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Circulating tumor colon

Cuijuan Yu, Hai Wang, Aaron Muscarella, Amit Goldstein, Huan-Chang Zeng, Yangjin Bae, Brendan H I Lee, Xiang H-F Zhang
Intra-iliac artery (IIA) injection is an efficient approach to introduce metastatic lesions of various cancer cells in animals. Compared to the widely used intra-cardiac and intra-tibial injections, IIA injection brings several advantages. First, it can deliver a large quantity of cancer cells specifically to hind limb bones, thereby providing spatiotemporally synchronized early-stage colonization events and allowing robust quantification and swift detection of disseminated tumor cells. Second, it injects cancer cells into the circulation without damaging the local tissues, thereby avoiding inflammatory and wound-healing processes that confound the bone colonization process...
September 26, 2016: Journal of Visualized Experiments: JoVE
Eugenio Zoni, Gabri van der Pluijm
The skeleton represents a common site of metastases for osteotropic cancers such as prostate and breast tumors and novel therapeutic targets and new markers for the monitoring of bone lesions are urgently needed. The formation of bone metastases is a complex process that starts at the level of the confined tumor and that is characterized by a dynamic crosstalk between the primary cancer and the future metastatic site, the bone. Factors released by the primary tumor contribute to prepare a fertile "soil", where a "pre-metastatic niche" is established prior to future colonization by cancer cells...
September 2016: Journal of Bone Oncology
Yongkun Sun, Wei Niu, Feng Du, Chunxia Du, Shuting Li, Jinwan Wang, Li Li, Fengqing Wang, Yu Hao, Chuan Li, Yihebali Chi
BACKGROUND: Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. METHODS: Anlotinib (5-16 mg) was orally administered in patients with solid tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1)...
October 4, 2016: Journal of Hematology & Oncology
Arun Satelli, Jiemiao Hu, Xueqing Xia, Shulin Li
Cancer cell signaling, growth, morphology, proliferation and tumorigenic potential are largely depending on the signaling molecules present naturally in the tumor microenvironment and the identification of key molecules that drive the tumor progression is critical for the development of new modalities for the prevention of tumor progression. High concentrations of vimentin in the blood of cancer patients have been reported, however the function of blood circulating vimentin remains unknown. Here, we investigated the functional role of exogenously supplemented vimentin on colon cancer cells and examined the Wnt Signaling activation and cancer cell invasion...
2016: Journal of Cancer
Angelika Riedl, Michaela Schlederer, Karoline Pudelko, Mira Stadler, Stefanie Walter, Daniela Unterleuthner, Christine Unger, Nina Kramer, Markus Hengstschläger, Lukas Kenner, Dagmar Pfeiffer, Georg Krupitza, Helmut Dolznig
3D cancer models are used as preclinical systems to mimic physiologic drug response. We provide evidence for robust changes of proliferation and metabolic capacity in 3D by systematically analyzing spheroids of colon cancer cell lines. Spheroids showed relative lower AKT/mTOR/S6K activities compared to cells cultured in 2D. We identified spatial alterations in signaling, as the level of phospho-rpS6 decreased from the spheroid surface to the center, closely recapitulating the tumor areas around vessels in vivo These 3D-models displayed augmented anti-tumor response to AKT/mTOR/S6K- or MAPK-pathway inhibition compared to 2D...
September 23, 2016: Journal of Cell Science
Sung Won Lim, Hang Lak Lee, Kang Nyeong Lee, Dae Won Jun, In Young Kim, Eunjin Kim, Hyein Ahn, Chan Kum Park
Myeloid sarcoma (MS) is an extramedullary involvement of immature myeloid proliferation. An isolated MS is defined as a myeloblastic tumor when it arises without any concomitant circulating disease. A diagnosis of MS is established using pathologic features including infiltration of myeloblasts and strong myeloperoxidase expression with negative cytokeratin immunohistochemical staining. We report a rare case of colonic MS without any peripheral blood abnormality. If the affected patient were left untreated, the MS could evolve into acute myeloid leukemia (AML) within one year...
September 25, 2016: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
Sandra Casimiro, Arlindo R Ferreira, André Mansinho, Irina Alho, Luis Costa
Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteotropic factors...
2016: International Journal of Molecular Sciences
Lukas Klumpp, Efe C Sezgin, Franziska Eckert, Stephan M Huber
Breast cancer, lung cancer and melanoma exhibit a high metastatic tropism to the brain. Development of brain metastases severely worsens the prognosis of cancer patients and constrains curative treatment options. Metastasizing to the brain by cancer cells can be dissected in consecutive processes including epithelial-mesenchymal transition, evasion from the primary tumor, intravasation and circulation in the blood, extravasation across the blood-brain barrier, formation of metastatic niches, and colonization in the brain...
2016: International Journal of Molecular Sciences
Tie-Jun Liang, Zhong-Mei Zhou, Ying-Qing Cao, Ming-Ze Ma, Xiao-Jun Wang, Kai Jing
In this study, we have demonstrated gemcitabine (GEM)-conjugated amphiphilic biodegradable polymeric drug carriers. Our aim was to increase the chemotherapeutic potential of GEM in colon cancer by forming a unique polymer-drug conjugates. The polymer-drug conjugate micelles were nanosized with a typical spherical shape. The GEM-conjugated methoxy poly(ethylene glycol)-poly(lactic acid) (GEM-PL) exhibited a controlled release of drug in both the pH conditions. The developed GEM-PL efficiently killed the HT29 cancers cells in a typical time dependent manner...
September 6, 2016: International Journal of Pharmaceutics
Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez, Maitane Izaguirre, José Luis Hernández-Lizoain, Jorge Baixauli, Pablo Martí, Víctor Valentí, Rafael Moncada, Camilo Silva, Javier Salvador, Gema Frühbeck
BACKGROUND: Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth. METHODS: Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study...
2016: PloS One
David Clever, Rahul Roychoudhuri, Michael G Constantinides, Michael H Askenase, Madhusudhanan Sukumar, Christopher A Klebanoff, Robert L Eil, Heather D Hickman, Zhiya Yu, Jenny H Pan, Douglas C Palmer, Anthony T Phan, John Goulding, Luca Gattinoni, Ananda W Goldrath, Yasmine Belkaid, Nicholas P Restifo
Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T-cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4(+)-regulatory T (Treg) cell induction, and restrain CD8(+) T cell effector function...
August 25, 2016: Cell
Adele Aronica, Laura Avagliano, Anna Caretti, Delfina Tosi, Gaetano Pietro Bulfamante, Marco Trinchera
BACKGROUND: CA19.9 antigen has been assumed as an abundant product of cancer cells, due to the reactivity found by immunohistochemical staining of cancer tissues with anti-CA19.9 antibody. METHODS: Expression and biosynthesis of type 1 chain Lewis antigens in the colon and the pancreas were studied by immunodetection in tissue sections and lysates, quantification of glycosyltransferase transcripts, bisulfite sequencing, and chromatin immunoprecipitation assays. RESULTS: CA19...
August 14, 2016: Biochimica et Biophysica Acta
Jean-Marc Pascussi, Julie Giraud, Emmanuelle Samalin, Fanny Grillet, Julie Pannequin
Metastatic process is described as a "dissemination of neoplastic cells in a distant secondary site, in which cells proliferate to develop a mass of cells partially differentiated". The vast majority of death in solid cancers is the consequence of metastasis development which lead to vital organ dysfunction. In the present review, either recent discoveries or controversial subjects associated with metastasis process will be discussed. Indeed epithelia-mesenchymal transition (EMT), circulating tumor cells, tumor dormancy, colonization in distant organ and cancer stem cells are tackled...
June 2016: Bulletin du Cancer
Anna Maria Rachiglio, Riziero Esposito Abate, Alessandra Sacco, Raffaella Pasquale, Francesca Fenizia, Matilde Lambiase, Alessandro Morabito, Agnese Montanino, Gaetano Rocco, Carmen Romano, Anna Nappi, R Vincenzo Iaffaioli, Fabiana Tatangelo, Gerardo Botti, Fortunato Ciardiello, Monica R Maiello, Antonella De Luca, Nicola Normanno
The circulating free tumor DNA (ctDNA) represents an alternative, minimally invasive source of tumor DNA for molecular profiling. Targeted sequencing with next generation sequencing (NGS) can assess hundred mutations starting from a low DNA input. We performed NGS analysis of ctDNA from 44 patients with metastatic non-small-cell lung carcinoma (NSCLC) and 35 patients with metastatic colorectal carcinoma (CRC). NGS detected EGFR mutations in 17/22 plasma samples from EGFR-mutant NSCLC patients (sensitivity 77...
July 19, 2016: Oncotarget
Qinqin Luo, Zhenye Xu, Lifang Wang, Mingyu Ruan, Guiyu Jin
Lung cancer is still the predominant cause of cancer-associated mortality worldwide. The bone metastasis of lung cancer brings great suffering to the patient. Previous advances have provided insights into the mechanism of bone metastasis. Previous research has investigated lung cancer stem cells and three steps were determined for the lung cancer cells to metastasize to the bone: i) Escaping from the primary tumor; ii) moving in the circulation; iii) colonizing in the bone. Key molecules are involved in each of these process...
August 2016: Molecular and Clinical Oncology
Tobias Piegeler, Thomas Winder, Sabine Kern, Bernhard Pestalozzi, Paul Magnus Schneider, Beatrice Beck-Schimmer
Circulating tumor cells (CTCs) in the blood of cancer patients have been demonstrated to be of prognostic value regarding metastasis and survival. The CellSearch(®) system has been certified for the detection of CTCs and as a prognostic tool in patients with metastatic breast, colon and prostate cancer. Few studies have evaluated the detection of CTCs originating from esophagogastric or pancreatic cancer with the CellSearch(®) system. In the present small pilot study, a total of 16 patients with either esophagogastric (n=8) or pancreatic (n=8) adenocarcinomas at various disease stages were randomly screened and included...
August 2016: Oncology Letters
Christina M van der Beek, Emanuel E Canfora, Kaatje Lenaerts, Freddy J Troost, Steven W M Olde Damink, Jens J Holst, Ad A M Masclee, Cornelis H C Dejong, Ellen E Blaak
Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men. In this randomized, double-blind crossover trial, six overweight/obese men [body mass index (BMI) 25-35 kg/m(2)] underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions...
November 1, 2016: Clinical Science (1979-)
Hassan Ashktorab, Pia Hermann, Mehdi Nouraie, Babak Shokrani, Edward Lee, Tahmineh Haidary, Hassan Brim, Ulrike Stein
BACKGROUND: Colorectal cancer is a preventable disease if caught at early stages. This disease is highly aggressive and has a higher incidence in African Americans. Several biomarkers and mutations of aggressive tumor behavior have been defined such as metastasis-associated in colon cancer 1 (MACC1) that was associated with metastasis in colorectal cancer patients. Here, we aim to assess colon tissue MACC1 protein and circulating MACC1 transcripts in colon preneoplastic and neoplastic African American patients...
2016: Journal of Translational Medicine
Ingrid Wernstedt Asterholm, Ja Young Kim-Muller, Joseph M Rutkowski, Clair Crewe, Caroline Tao, Philipp E Scherer
Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMβ, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMβ has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMβ plays a complex role in immune system regulation, and the impact of loss of function of RELMβ on colon cancer and metabolic regulation has not been fully elucidated...
September 2016: American Journal of Pathology
Jeanne Tie, Yuxuan Wang, Cristian Tomasetti, Lu Li, Simeon Springer, Isaac Kinde, Natalie Silliman, Mark Tacey, Hui-Li Wong, Michael Christie, Suzanne Kosmider, Iain Skinner, Rachel Wong, Malcolm Steel, Ben Tran, Jayesh Desai, Ian Jones, Andrew Haydon, Theresa Hayes, Tim J Price, Robert L Strausberg, Luis A Diaz, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Peter Gibbs
Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9...
July 6, 2016: Science Translational Medicine
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