tbuckley/cabot-search huggingface dataset:
Non-invasive diagnosis of early-stage lung cancer using high-throughput targeted DNA methylation sequencing of circulating tumor DNA (ctDNA)
Authors: Wenhua Liang, Yue Zhao, Weizhe Huang, Yangbin Gao, Weihong Xu, Jinsheng Tao, Meng Yang, Lequn Li, Wei Ping, Hui Shen, Xiangning Fu, Zhiwei Chen, Peter W. Laird, Xuyu Cai, Jian-Bing Fan, Jianxing He
Journal: Theranostics (2019)

Rational: LDCT screening can identify early-stage lung cancers yet introduces excessive false positives and it remains a great challenge to differentiate malignant tumors from benign solitary pulmonary nodules, which calls for better non-invasive diagnostic tools.Methods: We performed DNA methylation profiling by high throughput DNA bisulfite sequencing in tissue samples (nodule size < 3 cm in diameter) to learn methylation patterns that differentiate cancerous tumors from benign lesions.Then we filtered out methylation patterns exhibiting high background in circulating tumor DNA (ctDNA) and built an assay for plasma sample classification.Results: We first performed methylation profiling of 230 tissue samples to learn cancer-specific methylation patterns which achieved a sensitivity of 92.7% (88.3% -97.1%) and a specificity of 92.8% (89.3% -96.3%).These tissue-derived DNA methylation markers were further filtered using a training set of 66 plasma samples and 9 markers were selected to build a diagnostic prediction model.From an independent validation set of additional 66 plasma samples, this model obtained a sensitivity of 79.5% (63.5% -90.7%) and a specificity of 85.2% (66.3% -95.8%) for differentiating patients with malignant tumor (n = 39) from patients with benign lesions (n = 27).Additionally, when tested on gender and age matched asymptomatic normal individuals (n = 118), our model achieved a specificity of 93.2% (89.0%-98.3%).Specifically, our assay is highly sensitive towards early-stage lung cancer, with a sensitivity of 75.0%(55.0%-90.0%) in 20 stage Ia lung cancer patients and 85.7% (57.1%-100.0%) in 7 stage Ib lung cancer patients. Conclusions:We have developed a novel sensitive blood based non-invasive diagnostic assay for detecting early stage lung cancer as well as differentiating lung cancers from benign pulmonary nodules.
Serial mutational analysis to monitor disease evolution in blood from advanced non small cell lung cancer (NSCLC) patients (p).
Authors: Santiago Viteri Ramirez, Clara Mayo-de las Casas, Nuria Jordana-Ariza, Daniela Morales-Espinosa, Miguel Angel Molina-Vila, Niki Karachaliou, Maria Gonzalez Cao, Marc Simo-Perdigo, Jordi Bertran-Alamillo, Jordi Codony, Monica Garzon, Ana Perez-Rosado, Alejandro Martinez-Bueno, Xavier Gonzalez, Elena Ovalle, Rafael Rosell
Journal: Journal of Clinical Oncology (2015)

e19085 Background: Repeat biopsies of cancer p are useful for monitoring molecular evolution of the disease and the possible appearance or disappearance of key somatic mutations, particularly those conferring sensitivity or resistance to targeted therapies. However, in a significant percentage of advanced NSCLC p re-biopsies cannot safely be obtained and then mutational analysis in blood (“liquid biopsies”) can provide a useful alternative. Methods: We developed and validated a quantitative 5’-nuclease PCR based assay for determination of relevant somatic mutations in EGFR (exon 19 deletions, T790M and L858R), KRAS (codons 12-13) and BRAF in cell-free DNA (cfDNA) isolated from serum and plasma. The presence of specific peptide-nucleic acids (PNAs) designed to inhibit amplification of the wild-type allele allows for sensitive detection of the mutated allele. Serial serum and plasma samples from 10 advanced NSCLC p with confirmed mutations in tumor tissue (5 EGFR-mut and 5 KRAS-mut) were collected and analyzed, and the results correlated with clinical and radiological evolution of the disease. Results: Mutations were detected baseline in cfDNA of 4/5 p with EGFR mutation in tumor tissue. EGFR mutation levels in cfDNA dropped or disappeared in p responding to erlotinib/gefitinib treatment. Radiological and clinical progression to tyrosine kinase inhibitors was preceded by an increase in mutation burden and the appearance in cfDNA of the T790M resistance mutation. Good response to second and subsequent lines of therapy was again concomitant with decreased mutation levels in cfDNA, while progression was invariably associated with an increase in mutation burden. Similar behavior of KRAS mutation levels in cfDNA was observed in KRAS mutated p treated with chemotherapy. Conclusions: Serial quantification of EGFR and KRAS mutations in cfDNA isolated from serum and plasma of NSCLC patients constitutes a novel, non-invasive method to monitor the course of the disease in real-time and adjust treatment accordingly.
Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/β-catenin signaling
Authors: Ping Ji, Yongxin Zhou, Yibao Yang, Junlu Wu, Hao Zhou, Wenqiang Quan, Junjun Sun, Yiwen Yao, Anquan Shang, Chenzheng Gu, Bingjie Zeng, Jenni Firrman, Weidong Xiao, Robert Bals, Zujun Sun, Dong Li
Journal: Theranostics (2019)

Rationale: Antimicrobial peptides, such as cathelicidin LL-37/hCAP-18, are important effectors of the innate immune system with direct antibacterial activity.In addition, LL-37 is involved in the regulation of tumor cell growth.However, the molecular mechanisms underlying the functions of LL-37 in promoting lung cancer are not fully understood.Methods: The expression of LL-37 in the tissues and sera of patients with non-small cell lung cancer was determined through immunohistological, immunofluorescence analysis, and enzyme-linked immunosorbent assay.The animal model of wild-type and Cramp knockout mice was employed to evaluate the tumorigenic effect of LL-37 in non-small cell lung cancer.The mechanism of LL-37 involving in the promotion of lung tumor growth was evaluated via microarray analyses, recombinant protein treatment approaches in vitro, tumor immunohistochemical assays, and intervention studies in vivo.Results: LL-37 produced by myeloid cells was frequently upregulated in primary human lung cancer tissues.Moreover, its expression level correlated with poor clinical outcome.LL-37 activated Wnt/β-catenin signaling by inducing the phosphorylation of protein kinase B and subsequent phosphorylation of glycogen synthase kinase 3β mediated by the toll-like receptor-4 expressed in lung tumor cells.LL-37 treatment of tumor cells also decreased the levels of Axin2.In contrast, it elevated those of an RNA-binding protein (tristetraprolin), which may be involved in the mechanism through which LL-37 induces activation of Wnt/β-catenin.Conclusion: LL-37 may be a critical molecular link between tumor-supportive immune cells and tumors, facilitating the progression of lung cancer.
Hepatitis D: not a rare disease anymore: global update for 2017–2018
Authors: Dan-Ting Shen, Dong-Ze Ji, Hai-Yan Chen, Hemant Goyal, Shiyang Pan, Hua-Guo Xu
Journal: Gut (2019)

We sincerely appreciate Stockdale and colleagues1 for their critical consideration of our article. Herein, we tried to answer their concerns about the methodology of our meta-analysis.2 

We used hepatitis D virus (HDV) antibody (both IgM and IgG) seropositivity as a measure of overall burden of HDV seroprevalence. Although anti-HDV IgM Ab assays may fail to detect low titres of antibodies and underestimate HDV seroprevalence,3 patients with a negative anti-HDV IgM results are less likely to progress into clinical disease.4 Majority of the included studies in our article used anti-HDV antibody assays and only two mentioned the use of RNA assays for the prevalence of HDV. Therefore, considering the wide application of the anti-HDV antibody assay as a measure of HDV seroprevalence,5 we used the similar method in our meta-analysis.

We do not think it would be correct to extrapolate the prevalence of HBsAg based on our estimates of HDV seroprevalence among general population and mixed population (HBsAg carriers without risk factors such as intravenous drug use and high-risk sexual behaviours). This is because the general population and the mixed …
SAT-134-Hypercoagulopathy risk factors in liver cirrhosis due to nonalcoholic steatohepatitis and clinical manifestations of hypercoagulation during 5 years
Authors: Nataliya Virstyuk, Nataliya Matkovska, Iryna Vakalyuk, Mykola Bagriy, Oleg Virstyuk
Journal: Journal of Hepatology (2019)
Safety meta-analysis of clinical trials delivering TTFields to the upper torso
Authors: G.L. Ceresoli, M. Pless
Journal: Annals of Oncology (2019)

Background: Tumor Treating Fields (TTFields), a non-invasive, loco-regional, antimitotic treatment approved for glioblastoma (GBM), are delivered via transducer arrays to tumor region. Localized dermatitis underneath the arrays were main adverse events (AEs) reported in phase 3 GBM trials. The safety of TTFields was analyzed in two phase I-II studies in non-small-cell lung cancer (NSCLC) [EF-15, NCT00749346] and malignant pleural mesothelioma (MPM) [STELLAR, NCT02397928]. Methods: TTFields studies in this pooled analysis were EF-15 (n=41, advanced NSCLC; plus pemetrexed) and STELLAR (n=80, MPM; plus platinum and pemetrexed). TTFields were applied 12 - 18 hours/day at a frequency of 150 kHz. All patients received standard of care systemic chemotherapy for their disease in addition to TTFields. Severity and frequency of AEs, and association with TTFields treatment were evaluated (CTCAE criteria version 4.0). Results: Patients were aged 27-78 years: STELLAR: 67 (27-78) and EF-15: 63 (44-78), ECOG 0-1; 7 patients in EF-15 had ECOG 2. The incidence of grade 1-2 gastrointestinal (GI) toxicities was 35%. The most common low grade GI toxicities were: nausea (17%), vomiting (6%), constipation (10%) and diarrhea (6%). Grade 1-2 general disorders (16% fatigue and 11% asthenia) were common. Dyspnea Grade 1-2 (12%) and Grade 3-4 (5%) were considered related to standard chemotherapy or underlying disease. Grade 1-2 cardiovascular AEs were 7%; one case of severe arrhythmia (atrial flutter) was unrelated to TTFields. The only common TTFields-related adverse event was dermatitis below the transducer arrays. 59% patients had dermatological AEs: 53% Grade 1-2 dermatitis, 4% grade 3 dermatitis and 11% Grade 1-2 pruritus. Conclusions: Treatment of solid tumors with TTFields 150 kHz to the thorax did not result in serious AEs or treatment-related pulmonary, cardiac, hematological or gastrointestinal toxicities. Expected dermatological toxicity beneath the device transducer arrays was seen in 59% patients, and resolved after a short treatment break or termination of treatment. These safety results and encouraging survival outcomes support the potential use of TTFields therapy in NSCLC and mesothelioma. Clinical trial identification: NCT00749346 and NCT02397928. Legal entity responsible for the study: Novocure. Funding: Novocure. Disclosure: G.L. Ceresoli: Travel support: Novocure. All other authors have declared no conflicts of interest.
TCTAP A-030 1-year Clinical Outcomes of Patients Treated with 48 mm Everolimus Eluting Stent in Primary Percutaneous Coronary Intervention
Authors: Jia Min Chua, Jin Hyun Lee, Deanna Zhi-Lin Khoo, Jason Kwok Kong Loh, Fahim Haider Jafary, Paul J.L. Ong, Hee Hwa Ho
Journal: Journal of the American College of Cardiology (2019)
Gut microbiome interventions in human health and diseases
Authors: Pengqing Nie, Zhiqiang Li, Yimeng Wang, Yubing Zhang, Mengna Zhao, Jie Luo, Shiming Du, Zixin Deng, Jincao Chen, Yunfu Wang, Shi Chen, Lianrong Wang
Journal: Medicinal Research Reviews (2019)

Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome-based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.
SAT-471-Hepatic adenomatosis increases risk of hepatic adenoma bleeding
Authors: Chelsea Mcdermott, Christine Cho-Shing Hsu, Sameer Desale, Stephen Fernandez, Marco Ertreo, Reena C. Jha, Rohit S. Satoskar, Alexander T. Lalos, Amol S. Rangnekar, Arul M. Thomas, Coleman I. Smith, Thomas W. Faust
Journal: Journal of Hepatology (2019)
STAT5BN642H drives transformation of NKT cells: a novel mouse model for CD56+ T-LGL leukemia
Authors: Klara Klein, Agnieszka Witalisz-Siepracka, Barbara Maurer, Daniela Prinz, Gerwin Heller, Nicoletta Leidenfrost, Michaela Prchal-Murphy, Tobias Suske, Richard Moriggl, Veronika Sexl
Journal: Leukemia (2019)
Study of induction docetaxel, cisplatin, cetuximab and bevacizumab (TPE-A) followed by concurrent radiotherapy, cisplatin, cetuximab and bevacizumab (XPE-A) in patients with high-risk locally advanced head and neck cancer.
Authors: Grace M. Akinyi-Joseph, Ahmad Mouhamad Wehbe, Athanassios Argiris
Journal: Journal of Clinical Oncology (2015)

e22004 TITTLE: A Phase II Study of Induction Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A) in Patients With Locally Advanced Head and Neck Cancer. Background: The role of induction chemotherapy in the management of locally advanced squamous cell carcinoma of the head and neck (SCCHN) has long been debated. The incorporation of novel agents in the induction setting remains of interest. We sought to investigate dual inhibition of EGFR and VEGF along with chemotherapy in locally advanced SCCHN in a phase II clinical trial Methods: Eligibility included ECOG status 0-1, adequate laboratory parameters, no bleeding history or taking anticoagulation; p16+ with 10 pack-years or less were excluded. Patients (pts) received induction therapy with bevacizumab 15 mg/Kg, docetaxel 75 mg/m2, cetuximab (250 mg/m2 after loading dose of 400 mg/m2 on cycle 1, day 1) and cisplatin 75 mg/m2 (TPE-A) IV once a week repeated every 21 days for 3 cycles, with G-CSF support, with optional surgery for non-responders in the primary, followed by radiotherapy to a total dose of 70 Gy in 35 fractions/7 weeks concurrently w/bevacizumab 15 mg/Kg every 3 weeks, cetuximab weekly and cisplatin 30 mg/m2weekly (XPE-A). Primary end point was complete response rate after induction with a planned sample size of 33. The study was closed due to slow accrual. Results: Three pts were enrolled, all males, ages 51, 53, 67; stages T4aN2B-C all p16 negative. One of three pts had a complete response and remains progression-free more than 12 months. The two other pts relapsed at 6 and 12 months, respectively. Grade 3 drug-related adverse events (AEs) were grade 3 neutropenic fever (N = 1), hyponatremia (1), hypokalemia (1), hypophosphatemia (1), XRT dermatitis (1) and mucositis (1). There were no grade 4 AEs or serious bleeding. Conclusions: In this small number of pts we could provide evidence supporting the feasibility and safety of this multiagent regimen. However, it remains unclear whether bevacizumab and/or cetuximab add to the efficacy of chemoradiotherapy Clinical trial information: NCT01588431.
THU-386-Interim results of hepatitis prevention, control and elimination program in Ulaanbaatar, Mongolia
Authors: Purevjargal Bat-Ulzii, Oyungerel Lkhagva-Ochir, Delgerbat Boldbaatar, Zolzaya Davaadorj, Byambasuren Ochirsum, Khatantuul Boldbaatar, Uurtsaikh Baatarsuren, Altankhuu Murdorj, Dahgwahdorj Yagaanbuyant, Zulkhuu Genden, Naranbaatar Dashdorj, Naranjargal Dashdorj
Journal: Journal of Hepatology (2019)
TCTAP A-087 Impact of Contrast Injection on Intracoronary Pressure During Optical Coherence Tomography Pullback
Authors: Kunihiro Shimamura, Takashi Kubo, Yasushi Ino, Hiroki Emori, Yosuke Katayama, Masahiro Takahata, Naoki Maniwa, Yasutsugu Shiono, Yoshiki Matsuo, Hironori Kitabata, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2019)
LBP-32-The Natural History of Ferroportin Disease-First Results of the International, Multicenter EASL non-HFE Registry
Authors: Benedikt Schaefer, André Viveiros, Elena Corradini, Massimo Fiorini, Stefania Scarlini, Raffaela Rametta, Sara Pelucchi, Fabiana Busti, Hansi Weissensteiner, Sebastian Schoenherr, Lukas Forer, Nathan Subramaniam, Edouard Bardou-Jacquet, John Ryan, Olivier Loreal, Dorine Swinkels, Mayka Sanchez, Martina Muckenthaler, Alexander Drakesmith, Herbert Tilg, Günter Weiss, Igor Theurl, Florian Kronenberg, Domenico Girelli, Alberto Piperno, Antonello Pietrangelo, Luca Valenti, Graca Porto, Heinz ZOLLER
Journal: Journal of Hepatology (2019)
Recombinant hybrid protein of tumor necrosis factor in neoadjuvant treatment of patients with locally advanced breast cancer.
Authors: Natalia Podzorova, Liubov Yu Vladimirova, Elena Yurievna Zlatnik, Yury Valentinovich Przhedetsky
Journal: Journal of Clinical Oncology (2015)

e12020 Background: There is a clinical need to increase the efficiency of standard neoadjuvant treatment in breast cancer patients. But there is a few data on tumor necrosis factor drugs used in neoadjuvant treatment inlocally advanced breast cancer (LABC) patients. The aim of the study was to evaluate the efficacy of recombinant hybrid protein of tumor necrosis factor-alpha-thymosin-alpha1 (TNF-T) in neoadjuvant treatment of LABC. Methods: Eligibility criteria included LABC of IIB-IIIB stages, ECOG ≤ 1, adequate liver, kidney and bone marrow function, no brain metastases. Recombinant hybrid protein of TNF-T 200000 IU was used peritumorally (injected around the tumor) on D1-5 (30 min before cytostatics injection), combined with standard FAC or PA regimens. Results: 82 women were recruited between April 2012 – October 2013 (mean age 53.3±1.1 years). Group A (30 pts) received recombinant hybrid protein of TNF-T combined to PA (17) and FAC (13) up to 4 courses. Group B (52pts) received standard PA (28) and FAC (24). Tumor response (TR) in Group A was 80%(24) and in Group B 71.1%(37) (p < 0.05), including CR 16.6%(5) and 7.7%(4) correspondently (p < 0.05). Common toxicities in Group A were: neutropenia Gr1 – 15.9%(7 courses), nausea and vomiting Gr2– 27.2%(12), polyneuropathy Gr1/2 – 9%(4). TNF-T-specified toxicities were: hyperthermia Gr1 – 45.4%(20); local reaction (aula, pain Gr1) lasted for 24-48 hrs – 90.9%(40). Group B: neutropenia Gr 1/2 – 21.2%(28), nausea and vomiting Gr2– 32.5%(43), polyneuropathy Gr1/2 – 10,6%(14), diarrhea Gr1 – 4,5(6). All patients in Group A were operated successfully, no postoperative complications connected with recombinant hybrid protein of TNF-T use were observed. By the time of writing of the abstract OS in Group A was 28.4±1.1mos, in Group B was 26.1±1.4mos; EFS in Group A was 26.9±1.3mos, in Group B was 22.9±1.2mos (p < 0.05). Conclusions: The proposal method of injection peritumorally (around the tumor) of TNF-T is well-tolerated and allows to enhance an antitumor effect of cytostatics (complete response in particular) which is of great importance in neoadjuvant treatment.
Prognostic factors for the feasibility of chemotherapy and the Geriatric Prognostic Index (GPI) as risk profile for mortality before chemotherapy in the elderly.
Authors: Ab Aaldriks, J. W. R. Nortier
Journal: Journal of Clinical Oncology (2015)

e20533 Background: Comprehensive geriatric assessment (CGA) is a multidimensional method to detect frailty in elderly patients. Time saving could be accomplished by identifying those individual items that classify elderly cancer patients at risk for feasibility of chemotherapy and for mortality. Methods: Patients older than 70 years of age were assessed before the first chemotherapy administration. GA consisted of the Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Predictive individual items for feasibility of chemotherapy and mortality were entered in the multivariable logistic regression and Cox-regression models, and a three-item sum scale was constructed: the Geriatric Prognostic Index (GPI). Results: The 494 patients had a median age of 75 years (range 70-92 years). The majority of the patients had malignancies of the digestive tract (41.7%) followed by haematological tumors (22.3%). Three items of the MNA (‘psychological distress or acute disease in the past three months’, ‘neuropsychological problems’ and ‘using > 3 prescript drugs’) independently predicted for feasibility of chemotherapy. Two items of the MNA and one of the GFI (‘declining food intake in past 3 months’, ‘using > 3 prescript drugs’, and ‘dependence in shopping’) independently predicted for mortality. In comparison with patients without any positive item on the three-item Geriatric Prognostic Index (GPI), patients with one, two or three positive items had HRs of 1.58, 2.32, and 5.58, respectively (all P< 0.001), see figure 1. Conclusions: With only three items of the MNA, feasibility of chemotherapy can be predicted. The 3-item GPI may help to identify elderly cancer patients at elevated risk for mortality.