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Francesc Castro-Giner, Manuel C Scheidmann, Nicola Aceto
Circulating tumor cells (CTCs) are defined as those cells that detach from a cancerous lesion and enter the bloodstream. While generally most CTCs are subjected to high shear stress, anoikis signals, and immune attack in the circulatory system, few are able to survive and reach a distant organ in a viable state, possibly leading to metastasis formation. A large number of studies, both prospective and retrospective, have highlighted the association between CTC abundance and bad prognosis in patients with various cancer types...
2018: Frontiers in Medicine
Lucilla E Overdijk, Bart M P Rademaker, Paul J M van Kesteren, Peter de Haan, Robert K Riezebos, Oscar C H Haude
BACKGROUND: Transcervical resection of myoma or endometrium is a safe, hysteroscopic, minimally invasive procedure. However, intravasation of distension fluid is a common phenomenon during these procedures. In a previous study we observed venous gas emboli in almost every patient. The severity of hysteroscopic-derived embolization has been shown to be correlated to the amount of intravasation. In addition, paradoxical gas embolism, which is potentially dangerous, was observed in several patients...
February 14, 2018: Trials
Xiaojun He, Xiaopeng Guo, Hongsen Zhang, Xiangchuang Kong, Fan Yang, Chuansheng Zheng
TACE (transcatheter arterial chemoembolization) has been recognized as an effective palliative treatment option for patients with HCC, however, the medium-long term efficacy of it remains modest. LY2109761, a TGF-β receptor inhibitor, was confirmed to reduce tumor cell growth, intravasation, and metastatic dissemination of HCC cells through different molecular mechanisms. This study aims to investigate the treatment effect of combining TACE therapy with LY2109761- a TGF-β receptor I kinase inhibitor on suppressing tumor growth and metastasis in a rabbit VX2 tumor model...
January 2, 2018: Oncotarget
Kuldeep S Attri, Kamiya Mehla, Surendra K Shukla, Pankaj K Singh
Macrophages, apart from being the key effector cells of the innate immune system, also play critical roles during the development and progression of various complex diseases, including cancer. Tumor-associated macrophages, infiltrate tumors during different stages of cancer progression to regulate motility, invasion, and intravasation to metastatic sites. Macrophages can exist in different polarization states associated with unique function in tumors. Since tumor-associated macrophages constitute a very small proportion of tumor cells, analysis of gene expression pattern using normal extraction buffer-based methods remains a challenging task...
February 5, 2018: Scientific Reports
Elena I Deryugina, Ewa Zajac, Lior Zilberberg, Tomoki Muramatsu, Grishma Joshi, Branka Dabovic, Daniel Rifkin, James P Quigley
Latent transforming growth factor β (TGFβ)-binding proteins (LTBPs) are important for the secretion, activation, and function of mature TGFβ, especially so in cancer cell physiology. However, specific roles of the LTBPs remain understudied in the context of the primary tumor microenvironment. Herein, we investigated the role of LTBP3 in the distinct processes involved in cancer metastasis. By using three human tumor cell lines of different tissue origin (epidermoid HEp-3 and prostate PC-3 carcinomas and HT-1080 fibrosarcoma) and several metastasis models conducted in both mammalian and avian settings, we show that LTBP3 is involved in the early dissemination of primary cancer cells, namely in the intravasation step of the metastatic cascade...
January 19, 2018: Oncogene
Supriya Nagaraju, Danh Truong, Ghassan Mouneimne, Mehdi Nikkhah
Cancer is a major leading cause of disease-related death in the world. The severe impact of cancer can be attributed to poor understanding of the mechanisms involved in earliest steps of the metastatic cascade, specifically invasion into the surrounding stroma and intravasation into the blood capillaries. However, conducting integrated biological studies of invasion and intravasation have been challenging, within in vivo models and traditional in vitro assay, due to difficulties in establishing a precise tumor microenvironment...
January 15, 2018: Advanced Healthcare Materials
George S Karagiannis, John S Condeelis, Maja H Oktay
Tumors often overcome the cytotoxic effects of chemotherapy through either acquired or environment-mediated drug resistance. In addition, signals from the microenvironment obfuscate the beneficial effects of chemotherapy and may facilitate progression and metastatic dissemination. Seminal mediators in chemotherapy-induced metastasis appear to be a wide range of hematopoietic, mesenchymal and immune progenitor cells, originating from the bone marrow. The actual purpose of these cells is to orchestrate the repair response to the cytotoxic damage of chemotherapy...
January 6, 2018: Clinical & Experimental Metastasis
Nina Linde, Maria Casanova-Acebes, Maria Soledad Sosa, Arthur Mortha, Adeeb Rahman, Eduardo Farias, Kathryn Harper, Ethan Tardio, Ivan Reyes Torres, Joan Jones, John Condeelis, Miriam Merad, Julio A Aguirre-Ghiso
Cancer cell dissemination during very early stages of breast cancer proceeds through poorly understood mechanisms. Here we show, in a mouse model of HER2+ breast cancer, that a previously described sub-population of early-evolved cancer cells requires macrophages for early dissemination. Depletion of macrophages specifically during pre-malignant stages reduces early dissemination and also results in reduced metastatic burden at end stages of cancer progression. Mechanistically, we show that, in pre-malignant lesions, CCL2 produced by cancer cells and myeloid cells attracts CD206+/Tie2+ macrophages and induces Wnt-1 upregulation that in turn downregulates E-cadherin junctions in the HER2+ early cancer cells...
January 2, 2018: Nature Communications
Eri Sakai, Mizuho Nakayama, Hiroko Oshima, Yuta Kouyama, Atsushi Niida, Satoshi Fujii, Atsushi Ochiai, Keiichi I Nakayama, Koshi Mimori, Yutaka Suzuki, Chang Pyo Hong, Chan-Young Ock, Seong-Jin Kim, Masanobu Oshima
Colorectal cancer (CRC) is driven by the accumulation of driver mutations, but the contributions of specific mutations to different steps in malignant progression is not fully understood. In this study, we generated mouse models harboring different combinations of key CRC driver mutations (Apc, Kras, Tgfbr2, Trp53, Fbxw7) in intestinal epithelial cells to comprehensively investigate their roles in the development of primary tumors and metastases. Apc∆716 mutation caused intestinal adenomas and combination with Trp53R270H mutation or Tgfbr2 deletion induced submucosal invasion...
December 27, 2017: Cancer Research
Sanja Aveic, Diana Corallo, Elena Porcù, Marcella Pantile, Daniele Boso, Carlo Zanon, Giampietro Viola, Viktoryia Sidarovich, Elena Mariotto, Alessandro Quattrone, Giuseppe Basso, Gian Paolo Tonini
Neuroblastoma (NB) is an embryonal tumor with low cure rate for patients classified as high-risk. This class of NB tumors shows a very complex genomic background and requires aggressive treatment strategies. In this work we evaluated the efficacy of the novel multi-kinase inhibitor TP-0903 in impairing NB cells' growth, proliferation and motility. In vitro studies were performed using cell lines with different molecular background, and in vivo studies were done using the zebrafish experimental model. Our results confirmed a strong cytotoxicity of TP-0903 already at the sub-micro molar concentrations...
January 5, 2018: European Journal of Pharmacology
Chinwe R Onwuchekwa, Vaduneme K Oriji
Background: Infertility is a complex disorder with significant medical, psychological and economic problems. Aims: The aim of the study is to evaluate the structural abnormalities of the uterus and fallopian tubes in infertile women as elucidated by hysterosalpingography. Setting and Design: A retrospective study, conducted at the Radiology and Obstetric and Gynaecologic Departments of a tertiary health care institution. Materials and Methods: Evaluation of all consecutive patients in whom hysterosalpingographic (HSG) was performed for infertility between July 2013 and June 2015 in the Department of Radiology...
July 2017: Journal of Human Reproductive Sciences
Joseph A Sparano, Robert Gray, Maja H Oktay, David Entenberg, Thomas Rohan, Xiaonan Xue, Michael Donovan, Michael Peterson, Anthony Shuber, Douglas A Hamilton, Timothy D'Alfonso, Lori J Goldstein, Frank Gertler, Nancy E Davidson, John Condeelis, Joan Jones
Metastasis is the primary cause of death in early-stage breast cancer. We evaluated the association between a metastasis biomarker, which we call "Tumor Microenviroment of Metastasis" (TMEM), and risk of recurrence. TMEM are microanatomic structures where invasive tumor cells are in direct contact with endothelial cells and macrophages, and which serve as intravasation sites for tumor cells into the circulation. We evaluated primary tumors from 600 patients with Stage I-III breast cancer treated with adjuvant chemotherapy in trial E2197 (NCT00003519), plus endocrine therapy for hormone receptor (HR)+ disease...
2017: NPJ Breast Cancer
Kristine E Fasmer, Atle Bjørnerud, Sigmund Ytre-Hauge, Renate Grüner, Ingvild L Tangen, Henrica Mj Werner, Line Bjørge, Øyvind O Salvesen, Jone Trovik, Camilla Krakstad, Ingfrid S Haldorsen
Background Quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) may yield preoperative tumor biomarkers relevant for prognosis and therapy in cancer. Purpose To explore the value of preoperative DCE-MRI and DWI for the prediction of aggressive disease in endometrial cancer patients. Material and Methods Preoperative MRI (1.5-T) from 177 patients were analyzed and imaging parameters reflecting tumor microvasculature (from DCE-MRI) and tumor microstructure (from DWI) were estimated...
January 1, 2017: Acta Radiologica
Mattis Bertlich, Friedrich Ihler, Bernhard G Weiss, Saskia Freytag, Michael Strupp, Martin Canis
OBJECTIVE: The aim of this work was to evaluate the effect of tumor necrosis factor (TNF) and its neutralization with etanercept on the capability of cochlear pericytes to alter capillary diameter in the stria vascularis. METHODS: Twelve Dunkin-Hartley guinea pigs were randomly assigned to one of three groups. Each group was treated either with placebo and then placebo, TNF and then placebo, or TNF and then etanercept. Cochlear pericytes were visualized using diaminofluorescein-2-diacetate and intravasal blood flow by fluorescein-dextrane...
December 2017: Otology & Neurotology
Silvio Holzner, Stefan Brenner, Atanas Georgiev Atanasov, Daniel Senfter, Serena Stadler, Chi Huu Nguyen, Adryan Fristiohady, Daniela Milovanovic, Nicole Huttary, Sigurd Krieger, Zsuzsanna Bago-Horvath, Oliver de Wever, Ioannis Tentes, Ali Özmen, Walter Jäger, Helmut Dolznig, Verena Maria Dirsch, Robert Michael Mader, Liselotte Krenn, Georg Krupitza
Mechanisms how colorectal cancer (CRC) cells penetrate blood micro-vessel endothelia and metastasise is poorly understood. To study blood endothelial cell (BEC) barrier breaching by CRC emboli, an in vitro assay measuring BEC-free areas underneath SW620 cell spheroids, so called "circular chemorepellent induced defects" (CCIDs, appearing in consequence of endothelial retraction), was adapted and supported by Western blotting, EIA-, EROD- and luciferase reporter assays. Inhibition of ALOX12 or NF-κB in SW620 cells or BECs, respectively, caused attenuation of CCIDs...
January 2018: Food and Chemical Toxicology
Eng-Zhuan Ban, Munn-Sann Lye, Pei Pei Chong, Yoke-Yeow Yap, Siew Ying Crystale Lim, Hejar Abdul Rahman
BACKGROUND: 8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis...
2017: PloS One
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...
October 6, 2017: Oncotarget
Kentaro Sakurai, Tomoharu Miyashita, Mitsuyoshi Okazaki, Takahisa Yamaguchi, Yoshinao Ohbatake, Shinichi Nakanuma, Koichi Okamoto, Seisho Sakai, Jun Kinoshita, Isamu Makino, Keishi Nakamura, Hironori Hayashi, Katsunobu Oyama, Hidehiro Tajima, Hiroyuki Takamura, Itasu Ninomiya, Sachio Fushida, Kenichi Harada, John W Harmon, Tetsuo Ohta
BACKGROUND/AIM: Severe sepsis is associated with high morbidity and mortality rates. Inflammation and coagulation play pivotal roles in the pathogenesis of sepsis leading to multiple organ failure, especially in the liver. The aim of the present study was to assess the mechanism from sepsis to liver damage in a mouse model. MATERIALS AND METHODS: We created a sepsis model by injecting lipopolysaccharide (LPS) intraperitoneally in mice. At 0, 6, 12, and 24 h following intraperitoneal injection of LPS, mice were euthanised and analyzed...
November 2017: In Vivo
Yixiang Xu, Dong-Kee Lee, Zhen Feng, Yan Xu, Wen Bu, Yi Li, Lan Liao, Jianming Xu
Twist1 is an epithelial-mesenchymal transition (EMT)-inducing transcription factor (TF) that promotes cell migration and invasion. To determine the intrinsic role of Twist1 in EMT and breast cancer initiation, growth, and metastasis, we developed mouse models with an oncogene-induced mammary tumor containing wild-type (WT) Twist1 or tumor cell-specific Twist1 knockout (Twist1(TKO)). Twist1 knockout showed no effects on tumor initiation and growth. In both models with early-stage tumor cells, Twist1, and mesenchymal markers were not expressed, and lung metastasis was absent...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
Douglas S Micalizzi, Shyamala Maheswaran, Daniel A Haber
Advances in the enrichment and analysis of rare cells from the bloodstream have allowed for detection and characterization of circulating tumor cells (CTCs) from patients with cancer. The analysis of CTCs has provided significant insight into the metastatic process. Studies on the biology of CTCs have begun to elucidate the molecular mechanisms of CTC generation, intravasation, survival, interactions with components of the blood, extravasation, and colonization of distant organs. Additionally, the study of CTCs has exposed dramatic intrapatient and interpatient heterogeneity and their evolution over time...
September 15, 2017: Genes & Development
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