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https://www.readbyqxmd.com/read/29761931/the-intranuclear-pex-domain-of-mmp-involves-proliferation-migration-and-metastasis-of-aggressive-adenocarcinoma-cells
#1
Yuka Okusha, Takanori Eguchi, Chiharu Sogawa, Tatsuo Okui, Keisuke Nakano, Kuniaki Okamoto, Ken-Ichi Kozaki
Members of matrix metalloproteinase (MMP) family promote cancer cell migration, invasion, and metastasis through alteration of the tumor milieu, intracellular signaling pathways, and transcription. We examined gene expression signatures of colon adenocarcinoma cell lines with different metastatic potentials and found that rapidly metastatic cells powerfully expressed genes encoding MMP3 and MMP9. The non-proteolytic PEX isoform and proteolytic isoforms of MMPs were significantly expressed in the metastatic cells in vitro...
May 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29755119/predictive-potential-of-tumour-stroma-ratio-on-benefit-from-adjuvant-bevacizumab-in-high-risk-stage-ii-and-stage-iii-colon-cancer
#2
Stéphanie M Zunder, Gabi W van Pelt, Hans J Gelderblom, Christoph Mancao, Hein Putter, Rob A Tollenaar, Wilma E Mesker
BACKGROUND: The tumour-stroma ratio (TSR) has proven to be an independent prognostic factor in colon cancer. METHODS: Haematoxylin eosin tissue slides of patients from the AVANT trial were microscopically scored for TSR and categorised as stroma -low or stroma -high. Scores were correlated to the primary and secondary endpoint disease-free survival (DFS) and overall survival (OS). RESULTS: Patients with stroma-high tumours (N = 339, 28%) had a significantly shorter DFS (p < 0...
May 14, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29747061/serrated-epithelial-colorectal-polyps-hyperplastic-polyps-sessile-serrated-adenomas-with-perineurial-stroma-clinicopathological-and-molecular-analysis-of-a-new-series
#3
Katharina Erlenbach-Wünsch, Michel Bihl, Arndt Hartmann, Gabriel M Groisman, Michael Vieth, Abbas Agaimy
Serrated colorectal fibroblastic polyps (FPs) are rare benign mucosal lesions composed of serrated epithelial crypts separated and distorted by intimately associated bland spindle cell proliferations with perineurial-like phenotype. We herein describe 21 new FPs affecting 10 females and 9 males aged 45 to 80 yrs. (mean, 62 yrs). Lesions originated in the sigmoid colon/rectosigmoid junction (n = 16), rectum (n = 2), and other parts of the colon (n = 3). Most patients had additional synchronous or metachronous polyps: classical adenomas (12 patients), sessile serrated adenoma/SSA (1 patient), hyperplastic polyps/HPs (7 patients), both HPs and adenomas (6 patients) and colorectal cancer (2 patients)...
May 4, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29742733/immunotherapy-for-pulmonary-squamous-cell-carcinoma-and-colon-carcinoma-with-pembrolizumab-a-case-report
#4
Yoshihiro Nozawa, Yuka Oka, Jun Oosugi, Shinichi Takemura
RATIONALE: Novel treatment strategies such as immunotherapy are being evaluated to further improve the outcomes of colorectal cancer patients. To our knowledge, this is the first report to show both the successful treatment of pulmonary squamous cell carcinoma (SCC) with pembrolizumab alongside histological and immunohistochemical findings of resected colon cancer under immunotherapy for lung cancer. PATIENT CONCERNS: This patient was a 70-year-old man who presented with a right lung tumor and simultaneous adenocarcinoma of the sigmoid colon...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29731999/periostin-attenuates-tumor-growth-by-inducing-apoptosis-in-colitis-related-colorectal-cancer
#5
Yusuke Shimoyama, Keiichi Tamai, Rie Shibuya, Mao Nakamura, Mai Mochizuki, Kazunori Yamaguchi, Yoichi Kakuta, Yoshitaka Kinouchi, Ikuro Sato, Akira Kudo, Tooru Shimosegawa, Kennichi Satoh
Inflammatory bowel diseases, which are multifactorial autoimmune colitis diseases, are occurring with increasing prevalence. One of the most serious complications of these diseases is colorectal cancer. Here we investigated the role of periostin (Postn), a matricellular protein that interacts with various integrin molecules on the cell surface, in colitis-induced colorectal cancer. Immunohistochemistry of mouse and human colorectal cancer samples revealed that Postn was expressed in the stroma and was upregulated in close proximity to the cancer cells...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29731961/macrophages-induce-budding-in-aggressive-human-colon-cancer-subtypes-by-protease-mediated-disruption-of-tight-junctions
#6
Kari Trumpi, Nicola Frenkel, Timo Peters, Nicoline M Korthagen, Jennifer M J Jongen, Daniëlle Raats, Helma van Grevenstein, Yara Backes, Leon M Moons, Miangela M Lacle, Jan Koster, Danny Zwijnenburg, Inne H M Borel Rinkes, Onno Kranenburg
Primary human colorectal tumors with a high stromal content have an increased capacity to metastasize. Cancer-associated fibroblasts (CAFs) promote metastasis, but the contribution of other stromal cell types is unclear. Here we searched for additional stromal cell types that contribute to aggressive tumor cell behavior. By making use of the 'immunome compendium'-a collection of gene signatures reflecting the presence of specific immune cell-types-we show that macrophage signatures are most strongly associated with a high CAF content and with poor prognosis in multiple large cohorts of primary tumors and liver metastases...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29680688/absolute-cosine-based-svm-rfe-feature-selection-method-for-prostate-histopathological-grading
#7
Shahnorbanun Sahran, Dheeb Albashish, Azizi Abdullah, Nordashima Abd Shukor, Suria Hayati Md Pauzi
OBJECTIVE: Feature selection (FS) methods are widely used in grading and diagnosing prostate histopathological images. In this context, FS is based on the texture features obtained from the lumen, nuclei, cytoplasm and stroma, all of which are important tissue components. However, it is difficult to represent the high-dimensional textures of these tissue components. To solve this problem, we propose a new FS method that enables the selection of features with minimal redundancy in the tissue components...
April 18, 2018: Artificial Intelligence in Medicine
https://www.readbyqxmd.com/read/29629944/human-endometriosis-tissue-microarray-reveals-site-specific-expression-of-estrogen-receptors-progesterone-receptor-and-ki67
#8
Mariano Colón-Caraballo, Miosotis García, Adalberto Mendoza, Idhaliz Flores
Most available therapies for endometriosis are hormone-based and generally broadly used without taking into consideration the ovarian hormone receptor expression status. This contrasts strikingly with the standard of care for other hormone-based conditions such as breast cancer. We therefore aimed to characterize the expression of ovarian steroid hormone receptors for estrogen alpha (ESR1), estrogen beta (ESR2), and progesterone (PGR) in different types of endometriotic lesions and eutopic endometrium from women with endometriosis and controls using a tissue microarray (TMA)...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29628185/revisiting-colorectal-cancer-animal-model-an-improved-metastatic-model-for-distal-rectosigmoid-colon-carcinoma
#9
Rui Caetano-Oliveira, Marcos António Gomes, Ana Margarida Abrantes, Edgar Tavares-Silva, Marco Carvalho Oliveira, Mafalda Laranjo, Débora Basílio Queirós, João Casalta-Lopes, Salomé Pires, Lina Carvalho, Rosa Gouveia, Paulo Rodrigues Santos, Denise Gonçalves Priolli, José Guilherme Tralhão, Maria Filomena Botelho
Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model. We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1 × 107 cells/animal) in RNU rats (n = 55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon...
March 13, 2018: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/29626120/a-new-method-for-tumor-imaging-by-targeting-cancer-associated-fibroblasts
#10
Anastasia Loktev, Thomas Lindner, Walter Mier, Jürgen Debus, Annette Altmann, Dirk Jäger, Frederik Giesel, Clemens Kratochwil, Philippe Barthe, Christian Roumestand, Uwe Haberkorn
The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the focus is notably on a subpopulation of stromal cells, known as cancer-associated fibroblasts (CAFs), which are present in more than 90% of epithelial carcinomas including pancreatic, colon and breast cancer. CAFs feature a high expression of fibroblast activation protein (FAP), which is not detectable in adult normal tissue but associated with a poor prognosis in cancer patients...
April 6, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29623978/in-vitro-elucidation-of-the-role-of-pericellular-matrix-in-metastatic-extravasation-and-invasion-of-breast-carcinoma-cells
#11
Marie-Elena Brett, Heather E Bomberger, Geneva R Doak, Matthew A Price, James B McCarthy, David K Wood
Numerous studies have demonstrated the importance of altered hyaluronan metabolism to malignant progression of multiple tumor types, including breast carcinomas. Increased hyaluronan (HA) metabolism in the stroma of primary tumors promotes activation of oncogenic signaling pathways that impact tumor initiation, growth, and invasion. Carcinoma cell synthesis and assembly of HA-rich pericellular matrices induces a stromal-independent phenotype, which is associated with cancer progression. Although the pro-tumorigenic role of stromal HA is well established, a novel but unexplored hypothesis is that carcinoma cell-associated HA pericellular matrices promote metastasis of circulating tumor cells...
April 6, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29575602/exosomal-tetraspanins-as-regulators-of-cancer-progression-and-metastasis-and-novel-diagnostic-markers
#12
REVIEW
Rama Rao Malla, Santhi Pandrangi, Seema Kumari, Murali Mohan Gavara, Anil Kumar Badana
Exosomes are cell-cell communicators emerging as a new paradigm for noninvasive diagnosis and prognosis of treatment response. Exosomal tetraspanin proteins like CD63, CD9 and CD81 play a critical role in sorting, selective recruitment of biomolecules, target selection, cell-specific entry, capturing, angiogenesis and vasculogenesis. These tetraspanins are being used as markers for oral, colorectal and colon cancers and glioblastoma. However, exosomal markers with robust specificity for early detection of carcinomas are the furthest along...
March 25, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29558947/does-heterogeneity-matter-in-the-estimation-of-tumour-budding-and-tumour-stroma-ratio-in-colon-cancer
#13
Ann C Eriksen, Johnnie B Andersen, Jan Lindebjerg, René dePont Christensen, Torben F Hansen, Sanne Kjær-Frifeldt, Flemming B Sørensen
BACKGROUND: Tumour budding (TB) and Tumour Stroma Ratio (TSR) may be rewarding in the treatment stratification of patients with stage II colon cancer. However, lack of standardization may exclude these parameters from being used in a clinical setting. The purpose of this methodologic study was to compare stereology with semi-quantitative estimations of TSR, to investigate the intra-tumoural heterogeneity of TB and TSR, and to assess the intra- and inter-observer agreement. METHODS: Three paraffin embedded tumour blocks, one of them representing the deepest invasive front, were selected from each of 43 patients treated for stage II colon cancer...
March 20, 2018: Diagnostic Pathology
https://www.readbyqxmd.com/read/29551360/complement-5a-stimulates-macrophage-polarization-and-contributes-to-tumor-metastases-of-colon-cancer
#14
Chunmei Piao, Wen-Mei Zhang, Tao-Tao Li, Cong-Cong Zhang, Shulan Qiu, Yan Liu, Sa Liu, Ming Jin, Li-Xin Jia, Wen-Chao Song, Jie Du
Inflammatory cells such as macrophages can play a pro-tumorigenic role in the tumor stroma. Tumor-associated macrophages (TAMs) generally display an M2 phenotype with tumor-promoting activity; however, the mechanisms regulating the TAM phenotype remain unclear. Complement 5a (C5a) is a cytokine-like polypeptide that is generated during complement system activation and is known to promote tumor growth. Herein, we investigated the role of C5a on macrophage polarization in colon cancer metastasis in mice. We found that deficiency of the C5a receptor (C5aR) severely impairs the metastatic ability of implanted colon cancer cells...
March 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29467240/identification-isolation-and-characterization-of-human-lgr5-positive-colon-adenoma-cells
#15
Michael K Dame, Durga Attili, Shannon D McClintock, Priya H Dedhia, Peter Ouillette, Olaf Hardt, Alana M Chin, Xiang Xue, Julie Laliberte, Erica L Katz, Gina M Newsome, David R Hill, Alyssa J Miller, Yu-Hwai Tsai, David Agorku, Christopher H Altheim, Andreas Bosio, Becky Simon, Linda C Samuelson, Jay A Stoerker, Henry D Appelman, James Varani, Max S Wicha, Dean E Brenner, Yatrik M Shah, Jason R Spence, Justin A Colacino
The intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, whereas less is known about human intestinal stem cells owing to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC)-associated genes...
March 14, 2018: Development
https://www.readbyqxmd.com/read/29463593/interleukin-33-signaling-restrains-sporadic-colon-cancer-in-an-interferon-%C3%AE-dependent-manner
#16
Moritz F Eissmann, Christine Dijkstra, Merridee A Wouters, David Baloyan, Dmitri Mouradov, Paul M Nguyen, Mercedes Davalos-Salas, Tracy L Putoczki, Oliver M Sieber, John M Mariadason, Matthias Ernst, Frederick Masson
Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell death. The epithelium and stroma of the intestine express large amounts of IL33 and its receptor St2. IL33 is therefore continuously released during homeostatic turnover of the intestinal mucosa. Although IL33 can prevent colon cancer associated with inflammatory colitis, the contribution of IL33 signaling to sporadic colon cancer remains unknown. Here, we utilized a mouse model of sporadic colon cancer to investigate the contribution of IL33 signaling to tumorigenesis in the absence of preexisting inflammation...
April 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29457843/the-tumour-stroma-ratio-in-colon-cancer-the-biological-role-and-its-prognostic-impact
#17
REVIEW
Gabi W van Pelt, Tessa P Sandberg, Hans Morreau, Hans Gelderblom, J Han J M van Krieken, Rob A E M Tollenaar, Wilma E Mesker
The tumour microenvironment consists of a complex mixture of non-neoplastic cells, including fibroblasts, immune cells and endothelial cells embedded in the proteins of the extracellular matrix. The tumour microenvironment plays an active role in tumour behaviour. By interacting with cancer cells, it influences disease progression and the metastatic capacity of the tumour. Tumours with a high amount of stroma correspond to poor patient prognosis. The tumour-stroma ratio (TSR) is a strong independent prognostic tool in colon cancer and provides additional value to the current clinically used tumour-node-metastasis classification...
February 19, 2018: Histopathology
https://www.readbyqxmd.com/read/29448309/the-value-of-additional-bevacizumab-in-patients-with-high-risk-stroma-high-colon-cancer-a-study-within-the-quasar2-trial-an-open-label-randomized-phase-3-trial
#18
Anouck Huijbers, Gabi W van Pelt, Rachel S Kerr, Elaine C Johnstone, Rob A E M Tollenaar, David J Kerr, Wilma E Mesker
INTRODUCTION: Patients with a high stroma percentage within the primary tumor have a poor prognosis. In this study, we investigate whether anti-angiogenic therapy might improve survival of patients with a stroma-high profile with potentially increased angiogenesis. MATERIALS AND METHODS: Tissue samples of the primary tumor of 965 colon cancer patients participating in the QUASAR2 trial were analyzed for tumor-stroma ratio (TSR). Stroma-high (>50%) and stroma-low (≤50%) groups were evaluated with respect to survival...
February 15, 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29408993/effects-of-histone-methyltransferase-inhibition-in-endometriosis
#19
Mariano Colón-Caraballo, Annelyn Torres-Reverón, John Lee Soto-Vargas, Steven Young, Bruce Lessey, Adalberto Mendoza, Raúl Urrutia, Idhaliz Flores
Although the histone methyltransferase EZH2 and its product H3K27me3 are well studied in cancer, little is known about their role and potential as therapeutic targets in endometriosis. We have previously reported that endometriotic lesions are characterized by global enrichment of H3K27me3. Therefore, we aimed to 1) characterize the expression levels of EZH2 in endometriotic tissues, 2) assess H3K27me3 enrichment in candidate genes promoter regions, and 3) determine if pharmacological inhibition of EZH2 impacts migration, proliferation, and invasion of endometriotic cells...
February 2, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29367760/ros-release-by-ppar%C3%AE-%C3%AE-null-fibroblasts-reduces-tumor-load-through-epithelial-antioxidant-response
#20
Eddie Han Pin Tan, Ming Keat Sng, Ivan Shun Bo How, Jeremy Soon Kiat Chan, Jiapeng Chen, Chek Kun Tan, Walter Wahli, Nguan Soon Tan
Tumor stroma has an active role in the initiation, growth, and propagation of many tumor types by secreting growth factors and modulating redox status of the microenvironment. Although PPARβ/δ in fibroblasts was shown to modulate oxidative stress in the wound microenvironment, there has been no evidence of a similar effect in the tumor stroma. Here, we present evidence of oxidative stress modulation by intestinal stromal PPARβ/δ, using a FSPCre-Pparb/d-/- mouse model and validated it with immortalized cell lines...
January 25, 2018: Oncogene
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