tbuckley/cabot-search huggingface dataset:
Application of liquid biopsy to uncover critical cancer insights using the GeneReader NGS system.
Authors: Luisa Andruzzi
Journal: Journal of Clinical Oncology (2017)

e13102 Background: NGS studies of cancer are primarily based on studies of FFPE samples, the use of which is limited by surgical feasibility, tissue availability and patient preference. An emerging field of study is focused on circulating-free DNA (cfDNA), sometimes termed “Liquid Biopsy”. While holding great promise as the future of cancer understanding and management, the liquid biopsy field is still nascent, lacking an integrated NGS workflow solution with proven performance. Methods: QIAGEN is an established expert in the field of sample preparation for liquid biopsy. The combination of the QIAamp Circulating Nucleic Acid Kit, the GeneReader NGS System using a new proprietary sequencing chemistry, and an optimized bioinformatics solution, provides the first fully integrated workflow specifically designed for analyzing cfDNA. A set of liquid biopsy samples from non-small cell lung cancer (NSCLC) patients and cfDNA reference standards (Horizon), with allelic frequency down to 1%, were used for this study. cfDNA was extracted from the liquid biopsy samples, and run through the QIAGEN GeneReader workflow. Variants were analysed using the QIAGEN Clinical Insight (QCI™) Analyze for liquid biopsy. Results: Expected mutations in all genes (EGFR, KRAS, NRAS, PI3KCA) were identified and verified, at 100% concordance with reported in ddPCR studies. Both single nucleotide and insertion-deletion variants were correctly detected down to a 1% allele frequency threshold which was reproducible between repeat runs. No significant difference was observed between cfDNA reference standards and clinical liquid biopsy samples. Conclusions: These data exhibit high sensitivity and performance consistency of liquid biopsy analysis with the GeneReader system. This study systematically demonstrates the accuracy of a cfDNA assay combined with the robustness of a fully integrated NGS system. As such, laboratories interested in conducting liquid biopsy studies can leverage this study and the system to implement an NGS workflow.
Efficacy and safety of sofosbuvir-based regimens for treatment in chronic hepatitis C genotype 1 patients with moderately impaired renal function
Authors: Hyun Phil Shin, Ji-Ae Park, Blaire Burman, Richard A. Kozarek, Asma Siddique
Journal: Clinical and Molecular Hepatology (2017)

Treatment of chronic hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) is essential. The availability of sofosbuvir (SOF) has dramatically improved overall HCV cure rates, however there is insufficient data regarding its use in patients with CKD. We evaluated SOF in patients with hepatitis C genotype 1 (G1) and moderately impaired renal function.We retrospectively reviewed all patients treated with a SOF-based regimen from December 2013 through September 2015 at Virginia Mason Medical Center. Data was then collected for HCV G1 patients with stage 3 CKD.A total of 28 patients with HCV G1 and stage 3 CKD were treated with a SOF-based regimen. Twenty-one patients had stage 3A CKD (estimated glomerular filtration rate [eGFR] 45-60 mL/min/1.73m2) and 7 patients had stage 3B CKD (eGFR 30-45 mL/min/1.73m2). The overall rate of sustained virologic response (SVR) 12 weeks after completion of therapy (SVR12) was 85.7% (24/28). SVR12 in stage 3A CKD patients was 81.0% (17/21) and in stage 3B CKD patients, SVR12 was 100% (7/7). Based on the treatment regimen used, the SVR12 was 81.8% (9/11), 92.3% (12/13), and 75.0% (3/4) for SOF/ledipasvir (LDV), SOF/simeprevir (SIM), and SOF/pegylated interferon (PEG)/ribavirin (RBV), respectively. Greater than 30% reduction eGFR was observed in 4 out of 28 patients.SOF-based regimens resulted in high SVR12 rates in patients with moderately impaired renal function. During therapy, HCV patients with CKD should be carefully monitored for worsening renal function.
Benefits and Harms of Plant-Based Cannabis for Posttraumatic Stress Disorder
Authors: Maya E. O'Neil, Shannon M. Nugent, Benjamin J. Morasco, Michele Freeman, Allison Low, Karli Kondo, Bernadette Zakher, Camille Elven, Makalapua Motu'apuaka, Robin Paynter, Devan Kansagara
Journal: Annals of Internal Medicine (2017)

Background: Cannabis is available from medical dispensaries for treating posttraumatic stress disorder (PTSD) in many states of the union, yet its efficacy in treating PTSD symptoms remains uncertain. Purpose: To identify ongoing studies and review existing evidence regarding the benefits and harms of plant-based cannabis preparations in treating PTSD in adults. Data Sources: MEDLINE, the Cochrane Library, and other sources from database inception to March 2017. Study Selection: English-language systematic reviews, trials, and observational studies with a control group that reported PTSD symptoms and adverse effects of plant-based cannabis use in adults with PTSD. Data Extraction: Study data extracted by 1 investigator was checked by a second reviewer; 2 reviewers independently assessed study quality, and the investigator group graded the overall strength of evidence by using standard criteria. Data Synthesis: Two systematic reviews, 3 observational studies, and no randomized trials were found. The systematic reviews reported insufficient evidence to draw conclusions about benefits and harms. The observational studies found that compared with nonuse, cannabis did not reduce PTSD symptoms. Studies had medium and high risk of bias, and overall evidence was judged insufficient. Two randomized trials and 6 other studies examining outcomes of cannabis use in patients with PTSD are ongoing and are expected to be completed within 3 years. Limitation: Very scant evidence with medium to high risk of bias. Conclusion: Evidence is insufficient to draw conclusions about the benefits and harms of plant-based cannabis preparations in patients with PTSD, but several ongoing studies may soon provide important results. Primary Funding Source: U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO: CRD42016033623)
Cell-free DNA for treatment monitoring and outcome predictor in head and neck cancer.
Authors: Julia Beck, Markus Schirmer, Margret Rave-Fraenk, Howard Urnovitz, Kirsten Bornemann-Kolatzki, William Marvin Mitchell, Michael Oellerich, Ekkehard SchÃ¼tz, Martin Canis
Journal: Journal of Clinical Oncology (2017)

6055 Background: Copy number instability (CNI) signatures of cancers can be readily detected by Next Generation Sequencing of plasma cell-free DNA (cfDNA). HPV detected in oropharyngeal carcinomas is currently the only prognostic biomarker available. We report here CNI scores for disease monitoring of Head and Neck Cancers (HNC) with potential predictive value for personalized therapeutic options. Methods: A total of 132 plasma samples were collected from 54 HNC patients under informed consent and IRB approval. cfDNA was extracted from plasma, ~20M paired-end NGS mappable reads (reference: HG19) per sample were generated and CNI scores were calculated by read counting statistics. After unblinding CNI scores were evaluated as diagnostic parameter for association with disease characteristics and progression. Survival analysis was conducted after dichotomization of baseline CNI scores at a value of 31 corresponding to the 97.5 th percentile of a normal reference group (RG, n = 141). Results: CNI scores above the 97.5 th RG percentile were detected in 40 out of 54 (74%) treatment naïve baseline samples. 29 patients with tumors ≤ T3 (62%, n = 42) and 11 out of 12 (92%) with T4 tumors had CNI scores &gt; 31, with significantly higher CNI scores (p = 0.04) seen for T4 tumors. Higher CNI scores were also found in patients with tumor lymph node invasion (n = 37; median: 381, Q25-Q75: 57-1573) compared to negative lymph nodes (pN0, n = 17; 27, 19-64, p= 0.0004). A steep decline of CNI scores was detected after surgical resection, with increasing CNI scores in later disease progression. The pre-operative CNI scores were a stronger predictor of time to recurrence (p = 7*10 -5 ) than the pN status (p = 0.05) (Cox regression). High baseline CNIs ( &gt; 31) strongly correlated with time to recurrence (Kaplan-Meier log-rank p = 0.018) with a median of 20 months and median overall survival of 30 months in the high CNI group, neither reached in the low CNI-score group (60 m follow-up). Conclusions: Chromosomal instability within HNC was quantified from plasma cfDNA as CNI score. The CNI score may serve as better predictor for the time to recurrence interval than pN status. The data suggests that cfDNA analysis as CNI score may serve as real-time marker of treatment efficacy and outcome.
Response to: ‘The GRAPPA-OMERACT initiative to standardise outcomes in Psoriatic Arthritis clinical trials and longitudinal observational studies’ by Tillet <i>et al</i>
Authors: Sofia Ramiro, Josef S Smolen, Robert B M Landewé, Désirée van der Heijde, Laure Gossec
Journal: Annals of the Rheumatic Diseases (2017)

We thank Tillet et al for their comments1 on our letter to the editor entitled ‘How are enthesitis, dactylitis and nail involvement measured and reported in recent clinical trials of psoriatic arthritis? A systematic literature review’.2 We appreciate that the authors are in agreement with our view regarding the clear need for the …
Prognostic Value of Clonal Evolution at the Time of Diagnosis in Patients with Chronic Myeloid Leukemia Treated with Frontline Tyrosine Kinase Inhibitors
Authors: Ahmad Alhuraiji, Hagop M. Kantarjian, Elias J. Jabbour, Prajwal Chaitanya Boddu, Farhad Ravandi, Gautam Borthakur, Courtney D DiNardo, Naval Daver, Tapan M. Kadia, Naveen Pemmaraju, Sherry Pierce, Guillermo Garcia-Manero, Jorge E. Cortes
Journal: Blood (2016)
Mediastinal large B cell lymphoma with sclerosis (MLBCLwS). Therapeutic results in 180 consecutive PTS: MACOP/VACOP-B improves the long term outcome. G
Authors: Todeschini S Secchi, M. Lazzarino, E. Morra, U. Vitolo, M. Bertini, A. Ambrosetti, E. Gallo, F. Pasini, L. Orsucci, L. Gargantini, E. Brusamolino, E. Orlandi, A. Gabbas, C. Tarella, G. Rossi, Anna Marina Liberati, F. Menestrina, M. Paulli, C. Palestro, M. Cantini, G. Pizzolo, G. Perona
Journal: Blood (2000)
Role of the lncRNA ABHD11-AS1 in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC
Authors: Dan-Dan Wu, Xi Chen, Kai-Xuan Sun, Li-Li Wang, Shuo Chen, Yang Zhao
Journal: Molecular Cancer (2017)

There is increasing evidence in support of the role of lncRNAs in tumor cell proliferation, differentiation and apoptosis.We examined the expression of the lncRNA ABHD11-AS1 in epithelial ovarian cancer (EOC) tissues and normal ovarian tissues by real-time quantitative PCR (qRT-PCR). After inducing ABHD11-AS1 downregulation by small interfering RNA (siRNA) or ABHD11-AS1 overexpression by plasmid transfection, we examined the EOC cell phenotypes and expression of related molecules.Expression of the lncRNA ABHD11-AS1 in EOC tissues was higher than that in normal ovarian tissue. It was positively associated with the tumor stage (stage I/II vs. stage III/IV), and it was lower in the well-differentiated group than in the poorly/moderately differentiated group. Overexpression of ABHD11-AS1 in the ovarian cancer cell lines A2780 and OVCAR3 promoted ovarian cancer cell proliferation, invasion and migration, and inhibited apoptosis. Silencing of ABHD11-AS1 had the opposite effect. Subcutaneous injection of tumor cells in nude mice showed that ABHD11-AS1 could significantly promote tumor growth. In addition, intraperitoneal injection of tumor cells in the nude mice resulted in an increase in the metastatic ability of the tumor. Further, overexpression of ABHD11-AS1 upregulated the expression of RhoC and its downstream molecules P70s6k, MMP2 and BCL-xL. Silencing of ABHD11-AS1 had the opposite effect. The RNA pull-down assay showed that ABHD11-AS1 can combine directly with RhoC. Silencing of RhoC was found to inhibit the cancer-promoting effects of lncRNA ABHD11-AS1. Thus, it seems that RhoC is a major target of the lncRNA ABHD11-AS1.This is the first study to demonstrate the role of RhoC in the tumor-promoting effects of the lncRNA ABHD11-AS1. The present findings shed light on new therapeutic targets for ovarian cancer treatment.
Epigenetic drivers of tumourigenesis and cancer metastasis
Authors: Aniruddha Chatterjee, Euan J. Rodger, Michael R. Eccles
Journal: Seminars in Cancer Biology (2017)

Since the completion of the first human genome sequence and the advent of next generation sequencing technologies, remarkable progress has been made in understanding the genetic basis of cancer. These studies have mainly defined genetic changes as either causal, providing a selective advantage to the cancer cell (a driver mutation) or consequential with no selective advantage (not directly causal, a passenger mutation). A vast unresolved question is how a primary cancer cell becomes metastatic and what are the molecular events that underpin this process. However, extensive sequencing efforts indicate that mutation may not be a causal factor for primary to metastatic transition. On the other hand, epigenetic changes are dynamic in nature and therefore potentially play an important role in determining metastatic phenotypes and this area of research is just starting to be appreciated. Unlike genetic studies, current limitations in studying epigenetic events in cancer metastasis include a lack of conceptual understanding and an analytical framework for identifying putative driver and passenger epigenetic changes. In this review, we discuss the key concepts involved in understanding the role of epigenetic alterations in the metastatic cascade. We particularly focus on driver epigenetic events, and we describe analytical approaches and biological frameworks for distinguishing between "epi-driver" and "epi-passenger" events in metastasis. Finally, we suggest potential directions for future research in this important area of cancer research.
Molecular epidemiology of <i>Pseudomonas aeruginosa</i> in an unsegregated bronchiectasis cohort sharing hospital facilities with a cystic fibrosis cohort
Authors: Philip J Mitchelmore, Joanna Randall, Matthew J Bull, Karen A Moore, Paul A O’Neill, Konrad Paszkiewicz, Eshwar Mahenthiralingam, Chris J Scotton, Christopher D Sheldon, Nicholas J Withers, Alan R Brown
Journal: Thorax (2017)

While Pseudomonas aeruginosa (PA) cross-infection is well documented among patients with cystic fibrosis (CF), the equivalent risk among patients with non-CF bronchiectasis (NCFB) is unclear, particularly those managed alongside patients with CF. We performed analysis of PA within a single centre that manages an unsegregated NCFB cohort alongside a segregated CF cohort. We found no evidence of cross-infection between the two cohorts or within the segregated CF cohort. However, within the unsegregated NCFB cohort, evidence of cross-infection was found between three (of 46) patients. While we do not presently advocate any change in the management of our NCFB cohort, longitudinal surveillance is clearly warranted.
Multicenter Comparison of 22C3 PharmDx (Agilent) and SP263 (Ventana) Assays to Test PD-L1 Expression for NSCLC Patients to Be Treated with Immune Checkpoint Inhibitors
Authors: Antonio Marchetti, Massimo Barberis, Renato Franco, Graziano De Luca, Maria Vittoria Pace, Stefania Staibano, Marco Volante, Fiamma Buttitta, Elena Guerini-Rocco, Luisella Righi, Tommaso D’antuono, Giorgio V. Scagliotti, Carmine Pinto, Gaetano De Rosa, Mauro Papotti
Journal: Journal of Thoracic Oncology (2017)
Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins
Authors: Jonathan Elegheert, Vedrana Cvetkovska, Amber J. Clayton, Christina Heroven, Kristel M. Vennekens, Samuel N. Smukowski, Michael C. Regan, Wanyi Jia, Alexandra C. Smith, Hiro Furukawa, Jeffrey N. Savas, Joris de Wit, Jo Begbie, Ann Marie Craig, A. Radu Aricescu
Journal: Neuron (2017)
Outcomes After Transplantation of Donor Hearts With Improving Left Ventricular Systolic Dysfunction
Authors: Shivank Madan, Omar Saeed, Peter Vlismas, Ioanna Katsa, Snehal R Patel, Julia J Shin, William A Jakobleff, Daniel J Goldstein, Daniel B Sims, Ulrich P Jorde
Journal: Journal of the American College of Cardiology (2017)
Ferritin nanocage with intrinsically disordered proteins and affibody: A platform for tumor targeting with extended pharmacokinetics
Authors: Na Kyeong Lee, Eun Jung Lee, Soyoun Kim, Gi-hoon Nam, Minwoo Kih, Yeonsun Hong, Cherlhyun Jeong, Yoosoo Yang, Youngro Byun, In-San Kim
Journal: Journal of Controlled Release (2017)
AB0850 Helicobacter pylori infection and osteoporosis in post monopausal women
Authors: N Abdolahi, M Aghaei, M Naghdi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoprosis is a health problem that if is left untreated,can lead to serious health &amp; economical complications.It is also very common in postmenopausal women. Mineral deficiency, smoking, low BMI, some certain diseases and some medications can also cause osteoprosis. H.Pylori infection can also increase levels of inflammatory cytokines and bone turn over regulatory cytokines,as a result, it is likely that H. pylori infected patients are at increased risk for osteoprosis. <h3>Objectives</h3> the present study was done to understanding the association between H.Pylori seropositivity and osteoprosis in postmenopausal women. <h3>Methods</h3> The study population consisted of 34 osteoporotic patients and 73 healthy controls. Serum levels of h.pylori antibody (IgA,IgG) were measured by ELISA method. <h3>Results</h3> There was no difference in levels of IgA and IgG h.pylori antibody between patients and healthy controls IgA seropositivity was 70.6% in osteoporotic women and 54.8% in healty women (p value: 0.1). Also H. pylori IgG seropositivity was 82% in osteoporotic women and 75.3% in healthy women (p value: 0.4). We didnot find any correlation between H. pylori seropositivity and bone mineral density in post menopausal women. <h3>Conclusions</h3> In this study, we found that Helicobacter pylori infection does not increase the osteoporotic chance and is not a reliable risk factor for osteoporosis. greater sampele size, gastric biopsy to detect atrophic gastritis, bone turn over factors and Cag detection is recommended in order to achieve more accurate results <h3>References</h3> Shih-Chun Lin, Malcolm Koo, and Kun-Wei Tsai. Association between Helicobacter pylori Infection and Risk of Osteoporosis in Elderly Taiwanese Women with Upper Gastrointestinal Diseases: A Retrospective Patient Record Review, Gastroenterology Research and Practice, 2014;2014:814756. Kakehasi A.M, Mendes C.M.C, Coelho L.G.V, et al "The presence of Helicobacter pylori in postmenopausal women is not a factor to the decrease of bone mineral density," Arquivos de Gastroenterologia, vol. 44, no. 3, pp. 2007,266–270. Figura N, Gennari.L, Merlotti et al., "Prevalence of Helicobacter pylori infection in male patients with osteoporosis and controls," Digestive Diseases and Sciences, vol. 50, no. 5, pp. 2005, 847–852. Asaoka D, Nagahara A, Hojo M, Sasaki H, Shimada Y, Yoshizawa T, Osada T, Watanabe S. The Relationship between H. pylori Infection and Osteoporosis in Japan. Gastroenterol Res Pract. 2014;2014:340765. <h3>Disclosure of Interest</h3> None declared
The expression level and prognostic value of PD-L1 and PD-1 in cervical carcinoma patients.
Authors: Songan Zhang, Yong Xing Bao, Niyazi Huerxidan, Pan Liu, Huarong Zhao, Tuluwengjiang Gulixian, Yang Zhang, Lei Xiao, Weipeng Su, Sidike Dilidaer, Jianwei Ye
Journal: Journal of Clinical Oncology (2017)

e14501 Background: By testing the expression of PD-L1 in tissues and expression of PD-1 in matched blood samples in the cohort of cervical cancers patients and cervical benign disease patients, investigate the correlation between the expression level and their prognostic value. Methods: 70 tissue samples of cervical squamous cell carcinoma and 70 tissue samples of cervical benign lesion were collected respectively, and 24 cases of the cervical squamous cell carcinoma had matched peripheral blood samples, compared to 30 cases with matched peripheral blood samples in benign lesions. Immunohistochemistry was used to detect the expression of PD-L1 in the tissues. Flow cytometry was used to detect the proportion of CD4+PD-1+ and CD8+PD-1+ subsets in peripheral blood. Log-rank and COX regression were employed to analyze the survival time, clinical features and the information above. Results: There was no difference among age, marriage age, times of pregnancy, age of menarche, menopause, ethnic cultural level and occupation, except for family history of cancer. The portion of CD4+PD-1+ T cells and CD8+PD-1+ T cells in peripheral blood positively correlated with the expression of PD-L1 in tissue samples of cervical squamous cell carcinoma patients (R2 = 0.734, P = 0.000; R2 = 0.66, P = 0.000), while there were less correlation in cervical benign patients (R2 = 0.138, P = 0.043; R2 = 0.174, P = 0.022). There were significantly differences in the portion of CD8+PD-1+T cells and PD-L1+ cancer cells between cervical cancer group and cervical benign disease group (P = 0.000, P = 0.002). The portion of CD8+PD-1+ T cells correlated with the status of menopause (chi square = 7.152, P = 0.012). There was no relationship among the tumor size, differentiation, depth of invasion and PD-1 expression in peripheral blood cervical cancer group or cervical benign disease group. Conclusions: The cervical squamous cancer patients had more CD4+PD-1+ T cells in peripheral blood and PD-L1+ cells in tissues, which correlated to the grading and prognosis of the tumor.
循環腫瘍細胞の高感度分離のためのグラフェン酸化物で官能化したポリエステル布層【Powered by NICT】
Authors: Bu Jiyoon, Kim Young Jun, Kang Yoon-Tae, Lee Tae Hee, Kim Jeongsuk, Cho Young-Ho, Han Sae-Won
Journal: Biomaterials (2017)
Low-Dose Radioactive Iodine Ablation Is Sufficient in Patients With Small Papillary Thyroid Cancer Having Minor Extrathyroidal Extension and Central Lymph Node Metastasis (T3 N1a)
Authors: Minjung Seo, Yon Seon Kim, Jong Cheol Lee, Myung Woul Han, Eun Sook Kim, Kyung Bin Kim, Seol Hoon Park
Journal: Clinical Nuclear Medicine (2017)

The aim of this study was to evaluate the effectiveness of low-dose radioactive iodine (RAI) ablation in patients with small papillary thyroid cancer (PTC) exhibiting microscopic extrathyroidal extension (mETE) and central lymph node (CLN) metastasis.Among patients who underwent RAI ablation between March 2007 and February 2014, those who had small PTCs (≤2 cm), as well as mETE and CLN metastasis (T3 N1a M0), were enrolled. Response to ablation and long-term outcomes were assessed and compared according to the administered RAI dose. Factors associated with unsuccessful ablation were also determined.A total of 180 patients were included in the study. Eighty-eight patients had been treated with 1110 MBq (low-dose group) and 92 with 2960 MBq (high-dose group) of RAI. There were no significant differences in the responses to ablation (P = 0.810) and long-term outcomes (P = 0.663) between both groups. Among all patients enrolled, 13 did not achieve successful ablation at long-term follow-up. Logistic regression found that a high ratio of metastatic nodes was a significant factor for predicting unsuccessful ablation.Low-dose RAI ablation did not produce significantly different responses or long-term outcomes in patients with small PTCs exhibiting mETE and CLN metastasis. These findings suggest that low-dose ablation may be sufficient in this specific group of intermediate-risk patients, although careful selection is required for patients with a high ratio of metastatic nodes.