tbuckley/cabot-search huggingface dataset:
Genistein enhances cell kill in cisplatin-sensitive and resistant ovarian cancer cells
Authors: Leigh A. Solomon, Adnan R. Munkarah, Veronica L. Schimp, Shadan Ali, Fazlul H. Sarkar
Journal: Cancer Research (2005)

1502  Purpose: Platinum-resistance continues to be a major problem in the management of epithelial ovarian cancer (EOC). Response to various chemotherapeutic agents is poor in patients determined platinum-resistant. Genistein, a soy isoflavone, has been shown to enhance the effect of chemotherapy in pancreatic cancer cells by reversing chemo-resistance pathways. The goal of this study is to investigate the in-vitro effects of combination therapy with genistein and cisplatinum in platinum-sensitive and resistant epithelial ovarian cancer cells. Materials/Methods: The cisplatinum-sensitive human epithelial ovarian cancer cell line A2780 and its cisplatinum-resistant clone C200 were obtained and grown in RPMI 1640 media with L-glutamine, insulin, 10% fetal bovine serum and penicillin and streptomycin. Cells were subjected to treatments consisting of media alone for control, genistein 10μM, cisplatinum at various concentrations (range 100 to 500nM) and the combination of genistein and cisplatinum 24 hours after plating. The cell viability was analyzed at 48 and 72 hours after treatment with the MTT colorimetric assay. Statistical analysis was performed using the unpaired t-test with 95% confidence intervals. Results: Treatment of A2780 and C200 cells with 10μM genistein alone for 72 hours resulted in a reduction in cell survival of 43.5% and 22.8%, respectively. In the A2780 cell line, treatment with cisplatinum at concentrations ranging form 100 to 500 nm resulted in significant cell kill ranging from 17% to 63% after 72 hours of exposure. The combination treatment with 10 μM genistein and similar concentrations of cisplatinum significantly enhanced the cytotoxic effect of cisplatinum alone, increasing cell kill to 49 to 73% (P
The Addition of a Defibrillator to Resynchronization Therapy Decreases Mortality in Patients With Nonischemic Cardiomyopathy
Authors: Bethany Doran, Chaoqun Mei, Paul D. Varosy, David P. Kao, Leslie A. Saxon, Arthur M. Feldman, David DeMets, Michael R. Bristow
Journal: JACC Heart Failure (2021)

The aim of this study was to determine whether patients with heart failure with reduced ejection fraction (HFrEF) due to nonischemic etiology eligible for cardiac resynchronization therapy (CRT) benefit from an implantable cardioverter-defibrillator (ICD). It is uncertain whether CRT with an ICD (CRT-D) compared to without an ICD (CRT-P) is associated with a survival benefit in patients with nonischemic etiologies of HFrEF. Analyses of the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial were performed, using Cox proportional hazards modeling stratified by HFrEF etiology of nonischemic cardiomyopathy (NICM) or ischemic cardiomyopathy (ICM). The primary outcome was all-cause mortality (ACM), and secondary outcomes were the combination of cardiovascular mortality or heart failure hospitalization and sudden cardiac death. Among patients randomized to CRT (n = 1,212), 236 (19.5%) died, 131 and 105 in the CRT-P and CRT-D arms, respectively. The unadjusted and adjusted hazard ratios (HRs) for CRT-D versus CRT-P were both 0.84 (95% confidence interval [CI]: 0.65 to 1.09) for ACM, with a significant device-etiology interaction (pinteraction = 0.015 adjusted; pinteraction = 0.040 unadjusted). In patients with NICM (n = 555), CRT-D versus CRT-P was associated with reduced ACM (adjusted HR: 0.54; 95% CI: 0.34 to 0.86), while patients with ICM (n = 657) did not exhibit a between-device reduction in ACM (adjusted HR: 1.05; 95% CI: 0.77 to 1.44). The effects of CRT-D versus CRT-P on sudden cardiac death (advantage CRT-D) and cardiovascular mortality or heart failure hospitalization (no difference between CRT-P and CRT-D) were similar between the 2 HFrEF etiologies. COMPANION patients with NICM exhibited a decrease in ACM associated with CRT-D but not CRT-P treatment, whereas patients with ICM did not.
Distinct MiR-126 Expression Describes a Non-Genetic but Functional Intra-Tumoral Heterogeneity in Primary Human B-ALL and Can be Prospectively Used to Identify Aggressive Subclones in NSG Mice
Authors: Carolina Caserta, Matteo Maria Naldini, Silvia Nucera, Davide Cittaro, Giacomo Desantis, Francesca Pavesi, Grazia Fazio, Giovanni Cazzaniga, Fabio Ciceri, Bernhard Gentner
Journal: Blood (2017)
109P Subsequent therapies after progressing to CDK4/6 inhibition (CDK4/6i) in hormone receptor positive/HER2 negative (HR+/HER2-) advanced breast cancer (ABC)
Authors: J.C. Laguna, F. Brasó-Maristany, T. Pascual, A. Rodriguez Hernandez, N. Chic, F. Schettini, E. Sanfeliu Torres, B. Gonzalez-Farre, D. Martínez, P. Galván, V. Díez-Guardia, B. Adamo, M. Vidal, M.C. Guillen Sacoto, R. Moreno, A. Prat, M. Muñoz, O. Martínez-Sáez
Journal: Annals of Oncology (2021)
Skeletal Muscle-Specific Deletion of STAT3 Impaired Angiogenesis During Hindlimb Ischemia
Authors: Ohshima Hideki, Yasukawa Hideo, Nagata Takanobu, Kyogoku Sachiko, Ohba Toyoharu, Mawatari Kazutoshi, Futamata Nobuyoshi, Sasaki Kenichiro, Imaizumi Tsutomu
Journal: Circulation (2011)
Retinal biomarkers in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis
Authors: Yi-Jun Ge, Wei Xu, Ya-Nan Ou, Yi Qu, Ya-Hui Ma, Yu-Yuan Huang, Xue-Ning Shen, Shi-Dong Chen, Lan Tan, Qian-Hua Zhao, Jin-Tai Yu
Journal: Ageing Research Reviews (2021)
CalTrack: High-Throughput Automated Calcium Transient Analysis in Cardiomyocytes
Authors: Yiangos Psaras, Francesca Margara, Marcelo Cicconet, Alexander J. Sparrow, Giuliana G. Repetti, Manuel Schmid, Violetta Steeples, Jonathan A.L. Wilcox, Alfonso Bueno-Orovio, Charles S. Redwood, Hugh C. Watkins, Paul Robinson, Blanca Rodriguez, Jonathan G. Seidman, Christine E. Seidman, Christopher N. Toepfer
Journal: Circulation Research (2021)

[Figure: see text].
A participant-derived xenograft model of HIV enables long-term evaluation of autologous immunotherapies
Authors: Chase D. McCann, Christiaan H. van Dorp, Ali Danesh, Adam R. Ward, Thomas R. Dilling, Talia M. Mota, Elizabeth Zale, Eva M. Stevenson, Shabnum Patel, Chanson J. Brumme, Winnie Dong, Douglas S. Jones, Thomas L. Andresen, Bruce D. Walker, Zabrina L. Brumme, Catherine M. Bollard, Alan S. Perelson, Darrell J. Irvine, R. Brad Jones
Journal: The Journal of Experimental Medicine (2021)

HIV-specific CD8+ T cells partially control viral replication and delay disease progression, but they rarely provide lasting protection, largely due to immune escape. Here, we show that engrafting mice with memory CD4+ T cells from HIV+ donors uniquely allows for the in vivo evaluation of autologous T cell responses while avoiding graft-versus-host disease and the need for human fetal tissues that limit other models. Treating HIV-infected mice with clinically relevant HIV-specific T cell products resulted in substantial reductions in viremia. In vivo activity was significantly enhanced when T cells were engineered with surface-conjugated nanogels carrying an IL-15 superagonist, but it was ultimately limited by the pervasive selection of a diverse array of escape mutations, recapitulating patterns seen in humans. By applying mathematical modeling, we show that the kinetics of the CD8+ T cell response have a profound impact on the emergence and persistence of escape mutations. This “participant-derived xenograft” model of HIV provides a powerful tool for studying HIV-specific immunological responses and facilitating the development of effective cell-based therapies.
Abstract 13109: Oral and Intravenous Iron Therapy for Iron Deficiency Anemia After Cardiac Surgery
Authors: Venturini Elio, Venturini Veronica, Francesco Giallauria
Journal: Circulation (2020)

Introduction: cardiac surgery is associated with a high risk to develop iron deficiency anemia (IDA) with impact on the Cardiac Rehabilitation (CR) program. Sucrosomial Iron (SI) is a new oral iron with good gastrointestinal compliance and bioavailability Hypothesis: to compare SI with Ferric Carboxymaltose (FCM) i.v. the gold standard treatment for IDA. Methods: 67 consecutive patients admitted to a CR unit after cardiac surgery (27 CABG, 29 valves/aortic surgery, 11 CABG+valves) were alternately treated with SI or FCM. Blood parameters were assessed at the admission (8-10 days after surgery) (T1), at discharge (18-22 days after surgery) (T2) and 10 days from discharge (T3). The study design provides for a single dose of 1000 mg of FCM at T1 or a dose of 120 mg of SI per day for the first 8-10 days after T1; then SI was scaled to 30 mg/die up to T3. Two groups were comparable in terms of age (SI vs FCM: 67.3 ± 12.8 vs 70.2 ± 12.2) and ejection fraction (SI vs FCM: 52.7% ± 7.8 vs 53.9% ± 5.4). Because the small sample size, non-normal distributed longitudinal variables were logarithmically transformed, to guarantee the maximum possible power to the analysis. Results: data are shown in the following table. At T1, two treatment groups showed no statistically significant difference. Hemoglobin significantly increased in both groups, without significant difference at T3. Transferrin saturation and Sideremia significantly increase in both groups, although the correction is faster with FCM. Ferritin, elevated to baseline for inflammatory condition after surgery, is reduced in the SI group, while it increases significantly in FCM group. Conclusions: SI is able to correct post-surgical IDA in times and ways comparable to i.v. FCM. The hyperferritinemia observed with FCM at T2 may be due to a low-grade pro-inflammatory effect correlated to the high level of iron deposition in macrophages. SI is able to recover IDA and to achieve normal Ferritin values, avoiding the risk of hyperferritinemia.
Abstract 12962: Prognostic Value of Simultaneous Hybrid <sup>18</sup> F-fluorodeoxyglucose Positron Emission Tomography/magnetic Resonance Imaging in Cardiac Sarcoidosis
Authors: Takatoyo Kiko, Masayoshi Oikawa, ATSUSHI KOBAYASHI, Akiomi YOSHIHISA, Takayoshi Yamaki, Yasuchika Takeishi
Journal: Circulation (2020)

Background: Cardiac magnetic resonance imaging with late gadolinium enhancement (LGE) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) are widely used modalities for the diagnosis of cardiac sarcoidosis. The aim of this study was to examine the prognostic value of simultaneous hybrid 18 F-FDG PET/MRI in cardiac sarcoidosis. Methods: Forty-three consecutive patients with suspected cardiac sarcoidosis underwent cardiac FDG PET/MRI. The patients were categorized based on the presence or absence of LGE and/or FDG uptake in the myocardium. The end points were defined as composite of all-cause death, sustained ventricular tachyarrhythmia, hospitalization due to decompensated heart failure and a decline of left ventricular ejection fraction more than 10%. Results: During the median follow-up of 3.7 ± 1.3 years, there were 16 (33%) adverse events. Accumulated event rate was higher in the LGE positive group than in the LGE negative group (log-rank, P &lt; 0.001, Figure A) Additionally, the FDG positive group showed higher adverse event rate than the FDG negative group (P &lt; 0.001, Figure B). Furthermore, adverse event rate was highest in the both PET- and LGE-positive group among 4 groups (P &lt; 0.001, Figure C). In the Cox proportional hazard analysis adjusted for other potential confounding factors, the presence of LGE and the presence of FDG uptake were independent predictors of adverse events (LGE: HR 11.1, 95% CI 1.3-92.4, P = 0.013; FDG: HR 4.4, 95% CI 1.4-13.2, P = 0.007) in cardiac sarcoidosis. Conclusion: Simultaneous cardiac PET/MRI with FDG identifies patients at higher risk for adverse events in patients with cardiac sarcoidosis.
Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study
Authors: Oliver Zivanovic, Dennis S. Chi, Qin Zhou, Alexia Iasonos, Jason A. Konner, Vicky Makker, Rachel N. Grisham, Amy K. Brown, Stacy Nerenstone, John P. Diaz, Eric D. Schroeder, Carrie L. Langstraat, Viktoriya Paroder, Yulia Lakhman, Krysten Soldan, Katy Su, Ginger J. Gardner, Vaagn Andikyan, Jianxia Guo, Elizabeth L. Jewell, Kara Long Roche, Tiffany Troso-Sandoval, Stuart M. Lichtman, Lea A. Moukarzel, Kimberly Dessources, Nadeem R. Abu-Rustum, Carol Aghajanian, William P. Tew, Jan Beumer, Yukio Sonoda, Roisin E. O'Cearbhaill
Journal: Journal of Clinical Oncology (2021)

The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery.Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics.Of 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard (P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory.HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.
Abstract #1084: PXR agonist Rifampicin induces growth-arrest and apoptosis in CD133+ brain tumor stem cells
Authors: Sharmistha Chakraborty, Saravanan Kanakasabai, John Bright
Journal: Cancer Research (2009)

Brain tumors are among the most devastating cancers that present unique challenges to therapy and pose major health problems around the world. Glioblastoma is the common brain tumorwith a median survival of less than one year fromthe time of diagnosis. Standard therapy for glioma consistsof surgical resectionfollowed by radiotherapy and chemotherapy, which have side-effects and limited efficacy. Multi-drug resistance and recurrence are some of the challenges that warrant new targets and therapies for successful treatment of brain tumors. Brain tumor stem cells (BTSCs) are a small population of cancer cells that promotes recurrence, growth and angiogenesis of brain tumor. Typical therapies target tumor cells while sparing the BTSCs, which have high tumorigenecity and drug resistance. Nuclear receptors are a family of ligand-dependent transcription factors that regulate cell growth, differentiation and homeostasis. Pregnane X receptor (PXR; NR1I2) is an orphan nuclear hormone receptor that functions as xenosensor to protect from chemical challenges. Rifampicin is a PXR agonist that induces PXR/RXR heterodimerization, expression of xenobiotic enzymes and clearance of toxic substances. However, the role of PXR in the regulation of brain tumor and BTSCs is not known. In this study we examined the use of PXR to target BTSCs for the treatment of brain tumors. We isolated CD133+ BTSCs from T98G and U87MG human glioma cells and expanded them as gliospheres in neurobasal medium with B27, EGF and bFGF. Real-time PCR analysis showed that the T98G and U87MG glioma cells express low levels of PXR mRNA and that increased significantly in BTSCs expanded as gliospheres. Western blot analysis showed that U87MG and T98G glioma cells express low levels of PXR protein that also significantly increased in BTSC. Interestingly, in vitro treatment with Rifampicin, a PXR agonist, induced a dose-dependent inhibition of gliosphere formation and expansion of CD133+ BTSCs. 3H Thymidine uptake and WST-1 assays showed that Rifampicin inhibits the proliferation and survival of BTSCs in culture. Propidium iodide staining and flow cytometry revealed that Rifampicin induces cell cycle arrest in BTSCs in culture. Further analysis by Anexin V staining and flow cytometry confirmed that Rifampicin induces apoptosis in BTSCs and glioma cells in a dose-dependent manner in culture. Transplantation (s.c.) of T98G and U87MG-derived BTSCs at the lower dorsum of nude mice resulted in the development of solid tumors in 7 to 15 days. Interestingly, the mice treated (i.p.) with 100 \#956;g Rifampicin resulted in a significant reduction in the size of BTSC-induced solid tumor growth in nude mice. These findings highlight the fact that PXR and its agonists could be used to target BTSCs for the treatment of brain tumors.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1084.
Social inequalities and hospital admission for unintentional injury in young children in Scotland: A nationwide linked cohort study
Authors: Paul M. Henery, Ruth Dundas, S. Vittal Katikireddi, Alastair Leyland, Rachael Wood, Anna Pearce
Journal: The Lancet Regional Health - Europe (2021)

Unintentional injury is a leading cause of death/disability, with more disadvantaged children at greater risk. Understanding how inequalities vary by injury type, age, severity, and place of injury, can inform prevention.For all Scotland-born children 2009-2013 (n=195,184), hospital admissions for unintentional injury (HAUI) were linked to socioeconomic circumstances (SECs) at birth: area deprivation via the Scottish Index of Multiple Deprivation (SIMD), mother's occupational social class, parents' relationship status. HAUI was examined from birth-five, and during infancy. We examined HAUI frequency, severity, injury type, and injury location (home vs. elsewhere). We estimated relative inequalities using the relative indices of inequality (RII, 95% CIs), before and after adjusting for demographics and other non-mediating SECs.More disadvantaged children were at greater risk of any HAUI from birth-five, RII: 1•59(1•49-1•70), 1•74(1•62-1•86), 1•97(1•84-2•12) for area deprivation, maternal occupational social class, and relationship status respectively. These attenuated after adjustment (1•15 [1•06-1•24], 1.22 [1•12-1•33], 1.32 [1•21-1•44]). Inequalities were greater for severe (vs. non-severe), multiple (vs. one-off) and home (vs. other location) injuries. Similar patterns were seen in infancy, excluding SIMD-inequalities in falls, where infants living in more disadvantaged neighbourhoods were at lower risk (0•79 [0•62-1•00]). After adjustment, reverse SIMD-gradients were also observed for all injuries and poisonings.Children living in more disadvantaged households are more likely to be injured across multiple dimensions of HAUI in Scotland. Upstream interventions which tackle family-level disadvantage may be most effective at reducing childhood HAUI.Wellcome Trust, Medical Research Council, Scottish Government Chief Scientist Office.
Abstract P193: Psychosocial Profiles And Hypertension Control: Results From The Multi-ethnic Study Of Atherosclerosis (MESA)
Authors: Emily A Vargas, Kiarri N Kershaw, Diana Chirinos, Mandy Wong, Susan A Everson-Rose
Journal: Circulation (2021)

Introduction: Increasing research demonstrates psychosocial factors are associated with blood pressure control (BPC) among individuals with hypertension. To date, little research has examined multiple psychosocial factors simultaneously to identify distinguishing profiles among individuals with hypertension. The association of psychosocial profiles and BPC remains unknown. Thus, the goal of this study was to characterize the psychosocial profiles of individuals with hypertension and assess whether they are associated with BPC over 14 years. Hypothesis: We hypothesize that discrete psychosocial profiles will emerge, and they will be associated with BPC longitudinally. Methods: We included 2,665 MESA participants (38.57% Black; 55.43% Female) with prevalent hypertension in 2002-2004. Latent Profile Analysis (LPA) was used to identify distinct psychosocial profiles based on a combination of nine psychosocial variables (Table). We used generalized estimating equations to determine associations of the psychosocial profiles with BPC, defined as systolic blood pressure (SBP) &lt; 140 mm Hg and diastolic blood pressure (DBP) &lt; 90 mm Hg. Results: The LPA revealed an optimal model of three psychosocial profile groups (AIC 121,229; entropy = .88) namely “Healthy”, “Depressed Mood” and “Discriminated Against”. There were no significant differences in BPC of both targets (SBP and DBP) combined across the profiles. Examining SBP and DBP separately, participants in the “Depressed Mood” profile group were 60% less likely [95% CI: 0.43, 0.84] to have their DBP &lt; 90 mm Hg as compared to the “Healthy” profile in the unadjusted model, but there was no association with covariate adjustment. Conclusions: Discrete psychosocial profiles exist among individuals with hypertension, but were not associated with BPC after full covariate adjustment.
Abstract 15629: Optimal Metrics for Assessing Donor-recipient Size Mismatch in Pediatric Heart Transplantation: A PHTS Multi-institutional Analysis
Authors: Shahnawaz Amdani, Othman Aljohani, James K Kirklin, Ryan Cantor, Devin Koehl, Kurt Schumacher, Deipanjan Nandi, Michael Khoury, William Dreyer, Kristen Rose-Felker, Colleen M Nasman, Mariska Kemna
Journal: Circulation (2020)

Introduction: Traditional weight &amp; height ratios as measures of donor-recipient (D-R) matching have been challenged in adult heart transplantation (HT). The optimal metrics for D-R matching in pediatric HT remain unclear, and were evaluated in the present study. Methods: All primary pediatric HT recipients in the Pediatric Heart Transplant Society database transplanted from 1993-2019 were included. Multiple metrics of size matching - height, weight, body mass index (BMI), body surface area (BSA), predicted heart mass (PHM) and total cardiac volume (TCV) were assessed to identify the metrics that would best predict 1-year post-transplant (PTx) graft loss (death/re-transplant). Kaplan-Meier analyses (risk unadjusted) and multivariate Cox proportional hazard models (risk adjusted) were used to assess the effect of differences of various size matching metrics on survival. Results: Among 6903 D-R pairs, multivariable hazard modeling identified the following risk factors for PTx mortality: female sex, black race, bilirubin, ECMO, VAD, mechanical ventilation, ICU admission at the time of transplant, presence of congenital heart disease, early era of transplant, donor ischemic time and cardiopulmonary bypass time. After adjusting for all covariates, increasing size mismatch by height, BSA, or PHM was associated with increased 1-year PTx graft loss, with a disproportionately higher hazard for undersized donors than oversized donors (Figure). Weight, BMI and TCV were not predictive of 1-year PTx graft loss on multivariate analysis. Conclusions: In pediatric HT recipients, increasing size mismatch by height, BSA and PHM is associated with increased 1-year PTx graft loss. Undersizing donors appears to carry a higher risk than oversizing.