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R C Schoonbeek, P G Pieper, Y J van Slooten, H G Freling, G T Sieswerda, A P J van Dijk, M R M Jongbloed, M C Post, B J Bouma, R M F Berger, T Ebels, J P van Melle
OBJECTIVES: N-terminal B‑type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and a prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients with a prosthetic valve and investigate its relationship with cardiac function and exercise capacity. METHODS: In this multi-centre cross-sectional observational study, data regarding medical history, echocardiography, exercise testing (VO2peak) and laboratory blood evaluation (including NT-proBNP) were collected in ACHD patients with a single prosthetic valve (either homografts, heterografts or mechanical valves)...
November 2016: Netherlands Heart Journal
Stéphane Kajingu Enciso, Maxime Elens, Jean Rubay
We report a case of successful heterograft aortic valve replacement following an impede Ross procedure in a 48-year-old man presenting with a congenital bicuspid pulmonary valve. The patient was admitted for aortic valve stenosis that required an aortic valve replacement (AVR). Owing to his young age and reluctance to long-term anticoagulation therapy, it was decided to do an AVR by pulmonary autograft. During surgery, the anatomical unsuitability of the graft was discovered leading to the procedure's readjustment...
August 22, 2016: Acta Chirurgica Belgica
Joao S Soares, Kristen R Feaver, Will Zhang, David Kamensky, Ankush Aggarwal, Michael S Sacks
The use of replacement heart valves continues to grow due to the increased prevalence of valvular heart disease resulting from an ageing population. Since bioprosthetic heart valves (BHVs) continue to be the preferred replacement valve, there continues to be a strong need to develop better and more reliable BHVs through and improved the general understanding of BHV failure mechanisms. The major technological hurdle for the lifespan of the BHV implant continues to be the durability of the constituent leaflet biomaterials, which if improved can lead to substantial clinical impact...
August 9, 2016: Cardiovascular Engineering and Technology
Hartzell V Schaff
No abstract text is available yet for this article.
August 23, 2016: Circulation
Hamid Reza Davari, Mohammad Bagher Rahim, Nader Tanideh, Mahsa Sani, Hamid Reza Tavakoli, Ali Reza Rasekhi, Ahmad Monabati, Omid Koohi-Hosseinabadi, Siavash Gholami
OBJECTIVES: Large diaphragmatic defects are still a challenging issue for reconstruction using either synthetic prosthesis or bioprosthesis. To evaluate the possibility of using diaphragm allograft as a natural bioprosthesis in humans, we conducted a two-group study and compared cryopreserved and decellularized diaphragmatic heterograft patched in a canine model. METHODS: At the end of organ harvesting from a human donor, the left hemidiaphragm was taken to the laboratory in phosphate-buffered saline solution...
October 2016: Interactive Cardiovascular and Thoracic Surgery
Jun-Xi Xiang, Xing-Long Zheng, Rui Gao, Wan-Quan Wu, Xu-Long Zhu, Jian-Hui Li, Yi Lv
BACKGROUND: The potential application of decellularized liver scaffold for liver regeneration is limited by severe shortage of donor organs. Attempt of using heterograft scaffold is accompanied with high risks of zoonosis and immunological rejection. We proposed that the spleen, which procured more extensively than the liver, could be an ideal source of decellularized scaffold for liver regeneration. METHODS: After harvested from donor rat, the spleen was processed by 12-hour freezing/thawing x 2 cycles, then circulation perfusion of 0...
October 2015: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Robert M Hoffman
The majority of human solid tumours do not metastasize when grown subcutaneously in immunocompromised mice; this includes patient-derived xenograft (PDX) models. However, orthotopic implantation of intact tumour tissue can lead to metastasis that mimics that seen in patients. These patient-derived orthotopic xenograft (PDOX) models have a long history and might better recapitulate human tumours than PDX models.
August 2015: Nature Reviews. Cancer
Ruth Rodriguez-Barrueco, Jiyang Yu, Laura P Saucedo-Cuevas, Mireia Olivan, David Llobet-Navas, Preeti Putcha, Veronica Castro, Eva M Murga-Penas, Ana Collazo-Lorduy, Mireia Castillo-Martin, Mariano Alvarez, Carlos Cordon-Cardo, Kevin Kalinsky, Matthew Maurer, Andrea Califano, Jose M Silva
HER2-positive (HER2(+)) breast adenocarcinomas are a heterogeneous group in which hormone receptor (HR) status influences therapeutic decisions and patient outcome. By combining genome-wide RNAi screens with regulatory network analysis, we identified STAT3 as a critically activated master regulator of HR(-)/HER2(+) tumors, eliciting tumor dependency in these cells. Mechanistically, HR(-)/HER2(+) cells secrete high levels of the interleukin-6 (IL-6) cytokine, inducing the activation of STAT3, which in turn promotes a second autocrine stimulus to increase S100A8/9 complex (calprotectin) production and secretion...
August 1, 2015: Genes & Development
Sun-Hwa Lee, Jun Hwa Hong, Hwan Ki Park, Jun Seok Park, Bo-Kyung Kim, Jung-Yi Lee, Ji Yun Jeong, Ghil Suk Yoon, Masahiro Inoue, Gyu-Seog Choi, In-Kyu Lee
Primary cultures of cancer cells are useful for developing personalized medicine. In this study, we characterized three lines of three-dimensional (3D) tumor spheroids established directly from tumor tissues of patients with colorectal cancers (CRCs). Each line mainly included EpCAM-positive cells and cells expressing putative cancer stem cell markers such as CD133, CD44, CD24, ALDH1, and LGR5. These characteristic stem cell markers remained identically for months in vitro. Short tandem repeat genotyping suggested that genetic fingerprints of these tumor spheroids were similar to those of the original tumor tissues from which they were derived...
October 10, 2015: Cancer Letters
Lenard Conradi, Andreas Schaefer, Goetz C Mueller, Moritz Seiffert, Helmut Gulbins, Stefan Blankenberg, Hermann Reichenspurner, Hendrik Treede, Patrick Diemert
BACKGROUND AND AIM OF THE STUDY: Carcinoid heart valve disease (CHVD) occurs as the cardiac manifestation of carcinoid syndrome (also known as Hedinger's syndrome), which develops secondary to neuroendocrine tumor activity. CHVD almost exclusively affects right-sided heart valves, since circulating serotonin is metabolized by pulmonary endothelial cells, thus sparing left-sided valves. Replacement of the tricuspid and pulmonary valve is a well-established and feasible therapeutic option for these patients...
January 2015: Journal of Heart Valve Disease
Angela B De La Fuente, Gregory A Wright, Jane M Olin, Francis G Duhay, Boguslaw Kapelak, Maciek Bochenek, Krzysztof Bartus, Jerzy Sadowski
BACKGROUND AND AIM OF THE STUDY: Structural valve deterioration (SVD) is the leading failure mode of bioprosthetic heart valves. The Edwards Integrity-Preservation (EIP™) technology was developed to permanently block tissue calcium-binding sites and allow for non-aqueous valve storage. The study aim was to evaluate the efficacy of tissue anti-calcification, valve performance, durability, and safety. METHODS: Bovine pericardial tissue with EIP technology was compared to industry-standard Carpentier-Edwards ThermaFix® and Xenologix® treatments...
January 2015: Journal of Heart Valve Disease
Joel Price, David Glineur, Laurent De Kerchove, Gebrine El Khoury
BACKGROUND AND AIM OF THE STUDY: Mitral annular calcification (MAC) represents a significant challenge in mitral valve (MV) surgery. Techniques to decalcify the mitral annulus significantly increase operative complexity and risk. MV repair can be particularly difficult in this setting. Mid-term outcomes following MV surgery with extensive annular decalcification were examined, with attention focused on the feasibility and outcomes of MV repair in this setting. METHODS: Among 1,485 patients undergoing MV surgery between 1999 and 2008 at the authors' institutions, 24 (1...
January 2015: Journal of Heart Valve Disease
John W Cassidy, Carlos Caldas, Alejandra Bruna
Preclinical models often fail to capture the diverse heterogeneity of human malignancies and as such lack clinical predictive power. Patient-derived tumor xenografts (PDX) have emerged as a powerful technology: capable of retaining the molecular heterogeneity of their originating sample. However, heterogeneity within a tumor is governed by both cell-autonomous (e.g., genetic and epigenetic heterogeneity) and non-cell-autonomous (e.g., stromal heterogeneity) drivers. Although PDXs can largely recapitulate the polygenomic architecture of human tumors, they do not fully account for heterogeneity in the tumor microenvironment...
August 1, 2015: Cancer Research
Rushika M Perera, Svetlana Stoykova, Brandon N Nicolay, Kenneth N Ross, Julien Fitamant, Myriam Boukhali, Justine Lengrand, Vikram Deshpande, Martin K Selig, Cristina R Ferrone, Jeff Settleman, Gregory Stephanopoulos, Nicholas J Dyson, Roberto Zoncu, Sridhar Ramaswamy, Wilhelm Haas, Nabeel Bardeesy
Activation of cellular stress response pathways to maintain metabolic homeostasis is emerging as a critical growth and survival mechanism in many cancers. The pathogenesis of pancreatic ductal adenocarcinoma (PDA) requires high levels of autophagy, a conserved self-degradative process. However, the regulatory circuits that activate autophagy and reprogram PDA cell metabolism are unknown. Here we show that autophagy induction in PDA occurs as part of a broader transcriptional program that coordinates activation of lysosome biogenesis and function, and nutrient scavenging, mediated by the MiT/TFE family of transcription factors...
August 20, 2015: Nature
Felix Dietlein, Bastian Kalb, Mladen Jokic, Elisa M Noll, Alexander Strong, Lars Tharun, Luka Ozretić, Helen Künstlinger, Kato Kambartel, Winfried J Randerath, Christian Jüngst, Anna Schmitt, Alessandro Torgovnick, André Richters, Daniel Rauh, Florian Siedek, Thorsten Persigehl, Cornelia Mauch, Jirina Bartkova, Allan Bradley, Martin R Sprick, Andreas Trumpp, Roland Rad, Dieter Saur, Jiri Bartek, Jürgen Wolf, Reinhard Büttner, Roman K Thomas, H Christian Reinhardt
KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell-cycle checkpoint-abrogating Chk1- and MK2 inhibitors, specifically in KRAS- and BRAF-driven cells. Mechanistically, we show that KRAS-mutant cancer displays intrinsic genotoxic stress, leading to tonic Chk1- and MK2 activity...
July 2, 2015: Cell
Mei-Hong Li, Rolf Swenson, Miriam Harel, Sampa Jana, Erik Stolarzewicz, Timothy Hla, Linda H Shapiro, Fernando Ferrer
The bioactive lipid sphingosine-1-phosphate (S1P) and its receptors (S1P1-5) play critical roles in many pathologic processes, including cancer. The S1P axis has become a bona fide therapeutic target in cancer. JTE-013 [N-​(2,​6-​dichloro-​4-​pyridinyl)-​2-​[1,​3-​dimethyl-​4-​(1-​methylethyl)-​1H-​pyrazolo[3,​4-​b]pyridin-​6-​yl]-​hydrazinecarboxamide], a known S1P2 antagonist, suffers from instability in vivo. Structurally modified, more potent, and stable S1P2 inhibitors would be desirable pharmacological tools...
September 2015: Journal of Pharmacology and Experimental Therapeutics
Jessica Wobb, Sarah A Krueger, Jonathan L Kane, Sandra Galoforo, Inga S Grills, George D Wilson, Brian Marples
PURPOSE: To evaluate the efficacy of low-dose pulsed radiation therapy (PRT) in 2 head and neck squamous cell carcinoma (HNSCC) xenografts and to investigate the mechanism of action of PRT compared with standard radiation therapy (SRT). METHODS AND MATERIALS: Subcutaneous radiosensitive UT-SCC-14 and radioresistant UT-SCC-15 xenografts were established in athymic NIH III HO female mice. Tumors were irradiated with 2 Gy/day by continuous standard delivery (SRT: 2 Gy) or discontinuous low-dose pulsed delivery (PRT: 0...
July 15, 2015: International Journal of Radiation Oncology, Biology, Physics
James W T Yates, Phillippa Dudley, Jane Cheng, Celina D'Cruz, Barry R Davies
PURPOSE: Intermittent dosing of inhibitors of the PI3K/AKT/mTOR network offers the potential to maximize the therapeutic margin. Here, we validate a predictive modeling approach to establish the relative efficacy of continuous and two intermittent dosing schedules of the AKT inhibitor AZD5363. METHODS: A mathematical model of pharmacokinetics, pharmacodynamics and anti-tumor effect was constructed based upon experimental data from dosing regimens that give constant and transient inhibition of the AKT pathway...
August 2015: Cancer Chemotherapy and Pharmacology
Chen Tian, Yong Yu, Yongsheng Jia, Lei Zhu, Yizhuo Zhang
Although aberrant Notch activation contributes to leukemogenesis in T cells, the role of Notch pathway in acute myeloid leukemia (AML) remains controversial. To address this issue, we compared the expression levels of its downstream effector HES1 and p21 in bone marrow mononuclear cells (BMNCs) from 30 newly diagnosed AML patients and three AML cell lines to normal BMNCs. The results showed that both of them were downregulated in AML cells. In vitro, induced activation of HES1 by retrovirus in AML cell lines consistently led to AML cell growth arrest and apoptosis induction, which was associated with enhanced p21 expression...
September 2015: Annals of Hematology
Garyfalia Karponi, Nikoletta Psatha, Carsten Werner Lederer, Jennifer Eileen Adair, Fani Zervou, Nikolaos Zogas, Marina Kleanthous, Constantinos Tsatalas, Achilles Anagnostopoulos, Michel Sadelain, Isabelle Rivière, George Stamatoyannopoulos, Evangelia Yannaki
Globin gene therapy requires abundant numbers of highly engraftable, autologous hematopoietic stem cells expressing curative levels of β-globin on differentiation. In this study, CD34+ cells from 31 thalassemic patients mobilized with hydroxyurea+granulocyte colony-stimulating factor (G-CSF), G-CSF, Plerixafor, or Plerixafor+G-CSF were transduced with the TNS9.3.55 β-globin lentivector and compared for transducibility and globin expression in vitro, as well as engraftment potential in a xenogeneic model after partial myeloablation...
July 30, 2015: Blood
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