tbuckley/cabot-search huggingface dataset:
CONCORDANCE study: An observational, multicenter, prospective study to evaluate concordance of detecting EGFR mutations by circulating tumor-free DNA versus tissues biopsy in NSCLC.
Authors: Kumar Prabhash, Bivas Biswas, Sachin Khurana, Ullas Batra, Ghanashyam Biswas, Suresh Hariram Advani, P Mohapatra, Senthill J Rajappa, Ajay Sharma, Shekar Patil, Palanki Satya Dattatreya, Dr.Sachin Almel, Gautam Goyal, Rakesh Roy, Narayanankutty Warrier
Journal: Journal of Clinical Oncology (2020)

e21615 Background: Epidermal growth factor receptor (EGFR) mutations on circulating tumour free DNA (ctDNA) by liquid biopsy is suitable option in those with difficulty in obtaining tissue samples. Correlation in tissue and plasma results of EFGRm has not been established in the Indian population . 1,2,3 This study was done to investigate the utility of ctDNA for EGFRm testing with Next-Generation Sequencing (NGS) in a real-world diagnostic setting. Methods: This is a multicentre, prospective, diagnostic observational study in 245 newly diagnosed treatment naïve, histologically confirmed, advanced lung adenocarcinoma patients. This was a single visit study. The primary objective of the study was to determine the level of concordance between EGFR mutation status obtained by tissue and ctDNA from blood (plasma) based testing in terms of overall concordance, sensitivity &amp; specificity. Study was registered at Clinicaltrials.gov NCT03562819 &amp; CTRI/2018/08/015290. Results: Seventy-five (30.6%) and eighty-four (34.3%) subjects showed positive mutation status by plasma &amp; tissue testing respectively. The overall concordance of 82.9% was observed between tissue and ctDNA (Plasma) based testing. Sensitivity of EGFR mutation status between ctDNA and tissue was observed for EGFR mutation subtypes was observed to be 100% while specificity was observed to be 90.1%. Plasma and tissue sample testing detected 1.2% (n = 3) and 2.4% (n = 6) positive in exon 20 T790M EGFR mutation, respectively. In terms of secondary outcomes, plasma sample testing detected 16.7% (n = 41) positive for Exon 19 deletions type EGFR mutation followed Exon 21 L858R [11.4% (n = 28)]. Conclusions: CONCORDANCE, a real-world study in Indian patients suggest that ctDNA testing for EGFR mutation analysis is a diagnostic option in newly diagnosed lung adenocarcinoma patients. EGFR Mutation testing in ctDNA, being non-invasive and especially in patients without available/evaluable tumor sample may enable more patients to receive appropriate targeted therapies. [Table: see text]
Role of epigenetic regulators in single-base substitution patterns in AML.
Authors: Madhuri Paul, Frank J Scarpa, Wendy A Wolfson, Lawrence Weiss, Vincent Anthony Funari, Forrest Blocker
Journal: Journal of Clinical Oncology (2020)

e19500 Background: Incidence of Acute Myeloid Leukemia (AML) increases with age, as does Clonal Hematopoiesis of indeterminate Potential (CHiP), wherein specific genes are mutated in healthy individuals. Single Base pair Substitutions (SBS) are associated with aging and AML, most commonly C&gt;T. G&gt;A transitions are found in a similar prevalence in all age groups, although the number of mutations are higher in older age groups and associated with therapy. Determining a pattern of SBS in leukemia that is distinct from aging has been a challenge. Methods: We performed mutational signature analysis on 10,152 mutations in 3,575 unique suspected AML patient bone marrow, peripheral blood, or FFPE tissue samples. Samples were evaluated using an all exon amplicon based 27 gene next generation sequencing panel. The cohort was divided into 5 groups based on age (0-14, 15-39, 40-54, 55-65, and &gt;65 years), as well as into three gene mutation groups 1) TET2 WT (n=7,479 mutations), 2) TET2/DNMT3A WT (n=6,701) and 3) TET2/DNMT3A WT with chromatin regulators WT (ASXL1, ATRX, BCOR, BCORL1, EZH2, PHF6, RAD21, SMC1A, SMC3, STAG2; n=3627 mutations). Results: Predominant SBS were C&gt;T (42.7%) and G&gt;A (59.0%) transitions across all age groups. The percentage of C&gt;T SBS increased with age: 0-14 years cohort (18.0% of cases; 1.5% of mutations) to &gt;65 years cohort (58.8% of cases; 39.6% of mutations). There was no significant change in the prevalence of G&gt;A mutations with age, however, the total number of mutations did increase with age (0-14 0.2% vs &gt;65 39.6%). In each of the gene mutation groups, the number of C&gt;T and G&gt;A total mutations decreases as TET2 MT (42.7% and 59.0%), TET2 WT (27.0% and 45.1%), TET2/DNMT3A WT (20.8% and 34.3%), and TET2/DNMT3A WT with WT chromatin regulators (10.1% and 25.5%). Conclusions: In this study, both the prevalence and number of mutations in AML patients increases with age for C&gt;T transitions, but for G&gt;A transitions only the number of mutations increases with age, consistent with previously reported studies. In this data set, by removing mutations in TET2, TET2 and DNMT3A, TET2 and DNMT3A with genes that regulate chromatin accessibility, the number of C&gt;T and G&gt;A transitions decreases in order of effect, with the chromatin modifiers having the largest effect. The effect of removing these mutations suggests a mechanism driving leukemogenesis whereby DNMT3A methylates cytosine, TET2 deaminates this methylated cytosine, and finally chromatin modifiers regulate accessibility to these methylation sites, thereby modulating downstream oncologic pathways.
冠心病介入术后的用药问题
Authors: 韩志华, 王长谦
Journal: BMJ (2012)

冠心病的治疗措施主要包括内科药物、冠状动脉(冠脉)介入术及冠脉搭桥术.对冠心病而言,冠脉介入术如同修好了一条大路,但是术后大路的维护、道路的畅通还是离不开内科药物治疗.因此,从一定程度上来说,冠脉介入术后合理用药,是决定手术临床是否成功及远期疗效好坏的至关重要的因素.作为基层医疗单位的医务人员,常常会面临许多冠脉介入术后日常门诊随访的患者,在其用药上要注意以下几个问题。
A case of hemodialysis-related hepatic encephalopathy
Authors: Yang Gao, Lili Kong, Qingfei Xiao, Yuezhu Zhao, Ying Zhao
Journal: BMJ (2019)

报道1例血液透析的后半程出现意识障碍伴血氨增高患者的临床资料，排除透析失衡综合征和尿毒症性脑病后，高度警惕血液透析诱发的肝性脑病，通过调节血气分析中的碱剩余，减轻血液透析引起短暂的全身偏碱状态，并稳定血流动力学，病情缓解。
Quality of life, vascular endothelial growth factor inhibition, and survival outcomes with combination oral metronomic therapy in platinum refractory epithelial ovarian carcinoma: Results from a randomized study.
Authors: Aparna Sharma, Sachin Khurana, Prabhat Singh Malik, Mayank Singh, Sandeep Mathur, Sunesh Kumar, Vishnu kumar Sreenivas, Lalit Kumar
Journal: Journal of Clinical Oncology (2020)

6048 Background: Patients with recurrent and refractory epithelial ovarian cancer (EOC) have dismal outcomes. We evaluated a combination of oral metronomic therapy in platinum refractory EOC vis-à-vis angiogenic marker expression and its impact on patient reported outcomes. Methods: Between October 2017 and September 2019, 75 patients were randomized to receive etoposide (VP-16) (50 mg daily for 14 days) cyclophosphamide (50 mg daily for 28 days) (Arm A, n = 38) or etoposide (VP-16) (50 mg daily for 14 days) cyclophosphamide (50 mg daily for 28 days) and pazopanib (400 mg daily 28 days) every 28 days (Arm B, n = 37). Eligibility criteria included histopathological diagnosis of EOC, platinum refractory disease and ECOG performance status 0-2. Primary endpoint was serological progression free survival (PFS) as defined by Rustin criteria. Quality of Life (QoL) (evaluated using the EORTC QLQC30 and OV 28 questionnaires) and serum vascular endothelial growth factor (VEGF) were ascertained at baseline and after 3 rd and 6 th cycle. Intention to treat analysis was done. Results: Baseline characteristics were well matched in 2 arms. At a median follow up 14.4 months (95% CI 13.2-15.7), the median serological PFS is better for patients in Arm B 5.1 months (95%CI 3.13-10.33) compared to 3.4 months (95%CI 3-6.53) in arm A ( P= 0.045). Median overall survival (OS) is not reached in arm B versus 11.2 months (95%CI 5.66-NR) in arm A (P= 0.032). Disease progression was seen in 42.1% (n = 16) in Arm A versus 40.5 %(n = 15) in arm B ( P= 0.40). Sixteen patients are maintaining response. Mucositis (29.7% n = 11) and fatigue (13.5%, n = 5) were more in the pazopanib-containing arm ( P= 0.36). Serum VEGF demonstrated significant decline with subsequent cycles of therapy {median values (range): Arm A, baseline; 466.0 pg/mL(123.9-1930) vs. 6 cycles; 92.05pg/ mL(42.34-279.5) P&lt; 0.0001; Arm B, baseline; 382.0 pg/mL(49.44-2054.0) vs 6 cycles; 119.7 pg/mL(18.20-367.5) P= 0.013} without any difference between the two arms ( P= 0.18). QoL symptom scales in both QLQC 30 and OV 28 questionnaires indicated small but significant improvement in pazopanib arm ( P= 0.02) without differences in global (p = 0.96) and physical functioning scales. ( P= 0.68). Conclusions: Addition of pazopanib to etoposide and cyclophosphamide resulted in improvement in serological PFS and OS with a well-tolerated toxicity profile and modest improvement in QoL.Serum VEGF expression requires validation in a larger cohort. Clinical trial information: CTRI/2017/10/010219.
Impact of renal impairment on clinical outcomes in patients (pts) with locally advanced or metastatic (LA/M) urinary tract carcinoma (UTC) treated with atezolizumab (atezo): Analysis of the international SAUL study.
Authors: Margitta Retz, Florian Seseke, Giuseppe Luigi Banna, Ugo De Giorgi, Thomas Powles, Umberto Basso, Raymond S. McDermott, Anna Llado, Wen-Pin Su, Cristina Ligia Cebotaru, Javier Puente, Alvaro Montesa, Jacques De Greve, Zsuzsanna Kahan, Urbano Anido Herranz, Sabine de Ducla, Julie Pavlova, Simon Fear, Cora N. Sternberg
Journal: Journal of Clinical Oncology (2020)

5036 Background: Atezo, which targets PD-L1, is an approved therapy for LA/M urothelial carcinoma based on the IMvigor210 and IMvigor211 trials. The single-arm SAUL study (NCT02928406) showed consistent activity and safety in a broader population, including understudied scenarios, eg pts with renal impairment or other IMvigor211 exclusion criteria. Methods: Pts with LA/M UTC received atezo 1200 mg q3w until disease progression or unacceptable toxicity. The primary endpoint was safety; secondary endpoints included overall response rate (ORR) and overall survival (OS). Post hoc analyses explored outcomes in pts classified as: chemotherapy (CT) ineligible (calculated creatine clearance [CrCl] 15– &lt; 30 mL/min); cisplatin ineligible and carboplatin eligible (CrCl 30– &lt; 60 mL/min); or cisplatin eligible (CrCl ≥60 mL/min). Results: Of 1004 enrolled pts, 46 (5%) were classified as CT ineligible and 420 (42%) as cisplatin ineligible. Results are summarized below. Conclusions: These post hoc analyses suggest pts typically considered cisplatin or CT ineligible are candidates for atezo. Pts with renal impairment achieved similar ORR and DCR to pts with CrCl ≥60 mL/min, without increased toxicity. Imbalances in pt characteristics may explain numerical differences in OS. Clinical trial information: NCT02928406 . [Table: see text]
Effects of short message service platform system on return visit rate, glycosylated hemoglobin level and glucose control rate for diabetics
Authors: Lingyu Zheng, Aili Zhang, Jia Lü, Jing Zhan
Journal: BMJ (2014)

A total of 296 patients were randomly divided into short message group (n=153) and non short message group (n=143). The former group received short message service (SMS) for follow-ups while the latter group had routine oral follow-ups. The return visit rate, recall rate of glycosylated hemoglobin (HbA1c), HbA1c level and glucose control rate for diabetics were assessed after one-year follow-up. The return visit rate (96%) and recall rate of HbA1c (78%) in the short message group were significantly higher than those in the non-short message group (59%, 25%, P<0.01 for both). The HbA1c level after one-year follow-up (6.51±0.74)% was lower than that one year before (6.85±1.26)% in the short message group. The glucose control rate after one year (82%) were significantly higher than that one year before in the short message group (65%) and that after one year in the non-short message group(59%, P<0.01). Use of SMS platform system for follow-ups and health education can effectively improve the return visit rate and glucose control rate, lower the HbA1c level. in diabetics.


Key words: 
Diabetes management, diabetes msllitus; Short message service platform system
药物 Tildrakizumab 治疗斑块型银屑病的研究
Authors: A.B. Kimball, K.A. Papp, K. Reich, M. Gooderham, Q. Li, N. Cichanowitz, C. La Rosa, A. Blauvelt
Journal: British Journal of Dermatology (2020)

Tildrakizumab 是一种相当新型的药物,称为生物制剂,用于治疗中度至重度牛皮癣。这种药物可以防止体内一种与炎症有关的特定分子的活动,这种分子被称为细胞因子白细胞介素 (IL)‐23p19。 先前的研究表明,它优于安慰剂(一种非活性物质,像“糖丸”一样)和一种旧的生物制剂,即 TNF 抑制剂 Etanercept。然而,试验很少反映出现实世界的经历,患者可能会从一种药物换到另一种药物,改变药物剂量或中断治疗,例如因为感染而这样做。 作者(位于美国、加拿大和德国)回顾了两项研究的结果,一项是将两种不同剂量的 Tildrakizumab(每天 100 mg 或 200 mg)与安慰剂进行比较,另一项是将其与 Etanercept 进行比较,其中纳入总共 1862 名患有中度到重度斑块型银屑病的成年患者。 在研究过程中,重新随机分配治疗。他们发现,对 Tildrakizumab 的应答是持续的(这意味着它持续起作用),没有出现一些使用 Etanercept 的患者中出现的继发性失败(在最初满意的应答后对药物的应答性下降),并且在治疗中断后,重新使用药物仍能有效地控制银屑病。总体而言,该药物耐受性良好,这意味着其副作用很小。 本摘要涉及研究:在持续给药、治疗中断、剂量调整和从 Etanercept 转换过来的情况下 Tildrakizumab 治疗斑块型银屑病的有效性和安全性: 来自 III 期研究的结果。
Abstract A10: Glioma cell-free DNA methylation marker for diagnosis and monitoring
Authors: Thais Sabedot, Tathiane Malta, James Snyder, Kevin Nelson, Michael Wells, Ana deCarvalho, Abir Mukherjee, Dhan Chitale, Maritza Mosella, Karam Asmaro, Adam Robin, Mark Rosenblum, Tom Mikkelsen, Jack Rock, Laila Poisson, Ian Lee, Tobias Walbert, Steven Kalkanis, Ana Valeria Castro, Houtan Noushmehr
Journal: Clinical Cancer Research (2020)

Abstract Genome-wide DNA-methylation profiling has shown that epigenetic abnormalities are biologically and clinically important signs in glioma and can be used to classify these tumors into distinct prognostic groups. Thus far, DNA methylation profiling of gliomas has required surgically resected tissue. Because gliomas release tumoral material into biofluids, such as blood, we developed a method using a liquid biopsy (LB) for minimally invasive surveillance of the tumor. We performed a genome-wide CpG methylation profile of cell-free DNA extracted from serum of patients with primary glioma (N=48) and during clinical follow-up (N=33). We used a supervised machine learning (ML) approach to identify glioma-specific epigenetic signatures in the LB (eLB) (N=1000, false-discovery rate &amp;lt; 0.003) to distinguish patients with glioma from those without glioma. The epigenetic profiles of matched tumor tissue showed that there was 67% concordance between the eLB signatures of the glioma in serum and tissue. Using these signatures as input for ML, we derived the glioma epigenetic liquid biopsy (GeLB) score. An independent validation study (68 gliomas and 65 nongliomas) showed that a GeLB score ≥ 50% could predict with 96% accuracy (sensitivity = 97.1% and specificity = 95.9%) whether a patient had glioma or not. Changes in GeLB score also reflected clinicopathologic changes observed during surveillance (e.g., progression, pseudoprogression, or response to a clinical trial drug). Our results suggest that the GeLB score could be used as a complementary approach to diagnose glioma and follow up patients postsurgically. Finally, we provide an online tool for predicting glioma based on the cell-free DNA methylome (hbtc.shinyapps.io/GeLB/). Citation Format: Thais Sabedot, Tathiane Malta, James Snyder, Kevin Nelson, Michael Wells, Ana deCarvalho, Abir Mukherjee, Dhan Chitale, Maritza Mosella, Karam Asmaro, Adam Robin, Mark Rosenblum, Tom Mikkelsen, Jack Rock, Laila Poisson, Ian Lee, Tobias Walbert, Steven Kalkanis, Ana Valeria Castro, Houtan Noushmehr. Glioma cell-free DNA methylation marker for diagnosis and monitoring [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A10.
Risk of Hospitalization With Hemorrhage Among Older Adults Taking Clarithromycin vs Azithromycin and Direct Oral Anticoagulants
Authors: Kevin Hill, Ewa Sucha, Emily Rhodes, Marc Carrier, Amit X. Garg, Ziv Harel, Gregory L. Hundemer, Edward G. Clark, Greg Knoll, Eric McArthur, Manish M. Sood
Journal: JAMA Internal Medicine (2020)

Clarithromycin is a commonly prescribed antibiotic associated with higher levels of direct oral anticoagulants (DOACs) in the blood, with the potential to increase the risk of hemorrhage.To assess the 30-day risk of a hospital admission with hemorrhage after coprescription of clarithromycin compared with azithromycin among older adults taking a DOAC.This population-based, retrospective cohort study was conducted among adults of advanced age (mean [SD] age, 77.6 [7.2] years) who were newly coprescribed clarithromycin (n = 6592) vs azithromycin (n = 18 351) while taking a DOAC (dabigatran, apixaban, or rivaroxaban) in Ontario, Canada, from June 23, 2009, to December 31, 2016. Cox proportional hazards regression was used to examine the association between hemorrhage and antibiotic use (clarithromycin vs azithromycin). Statistical analysis was performed from December 23, 2019, to March 25, 2020.Hospital admission with major hemorrhage (upper or lower gastrointestinal tract or intracranial). Outcomes were assessed within 30 days of a coprescription.Among the 24 943 patients (12 493 women; mean [SD] age, 77.6 [7.2] years) in the study, rivaroxaban was the most commonly prescribed DOAC (9972 patients [40.0%]), followed by apixaban (7953 [31.9%]) and dabigatran (7018 [28.1%]). Coprescribing clarithromycin vs azithromycin with a DOAC was associated with a higher risk of a hospital admission with major hemorrhage (51 of 6592 patients [0.77%] taking clarithromycin vs 79 of 18 351 patients [0.43%] taking azithromycin; adjusted hazard ratio, 1.71 [95% CI, 1.20-2.45]; absolute risk difference, 0.34%). Results were consistent in multiple additional analyses.This study suggests that, among adults of advanced age taking a DOAC, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically significantly greater 30-day risk of hospital admission with major hemorrhage.
Abstract IA21: Elucidating and targeting mechanisms of single-cell state maintenance: From N-of-1 to N-of-1-of-1 studies
Authors: Andrea Califano
Journal: Cancer Research (2020)

Abstract We have developed network-based methodologies for the systematic identification, validation, and pharmacologic targeting of a new class of therapeutic targets. These targets comprise Master Regulator proteins, whose concerted aberrant activity within tightly regulated modules (tumor checkpoints) is responsible for the mechanistic implementation and maintenance of specific tumor cell states. By leveraging these methodologies, we have developed OncoTreat, a NY CLIA-certified test that leverages large-scale drug-perturbation assays to systematically identify drugs and drug combinations whose mechanism of action is specifically effective in abrogating tumor checkpoint activity, on an individual patient basis. These tests have shown 60% validation rate across 39 predicted drugs that were validated in PDX models from patients who had failed multiple standard-of-care therapies. In this talk, we will introduce these concepts and then demonstrate their application to elucidating drugs capable of targeting transcriptionally distinct tumor niches by single-cell analysis (N-of-1-of-1 studies). In particular, we will show identification and validation, in vivo, of drugs targeting the stemlike progenitor niche of breast adenocarcinomas and the four transcriptionally distinct single-cell subtypes identified in glioblastoma patients. Citation Format: Andrea Califano. Elucidating and targeting mechanisms of single-cell state maintenance: From N-of-1 to N-of-1-of-1 studies [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA21.
Autoimmune and inflammatory diseases following COVID-19
Authors: Caroline Galeotti, Jagadeesh Bayry
Journal: Nature Reviews Rheumatology (2020)

Emerging reports show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection precedes the appearance of various autoimmune and autoinflammatory diseases, including paediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), thus adding to the growing mystery of this virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae.
Ticagrelor inhibits the NLRP3 inflammasome to protect against inflammatory disease independent of the P2Y12 signaling pathway
Authors: Bo Huang, Yufeng Qian, Shujun Xie, Xianhua Ye, Hanwen Chen, Zhifeng Chen, Lihuan Zhang, Jinming Xu, Hu Hu, Shenglin Ma, Paul Héroux, Di Wang, Han-Ming Shen, Yihua Wu, Dajing Xia
Journal: Cellular and Molecular Immunology (2020)
Single UM171 Expanded Cord Blood Transplant Is Feasible, Safe, and Permits Transplantation of Better HLA Matched Cords with Very Low Transplant Related Mortality
Authors: Sandra Cohen, Jean Roy, Silvy Lachance, Anne Marinier, Denis-Claude Roy, Jean-Sébastien Delisle, Lambert Busque, Pierre Caudrelier, Fannie Larochelle, Philippe Bouchard, Jean Roy, Nadia M. Bambace, Léa Bernard, Thomas L Kiss, Sébastien Lemieux, Peter W. Zandstra, Guy Sauvageau
Journal: Blood (2017)
Abstract AP12: FOXM1 INDUCES DNA REPLICATION STRESS AND PROMOTES GENOMIC INSTABILITY DOWNSTREAM OF CYCLIN E1 IN HIGH-GRADE SEROUS OVARIAN CANCER
Authors: Carter J Barger, Kajal Biswas, Linda Chee, Ronny Drapkin, Shyam Sharan, Adam R. Karpf
Journal: Clinical Cancer Research (2019)

Abstract PURPOSE: Genomic instability (GI) is a hallmark of high-grade serous ovarian cancer (HGSC), and induction of the FOXM1 transcription factor regulatory network is the second most frequent genetic alteration in HGSC. FOXM1 expression is associated with cancer GI, but the mechanistic link is unknown. DNA replication stress (DRS), which involves altered replication fork dynamics, is a key contributor to cancer GI. FOXM1 and cyclin E1 (CCNE1) are both expressed in STIC lesions in the fallopian tube epithelium (FTE), and CCNE1-CDK2 enhances FOXM1 transcriptional activity. Based on these observations, we hypothesized that: 1) FOXM1 is linked to cancer GI through the induction of DRS, and 2) FOXM1 promotes GI downstream of CCNE1, by promoting unscheduled M phase entry in cells that have not completed DNA synthesis. METHODS: We determined associations between FOXM1 and markers of DRS and GI in TCGA HGSC data. We overexpressed FOXM1c and a DNA binding domain mutant (DBD) in immortalized FTE cells and characterized the impact on DRS, DNA replication, and DNA damage. We determined the impact of CCNE1 on FOXM1 expression in immortalized FTE cells. We determined the combined effect of CCNE1 and FOXM1 on GI in FTE cells. RESULTS: FOXM1 was significantly associated with markers of DRS (CHK1-Ser345) and GI (fractional copy number altered genome (CNA)) in TCGA HGSC data. FOXM1 expression, but not its DBD mutant, induced biomarkers of DRS and DNA damage in hTERT/mutant Tp53 immortalized FTE cells. Unexpectedly, FOXM1c increased DNA replication fork rate in FTE cells. Increased fork rate is a novel and recently recognized cause of DRS. CCNE1 expression in FTE cells induced and activated FOXM1, promoting mitotic entry. FOXM1 and CCNE1 co-expression in FTE cells induced an expression signature of GI, and TCGA HGSC tumors with FOXM1 and CCNE1 co-expression showed significantly increased GI. CONCLUSIONS: We demonstrate that FOXM1 induces DRS and DNA damage in FTE cells, providing an explanation for the known link between FOXM1 and GI. Notably, FOXM1 induces a novel form of DRS involving increased replication fork rate. We show that CCNE1 activates FOXM1, which in turn promotes mitotic entry and GI. These data reveal a potentially major form of oncogenic collaboration in HGSC, and has implications for HGSC treatment approaches that promote DRS or inhibit the cellular DRS response. . Citation Format: Carter J Barger, Kajal Biswas, Linda Chee, Ronny Drapkin, Shyam Sharan, Adam R. Karpf. FOXM1 INDUCES DNA REPLICATION STRESS AND PROMOTES GENOMIC INSTABILITY DOWNSTREAM OF CYCLIN E1 IN HIGH-GRADE SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP12.