m6A-antibody dot blots, respectively. RESULTS Quantification of m6A abundance in IDH1MUT patient tumor samples and patient-derived gliomaspheres revealed an increase in m6A content compared to IDH1WT samples. Forced expression of IDH1MUT in HEK293T, NHA, and U87 cells increased intracellular D-2-HG content and global m6A abundance in purified RNA. Additionally, D-2-HG treatment of IDH1WT cell lines increased m6A abundance, including in IDH1WT gliomaspheres. Conversely, inhibition of D-2-HG generation in IDH1MUT cell lines decreased m6A abundance. Data will also be presented suggesting that increased m6A abundance is associated with decreased cellular proliferation. CONCLUSIONS These results indicate that increased intracellular D-2-HG arising in the context of IDH1MUT mediates increases in RNA m6A methylation in glioma. The association with m6A hypermethylation and reduced growth suggests that RNA methylation provides a novel therapeutic target.
Th1 Cytokine Polymorphism Gene: TNF-Alpha -857C/T Affects the Pathogenesis and Progression of Acute Myeloid Leukemia
Authors: Kana Soma, Gotoh Nanami, Tetsuhiro Kasamatsu, Yuki Murakami, Rei Ishihara, Maaya Awata, Eiko Yamane, Masanobu Sunaga, Yuta Asao, Nao Hashimoto, Yoshiyuki Ogawa, Hiroaki Shimizu, Takuma Ishizaki, Akihiko Yokohama, Norifumi Tsukamoto, Hiroshi Handa, Toru Sakura, Satoru Takada, Takayuki Saitoh
Journal: Blood (2019)
ALK Mutation Status Before and After Alectinib Treatment in Locally Advanced or Metastatic ALK-Positive NSCLC: Pooled Analysis of Two Prospective Trials
Authors: Johannes Noé, Alex Lovejoy, Sai-Hong Ignatius Ou, Stephanie J. Yaung, Walter Bordogna, Daniel M. Klass, Craig A. Cummings, Alice T. Shaw
Journal: Journal of Thoracic Oncology (2019)

The effectiveness of ALK receptor tyrosine kinase (ALK) inhibitors can be limited by the development of ALK resistance mutations. This exploratory analysis assessed the efficacy of alectinib in patients with NSCLC and ALK point mutations using pooled data from two single-arm phase II studies.Studies NP28673 and NP28761 enrolled adults with locally advanced/metastatic ALK-positive NSCLC who had progressed on crizotinib. ALK mutation analysis was conducted on cell-free DNA from 187 patients post-crizotinib/pre-alectinib, and from 49 of these patients who subsequently progressed on alectinib.Baseline characteristics were generally balanced across patient subgroups. At baseline, 34 distinct ALK mutations were identified in 48 of 187 patients (25.7%). Median investigator-assessed progression-free survival was longer in patients without ALK single-nucleotide variants (n = 138) versus those with (n = 48): 10.2 months (95% confidence interval [CI]: 8.1-14.3) versus 5.6 months (95% CI: 4.5-10.9), respectively. Sixteen of 32 patients (50%) with ALK resistance mutations to crizotinib achieved an investigator-assessed response to alectinib (all partial responses); most of these ALK mutations were known to be sensitive to alectinib. Analysis of plasma samples obtained post-progression on alectinib revealed that 26 of 49 (53%) samples harbored 16 distinct ALK mutations, with known alectinib-resistance mutations, I1171 T/N/S, G1202R, and V1180L, observed in 15 of 49 (31%) tumors.Alectinib appears clinically active against ALK rearrangements and mutations, as well as several ALK variants that can cause resistance to crizotinib. The use of cell-free DNA in plasma samples may be an alternative noninvasive method for monitoring resistance mutations during therapy.
A phase II trial of cetuximab in high-risk premalignant lesions of the upper aerodigestive tract.
Authors: Joseph A Califano, Robert L. Ferris, Joel Brian Epstein, Marion Boyd Gillespie, Lawrence Eric Feldman, Michael K. Gibson, Kristen B. Pytynia, Zubair Khan
Journal: Journal of Clinical Oncology (2012)

5528 Background: High risk head and neck premalignancy includes patients with prior HNSCC and loss of heterozygosity (LOH). These patients demonstrate 30-60% rates of progression to malignancy despite conventional surgical excision. We performed a phase II trial using short term therapy with cetuximab, a humanized monoclonal antibody directed against EGFR, in the treatment of high risk premalignant lesions of the UADT. Methods: Inclusion criteria required; 1) presence of 3p, 9p21, or 17p LOH, and/or 2) surgically unresectable high grade premalignant lesions, and/or 3) high grade premalignancy after curative therapy for HNSCC. Patients received cetuximab 400 mg/m 2 on week one followed by 250 mg/m 2 on week 2-8 or observation, with the option for crossover to cetuximab for patients originally randomized to the observation arm. Histologic grade (1=benign, 2=mild dysplasia, 3=moderate dysplasia, 4=severe dysplasia/carcinoma in situ, 5=invasive cancer) and change in grade of dysplasia was evaluated. Results: 19 patients were enrolled. Two patients discontinued therapy due to toxicity. We noted a decrease in grade of dysplasia in the cetuximab treated group (-1.0) vs. the observation group (-0.2), (Wilcoxon test p value = 0.18). In the observation group, 0/5 patients (0%) underwent complete resolution of dysplasia; while 4/12 (33.3%) treated patients had no remaining dysplasia after therapy (p = 0.26), three of these patients had complete resolution of dysplastic changes after cetuximab therapy alone. Of these three patients, two have had no recurrence of leukoplakia or dysplasia at 1.5 and 2 years. One patient treated with oral cavity dysplasia has had no recurrence of dysplasia or lesions within the oral cavity, but developed a hypopharyngeal cancer at 1.5 years after trial completion. Of 5 patients randomized to observation, three underwent crossover to cetuximab therapy, and two of these three patients had complete resolution of dysplasia. Conclusions: EGFR blockade with cetuximab alone can result in significant, durable, and complete clinical and histological resolution of moderate to severe dysplasia in at least a subset of high risk patients.
Moffitt Cancer Center 2-Year Single-Institution Experience with Next-Generation Sequencing Minimal Residual Disease Detection: Clinical Utility, Application, and Correlation with Outcomes in Plasma Cell and Lymphoid Malignancies
Authors: Mohammad O Hussaini, Jaya Srivastava, Lik Wee Lee, Taiga Nishihori, Bijal Shah, Melissa Alsina, Rachid Baz, Javier Pinilla Ibarz, Kenneth H. Shain
Journal: Blood (2019)
Sorafenib treatment of clear-cell renal cell carcinoma (CCRCC) and colorectal carcinoma (CRC) cells: Differential effects on gene expression and cell death pathways
Authors: S. A. Vaziri, A. Al-Hazzouri, D. R. Grabowski, M. K. Ganapathi, R. M. Bukowski, R. Ganapathi
Journal: Journal of Clinical Oncology (2007)

15612 Background: The von Hippel Lindau gene (VHL) is often mutated in CCRCC and leads to loss of VHL protein (pVHL) expression. Sorafenib is a TKI with clinical activity in metastatic CCRCC. Studies to define mechanisms governing anti-tumor activity of this agent in CCRCC or CRC cell lines that express wild-type pVHL were conducted. Methods: We evaluated CAKI-1 (CCRCC) and HCT- 116/p53 +/+ (CRC) cell lines as model systems expressing wild-type pVHL. Cells were treated at 37°C in an atmosphere of normoxia (21% O 2 ) or hypoxia (1% O 2 ), 5% CO 2 and the remainder N 2 in the absence (control) or presence of sorafenib (2.5–20 μM) for 24–96 hours. Expression of target angiogenesis, apoptotic and anti-apoptotic genes was determined by real-time RT- PCR. Fluorescence microscopy following staining with Hoechst 33342 plus propidium iodide was used to analyze cell death by apoptosis and/or necrosis. Caspase-3 activity was measured using the target substrate DEVD-AFC. Results: In CAKI-1 and HCT-116 cells, exposure to 1% O 2 relative to 21% O 2 , led to increased expression (2 to 6-fold) of angiogenesis (VEGF) and anti-apoptosis (TNFAIP3 &amp; MCF2) genes. However, in an atmosphere of 1% O 2 relative to 21% O 2, a decreased (&gt;2-fold) and increased (&gt;3-fold) expression of the apoptotic (TNFRSF25) gene was observed in CAKI-1 cells and HCT-116 cells. Sorafenib treatment (7.5 μM) of CAKI-1 cells in 1% O 2 led to a &gt;3–4-fold decrease in expression of the VEGF and TNFAIP3 and a 3-fold increase TNFRSF25 genes. Following treatment with 10 μM sorafenib for 48h, cell death was &gt;80% by necrosis in CAKI-1 cells and &gt;95% by apoptosis in HCT-116 cells. Apoptotic cell death in the HCT-116 was also confirmed by increased caspase-3 activity in cell extracts following sorafenib treatment. Apoptotic cell death or necrotic cell death induced by sorafenib was unaffected by normoxia or hypoxia. Conclusions: In contrast to CCRCC cells, hypoxia led to upregulation of the apoptotic gene TNFRSF25 in the CRC cells. Anti- proliferative effects of sorafenib were primarily by necrosis in CCRCC cells and by apoptosis in CRC cells. No significant financial relationships to disclose.
Developing Single Cell Live Imaging Strategies to Determine MEP Fate and Predict Potential
Authors: Vanessa M Scanlon, Maria Kochugaeva, Juliana Xavier-Ferrucio, Yi-Chien Lu, Nayoung Kwon, Anisha Laumas, Matthew Cenci, Kalyani Lawrence, Katie Barden, Colin Holbrook, Andrew Tri Van Ho, Helen M. Blau, Andre Levchenko, Diane S. Krause
Journal: Blood (2019)
Endogenous Depression in General Practice
Authors: A. K. Gordon
Journal: BMJ (1947)

remember rightly, gastroscopy has been reported as confirming this supposition.In view of the utter uselessness of all treatment up till now any therapeutic measure would be welcome.The peculiar sensi- tivity of the skin would suggest a trial of "' benadryl."This might be a valuable measure in those cases with feye lesions where any decrease of inflammation would mitigate the cumu- lative and recurrent damage to these organs.-Iam, etc., Oxford.
The Clinical Association and Prognostic Impact of IL1RAP Expression in Patients with De Novo Acute Myeloid Leukemia
Authors: Chao-Hung Wei, Cheng-Hong Tsai, Jih-Luh Tang, Yuan-Yeh Kuo, Feng-Ming Tien, Chien-Chin Lin, Mei-Hsuan Tseng, Yen-Ling Peng, Ming-Chih Liu, Chia-Wen Liu, Ming Yao, Liang-In Lin, Wen-Chien Chou, Chien-Yu Chen, Hsin-An Hou, Hwei-Fang Tien
Journal: Blood (2019)
CBMT-36. INITIAL EXPERIENCE WITH HYPERPOLARIZED [2-13C]PYRUVATE MR IMAGING IN PATIENTS WITH IDH-MUTANT GLIOMA
Authors: Adam Autry, Brian Chung, Hsin-Yu Chen, Jeremy Gordon, Marisa Lafontaine, Susan Chang, Javier Villanueva-Meyer, Peder Larson, Daniel Vigneron, Yan Li
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Hyperpolarized (HP) carbon-13 MR imaging allows for real-time non-invasive measurement of metabolism. Using HP [2-13C]pyruvate as a molecular probe enables the measurement of both aerobic glycolysis ([2-13C]lactate) and oxidative metabolism (such as [5-13C]glutamate and [5-13C]glutamine). This study presents the initial patient experience of acquiring HP [2-13C]pyruvate MR spectroscopic data. METHODS Two patients who presented with IDH-mutant gliomas (43 year-old male, grade II astrocytoma, RT/TMZ; 33 year-old female, grade III oligodendroglioma, no RT/TMZ) considered radiologically stable post resection were imaged using a 2D chemical shift imaging (CSI) sequence (15.6–18.8cm3 spatial resolution, 20s acquisition), following injection of 0.43mL/kg of 250mM HP [2-13C]pyruvate. HP [2-13C]pyruvate, [5-13C]glutamate, [5-13C]glutamine, and [2-13C]lactate resonances were quantified within a lesion voxel and contralateral normal-appearing voxel. The proton images were aligned to HP data enabled quantification of apparent diffusion coefficients (ADC), perfusion peak height (PH), and MR spectroscopy choline-to-N-acetyl-aspartate indices (CNI). ADC (nADC) and PH (nPH) values were normalized by the median value in normal-appearing white matter. RESULTS Proton exams revealed no Gd-enhancement lesions. For the T2-hyperintense lesion (T2L), volumeT2L=18.4/4.2cc (Patient#1/Patient#2); median ADCT2L =1.86/1.64; max CNIT2L=3.2/6.5; 90th percentile nPHT2L =1.09/2.11. HP data displayed maximum signal-to-noise ratios (SNR) for [2-13C]pyruvate, [5-13C]glutamate, [5-13C]glutamine, and [2-13C]lactate of 1360, 44, 27, and 400, respectively. The HP CSI data contained 15.9/13.7 %T2L; 15.1/4.1 %NAWM; 15.7/22.0 %GM (Patient#1/Patient#2) in selected lesion voxels, while contralateral voxels had %NAWM:%GM of Lesions demonstrated a reduced HP glutamate/pyruvate ratio [#1: 0.0089/0.0102 (lesion/normal voxel); #2: 0.0170/0.0269] and an elevated HP glutamate-to-glutamine ratio in both patients [#1: 0.81/0.66; #2: 0.84/0.66]. DISCUSSION This first patient experience with HP [2-13C]pyruvate showed adequate SNR for quantifying HP [2-13C]pyruvate, [5-13C]glutamate, [5-13C]glutamine, and [2-13C]lactate resonances. Future studies will optimize imaging protocols and expand the patient cohort to evaluate aberrant metabolism related to IDH-mutant tumor.
Ampicillin for Typhoid Carriers
Authors: P. Troy
Journal: BMJ (1964)

MEDIBCRTISOHNALthat the changes in urinary-oestrogens excre- tion after oophorectomy or adrenalectomy cannot be related to clinical benefit.6A possible conclusion is, therefore, that the benefit that follows oophorectomy or adrenalectomy in some patients with breast cancer is due not so much to removal of oestrogen as to the consequent liberation of gonadotrophins that follows such ablation therapy.In other words breast cancer in the younger woman may not be so much "oestrogen dependent" as "pituitary dependent."'There is, of course, other evidence that points to the same conclusion, but I hesitate to repeat this evidence in a letter.I would add only that my suggestion should lead logically to a trial of human pituitary gonadotrophin administration in patients with breast cancer failing to respond to castration.A similar trial was suggested in the treatment of cases showing a low gonadotrophin excretion after adrenalectomy.8The absence of reports of such trials in the literature to date reflects the difficulty of procuring adequate supplies of human pituitary gonadotrophin for thera- peutic trial, but I hope that this will be remedied in the near future.-Iam, etc.,
Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration
Authors: Jasmina Zivanovic, Emilia Kouroussis, Joshua B. Kohl, Bikash Adhikari, Biljana Bursac, Sonia Schott-Roux, Dunja Petrovic, Jan Lj. Miljkovic, Daniel Thomas-Lopez, Youngeun Jung, Marko Miler, Sarah Mitchell, Verica Milosevic, Jose Eduardo Gomes, Moran Benhar, Bruno Gonzalez-Zorn, Ivana Ivanovic-Burmazovic, Roberta Torregrossa, James R. Mitchell, Matthew Whiteman, Guenter Schwarz, Solomon H. Snyder, Bindu D. Paul, Kate S. Carroll, Milos R. Filipovic
Journal: Cell Metabolism (2019)
One-Year Efficacy and Safety from a Phase 3 Trial of Ravulizumab in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria Receiving Prior Eculizumab Treatment
Authors: Austin Kulasekararaj, Anita Hill, Saskia Langemeijer, Richard A. Wells, F. Ataulfo Gonzalez-Fernandez, Anna Gaya, Emilio Ojeda Gutierrez, Caroline I. Piatek, Lindsay D Mitchell, Kensuke Usuki, Alberto Bosi, Robert A. Brodsky, Masayo Ogawa, Ji Yu, Stephan Ortiz, Alexander Röth, Jong-Wook Lee, Régis Peffault de Latour
Journal: Blood (2019)
PATH-30. TARGETED THERAPIES FOR PEDIATRIC LOW-GRADE GLIOMAS: A CASE SERIES
Authors: Nidhi Shah, Andrew Walter, Gurcharanjeet Kaur
Journal: Neuro-Oncology (2019)

Abstract Pediatric central nervous system (CNS) malignancies are the most common malignancies of childhood. The standard treatment plan for most CNS malignancies involves surgery, chemotherapy, radiation, and/or a combination of above therapies. Unresectable symptomatic low grade gliomas, such as pilocytic astrocytomas and gangliogliomas, are slow growing tumors that are typically responsive to a single course of intravenous chemotherapy, but in select patients these WHO grade I or II tumors can recur and be refractory to multiple courses. Molecular diagnostics can offer valuable insight into the tumor microenvironment, where targeted therapies can be offered for specific actionable mutations. Here we report a case series of 3 pediatric patients, with unique CNS malignancies, currently on targeted therapies for tumor-specific somatic mutations. Patient A is a 5 year old male with unresectable Neurofibromatosis-1 related plexiform neurofibroma of the nasopharyngeal space as well as optic pathway glioma, with a mutation of the MAPK/ERK pathway. Patient B is a 6 year old male with recurrent, refractory pilocytic astrocytoma of the optic pathway and hypothalamus, with progression through several courses of intravenous chemotherapy, noted to have somatic NACC2-NTRK mutation. Patient C is a 17 year old female with unresectable, pontomedullary ganglioglioma, noted to have BRAF-V600E mutation. Patient A is treated with Selumetinib, for about 6 months, with near resolution of nasopharyngeal mass. Patient B is treated with Larotrectinib, for about 3 months, with stability of clinical symptoms. Patient C is treated with Vemurafenib, for about 10 months, with stability of lesion size and patient-reported clinical improvement. No adverse events were noted for any of these patients and all medications were administered orally. Significant improvement in quality of life was reported, as they did not have central lines or bone marrow suppression. Targeted inhibitors provide a reasonable treatment option for relapsed, refractory CNS malignancies with actionable mutations.
SCIDOT-14. ENHANCING BRAIN RETENTION OF A KIF11 INHIBITOR SIGNIFICANTLY IMPROVES ITS EFFICACY IN A MOUSE MODEL OF GLIOBLASTOMA
Authors: Gautham Gampa, Rajappa Kenchappa, Afroz Mohammad, Karen Parrish, Minjee Kim, Jann Sarkaria, Steven Rosenfeld, William Elmquist
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma, the most common and lethal of brain tumors, is both highly invasive and proliferative. This allows tumor cells to infiltrate into regions of the brain with an intact blood brain barrier and be protected from effective therapeutics. Thus, an ideal glioblastoma therapy needs to target cellular components that drive both invasion and proliferation, with inhibitors that penetrate the blood brain barrier. The mitotic kinesin KIF11 meets these criteria and it can be targeted with ispinesib, a highly specific small molecule inhibitor. However, to be effective, ispinesib needs to cross the blood brain barrier and be retained within brain long enough to target glioblastoma cells when they are vulnerable, during mitosis.. We have examined the factors that affect distribution of ispinesib to both brain and glioblastoma. We find that delivery of ispinesib is limited by P-gp and Bcrp-mediated drug efflux at the blood brain barrier. Consequently, ispinesib levels are significantly lower in the infiltrative tumor margin relative to the tumor core, where the blood brain barrier is defective. We also show that elacridar—an inhibitor of the P-gp and Brcp efflux transporters—enhances delivery of ispinesib, and that co-administration of ispinesib with elacridar markedly slows tumor proliferation and prolongs survival in a mouse model of this disease. These results demonstrate the feasibility and efficacy of combining a potentially ideal therapeutic with a compound that enhances brain retention of this therapeutic, and provides support for utilizing this approach in clinical investigations of KIF11 inhibitors in GBM.
Identification of Clonal Immunoglobulin λ Light-Chain Gene Rearrangements in AL Amyloidosis Using Next Generation Sequencing
Authors: Kenji Kimura, Shokichi Tsukamoto, Kanji Miyazaki, Chika Kawajiri-Manako, Bahityar Rahmutulla, Masaki Fukuyo, Nagisa Oshima-Hasegawa, Shio Mitsukawa, Yusuke Takeda, Naoya Mimura, Masahiro Takeuchi, Chikako Ohwada, Tohru Iseki, Keisuke Matsusaka, Koutaro Yokote, Atsushi Kaneda, Tadao Ishida, Kenshi Suzuki, Chiaki Nakaseko, Emiko Sakaida
Journal: Blood (2019)
The Use of Next Generation Gene Sequencing to Measure Minimal Residual Disease in Patients with AL Amyloidosis and Low Plasma Cell Burden: A Feasibility Study
Authors: Shayna Sarosiek, Vaishali Sanchorawala, Mariateresa Fulcinti, Allison P. Jacob, Nikhil C. Munshi, Cindy Varga
Journal: Blood (2019)
Investigation of the mechanisms of resistance to osimertinib in patients with T790M-associated NSCLC
Authors: M. Stepanova, F. Moiseenko, A. Zhabina, V. Klimenko, N. Rysev, A. Myslik, E. Artemieva, K. Shelekhova, A. Bogdanov, N. Volkov, V. Moiseenko
Journal: Annals of Oncology (2019)
Noncanonical immunomodulatory activity of complement regulator C4BP(β-) limits the development of lupus nephritis
Authors: Ana Luque, Inmaculada Serrano, Elia Ripoll, Catarina Malta, Montserrat Gomà, Anna M. Blom, Josep M. Grinyó, Santiago Rodríguez de Córdoba, Joan Torras, Josep M. Aran
Journal: Kidney International (2019)
Cardiovascular Effects of Switching From Tobacco Cigarettes to Electronic Cigarettes
Authors: Jacob George, Muhammad Hussain, Thenmalar Vadiveloo, Sheila Ireland, Pippa Hopkinson, Allan D. Struthers, Peter T. Donnan, Faisel Khan, Chim C. Lang
Journal: Journal of the American College of Cardiology (2019)

E-cigarette (EC) use is increasing exponentially worldwide. The early cardiovascular effects of switching from tobacco cigarettes (TC) to EC in chronic smokers is unknown. Meta-analysis of flow-mediated dilation (FMD) studies indicate 13% lower pooled, adjusted relative risks of cardiovascular events with every 1% improvement in FMD.This study sought to determine the early vascular impact of switching from TC to EC in chronic smokers.The authors conducted a prospective, randomized control trial with a parallel nonrandomized preference cohort and blinded endpoint of smokers ≥18 years of age who had smoked ≥15 cigarettes/day for ≥2 years and were free from established cardiovascular disease. Participants were randomized to EC with nicotine or EC without nicotine for 1 month. Those unwilling to quit continued with TC in a parallel preference arm. A propensity score analysis was done to adjust for differences between the randomized and preference arms. Vascular function was assessed by FMD and pulse wave velocity. Compliance with EC was measured by carbon monoxide levels.Within 1 month of switching from TC to EC, there was a significant improvement in endothelial function (linear trend β = 0.73%; 95% confidence interval [CI]: 0.41 to 1.05; p < 0.0001; TC vs. EC combined: 1.49%; 95% CI: 0.93 to 2.04; p < 0.0001) and vascular stiffness (-0.529 m/s; 95% CI: -0.946 to -0.112; p = 0.014). Females benefited from switching more than males did in every between-group comparison. Those who complied best with EC switch demonstrated the largest improvement. There was no difference in vascular effects between EC with and without nicotine within the study timeframe.TC smokers, particularly females, demonstrate significant improvement in vascular health within 1 month of switching from TC to EC. Switching from TC to EC may be considered a harms reduction measure. (Vascular Effects of Regular Cigarettes Versus Electronic Cigarette Use [VESUVIUS]; NCT02878421; ISRCTN59133298).