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https://www.readbyqxmd.com/read/28923855/mitosis-mediated-intravasation-in-a-tissue-engineered-tumor-microvessel-platform
#1
Andrew D Wong, Peter C Searson
Intravasation involves the migration of tumor cells across the local endothelium and escape into vessel flow. While tumor cell invasiveness has been correlated to increased intravasation, the details of transendothelial migration and detachment into circulation are still unclear. Here we analyzed the intravasation of invasive human breast cancer cells within a tissue-engineered microvessel model of the tumor microenvironment. Using live-cell fluorescence microscopy, we captured 2,330 hours of tumor cell interactions with functional microvessels and provide evidence for a mitosis-mediated mechanism where tumor cells located along the vessel periphery are able to disrupt the vessel endothelium through cell division and detach into circulation...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28902380/-organ-interactions-heart-and-kidney
#2
Daniel Salleck, Stefan John
The interactions between heart and kidney are various and of clinical relevance. Worsening of one organ often influences the function of the other. With NYHA and KDIGO we have classification systems for heart and kidney failure and those should be used for cardiorenal systems as well. Furthermore there is a useful classification system for cardiorenal syndromes itself. Cardiorenal syndrome is a complex illness which should be treated by interdisciplinary medical teams. A key roll in pathophysiology is the renin-angiotensin-aldosteron-system (RAAS)...
September 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28895920/emt-and-treatment-resistance-in-pancreatic-cancer
#3
REVIEW
Nicola Gaianigo, Davide Melisi, Carmine Carbone
Pancreatic cancer (PC) is the third leading cause of adult cancer mortality in the United States. The poor prognosis for patients with PC is mainly due to its aggressive course, the limited efficacy of active systemic treatments, and a metastatic behavior, demonstrated throughout the evolution of the disease. On average, 80% of patients with PC are diagnosed with metastatic disease, and the half of those who undergo surgery and adjuvant therapy develop liver metastasis within two years. Metastatic dissemination is an early event in PC and is mainly attributed to an evolutionary biological process called epithelial-to-mesenchymal transition (EMT)...
September 12, 2017: Cancers
https://www.readbyqxmd.com/read/28875379/tumor-vessel-disintegration-by-maximum-tolerable-pfkfb3-blockade
#4
Lena-Christin Conradi, Aleksandra Brajic, Anna Rita Cantelmo, Ann Bouché, Joanna Kalucka, Andreas Pircher, Ulrike Brüning, Laure-Anne Teuwen, Stefan Vinckier, Bart Ghesquière, Mieke Dewerchin, Peter Carmeliet
Blockade of the glycolytic activator PFKFB3 in cancer cells (using a maximum tolerable dose of 70 mg/kg of the PFKFB3 blocker 3PO) inhibits tumor growth in preclinical models and is currently being tested as a novel anticancer treatment in phase I clinical trials. However, a detailed preclinical analysis of the effects of such maximum tolerable dose of a PFKFB3 blocker on the tumor vasculature is lacking, even though tumor endothelial cells are hyper-glycolytic. We report here that a high dose of 3PO (70 mg/kg), which inhibits cancer cell proliferation and reduces primary tumor growth, causes tumor vessel disintegration, suppresses endothelial cell growth for protracted periods, (model-dependently) aggravates tumor hypoxia, and compromises vascular barrier integrity, thereby rendering tumor vessels more leaky and facilitating cancer cell intravasation and dissemination...
September 5, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28846105/c-reactive-protein-binds-to-integrin-%C3%AE-2-and-fc%C3%AE-receptor-i-leading-to-breast-cell-adhesion-and-breast-cancer-progression
#5
E-S Kim, S Y Kim, M Koh, H-M Lee, K Kim, J Jung, H S Kim, W K Moon, S Hwang, A Moon
C-reactive protein (CRP) is an acute phase protein synthesized upon the inflammatory responses, associated with breast cancer. The process of tumor cell invasion and metastasis involves the adherence of cells to the extracellular matrix via integrin as a receptor for matrix molecules. The present study investigated the role of CRP in the adhesive phenotype of breast cells and the underlying mechanisms. Here, we first showed that CRP induces adhesion of MCF10A human breast epithelial cells through the activation of integrin α2 signaling...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28838996/the-selective-tie2-inhibitor-rebastinib-blocks-recruitment-and-function-of-tie2hi-macrophages-in-breast-cancer-and-pancreatic-neuroendocrine-tumors
#6
Allison S Harney, George S Karagiannis, Jeanine Pignatelli, Bryan D Smith, Ece Kadioglu, Scott C Wise, Molly M Hood, Michael D Kaufman, Cynthia B Leary, Wei-Ping Lu, Gada Al-Ani, Xiaoming Chen, David Entenberg, Maja H Oktay, Yarong Wang, Lawrence Chun, Michele De Palma, Joan G Jones, Daniel L Flynn, John S Condeelis
Tumor-infiltrating myeloid cells promote tumor progression by mediating angiogenesis, tumor cell intravasation and metastasis, which can offset the effects of chemotherapy, radiation, and anti-angiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cells and pro-tumoral Tie2-expressing macrophages in mouse models of metastatic cancer. Rebastinib reduces tumor growth and metastasis in an orthotopic mouse model of metastatic mammary carcinoma through reduction of Tie2+ myeloid cell infiltration, anti-angiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2Hi/Vegf-AHi macrophages in the tumor microenvironment of metastasis (TMEM)...
August 24, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28830617/cancer-promoting-mechanisms-of-tumor-associated-neutrophils
#7
REVIEW
Brian Hurt, Richard Schulick, Barish Edil, Karim C El Kasmi, Carlton Barnett
IMPORTANCE: Neutrophils have classically been considered to mount a defensive response against tumor cells, yet recent evidence suggests tumors modulate neutrophil function to support tumor growth and progression. OBSERVATIONS: Tumor-associated neutrophils (TANs) are phenotypically distinct from circulating neutrophils in terms of their surface protein composition and cyto/chemokine activity and response. Although TANs have been shown to both promote and inhibit tumor advancement, the preponderant activity augments tumor progression...
August 10, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/28819860/circulating-tumor-cells-markers-and-methodologies-for-enrichment-and-detection
#8
M J Alvarez Cubero, J A Lorente, I Robles-Fernandez, A Rodriguez-Martinez, J L Puche, M J Serrano
Cancer is a leading cause of disease worldwide; however, nowadays many points of its initiation processes are unknown. In this chapter, we are focusing on the role of liquid biopsies in cancer detection and progression. CTCs are one of the main components of liquid biopsies, they represent a subset of tumor cells that have acquired the ability to disseminate from the primary tumor and intravasate to the circulatory system. The greatest challenge in the detection of CTCs is their rarity in the blood. Human blood consists of white blood cells (5-10 × 10(6)/mL), red blood cells (5-9 × 10(9)/mL), and platelets (2...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28763139/tumor-endothelial-cells-accelerate-tumor-metastasis
#9
REVIEW
Nako Maishi, Kyoko Hida
Tumor metastasis is the main cause of cancer-related death. Understanding the molecular mechanisms underlying tumor metastasis is crucial to control this fatal disease. Several molecular pathways orchestrate the complex biological cell events during a metastatic cascade. It is now well known that bidirectional interaction between tumor cells and their microenvironment, including tumor stroma, is important for tumor progression and metastasis. Tumor stromal cells, which acquire their specific characteristics in the tumor microenvironment, accelerate tumor malignancy...
August 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/28759964/extracorporeal-perfusion-reduced-to-a-one-way-infusion
#10
Christian D Taeger, Oliver Friedrich, Raymund E Horch, Caroline Drechsler, Annika Weigand, Fabio Hopf, Carol I Geppert, Frank Münch, Torsten Birkholz, Carina Wenzel, Sebastian Geis, Lukas Prantl, Rainer Buchholz, Konstantin Präbst
BACKGROUND: Extracorporeal perfusion (EP) is moving into focus of research in reconstructive and transplantation medicine for the preservation of amputates and free tissue transplants. The idea behind EP is the reduction of ischemia-related cell damage between separation from blood circulation and reanastomosis of the transplant. Most experimental approaches are based on a complex system that moves the perfusate in a circular course. OBJECTIVE AND METHODS: In this study, we aimed to evaluate if a simple perfusion by an infusion bag filled with an electrolyte solution can provide acceptable results in terms of flow stability, oxygen supply and viability conservation for EP of a muscle transplant...
July 25, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28738216/early-time-related-course-of-image-findings-in-postmortem-mri-typical-findings-and-observer-agreement-in-a-porcine-model
#11
Frank Oliver Henes, Marc Regier, Peter Bannas, Marlen Henker, Axel Heinemann, Jan Sperhake, Philipp G C Begemann, Gerhard Adam, Michael Groth
PURPOSE: To assess early time-related image findings in postmortem magnetic resonance imaging (MRI) and to evaluate observer agreement in a porcine model. MATERIAL AND METHODS: Three pigs were examined by MRI at 15 different time points in the first 36h after death. Two observers independently recorded the postmortem interval (PMI) to the appearance of fluid collection (pleural space, interlobar and interlobular pulmonary fissures and hepatic interlobar fissures), gas accumulation (intrahepatic and intracardial) and blood clotting (aorta and intrahepatic venous vessels)...
September 2017: Legal Medicine
https://www.readbyqxmd.com/read/28733631/vgll4-selectively-represses-yap-dependent-gene-induction-and-tumorigenic-phenotypes-in-breast-cancer
#12
Yinglong Zhang, He Shen, Henry G Withers, Nuo Yang, Kayla E Denson, Ashley L Mussell, Alexander Truskinovsky, Qingyu Fan, Irwin H Gelman, Costa Frangou, Jianmin Zhang
Members of the mammalian Vestigial-like (VGLL) family of transcriptional cofactors activate genes in response to a wide variety of environmental cues. Recently, VGLL proteins have been proposed to regulate key signaling networks involved in cancer development and progression. However, the biological and clinical significance of VGLL dysregulation in human breast cancer pathogenesis remains unknown. Here, we report that diminished VGLL4 expression, but not VGLL1-3, correlated with both shorter relapse-free survival and shorter disease-specific survival of cancer patients with different molecular subtypes of breast cancer...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28730545/platelet-first-responders-in-wound-response-cancer-and-metastasis
#13
REVIEW
David G Menter, Scott Kopetz, Ernest Hawk, Anil K Sood, Jonathan M Loree, Paolo Gresele, Kenneth V Honn
Platelets serve as "first responders" during normal wounding and homeostasis. Arising from bone marrow stem cell lineage megakaryocytes, anucleate platelets can influence inflammation and immune regulation. Biophysically, platelets are optimized due to size and discoid morphology to distribute near vessel walls, monitor vascular integrity, and initiate quick responses to vascular lesions. Adhesion receptors linked to a highly reactive filopodia-generating cytoskeleton maximizes their vascular surface contact allowing rapid response capabilities...
July 20, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28718427/signatures-of-breast-cancer-metastasis-amenable-to-interpretation
#14
Madeleine J Oudin, Frank B Gertler
Mena(INV), an isoform of the motility regulator protein Mena, contributes to prometastatic phenotypes. Tumor microenvironment of metastasis (TMEM), a three-cell structure associated with intravasation, contains a stationary Mena-expressing tumor cell. TMEM density and Mena(INV) expression both correlate with poor clinical outcome in breast cancer patients. However, is Mena(INV) involved in TMEM assembly and function?
January 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28707199/radiation-induced-inflammatory-cascade-and-its-reverberating-crosstalks-as-potential-cause-of-post-radiotherapy-second-malignancies
#15
REVIEW
Sonia Gandhi, Sudhir Chandna
The disease-free survival following radiotherapy is often limited by the development of second/secondary cancers. This significant impediment to effective cancer treatment implicated even in the modern-day radiotherapy needs to be countered effectively. Critical analysis reveals that besides achieving effective tumor control, radiotherapy elicits certain cellular and systemic inflammatory events in tumor infiltrate, which remain relatively stable and tend to facilitate "in-field" or "out of field" oncogenesis in due course of time...
July 13, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28700115/lkb1-pro-oncogenic-activity-triggers-cell-survival-in-circulating-tumor-cells
#16
Elisabeth Katharina Trapp, Leonie Majunke, Beate Zill, Harald Sommer, Ulrich Andergassen, Julian Koch, Nadia Harbeck, Sven Mahner, Thomas Wolfram Paul Friedl, Wolfgang Janni, Brigitte Rack, Marianna Alunni-Fabbroni
During intravasation, circulating tumor cells (CTCs) detach from the epithelium of origin and begin the Epithelial-to Mesenchymal-Transition (EMT) process, where they lose epithelial features and pass through the endothelium to enter circulation. Although detachment from the extracellular matrix is a strong source of metabolic stress, which induces anoikis, CTCs can survive. Recently, the tumor suppressor liver kinase B1 (LKB1) has gained attention for its role as a proto-oncogene in restoring the correct ATP/AMP ratio during metabolic stress...
July 12, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28679654/neoadjuvant-chemotherapy-induces-breast-cancer-metastasis-through-a-tmem-mediated-mechanism
#17
George S Karagiannis, Jessica M Pastoriza, Yarong Wang, Allison S Harney, David Entenberg, Jeanine Pignatelli, Ved P Sharma, Emily A Xue, Esther Cheng, Timothy M D'Alfonso, Joan G Jones, Jesus Anampa, Thomas E Rohan, Joseph A Sparano, John S Condeelis, Maja H Oktay
Breast cancer cells disseminate through TIE2/MENA(Calc)/MENA(INV)-dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we show that chemotherapy increases the density and activity of TMEM sites and Mena expression and promotes distant metastasis. Moreover, in the residual breast cancers of patients treated with neoadjuvant paclitaxel after doxorubicin plus cyclophosphamide, TMEM score and its mechanistically connected MENA(INV) isoform expression pattern were both increased, suggesting that chemotherapy, despite decreasing tumor size, increases the risk of metastatic dissemination...
July 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28618402/epithelial-to-mesenchymal-transition-circulating-tumor-cells-and-cancer-metastasis-mechanisms-and-clinical-applications
#18
REVIEW
Xiao-Xiang Jie, Xiao-Yan Zhang, Cong-Jian Xu
Epithelial-to-mesenchymal transition (EMT) endows epithelial cells with enhanced motility and invasiveness, allowing them to participate in many physiological and pathological processes. Epithelial-to-mesenchymal transition contributes to the generation of circulating tumor cells (CTCs) in epithelial cancers because it increases tumor cell invasiveness, promotes tumor cell intravasation and ensures tumor cell survival in the peripheral system. Although the contribution of epithelial-to-mesenchymal transition to tumor cell invasiveness has been confirmed, the role epithelial-to-mesenchymal transition plays in metastasis remains debated...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604765/mlk3-regulates-fra-1-and-mmps-to-drive-invasion-and-transendothelial-migration-in-triple-negative-breast-cancer-cells
#19
C Rattanasinchai, B J Llewellyn, S E Conrad, K A Gallo
Mixed-lineage kinase 3 (MLK3), a mitogen-activated protein kinase kinase kinase (MAP3K), has critical roles in metastasis of triple-negative breast cancer (TNBC), in part by regulating paxillin phosphorylation and focal adhesion turnover. However the mechanisms and the distinct step(s) of the metastatic processes through which MLK3 exerts its influence are not fully understood. Here we report that in non-metastatic, estrogen receptor-positive breast cancer (ER+ BC) cells, induced MLK3 expression robustly upregulates the oncogenic transcription factor, FOS-related antigen-1 (FRA-1), which is accompanied by elevation of matrix metalloproteinases (MMPs), MMP-1 and MMP-9...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28560677/mesenchymal-epithelial-transition-and-circulating-tumor-cells-in-small-cell-lung-cancer
#20
Gerhard Hamilton, Barbara Rath
Cancer patients die of metastatic disease but knowledge regarding individual steps of this complex process of intravasation, spread and extravasation leading to secondary lesions is incomplete. Subpopulations of tumor cells are supposed to undergo an epithelial-mesenchymal transition (EMT), to enter the bloodstream and eventually establish metastases in a reverse process termed mesenchymal-epithelial transition (MET). Small cell lung cancer (SCLC) represents a unique model to study metastatic spread due to early dissemination and relapse, as well as availability of a panel of circulating cancer cell (CTC) lines recently...
2017: Advances in Experimental Medicine and Biology
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