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https://www.readbyqxmd.com/read/28133201/-long-term-survival-in-response-to-multimodality-therapy-in-a-patient-with-invasive-pancreatic-cancer-with-cyst-formation
#1
Hironobu Makino, Hisashi Kametaka, Tadaomi Fukada, Kazuhiro Seike, Akio Hasegawa, Masaru Isozaki
The patient was a 61-year-old man. Computed tomography(CT)in April 2007 revealed a pancreatic cyst in the tail of the pancreas. Rapid enlargement was noted in November 2007, and the patient was referred to the surgery department. CT showed a cystic lesion containing a nodular shadow in the pancreatic tail. Tumor marker measurements yielded normal carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels, but the duke pancreatic monoclonal antigen type 2(DUPAN-2)level was elevated. A diagnosis of mucinous cystic neoplasm(MCN)of the pancreas was made in December 2007, and distal pancreatectomy and partial colectomy were performed...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28130225/cellular-model-of-colon-cancer-progression-reveals-signatures-of-mrnas-mirna-lncrnas-and-epigenetic-modifications-associated-with-metastasis
#2
Matjaz Rokavec, David Horst, Heiko Hermeking
Here we developed and comprehensively characterized a cellular model of colon cancer progression consisting of four defined derivatives of a colon cancer cell line that resulted from consecutive epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT/MET) and phenotypically recapitulate the metastatic cascade. Initial EMT was induced by prolonged exposure to IL-6, a cytokine also generated by the tumor-stroma. Genome-wide characterization of transcriptional (mRNA, miRNA, lncRNA) and epigenetic (DNA methylation, H3K4me3, H3K79me3, and H3K27me3 histone modifications) profiles of the cell derivatives, combined with correlative analyses of expression, methylation, and clinical data from the TCGA-COAD database gave insights into the molecular basis of their phenotypic changes...
January 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28041973/prognostic-significance-of-stromal-grem1-expression-in-colorectal-cancer
#3
Bo Gun Jang, Hye Sung Kim, Weon Young Chang, Jeong Mo Bae, Hyeon Jeong Oh, Xianyu Wen, Seorin Jeong, Nam Yun Cho, Woo Ho Kim, Gyeong Hoon Kang
Cancer associated fibroblasts (CAFs) are the dominant cell population in the cancer stroma. Gremlin 1 (GREM1), an antagonist of the bone morphogenetic protein pathway, is expressed by CAFs in a variety of human cancers. However, its biological significance for cancer patients is largely unknown. We applied RNA in situ hybridization (ISH) to evaluate the prognostic value of stromal GREM1 expression in a large cohort of 670 colorectal cancers (CRCs). Overall GREM1 expression in CRCs was lower than that of the matched normal mucosa, and GREM1 expression had a strong positive correlation with BMI1 and inverse correlations with EPHB2 and OLFM4...
December 29, 2016: Human Pathology
https://www.readbyqxmd.com/read/28034806/targeting-the-extracellular-matrix-of-ovarian-cancer-using-functionalized-drug-loaded-lyophilisomes
#4
Sophieke C H A van der Steen, René Raavé, Sjoerd Langerak, Laurens van Houdt, Sander M J van Duijnhoven, Sanne A M van Lith, Leon F A G Massuger, Willeke F Daamen, William P Leenders, Toin H van Kuppevelt
Epithelial ovarian cancer is characterized by a high mortality rate and is in need for novel therapeutic avenues to improve patient outcome. The tumor's extracellular matrix ("stroma") offers new possibilities for targeted drug-delivery. Recently we identified highly sulfated chondroitin sulfate (CS-E) as a component abundantly present in the ovarian cancer extracellular matrix, and as a novel target for anti-cancer therapy. Here, we report on the functionalization of drug-loaded lyophilisomes (albumin-based biocapsules) to specifically target the stroma of ovarian carcinomas with the potential to eliminate cancer cells...
April 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28031408/predictive-outcomes-for-her2-enriched-cancer-using-growth-and-metastasis-signatures-driven-by-sparc
#5
Leandro N Güttlein, Lorena G Benedetti, Cristóbal Fresno, Raúl G Spallanzani, Sabrina F Mansilla, Cecilia Rotondaro, Ximena L Raffo Iraolagoitia, Edgardo Salvatierra, Alicia I Bravo, Elmer A Fernández, Vanesa Gottifredi, Norberto W Zwirner, Andrea S Llera, Osvaldo L Podhajcer
Understanding the mechanism of metastatic dissemination is crucial for the rational design of novel therapeutics. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein which has been extensively associated with human breast cancer aggressiveness although the underlying mechanisms are still unclear. Here, shRNA-mediated SPARC knockdown greatly reduced primary tumor growth and completely abolished lung colonization of murine 4T1 and LM3 breast malignant cells implanted in syngeneic BALB/c mice...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28013338/colon-cancer-cell-derived-12-s-hete-induces-the-retraction-of-cancer-associated-fibroblast-via-mlc2-rho-rock-and-ca-2-signalling
#6
Serena Stadler, Chi Huu Nguyen, Helga Schachner, Daniela Milovanovic, Silvio Holzner, Stefan Brenner, Julia Eichsteininger, Mira Stadler, Daniel Senfter, Liselotte Krenn, Wolfgang M Schmidt, Nicole Huttary, Sigurd Krieger, Oskar Koperek, Zsuzsanna Bago-Horvath, Konstantin Alexander Brendel, Brigitte Marian, Oliver de Wever, Robert M Mader, Benedikt Giessrigl, Walter Jäger, Helmut Dolznig, Georg Krupitza
Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models...
December 24, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27991924/cooperation-among-heterogeneous-prostate-cancer-cells-in-the-bone-metastatic-niche
#7
K Shahriari, F Shen, A Worrede-Mahdi, Q Liu, Y Gong, F U Garcia, A Fatatis
The growth of disseminated tumor cells into metastatic lesions depends on the establishment of a favorable microenvironment in the stroma of the target organs. Here we show that mice treated with anakinra, an antagonist of the interleukin (IL)-1β receptor (IL-1R), or harboring a targeted deletion of IL-1R are significantly less prone to develop bone tumors when inoculated in the arterial circulation with human prostate cancer (PCa) cells expressing IL-1β. Interestingly, human mesenchymal stem cells exposed in vitro to medium conditioned by IL-1β-expressing cancer cells responded by upregulating S100A4, a marker of cancer-associated fibroblasts (CAFs), and this effect was blocked by anakinra...
December 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27942988/investigation-of-malignant-transformation-of-sporadic-adenomas-of-colon-by-fluorimetry
#8
Yu S Korneva, A E Dorosevich, V S Maryakhina
In this work, biochemical changes in sporadic adenoma during progression to colon cancer have been detected by spectral techniques. It is shown that spectra of all types of adenomas as well as adenocarcinoma have two maxima at 265 ÷ 270 nm and at 330 ÷ 340 nm. The first maximum is primarily defined by tryptophan containing peptides. The second maximum of the spectra is in the main defined by collagen presence in stroma of tumors and normal mucosa. Progression of precancer lesions to advanced cancer leads to increase of NADH concentration impacting on the second maximum of spectra...
February 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/27925182/proteomics-analysis-of-differential-protein-expression-identifies-heat-shock-protein-47-as-a-predictive-marker-for-lymph-node-metastasis-in-patients-with-colorectal-cancer
#9
Koichiro Mori, Yuji Toiyama, Kohei Otake, Hiroyuki Fujikawa, Susumu Saigusa, Junichiro Hiro, Minako Kobayashi, Masaki Ohi, Koji Tanaka, Yasuhiro Inoue, Yuhko Kobayashi, Issei Kobayashi, Yasuhiko Mohri, Ajay Goel, Masato Kusunoki
The discovery of biomarkers to predict the potential for lymph node (LN) metastasis in patients with colorectal cancer (CRC) is essential for developing improved strategies for treating CRC. In the present study, they used isobaric tags for relative and absolute quantitation to conduct a proteomic analysis designed to identify novel biomarkers for predicting LN metastasis in patients with CRC. They identified 60 differentially expressed proteins specifically associated with LN metastasis in CRC patients and classified the molecular and functional characteristics of these proteins by bioinformatic approaches...
March 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27853865/adequately-defining-tumor-cell-proportion-in-tissue-samples-for-molecular-testing-improves-interobserver-reproducibility-of-its-assessment
#10
Benoît Lhermitte, Caroline Egele, Noëlle Weingertner, Damien Ambrosetti, Bérengère Dadone, Valérie Kubiniek, Fanny Burel-Vandenbos, John Coyne, Jean-François Michiels, Marie-Pierre Chenard, Etienne Rouleau, Jean-Christophe Sabourin, Jean-Pierre Bellocq
Gene mutation status assessment of tumors has become standard practice in diagnostic pathology. This is done using samples comprising tumor cells but also non-tumor cells, which may dramatically dilute the proportion of tumor DNA and induce false negative results. Increasing sensitivity of molecular tests presently allows detection of a targeted mutation in a sample with a small percentage of tumor cells, but assessment of tumor cellularity remains essential to adequately interpret the results of molecular tests...
January 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27826041/smc1a-recruits-tumor-associated-fibroblasts-tafs-and-promotes-colorectal-cancer-metastasis
#11
Pengyang Zhou, Nan Xiao, Jian Wang, Zhanhuai Wang, Shuchun Zheng, Siyang Shan, Jianping Wang, Jinlin Du, Jianwei Wang
Tumor-associated-fibroblasts (TAFs) are the most important host cells in the stroma and take part in extracellular matrix construction and cancer colony development. During cancer colonization, seed cells from primary tumor can reconstruct the microenvironment by recruiting circulating cancer cells and TAFs to the metastasis site. Previous studies have established that SMC1A, a subunit of cohesin, is an important trigger signal for liver metastasis in colorectal cancer. We investigated the particular effects as well as the underlying mechanism of SMC1A on TAFs recruitment during liver metastasis of colorectal cancer...
January 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27805003/image-analysis-derived-metrics-of-histomorphological-complexity-predicts-prognosis-and-treatment-response-in-stage-ii-iii-colon-cancer
#12
Artur Mezheyeuski, Ina Hrynchyk, Mia Karlberg, Anna Portyanko, Lars Egevad, Peter Ragnhammar, David Edler, Bengt Glimelius, Arne Östman
The complexity of tumor histomorphology reflects underlying tumor biology impacting on natural course and response to treatment. This study presents a method of computer-aided analysis of tissue sections, relying on multifractal (MF) analyses, of cytokeratin-stained tumor sections which quantitatively evaluates of the morphological complexity of the tumor-stroma interface. This approach was applied to colon cancer collection, from an adjuvant treatment randomized study. Metrics obtained with the method acted as independent markers for natural course of the disease, and for benefit of adjuvant treatment...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27804849/when-neighbors-talk-colon-cancer-cell-invasion-and-tumor-microenvironment-myofibroblasts
#13
Jolien Bridelance, Zuzanna Drebert, Olivier De Wever, Marc Bracke, Ilse M Beck
Historically, the word cancer is derived from the Latin cancer, as the red swollen arteries near a tumor reminded the physician Galenus and his fellow Romans of a red crab. Currently, cancer remains the disease to beat as it remains a leading cause of death worldwide (WHO). Tumors do not simply consist out of cancer cells, as they can recruit normal cells, which will form the tumor-associated stroma. These stromal cells together with the extracellular matrix, constitute the tumor microenvironment. Reciprocal communication between tumor-associated stromal cells and cancer cells is important for the induction of epithelial-to-mesenchymal transition and invasion...
October 28, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27637888/mutant-p53-together-with-tgf%C3%AE-signaling-influence-organ-specific-hematogenous-colonization-patterns-of-pancreatic-cancer
#14
Yi Zhong, Anne Macgregor-Das, Tyler Saunders, Martin C Whittle, Alvin Makohon-Moore, Zachary A Kohutek, Justin Poling, Brian T Herbst, Breanna M Javier, Leslie Cope, Steven D Leach, Sunil R Hingorani, Christine A Iacobuzio-Donahue
Purpose: TP53 and the TGFβ pathway are major mediators of pancreatic cancer metastasis. The mechanisms by which they cause hematogenous metastasis have not been fully explored.Experimental Design:KPC (LSL-KRAS(G12D/+);LSL-Trp53(R172H/+); Ptf1a(Cre/+)) mice were generated, and the frequency and morphology of organ-specific hematogenous metastases compared with that seen in KPTC and KTC littermates (Tgfbr2(+/-)). Key findings were validated in primary cells from each genotype and samples of human pancreatic cancer liver metastases...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27605398/glycoprotein-asporin-as-a-novel-player-in-tumour-microenvironment-and-cancer-progression
#15
Dana Simkova, Gvantsa Kharaishvili, Eva Slabakova, Paul G Murray, Jan Bouchal
BACKGROUND: Small leucine rich proteoglycans (SLRPs), major non-collagen components of the extracellular matrix (ECM), have multiple biological roles with diverse effects. Asporin, a member of the SLRPs class I, competes with other molecules in binding to collagen and affects its mineralization. Its role in cancer is only now being elucidated. METHODS: The PubMed online database was used to search relevant reviews and original articles. Furthermore, altered asporin expression was analysed in publicly available genome-wide expression data at the Gene Expression Omnibus database...
December 2016: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/27587539/metabolic-plasticity-as-a-determinant-of-tumor-growth-and-metastasis
#16
REVIEW
Camille Lehuédé, Fanny Dupuy, Rebecca Rabinovitch, Russell G Jones, Peter M Siegel
Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. Different stages of the metastatic cascade can also present distinct metabolic challenges to disseminating cancer cells. However, little is known regarding how changes in cellular metabolism, both within the cancer cell and the metastatic microenvironment, alter the ability of tumor cells to colonize and grow in distinct secondary sites...
September 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27561878/highly-increased-125i-jr11-antagonist-binding-in-vitro-reveals-novel-indications-for-sst2-targeting-in-human-cancers
#17
Jean Claude Reubi, Beatrice Waser, Helmut R Maecke, Jean E Rivier
There is recent in vitro and in vivo evidence that somatostatin receptor sst2 antagonists are better tools to target neuroendocrine tumors (NET) than sst2 agonists. Indeed, antagonists bind to a greater number of sst2 sites than agonists. Whether sst2 antagonists could be used successfully to target non-NET tumors, expressing low sst2 density, is unknown. Here, we compare quantitatively (125)I-JR11 sst2 antagonist binding in vitro with that of the sst2 agonist (125)I-Tyr3-octreotide in large varieties of non-NET and NET...
August 25, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27553580/women-with-endometriosis-have-higher-comorbidities-analysis-of-domestic-data-in-taiwan
#18
REVIEW
Sen-Wen Teng, Huann-Cheng Horng, Chi-Hong Ho, Ming-Shyen Yen, Hsiang-Tai Chao, Peng-Hui Wang
Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases...
November 2016: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/27543333/stromal-uptake-and-transmission-of-acid-is-a-pathway-for-venting-cancer-cell-generated-acid
#19
Alzbeta Hulikova, Nicholas Black, Lin-Ting Hsia, Jennifer Wilding, Walter F Bodmer, Pawel Swietach
Proliferation and invasion of cancer cells require favorable pH, yet potentially toxic quantities of acid are produced metabolically. Membrane-bound transporters extrude acid from cancer cells, but little is known about the mechanisms that handle acid once it is released into the poorly perfused extracellular space. Here, we studied acid handling by myofibroblasts (colon cancer-derived Hs675.T, intestinal InMyoFib, embryonic colon-derived CCD-112-CoN), skin fibroblasts (NHDF-Ad), and colorectal cancer (CRC) cells (HCT116, HT29) grown in monoculture or coculture...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27492255/stromal-hedgehog-signalling-is-downregulated-in-colon-cancer-and-its-restoration-restrains-tumour-growth
#20
Marco Gerling, Nikè V J A Büller, Leonard M Kirn, Simon Joost, Oliver Frings, Benjamin Englert, Åsa Bergström, Raoul V Kuiper, Leander Blaas, Mattheus C B Wielenga, Sven Almer, Anja A Kühl, Erik Fredlund, Gijs R van den Brink, Rune Toftgård
A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC) has been proposed. In CRC and other solid tumours, Hh ligands are upregulated; however, a specific Hh antagonist provided no benefit in a clinical trial. Here we use Hh reporter mice to show that downstream Hh activity is unexpectedly diminished in a mouse model of colitis-associated colon cancer, and that downstream Hh signalling is restricted to the stroma. Functionally, stroma-specific Hh activation in mice markedly reduces the tumour load and blocks progression of advanced neoplasms, partly via the modulation of BMP signalling and restriction of the colonic stem cell signature...
August 5, 2016: Nature Communications
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