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endothelial heterogeneity

Anemari Horvat, Nina Vardjan
To maintain a high level of specificity and normal cell function, the cyclic adenosine monophosphate (cAMP) pathway is tightly regulated in space and time. Recent advances in cAMP reporter technology have provided insights into spatial-temporal characteristics of cAMP signalling in individual living cells, including astrocytes. Astrocytes are glial cells in the central nervous system with many homeostatic functions. In contrast to neurons, astrocytes are electrically silent, but, in response to extracellular stimuli through activation of surface receptors, they can increase intracellular levels of secondary messengers, e...
June 13, 2018: Neuroscience Letters
Erdem Kucukal, Anton Ilich, Nigel S Key, Jane A Little, Umut A Gurkan
In sickle cell disease (SCD), 'disease severity' associates with increased RBC adhesion to quiescent endothelium, but the impact on activated endothelium is not known. Increased concentrations of free heme result from intravascular hemolysis in SCD. Heme is essential for aerobic metabolism, and plays an important role in numerous biological processes. Excess free heme induces reactive oxygen species generation and endothelial activation, which are associated with cardiovascular disorders including atherosclerosis, hypertension, and thrombosis...
June 15, 2018: American Journal of Hematology
Surendra R Punganuru, Hanumantha Rao Madala, Constantinos M Mikelis, Anshuman Dixit, Viswanath Arutla, Kalkunte S Srivenugopal
Tumor heterogeneity and drug resistance pose severe limitations to chemotherapy of colorectal cancers (CRCs) necessitating innovative approaches to trigger multiple cytocidal events for increased efficacy. Here, we developed a hybrid drug called KSS19 by combining the COX-2 selective NSAID rofecoxib with the cis-stilbene found in combretastatin A4 (CA4), a problematic, but potent antimicrotubule and anti-angiogenesis agent. The structural design of KSS19 completely prevented the isomerization of CA4 its biologically inactive trans-form...
May 25, 2018: Oncotarget
Kideok Jin, Niranjan B Pandey, Aleksander S Popel
BACKGROUND: Metastatic triple-negative breast cancer (TNBC) is a heterogeneous and incurable disease. Numerous studies have been conducted to seek molecular targets to treat TNBC effectively, but chemotherapy is still the main choice for patients with TNBC. We have previously presented evidence of the important roles of interleukin-6 (IL-6) and chemokine (C-C motif) ligand 5 (CCL5) in TNBC tumor growth and metastasis. These experiments highlighted the importance of the crosstalk between cancer cells and stromal lymphatic endothelial cells (LECs) in tumor growth and metastasis...
June 14, 2018: Breast Cancer Research: BCR
Virginia H Huxley, Scott S Kemp, Christine Schramm, Steve Sieveking, Susan Bingaman, Yang Yu, Isabella Zaniletti, Kevin Stockard, Jianjie Wang
KEY POINTS: Endothelial dysfunction is an early hallmark of multiple disease states that also display sex differences with respect to age of onset, frequency, and severity. Results of in vivo studies of basal and stimulated microvascular barrier function revealed sex differences difficult to ascribe to specific cells or environmental factors. The present study evaluated endothelial cells (EC) isolated from macro- and/or microvessels of reproductively mature rats under the controlled conditions of low-passage culture to test the assumption that EC phenotype would be sex-independent...
June 9, 2018: Journal of Physiology
Joseph Candiello, Taraka Sai Pavan Grandhi, Saik Kia Goh, Vimal Vaidya, Maya Lemmon-Kishi, Kiarash Rahmani Eliato, Robert Ros, Prashant N Kumta, Kaushal Rege, Ipsita Banerjee
Organoids, which exhibit spontaneous organ specific organization, function, and multi-cellular complexity, are in essence the in vitro reproduction of specific in vivo organ systems. Recent work has demonstrated human pluripotent stem cells (hPSCs) as a viable regenerative cell source for tissue-specific organoid engineering. This is especially relevant for engineering islet organoids, due to the recent advances in generating functional beta-like cells from human pluripotent stem cells. In this study, we report specific engineering of regenerative islet organoids of precise size and cellular heterogeneity, using a novel hydrogel system, Amikagel...
May 25, 2018: Biomaterials
Trivia Frazier, Stephen Lee, Annie Bowles, Julie Semon, Bruce Bunnell, Xiying Wu, Jeffrey Gimble
Adipose tissue is now recognized as a functional organ that contains cellular heterogeneity and diversity within anatomical depots. The stromal vascular fraction (SVF) of adipose contains endothelial progenitors, fibroblasts, lymphocytes, monocyte/macrophages, pericytes, pre-adipocytes, and stromal/stem cells, among others. In recent years, there has been a growing appreciation of the influence of age and gender in the field of stem cell biology. Yet few studies have evaluated the influence of biological age or sex on either SVF cell heterogeneity or immunophenotype...
June 8, 2018: Adipocyte
Savneet Kaur, Rashi Sehgal, Saggere M Shastry, Geoffrey McCaughan, Helen M McGuire, Barbara Fazekas St de Groth, Shiv Sarin, Nirupma Trehanpati, Devanshi Seth
Background and Aim: Endothelial progenitor cells (EPCs) have been implicated in liver injury and repair. However, the phenotype and potential of these heterogenous EPCs remain elusive. In particular, their involvement in the pathogenesis of alcoholic liver cirrhosis (ALC) remains unclear. The current study extensively characterized the phenotype and functions of EPCs to understand their role in ALC pathogenesis. Methods: Circulating EPCs were identified as CD34+CD133+CD31+ cells by flow cytometer in ALC patients ( n = 7) and healthy controls (HC, n = 7)...
2018: Frontiers in Physiology
Antonino Di Stefano, Teresa Coccini, Elisa Roda, Cinzia Signorini, Bruno Balbi, Giuseppe Brunetti, Piero Ceriana
Background and aims: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by different phenotypes with either bronchial airways alterations or emphysema prevailing. As blood biomarkers could be clinically useful for COPD stratification, we aimed at investigating the levels of blood biomarkers in COPD patients differentiated by phenotype: prevalent chronic airway disease versus emphysema. Methods: In 23 COPD patients with prevalent airway disease (COPD-B), 22 COPD patients with prevalent emphysema (COPD-E), 9 control smokers (CSs), and 18 control nonsmokers (CNSs), we analyzed the expression levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, epidermal growth factor (EGF), monocyte chemotactic protein (MCP)-1, and vascular endothelial growth factor by enzyme-linked immunosorbent assay in plasma/serum; glutathione peroxidase and superoxide dismutase (SOD)-1 by immunochemical kits in plasma; and free F2-isoprostanes (F2-IsoPs) by gas chromatography in plasma...
2018: International Journal of Chronic Obstructive Pulmonary Disease
Kristin Pogoda, Petra Kameritsch, Hanna Mannell, Ulrich Pohl
Vascular endothelial cells, as well as smooth muscle cells, show heterogeneity with regard to their receptor expression and reactivity. For the vascular wall to act as a functional unit, the various cells' responses require integration. Such an integration is not only required for a homogeneous response of the vascular wall, but also for the vasomotor behaviour of consecutive segments of the microvascular arteriolar tree. Since flow resistances of individual sections are connected in series, sections require synchronization and coordination manner to allow effective changes of conductivity and blood flow...
June 2, 2018: Acta Physiologica
Xiuping Ding, Jujie Sun, Tingyong Fan, Baosheng Li
RATIONALE: Despite the approval of antiangiogenic therapy for high grade glioma (HGG) patients, survival benefits are still limited. New treatment plans have always been developed to improve the survival. PATIENT CONCERNS: A 26-year-old woman was admitted to our hospital for distending pain of head and eye. DIAGNOSES: Resonance imaging (MRI) revealed a large spherical heterogeneously enhancing, mixed cystic and solid mass in the right frontal region, and the midline shifted...
June 2018: Medicine (Baltimore)
Matteo Santoni, Francesco Massari, Francesco Piva, Francesco Carrozza, Vincenzo Di Nunno, Alessia Cimadamore, Angelo Martignetti, Rodolfo Montironi, Nicola Battelli
Renal cell carcinoma (RCC) represents a heterogeneous group of cancers with distinct histological features, molecular alterations, prognosis, and response to therapy. Target agents directed against vascular endothelial growth factor and its receptor and mammalian target of rapamycin (mTOR) inhibitors have completely changed the landscape of RCC. However, the rate of complete response is still low, thus supporting the research of novel therapeutic agents. Area covered: The authors describe the chemical features of tivozanib, its pharmacodynamic and pharmacokinetic properties, and the results obtained in human phase I-III clinical trials...
May 31, 2018: Expert Opinion on Pharmacotherapy
Irina N Mikhaylova, Irina Zh Shubina, George Z Chkadua, Natalia N Petenko, Lidia F Morozova, Olga S Burova, Robert Sh Beabelashvili, Kermen A Parsunkova, Natalia V Balatskaya, Dmitrii K Chebanov, Vadim I Pospelov, Valeria V Nazarova, Anastasia S Vihrova, Evgeny A Cheremushkin, Alvina A Molodyk, Mikhail V Kiselevsky, Lev V Demidov
Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease. We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment...
May 11, 2018: Oncotarget
Betsy Annel González-Quezada, Uriel Francisco Santana-Bejarano, Alfredo Corona-Rivera, Helia Judith Pimentel-Gutiérrez, Rocío Silva-Cruz, Citlalli Ortega-De-la-Torre, Ramón Franco-Topete, Karina Franco-Topete, Manuel Willebaldo Centeno-Flores, Víctor Manuel Maciel-Gutiérrez, Jorge Román Corona-Rivera, Juan Armendáriz-Borunda, Lucina Bobadilla-Morales
Colorectal cancer (CRC) is the fourth leading worldwide cause of cancer-associated mortalities. Nuclear factor-κB (NF-κB) is a transcriptional regulator of multiple genes associated with CRC. Tumor tissue were compared with normal adjacent mucosa from 30 sporadic patients with CRC were investigated. A total of 8 non-CRC patients were analyzed as a control group. In the present study, the protein expression of NF-κB/p65 was detected by immunohistochemistry, and the gene expression profiles of cyclin D1 (CCND1) , prostaglandin-endoperoxide synthase 2, vascular endothelial growth factor A, matrix metallopeptidase 9, BCL2 apoptosis regulator (BCL2) , BCL2 like 1, nitric oxide synthase 2, tumor necrosis factor and arachidonate lipoxygenase were detected by reverse transcription-quantitative polymerase chain reaction...
May 2018: Oncology Letters
Yoshiyasu Matsumoto, Hiroshi Kashimura, Kenta Aso, Hiroaki Saura, Mitsumasa Osakabe, Akira Kurose
BACKGROUND: Hemorrhage at presentation in primary central nervous system (CNS) lymphoma is rare. We encountered a case of primary CNS lymphoma presenting as a growing intracerebral hemorrhage. CASE DESCRIPTION: An 80-year-old man presented with mild dysarthria. Computed tomography (CT) demonstrated a round, high-density mass with surrounding vasogenic edema in the left frontal lobe. Although the patient was placed on antihypertensive therapy for suspected subacute subcortical hemorrhage, neurological symptoms gradually worsened...
May 23, 2018: World Neurosurgery
J C Kohn, T Abdalrahman, K L Sack, C A Reinhart-King, T Franz
Within the artery intima, endothelial cells respond to mechanical cues and changes in subendothelial matrix stiffness. Recently, we found that the aging subendothelial matrix stiffens heterogeneously and that stiffness heterogeneities are present on the scale of one cell length. However, the impacts of these complex mechanical micro-heterogeneities on endothelial cells have not been fully understood. Here, we simulate the effects of matrices that mimic young and aged vessels on single- and multi-cell endothelial cell models and examine the resulting cell basal strain profiles...
May 25, 2018: Biomechanics and Modeling in Mechanobiology
Yeonhwa Song, Jin-Sun Kim, Se-Hyuk Kim, Yoon Kyung Park, Eunsil Yu, Ki-Hun Kim, Eul-Ju Seo, Heung-Bum Oh, Han Chu Lee, Kang Mo Kim, Haeng Ran Seo
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has poor prognosis. Specially, patients with HCC usually have poor tolerance of systemic chemotherapy, because HCCs develop from chronically damaged tissue that contains considerable inflammation, fibrosis, and cirrhosis. Since HCC exhibits highly heterogeneous molecular characteristics, a proper in vitro system is required for the study of HCC pathogenesis. To this end, we have established two new hepatitis B virus (HBV) DNA-secreting HCC cell lines from infected patients...
May 25, 2018: Journal of Experimental & Clinical Cancer Research: CR
Nikos Karaiskos, Mahdieh Rahmatollahi, Anastasiya Boltengagen, Haiyue Liu, Martin Hoehne, Markus Rinschen, Bernhard Schermer, Thomas Benzing, Nikolaus Rajewsky, Christine Kocks, Martin Kann, Roman-Ulrich Müller
Background Three different cell types constitute the glomerular filter: mesangial cells, endothelial cells, and podocytes. However, to what extent cellular heterogeneity exists within healthy glomerular cell populations remains unknown. Methods We used nanodroplet-based highly parallel transcriptional profiling to characterize the cellular content of purified wild-type mouse glomeruli. Results Unsupervised clustering of nearly 13,000 single-cell transcriptomes identified the three known glomerular cell types...
May 24, 2018: Journal of the American Society of Nephrology: JASN
Angela Pucci, Claudia Mattioli, Marco Matteucci, Daniele Lorenzini, Francesca Panvini, Simone Pacini, Chiara Ippolito, Michele Celiento, Andrea De Martino, Amelio Dolfi, Beatrice Belgio, Uberto Bortolotti, Fulvio Basolo, Giovanni Bartoloni
Cardiac myxomas are rare tumors with a heterogeneous cell population including properly neoplastic (lepidic), endothelial and smooth muscle cells. The assessment of neoplastic (lepidic) cell differentiation pattern is rather difficult using conventional light microscopy immunohistochemistry and/or whole tissue extracts for mRNA analyses. In a preliminary study, we investigated 20 formalin-fixed and paraffin-embedded cardiac myxomas by means of conventional immunohistochemistry; in 10/20 cases, cell differentiation was also analyzed by real-time RT-PCR after laser capture microdissection of the neoplastic cells, whereas calretinin and endothelial antigen CD31 immunoreactivity was localized in 4/10 cases by double immunofluorescence confocal microscopy...
May 22, 2018: Heart and Vessels
Rossana Berardi, Mariangela Torniai, Stefano Partelli, Corrado Rubini, Silvia Pagliaretta, Agnese Savini, Vanessa Polenta, Matteo Santoni, Riccardo Giampieri, Sofia Onorati, Federica Barucca, Alberto Murrone, Francesca Bianchi, Massimo Falconi
Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood...
2018: PloS One
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