tbuckley/cabot-search huggingface dataset:
High concentration of plasma cell free DNA alerted progressive and recurrent disease in children with high risk neuroblastoma.
Authors: Yan Su, Lijun Wang, Chiyi Jiang, Zhixia Yue, Fan Hongjun, Huimin Hong, Chao Duan, Mei Jin, Dawei Zhang, Lihua Qiu, Xianfeng Cheng, Zhong Xu, Xiaoli Ma
Journal: Journal of Clinical Oncology (2019)

e21506 Background: Neuroblastoma (NB) happens most frequently among babies and it is also the third-most common cancer in children after leukemia and brain tumor. The unexpected occurrence of NB progression and relapse accounts for the low survival free event rates, therefore finding an effective biomarker to predict the progressive and recurrent events is urgent. Methods: A total of 116 NB patients with high risk (HR-NB) from Beijing Children’s Hospital between February 1, 2015 and December 31, 2017 were recruited. All patients received the regular multiple-disciplinary treatments and then followed the evaluation for therapeutic response according to the standards of Response Evaluation Criteria in Solid Tumors (RECIST). Blood samples were collected to quantify cell-free DNA levels at important time points including one week before or the beginning of maintenance stage, every or every three month after the beginning of maintenance stage, diagnosis of progression and recurrence. Results: Results showed that 36 HR-NB patients developed progressive disease (PD) and recurrent disease. More intriguingly, cfDNA concentration was extremely higher in NB patients with progression and recurrence than those with events free (29.34 ng/ml VS 10.32 ng/ml), and increasing cfDNA levels happened at least 0.55 months before the progression and recurrence was confirmed. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), it showed that the area of cfDNA level was 0.67 at 12.93 ng/ml with 62.5% sensitivity and 71.3% specificity. Conclusions: Taken together, it was suggested increasing cfDNA concentration in plasma may benefit to warn the incurrence of progression and recurrence in NB patients in clinic, which will help clinicians win much more valuable time to save patients’ lives.
Prospects for Diminishing the Impact of Nonamyloid Small-Vessel Diseases of the Brain
Authors: Anne Joutel
Journal: The Annual Review of Pharmacology and Toxicology (2019)

Small-vessel diseases (SVDs) of the brain are involved in about one-fourth of ischemic strokes and a vast majority of intracerebral hemorrhages and are responsible for nearly half of dementia cases in the elderly. SVDs are a heavy burden for society, a burden that is expected to increase further in the absence of significant therapeutic advances, given the aging population. Here, we provide a critical appraisal of currently available therapeutic approaches for nonamyloid sporadic SVDs that are largely based on targeting modifiable risk factors. We review what is known about the pathogenic mechanisms of vascular risk factor–related SVDs and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most frequent hereditary SVD, and elaborate on two mechanism-based therapeutic approaches worth exploring in sporadic SVD and CADASIL. We conclude by discussing opportunities and challenges that need to be tackled if efforts to achieve significant therapeutic advances for these diseases are to be successful.
Comparing three validated methods of patient self-reported fatigue in a prospective randomized clinical trial.
Authors: Katherine Sams, L. Doug Case, Glenn Jay Lesser, Michelle Joy Naughton, Susan Kidwell Williford, Jeffrey Kent Giguere, Astrid Garino, Mara Vitolins, Edward G. Shaw
Journal: Journal of Clinical Oncology (2012)

9108 Background: Fatigue can be measured with different validated assessment instruments in symptom management trials. Methods: Between 2004-2009, the Wake Forest CCOP Research Base protocol 97202 randomized 236 women receiving adjuvant chemotherapy for newly diagnosed breast cancer to Coenzyme Q10 supplementation vs placebo. The primary endpoint was change in self-reported fatigue. Patients (pt) were assessed at baseline, 8, 16, and 24 weeks (wk) with 3 instruments: 1) Profile of Mood States – Fatigue (POMS; 7 questions; scored 0-4); 2) Functional Assessment of Cancer Treatment – Fatigue (FACIT; 13 questions; scored 0-4); and 3) Visual Analog Scale (VAS; one scale; scored 0-10). For comparison, each instrument was rescaled from 0 to 100; higher numbers indicate worse fatigue. Results: CoQ10 did not significantly affect fatigue (Lesser G et al, ASCO Proc., 2010). All 3 measures demonstrated an increase in fatigue after chemotherapy initiation at 8 &amp; 16 wks with trend towards baseline levels at 24 wks. The fatigue measures were highly correlated: r ≥ 0.8 for all pairwise associations at all times. However, their scores varied. The Table shows mean rescaled scores for pt below/above the median fatigue level, calculated by taking mean of the three scores averaged across the four time periods. In general, POMS tended to give the lowest and VAS the highest scores, but differences between POMS and FACIT and FACIT and VAS depended on mean fatigue level. For pt experiencing lower (&lt;median) fatigue, FACIT and VAS scores were similar, while POMS scores were significantly lower. For higher (&gt;median) fatigue, POMS and FACIT scores were similar, while VAS was significantly higher. Conclusions: While POMS, FACIT, and VAS scores were highly correlated, their scale scores varied depending on the level of fatigue experienced by the pt. Fatigue assessment methods in clinical trials should be selected carefully as they do not always give equivalent results. Supported by NCI/DCP grant U10 CA81851. [Table: see text]
Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study
Authors: Sigrun A.J. Schmidt, Morten Olsen, Morten Schmidt, Christian Vestergaard, Sinéad M. Langan, Mette S. Deleuran, Jette L. Riis
Journal: Journal of the American Academy of Dermatology (2019)

Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation. To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation. Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review. We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors. Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data. Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low.
Effect of radiation on outcome of types II and III PPB: A report from the International Pleuropulmonary Blastoma Registry.
Authors: Gretchen M Williams, John R. Priest, Marsha J Finkelstein, Anne Harris, Leslie Ann Doros, Christian Kratz, Kris Ann Pinekenstein Schultz, D Ashley Hill, Louis P Dehner, Yoav H. Messinger
Journal: Journal of Clinical Oncology (2012)

9521 Background: Pleuropulmonary blastoma (PPB) is a rare dysembryonic lung neoplasm of early childhood with progression from a purely cystic (Type I) lesion to a solid high-grade sarcoma Type III (T-III), or a mixed solid/cystic stage Type II (T-II). Surgery and chemotherapy are required for T-II and T-III PPB, but the benefit of radiation therapy for T-II and T-III PPB is debated and is being evaluated in this study. Methods: This is a retrospective analysis of central pathology-reviewed Types II and III PPB from the IPPBR. Treatments were chosen by physician, were not randomized, and included surgery and chemotherapy. The outcome of patients treated with upfront radiation (before progression or relapse) was compared to patients who did not receive radiation. Event-free survival (EFS) and overall survival (OS) were determined to last follow-up, using the Kaplan-Meier analysis, with log-rank test. Results: Outcome for 212 patients (117 Type-II and 95 Type III) was significantly better for T-II than T-III: EFS for T-II was 68.1% vs. T-III 45.7% (P=0.002), and OS for T-II was 75.2% vs. T-III 57.9% (p=0.01). Excluding patients with incomplete therapy information, 174 were treated with surgery and chemotherapy. Of these 44 (25%) also received radiation therapy; 130 patients did not. The table below shows comparison of radiated vs. non-radiated. Radiation provided no additional survival benefit, overall or by tumor Type. Multivariate analysis showed that gender and extent of primary tumor resection (biopsy vs. gross total resection) had no effect on outcome, however T-II vs. T-III retained prognostic significance. Conclusions: For this collection of advanced-type PPB, outcome is significantly better for T-II than T-III. For patients treated initially with surgery and chemotherapy, adding radiation therapy offered no improvement in event-free or overall survival. Limitations of this study include its retrospective nature and non-uniform treatment regimens. [Table: see text]
Histone chaperone FACT complex mediates oxidative stress response to promote liver cancer progression
Authors: Jialing Shen, Mengnuo Chen, Derek Lee, Cheuk-Ting Law, Lai Wei, Felice Ho-Ching Tsang, Don Wai-Ching Chin, Carol Lai-Hung Cheng, Joyce Man-Fong Lee, Irene Oi-Lin Ng, Carmen Chak-Lui Wong, Chun-Ming Wong
Journal: Gut (2019)

Facilitates Chromatin Transcription (FACT) complex is a histone chaperone participating in DNA repair-related and transcription-related chromatin dynamics. In this study, we investigated its oncogenic functions, underlying mechanisms and therapeutic implications in human hepatocellular carcinoma (HCC).We obtained HCC and its corresponding non-tumorous liver samples from 16 patients and identified FACT complex as the most upregulated histone chaperone by RNA-Seq. We further used CRISPR-based gene activation and knockout systems to demonstrate the functions of FACT complex in HCC growth and metastasis. Functional roles and mechanistic insights of FACT complex in oxidative stress response were investigated by ChIP assay, flow cytometry, gene expression assays and 4sU-DRB transcription elongation assay. Therapeutic effect of FACT complex inhibitor, Curaxin, was tested in both in vitro and in vivo models.We showed that FACT complex was remarkably upregulated in HCC and contributed to HCC progression. Importantly, we unprecedentedly revealed an indispensable role of FACT complex in NRF2-driven oxidative stress response. Oxidative stress prevented NRF2 and FACT complex from KEAP1-mediated protein ubiquitination and degradation. Stabilised NRF2 and FACT complex form a positive feedback loop; NRF2 transcriptionally activates the FACT complex, while FACT complex promotes the transcription elongation of NRF2 and its downstream antioxidant genes through facilitating rapid nucleosome disassembly for the passage of RNA polymerase. Therapeutically, Curaxin effectively suppressed HCC growth and sensitised HCC cell to sorafenib.In conclusion, our findings demonstrated that FACT complex is essential for the expeditious HCC oxidative stress response and is a potential therapeutic target for HCC treatment.
Volumetric Liver Fat Fraction Determines Grade of Steatosis More Accurately Than Controlled Attenuation Parameter in Patients With Nonalcoholic Fatty Liver Disease
Authors: Syaman Harry, Lee Lee Lai, Nik Raihan Nik Mustapha, Yang Faridah Abdul Aziz, Anushya Vijayananthan, Kartini Rahmat, Sanjiv Mahadeva, Wah Kheong Chan
Journal: Clinical Gastroenterology and Hepatology (2019)
Abiraterone in “High-” and “Low-risk” Metastatic Hormone-sensitive Prostate Cancer
Authors: Alex P. Hoyle, Adnan Ali, Nicholas D. James, Adrian Cook, Christopher C. Parker, Johann S. de Bono, Gerhardt Attard, Simon Chowdhury, William R. Cross, David P. Dearnaley, Christopher D. Brawley, Clare Gilson, Fiona Ingleby, Silke Gillessen, Daniel M. Aebersold, Rob J. Jones, David Matheson, Robin Millman, Malcolm D. Mason, Alastair W.S. Ritchie, Martin Russell, Hassan Douis, Mahesh K.B. Parmar, Matthew R. Sydes, Noel W. Clarke
Journal: European Urology (2019)
Translational study associated to a phase II study evaluating the activity of pazopanib in patients (pts) with advanced/metastatic liposarcoma (LPS): A joint Spanish Sarcoma Group (GEIS) and German Interdisciplinary Sarcoma Group (GISG) study.
Authors: Claudia Maria Valverde Morales, Antonio Fernandez Serra, Marta Ramírez-Calvo, Jose A. Lopez-Martin, Cleofe Romagosa, Juan Antonio Carrasco, Sebastian Bauer, Javier Martinez Trufero, Josefina Cruz Jurado, Peter Reichardt, Cesar Serrano, Viktor Grünwald, Pablo Luna Fra, Oscar Persiva, Diego Varona, Rafael Morales-Barrera, Bernd Kasper, Javier Martin Broto, Amparo Ruiz-Sauri, Jose Antonio Lopez-Guerrero
Journal: Journal of Clinical Oncology (2019)

11067 Background: GEIS 30 was a phase II study showing moderate activity of pazopanib in well-differentiated/dedifferentiated LPS (cohort A:37 pts, Progression free Survival (PFS) at 12 weeks (w) 43.2%) and no activity in Myxoid/round cell LPS (cohort B: 15 pts, PFS at 12w 13.3%). The present study aims to identify tumor and plasma biomarkers that are differently expressed in long responders (LRs) PFS &gt; 24 w. Methods: Serum samples and paraffin-blocks at diagnosis were collected for 28 pts in cohort A and 11 in B. A total of 13 pts were LRs. Serum samples were obtained at baseline, after 3 w of treatment and at progression. A panel of 15 cytokines and growth factors were evaluated using Luminex technology (Millipore). Paraffin-blocks were evaluated for microvessel density (MVD) by CD31 immunostaining and Image Pro-Plus 7.0 Image Analysis System (Media-Cybernetics). For RNA expression analysis, the Oncology Biomarker Panel with probes for 2559 transcripts was used (HTG Molecular Diagnostics). Results: Serum cytokines showed that expression of angiopoietin (AGO) and BMP9 decreases during treatment, whereas GCSF increases. In addition, AGO and BMP overexpression at baseline was associated with worse prognosis in arm A (p = 0.09) and B (p = 0.01) respectively. No differences between study arms and outcome were appreciated by MVD. Gene expression revealed differences in some immunomodulators: PDL-1 was correlated with serum cytokines VEGFD (p = 0.04) and LEPTIN (p = 0.02); and PD-1 with VEGFD (p = 0.04), LEPTIN (p = 0.02), VEGFA (p = 0.02) and ANGIO (p = 0.03). PD1, in addition,was overexpressed in LRs (p = 0.05). Interestingly, three groups were identified in cohort A according to gene expression: Cluster 1, characterized by short-responder patients with the shortest overall survival, whereas cluster 3 (40% LRs) and 2 (63.6% LRs) showed longer survival rates (14.3%, 45.5% and 30% respectively) (p = 0.001). Conclusions: Gene expression profiling unveils three WD/DD-LPS biotypes according to their response to pazopanib, which could be potentially used to select pts for treatment
Matrix metalloproteinase 2 (<i>MMP2</i>) polymorphism, <i>Helicobacter pylori</i> (HP) infection and esophageal adenocarcinoma (EA) risk
Authors: G. Liu, M. Fruh, W. Zhou, R. Zhai, L. Su, R. S. Heist, J. C. Wain, T. J. Lynch, F. A. Shepherd, D. C. Christiani
Journal: Journal of Clinical Oncology (2007)

10553 Background: Epidemiologic studies suggest that HP infection protects against EA risk, as HP-mediated chronic atrophic gastritis reduces acid reflux. Genetic variations may modify the host response to HP infection and alter this risk. MMP2 expression is commonly upregulated in HP infections. We hypothesize that a functional MMP2 promoter polymorphism (-C1306T) that abolishes a Sp1 binding site and decreases promoter activity will also reduce the protective effects of HP infections in EA risk. Methods: HP status was determined in 98 EA patients and 101 age and gender matched healthy controls, using a commercially available serum immunoblotting kit (Helicoblot 2.1, Genelabs Diagnostics) that measures ever, current, CagA+ and VacA+ HP infections. Genotyping was performed using TaqMan. Data were analyzed using unconditional logistic regression. Results: 39% of cases and 44% of controls (P=0.69) had MMP2 variants (T/T or C/T). 36% of cases and 42% of controls were ever HP infected (P= 0.35). In individuals carrying the MMP2 wild type (CC) genotype, ever HP infection was strongly protective against EA [Odds Ratio (OR) 0.32: 95% CI, 0.13–0.75; P=0.008]. In contrast, in individuals carrying the MMP2 variants that are associated with lower promoter activity, this protective effect was lost (OR 1.76; 95% CI, 0.06–5.2; P= 0.30). Similar results were found when evaluating the MMP2 and current, CagA or VacA infection. Statistical interactions between MMP2 genotype and ever HP infection (P=0.027) and between MMP2 genotype and VacA+ infection (P= 0.035) were significant. Conclusions: We are the first to report that host factors such as the MMP2 polymorphism modulate the role of HP infection in EA susceptibility. No significant financial relationships to disclose.
Evaluation of a FLT3 Bite® for Acute Myeloid Leukemia
Authors: Rebecca Goldstein, Anja Henn, Priya Koppikar, Ivonne Archibeque, Brendon Frank, Mercedesz Balazs, Christoph Dahlhoff, Tobias Raum, Chi-Ming Li, Joachim Wahl, Dan Rock, Oliver Thomas, Christine Karbowski, Christina Krupka, Marion Subklewe, Angela Coxon, Tara Chapman-Arvedson
Journal: Blood (2017)
Coping with end-of-life stress (EOLS): Poetry as a therapeutic communication intervention.
Authors: Frank L. Meyskens, Johanna F Shapiro, Julia Reinhart Lupton
Journal: Journal of Clinical Oncology (2019)

e23172 Background: Attempts to alleviate EOLS via system changes have been variably successful. Manualized psychotherapeutic interventions have been of some usefulness. Participation in narrative communication has been widely adopted to address stress produced by life threatening events, whether by trauma or acute illness. More recently narrative form of communication has been extended to the EOL time period with some early evidence of limited benefit. Poetry involves a different realm of mental involvement and should impact on existential stressors. However, its use in improving the quality of life during the EOL period has not been explored. Methods: Two open symposia entitled “Healing and Hope: An Evening of Poetry by Patients, Family Members, and Health Professionals“ were held at the University of California-Irvine on February 22, 2018 and January 10, 2019. There were 155 attendees(80, 2018; 75,2019). 20 attendees at the 2019 event also participated in a workshop directed toward writing poetry. Results: Event reports from all 11 Medical Humanities students registered for the Symposia as a required colloqium event were very positive as were essays from 3 medical students in the Art of Doctoring class in attendance. The results and impact of the Symposia were eloquently summarized by another one of the medical students who attended: “The poetry tellers read poems that were very powerful and I was able to hear their pains, joys, and regrets. I enjoyed the discussions held after each panel was finished, which allowed me to hear some of the thoughts of the audience and connect with them. The whole experience was amazing: It really felt like we were all connected via poetry and I think that produced an environment where we could cope with emotions brought by illnesses and medicine.” Conclusions: Poetry reading, writing, and speaking should be explored as a novel educational approach and possible therapeutic tool to address existential stressors produced during and by the EOL time period in an increasingly aging patient population that and results in the well-known diminishment or destruction of their quality of life.
Playing Word Games
Authors: Susan Frances Martinello
Journal: JAMA (2019)

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