tbuckley/cabot-search huggingface dataset:
T cells bearing anti-CD19 and/or anti-CD38 chimeric antigen receptors effectively abrogate primary double-hit lymphoma cells
Authors: Keichiro Mihara, Tetsumi Yoshida, Yoshifumi Takei, Naomi Sasaki, Yoshihiro Takihara, Junya Kuroda, Tatsuo Ichinohe
Journal: Journal of Hematology & Oncology (2017)

Patients with B cell lymphomas bearing MYC translocation combined with translocation involving other genes, such as BCL2, BCL3, or BCL6, defined as double-hit lymphoma (DHL), have a poor prognosis. Recent studies expanded the concept to include double-expressing lymphoma (DEL) that co-overexpresses MYC protein with either of those proteins. Accordingly, we defined cytogenetic DHL and DEL as primary DHL. An adoptive T cell immunotherapy with a chimeric antigen receptor (CAR) has been clinically shown to exhibit cytotoxicity in refractory neoplasias. We revealed the marked cytotoxicity of anti-CD19- and/or anti-CD38-CAR T cells against primary DHL cells from patients. CD19- and/or CD38-specific T cells were co-cultured with cytogenetic DHL (n = 3) or DEL (n = 2) cells from five patients for 3 days. We examined whether T cells retrovirally transduced with each vector showed cytotoxicity against DHL cells. Anti-CD19- and/or anti-CD38-CAR T cells were co-cultured with primary DHL cells at an E:T ratio of 1:2 for 3 days. Anti-CD19- and anti-CD38-CAR T cells completely abrogated these DHL cells, respectively. Anti-CD19-CAR T cells synergistically exerted collaborative cytotoxicity against these primary DHL cells with anti-CD38-CAR T cells. Therefore, refractory DHL cells can be efficiently abrogated by the clinical use of T cells with anti-CD19- and/or anti-CD38-CAR.
Survival and Complications Following Surgery and Radiation for Localized Prostate Cancer: An International Collaborative Review
Authors: Christopher J.D. Wallis, Adam Glaser, Jim C. Hu, Hartwig Huland, Nathan Lawrentschuk, Daniel Moon, Declan G. Murphy, Paul L. Nguyen, Matthew J. Resnick, Robert K. Nam
Journal: European Urology (2017)
NEUROMUSCULAR TRAINING EFFECTS ON THE STIFFNESS PROPERTIES OF THE KNEE JOINT AND LANDING BIOMECHANICS OF YOUNG FEMALE RECREATIONAL ATHLETES
Authors: Dan Wang, Giuseppe De Vito, Massimiliano Ditroilo, Eamonn Delahunt
Journal: British Journal of Sports Medicine (2017)

Background Stiffness properties of the knee joint and landing biomechanics are important factors linked to injury risk. Neuromuscular training may mitigate the risk injury and simultaneously improve sports performance. Objective To investigate the effect of neuromuscular training on the stiffness properties of the knee joint and landing biomechanics of young female recreational athletes. Design Quasi-experimental study. Setting Biomechanics laboratory. Participants Twenty-six female recreational athletes. Interventions Intervention group: combined plyometric (drop jump movements, cutting techniques with quick reactions and maximal effort) and resistance (body-weight, dumbbell and Thera-Band ® exercises) training, 3 times/week for 6 weeks; control group: regular physical activity. Main Outcome Measurements Peak torque of the knee extensors, relaxed and contracted muscle stiffness of the vastus lateralis, knee joint musculoarticular stiffness (MAS), and drop vertical jump (DVJ) performance were assessed pre- and post-intervention. Results Post-intervention MAS increased significantly ( pre- 1657.58±338.53 Nm −1 , post- 1930.79±419.15 Nm −1 ) in the intervention group only. Additionally, compared with the control group the intervention group exhibited an increased rate of torque development ( pre- 905.13±90.31 Nms −1 , post- 1076.35±93.14 Nms −1 ), decreased knee valgus ( pre- 7.86±5.86 °; post- 2.48±5.34 °), increased maximum knee flexion ( pre- 73.17±9.32 °; post- 79.68±9.70 °), increased flight time ( pre- 0.43±0.04 s; post- 0.46±0.03 s), an increase in DVJ height ( pre- 0.23±0.04 m; post- 0.26±0.04 m), as well as decreased peak ground reaction force of the first ( pre- 2.44±0.60 Nkg −1 ; post- 1.83± 0.47 Nkg −1 ) and second landings ( pre- 2.34±0.86 Nkg −1 ; post- 2.06±0.92 Nkg −1 ) of the DVJ. Conclusions Neuromuscular training can improve the stiffness characteristics of the knee joint and landing biomechanics of recreational female athletes.
Outcomes of hematopoietic cell transplantation using donors or recipients with inherited chromosomally integrated HHV-6
Authors: Joshua A. Hill, Amalia S. Magaret, Ruth Hall-Sedlak, Anna Mikhaylova, Meei-Li Huang, Brenda M. Sandmaier, John A. Hansen, Keith R. Jerome, Danielle M. Zerr, Michael Boeckh
Journal: Blood (2017)
Increased IL-13 expression is independently associated with neo-osteogenesis in patients with chronic rhinosinusitis
Authors: Sakiko Oue, Mahnaz Ramezanpour, Sathish Paramasivan, Dijana Miljkovic, Clare M. Cooksley, Ahmed Bassiouni, Judy Ou, Alkis J. Psaltis, Peter-John Wormald, Sarah Vreugde
Journal: Journal of Allergy and Clinical Immunology (2017)
Association Between Indulgent Descriptions and Vegetable Consumption: Twisted Carrots and Dynamite Beets
Authors: Bradley P. Turnwald, Danielle Z. Boles, Alia J. Crum
Journal: JAMA Internal Medicine (2017)

This observational study examines the association of labeling vegetables with indulgent descriptions and overall vegetable consumption compared with labeling vegetables with basic or health-focused labels.
Abstract 277: Development of Anxiety- and Depression-Like Behavior in Mice After Myocardial Infarction
Authors: Anna Frey, Sandy Popp, Antonia Post, Marc Lehmann, Anna-Leena Sirén, Georg Ertl, Klaus-Peter Lesch, Stefan Frantz
Journal: Circulation Research (2012)

Objective: Anxiety and depression are common and independently predict mortality in patients with heart failure. The mechanisms of these interrelations are still unclear. Consequently, we developed a model in C57BL/6 mice with experimental myocardial infarction (MI) and heart failure to study anxiety- or depression-like behavior. Methods: Heart failure was achieved after coronary artery ligation in 13 mice; 16 sham operated mice acted as controls. Left ventricular (LV) remodeling was assessed by echocardiography, infarct size by histology. Sucrose preference test was performed over a period of 8 weeks to assess depression-like behavior. The elevated plus maze (EPM), the light-dark box (LDB) and the open field (OF) tests were subsequently applied to determine general disinterest and anxiety-like behavior. Finally, the histological and immunohistochemical evaluation of the brain was performed. Results: Mice with MI size of at least 30% of LV (averaged 50±3%; increase in diastolic LV diameter from 0.40±0.02 cm to 0.62±0.03 cm) showed diminished intake (p=0.029) and preference (p=0.029) for sucrose solution. Besides, MI mice exhibited reduced exploratory behavior and markedly lower interest in unfamiliar environments, indicated by an increase in center time (p=0.016) and a reduced number of vertical rears (p=0.037) in the EPM. An increased latency to the first rear (p=0.018), covered shorter distances (p=0.048) and spent less time moving (p=0.028) in the OF were found in MI mice. MI did not affect anxiety-related measures in all three tests (all p&gt;0.05). MI mice showed normal brain morphology with normal neuronal morphology and neuropil structure, also confirmed by normal expression of selected neuronal markers. Markers for neurodegeneration, apoptosis or inflammation showed no abnormalities in MI mice. Conclusions: Mice with MI exhibited anhedonia-like behavior, which was accompanied by other characteristics of depression-like behavior, such as decreased exploratory activity and interest in novelty. Hence, MI caused distinct behavioral changes in mice comparable to symptoms observed in humans with heart failure and comorbid depression, but did not affect anxiety-like behavior. The model is suitable for further mechanistic studies.
Abstract 346: A Novel Interaction Between E2F and β-adrenergic Pathways Regulates Survival and Growth in Murine Myocardium
Authors: Jennifer L Major, Maysoon Salih, Balwant S Tuana
Journal: Circulation Research (2015)

The E2F/Pocket protein (Rb) pathway regulates cell growth, differentiation, and death by modulating gene expression. We previously examined this pathway in myocardium via manipulation of E2F6, which represses gene activity independently of Rb. Mice with cardiac specific expression of E2F6 develop dilated cardiomyopathy (DCM) without any signs of hypertrophic growth. We assessed the mechanisms of the apparent failure of compensatory growth as well as their response to the β-adrenergic agonist isoproterenol (iso). E2F6 transgenic (Tg) mice present with left ventricle dilation and significantly reduced ejection fraction as early as 2 weeks which persists into adulthood, but with no apparent increase in left ventricle weight: body weight (LVW:BW). E2F6-Tg mice treated with iso show double the increase in LVW: BW than their Wt counterparts (32% vs 16%, p-value: 0.007). Western blot revealed a specific activation of the β2-adrenergic pathway in Tg myocardium under basal conditions including a ~2-fold increase in β2-adrenergic receptors (β2-AR) (p-value: 8.9E-05), protein kinase A catalytic subunit (PKA-C) (p-value: 0.0176), activated c-SRC tyrosine-protein kinase (p-value: 0.0002), and an induction of the anti-apoptotic gene Bcl2. In contrast, a ~70% decrease in the cardiac growth regulator: AKT1 (p-value 0.0001) and a 4-fold increase in cyclic AMP dependent phosphodiesterase 4D (PDE4D), the negative regulator of PKA activity, was evident in Tg myocardium. The expression of E2F3 was de-regulated by E2F6, but was restored by iso while Rb expression was down-regulated. Thus deregulation of E2F/Rb pathway by E2F6 altered the β-adrenergic signaling pathway such that survival signaling was activated while hypertrophy was repressed resulting in the development of DCM without any increase in muscle mass. These data reveal a novel interplay between E2F and the β adrenergic pathway which regulate cardiac growth and fate.
Trastuzumab combined with doublet or single-agent chemotherapy as a first-line treatment for HER2-positive metastatic breast cancer.
Authors: Yunfang Yu, Ying Wang, Kai Chen, Tuping Fu, Herui Yao
Journal: Journal of Clinical Oncology (2017)

e12511 Background: To investigate the efficacy and safety of doublet vs. single-agent chemotherapy (CT) plus trastuzumab as first-line treatments for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). Methods: We searched for randomized clinical trials (RCTs) that investigated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcome measures for this analysis included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Meta-analyses and trial sequential analyses (TSA) were conducted. The study quality was evaluated using the GRADE framework. The PROSPERO registry number is CRD42016043766. Results: The results from four RCTs that included 1,044 participants were pooled. Moderate-quality evidence indicated that doublet CT+H better correlated with prolonged PFS (hazard ratio [HR] = 0.69, 95% confidence interval (CI) 0.63 to 0.75, P &lt; 0.0001) and OS (HR = 0.90, 95% CI 0.88 to 0.92, P &lt; 0.0001) than did single-agent CT+H; however, moderate-quality evidence indicated there was no significant difference between the two drug regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98 to 1.17, P = 0.157), as confirmed by TSA, which indicated that the cumulative Z-curve entered the futility area. There was moderate-quality evidence that the treatment-related grade 3 to 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000; number needed to treat to harm (NNTH) = 20), nausea/vomiting (RR = 4.26, P = 0.002; NNTH = 25), diarrhea (RR = 2.81, P = 0.002; NNTH = 25), and stomatitis (RR = 5.02, P= 0.003; NNTH = 25) were more frequent with doublet CT+H than single-agent CT+H. Conclusions: Doublet CT+H is associated with longer PFS and OS than single-agent CT+H when used as a first-line therapy for HER2-positive MBC.
Drinking Water Salinity and Raised Blood Pressure: Evidence from a Cohort Study in Coastal Bangladesh
Authors: Pauline F.D. Scheelbeek, Muhammad A.H. Chowdhury, Andy Haines, Dewan S. Alam, Mohammad A. Hoque, Adrian P. Butler, Aneire E. Khan, Sontosh K. Mojumder, Marta A.G. Blangiardo, Paul Elliott, Paolo Vineis
Journal: Environmental Health Perspectives (2017)

Background: Millions of coastal inhabitants in Southeast Asia have been experiencing increasing sodium concentrations in their drinking-water sources, likely partially due to climate change. High (dietary) sodium intake has convincingly been proven to increase risk of hypertension; it remains unknown, however, whether consumption of sodium in drinking water could have similar effects on health. Objectives: We present the results of a cohort study in which we assessed the effects of drinking-water sodium (DWS) on blood pressure (BP) in coastal populations in Bangladesh. Methods: DWS, BP, and information on personal, lifestyle, and environmental factors were collected from 581 participants. We used generalized linear latent and mixed methods to model the effects of DWS on BP and assessed the associations between changes in DWS and BP when participants experienced changing sodium levels in water, switched from "conventional" ponds or tube wells to alternatives [managed aquifer recharge (MAR) and rainwater harvesting] that aimed to reduce sodium levels, or experienced a combination of these changes. Results: DWS concentrations were highly associated with BP after adjustments for confounding factors. Furthermore, for each 100mg/L reduction in sodium in drinking water, systolic/diastolic BP was lower on average by 0.95/0.57mmHg, and odds of hypertension were lower by 14%. However, MAR did not consistently lower sodium levels. Conclusions: DWS is an important source of daily sodium intake in salinity-affected areas and is a risk factor for hypertension. Considering the likely increasing trend in coastal salinity, prompt action is required. Because MAR showed variable effects, alternative technologies for providing reliable, safe, low-sodium fresh water should be developed alongside improvements in MAR and evaluated in "real-life" salinity-affected settings. https://doi.org/10.1289/EHP659
Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): Preliminary data from KEYNOTE-086 cohort B.
Authors: Sylvia Adams, Sherene Loi, Deborah Toppmeyer, David W. Cescon, Michele De Laurentiis, Rita Nanda, Eric P. Winer, Hirofumi Mukai, Kenji Tamura, Anne Armstrong, Minetta C. Liu, Hiroji Iwata, Larisa Ryvo, Pauline Wimberger, Deborah Card, Yu Ding, Vassiliki Karantza, Peter Schmid
Journal: Journal of Clinical Oncology (2017)

1088 Background: Standard first-line treatment for mTNBC is chemotherapy. However, outcomes are poor, and new treatment options are needed. Cohort B of KEYNOTE-086 (NCT02447003) assessed the safety and antitumor activity of pembrolizumab as first-line therapy for patients (pts) with PD-L1–positive mTNBC. Methods: Men and women with centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, ECOG PS 0-1, and a tumor PD-L1 combined positive score (CPS) ≥1% received pembrolizumab 200 mg Q3W for 24 mo or until disease progression, intolerable toxicity, or investigator or pt decision. Tumor imaging was performed Q9W for 12 mo and Q12W thereafter. Clinically stable pts with PD could remain on pembrolizumab until PD was confirmed on subsequent assessment. Primary end point was safety. Secondary end points included ORR, DOR, and PFS (RECIST v1.1, central review). Planned enrollment was 80 pts. This analysis included all pts who had ≥18 wk of follow-up as of Nov 10, 2016. Results: 79 of the first 137 pts with PD-L1–evaluable tumors (58%) had PD-L1 CPS ≥1%. Of the first 52 pts enrolled, 100% were women, median age was 53 y, 40% had elevated LDH, 69% had visceral metastases, and 87% received prior (neo)adjuvant therapy. After a median follow-up of 7.0 mo (range 4.4-12.5), 15 (29%) pts remained on pembrolizumab. Treatment-related AEs occurred in 37 (71%) pts, most commonly fatigue (31%), nausea (15%), and diarrhea (13%). 4 (8%) pts experienced 5 grade 3-4 treatment-related AEs: back pain, fatigue, hyponatremia, hypotension, and migraine (n = 1 each). No pts died or discontinued pembrolizumab due to an AE. ORR was 23% (95% CI 14%-36%). Best overall response was CR in 4%, PR in 19%, SD in 17%, PD in 58%, and not assessed in 2%. Median time to response was 8.7 wk (range 8.1-17.7). Median DOR was 8.4 mo (range, 2.1+ to 8.4), with 8 (67%) responses ongoing at cutoff. Median PFS was 2.1 mo (95% CI, 2.0-3.9); estimated 6-mo PFS rate was 29%. Conclusions: Data from the first 52 pts enrolled in KEYNOTE-086 cohort B suggest that pembrolizumab monotherapy has a manageable safety profile and promising antitumor activity as first-line therapy for PD-L1–positive mTNBC. Clinical trial information: NCT02447003.
Unfolding the Clinical Potential of DNA and Protein Origami
Authors: Tracy Hampton
Journal: JAMA (2017)

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Sentinel lymph node biopsy using indocyanine green fluorescence navigation method after neoadjuvant chemotherapy for patients with clinically node-positive breast cancer.
Authors: Kazuhiko Yamagami, Hajime Matsumoto, Takashi Hashimoto, Seiji Yanai, Sachiko Yuen, Hitomi Kuramitu, You Ichinose, Teruyuki Deai, Masakazu Toi
Journal: Journal of Clinical Oncology (2017)

e12108 Background: Sentinel lymph node biopsy (SNB) for initially clinically node-positive (cN1) after neoadjuvant chemotherapy (NAC) is controversial. Even if approximately 40% of node positive disease converts to node negative after NAC, SNB using blue dye (BD) and/or radioisotope (RI) agent showed the high false-negative rate (FNR) (SENTINA, ACOSOG Z1071). These trials showed the accuracy of SNB was closely related to the number of sentinel lymph nodes (SNs) removed. We presented the efficacy of indocyanine green (ICG) fluorescence navigation method for SNB in clinically node-negative (cN0) patients (ASCO2008). The ICG method can provide higher numbers of SNs and it helps to identify lymph nodes with the remained metastases. Methods: Of 1900 patients (Jan. 2010 - Dec. 2016), 242 women with cN0 or cN1 received NAC: Group 0 (cN0 before NAC, n=150), Group 1 (cN1 converted ycN0 after NAC, n=71) , Group 2 (cN1 remained ycN1 after NAC, n=21). Node status was evaluated by ultrasound. All patients underwent SNB using both ICG- and BD-method together. Fluorescence images were obtained by a CCD camera with a cut filter as a detector, light emitting diodes at 760nm as the light source. ALND was performed in Group1 and Group 2. Results: Pathological complete nodal response rate (pcNRR) was 48.4%. Table shows the number of SNs removed by ICG or BD. SNs detection rates (ICG, BD): Group 0 (98.7%, 84.7%), Group 1 (98.6%, 83.1%), Group 2 (85.7%, 47.6%). Resulting of a FNR (ICG, BD): Group 1 (5.7%, 15.3%), Group 2 (22.2%, 60.0%). Conclusions: The pcNRR and a FNR of BD in Group 1 were similar to those of SENTINA or ACOSOGZ 1071 trials. In patients who converted from cN1 to ycN0, the fluorescent ICG method showed a high detection rate of SNs and a low FNR. [Table: see text]
Abstract #5116: 5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells
Authors: Jae Eun Shin, Eun Jeong Choi, Sumi Bae, Jiyun Kim, Mijung Han, Woong Shick Ahn
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

We investigated the effects of combined treatment with 5-fluorouracil and apigenin on proliferation and apoptosis, as well as the underlying mechanism, in human breast cancer MDA-MB-453 cells. The MDA-MB-453 cells, which have been shown to overexpress ErbB2, were resistant to 5-fluorouracil; 5-fluorouracil exhibited a small dose-dependent anti-proliferative effect, with an IC50 of 90 \#956;M. Interestingly, combined treatment with apigenin significantly decreased the resistance. Cellular proliferation was significantly inhibited in cells exposed to 5-fluorouracil at its IC50 and apigenin (5, 10, 50, and 100 \#956;M), compared with proliferation in cells exposed to 5-fluorouracil alone. This inhibition in turn led to apoptosis, as evidenced by an increased number of apoptotic cells and the activation of caspase-3. To investigate the mechanism by which the combination of 5-fluorouracil and apigenin induces apoptosis, ErbB2 expression was analyzed. The level of ErbB2 was unchanged by 5-fluorouracil alone but was drastically reduced in cells treated with 5-fluorouracil plus apigenin. Moreover, compared with 5-fluorouracil alone, 5-fluorouracil in combination with apigenin at concentrations >10 \#956;M exerted a pro-apoptotic effect via the inhibition of Akt expression. Taken together, our results suggest that 5-fluorouracil acts synergistically with apigenin to inhibit cell growth and to induce apoptosis via the downregulation of ErbB2 expression and Akt signaling.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5116.