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Cancer evolution

Andrzej T Slominski, Michal A Zmijewski, Przemyslaw M Plonka, Jerzy P Szaflarski, Ralf Paus
The skin, a self-regulating protective barrier organ, is empowered with sensory and computing capabilities to counteract the environmental stressors to maintain/restore disrupted cutaneous homeostasis. These complex functions are coordinated by a cutaneous neuro-endocrine system that also communicates in a bidirectional fashion with the central nervous, endocrine and immune systems, all acting in concert to control body homeostasis. While ultraviolet energy (UV) has played an important role in the origin and evolution of life, UV absorption by the skin not only triggers mechanisms that defend skin integrity and regulate global homeostasis, but also induces skin pathology (e...
March 12, 2018: Endocrinology
Barry H Smith, Lawrence S Gazda, Thomas J Fahey, Angelica Nazarian, Melissa A Laramore, Prithy Martis, Zoe P Andrada, Joanne Thomas, Tapan Parikh, Sudipta Sureshbabu, Nathaniel Berman, Allyson J Ocean, Richard D Hall, David J Wolf
Objective: The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival (OS) responses, to the use of one such system, implantable macrobeads [RENCA macrobeads (RMBs)], in phase I and IIa clinical trials in advanced, treatment-resistant metastatic colorectal cancer (mCRC) are described here...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
C Bascoul-Mollevi, Marion Savina, Amélie Anota, Antoine Barbieri, David Azria, Franck Bonnetain, Sophie Gourgou
BACKGROUND AND OBJECTIVE: Health-related quality of life (HRQoL) has become one relevant and available alternative endpoint of clinical trials in cancer research to evaluate efficiency of care both for the patient and health system. HRQoL in oncology is mainly assessed using the 30-item European Organisation for Research and Treatment of Cancer Quality of Life-Questionnaire Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 questionnaire is usually assessed at different times along the clinical trials in order to analyze the kinetics of HRQoL evolution and to fully assess the impact of the treatment on the patient's HRQoL level...
May 2018: Computer Methods and Programs in Biomedicine
Kelly Kyker-Snowman, Bracha Erlanger Avigdor, Mansoor Nasim, Ashley Cimino-Mathews, Sarah J Wheelan, Pedram Argani, Ben Ho Park
BACKGROUND/PURPOSE: Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of human cancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. EXPERIMENTAL DESIGN/METHODS: Here, we present a case report of a patient's primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER negative...
March 15, 2018: Breast Cancer Research and Treatment
Maeva Dufies, Damien Ambrosetti, Sonia Boulakirba, Anne Calleja, Coline Savy, Nathan Furstoss, Marwa Zerhouni, Julien Parola, Lazaro Aira-Diaz, Sandrine Marchetti, Francois Orange, Sandra Lacas-Gervais, Frederic Luciano, Arnaud Jacquel, Guillaume Robert, Gilles Pagès, Patrick Auberger
Polo-like kinases (Plks) define a highly conserved family of Ser/Thr kinases with crucial roles in the regulation of cell division. Here we show that Plk1 is cleaved by caspase 3, but not by other caspases in different hematopoietic cell lines treated with competitive inhibitors of the ATP-binding pocket of Plk1. Intriguingly, Plk1 was not cleaved in cells treated with Rigosertib, a non-competitive inhibitor of Plk1, suggesting that binding of the inhibitor to the ATP binding pocket of Plk1 triggers a conformational change and unmasks a cryptic caspase 3 cleavage site on the protein...
February 16, 2018: Oncotarget
Yanchun Ma, Kun Chen, Zhenhua Yang, Ming Guan
Lung cancer is the most common type of malignancy to metastasize to the brain, with the median survival time of patients being 6-11 months. In the present study, the aim was to compare the actionable gene mutation profiles of primary lung adenocarcinoma (LC) samples and LC brain metastasis (LCBM) samples through targeted sequencing. Next generation sequencing (NGS) of 13 formalin-fixed, paraffin-embedded LC samples and 15 LCBM samples was performed using a customized OncoAim™ cancer panel and OncoAim™ RNA fusion panel on the MiSeq platform...
April 2018: Oncology Letters
Takahiro Nakagomi, Taichiro Goto, Yosuke Hirotsu, Daichi Shikata, Yujiro Yokoyama, Rumi Higuchi, Kenji Amemiya, Kenichiro Okimoto, Toshio Oyama, Hitoshi Mochizuki, Masao Omata
Objectives: Pulmonary sarcomatoid carcinomas are rare and generally aggressive tumors composed of carcinomatous and sarcomatous components; however, the evolution of sarcomatoid cancer has not been elucidated. Here, we aimed to evaluate the mutational profiles and phylogeny of sarcomatoid carcinomas using next generation sequencing and in-silico analysis to facilitate the development of novel therapies. Methods: Four patients who underwent surgery for sarcomatoid cancer were enrolled...
February 13, 2018: Oncotarget
Geneviève Dom, Sandra Frank, Sebastien Floor, Pashalina Kehagias, Frederick Libert, Catherine Hoang, Guy Andry, Alex Spinette, Ligia Craciun, Nicolas de Saint Aubin, Christophe Tresallet, Frederique Tissier, Frederique Savagner, Samira Majjaj, Ilse Gutierrez-Roelens, Etienne Marbaix, Jacques E Dumont, Carine Maenhaut
Non-autonomous thyroid nodules are common in the general population with a proportion found to be cancerous. A current challenge in the field is to be able to distinguish benign adenoma (FA) from preoperatively malignant thyroid follicular carcinoma (FTC), which are very similar both histologically and genetically. One controversial issue, which is currently not understood, is whether both tumor types represent different molecular entities or rather a biological continuum. To gain a better insight into FA and FTC tumorigenesis, we defined their molecular profiles by mRNA and miRNA microarray...
February 13, 2018: Oncotarget
Thais Roque, Laurent Risser, Veerle Kersemans, Sean Smart, Danny Allen, Paul Kinchesh, Stuart Gilchrist, Ana L Gomes, Julia A Schnabel, Michael A Chappell
Predicting tumor growth and its response to therapy remains a major challenge in cancer research and strongly relies on tumor growth models. In this paper, we introduce, calibrate, and verify a novel image-driven reaction-diffusion model of avascular tumor growth. The model allows for proliferation, death and spread of tumor cells, and accounts for nutrient distribution and hypoxia. It is constrained by longitudinal time series of dynamic contrast-enhancement-MRI images. Tumor specific parameters are estimated from two early time points and used to predict the spatio-temporal evolution of the tumor volume and cell densities at later time points...
March 2018: IEEE Transactions on Medical Imaging
Jihad Kaouk, Daniel Sagalovich, Juan Garisto
Prostate cancer (PCa) is the most common malignancy among men in the western world.1 Organ confined PCa treatment relies on a precise evaluation of the primary disease site. With the evolution of technology, prostate imaging modalities such as magnetic resonance imaging (MRI) are being used to localize PCa lesions dramatically impacting the management of this urologic malignancy2 . This article is protected by copyright. All rights reserved.
March 13, 2018: BJU International
Wataru Jomoto, Masao Tanooka, Hiroshi Doi, Keisuke Kikuchi, Chiemi Mitsuie, Yusuke Yamada, Toru Suzuki, Toshiko Yamano, Reiichi Ishikura, Noriko Kotoura, Shingo Yamamoto
We sought to develop a surgical navigation system using magnetic resonance angiography (MRA) and a three-dimensional (3D) printer for robot-assisted radical prostatectomy (RARP). Six patients with pathologically proven localized prostate cancer were prospectively enrolled in this study. Prostate magnetic resonance imaging (MRI), consisting of T2-weighted sampling perfection with application-optimized contrasts using different flip-angle evolutions (SPACE) and true fast imaging with steady-state precession (true FISP), reconstructed by volume rendering, was followed by dynamic contrast-enhanced MRA performed with a volumetric interpolated breath-hold examination (VIBE) during intravenous bolus injection of gadobutrol...
January 2, 2018: Curēus
Rui Hao, Yan Qiang, Xiaofei Yan
The accurate segmentation of pulmonary nodules is an important preprocessing step in computer-aided diagnoses of lung cancers. However, the existing segmentation methods may cause the problem of edge leakage and cannot segment juxta-vascular pulmonary nodules accurately. To address this problem, a novel automatic segmentation method based on an LBF active contour model with information entropy and joint vector is proposed in this paper. Our method extracts the interest area of pulmonary nodules by a standard uptake value (SUV) in Positron Emission Tomography (PET) images, and automatic threshold iteration is used to construct an initial contour roughly...
2018: Computational and Mathematical Methods in Medicine
Eva E Tejerina, Rebeca Padilla, Elena Abril, Fernando Frutos-Vivar, Aida Ballen, José María Rodríguez-Barbero, José Ángel Lorente, Andrés Esteban
We evaluate the evolution over time of discrepancies between clinical diagnoses and post-mortem findings in critically ill patients, and to assess the factors associated with these discrepancies. We conducted a prospective study of all consecutive patients who underwent autopsy autopsies in a medical-surgical ICU between January 2008 and December 2015. Among 7.655 patients admitted to our ICU, 671 (8.8%) died. Clinical autopsy was performed in 215 (32%) patients. Major missed diagnoses were noted in 38 patients (17...
March 9, 2018: Human Pathology
Pingyu Nan, Darragh M Walsh, Kerry A Landman, Barry D Hughes
Motivated by in vitro time-lapse images of ovarian cancer spheroids inducing mesothelial cell clearance, the traditional agent-based model of cell migration, based on simple volume exclusion, was extended to include the possibility that a cell seeking to move into an occupied location may push the resident cell, and any cells neighbouring it, out of the way to occupy that location. In traditional discrete models of motile cells with volume exclusion such a move would be aborted. We introduce a new shoving mechanism which allows cells to choose the direction to shove cells that expends the least amount of shoving effort (to account for the likely resistance of cells to being pushed)...
2018: PloS One
Ke-Chih Lin, Gonzalo Torga, Amy Wu, Joshua D Rabinowitz, Wesley J Murray, James C Sturm, Kenneth J Pienta, Robert Austin
We have improved our microfluidic cell culture device that generates an in vitro landscape of stress heterogeneity. We now can do continuous observations of different cancer cell lines and carry out downstream analysis of cell phenotype as a function of position on the stress landscape. We use this technology to probe adaption and evolution dynamics in prostate cancer cell metapopulations under a stress landscape of a chemotherapeutic drug (docetaxel). The utility of this approach is highlighted by analysis of heterogenous prostate cancer cell motility changes as a function of position in the stress landscape...
December 2017: Convergent Science Physical Oncology
Andrew Brandmaier, Sheng-Qi Hou, Sandra Demaria, Silvia C Formenti, Wen H Shen
BACKGROUND: PTEN is well known to function as a tumor suppressor that antagonizes oncogenic signaling and maintains genomic stability. The PTEN gene is frequently deleted or mutated in human cancers and the wide cancer spectrum associated with PTEN deficiency has been recapitulated in a variety of mouse models of Pten deletion or mutation. Pten mutations are highly penetrant in causing various types of spontaneous tumors that often exhibit resistance to anticancer therapies including immunotherapy...
June 2017: Frontiers in Biology
John O Schorge, Amy J Bregar, John Durfee, Ross S Berkowitz
Joe V. Meigs was a visionary clinician and an early adopter of radical techniques in the surgical treatment of ovarian cancer. His 1934 textbook "Tumors of the Female Pelvic Organs", consolidated his approach to this "hopeless" disease, with pearls on diagnosis, outcomes, and even speculations about the benefits of minimally invasive surgery. Decades before adjuvant chemotherapy would prove of value, and in an era when sophisticated statistics were unheard of, he nonetheless tried to eke out what benefits he could using the methods available in his time...
March 7, 2018: Gynecologic Oncology
Céline Mascaux, Ming-Sound Tsao, Fred R Hirsch
Precision medicine commonly refers to the selection of the most effective cancer treatments based on the presence of specific biomarkers (eg, genomic abnormalities) in a patient's tumor. Therefore, genomic testing is used to identify patients whose tumors harbor the vulnerability that is sensitive to corresponding targeted therapies. This approach allows for the selection of patients who have the greatest chance of deriving benefit from the treatments, reduces toxicity, and significantly improves outcome; precision medicine is recommended for advanced non-small cell lung cancer...
March 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Ravi Kiran Deevi, Arman Javadi, Jane McClements, Jekaterina Vohhodina, Kienan Savage, Maurice Bernard Loughrey, Emma Evergren, Frederick Charles Campbell
Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring...
March 9, 2018: Journal of Pathology
Marc Lenoir, Cansel Ustunel, Sandya Rajesh, Jaswant Kaur, Dimitri Moreau, Jean Gruenberg, Michael Overduin
Sorting nexins anchor trafficking machines to membranes by binding phospholipids. The paradigm of the superfamily is sorting nexin 3 (SNX3), which localizes to early endosomes by recognizing phosphatidylinositol 3-phosphate (PI3P) to initiate retromer-mediated segregation of cargoes to the trans-Golgi network (TGN). Here we report the solution structure of full length human SNX3, and show that PI3P recognition is accompanied by bilayer insertion of a proximal loop in its extended Phox homology (PX) domain. Phosphoinositide (PIP) binding is completely blocked by cancer-linked phosphorylation of a conserved serine beside the stereospecific PI3P pocket...
March 8, 2018: Nature Communications
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