tbuckley/cabot-search huggingface dataset:
Changes in circulating endothelial cells (CECs) during treatment with cisplatin-based chemotherapy for testicular cancer
Authors: R. Altena, E. C. De Haas, A. G. Tibbe, A. J. Smit, A. van Roon, C. Meijer, M. H. Boezen, J. van der Meer, D. T. Sleijfer, J. A. Gietema
Journal: Journal of Clinical Oncology (2009)

e16009 Background: Chemotherapy (CT)-induced endothelial damage is an important pathogenic factor for cardiovascular morbidity in testicular cancer (TC) patients (pts). Therefore, we studied early markers of endothelial damage as predictors of cancer treatment-related cardiovascular morbidity. Methods: We prospectively assessed markers of endothelial damage in TC pts treated at the University Medical Center Groningen, before, during, 4 weeks and one year after completion of standard CT (3 or 4 three weekly cycles with bleomycin, etoposide and cisplatin). The number of circulating endothelial cells (CECs), identified by CD146+, CD105+ and CD45− using the CellSearch system, and plasma levels of von Willebrand Factor (vWF) were measured. Results: 30 TC pts were included (median age 34 years, range 20–47). Before start of CT, CECs were not associated with disease stage or leukocyte count. The number of CECs progressively increased over the 9–12 week CT period [baseline: median (range) 25/mL (6–137); maximum number during CT: 134/mL (28–320; p&lt;0.001); 4 weeks after completion of CT: 66/mL (18–316; p=0.005)]. One year post treatment, CECs were not different from baseline [N= 10; 13/mL (6–31; p=0.263)]. vWF levels also progressively increased during CT [baseline: median 105% (range 50–377); maximum level during CT: 289% (175–464; p&lt;0.001); 4 weeks after completion of CT: vWF 124% (56–274; p=0.149)]. One year after CT, vWF levels were 115% (61–184; p=0.285). During CT, numbers of CECs and vWF levels correlated positively (r=0.283; p&lt;0.001), whereas maximum CECs increase and maximum vWF increase were not associated (r=0.098; p=0.605). Two pts had a cerebral infarction during CT. In one pt, vWF increased before the event; in both pts CECs increased directly afterwards. Conclusions: During CT for disseminated TC, CECs and vWF progressively increased during consecutive cycles. CECs remained increased 4 wks after completion of CT, whereas vWF returned to baseline levels. The magnitude of changes was not equal in every pt. Therefore, both CECs and vWF might be early predictive markers for chemotherapy-induced cardiovascular toxicity, and may serve as intermediate endpoint in intervention studies. [Table: see text]
Utilisation of the ESMO-MCBS in practice of HTA
Authors: C. Wild, N. Grössmann, P.V. Bonanno, A. Bucsics, J. Furst, K. Garuoliene, B. Godman, J. Gulbinovič, J. Jones, M.K. Pomorski, R. Emprechtinger
Journal: Annals of Oncology (2016)
High Body Mass Index (BMI) in North American Elderly Diffuse Large B-Cell Lymphoma (DLBCL) Patients Treated with Rituximab (R)-CHOP Compensates for Negative Impact of Male Gender
Authors: Zheng Zhou, Alfred W. Rademaker, Leo I. Gordon, Ann S. LaCasce, Allison Crosby-Thompson, Ann Vanderplas, Gregory A Abel, Maria A. Rodriguez, Auayporn Nademanee, Mark Kaminski, Myron S. Czuczman, Michael M. Millenson, Joyce Niland, Andrew D. Zelenetz, Jonathan W. Friedberg, Jane N. Winter
Journal: Blood (2014)
Assessment of Imaging Modalities and Response Metrics in Ewing Sarcoma: Correlation With Survival
Authors: Vadim S. Koshkin, Vanessa Bolejack, Lawrence H. Schwartz, Richard L. Wahl, Rashmi Chugh, Denise K. Reinke, Binsheng Zhao, Joo H. O, Shreyaskumar R. Patel, Scott M. Schuetze, Laurence H. Baker
Journal: Journal of Clinical Oncology (2016)

Despite the rapidly increasing use of [18F]fluorodeoxyglucose (FDG) -positron emission tomography (PET), the comparison of anatomic and functional imaging in the assessment of clinical outcomes has been lacking. In addition, there has not been a rigorous evaluation of how common radiologic criteria or the location of the radiology reader (local v central) compare in the ability to predict benefit. In this study, we aimed to compare the effectiveness of various radiologic response assessments for the prediction of overall survival (OS) within the same data set of patients with sarcoma.We analyzed assessments made during a clinical trial of a novel IGF1R antibody in Ewing sarcoma: PET Response Criteria in Solid Tumors (PERCIST) for functional imaging and WHO criteria (performed locally and centrally), RECIST, and volumetric analysis for anatomic imaging. We compared the effectiveness of the various criteria for the prediction of progression and survival.For volume analysis, progression-defined as cumulative lesion volume increase of 100% at 6 weeks-was the optimal cutoff for decreased OS (P < .001). Assessment of the day-9 FDG-PET scan was associated with reduced OS in progressors compared with nonprogressors (P = .001) and with improved OS in responders compared with nonresponders. Significant variations in response (18% to 44%) and progression (9% to 50%) were observed between the different criteria. The comparison of central and local interpretation of anatomic imaging produced similar outcomes. PET was superior to anatomic imaging in identification of a response. Volume analysis identified the most responders among the anatomic imaging criteria.An early signal with FDG-PET on day 9 and volume analysis were the best predictors of benefit. Validation of the volumetric analysis is required.
Predicting metastasized seminoma using gene expression.
Authors: M. Port, C. Ruf, M. Linbecker, H. U. Schmelz, W. Wagner, V. Meineke, M. Abend
Journal: Journal of Clinical Oncology (2010)

e15017 Background: The aim of the study was the separation of metastasized and non metastasized seminoma using gene expression in primary tumor. Identification of a hypothetical metastatic phenotype could result in prediction of occult metastatic disease in order to avoid unnecessary therapeutic and diagnostic interventions. Methods: Total RNA was isolated from metastasized, occult metastasized and non-metastasized seminoma (n=12, clinical Stage (cS) IIa-III; n=2 occult metastasis in primary staging; n=38, clinical Stage I (cSI)) and corresponding normal tissues (n=8, n=2 and n=26). The RNA was converted into cDNA and RTQ-PCR was run on 94 gene candidates selected from previous work. Normalized gene expression of these genes was analyzed using logistic regression analysis. Results: Five out of 94 genes, namely DRD1, FAM71F2, EFHC2, LOC389199 and C19orf54, showed a significant association with metastasis status using univariate logistic regression analysis. Concordance was in the range of 69.6-79.9% and could be increased up to 87.7% by a bivariate model including DRD1 and FAM71F2. No further improvement could be accomplished by adding other variables and employing a forward, backward or stepwise selection procedure. The expression of DRD1 and FAM71F2 made it possible to identify all metastasized seminoma (100% sensitivity) and to identify occult metastasized with sensitivity of 100% and 67%, respectively. Metastasized seminoma could be diagnosed at a cutoff (probability level) of 0.12 with 100% sensitivity and 58% specificity. Conclusions: This method might allow discriminating between occult metastasized and non metastasized seminoma, where computed tomography fails, and help reducing unnecessary therapies in non-metastasized patients. No significant financial relationships to disclose.
An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth
Authors: Lakmali Atapattu, Nayanendu Saha, Chanly Chheang, Moritz F. Eissman, Kai Xu, Mary E. Vail, Linda Hii, Carmen Llerena, Zhanqi Liu, Katja Horvay, Helen E. Abud, Ulrike Kusebauch, Robert L. Moritz, Bi-Sen Ding, Zhongwei Cao, Shahin Rafii, Matthias Ernst, Andrew M. Scott, Dimitar B. Nikolov, Martin Lackmann, Peter W. Janes
Journal: The Journal of Experimental Medicine (2016)

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance.
Detection of Th1 Driven T-Cell Responses in Peripheral Could Guide Individualized Immunosuppression and Risk of Viral Reactivation Under GvHD Prophylaxis Following Allogeneic Stem Cell Transplantation.
Authors: Judith Feucht, Kathrin Opherk, Cornelia Neinhaus, Simone Kayser, Wolfgang A. Bethge, Rupert Handgretinger, Peter Lang, Tobias F. Feuchtinger
Journal: Blood (2012)
Abstract 1115: Targeted RNA sequencing improves transcript analysis in cancer samples
Authors: Ling Lin, Ryan Abo, Deniz Dolcen, Rachel Paquette, Angelica Laing, Luc de Waal, Aaron Thorner, Matthew Ducar, Liuda Ziaugra, Bruce Wollison, Marc Breneiser, William Hahn, Matthew Meyerson, Paul Van Hummelen, Laura MacConaill
Journal: Cancer Research (2015)

Abstract RNA sequencing (RNA-seq) is a transcriptome profiling technology that provides multiple levels of insight into the genome. In addition to expression levels (transcript abundance), it generates endpoints such as alternative splicing, somatic mutations and rearrangements, which may have functional consequences in cancer. Although somatic mutations are generally identified by DNA sequencing, RNA-seq has the advantage of detecting allele-specific expression affecting a variant allele, as well as functional chimeric transcripts that result from structural rearrangements. Compared to microarray technologies, RNA-seq can provide additional information about novel transcripts. Due to the complexity of the human transcriptome and the variability of gene abundance, the cost of whole transcriptome sequencing to achieve sufficient coverage to detect these types of alterations remains high. To explore the feasibility of a more cost-effective method, we compared the performance of three different RNA-seq methods: whole-transcriptome-, exome-, and targeted RNA-seq, using RNA derived from cancer cell lines and Formaldehyde Fixed-Paraffin Embedded (FFPE) samples. For whole-transcriptome preparation, we used the Illumina TruSeq Stranded mRNA and total RNA kits for cell line and FFPE samples, respectively. Exome-RNAseq was performed using the Illumina Access kit. The libraries from whole-transcriptome RNAseq were subjected to hybridization capture using OncoPanel-an Agilent SureSelect baitset of 500 cancer-related genes. Compared to whole-transcriptome, exome- and targeted-RNA-seq demonstrated (1) higher coding exon coverage and multiplexing capability; (2) reduced rRNA composition to 1%; (3) comparable gene abundance information and (4) over 90% of reads aligned to coding exon regions in FFPE samples, compare to ∼30% when using whole transcriptome method. In conclusion, we demonstrated that exome- and targeted RNA-seq provide a cost-effective way to analyze a subset of the transcriptome. Furthermore, targeted RNA-seq can be highly multiplexed and is therefore amenable for large-scale tumor profiling in clinical or research settings. Citation Format: Ling Lin, Ryan Abo, Deniz Dolcen, Rachel Paquette, Angelica Laing, Luc de Waal, Aaron Thorner, Matthew Ducar, Liuda Ziaugra, Bruce Wollison, Marc Breneiser, William Hahn, Matthew Meyerson, Paul Van Hummelen, Laura MacConaill. Targeted RNA sequencing improves transcript analysis in cancer samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1115. doi:10.1158/1538-7445.AM2015-1115
A Threshold of Systemic MAGE-A Gene Expression Predicting Survival in Resected Non–Small Cell Lung Cancer
Authors: Ingo Mecklenburg, Wulf Sienel, Severin Schmid, Bernward Passlick, Peter Kufer
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Quantitative measurement of minimal residual disease predicting recurrence in individual cancer patients is available only in very few indications, such as acute lymphoblastic leukemia, but is still missing in most solid tumors, including non–small cell lung cancer (NSCLC). Experimental Design: MAGE-A expression levels in blood and bone marrow determined as calibrator-normalized relative ratios by quantitative multimarker real-time RT-PCR for transcript amplification of MAGE-A1, -A2, -A3/6, -A4, -A10, and -A12 in 94 patients with completely resected NSCLC were correlated with survival in a clinical study. Results: Patients with MAGE-A expression levels ≥0.2 in at least one sample of bone marrow or blood at tumor surgery had a significantly reduced overall (P = 0.007), cancer-free (P = 0.002), and distant metastasis–free survival (P &amp;lt; 0.001) versus patients below 0.2 in all samples without significant difference in locoregional recurrence–free survival. The corresponding HRs (≥0.2 vs. &amp;lt;0.2) for death, cancer-related death, and development of distant metastasis were 2.56 [95% confidence interval (CI), 1.42–4.63], 3.32 (95% CI, 1.66–6.61), and 4.03 (95% CI, 1.77–9.18), respectively. Five-year Kaplan–Meier estimates of distant metastasis–free survival were 43% (MAGE-A ≥ 0.2) versus 87% (MAGE-A &amp;lt; 0.2). Conclusions: MAGE-A expression in blood or bone marrow at tumor surgery is an independent predictor of survival in resected NSCLC. The reliable prediction of distant metastasis in individual patients with a statistically proven impact on overall survival may help to refine patient selection for adjuvant therapy urgently needed, especially in the clinical management of elderly patients. Clin Cancer Res; 23(5); 1213–9. ©2016 AACR.
Technologic advancements and error rates in radiation therapy (RT) delivery.
Authors: D. N. Margalit, K. Heckman, Y. Chen, P. J. Catalano, T. Vivenzio, K. Nissen, P. Mauch, A. K. Ng
Journal: Journal of Clinical Oncology (2010)

6141 Background: Technologic advances in RT delivery have the potential to reduce errors via increased automation and built-in quality assurance (QA) safeguards. Intensity modulated radiation therapy (IMRT) is an increasingly utilized technology that delivers highly-conformal radiation by using multiple beams and beam angles. Although IMRT is more technically complex than traditional 2-dimensional (2D) and 3-dimensional (3D) RT techniques, it requires more QA safeguards and is highly automated, which may reduce the risk of human error. We hypothesized that IMRT is associated with a lower error rate in RT delivery than 2D and 3D RT delivery techniques. Methods: All errors in external beam RT delivery were prospectively recorded via a non-punitive error-reporting system at Brigham and Women's Hospital and the Dana Farber Cancer Institute. Errors are defined as any unplanned deviation from the intended RT treatment and are reviewed during a monthly departmental quality improvement meeting. We performed a retrospective analysis of all errors since the routine use of IMRT in our department, from January 2004 to July 2009. Fisher's exact test was used to determine the association between treatment technique (IMRT vs. 2D/3D) and errors. Effect estimates were computed using logistic regression. Results: There were 155 errors in RT delivery out of 241,546 individual treatments (0.064%). There were significantly fewer errors with the use of IMRT compared with traditional 2D/3D techniques (0.033% vs. 0.072%, p = 0.001). The odds of errors with IMRT were 54% lower than the odds of errors with 2D/3D RT (OR = 0.46, [0.28, 0.74]). The most common errors were incorrect patient isocenter setup (23 errors), block misplacement (16 errors), and computer mis-entry of treatment parameters (13 errors). No errors were considered to have a clinically significant impact on the patient. Conclusions: Despite increased plan complexity, IMRT is associated with a lower rate of reported errors in RT delivery than traditional 2D/3D techniques. Together with practice-based quality improvement procedures, technological advancements in RT delivery may improve patient safety. No significant financial relationships to disclose.
The ability of the ABCD<sup>2</sup>score to predict stroke 1 year after TIA or minor stroke was assessed
Authors: Graeme J. Hankey
Journal: Annals of Internal Medicine (2016)

Source Citation Amarenco P, Lavallée PC, Labreuche J, et al; TIAregistry.org Investigators. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374:1533-42. 27096581
Mortality for non-AIDS-defining cancers among people with AIDS.
Authors: A. Zucchetto, B. Suligoi, A. De Paoli, S. Pennazza, M. Spina, S. Bruzzone, G. Rezza, U. Tirelli, L. Dal Maso, D. Serraino
Journal: Journal of Clinical Oncology (2010)

1590 Background: In the era of highly active antiretroviral therapies, the impact of non-AIDS-defining cancers on mortality of people with HIV/AIDS has been rarely quantified. To evaluate the risk of death for non-AIDS-defining cancers, among Italian people with AIDS (PWA). Methods: Population-based, retrospective, cohort study. 10,391 Italian citizens, aged 15 years or more, diagnosed with AIDS, in Italy, between 1999 and 2006, were included in the study. Record-linkage with mortality databases of the Italian Institute of Statistics was carried out to retrieve vital status and death certificates. Follow-up was calculated from date of AIDS diagnosis to date of death, or to December 31, 2006 for PWA who were still alive. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs), in comparison with the Italian population, were calculated for each non-AIDS-defining cancer, which was the underlying cause of death. Results: Among 3,209 deceased PWA, 7.4% died for non-AIDS-defining cancers, with a SMR of 6.6 (95% CI 5.8-7.5). Significantly elevated SMRs were found for several cancer types, notably for Hodgkin lymphoma (SMR = 174, 95% CI 115-251), and cancers of liver (SMR = 11.1, 95% CI 7.4-16.1), brain (SMR = 10.0, 95% CI 5.4-16.8), head and neck (SMR = 8.2, 95% CI 4.8-12.9), lung (SMR = 5.9, 95% CI 4.4-7.6), and myeloma and leukaemias (SMR = 5.9, 95% CI 2.8- 10.8). Overall mortality for non-AIDS-defining cancers was particularly high among injecting drug users (SMR = 15.5, 95% CI 12.5-18.9). Conclusions: The finding of elevated SMRs for non-AIDS-defining cancers should be interpreted as the joint result of the increased incidence and of the worse prognosis for these malignancies among PWA. They also reveal the importance of monitoring the cancer burden on mortality of PWA. No significant financial relationships to disclose.
Mutations in the Gene of Neutrophil Elastase Associated with Congenital Neutropenia Lead to Alteration of Intracellular Trafficking and Proteolytic Function of NE Protein.
Authors: Carmela Beger, Inga Koellner, Cornelia Zeidler, Manuela Germeshausen, Nils von Neuhoff, Brigitte Schlegelberger, Karl Welte
Journal: Blood (2004)
<i>Candida</i> infections in patients with psoriasis and psoriatic arthritis treated with interleukin-17 inhibitors and their practical management
Authors: D.M. Saunte, U. Mrowietz, L. Puig, C. Zachariae
Journal: British Journal of Dermatology (2016)

The recognition of the central role of interleukin (IL)‐17A in the pathogenesis of psoriasis has led to the development of several monoclonal antibodies targeting this cytokine or its receptors for therapeutic purposes. IL‐17A also plays an important role in immunological protection against infections, especially those due to Candida spp., as evidenced by findings in patients with genetic defects in IL‐17‐related immune responses. To assess the potential of anti‐IL‐17 treatment to promote Candida infections, here we have systematically reviewed published clinical trials of patients with psoriasis or psoriatic arthritis. Candida infections were reported in 4·0% of patients treated with brodalumab, 1·7% with secukinumab and 3·3% with ixekizumab vs. 0·3%, 2·3% and 0·8% of those assigned to placebo, ustekinumab or etanercept, respectively. Although the incidence of Candida infection was found to be increased by only a small degree during anti‐IL‐17 therapy, patients undergoing such treatment should be monitored for fungal infection and treated as necessary. We propose adoption of the recently updated recommendations for the practical management of Candida infection in patients administered IL‐17 inhibitors.
“Weekend effect” for emergency general surgery has almost disappeared, study shows
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The risk of death following emergency admission for general surgery has fallen significantly since 2000 and is no more likely following admission at the weekend than it is following admission midweek, a study published in the British Journal of Surgery has shown.1

Historically there has been a significantly increased risk of death from operations undertaken at the weekend, but that gap had narrowed substantially in recent years to become no longer significant, the results showed.

Researchers analysed data on general surgical admissions to NHS hospitals in the Northern Deanery in England between 2000 and 2014. There were 12 100 in-hospital deaths within 30 days of admission (3.3%), but …
Clinical Manifestations and Bleeding Episodes Among Heterozygote Individuals of Factor XIII Deficiency, a Short Term Prospective Study
Authors: Majid Naderi, Akbar Dorgalaleh, Shaban Alizadeh, Shadi Tabibian, Soudabeh Hosseini, Maryam Sadat Hosseini, Mehran Karimi
Journal: Blood (2014)
Erythropoietin stimulates normal endothelial progenitor cell-mediated endothelial turnover, but attributes to neovascularization only in the presence of local ischemia
Authors: B. Dean Westenbrink, Hisko Oeseburg, Pim Van der Harst, Adriaan A. Voors, Regien G. Schoemaker, Dirk J. van Veldhuisen, Wiek H. van Gilst, Rudolf de Boer
Journal: Journal of the American College of Cardiology (2008)
Economic Impact of Surgical Complications on Hospitals—Reply
Authors: Mark A. Healy, Justin B. Dimick
Journal: JAMA Surgery (2016)

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