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Neprilysin and breast cancer

Emmanouil Lymperis, Aikaterini Kaloudi, Werner Sallegger, Ingrid L Bakker, Eric P Krenning, Marion DeJong, Theodosia Maina, Berthold Artur Nock
Recent advances in oncology involve the use of diagnostic/therapeutic radionuclide-carrier pairs that target cancer cells, offering exciting opportunities for personalized patient treatment. Theranostic gastrin-releasing peptide receptor (GRPR)-directed radiopeptides have been proposed for the management of GRPR-expressing prostate and breast cancers. We have recently introduced the PET tracer 68Ga-SB3 (SB3, DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt), a receptor-radioantagonist that enables the visualization of GRPR-positive lesions in human...
April 17, 2018: Bioconjugate Chemistry
Nuray Erin, Tümay İpekçi, Bahar Akkaya, İrem Hicran Özbudak, Mehmet Baykara
Calcitonin Gene-related Peptide (CGRP), Vasoactive Intestinal Peptide (VIP) and Substance P (SP) are sensory neuropeptides which may alter cancer growth through modulation of chronic inflammation. We recently reported that SP suppresses breast cancer growth and metastasis through neuroimmune modulation. These neuropeptides are hydrolyzed by Neprilysin (NEP) to bioactive fragments. Decreased activity of NEP was reported in clear cell and chromophobe type renal cell carcinoma (RCC). It is however not known how the levels of neuropeptides hydrolyzed with NEP changes in RCC...
December 2016: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
Esra Arslan Aydemir, Ece Şimşek, Aylin Fidan Korcum, Kayahan Fişkin
Angiogenesis, the formation of new blood vessels, is regarded as a key cancer cell property. Endostatin (ES) is a potential antiangiogenic agent and it may be useful when implemented in combination with other cancer therapeutic strategies. The present study investigated the in vitro effects of ES, radiotherapy (RT) or combination therapy (ES + RT) on two important proteases, a disintegrin and metalloproteinase domain‑containing protein 10 (ADAM10) and neprilysin (NEP) in 4T1 mouse breast cancer cells and the more metastatic phenotype of 4THMpc breast cancer cells...
September 2016: Molecular Medicine Reports
H M Stephen, R J Khoury, P R Majmudar, T Blaylock, K Hawkins, M S Salama, M D Scott, B Cosminsky, N K Utreja, J Britt, R E Conway
In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion...
2016: Oncogenesis
Ece Şimşek, Esra Aydemir, Aylin Fidan Korcum, Kayahan Fişkın
The aim of the present study was to investigate the effects of thalidomide, a drug known for its anti‑angiogenic and antitumor properties, at its cytotoxic dose previously determined as 40 µg/ml (according to four cytotoxic test results). The effect of the drug alone and in combination with radiotherapy using Cobalt 60 (60Co) at 45 Gy on the enzymatic activity of substance‑P degrading A disintegrin and metalloproteinase (ADAM)10 and neprilysin (NEP) was investigated in the mouse breast cancer cell lines 4T1 and 4T1 heart metastases post‑capsaicin (4THMpc)...
February 2015: Molecular Medicine Reports
Sayantan H Jana, Bharti M Jha, Chandni Patel, Dipan Jana, Anshul Agarwal
BACKGROUND AND AIMS: Breast cancer is one of the leading causes of mortality in Indian women. Although breast cancer is an epithelial malignancy, stroma plays a key role in its development and pathogenesis. Stromal markers are now emerging as novel markers in assessing the prognosis of invasive breast cancer and have not been studied extensively till date. The aim of the present study is to study the stromal expression of CD10 in breast carcinoma, find its relationship with other prognostic markers and study the role stroma plays in breast cancer pathogenesis...
October 2014: Indian Journal of Pathology & Microbiology
Heidi N Hilton, N Santucci, A Silvestri, S Kantimm, L I Huschtscha, J D Graham, C L Clarke
The epithelium of the human breast is made up of a branching ductal-lobular system, which is lined by a single layer of luminal cells surrounded by a contractile basal cell layer. The co-ordinated development of stem/progenitor cells into these luminal and basal cells is fundamentally important for breast morphogenesis. The ovarian steroid hormones, progesterone (P) and 17β-estradiol, are critical in driving this normal breast development, yet ovarian activity has also been shown to be a major driver of breast cancer risk...
February 2014: Breast Cancer Research and Treatment
Imran Haruna Abdulkareem, Maria Blair
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor gene deleted or mutated in many human cancers such as glioblastoma, spinal tumors, prostate, bladder, adrenals, thyroid, breast, endometrium, and colon cancers. They result from loss of heterozygosity (LOH) for the PTEN gene on chromosome 10q23. Previous studies reported that various drugs, chemicals, and foods can up-regulate PTEN mRNA and protein expression in different cell lines, and they may be useful in the future prevention and/or treatment of these cancers...
March 2013: Nigerian Medical Journal: Journal of the Nigeria Medical Association
Thi-Ngoc Diem Vo, Eiji Mekata, Tomoko Umeda, Hajime Abe, Yuki Kawai, Tsuyoshi Mori, Yoshihiro Kubota, Hisanori Shiomi, Shigeyuki Naka, Tomoharu Shimizu, Satoshi Murata, Hiroshi Yamamoto, Mitsuaki Ishida, Tohru Tani
BACKGROUND: Early diagnosis and treatment for breast cancers has greatly improved in recent years, however, subset of this disease with early recurrence have remained to be unpredictable. Several studies has addressed that strong CD10 expression in tumor stroma is associated with poor survival rate of breast cancers, but no correlation between CD10 expression and disease-free survival has been elucidated yet. For these reasons, this study with modified immunohistochemical (IHC) staining evaluated the expression of CD10 in invasive breast carcinomas (IBCs) and analyzed correlations between CD10 expression on tumor cells, stromal cells and myeloid-like cells with clinicopathological parameters and recurrence status...
March 2015: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Dellyana R Boberg, Meire S Batistela, Micheli Pecharki, Enilze M S F Ribeiro, Iglenir J Cavalli, Rubens S Lima, Cícero A Urban, Lupe Furtado-Alle, Ricardo L R Souza
Gene amplifications and deletions are common changes in human cancer cells. Previous studies indicate that the regions, where the ACHE (7q22) and BCHE (3q26.1-q26.2) genes are localized, are suffering such structural modifications in breast cancer. Therefore, the products of these genes, acetylcholinesterase and butyrylcholinesterase, respectively, are related to the process of cell differentiation and proliferation, as well as apoptosis. This study also included two other genes involved in tumorigenesis, the EPHB4 (7q22...
March 25, 2013: Chemico-biological Interactions
Nuray Erin, Ozlem Duymuş, Saffet Oztürk, Necdet Demir
Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis...
November 10, 2012: Regulatory Peptides
Munenori Ide, Toshihide Kato, Kyoichi Ogata, Erito Mochiki, Hiroyuki Kuwano, Tetsunari Oyama
BACKGROUND: Keratin 17 (K17) is regarded as a basal/myoepithelial cell keratin and is known to be inducible in activated keratinocytes. The high frequency of K17 expression in pancreaticobiliary nonmucinous adenocarcinoma or basal-like breast carcinoma has previously been described. However, its expression in gastric cancer (GC) is controversial. METHODS: We investigated the clinicopathological features and prognostic significance of 192 patients with GC by immunohistochemical staining of tissue microarrays...
October 2012: Annals of Surgical Oncology
Christine Desmedt, Samira Majjaj, Naima Kheddoumi, Sandeep K Singhal, Benjamin Haibe-Kains, Frank El Ouriaghli, Carole Chaboteaux, Stefan Michiels, Françoise Lallemand, Fabrice Journe, Hughes Duvillier, Sherene Loi, John Quackenbush, Sophie Dekoninck, Cédric Blanpain, Laurence Lagneaux, Nawal Houhou, Mauro Delorenzi, Denis Larsimont, Martine Piccart, Christos Sotiriou
PURPOSE: There is growing evidence that interaction between stromal and tumor cells is pivotal in breast cancer progression and response to therapy. Based on earlier research suggesting that during breast cancer progression, striking changes occur in CD10(+) stromal cells, we aimed to better characterize this cell population and its clinical relevance. EXPERIMENTAL DESIGN: We developed a CD10(+) stroma gene expression signature (using HG U133 Plus 2.0) on the basis of the comparison of CD10 cells isolated from tumoral (n = 28) and normal (n = 3) breast tissue...
February 15, 2012: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Wael S Ibrahim
BACKGROUND: Phyllodes tumors are group of biphasic fibroepithelial tumors of the breast of varying malignant potential, ranging from benign tumors to fully malignant sarcomas. According to the Egyptian National Cancer Institute, female malignant cases showed appreciable increase in the recent time period for breast cancer with the malignant phyllodes tumors representing 0.41% of cases in the year 2003-2004. AIMS: This is an immunohistochemical study to compare CD10 expression in benign, borderline, and malignant phyllodes tumors, in order to highlight its diagnostic and prognostic values...
October 2011: Indian Journal of Pathology & Microbiology
Patricia J Keller, Lisa M Arendt, Adam Skibinski, Tanya Logvinenko, Ina Klebba, Shumin Dong, Avi E Smith, Aleix Prat, Charles M Perou, Hannah Gilmore, Stuart Schnitt, Stephen P Naber, Jonathan A Garlick, Charlotte Kuperwasser
Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM(+)) and basal/myoepithelial (CD10(+)). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer...
February 21, 2012: Proceedings of the National Academy of Sciences of the United States of America
Nicholas W Bateman, Mai Sun, Brian L Hood, Melanie S Flint, Thomas P Conrads
Breast cancer is a highly heterogeneous disease, an observation that underscores the importance of elucidating conserved molecular characteristics, such as gene and protein expression, across breast cancer cell types toward providing a greater understanding of context-specific features central to this disease. Motivated by the goal of defining central biological themes across breast cancer cell subtypes, we conducted a global proteomic analysis of three breast cancer cell lines, MCF7, SK-BR-3, and MDA-MB-231, and compared these to a model of nontransformed mammary cells (MCF10A)...
October 1, 2010: Journal of Proteome Research
O Rögelsperger, C Ekmekcioglu, W Jäger, M Klimpfinger, R Königsberg, D Krenbek, F Sellner, T Thalhammer
Activation of the G-protein-coupled receptor (GPCR) for melatonin (MT1) suppresses breast cancer cell growth in experimental models. To elucidate whether MT1 might play a role in cancer cells positive for the stem cell marker nestin, we assessed paired carcinomatous (Ca) and adjacent noncancerous (NCa) samples from 42 patients with primary breast cancer for MT1 and nestin by double immunofluorescence staining and quantitative image analysis with Tissue-Quest software. MT1 was located in luminal and myoepithelial cells in milk ducts and in tumor cells in 40/42 and 39/42 of NCa and Ca specimens, respectively, independent of hormone receptor and HER-2 status...
May 2009: Journal of Pineal Research
Yuji Ohtsuki, Naoto Kuroda, Tatsuo Umeoka, Ryohei Watanabe, Kenji Ochi, Yuhei Okada, Gang-Hong Lee, Mutsuo Furihata
To evaluate the peculiar "inside-out" pattern in micropapillary (MP) carcinoma, we investigated the usefulness of KL-6 antibody in the assessment of the MP pattern of cancers, in comparison with antibodies to epithelial membrane antigen (EMA), MUC1 (CD227), and CD 10. Immunohistochemical investigation was performed on specimens exhibiting an MP pattern obtained from 12 persons with cancer: 4 with breast carcinoma, 3 with carcinoma of the urinary bladder, and 5 with colonic carcinoma. Immunohistochemical study with KL-6, EMA, and MUC1 antibodies revealed similar continuous linear positive patterns restricted to the surface of the MP pattern in both breast and urinary bladder cancers, revealing the peculiar "inside-out" morphology...
June 2009: Medical Molecular Morphology
Denis Ravel, Vincent Dubois, Jérôme Quinonero, Florence Meyer-Losic, Jeanpierre Delord, Philippe Rochaix, Céline Nicolazzi, Fabien Ribes, Catherine Mazerolles, Elise Assouly, Karine Vialatte, Inès Hor, Jonathan Kearsey, André Trouet
PURPOSE: There is a clear clinical need for cytotoxic drugs with a lower systemic toxicity. DTS-201 (CPI-0004Na) is a peptidic prodrug of doxorubicin that shows an improved therapeutic index in experimental models. The purpose of the current study was to complete its preclinical characterization before initiation of phase I clinical trials. EXPERIMENTAL DESIGN: The preclinical development program consisted of a detailed assessment of the general and cardiac toxicity profiles of DTS-201 in mice, rats, and dogs, together with mass balance and antitumoral efficacy studies in rodents...
February 15, 2008: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Martin Smollich, Martin Götte, George W Yip, Eng-Siang Yong, Christian Kersting, Jeanett Fischgräbe, Isabel Radke, Ludwig Kiesel, Pia Wülfing
Endothelin-1 (ET-1) and its receptors, ET(A)R and ET(B)R, are overexpressed in breast carcinomas. However, little is known about the relevance of endothelin-converting enzyme-1 (ECE-1) and ET-1 degrading neprilysin (NEP). In this study, expression of ECE-1 and NEP was determined in 600 breast cancer tissue samples by immunohistochemistry; staining results were correlated with clinicopathological parameters. For ECE-1 expression, we found a significant correlation with VEGF (P < 0.001) and ET(A)R expression (P = 0...
December 2007: Breast Cancer Research and Treatment
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