tbuckley/cabot-search huggingface dataset:
Abstract 18971: Heart Transplantation for Adult Patients With Congenital Heart Disease: Are the Outcomes Still Worse Than in the General Population in 2015?
Authors: Diego Moguillansky, Biagio A Pietra, Frederick J Fricker, Mark S Bleiweis
Journal: Circulation (2015)

Introduction: Short and medium term outcome after heart transplantation has steadily improved over the last few decades. Outcomes for adult patients with congenital heart disease (ACHD) who undergo transplantation are generally considered to be less favorable. Hypothesis: We hypothesized that the development of heart teams that specialize in ACHD would lead to improved outcomes after transplantation in this population. Methods: We reviewed the records of all patients undergoing first heart transplant at a university center with a dedicated ACHD team over the last 10 years. Patients undergoing re-transplantation were excluded. We looked at short (30 days) and medium term (1 year) survival after heart transplantation in ACHD patients. Results: Between 1/1/05 and 6/10/15, 258 patients underwent heart transplantation. Of the 258 patients, 17 were re-transplants and were excluded. Of the remaining 241 patients, 12 were ACHD patients and 229 were transplanted for other diagnosis (general group). In the general group 184 of 212 (86.8%) patients were alive at 1 year (the remaining 17 did not have sufficient follow up to be included in the 1-year survival analysis). In the ACHD group 9 of 9 patients (100%) were alive at 1 year. The remaining 3 ACHD patients with insufficient follow up to be included in the 1-year survival analysis were still alive 2.5-9.5 months after transplant, such that all 12 ACHD patients survived at least 30 days and were discharged home after heart transplant. At the end of the study period 160 of 229 (70%) patients were still alive in the general group, compared to 8 of 12 (66.7%) in the ACHD group. Conclusions: Short and medium term survival after heart transplantation appears to be no worse for selected ACHD patients compared to the general population. Larger studies with longer follow up are needed to confirm our findings and clarify the intermediate and long-term outcomes of ACHD patients undergoing heart transplantation in the modern era.
Use of Mathematical Modeling to Compare and Predict Hemodynamic Effects Between Hybrid and Surgical Norwood Palliations for Hypoplastic Left Heart Syndrome
Authors: Tain-YenHsia, DariaCosentino, ChiaraCorsini, GiancarloPennati, GabrieleDubini, FrancescoMigliavacca
Journal: Circulation (2011)

Background—Combining bilateral pulmonary artery banding with arterial duct stenting, the hybrid approach achieves stage 1 palliation for hypoplastic left heart syndrome with different flow characteristics than those after the surgical Norwood procedures. Accordingly, we used computational modeling to assess some of these differences, including influence on systemic and cerebral oxygen deliveries. Methods and Results—A 3-dimensional computational model of hybrid palliation was developed by the finite volume method, along with models of the Norwood operation with a modified Blalock-Tausig or right ventricle–to–pulmonary artery shunt. Hybrid circulation was modeled with a 7-mm ductal stent and bilateral pulmonary artery banding to a 2-mm diameter. A 3.5-mm conduit was used in the Blalock-Tausig shunt model, whereas a 5-mm conduit was used in the right ventricle–to–pulmonary artery shunt model. Coupled to all the models was an identical hydraulic network that described the entire circulatory system based on p...
Conference on the Role of the Renal Pressor System in Maintenance of Experimental Renal Hypertension
Authors: Harrygoldblatt
Journal: Circulation (1958)

The hypothetical presence of increased circulating renin or hypertensin in chronic renal hypertension was debated; eventually it was agreed that methods were too insensitive for accurate assay. Pressor amounts of infused renin could not be detected by some methods of bioassay (Dr. Wakerlin). Hypertensinase activity in blood may destroy the end product before the assay can be performed (Dr. Blaquier). Perhaps rapid tissue removal from circulating blood may account for the inadequacy of the results (Dr. Skeggs). Previous experiments to detect these substances in circulating hypertensive blood have been indecisive (Dr. Braun-Menendez) or only weakly positive (Drs. Goldblatt and Skeggs) and the clear-cut depressor effects of antirenin might act on a hypothetical nonpressor action of renin (Dr. Wakerlin). Dr. Helmer commented on the sustained pressor substance found in renal vein blood of hypertensive rats. Dr. Grollman believed chronic renal hypertension to be due to interference with an essential function o...
Adiponectin Suppresses Pathological Microvessel Formation in Retina Through Modulation of Tumor Necrosis Factor-α Expression
Authors: AkikoHiguchi, KojiOhashi, ShinjiKihara, KennethWalsh, NoriyukiOuchi
Journal: Circulation Research (2009)

The fat-derived hormone adiponectin has been shown to have a protective role in macrovascular disorders. However, nothing is known about the function of adiponectin in retinal microvessel disease. Here, we investigated the causal role of adiponectin in retinal vessel formation and inflammation under conditions of hypoxia. When neonatal mice were subjected to ischemia-induced retinopathy, pathological retinal neovascularization during ischemia was exacerbated in adiponectin-knockout (APN-KO) mice compared with wild-type mice (neovascular area: 17.0±1.0% versus 11.7±0.6%, respectively). APN-KO mice also exhibited increased leukocyte adhesion (2.3±0.4-fold) and tumor necrosis factor (TNF)-α expression (2.6±0.2-fold) in hypoxic retina. Adenovirus-mediated overexpression of adiponectin attenuated hypoxia-induced pathological retinal neovascularization by 35% in wild-type mice and by 40% in APN-KO mice and leukostasis by 64% in wild-type mice and by 75% in APN-KO mice, which were associated with reduced TNF-α p...
12 Weeks of a Ribavirin‐Free Sofosbuvir and Nonstructural Protein 5A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation
Authors: Pauline Houssel‐Debry, Audrey Coilly, Claire Fougerou‐Leurent, Caroline Jezequel, Christophe Duvoux, Victor De Ledinghen, Sylvie Radenne, Nassim Kamar, Vincent Leroy, Vincent Di Martino, Louis D'Alteroche, Valérie Canva, Filomena Conti, Jerome Dumortier, Hélène Montialoux, Pascal Lebray, Danielle Botta‐Fridlund, Albert Tran, Christophe Moreno, Christine Silvain, Camille Besch, Philippe Perre, Claire Francoz, Armando Abergel, François Habersetzer, Maryline Debette‐Gratien, Carole Cagnot, Alpha Diallo, Stéphane Chevaliez, Emilie Rossignol, Aurélie Veislinger, Jean‐Charles Duclos‐Vallee, Georges‐Philippe Pageaux
Journal: Hepatology (2018)

Sofosbuvir (SOF) combined with nonstructural protein 5A (NS5A) inhibitors has demonstrated its efficacy in treating a recurrence of hepatitis C virus (HCV) after liver transplantation (LT). However, the duration of treatment and need for ribavirin (RBV) remain unclear in this population. Our aim was to determine whether LT recipients could be treated with an SOF + NS5A inhibitor-based regimen without RBV for 12 weeks post-LT. Between October 2013 and December 2015, 699 LT recipients experiencing an HCV recurrence were enrolled in the multicenter ANRS CO23 CUPILT cohort. We selected patients receiving SOF and NS5A inhibitor ± RBV and followed for at least 12 weeks after treatment discontinuation. The primary efficacy endpoint was a sustained virological response 12 weeks after the end of treatment (SVR12). Among these 699 patients, 512 fulfilled the inclusion criteria. Their main characteristics were: 70.1% genotype 1, 18.2% genotype 3, 21.1% cirrhosis, and 34.4% previously treated patients. We identified four groups of patients according to their treatment and duration: SOF + NS5A without RBV for 12 (156 patients) or 24 (239 patients) weeks; SOF + NS5A + RBV for 12 (47 patients) or 24 (70 patients) weeks. SVR12 values reached 94.9%, 97.9%, 95.7%, and 92.9%, respectively (P = 0.14). Only 20 patients experienced a treatment failure. Under multivariate analysis, factors such as fibrosis stage, previous treatment, HCV genotype, and baseline HCV viral load did not influence SVR12 rates in the four groups (P = 0.21). Hematological adverse events (AEs) were more common in the RBV group: anemia (P < 0.0001) and blood transfusion (P = 0.0001).SOF + NS5A inhibitors without RBV for 12 weeks constituted reliable therapy for recurrent HCV post-LT with an excellent SVR12 whatever the fibrosis stage, HCV genotype, and previous HCV treatment. (Hepatology 2018; 00:000-000).
Abstract 3323: Role of RNA methyltransferase METTL3 in melanoma
Authors: Ujwal Dahal, Kang Le, Mamta Gupta
Journal: Cancer Research (2018)

Abstract Melanoma is the sixth most common cancer in the USA. Introduction of BRAF inhibitors and advances in cancer immunotherapy has greatly improved treatment of melanoma, however, the problem of tumour relapse and therapy resistance persists. Better understanding of the mechanism of development of the diseases is urgently needed to improve therapeutic intervention. Role of DNA and histone modifications have been well established in several diseases, however, RNA modifications, specifically, N6 methyl adenosine (m6A), has only recently begun to be shown to play critical role in cancer. m6A plays crucial roles in mRNA stability, splicing, export, translation and decay and is regulated by: methyltransferase complex proteins METTL3, METTL14, and WTAP; the demethylases FTO and ALKBH5, and the m6A reader proteins. In the present study, we uncover the role of RNA methyltransferase METTL3 in human melanoma cells. METTL3 expression was assessed in 8 melanoma cell lines (A375, A375MA2, A2058, WM164, 451Lu, WM793, SKMEL2, WM3918). Western blotting data revealed METTL3 to be upregulated in seven melanoma cell lines (except A2058) relative to normal melanocytes. To uncover the role of METTL3 in melanoma, we knockdown METTL3 with lentiviral shRNA and studied the effect on melanoma cells tumorigenesis. The colony formation assay revealed reduced colony number in the METTL3 knockdown A375, A375MA2 and WM793 cells relative to the scrambled control cells. The main cause of melanoma associated fatality is its metastatic dissemination we therefore, next sought to investigate whether METTL3 could affect melanoma cells migration and invasiveness. We performed migration and invasion assays to detect the migratory potential of control or METTL3 knockdown A375, A375MA2 and WM793 cells. Interestingly, both migration and invasion was found to be reduced in METTL3 knockdown cells in all the three cell lines examined. RNA dot blot assay demonstrated a decreased m6A level in total RNA of the METTL3 knockdown cells relative to control cells. p16 and p53 mRNA were found to be enriched in m6A immunoprecipitated samples as compared to IgG control, pointing towards a potential role of m6A in regulating expression of melanoma associated genes. Ongoing effort is aimed at identifying what known or novel regulators of the migratory/invasive cascade is regulated by METTL3 and whether it is through m6A mediated or independent mechanisms. In summary, we have shown that METTL3 is overexpressed in human melanoma and play an important role in metastasis. Citation Format: Ujwal Dahal, Kang Le, Mamta Gupta. Role of RNA methyltransferase METTL3 in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3323.
Abstract 4725: Blockade of cyclin D-CDK4/6 sensitizes immune-refractory tumor cells to tumor antigen-specific T cell-mediated cytotoxicity by repressing SCP3-NANOG axis
Authors: Se Jin Oh, Tae Woo Kim
Journal: Cancer Research (2018)

Abstract Antitumor immune drives tumor cell to acquire immune-refractory phenotypes. Previously, we demonstrated tumor antigen-specific T cells edited them resistant to CTL killing and enriched NANOGhigh cancer stem cell-like (CSC-like) cells. In this study, in an effort to elucidate targetable pathways of immune-edited tumor cells with the multiaggressiveness, we show synaptonemal complex protein 3 (SCP3), a member of Cor1 family, which is overexpressed in the immune-edited cells, upregulates NANOG by hyperactivating cyclin D1-CDK4/6 axis. The SCP3-cyclin D1-CDK4/6 axis was preserved across various types of human cancer and, notably, negatively correlated with the progression-free survival of cervical cancer patients. Moreover, targeting CDK4/6 with its inhibitor, palbociclib, succeeded in reversing the multiaggressive phenotypes of immune-edited tumor cells, and led to long-term control of the disease. Collectively, our findings establish a firm molecular link of multiaggressiveness among SCP3, NANOG, cyclin D1, and CDK4/6, and identify CDK4/6 inhibitors as an actionable drug for controlling SCP3high immune-refractory cancer. Citation Format: Se Jin Oh, Tae Woo Kim. Blockade of cyclin D-CDK4/6 sensitizes immune-refractory tumor cells to tumor antigen-specific T cell-mediated cytotoxicity by repressing SCP3-NANOG axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4725.
Prospective outcomes trial of immediate, implant breast reconstruction using acellular dermal matrix (POBRAD Trial): Pilot series results.
Authors: David Westbroek, Michael Douek
Journal: Journal of Clinical Oncology (2012)

1131 Background: Acellular dermal matrices (ADM) are biological meshes of dermal origin (allo- or xenografts) stripped of all cellular components leaving a structurally intact and immunologically inert extracellular matrix. They are currently in use as adjunctive subdermal scaffolding during implant breast reconstruction to optimise aesthetic outcome. Despite current use in clinical practice there is no prospective data on their clinical efficacy, associated complication rates and cost-benefit analysis. These are the endpoints of our pilot cohort series, intended to provide baseline event rates to help power a multi-centre prospective, phase II, outcomes cohort study. Methods: From July 2011 to January 2012 and with our institution review board's approval - 20 consecutive patients undergoing immediate, implant breast reconstruction were prospectively accrued to the study. Primary endpoints: 30-day complication rates; Secondary endpoints: cosmetic outcome and cost-benefit analysis. Indications for mastectomy included therapeutic intent and/or risk reduction. The ADM used in all cases was SurgiMend PRS (TEI Bioscience Inc. Boston, MA). Results: Preliminary 30 day complication rates are in keeping with peer reviewed estimates for implant based breast reconstruction. Sub-set analysis of cosmetic outcome and cost-benefit ratio's are currently pending. In overview, ADM's appear to deliver the aesthetic benefit of autologous- implant cover (eg. latissimus dorsi myocutaneous flap) without the downside of donorsite morbidity and prolonged in-patient admission. Conclusions: This is to our knowledge the only prospectively accrued dataset seeking to critically evaluate the clinical efficacy, cost-benefit value and enhanced aesthetic utillity of ADMs (SurgiMend PRS) in the immediate breast reconstruction setting. The early results provide new evidence in support of the use ADMs in breast reconstruction and validate our intention to extend the study to a multicentre trial.
Abstract 5432: Cancer-induced hypercalcemia promotes breast cancer progression via AP-1 transcription factor mediated upregulation of malignancy-associated genes
Authors: Heather K. Beasley, Sarrah E. Widatalla, Stephen D. Williams, Diva S. Whalen, Olga Y. Korolkova, Amos M. Sakwe
Journal: Cancer Research (2018)

Abstract Cancer-induced hypercalcemia (CIH), is common in breast cancer patients with metastatic disease and in up to 30% of cases with solid tumors without evidence of metastasis. However, its role in the development of large and aggressive breast tumors remain poorly understood. In this study, we show that prolong exposure of triple negative breast cancer (TNBC) cells to high Ca2+ is accompanied by reduced sensitivity of the calcium sensing receptor to high Ca2+, increased growth and tumor cell motility. Gene expression profiling of TNBC cells cultured at high Ca2+ (5.0 mM) revealed that in addition to early response genes (FOS/FOSB), high extracellular Ca2+ also modulated the expression of MAGEC2/CT10 and PAI-2 and other malignancy associated genes (MAGs). To determine whether the expression of MAGs is regulated by FOS/FOSB we show that down regulation of FOSB strongly inhibited the high Ca2+-induced expression of MAGEC2 and that FOSB, as a component of the AP-1 transcription factor bound to the MAGEC2 promoter at high Ca2+. We also show that down regulation of MAGEC2 or FOSB affected the migration and proliferation of TNBC cells at high Ca2+. These data suggest that high Ca2+-induced expression of malignancy promoting genes such as MAGEC2/CT10 underlie the successful tumor cell survival, growth and/or motility in calcium-rich microenvironments and presumably, during the hypercalcemia prone late stages of the disease. This research is supported by NIH/NIGMS 5SC2 CA170244 and 1SC1 CA211030, NIH/NCI 2U54CA 163069-07 Citation Format: Heather K. Beasley, Sarrah E. Widatalla, Stephen D. Williams, Diva S. Whalen, Olga Y. Korolkova, Amos M. Sakwe. Cancer-induced hypercalcemia promotes breast cancer progression via AP-1 transcription factor mediated upregulation of malignancy-associated genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5432.
Dual-Chamber Pacing in the Treatment of Neurally Mediated Tilt-Positive Cardioinhibitory Syncope
Authors: RichardSutton, MicheleBrignole, CarloMenozzi, AntonioRaviele, PaoloAlboni, PaoloGiani, AngelMoya
Journal: Circulation (2000)

Background—This study was performed to compare implantation of a DDI pacemaker with rate hysteresis with no implant in respect to syncopal recurrences in patients with severe cardioinhibitory tilt-positive neurally mediated syncope. Methods and Results—Forty-two patients from 18 European centers were randomized to receive a DDI pacemaker programmed to 80 bpm with hysteresis of 45 bpm (19 patients) or no pacemaker (23 patients). Inclusion criteria were ≥3 syncopes over the last 2 years and a positive cardioinhibitory (Vasovagal Syncope International Study types 2A and 2B) response to tilt testing. The median number of previous syncopal episodes was 6; asystolic response to tilt testing was present in 36 patients (86%) (mean asystole, 13.9±10.2 seconds). All patients were followed up for a minimum of 1.0 years and a maximum of 6.7 years (mean, 3.7±2.2). One patient (5%) in the pacemaker arm experienced recurrence of syncope compared with 14 patients (61%) in the no-pacemaker arm (P=0.0006). In the no-pacema...
Biventricular Circulatory Support With Two Miniaturized Implantable Assist Devices
Authors: ThomasKrabatsch, EvgenijPotapov, AlexanderStepanenko, MartinSchweiger, MarianKukucka, MichaelHuebler, EwaldHennig, RolandHetzer
Journal: Circulation (2011)

Background—Up to 30% of patients with end-stage heart failure experience biventricular failure that requires biventricular mechanical support. For these patients, only bulky extracorporeal or implantable displacement pumps or the total artificial heart have been available to date, which enables only limited quality of life for the patients. It was our goal to evaluate a method that would allow the use of 2 implantable centrifugal left ventricular assist devices as a biventricular assist system. Methods and Results—Seventeen patients have been implanted with 2 HeartWare HVAD pumps, 1 as a left ventricular assist device and 1 as a right ventricular assist device. Seventy-seven percent of the patients had idiopathic dilated or ischemic cardiomyopathy. Their age ranged from 29 to 73 years (mean 51.8±14.5 years), and 11 (64.7%) received intravenous catecholamine support preoperatively. The right ventricular assist device pump was implanted into the right ventricular free wall. The afterload of this pump was ar...
Abstract 5768: MG1122, a whole IgG-like bispecific antibody targeting mesothelin and CD3, induces T cell-mediated killing of MSLN-expressing tumor cells
Authors: Yun-Jung Lee, Okjae Lim, Munkyung Kim, Jeewon Lee, Kisu Kim, Junhong Jung, SuA Lee, Sung Keun Kim, Haenaem Kwon, Yangmi Lim, Yong Yea Park, Jonghwa Won
Journal: Cancer Research (2018)

Abstract Mesothelin (MSLN) is an antigen overexpressed in several malignancies, including mesothelioma and ovarian and pancreatic adenocarcinoma. It has been studied as a marker for diagnosis and a target for immunotherapy. Here, we adopted a bispecific antibody format for recruiting cytotoxic T cells to kill tumor cells. MG1122 is a novel, whole IgG-like bispecific antibody which recognizes CD3 on T cells and MSLN on tumor cells. MG1122 induced effective killing of MSLN-expressing tumor cells. This response was associated with robust activation of T cells as shown by nuclear factor of activated T cells (NFAT) activation, CD25 and CD69 upregulation and increased cytokine release. In addition, using a live cell analysis system, we found that levels of activated caspase 3/7 were amplified in the tumor cells by MG1122 treatment. Although MSLN is a surface antigen, it also exists as a secreted isoform, which can lead to tumor evasion against MSLN targeting antibodies. However, despite the high concentration of soluble MSLN, MG1122 still effectively bound and showed strong killing effects against MSLN-expressing tumor cells. Taken together, our MSLN/CD3 bispecific antibody, MG1122 offers a promising opportunity to redirect T cells to kill MSLN-expressing cancer cells. Citation Format: Yun-Jung Lee, Okjae Lim, Munkyung Kim, Jeewon Lee, Kisu Kim, Junhong Jung, SuA Lee, Sung Keun Kim, Haenaem Kwon, Yangmi Lim, Yong Yea Park, Jonghwa Won. MG1122, a whole IgG-like bispecific antibody targeting mesothelin and CD3, induces T cell-mediated killing of MSLN-expressing tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5768.