tbuckley/cabot-search huggingface dataset:
RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma
Authors: E Viziteu, B Klein, J Basbous, Y-L Lin, C Hirtz, C Gourzones, L Tiers, A Bruyer, L Vincent, C Grandmougin, A Seckinger, H Goldschmidt, A Constantinou, P Pasero, D Hose, J Moreaux
Journal: Leukemia (2017)

Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients. Interestingly, RECQ1 knockdown inhibits cells growth and induces apoptosis in MMCs. Moreover, RECQ1 depletion promotes the development of DNA double-strand breaks, as evidenced by the formation of 53BP1 foci and the phosphorylation of ataxia-telangiectasia mutated (ATM) and histone variant H2A.X (H2AX). In contrast, RECQ1 overexpression protects MMCs from melphalan and bortezomib cytotoxicity. RECQ1 interacts with PARP1 in MMCs exposed to treatment and RECQ1 depletion sensitizes MMCs to poly(ADP-ribose) polymerase (PARP) inhibitor. DNMT inhibitor treatment results in RECQ1 downregulation through miR-203 deregulation in MMC. Altogether, these data suggest that association of DNA damaging agents and/or PARP inhibitors with DNMT inhibitors may represent a therapeutic approach in patients with high RECQ1 expression associated with a poor prognosis.
The Irreversible Proteasome Inhibitor Carfilzomib Interacts Synergistically with the Selective HDAC6 Inhibitor ACY1215 in ABC- and GC-DLBCL and Mantle Cell Lymphoma Sensitive or Resistant to Bortezomib.
Authors: Girija Dasmahapatra, Hiral Patel, Jawad T.J. Al-Khafaji, Richard I Fisher, Jonathan W. Friedberg, Steven Grant
Journal: Blood (2012)
Use of quantitative histomorphometrics to classify disease progression in HPV-positive squamous cell carcinoma.
Authors: Sahirzeeshan Ali, James S. Lewis, Anant Madabhushi
Journal: Journal of Clinical Oncology (2012)

73 Background: Oropharyngeal squamous cell carcinoma (SCC) is now recognized as distinct because of its strong association with high-risk human papillomavirus (HPV) and favorable prognosis. Although these tumors have some specific morphologic features, none have been shown to predict prognosis, particularly on small specimens such as biopsies. Methods: We present a novel cluster cell graph (CCG) that is computationally efficient and provides an effective tool to quantitatively describe histopathologic images according to the spatial distribution and clustering of cells. CCG is generated by firstly automatically identifying all cells/nuclei within the histologic image and then identifying nuclear clusters. These clusters are then represented via a single node corresponding to center of mass of the cluster. Any pair of nodes is connected via a link if the probability of such an association is greater than a pre-defined threshold, the probability being calculated as a decaying function of the Euclidean distance between node pairs. Once links have been identified between cluster nodes, subgraphs are constructed as series of topological features defined on each node of the subgraph, i.e., local graph metrics (e.g. clustering coefficients and skewness of edge lengths). Results: We leverage CCG to capture structural characteristics of HPV-related (p16+) oropharyngeal SCC (oSCC) from formalin-fixed, paraffin-embedded tissue microarray images. A series of quantitative histomorphometric descriptors are extracted for each image and used to train a random forest (RF) classifier to distinguish patients with p16+ oSCC who develop disease progression from those that do not. Over 25 runs of 3-fold cross validation in a cohort of 140 studies (116 non-progressors and 26 progressors) the RF classifier yielded a mean accuracy of over 87% in distinguishing between progressors and non-progressors. Conclusions: The ability to quantitatively describe the spatial distribution/clustering of nuclei via CCG allows for building of classifiers that can distinguish between progressors and non-progressors in p16+ oSCC tissue images. The approach should be extensible to outcome prediction for other cancers as well.
Clinicopathological analysis of programmed death-ligand 1 (PD-L1) expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) in surgically resected non-small cell lung cancer (NSCLC) patients (pts)
Authors: K. Saruwatari, G. Ishii, S. Nomura, K. Kirita, S. Umemura, S. Matsumoto, K. Yoh, S. Niho, H. Ohmatsu, M. Tsuboi, M. Kowanetz, M. Sakai, J. Itabashi, Y. Kamihara, R. Shiokawa, A. Morioka, M. Ueda, K. Goto
Journal: Annals of Oncology (2016)
Bridging efforts to longitudinally improve and evaluate venous thromboembolism prophylaxis uptake in hospitalized cancer patients through interprofessional teamwork (BELIEVE IT): A study by Princess Margaret Cancer Centre.
Authors: Jack Toshimine Seki, Triyu Vather, Vishal Kukreti, Monika Karolina Krzyzanowska
Journal: Journal of Clinical Oncology (2012)

170 Background: Thromboprophylaxis continues to be underutilized in hospitalized cancer patients despite the demonstrable risk of venous thromboembolism (VTE). Our study evaluated institutional VTE prophylaxis rates after devising a series of strategic interventions to longitudinally improve adherence rates over a period of eight years. Methods: Solid tumour patients admitted between 2004 and 2012 were selected as the primary study population for analysis. The bleeding risk associated with thromboprophylaxis was discernibly minimal. Guidelines were developed and formalized into an institutional thromboprophylaxis policy. Educational in-services were provided to physicians, nurses and pharmacists to review the most updated guidelines and tools added to encourage compliance to VTE prophylaxis. Support also arose from clinical members of the Cancer Quality Committee. An amalgamation of manual and electronic audit formats were undertaken to asses VTE prophylaxis rates prior to, and following strategy implementation. These audit formats either comprised of visiting inpatient units and examining anticoagulant orders on a per-patient basis, or viewing patient consensus reports and active anticoagulant orders electronically. Results: At the 2004 outset, 11 (19.3%) patients received appropriate pharmacological prophylaxis, and thus formed the baseline of our analysis. Post-2009 policy implementation and educational sessions, 46.5% of an eligible 185 inpatients were administered thromboprophylaxis. Following a two-year grace period to allow for policy acceptance, a series of three audits were conducted in 2011 for which an average prophylaxis rate of 62.3% resulted. In 2012, following awareness by clinicians of previous rates and rigorous strategy execution, a 96.7% rate was achieved and maintained five weeks thereafter. Conclusions: A reproducible 96.7% prophylaxis rate was the result of our cumulative eight-year efforts. A multidisciplinary approach is critical to improving thromboprophylaxis uptake rates and ensuring long-term sustainability of this outcome.
Optimal indications for second-line chemotherapy in advanced gastric cancer.
Authors: Hiroko Hasegawa, Kazumasa Fujitani, Shoichi Nakazuru, Motohiro Hirao, Eiji Mita, Toshimasa Tsujinaka
Journal: Journal of Clinical Oncology (2012)

105 Background: It remains uncertain whether every patient with advanced gastric cancer (AGC) who progresses after first-line chemotherapy should receive second-line chemotherapy. We conducted the present study to identify the optimal indications for second-line chemotherapy. Methods: In this retrospective study, 101 patients were included in univariate and multivariate analyses to identify clinicopathological variables independently associated with longer survival post progression (SPP), defined as the time from recognition of disease progression on first-line chemotherapy to death from any cause or last follow-up. Results: Median SPP of all patients was 340 days. On multivariate analysis, both performance status (PS) 2 (hazard ratio (HR), 14.234; 95% confidence interval (CI), 2.766–73.258), serum albumin (Alb) level &lt; 3.5 g/dl (HR, 2.088; 95% CI, 1.047–4.060) at initiation of second-line chemotherapy, and time to progression (TTP) &lt; 170 days on first-line chemotherapy (HR, 2.497; 95% CI, 1.227–5.083) were identified as independent prognostic factors for shorter SPP. Median SPP was 496, 375, and 232 days in patients with 0, 1, and 2 of these 3 negative prognostic factors, respectively (p = 0.0002). Conclusions: The present study suggests that second-line chemotherapy would be less beneficial in patients with 2 or more of the following 3 negative prognostic factors: PS 2, Alb &lt; 3.5 g/dl at initiation of second-line chemotherapy, and TTP &lt; 170 days on first-line chemotherapy.
A phase Ib clinical trial of Ad-ISF35-transduced autologous cells in combination with fludarabine, cyclophosphamide, rituximab (FCR) for patients with fludarabine-refractory and/or del(17p)/p53-defective chronic lymphocytic leukemia (CLL).
Authors: J. E. Castro, L. S. Schwartzberg, J. Pinilla-Ibarz, T. J. Kipps, M. J. Cantwell
Journal: Journal of Clinical Oncology (2011)

6528 Background: CLL cells with del(17p) typically have loss of functional p53, rendering them refractory to chemotherapeutic agents. However, del(17p) CLL cells activated by CD40 ligand (CD154) are induced to express pro-apoptotic factors to overcome resistance to the cytotoxic activity of p53-dependent drugs, such as fludarabine. To examine whether a CD154-based therapeutic strategy can be developed in vivo for del(17p) and/or fludarabine-refractory CLL, a phase 1b clinical study evaluating an autologous cellular gene immunotherapy is being conducted. Autologous CLL cells transduced ex vivo with a replication-defective adenovirus vector encoding a membrane-stable, re-engineered form of CD154 (Ad-ISF35) are administered, followed by standard courses of FCR in subjects with fludarabine-refractory and/or del(17p) CLL. Methods: Subjects with fludarabine-refractory and/or del(17p) CLL receive three IV doses (one dose every two weeks) of 3x108 autologous Ad-ISF35-transduced CLL cells. Two weeks following the third dose of Ad-ISF35-transduced cells, subjects receive up to six monthly cycles of FCR. Study endpoints include analysis of safety and efficacy. Results: Nine subjects have been enrolled and six have completed the study with an overall response rate (ORR) of 50%. This includes two subjects (33%) with an ongoing complete response (CR) after a median follow-up of 17 months, and no detectable minimal residual disease (MRD) in one subject. One subject (17%) had a partial response (PR) with resolution of lymphocytosis, lymphadenopathy and splenomegaly. One subject had stable disease after ISF35 and two cycles of FCR. Two subjects had progressive disease. Three subjects continue on study. Infusion of Ad-ISF35-transduced cells has been well-tolerated with transient fever, malaise and fatigue after ISF35 and cytopenias after FCR treatment. Conclusions: These encouraging data suggest the combination of Ad-ISF35 plus chemoimmunotherapy could offer a valuable treatment option for patients who otherwise would be resistant to standard forms of therapy.
High‐density lipoprotein‐associated paraoxonase‐1 activity for prediction of adverse outcomes in outpatients with chronic heart failure
Authors: Muhammad Hammadah, Andreas P. Kalogeropoulos, Vasiliki V. Georgiopoulou, Malory Weber, Yuping Wu, Stanley L. Hazen, Javed Butler, W.H. Wilson Tang
Journal: European Journal of Heart Failure (2017)
Impact of duration of bevacizumab (Bev) treatment in the prognosis of adults with recurrent malignant gliomas.
Authors: Mohamed Ali Hamza, Charles A. Conrad, John Frederick De Groot, Mark R. Gilbert, Morris D. Groves, W. K. Alfred Yung, Vinay K. Puduvalli
Journal: Journal of Clinical Oncology (2012)

2064 Background: Bev is the standard treatment for patients with recurrent glioblastoma (GB) but is also used in treating recurrent anaplastic gliomas (AG). Differences in outcome between these groups and optimal duration of treatment with Bev in pts with recurrent malignant gliomas are not well defined. We examined the relationship between the duration of Bev treatment and the outcome in pts with GB and AG. Methods: In this retrospective chart and data review derived from our longitudinal database, we identified pts with recurrent AG and GB who were treated with Bev alone or Bev-containing regimens between 2005 and 2009; the data was analyzed to determine the overall survival (OS) and the progression free survival (PFS). Results: A total of 261 patients with recurrent malignant gliomas (196 with GB and 65 with AG) were identified. There was no significant difference between the median length of treatment between AG and GB (5.81±0.66 months vs. 6.77±0.52 months, p=0.32). PFS6 was 34.2% (95% CI, 27.8-41.3) for patients with GB and 44.2% (95% CI, 32.5-56.7) for patients with AG. Patients with GB who were treated ≥6 months had a significantly higher OS (29.13 months vs. 20.16 months, p= 0.001) compared to those treated &lt;6 months, and a significantly higher PFS compared to those treated &lt;6months (11.33 months vs. 3.7 months, p=0.0001). For patients with AG, although treatment ≥6 months had a significantly higher PFS (13.93 months vs. 3.53 months, p&lt;0.0001), OS was not significantly different (months 38.6 vs. 52.5 months, p=0.6) compared with those treated &lt;6 months. Conclusions: Length of treatment ≥6 mo with Bev or Bev-containing regimen was associated with improved PFS in both AG and GB but only the GB subgroup showed improved OS. These results suggest equivocal survival benefit in patients with AG with longer duration of bevacizumab treatment, which requires further study in prospective trials.
Long-Term Immune Reconstitution Following Stem Cell Transplantation in Chronic Lymphocytic Leukemia.
Authors: Kate E Hodgson, Gerardo Ferrer, Carmen Martinez, Manel Juan, Montserrat Rovira, Marta Aymerich, Laura Carretero, Francesc Fernandez, Enric Carreras, Emili Montserrat, Carol Moreno
Journal: Blood (2009)
Medial tibial stress syndrome can be diagnosed reliably using history and physical examination
Authors: M Winters, E W P Bakker, M H Moen, C C Barten, R Teeuwen, A Weir
Journal: British Journal of Sports Medicine (2017)

The majority of sporting injuries are clinically diagnosed using history and physical examination as the cornerstone. There are no studies supporting the reliability of making a clinical diagnosis of medial tibial stress syndrome (MTSS).Our aim was to assess if MTSS can be diagnosed reliably, using history and physical examination. We also investigated if clinicians were able to reliably identify concurrent lower leg injuries.A clinical reliability study was performed at multiple sports medicine sites in The Netherlands. Athletes with non-traumatic lower leg pain were assessed for having MTSS by two clinicians, who were blinded to each others' diagnoses. We calculated the prevalence, percentage of agreement, observed percentage of positive agreement (Ppos), observed percentage of negative agreement (Pneg) and Kappa-statistic with 95%CI.Forty-nine athletes participated in this study, of whom 46 completed both assessments. The prevalence of MTSS was 74%. The percentage of agreement was 96%, with Ppos and Pneg of 97% and 92%, respectively. The inter-rater reliability was almost perfect; k=0.89 (95% CI 0.74 to 1.00), p<0.000001. Of the 34 athletes with MTSS, 11 (32%) had a concurrent lower leg injury, which was reliably noted by our clinicians, k=0.73, 95% CI 0.48 to 0.98, p<0.0001.Our findings show that MTSS can be reliably diagnosed clinically using history and physical examination, in clinical practice and research settings. We also found that concurrent lower leg injuries are common in athletes with MTSS.
Mapping of Conformational Epitopes, and Analyze of the Distribution of Ig Isotypes and Subclasses Using a Semi-Quantitative Multiplex Assay in 6 Cases of Postpartum Acquired Hemophilia.
Authors: Geraldine Lavigne-Lissalde, Priscilla Lapalud, Claire Pouplard, Claude Granier, Jeanne-Yvonne Borg, Chantal Rotschild, Yves Gruel, Jean-François Schved
Journal: Blood (2008)
Hepatitis A among refugees, asylum seekers and migrants living in hosting facilities, Greece, April to December 2016
Authors: Kassiani Mellou, Anthi Chrisostomou, Theologia Sideroglou, Theano Georgakopoulou, Maria Kyritsi, Christos Hadjichristodoulou, Sotirios Tsiodras
Journal: Eurosurveillance (2017)

An increased number of hepatitis A cases among refugees, asylum seekers and migrants residing in hosting facilities in Greece were recorded between April and December 2016. In total, 177 laboratory-confirmed symptomatic cases were reported; of these, 149 (84%) occurred in hosting camps mostly among Syrian children under 15 years. All cases reported symptom onset after their entry into the country. Public health interventions focused on hygiene measures and vaccination.
Patient-reported outcomes on integrative therapies for pain, tension, and level of comfort.
Authors: Kamron Keep, Alan Shaw, Stephanie Leavell, Paige Wimmer, Amie Bartholomeus, Shelli Furniss, Cheary Haney, George Condit, Belen Milburn, MaryAnn Doshier, Norman Zuckerman, Thomas M. Beck, Dan Sayam Zuckerman
Journal: Journal of Clinical Oncology (2012)

58 Background: The 2007 National Health Interview Survey (NHIS) reported more than one-third of adults used some form of complementary and alternative medicine (CAM). An analysis of 2002 NHIS data found CAM use to be more prevalent among people with a prior diagnosis of cancer. In 1999, St. Luke’s Mountain States Tumor Institute (MSTI) began an integrative therapies program to meet this growing interest and provide evidence-based, safe CAM modalities for patients. The program continues to grow and offers programs such as massage, acupuncture, and pediatric music therapy. Methods: Patient reported outcomes are collected from patients using pre/post treatment assessments. Outpatient massage and acupuncture programs measure comfort levels pre/post treatment using a 0-10 scale (0 = very comfortable; 10 = worst discomfort). The inpatient massage program measures pre/post treatment pain and tension using a 0-10 scale (0 = no pain/tension; 10 = worst pain/tension). Finally, the MSTI pediatric music therapy program collects pre/post treatment pain outcomes using a FLACC scale, where each of the five categories Face (F), Legs (L), Activity (A), Cry (C) and Consolability (C) are scored from 0-2, which results in a total score 0-10. Results: Assessments from outpatient acupuncture and massage collected between July 1, 2011 to July 1, 2012 showed that patients had an average comfort score of 3.6 before acupuncture and 2.0 after acupuncture and an average comfort score of 3.4 before massage and 0.77 after massage (n=1300 estimate). Inpatient massage outcomes collected between Dec. 2011 – June 2012 showed an average pain score of 2.53 before massage and 0.41 after massage and an average tension score of 4.73 before massage and 0.52 after massage (n=52). MSTI pediatric music therapy outcomes collected from January-April 2012 showed an average FLACC score of 3.0 before music therapy and 0.72 after music therapy (n=68). Conclusions: Integrative therapies such as massage, acupuncture and pediatric music therapy show significant benefits in providing comfort and decreasing pain and tension in MSTI cancer patients. Opportunities remain to conduct research and set a standard of practice with integrative therapies.
ACTR-56. UPFRONT CHEMORADIOTHERAPY IN GRADE 2 LOW GRADE GLIOMA, A SINGLE INSTITUTION EXPERIENCE
Authors: Robert T. Wicks, Dineth Bandarage, Ryan T. Mott, Roy E. Strowd, Adrian W. Laxton, Stephen B. Tatter, Michael D. Chan, Glenn J. Lesser
Journal: Neuro-Oncology (2016)

A recent randomized phase III study demonstrated survival improvement with chemoradiotherapy (CRT) over radiotherapy (RT) alone for WHO Grade II gliomas (LGG). PCV chemotherapy, utilized in this trial, is not commonly used in the US. We analyze our retrospective dataset of predominantly temozolomide-based CRT. Retrospective review of 111 LGG patients (years 2000–2013) in a single institution pathology database was performed. We identified 51 patients with LGG that were treated with upfront RT. Characteristics including age, gender, high-risk features (age≥40, tumor size>6 cm, tumor crossing midline, neurologic deficit at diagnosis), and use of RT and chemotherapy were determined. 16 patients received CRT (14 of which received temozolomide), and 35 patients received RT alone (median dose 54Gy). 46 patients had high risk LGG (15/16 receiving CRT, 31/35 receiving RT alone). Survival and progression free survival, based on serial imaging and electronic medical records, were assessed. Kaplan Meier analysis was used to assess time to events, and log rank test was used to compare patients who received RT to those receiving CRT. 5-year progression free survival for patients receiving CRT was 72% versus 54% in patients receiving radiation alone (p=0.03). 5-year overall survival for patients receiving CRT was 93% versus 79% in patients receiving radiation alone (p=0.04). Cox Proportional Hazards analysis revealed that patients with biopsy alone (HR=7.24, p=0.03), RT alone (HR=4.08, p=0.04) and having neurologic deficit at presentation (HR=4.57, p<0.01) had increased risk of death. Cox Proportional Hazards analysis showed that use of upfront RT was the only factor that increased the risk of earlier recurrence (HR=2.72, p=0.03). Use of upfront predominantly temozolomide-based CRT had overall survival benefit over RT alone in a population of WHO grade II gliomas treated. CRT was the only factor in this study that predicted for improved time to recurrence.
CELSG CML 11 “ISTAHIT” Phase III Study – Planned Interim Analysis: High Doses of Imatinib Mesylate (800mg/day) Significantly Improve Rates of Major and Complete Cytogenetic Remissions (MCR, CCR) in Pretreated Ph+/BCR-ABL+ CML Patients in Chronic Phase.
Authors: Andreas L. Petzer, Dominik Wolf, Dominic Fong, Thomas Lion, Irina Dyagil, Zvenyslava Masliak, Darinka Boskovic, Laimonas Griskevicius, Sandra Lejniece, Stefan Goranov, Liana Gercheva, Aleksandar Stojanovic, Dontcho Peytchev, Nikolay Tzvetkov, Rasa Griniute, Radka Oucheva, Hanno Ulmer, Marthin Kwakkelstein, Gianluca Fincato, Guenther Gastl
Journal: Blood (2008)