tbuckley/cabot-search huggingface dataset:
Phase Ib study of open-label AMG 386 plus paclitaxel (P) and trastuzumab (T) or capecitabine (C) and lapatinib (L) in patients (pts) with HER2+ locally recurrent or metastatic breast cancer (MBC).
Authors: Hans Wildiers, Anthony Goncalves, Margaret Kemeny, Rachel Elizabeth Swart, Gilles Freyer, Nuwan Nanayakkara, Benjamin Wu, Cheryl Ann Pickett-Gies, Peter Andrew Kaufman
Journal: Journal of Clinical Oncology (2012)

529 Background: AMG 386, an investigational peptibody, reduces tumor angiogenesis by blocking interaction of angiopoietins 1 and 2 with the Tie2 receptor. This interim analysis evaluates the tolerability and efficacy of AMG 386 + P/T or C/L in HER2+ MBC. Methods: In part 1, pts in cohorts A1 and A3 (no prior 1 st -line MBC T or L ) received AMG 386 IV QW plus P 80 mg/m 2 IV QW and T 8 mg/kg loading dose, then 6 mg/kg Q3W; pts in cohorts B1 and B3 (history of failed 1 st -line MBC T treatment; no prior L or C) received AMG 386 IV QW plus C 1000 mg/m 2 PO Q12 hrs, days 1-14 Q21D and L 1250 mg PO QD. A1 and B1 received AMG 386 at 10 mg/kg; A3 and B3 received AMG 386 at 30 mg/kg. In part 2, cohorts were expanded to n = 20 if ≤ 1 of 6 or ≤ 2 of 9 pts had dose-limiting toxicities (DLTs). Primary endpoints were adverse events (AEs) and DLTs; secondary endpoints included efficacy and pharmacokinetics (PK). Interim results from A1, A3, and B1 will be presented. Results: 46 pts were enrolled at interim analysis; all received ≥ 1 dose of study treatment (A1, A3, B1; n = 20, 6, 20). The median follow-up for A1, A3, and B1 was 39.6, 22.7, and 31.3 wks. Across cohorts, there was 1 DLT in A1. AEs &gt; 50% were peripheral edema, diarrhea, fatigue and alopecia in A1 and A3 combined, and diarrhea, nausea, palmar-plantar erythrodysaesthesia syndrome (PPES), and peripheral edema in B1. AEs grade ≥3 occurring in &gt; 2 pts were peripheral neuropathy, peripheral sensory neuropathy, dyspnea (n = 5, 4, 3, respectively, in A1 and A3 combined); PPES, diarrhea, and neutropenia (n = 6, 5, 3, respectively, in B1). Objective response rates were 80% in A1, 50% in A3, and 50% in B1. Median (95% CI) progression-free survival was 14.5 mo (6.8-20.5) in A1 and 10.1 mo (3.7-14.7) in B1. Median duration of response (DOR) was 12.6 mo (4.3-20.2) in A1 and 8.5 mo (4.1-not evaluable) in B1. PFS and DOR were not yet evaluable in A3. No changes were apparent in any PK parameters in these combinations relative to within study or historical monotherapy PK data. Conclusions: In this ongoing phase 1b study of pts with HER2+ MBC, interim results suggest that adding AMG 386 to P/T or C/L is tolerable and has antitumor activity. Updated data will be presented.
Sun Protection Among Organ Transplant Recipients After Participation in a Skin Cancer Research Study
Authors: Rebecca I. Hartman, Adele C. Green, Louisa G. Gordon
Journal: JAMA Dermatology (2018)

Because of long-term immunosuppressive therapy, organ transplant recipients experience significantly elevated skin cancer risk1 and mortality.2 Because of increasing rates of transplantation and improved survival among organ transplant recipients, primary skin cancer prevention is essential for organ transplant recipients to reduce their skin cancer burden. Elsewhere we reported the sun protection behaviors among a subset of organ transplant recipients who were at especially high risk of skin cancer because of a history of actinic skin lesions. We found that approximately 50% of the study participants regularly practiced multiple sun protection measures.3 It has been shown elsewhere that specific educational interventions can improve the use of sun protection measures among organ transplant recipients.4 Here we report a significant increase in the number of organ transplant recipients who practiced multiple sun protection behaviors after participation in a skin cancer research study for at least 1 year without any specific educational intervention.
<i>RAS</i> mutations concordance in circulating tumor DNA (ctDNA) and tissue in metastatic colorectal cancer (mCRC): RASANC, an AGEO prospective multicenter study.
Authors: Jean-Baptiste Bachet, Olivier Bouche, Julien Taïeb, Olivier Dubreuil, Marie-Line Garcia, Aurelia Meurisse, Jean-Marc Gornet, Pascal Artru, Samy Louafi, Emilie Soularue, Isabelle Baumgaertner, Romain Coriat, David Tougeron, Thierry Lecomte, Florence Mary, Lysiane Marthey, Helene Blons, Valerie Taly, Franck Bonnetain, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2017)

11509 Background: RAS mutational status is required to prescribe anti-EGFR antibodies in mCRC. In comparison to molecular testing from tumor tissue, the characterization of RAS mutations in ctDNA is a promising and credible way to shorten the workflow. This study reports for the first time the performance of plasma testing in a large prospective series. Methods: Blood samples were prospectively collected before 1 st line chemotherapy in mCRC patients. ctDNA was centrally assessed by NGS using the colon lung cancer V2 Ampliseq panel and by methylation digital PCR assay (WIF or NPY). Tumor tissue testing was done according to routine practice in each center. We expect a minimal kappa coefficient of 0.7 to reflect concordance. In order to have a precision of ± 0.07 with an estimated 5% of non-exploitable data 425 pts had to be included. Results were analyzed separately in the whole study population and in the subgroup of pts with ctDNA evidenced either by the presence of at least 1 mutation or by the presence of 1 methylated biomarker. Results: From 07/2015 to 12/2016, 425 patients were included, and 406 plasma samples were available for analysis. A RAS mutation was detected in 183 plasma samples (45.1%) As compared to tumor mutational status the kappa coefficient was 0.68 (95%CI: 0.61-0.75) with a concordance of 83.7%. Primary tumor removal, metachronous status, absence of liver metastases and peritoneal carcinomatosis were significantly associated with mutant RAS tumor and negative plasma status. In the subgroup of 324 samples for which ctDNA was evidenced, kappa coefficient was 0.85 (95%CI: 0.80-0.91) with a concordance of 92.9%. 23 pts had discordant results: RAS mutation in tumor tissue and not in ctDNA (15 pts, 4.6%), RAS mutation detected in ctDNA but not in tumor tissue (8 pts, 2.5%). Rectal tumor, absence of liver metastases, peritoneal carcinomatosis and tumor tissue cellularity &lt; 10% were associated with discordant cases. Conclusions: We confirm, in this large prospective multicenter study, the high concordance rate for RAS status assessment between blood and tumor samples. This result argues for the use of blood testing in daily practice for pts with detectable ctDNA. Clinical trial information: NCT02502656.
A randomized, controlled pilot trial of the Emotional Faces Memory Task: a digital therapeutic for depression
Authors: Brian M. Iacoviello, James W. Murrough, Megan M. Hoch, Kathryn M. Huryk, Katherine A. Collins, Gary R. Cutter, Dan V. Iosifescu, Dennis S. Charney
Journal: npj Digital Medicine (2018)

Abstract There is an urgent need for more effective treatments for major depressive disorder (MDD). Digital therapeutics, such as computerized cognitive–emotional training interventions, represent a promising new strategy for treating MDD. Here we report a replication of efficacy of a digital cognitive–emotional training intervention designed to enhance cognitive control for emotional information-processing. In a randomized, double-blind, controlled study design, 51 participants with MDD in a current major depressive episode were randomly assigned to participate in a digital cognitive–emotional training regimen (Emotional Faces Memory Task (EFMT); n = 28) involving 18 sessions over 6 weeks, or an active control condition (CT; n = 23) involving computerized working memory training. MDD symptoms were assessed weekly using a clinician-rated measure (Hamilton Depression Rating Scale; Ham-D); and neurocognition (working memory), at baseline and study outcome. Mixed-effects model for repeated measures (MMRM) analysis of all participants randomized revealed a significantly greater reduction in MDD symptom severity (Ham-D) from baseline to outcome in the EFMT group (8.65 points) compared to the CT group (4.77 points) ( F (6,205) = 3.23, p = .005, d = 0.46). Ten of 28 EFMT participants achieved clinical response (≥50% reduction in symptoms) compared to 4 of 23 in CT. Both groups exhibited similar, small improvements in working memory. This replicated the preliminary efficacy of a digital cognitive–emotional training approach for the treatment of MDD. EFMT may be a feasible and effective intervention strategy for MDD, but future studies to elucidate its mechanism of action are warranted. This study is registered with Clinicaltrials.gov (NCT: 01934491).
Progression of Device-Detected Subclinical Atrial Fibrillation and the Risk of Heart Failure
Authors: Jorge A. Wong, David Conen, Isabelle C. Van Gelder, William F. McIntyre, Harry J. Crijns, Jia Wang, Michael R. Gold, Stefan H. Hohnloser, C.P. Lau, Alessandro Capucci, Gianluca Botto, Gerian Grönefeld, Carsten W. Israel, Stuart J. Connolly, Jeff S. Healey
Journal: Journal of the American College of Cardiology (2018)
Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses' Health Study): 30 year follow-up from a prospective cohort study
Authors: Nathalie Eckel, Yanping Li, Olga Kuxhaus, Norbert Stefan, Frank B Hu, Matthias B Schulze
Journal: The Lancet Diabetes & Endocrinology (2018)
Knowledge, attitudes, barriers, and practice of oncologists in promoting physical activity to cancer survivors: An international survey.
Authors: Sarah Jane Hardcastle, Robert Kane, Paola Chivers, Dana Hince, Andrew Dean, Paul Andrew Cohen
Journal: Journal of Clinical Oncology (2018)

103 Background: Few Survivors are meeting the American Cancer Society recommendations of 150-minutes of moderate-intensity physical activity (PA) per week. Despite patients' wishing to receive PA information from their oncologist, many do not receive PA guidance. Given that oncologists review their patients regularly and are perceived as authority figures, they are in a unique position to promote the uptake of durable PA. Future interventions that bypass the oncologist are unlikely to be scalable and hence there is a need to support oncologists to promote PA. The study aim was to investigate knowledge, attitudes, barriers and practices of oncologists toward PA in survivors, and the association between oncologists' own PA behaviour and PA promotion. Methods: Oncologists (n = 123) completed a survey based on the Theory of Planned Behavior (TPB). Participants reported PA promotion behaviour, PA involvement, attitudes, intentions, social norm, perceived behavioural control (PBC), confidence and knowledge of exercise prescription. Structural equation modelling (SEM) evaluated these associations. Results: Less than half of oncologists reported regularly promoting PA to patients (46%). Only 26% were physically active. TPB SEM pathways explained 54.6% of the variance in PA promotion (CFI = 0.905, SRMR = 0.040). Social norm, was the only significant pathway to intention, but also a significant indirect pathway to PA promotion (p = .007). Confidence to promote PA, PBC and intentions were direct significant pathways to PA promotion (p &lt; .05). Exploratory SEM pathways explained 19.6% of the variance in PA behaviour, which in turn explained 13.1% social norm, 10.7% attitude, 10.0% confidence and 17.8% PA promotion behaviour (CFI = 0.921, SRMR = 0.076). PA behaviour was a direct significant pathway to social norm, attitude, confidence, and PA promotion (p &lt; .05). Conclusions: Oncologists reported a modest ability to promote PA, low PA promotion rates and limited knowledge of exercise prescription. Patient PA promotion may be improved through strategies that increase oncologists' PBC, confidence and their own personal PA participation.
Blocking Properdin Prevents Complement-Mediated Hemolytic Uremic Syndrome and Systemic Thrombophilia
Authors: Yoshiyasu Ueda, Takashi Miwa, Damodar Gullipalli, Sayaka Sato, Daisuke Ito, Hangsoo Kim, Matthew Palmer, Wen-Chao Song
Journal: Journal of the American Society of Nephrology (2018)

Background Properdin (P) is a positive regulator of the alternative pathway of complement activation. Although P inhibition is expected and has been shown to ameliorate the alternative pathway of complement-mediated tissue injury in several disease models, it unexpectedly exacerbated renal injury in a murine model of C3 glomerulopathy. The role of P in atypical hemolytic uremic syndrome (aHUS) is uncertain. Methods We blocked P function by genetic deletion or mAb-mediated inhibition in mice carrying a factor H (FH) point mutation, W1206R (FH R/R ), that causes aHUS and systemic thrombophilia with high mortality. Results P deficiency completely rescued FH R/R mice from premature death and prevented thrombocytopenia, hemolytic anemia, and renal disease. It also eliminated macrovessel thrombi that were prevalent in FH R/R mice. All mice that received a function-blocking anti-P mAb for 8 weeks survived the experimental period and appeared grossly healthy. Platelet counts and hemoglobin levels were significantly improved in FH R/R mice after 4 weeks of anti-P mAb treatment. One half of the FH R/R mice treated with an isotype control mAb but none of the anti-P mAb-treated mice developed stroke-related neurologic disease. Anti-P mAb-treated FH R/R mice showed largely normal renal histology, and residual liver thrombi were detected in only three of 15 treated mice. Conclusions These results contrast with the detrimental effect of P inhibition observed in a murine model of C3 glomerulopathy and suggest that P contributes critically to aHUS pathogenesis. Inhibition of P in aHUS may be of therapeutic benefit.
Circular RNAs: a new frontier for cancer diagnosis and therapy
Authors: Miaoci Zhang, Yan Xin
Journal: Journal of Hematology & Oncology (2018)

In recent years, circular RNAs (circRNAs) have attracted considerable attention because they play a significant role in many fields of cancer biology. Additionally, it has become increasingly clear that circRNAs have the potential to make contributions to the successful application of individualized cancer medicine. This brief review introduces circRNAs by describing their potential as a biomarker and therapeutic target and discussing the possible strategies to target them. This review also presents the challenges that are encountered by circRNAs for their definitive entry into clinical practice. Clearly, our understanding of circRNAs helps to add a new dimension to the molecular structure of cancer and will provide many new opportunities for cancer treatment.
Impact of blood count recovery on outcomes of acute myeloid leukemia patients achieving morphologic leukemia-free state
Authors: Wen-Yan Cheng, Yong-Mei Zhu, Zhao Liu, Xiang-Qin Weng, Jing-Ni Sui, Yun-Shuo Chen, Shi-Yang Wang, Yang Shen
Journal: Blood Cancer Journal (2018)
Glomerular disease augments kidney accumulation of synthetic anionic polymers
Authors: Gary W. Liu, Alexander N. Prossnitz, Diana G. Eng, Yilong Cheng, Nithya Subrahmanyam, Jeffrey W. Pippin, Robert J. Lamm, Chayanon Ngambenjawong, Hamidreza Ghandehari, Stuart J. Shankland, Suzie H. Pun
Journal: Biomaterials (2018)
Vitamin A-decorated biocompatible micelles for chemogene therapy of liver fibrosis
Authors: Jian-Bin Qiao, Qian-Qian Fan, Lei Xing, Peng-Fei Cui, Yu-Jing He, Jing-Cheng Zhu, Lirui Wang, Tao Pang, Yu-Kyoung Oh, Chaofeng Zhang, Hu-Lin Jiang
Journal: Journal of Controlled Release (2018)
Plasma Cystatin C is a predictor of renal failure, hepatorenal syndrome, ACLF and mortality in patients with acutely decompensated liver cirrhosis
Authors: Daniel Markwardt, Lesca Holdt, Christian J. Steib, Andreas Benesic, Flemming Bendtsen, Marco Pavesi, Richard Moreau, Mauro Bernardi, Vicente Arroyo, Alexander L. Gerbes
Journal: Hepatology (2016)
Reactive Hyperemia in Legs of Dogs:
Authors: ROBERT J. BACHE, H. E. EDERSTROM
Journal: Circulation Research (1965)

1. In normal dogs 5- and 10-minute occlusions of the femoral artery were followed by periods of reactive hyperemia (RH) whose duration closely approximated the length of occlusion. The resulting vasodilatation repaid about 50% of the blood flow debt, which was calculated from the flow rate measured just prior to occlusion. 2. When the animal's body temperature was lowered to 32°C, the duration and percentage blood flow debt repaid decreased to about one-half and one-third, respectively, of that found at 40°C. Observations of RH during rewarming revealed progressive increases in debt repayment and duration of the hyperemic period. The temperature characteristics of RH suggested that thermolabile factors were responsible for the vasodilatation that resulted from arterial occlusion. 3. Venous occlusion was followed by RH that was considerably reduced, resulting in a debt repayment of about one-fourth of that attained after arterial occlusion. The possibility that high transmural pressure might be a factor in reducing the intensity of RH that followed venous blockage was investigated. However, when a pressure equivalent to that in the carotid artery was maintained in the vasculature by pumping venous blood into the leg with its artery and vein clamped, the RH following restoration of blood flow closely resembled that induced by arterial clamping only. When arterial blood was infused, RH was reduced to the level seen after simple venous occlusion. It was concluded from these results that during venous occlusion some arterial blood entered the vascular bed, and brought with it chemical factors that reduced the degree of vasodilatation. Since total absence of arterial blood inflow was required to cause maximal dilatation, it may be that oxygen lack was involved in relaxation of the vascular wall, as has been implied by the work of investigators using other techniques.
Facial processing abilities and social functioning in pediatric brain tumor survivors, children with autism spectrum disorder, and typically developing children.
Authors: Cole Brodsky, Emily Kauvar Shabason, Jane E. Minturn, Nathan Blum, Robert Schultz, John D Herrington, Matthew Hocking
Journal: Journal of Clinical Oncology (2018)

157 Background: Pediatric brain tumor survivors (PBTS) often experience late effects in social functioning that mirror those seen in children with autism spectrum disorder (ASD). This study evaluated group differences in facial processing abilities and social functioning between school-aged PBTS, children with ASD, and typically developing children (TDC). Methods: PBTS(n=40;65% male; mean age=13.9 years; mean age at diagnosis=5.8 years)were at least 5 years from tumor diagnosis,2 years from end of tumor-directed therapy and absent a multi-system genetic disorder or developmental delay before tumor diagnosis. Participants completed measures of IQ, facial affect/identity recognition(Victoria/Yale Face Processing Battery), and social functioning(Children’s Communication Checklist-2, Vineland Adaptive Behavior Scales,2 nd Ed. and Social Responsiveness Scale, 2 nd Ed.).PBTS data were compared to a previously collected sample of age, gender, and IQ-matched children with ASD(n=41)and TDC (n=39).One-way ANOVA evaluated differences between groups with Tukey post-hoc tests.Results: IQ for PBTS(m=100.9; SD=16.27),ASD(m=100.17; SD=17.09),and TDC(m=104.72; SD=14.0)were all in the average range.One-way ANOVA revealed group differences for facial identity recognition[ F (2,114)=4.8 η²=.09 , p=.01],facial affect recognition[ F (2, 114)=3.8 , η²=.07, p=.024],and all social functioning measures[ p=.000].Tukey tests revealed PBTS facial affect recognition to be significantly worse than TDC(p &lt; .05)and more comparable to youth with ASD for both facial affect and identity recognition.PBTS also showed worse social functioning than TDC and better than ASD youth across social measures( p’s &lt; .01).Conclusions: Findings suggest PBTS demonstrate impairments in facial affect and identity recognition and social functioning compared to TDC.PBTS facial processing abilities appear similar to those of youth with ASD.PBTS may benefit from multi-disciplinary interventions similar to those used in ASD to improve social functioning. Screening facial processing abilities may identify those at higher risk for social functioning deficits.
Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis
Authors: F. Poggio, M. Bruzzone, M. Ceppi, N.F. Pondé, G. La Valle, L. Del Mastro, E. de Azambuja, M. Lambertini
Journal: Annals of Oncology (2018)

The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety.A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy).Nine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46-2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37-4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51-2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49-1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46-1.63, P = 0.651) was observed. A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy.In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients.CRD42018080042.