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https://www.readbyqxmd.com/read/28812388/silk-nanoparticles-proof-of-lysosomotropic-anticancer-drug-delivery-at-single-cell-resolution
#1
John D Totten, Thidarat Wongpinyochit, F Philipp Seib
Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release is currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28793334/spheroid-growth-in-ovarian-cancer-alters-transcriptome-responses-for-stress-pathways-and-epigenetic-responses
#2
Trillitye Paullin, Chase Powell, Christopher Menzie, Robert Hill, Feng Cheng, Christopher J Martyniuk, Sandy D Westerheide
Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. These poor statistics are related to a lack of early symptoms and inadequate screening techniques. This results in the cancer going undetected until later stages when the tumor has metastasized through a process that requires the epithelial to mesenchymal transition (EMT). In lieu of traditional monolayer cell culture, EMT and cancer progression in general is best characterized through the use of 3D spheroid models...
2017: PloS One
https://www.readbyqxmd.com/read/28762604/tmeff2-shedding-is-regulated-by-oxidative-stress-and-mediated-by-adams-and-transmembrane-serine-proteases-implicated-in-prostate-cancer
#3
Katarzyna Gaweł-Bęben, Nazim Ali, Vincent Ellis, Gloria Velasco, Zaruhi Poghosyan, Ann Ager, Vera Knäuper
TMEFF2 is a type I transmembrane protein with two follistatin (FS) and one EGF-like domain over-expressed in prostate cancer, however its biological role in prostate cancer development and progression remains unclear, which may, at least in part, be explained by its proteolytic processing. The extracellular part of TMEFF2 (TMEFF2-ECD) is cleaved by ADAM17 and the membrane-retained fragment is further processed by the gamma-secretase complex. TMEFF2 shedding is increased with cell crowding, a condition associated with the tumour microenvironment, which was mediated by oxidative stress signalling, requiring jun-kinase (JNK) activation...
August 1, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28761938/down-regulation-of-hk7-in-the-sera-of-breast-cancer-and-benign-breast-disease-patients
#4
Samina Ejaz, Faiz-Ul-Hassan Nasim, Muhammad Ashraf, Gulzar Ahmad
INTRODUCTION: Breast cancer is known as a leading cause of cancer-related death among women all over the world. Biomarkers facilitate diagnosis at the earliest possible stage and better prognosis of the disease. Hence, may help to improve the overall survival rate among breast cancer patients. To find a better diagnostic/prognostic marker we evaluated human tissue kallikrein 7 (hK7) as biomarker of breast cancer. hK7 is a secreted serine protease having chymotrypsin like activity. Serum hK7 is known to have aberrant expression in ovarian and prostate cancer but has not been yet studied in breast cancer...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28755528/tissue-kallikrein-related-peptidase-4-klk4-a-novel-biomarker-in-triple-negative-breast-cancer
#5
Feng Yang, Michaela Aubele, Axel Walch, Eva Gross, Rudolf Napieralski, Shuo Zhao, Nancy Ahmed, Marion Kiechle, Ute Reuning, Julia Dorn, Fred Sweep, Viktor Magdolen, Manfred Schmitt
Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER and PR and the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded TNBC tumor tissue specimens...
July 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28755475/prostate-epithelium-basement-membrane-and-prostate-cell-biology-20-years
#6
Hernandes F Carvalho, Sebastião Roberto Taboga, Sérgio Luis Felisbino, Manoel F Biancardi
The basement membrane (BM) confines the epithelia and is an apparent barrier to metastasis. Progression to malignancy is associated with cancer cell's ability to breakdown the BM and to invade the adjacent stroma (Duffy 1992, Lochter et al., 1999). Invasion depends not only on their capacity to degrade BM components but also to survive the loss of cell-cell and cell-ECM adhesion, surpassing anoikis. Enhanced proteolysis of the cancer cell microenvironment is due to a repertoire of metalloproteinases (MMP) in disbalance with their endogenous inhibitors, such as the TIMPs, RECK and Kiss, as well as an increased in proteolytical enzymes, such as uPA (and other serine proteases) and ADAMs, capable of activating MMPs (Johnsen et al...
July 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28726978/analysis-of-the-substrate-specificity-of-factor-vii-activating-protease-fsap-and-design-of-specific-and-sensitive-peptide-substrates
#7
Emrah Kara, Dipankar Manna, Geir Åge Løset, Eric L Schneider, Charles S Craik, Sandip Kanse
Factor VII (FVII) activating protease (FSAP) is a circulating serine protease that is likely to be involved in a number of disease conditions such as stroke, atherosclerosis, liver fibrosis, thrombosis and cancer. To date, no systematic information is available about the substrate specificity of FSAP. Applying phage display and positional scanning substrate combinatorial library (PS-SCL) approaches we have characterised the specificity of FSAP towards small peptides. Results were evaluated in the context of known protein substrates as well as molecular modelling of the peptides in the active site of FSAP...
July 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28726057/macrophage-migration-inhibitory-factor-mif-modulates-trophic-signaling-through-interaction-with-serine-protease-htra1
#8
Åsa Fex Svenningsen, Svenja Löring, Anna Lahn Sørensen, Ha Uyen Buu Huynh, Simone Hjæresen, Nellie Martin, Jesper Bonnet Moeller, Maria Louise Elkjær, Uffe Holmskov, Zsolt Illes, Malin Andersson, Solveig Beck Nielsen, Eirikur Benedikz
Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cellular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the serine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF...
July 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28722823/rational-design-of-a-highly-potent-and-selective-peptide-inhibitor-of-pace4-by-salt-bridge-interaction-with-d160-at-position-p3
#9
Vahid Dianati, Azar Shamloo, Anna Kwiatkowska, Roxane Desjardins, Armand Soldera, Robert Day, Yves L Dory
PACE4, a member of the proprotein convertases (PCs) family of serine proteases, is a validated target for prostate cancer. Our group has developed a potent and selective PACE4 inhibitor: Ac-LLLLRVKR-NH2 . In seeking for modifications to increase the selectivity of this ligand toward PACE4, we replaced one of its P3 Val methyl groups with a basic group capable of forming a salt bridge with D160 of PACE4. The resulting inhibitor is eight times more potent than the P3 Val parent inhibitor and two times more selective over furin, because the equivalent salt bridge with furin E257 is not optimal...
July 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28700339/trypsin-protease-activated-receptor-2-signaling-contributes-to-pancreatic-cancer-pain
#10
Jiao Zhu, Xue-Rong Miao, Kun-Ming Tao, Hai Zhu, Zhi-Yun Liu, Da-Wei Yu, Qian-Bo Chen, Hai-Bo Qiu, Zhi-Jie Lu
Pain treatment is a critical aspect of pancreatic cancer patient clinical care. This study investigated the role of trypsin-protease activated receptor-2 (PAR-2) in pancreatic cancer pain. Pancreatic tissue samples were collected from pancreatic cancer (n=22) and control patients (n=22). Immunofluorescence analyses confirmed colocalization of PAR-2 and neuronal markers in pancreatic cancer tissues. Trypsin levels and protease activities were higher in pancreatic cancer tissue specimens than in the controls...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28697174/uv-radiation-promotes-melanoma-dissemination-mediated-by-the-sequential-reaction-axis-of-cathepsins-tgf-%C3%AE-1-fap-%C3%AE
#11
Petra Wäster, Kyriakos Orfanidis, Ida Eriksson, Inger Rosdahl, Oliver Seifert, Karin Öllinger
BACKGROUND: Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-α is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-α is not yet completely revealed. METHODS: Expression of FAP-α was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs...
August 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28693282/identification-of-hub-genes-and-pathways-associated-with-bladder-cancer-based-on-co-expression-network-analysis
#12
Dong-Qing Zhang, Chang-Kuo Zhou, Shou-Zhen Chen, Yue Yang, Ben-Kang Shi
The aim of the present study was to identify hub genes and signaling pathways associated with bladder cancer (BC) utilizing centrality analysis and pathway enrichment analysis. The differentially expressed genes (DEGs) were screened from the ArrayExpress database between normal subjects and BC patients. Co-expression networks of BC were constructed using differentially co-expressed genes and links, and hub genes were investigated by degree centrality analysis of co-expression networks in BC. The enriched signaling pathways were investigated by Kyoto Encyclopedia of Genes and Genomes database analysis based on the DEGs...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28686182/a-purified-serine-protease-from-nereis-virens-and-its-impaction-of-apoptosis-on-human-lung-cancer-cells
#13
Yunping Tang, Fangmiao Yu, Guomei Zhang, Zuisu Yang, Fangfang Huang, Guofang Ding
Nereis active protease (NAP) is a novel fibrinolytic active serine protease from the polychaete Nereis virens. In this study, NAP was purified from Nereis virens and the effects of NAP on human lung cancer cells were investigated. Our results indicated that NAP inhibited the proliferation and induced apoptosis of H1299 cells in a time- and dose-dependent manner. The loss of mitochondrial membrane potential, the activation of Bax and cleaved-caspase 3/9, the release of cytochrome C, and the suppression of Bcl-2 and poly-ADP ribose polymerase were observed in NAP-treated H1299 cells by flow cytometry and Western blotting...
July 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28672746/study-of-kallikrein-related-peptidase-6-klk6-and-its-complex-with-%C3%AE-1-antitrypsin-in-biological-fluids
#14
Dimitrios Korbakis, Antoninus Soosaipillai, Eleftherios P Diamandis
BACKGROUND: Human kallikrein-related peptidase 6 (KLK6) is a member of the kallikrein family of serine proteases. KLK6 is synthesized as a preproenzyme, mainly in tissues of the central nervous system (CNS), and secreted as an inactive precursor. Serum KLK6 is a biomarker of unfavorable prognosis for ovarian cancer, but its sensitivity for early detection is relatively low. Differential glycosylation of KLK6 has been identified in ascites fluid obtained from ovarian cancer patients, suggesting the presence of unique KLK6 isoforms in biological samples...
August 28, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28667026/htra1-down-regulation-induces-cisplatin-resistance-in-colon-cancer-by-increasing-xiap-and-activating-pi3k-akt-pathway
#15
Zhenfang Xiong, Zhonghua Fu, Jun Shi, Xiaozhen Jiang, Hongping Wan
The high temperature requirement factor A1 (HtrA1), a member of serine protease family, has been reported to be down-regulated in various cancer types and correlate with chemoresistance. However, the function of HtrA1 in colon cancer remains unclear. This study investigated the role of HtrA1 in cisplatin (CDDP) resistance of colon cancer. We found that HtrA1 was up-regulated in colon cancer cell line SW480 incubated with CDDP. By treating SW480 cells to a continuous exposure to CDDP, we developed CDDP-resistant SW480/CDDP cells and found that the mRNA and protein levels of HtrA1 were reduced...
May 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28637988/comparison-of-gene-expression-profiles-of-gingival-carcinoma-ca9-22-cells-and-colorectal-adenocarcinoma-ht-29-cells-to-identify-potentially-important-mediators-of-slpi-induced-cell-migration
#16
Tsuyoshi Takamura, Hisashi Suguro, Yoshikazu Mikami, Takashi Iwase, Yusuke Komiyama, Kayo Kuyama, Kazuo Komiyama, Hiderou Oki
Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor whose expression level is positively correlated with tumor aggressiveness and metastatic potential. However, the mechanism underlying SLPI-induced enhancement of malignant phenotype is not completely understood. The malignancy of cancer cells is highly dependent on cell migration activity. Our previous study revealed that gingival carcinoma Ca9-22 cells, but not colorectal adenocarcinoma HT-29 cells, expressed SLPI. Therefore, we investigated the migration activity of these two cell types to understand the nature of SLPI-mediated tumor aggressiveness and metastatic potential...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28609548/inhibitors-of-kallikrein-related-peptidases-an-overview
#17
REVIEW
Nicolas Masurier, Dominique P Arama, Chahrazade El Amri, Vincent Lisowski
Kallikrein-related peptidases (KLKs) are a family of 15 secreted serine proteases that are involved in various physiological processes. Their activities are subtly regulated by various endogenous inhibitors, ranging from metallic ions to macromolecular entities such as proteins. Furthermore, dysregulation of KLK activity has been linked to several pathologies, including cancer and skin and inflammatory diseases, explaining the numerous efforts to develop KLK-specific pharmacological inhibitors as potential therapeutic agents...
June 13, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28545186/gallium-nanoparticle-mediated-reduction-of-brain-specific-serine-protease-4-in-an-experimental-metastatic-cancer-model
#18
Enas M Moustafa, Marwa Abdelhameed Mohamed, Noura M Thabet
Purpose: Tumor growth and metastasis depend on angiogenesis; therefore, efforts are being made to develop specific angiogenic inhibitors. Gallium (Ga) is the second most common metal ion, after platinum, used in cancer treatment. Its activities are numerous and various. In the present study, we aimed to investigate the effect of Ga on brain metastasis arising from hepatocellular carcinoma (HCC). Materials and methods: Forty experimental rats (divided into 4 groups) received diethylnitrosamine (DEN) at a dose (20 mg/kg...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28544544/insulin-like-growth-factor-1-signaling-is-responsible-for-cathepsin-g-induced-aggregation-of-breast-cancer-mcf-7-cells
#19
Riyo Morimoto-Kamata, Satoru Yui
Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF-7 cells in a process that is dependent on E-cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG-mediated stimulation of cell aggregation...
August 2017: Cancer Science
https://www.readbyqxmd.com/read/28544403/serine-protease-inhibitor-kazal-type-1-spink1-downregulates-e-cadherin-and-induces-emt-of-hepatoma-cells-to-promote-hepatocellular-carcinoma-metastasis-via-the-mek-erk-signaling-pathway
#20
Hai Yan Ying, Chao Jie Gong, Yi Feng, Da Dao Jing, Lun Gen Lu
OBJECTIVE: To investigate serine protease inhibitor Kazal type 1 (SPINK1) expression and its influence on the prognosis of human hepatocellular carcinoma (HCC) and to explore the underlying molecular mechanisms involved. METHODS: Altogether 80 patients with HCC who underwent curative resection were followed up for a median of 58.6 months. SPINK1 expression was detected in the primary HCC samples by immunohistochemistry. Its role in tumor invasion and metastasis was evaluated in vitro by gene silencing using a small interfering RNA-mediated approach, recombinant SPINK1 and U0126 (an inhibitor of MEK/ERK)...
June 2017: Journal of Digestive Diseases
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