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https://www.readbyqxmd.com/read/27922627/blood-based-and-urinary-prostate-cancer-biomarkers-a-review-and-comparison-of-novel-biomarkers-for-detection-and-treatment-decisions
#1
REVIEW
R J Hendriks, I M van Oort, J A Schalken
BACKGROUND: The diagnosis of prostate cancer (PCa) is currently based on serum PSA testing and/or abnormal digital rectal examination and histopathologic evaluation of prostate biopsies. The main drawback of PSA testing is the lack of specificity for PCa. To improve early detection of PCa more specific biomarkers are needed. In the past few years, many new promising biomarkers have been identified; however, to date, only a few have reached clinical practice. METHODS: In this review, we discuss new blood-based and urinary biomarker models that are promising for usage in PCa detection, follow-up and treatment decision-making...
December 6, 2016: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/27921025/prostate-specific-antigen-rising-in-iranian-men-in-correlation-with-body-mass-index-fasting-blood-sugar-and-blood-lipid-profile
#2
Davood Arab, Arash Ardestani Zadeh, Majid Mirmohammadkhani, Azadeh Beiglarzadeh
BACKGROUND: Prostate-specific antigen (PSA) is a serine protease that is secreted by prostate cells and it is useful as a tumor marker for prostate cancer. OBJECTIVES: In this study, the relationship between some of metabolic factors and serum PSA level was investigated. MATERIALS AND METHODS: In this cross-sectional study, patients with urinary symptoms or for screening of the prostate cancer (after 50 years of age or 40 years with a family history of prostate cancer), were evaluated...
October 2016: Journal of Nephropathology
https://www.readbyqxmd.com/read/27910803/the-prognostic-and-predictive-value-of-tmprss2-erg-gene-fusion-and-erg-protein-expression-in-prostate-cancer-biopsies
#3
Kasper Drimer Berg
BACKGROUND: The clinical course of prostate carcinoma (PCa) is very heterogeneous. Consequently, a personalised approach for risk stratification and treatment planning is important. Recently, it has become evident that PCa, also at the genomic level, is heterogeneous. An early and common alteration is the gene fusion between the transmembrane protease serine 2 (TMPRSS2) gene and the v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene resulting in expression of the oncoprotein ERG...
December 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27870503/the-role-of-type-ii-transmembrane-serine-protease-mediated-signaling-in-cancer
#4
Lauren M Tanabe, Karin List
Pericellular proteases have long been implicated in carcinogenesis. Previous research focused on these proteins, primarily as extracellular matrix (ECM) protein degrading enzymes which allowed cancer cells to breach the basement membrane and invade surrounding tissue. However, recently, there has been a shift in the view of cell surface proteases, including serine proteases, as proteolytic modifiers of particular targets, including growth factors and protease-activated receptors, which are critical for the activation of oncogenic signaling pathways...
November 21, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27793045/serpin-e2-promotes-breast-cancer-metastasis-by-remodeling-the-tumor-matrix-and-polarizing-tumor-associated-macrophages
#5
Tatiana Smirnova, Laura Bonapace, Gwen MacDonald, Shunya Kondo, Jeffrey Wyckoff, Hilmar Ebersbach, Bérengère Fayard, Arno Doelemeyer, Marie-May Coissieux, Marinus R Heideman, Mohamed Bentires-Alj, Nancy E Hynes
The extracellular serine protease inhibitor serpinE2 is overexpressed in breast cancer and has been shown to foster metastatic spread. Here, we investigated the hypothesis that serpinE2 creates tumor-promoting conditions in the tumor microenvironment (TME) by affecting extracellular matrix remodeling. Using two different breast cancer models, we show that blocking serpinE2, either by knock-down (KD) in tumor cells or in response to a serpinE2 binding antibody, decreases metastatic dissemination from primary tumors to the lungs...
October 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27767076/direct-and-indirect-mechanisms-of-klk4-inhibition-revealed-by-structure-and-dynamics
#6
Blake T Riley, Olga Ilyichova, Mauricio G S Costa, Benjamin T Porebski, Simon J de Veer, Joakim E Swedberg, Itamar Kass, Jonathan M Harris, David E Hoke, Ashley M Buckle
The kallikrein-related peptidase (KLK) family of proteases is involved in many aspects of human health and disease. One member of this family, KLK4, has been implicated in cancer development and metastasis. Understanding mechanisms of inactivation are critical to developing selective KLK4 inhibitors. We have determined the X-ray crystal structures of KLK4 in complex with both sunflower trypsin inhibitor-1 (SFTI-1) and a rationally designed SFTI-1 derivative to atomic (~1 Å) resolution, as well as with bound nickel...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27721279/immunohistochemical-expression-of-ets-related-gene-transcriptional-factor-in-adenocarcinoma-prostate-and-its-correlation-with-gleason-score
#7
Rahul Mannan, Tejinder Singh Bhasin, Mridu Manjari, Gagandeep Singh, Puneet Kaur Bhatia, Sonam Sharma
BACKGROUND: Prostate carcinoma is the second leading cause of cancer-related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC) markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment...
October 2016: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/27716118/selective-depletion-of-tumour-suppressors-deleted-in-colorectal-cancer-dcc-and-neogenin-by-environmental-and-endogenous-serine-proteases-linking-diet-and-cancer
#8
Caroline M Forrest, Kara McNair, Maria C J Vincenten, L Gail Darlington, Trevor W Stone
BACKGROUND: The related tumour suppressor proteins Deleted in Colorectal Cancer (DCC) and neogenin are absent or weakly expressed in many cancers, whereas their insertion into cells suppresses oncogenic behaviour. Serine proteases influence the initiation and progression of cancers although the mechanisms are unknown. METHODS: The effects of environmental (bacterial subtilisin) and endogenous mammalian (chymotrypsin) serine proteases were examined on protein expression in fresh, normal tissue and human neuroblastoma and mammary adenocarcinoma lines...
October 6, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27706634/kallikrein-12-downregulation-reduces-ags-gastric-cancer-cell-proliferation-and-migration
#9
X S Li, X L He
Abnormal expression of the kallikrein (KLK) family of serine proteases closely correlates with onset, progression, and prognosis of endocrine gland-related malignant tumors. The aim of this study was to evaluate how downregulation of KLK12 influenced cell cycle and proliferation of the AGS gastric cancer cell line. KLK12 was detected by western blot in GES-1 normal gastric epithelial and AGS cells. AGS cells were transfected with KLK12 siRNA, a negative control siRNA, or subjected to a mock transfection, following which, we assessed mRNA and protein levels, cell proliferation, cell migration, and cell cycle progression...
August 29, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27698925/low-proteolytic-clipping-of-histone-h3-in-cervical-cancer
#10
Jorge Sandoval-Basilio, Nicolás Serafín-Higuera, Octavio D Reyes-Hernandez, Idanya Serafín-Higuera, Gabriela Leija-Montoya, Magali Blanco-Morales, Monica Sierra-Martínez, Roberto Ramos-Mondragon, Silvia García, Luz Berenice López-Hernández, Martha Yocupicio-Monroy, Sofia L Alcaraz-Estrada
Chromatin in cervical cancer (CC) undergoes chemical and structural changes that alter the expression pattern of genes. Recently, a potential mechanism, which regulates gene expression at transcriptional levels is the proteolytic clipping of histone H3. However, until now this process in CC has not been reported. Using HeLa cells as a model of CC and human samples from patients with CC, we identify that the H3 cleavage was lower in CC compared with control tissue. Additionally, the histone H3 clipping was performed by serine and aspartyl proteases in HeLa cells...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27689014/fibroblast-activation-protein-fap-as-a-novel-metabolic-target
#11
Miguel Angel Sánchez-Garrido, Kirk M Habegger, Christoffer Clemmensen, Cassie Holleman, Timo D Müller, Diego Perez-Tilve, Pengyun Li, Archita S Agrawal, Brian Finan, Daniel J Drucker, Matthias H Tschöp, Richard D DiMarchi, Alexei Kharitonenkov
OBJECTIVE: Fibroblast activation protein (FAP) is a serine protease belonging to a S9B prolyl oligopeptidase subfamily. This enzyme has been implicated in cancer development and recently reported to regulate degradation of FGF21, a potent metabolic hormone. Using a known FAP inhibitor, talabostat (TB), we explored the impact of FAP inhibition on metabolic regulation in mice. METHODS: To address this question we evaluated the pharmacology of TB in various mouse models including those deficient in FGF21, GLP1 and GIP signaling...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27687602/-ants-a-chemical-library-of-anticancer-molecules
#12
Angélique Vétillard, Wafa Bouzid
Animal venoms are complex mixtures containing simple organic molecules, proteins, peptides, and other bioactive elements with extraordinary biological properties associated with their ability to act on a number of molecular receptors in the process of incapacitating their target organisms. In such a context, arthropod venoms are invaluable sources of bioactive substances, with therapeutic interest but the limited availability of some venom such as those from ants, has restricted the potential that these biomolecules could represent...
2016: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/27683038/regulation-of-tumor-growth-by-circulating-full-length-chromogranin-a
#13
Curnis Flavio, Dallatomasina Alice, Mimma Bianco, Anna Gasparri, Angelina Sacchi, Barbara Colombo, Martina Fiocchi, Laura Perani, Massimo Venturini, Carlo Tacchetti, Suvajit Sen, Ricardo Borges, Eleonora Dondossola, Antonio Esposito, Sushil K Mahata, Corti Angelo
Chromogranin A (CgA), a neuroendocrine secretory protein, and its fragments are present in variable amounts in the blood of normal subjects and cancer patients. We investigated whether circulating CgA has a regulatory function in tumor biology and progression. Systemic administration of full-length CgA, but not of fragments lacking the C-terminal region, could reduce tumor growth in murine models of fibrosarcoma, mammary adenocarcinoma, Lewis lung carcinoma, and primary and metastatic melanoma, with U-shaped dose-response curves...
September 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27671677/spink6-promotes-metastasis-of-nasopharyngeal-carcinoma-via-binding-and-activation-of-epithelial-growth-factor-receptor
#14
Li-Sheng Zheng, Jun-Ping Yang, Yun Cao, Li-Xia Peng, Rui Sun, Ping Xie, Meng-Yao Wang, Dong-Fang Meng, Dong-Hua Luo, Xiong Zou, Ming-Yuan Chen, Hai-Qiang Mai, Ling Guo, Xiang Guo, Jian-Yong Shao, Bi-Jun Huang, Wei Zhang, Chao-Nan Qian
Nasopharyngeal carcinoma (NPC) has the highest rate of metastasis among head and neck cancers, and distant metastasis is the major reason for treatment failure. The underlying molecular mechanisms of NPC metastasis are not fully understood. Here we report the identification of serine protease inhibitor Kazal-type 6 (SPINK6) as a functional regulator of NPC metastasis via epidermal growth factor receptor (EGFR) signaling. SPINK6 mRNA was upregulated in tumor and highly metastatic NPC cells. Immunohistochemical staining of 534 NPCs revealed elevated SPINK6 expression as an independent unfavorable prognostic factor for overall, disease-free, and distant metastasis-free survival...
September 26, 2016: Cancer Research
https://www.readbyqxmd.com/read/27670069/the-structure-of-a-furin-antibody-complex-explains-non-competitive-inhibition-by-steric-exclusion-of-substrate-conformers
#15
Sven O Dahms, John W M Creemers, Yvonne Schaub, Gleb P Bourenkov, Thomas Zögg, Hans Brandstetter, Manuel E Than
Proprotein Convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of cancer and infectious diseases. Inhibitory camelid antibodies were developed, targeting the prototypical PC furin. Kinetic analyses of them revealed an enigmatic non-competitive mechanism, affecting the inhibition of large proprotein-like but not small peptidic substrates. Here we present the crystal structures of furin in complex with the antibody Nb14 and of free Nb14 at resolutions of 2...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27637160/serpinb3-and-b4-from-biochemistry-to-biology
#16
Yu Sun, Namratha Sheshadri, Wei-Xing Zong
Human SERPINB3 and SERPINB4 are evolutionary duplicated serine/cysteine protease inhibitors. Genomic analysis indicates that these paralogous genes were encoded from independent loci arising from tandem gene duplication. Although the two molecules share 92% identity of their amino acid sequences, they are distinct in the Reactive Center Loop (RCL) including a hinge region and catalytic sequences which accounts for altered substrate specificity. Elevated expression of the two molecules have been reported to contribute to numerous pathological conditions such as inflammatory diseases and cancer...
September 13, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27611765/structural-basis-for-the-zn-2-inhibition-of-the-zymogen-like-kallikrein-related-peptidase-10
#17
Mekdes Debela, Viktor Magdolen, Wolfram Bode, Hans Brandstetter, Peter Goettig
Although kallikrein-related peptidase 10 (KLK10) is expressed in a variety of human tissues and body fluids, knowledge of its physiological functions is fragmentary. Similarly, the pathophysiology of KLK10 in cancer is not well understood. In some cancer types, a role as tumor suppressor has been suggested, while in others elevated expression is associated with poor patient prognosis. Active human KLK10 exhibits a unique, three residue longer N-terminus with respect to other serine proteases and an extended 99-loop nearly as long as in tissue kallikrein KLK1...
September 9, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27590265/dependence-receptor-involvement-in-subtilisin-induced-long-term-depression-and-in-long-term-potentiation
#18
Trevor W Stone, L Gail Darlington, Caroline M Forrest
The serine protease subtilisin induces a form of long-term depression (LTD) which is accompanied by a reduced expression of the axo-dendritic guidance molecule Unco-ordinated-5C (Unc-5C). One objective of the present work was to determine whether a loss of Unc-5C function contributed to subtilisin-induced LTD by using Unc-5C antibodies in combination with the pore-forming agents Triton X-100 (0.005%) or streptolysin O in rat hippocampal slices. In addition we have assessed the effect of subtilisin on the related dependence receptor Deleted in Colorectal Cancer (DCC) and used antibodies to this protein for functional studies...
November 12, 2016: Neuroscience
https://www.readbyqxmd.com/read/27589737/the-iron-chelator-dp44mt-effectively-inhibits-human-oral-squamous-cell-carcinoma-cell-growth-in-vitro-and-in-vivo
#19
Jehn-Chuan Lee, Kun-Chun Chiang, Tsui-Hsia Feng, Yu-Jen Chen, Sung-Ting Chuang, Ke-Hung Tsui, Li-Chuan Chung, Horng-Heng Juang
Oral squamous cell carcinoma (OSCC) is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG) family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin) gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27584082/targeting-proprotein-convertases-in-furin-rich-lung-cancer-cells-results-in-decreased-in-vitro-and-in-vivo-growth
#20
Daniel E Bassi, Jirong Zhang, Catherine Renner, Andres J Klein-Szanto
Proprotein convertases (PCs) are serine proteases with an active role in the post-translational processing of numerous inactive proteins to active proteins including many substrates of paramount importance in cancer development and progression. Furin (PCSKC3), a well-studied member of this family, is overexpressed in numerous human and experimental malignancies. In the present communication, we treated two furin-overexpressing non-small cell carcinoma (NSCLC) cell lines (Calu-6 and HOP-62) with the PC inhibitor CMK (Decanoyl-Arg-Val-Lys-Arg-chloromethylketone)...
September 1, 2016: Molecular Carcinogenesis
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