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https://www.readbyqxmd.com/read/28212191/endothelial-cell-metabolism-an-update-anno-2017
#1
Laure-Anne Teuwen, Nihed Draoui, Charlotte Dubois, Peter Carmeliet
PURPOSE OF REVIEW: Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications. RECENT FINDINGS: Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO)...
February 15, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28211961/an-extended-vascular-model-for-less-biased-estimation-of-permeability-parameters-in-dce-t1-images
#2
Siamak P Nejad-Davarani, Hassan Bagher-Ebadian, James R Ewing, Douglas C Noll, Tom Mikkelsen, Michael Chopp, Quan Jiang
One of the key elements in dynamic contrast enhanced (DCE) image analysis is the arterial input function (AIF). Traditionally, in DCE studies a global AIF sampled from a major artery or vein is used to estimate the vascular permeability parameters; however, not addressing dispersion and delay of the AIF at the tissue level can lead to biased estimates of these parameters. To find less biased estimates of vascular permeability parameters, a vascular model of the cerebral vascular system is proposed that considers effects of dispersion of the AIF in the vessel branches, as well as extravasation of the contrast agent (CA) to the extravascular-extracellular space...
February 17, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28182306/effect-of-a-hypoxic-microenvironment-after-radiofrequency-ablation-on-residual-hepatocellular-cell-migration-and-invasion
#3
Yuyang Tong, Haiyun Yang, Xiaolin Xu, Jingliang Ruan, Ming Liang, Jiayi Wu, Baoming Luo
Clinical observations have shown that the boundary of tumor ablation is often less than safe border and that the use of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) may probably accelerate its recurrence and metastasis. RFA can cause the formation of a transition zone between normal liver tissues and necrotic coagulation, where blood stagnation and thrombosis expose residual cancer cells to a hypoxic microenvironment. As the blocked vessels are slowly reperfused, the oxygen supply is gradually restored...
February 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28178651/stromal-fibroblasts-present-in-breast-carcinomas-promote-tumor-growth-and-angiogenesis-through-adrenomedullin-secretion
#4
Zohra Benyahia, Nadège Dussault, Mylène Cayol, Romain Sigaud, Caroline Berenguer-Daizé, Christine Delfino, Asma Tounsi, Stéphane Garcia, Pierre-Marie Martin, Kamel Mabrouk, L'Houcine Ouafik
Tumor- or cancer-associated fibroblasts (TAFs or CAFs) are active players in tumorigenesis and exhibit distinct angiogenic and tumorigenic properties. Adrenomedullin (AM), a multifunctional peptide plays an important role in angiogenesis and tumor growth through its receptors calcitonin receptor-like receptor/receptor activity modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). We show that AM and AM receptors mRNAs are highly expressed in CAFs prepared from invasive breast carcinoma when compared to normal fibroblasts...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174262/role-of-vascular-normalization-in-benefit-from-metronomic-chemotherapy
#5
Fotios Mpekris, James W Baish, Triantafyllos Stylianopoulos, Rakesh K Jain
Metronomic dosing of chemotherapy-defined as frequent administration at lower doses-has been shown to be more efficacious than maximum tolerated dose treatment in preclinical studies, and is currently being tested in the clinic. Although multiple mechanisms of benefit from metronomic chemotherapy have been proposed, how these mechanisms are related to one another and which one is dominant for a given tumor-drug combination is not known. To this end, we have developed a mathematical model that incorporates various proposed mechanisms, and report here that improved function of tumor vessels is a key determinant of benefit from metronomic chemotherapy...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28173976/targeting-pfkfb3-in-the-endothelium-for-cancer-therapy
#6
Qi Yang, Peng Hou
In a recent article published in Cancer Cell, Cantelmo et al. showed that inhibition of endothelium glycolysis by targeting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) significantly impaired tumor metastasis by normalizing tumor vessels. In addition, as a promising therapeutic strategy, tumor vessel normalization by PFKFB3 blockade also improved the delivery and efficacy of chemotherapy.
February 4, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28163397/the-role-of-pdgfs-and-pdgfrs-in-colorectal-cancer
#7
REVIEW
Roberta M Manzat Saplacan, Loredana Balacescu, Claudia Gherman, Romeo I Chira, Anca Craiu, Petru A Mircea, Cosmin Lisencu, Ovidiu Balacescu
Introduction. Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide. Angiogenesis was reported as one important mechanism activated in colorectal carcinogenesis. Tumor microenvironment associated angiogenesis involves a large spectrum of signaling molecules and deciphering their role in colorectal carcinogenesis still represents a major challenge. The aim of our study is to point out the diagnosis and prediction role of PDGF family and their receptors in colorectal carcinogenesis...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28159518/targeting-ncam-expressing-neuroblastoma-with-polymeric-precision-nanomedicine
#8
Ela Markovsky, Anat Eldar-Boock, Dikla Ben-Shushan, Hemda Baabur-Cohen, Eilam Yeini, Evgeni Pisarevsky, Ariel Many, Sarit Aviel-Ronen, Iris Barshack, Ronit Satchi-Fainaro
Neural cell adhesion molecule (NCAM) expression is known to be associated with an aggressive biological behavior, increased metastatic capacity and expression of stem-cell markers in several tumor types. NCAM was also found to be expressed on tumor endothelial cells while forming new capillary-like tubes, but not on normal endothelial cells. An NCAM-targeted polymer-drug conjugate can be used both to target tumors expressing high levels of NCAM as well as the angiogenic vessels and cancer stem cells populations characterized by NCAM expression within tumors...
February 1, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28157429/chimeric-anti-human-podoplanin-antibody-nz-12-of-lambda-light-chain-exerts-higher-antibody-dependent-cellular-cytotoxicity-and-complement-dependent-cytotoxicity-compared-with-nz-8-of-kappa-light-chain
#9
Mika K Kaneko, Shinji Abe, Satoshi Ogasawara, Yuki Fujii, Shinji Yamada, Takeshi Murata, Hiroaki Uchida, Hideaki Tahara, Yasuhiko Nishioka, Yukinari Kato
Podoplanin (PDPN), a type I transmembrane 36-kDa glycoprotein, is expressed not only in normal cells, such as renal epithelial cells (podocytes), lymphatic endothelial cells, and pulmonary type I alveolar cells, but also in cancer cells, including brain tumors and lung squamous cell carcinomas. Podoplanin activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets, and the podoplanin/CLEC-2 interaction facilitates blood/lymphatic vessel separation. We previously produced neutralizing anti-human podoplanin monoclonal antibody (mAb), clone NZ-1 (rat IgG2a, lambda), which neutralizes the podoplanin/CLEC-2 interaction and inhibits platelet aggregation and cancer metastasis...
February 3, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28152577/complementary-actions-of-dopamine-d2-receptor-agonist-and-anti-vegf-therapy-on-tumoral-vessel-normalization-in-a-transgenic-mouse-model
#10
Norbert Chauvet, Nicola Romanò, Chrystel Lafont, Anne Guillou, Evelyne Galibert, Xavier Bonnefont, Paul Le Tissier, Monica Fedele, Alfredo Fusco, Patrice Mollard, Nathalie Coutry
Angiogenesis contributes in multiple ways to disease progression in tumors and reduces treatment efficiency. Molecular therapies targeting Vegf signaling combined with chemotherapy or other drugs exhibit promising results to improve efficacy of treatment. Dopamine has been recently proposed to be a novel safe antiangiogenic drug that stabilizes abnormal blood vessels and increases therapeutic efficacy. Here, we aimed to identify a treatment to normalize tumoral vessels and restore normal blood perfusion in tumor tissue with a Vegf receptor inhibitor and/or a ligand of dopamine G protein-coupled receptor D2 (D2R)...
February 2, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28146140/tumor-and-normal-thyroid-spheroids-from-tissues-to-zebrafish
#11
Valentina Cirello, Germano Gaudenzi, Elisa S Grassi, Carla Colombo, Leonardo Vicentini, Stefano Ferrero, Luca Persani, Giovanni Vitale, Laura Fugazzola
BACKGROUND: Multicellular spheroids represent an interesting experimental model with promising applications in the pre-clinical studies on anticancer drugs. We recently demonstrated that thyroid spheroids recapitulate the features of the original tissues, in either the differentiated and "stem-like" components. Here we were aimed to characterize thyroid spheroids and to investigate in vivo the proangiogenic potential of patient-derived xenografts (PDX) of spheroids obtained from papillary thyroid cancer (PTC) and the matched normal tissues...
January 31, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/28134764/the-pleiotropic-role-of-l1cam-in-tumor-vasculature
#12
REVIEW
Francesca Angiolini, Ugo Cavallaro
Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms...
January 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28134673/tolerability-and-long-term-outcomes-of-dose-painted-neoadjuvant-chemoradiation-to-regions-of-vessel-involvement-in-borderline-or-locally-advanced-pancreatic-cancer
#13
Jennifer Y Wo, Andrzej Niemierko, David P Ryan, Lawrence S Blaszkowsky, Jeffrey W Clark, Eunice L Kwak, Keith D Lillemoe, Lorraine N Drapek, Andrew X Zhu, Jill N Allen, Jason E Faris, Janet E Murphy, Ryan Nipp, Carlos Fernandez-Del Castillo, Cristina R Ferrone, Theodore S Hong
PURPOSE: We reviewed our experience involving patients with borderline resectable or locally advanced pancreatic cancer, treated with the dose-painted (DP) boost technique to regions of vessel involvement which preclude upfront surgical resection. We evaluated patient outcomes with respect to tolerability and treatment outcomes. MATERIALS AND METHODS: We retrospectively reviewed 99 patients with borderline resectable (n=25) or locally advanced pancreatic cancer (n=74) treated with DP-neoadjuvant chemoradiation from 2010 to 2015...
January 27, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28133764/neutrophils-promote-hepatic-metastasis-growth-through-fibroblast-growth-factor-fgf-2-dependent-angiogenesis
#14
Alex N Gordon-Weeks, Su Y Lim, Arseniy E Yuzhalin, Keaton Jones, Bostjan Markelc, Jon N Buzelli, Emmanouil Fokas, Yunhong Cao, Sean Smart, Ruth Muschel
: Hepatic metastases are amenable to ablation, however many patients are not suitable candidates for such therapy and recurrence is common. The tumor microenvironment is known to be essential for metastatic growth, yet identification of plausible targets for cancer therapy in the microenvironment has proven elusive. We found that human colorectal cancer liver metastases and murine gastrointestinal experimental liver metastases are infiltrated by neutrophils. Plasticity in neutrophils has recently been shown to lead to both pro- and anti- tumor effects...
January 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28124184/reelin-deficiency-delays-mammary-tumor-growth-and-metastatic-progression
#15
Elvira Khialeeva, Joan W Chou, Denise E Allen, Alec M Chiu, Steven J Bensinger, Ellen M Carpenter
Reelin is a regulator of cell migration in the nervous system, and has other functions in the development of a number of non-neuronal tissues. In addition, alterations in reelin expression levels have been reported in breast, pancreatic, liver, gastric, and other cancers. Reelin is normally expressed in mammary gland stromal cells, but whether stromal reelin contributes to breast cancer progression is unknown. Herein, we used a syngeneic mouse mammary tumor transplantation model to examine the impact of host-derived reelin on breast cancer progression...
March 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28123541/differential-effects-of-recombinant-human-endostatin-treatment-on-differentiated-and-undifferentiated-blood-vessels-in-lewis-lung-cancer
#16
Weijiang Fu, Jing Zhuo, Likuan Hu
In the present study, we evaluated the effects of recombinant human (rh-)endostatin treatment on differentiated and undifferentiated tumor vasculature in Lewis lung cancer for the first time. Lewis lung carcinoma models were established. The animals were treated daily with varying doses of rh-endostatin or physiological saline for 14 days. Intravital microscopy was performed following treatment. The expression of CD31 and CD34 was determined by immunohistochemical staining, and microvessel density (MVD) was determined...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28122521/neovascularization-of-hepatocellular-carcinoma-in-a-nude-mouse-orthotopic-liver-cancer-model-a-morphological-study-using-x-ray-in-line-phase-contrast-imaging
#17
Beilei Li, Yiqiu Zhang, Weizhong Wu, Guohao Du, Liang Cai, Hongcheng Shi, Shaoliang Chen
BACKGROUND: This study aimed to determine whether synchrotron radiation (SR)-based X-ray in-line phase-contrast imaging (IL-PCI) can be used to investigate the morphological characteristics of tumor neovascularization in a liver xenograft animal model. METHODS: A human hepatocellular carcinoma HCCLM3 xenograft model was established in nude mice. Xenografts were sampled each week for 4 weeks and fixed to analyze tissue characteristics and neovascularization using SR-based X-ray in-line phase contrast computed tomography (IL-XPCT) without any contrast agent...
January 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28122328/genome-wide-screen-identifies-a-novel-prognostic-signature-for-breast-cancer-survival
#18
Xuan Y Mao, Matthew J Lee, Jeffrey Zhu, Carissa Zhu, Sindy M Law, Antoine M Snijders
Large genomic datasets in combination with clinical data can be used as an unbiased tool to identify genes important in patient survival and discover potential therapeutic targets. We used a genome-wide screen to identify 587 genes significantly and robustly deregulated across four independent breast cancer (BC) datasets compared to normal breast tissue. Gene expression of 381 genes was significantly associated with relapse-free survival (RFS) in BC patients. We used a gene co-expression network approach to visualize the genetic architecture in normal breast and BCs...
January 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28120873/novel-approach-for-the-detection-of-intraperitoneal-micrometastasis-using-an-ovarian-cancer-mouse-model
#19
Ayesha B Alvero, Dongin Kim, Eydis Lima, Natalia J Sumi, Jung Seok Lee, Carlos Cardenas, Mary Pitruzzello, Dan-Arin Silasi, Natalia Buza, Tarek Fahmy, Gil Mor
Patients with epithelial ovarian cancer have the best overall survival when maximal surgical effort is accomplished. However, despite numerous technological advances, surgery still relies primarily on white-light reflectance and the surgeon's vision. As such, micrometastases are usually missed and most patients clinically classified as a complete responder eventually recur and succumb to the disease. Our objective is to develop optical enhancers which can aid in the visualization of ovarian cancer micrometastasis...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28115513/proton-pump-inhibitors-decrease-soluble-fms-like-tyrosine-kinase-1-and-soluble-endoglin-secretion-decrease-hypertension-and-rescue-endothelial-dysfunction
#20
Kenji Onda, Stephen Tong, Sally Beard, Natalie Binder, Masanaga Muto, Sevvandi N Senadheera, Laura Parry, Mark Dilworth, Lewis Renshall, Fiona Brownfoot, Roxanne Hastie, Laura Tuohey, Kirsten Palmer, Toshihiko Hirano, Masahito Ikawa, Tu'uhevaha Kaitu'u-Lino, Natalie J Hannan
Preeclampsia is a severe complication of pregnancy. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. Oxidative stress and vascular inflammation exacerbate the endothelial injury. A drug that can block these pathophysiological steps would be an attractive treatment option. Proton pump inhibitors (PPIs) are safe in pregnancy where they are prescribed for gastric reflux...
March 2017: Hypertension
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