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Kallikrein

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https://www.readbyqxmd.com/read/27908170/high-resolution-digital-autoradiographic-and-dosimetric-analysis-of-heterogeneous-radioactivity-distribution-in-xenografted-prostate-tumors
#1
Oskar V Timmermand, Jenny Nilsson, Sven-Erik Strand, Jörgen Elgqvist
PURPOSE: The first main aim of this study was to illustrate the absorbed dose rate distribution from (177)Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of (90)Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using (177)Lu-h11B6, directed against the human kallikrein 2 antigen...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27903863/internalization-of-secreted-antigen-targeted-antibodies-by-the-neonatal-fc-receptor-for-precision-imaging-of-the-androgen-receptor-axis
#2
Daniel L J Thorek, Philip A Watson, Sang-Gyu Lee, Anson T Ku, Stylianos Bournazos, Katharina Braun, Kwanghee Kim, Kjell Sjöström, Michael G Doran, Urpo Lamminmäki, Elmer Santos, Darren Veach, Mesruh Turkekul, Emily Casey, Jason S Lewis, Diane S Abou, Marise R H van Voss, Peter T Scardino, Sven-Erik Strand, Mary L Alpaugh, Howard I Scher, Hans Lilja, Steven M Larson, David Ulmert
Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. We report intracellular accumulation of a secreted antigen-targeted antibody (SATA) that can be used to characterize disease, guide therapy, and monitor response. AR-regulated human kallikrein-related peptidase 2 (free hK2) is a prostate tissue-specific antigen produced in prostate cancer and androgen-stimulated breast cancer cells...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27898009/effects-of-glycosylation-on-the-enzymatic-activity-and-mechanisms-of-proteases
#3
REVIEW
Peter Goettig
Posttranslational modifications are an important feature of most proteases in higher organisms, such as the conversion of inactive zymogens into active proteases. To date, little information is available on the role of glycosylation and functional implications for secreted proteases. Besides a stabilizing effect and protection against proteolysis, several proteases show a significant influence of glycosylation on the catalytic activity. Glycans can alter the substrate recognition, the specificity and binding affinity, as well as the turnover rates...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27889277/evaluating-the-four-kallikrein-panel-of-the-4kscore-for-prediction-of-high-grade-prostate-cancer-in-men-in-the-canary-prostate-active-surveillance-study
#4
Daniel W Lin, Lisa F Newcomb, Marshall D Brown, Daniel D Sjoberg, Yan Dong, James D Brooks, Peter R Carroll, Matthew Cooperberg, Atreya Dash, William J Ellis, Michael Fabrizio, Martin E Gleave, Todd M Morgan, Peter S Nelson, Ian M Thompson, Andrew A Wagner, Yingye Zheng
BACKGROUND: Diagnosis of Gleason 6 prostate cancer can leave uncertainty about the presence of undetected aggressive disease. OBJECTIVE: To evaluate the utility of a four kallikrein (4K) panel in predicting the presence of high-grade cancer in men on active surveillance. DESIGN, SETTING, AND PARTICIPANTS: Plasma collected before the first and subsequent surveillance biopsies was assessed for 718 men prospectively enrolled in the multi-institutional Canary PASS trial...
November 23, 2016: European Urology
https://www.readbyqxmd.com/read/27882085/knockdown-of-klk11-inhibits-cell-proliferation-and-increases-oxaliplatin-sensitivity-in-human-colorectal-cancer
#5
Zongbin Xu, Pan Chi, Jie Pan, Songfei Shen, Yanwu Sun, Xiaojie Wang, Xingrong Lu
It has been reported that kallikrein 11 (KLK11) is crucially involved in the development and progression of various types of cancer. However, the molecular mechanisms that underlie the involvement of KLK11 in aberrant colorectal cancer (CRC) cell growth remain largely unclear. The aim of the present study was to investigate the role of KLK11 and the effects of KLK11 on oxaliplatin (L-OHP) chemosensitivity by knocking down KLK11 in LOVO and HCT-8 cells. Loss-of-function assays revealed KLK11 inhibition significantly inhibited growth and induced apoptosis of CRC cells in vitro...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27867935/processing-of-factor-xii-during-inflammatory-reactions
#6
REVIEW
Bernard Nico Jukema, Steven de Maat, Coen Maas
The contact system was originally identified as an obsolete part of the coagulation system, but it has been repeatedly implicated in inflammatory states, such as infection, as well as in allergic- and chronic inflammatory disease. Under these conditions, there is surprisingly little evidence that factor XII (FXII) acts as a coagulation factor, and its activity appears to be mainly directed toward activation of the kallikrein-kinin system. The contact system factors interact with pathogens as well as cells of the (innate) immune system on several levels...
2016: Frontiers in Medicine
https://www.readbyqxmd.com/read/27863404/kallikrein-related-peptidase-6-induces-chemotherapeutic-resistance-by-attenuating-auranofin-induced-cell-death-through-activation-of-autophagy-in-gastric-cancer
#7
Tae Woo Kim, Seon-Jin Lee, Jong-Tae Kim, Sun Jung Kim, Jeong-Ki Min, Kwang-Hee Bae, Haiyoung Jung, Bo-Yeon Kim, Jong-Seok Lim, Young Yang, Do-Young Yoon, Yong-Kyung Choe, Hee Gu Lee
Kallikrein-related peptidase 6 (KLK6) is a biomarker of gastric cancer associated with poor prognosis. Mechanisms by which KLK6 could be exploited for chemotherapeutic use are unclear. We evaluated auranofin (AF), a compound with cytotoxic effects, in KLK6-deficient cells, and we investigated whether KLK6 expression induces autophagy and acquisition of drug resistance in gastric cancer. Using cultured human cells and a mouse xenograft model, we investigated how KLK6 affects antitumor-reagent-induced cell death and autophagy...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27858843/association-of-the-klk1-rs5516-g-allele-and-the-ace-d-allele-with-aortic-aneurysm-and-atherosclerotic-stenosis
#8
Yiming Zhang, Hongliang Huang, Yuliang Ma, Yifeng Sun, Guohua Wang, Liming Tang
OBJECTIVE: Atherosclerosis underlies aortic aneurysm (AA) and atherosclerotic stenosis (AS). Kallikrein-1 (KLK1) and angiotensin-converting enzyme (ACE) are 2 key molecules in kallikrein-kinin systems and renin-angiotensin systems, respectively, which are responsible for maintaining vascular balance and stability, playing important roles in atherosclerosis. We aimed to assess the involvement of single nucleotide polymorphism rs5516 in KLK1 as well as the insertion/deletion rs4646994 polymorphism in ACE in the development of AA and AS...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27848184/the-initiation-and-effects-of-plasma-contact-activation-an-overview
#9
Lisha Lin, Mingyi Wu, Jinhua Zhao
The plasma contact system sits atop the intrinsic coagulation cascade and plasma kallikrein-kinin pathway, and in vivo its activation contributes, respectively, to coagulation and inflammation mainly via two downstream pathways. This system has been widely investigated, its activation mechanisms by negatively charged surfaces and the interactions within its components, factor XII, prekallikrein and high molecular weight kininogen are well understood at the biochemical level. However, as most of the activators that have been discovered by in vitro experiments are exogenous, the physiological activators and roles of the contact system have remained unclear and controversial...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27845251/heparan-sulfate-heparin-glycosaminoglycan-binding-alters-inhibitory-profile-and-enhances-anticoagulant-function-of-conserved-amblyomma-americanum-tick-saliva-serpin-19
#10
Željko M Radulović, Albert Mulenga
Some serine protease inhibitor (serpin) regulators of essential life pathways bind glycosaminoglycans (GAGs) to enhance inhibitory functions and achieve physiologically relevant rates. This study demonstrates that highly conserved Amblyomma americanum tick saliva serpin 19 (AAS19), a broad-spectrum inhibitor of hemostasis and inflammation system proteases and anticoagulant, can bind heparan sulfate/heparin (HS)GAGs and that this interaction alters its function. Substrate hydrolysis and unpaired t-test analyses revealed that HSGAG binding caused rAAS19 inhibitory activity to: (i) significantly increase against blood clotting factors (f) IIa (thrombin) and fIXa, (ii) significantly reduce against fXa and fXIIa and (iii) moderate to no effect against trypsin, kallikrein, papain, and plasmin...
November 12, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27845041/a-secretome-analysis-reveals-that-ppar%C3%AE-is-upregulated-by-fractionated-dose-%C3%AE-irradiation-in-three-dimensional-keratinocyte-cultures
#11
Jeeyong Lee, Hyun-Ji Kim, Jae Youn Yi
Studies have shown that γ-irradiation induces various biological responses, including oxidative stress and apoptosis, as well as cellular repair and immune system responses. However, most such studies have been performed using traditional two-dimensional cell culture systems, which are limited in their ability to faithfully represent in vivo conditions. A three-dimensional (3D) environment composed of properly interconnected and differentiated cells that allow communication and cooperation among cells via secreted molecules would be expected to more accurately reflect cellular responses...
November 12, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27844409/expression-of-kallikrein-related-peptidase-6-in-primary-mucosal-malignant-melanoma-of-the-head-and-neck
#12
Julia Thierauf, Johannes A Veit, Jochen K Lennerz, Stephanie E Weissinger, Annette Affolter, Johannes Döscher, Christoph Bergmann, Andreas Knopf, Jennifer Grünow, Lisa Grünmüller, Cornelia Mauch, Peter K Plinkert, Thomas K Hoffmann, Jochen Hess
Mucosal melanomas of the head and neck (MMHN) are aggressive tumors with poor prognosis, different opposed to cutaneous melanoma. In this study, we characterized primary mucosal malignant melanoma for the expression of Kallikrein-related peptidase 6 (KLK6), a member of the KLK family with relevance to the malignant phenotype in various cancer types including cutaneous melanoma. Paraffin-embedded MMHN of 22 patients were stained immunohistochemically for KLK6 and results were correlated with clinical and pathological data...
November 14, 2016: Head and Neck Pathology
https://www.readbyqxmd.com/read/27834692/factor-xii-as-a-therapeutic-target-in-thromboembolic-and-inflammatory-diseases
#13
REVIEW
Katrin F Nickel, Andy T Long, Tobias A Fuchs, Lynn M Butler, Thomas Renné
Coagulation factor XII (FXII, Hageman factor) is a plasma protease that in its active form (FXIIa) initiates the procoagulant and proinflammatory contact system. This name arises from FXII's unique mechanism of activation that is induced by binding (contact) to negatively charged surfaces. Various substances have the capacity to trigger FXII contact-activation in vivo including mast cell-derived heparin, misfolded protein aggregates, collagen, nucleic acids, and polyphosphate. FXII deficiency is not associated with bleeding, and for decades, the factor was considered to be dispensable for coagulation in vivo...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27831591/new-genetic-association-for-the-kinin-system-the-l-arginine-connection-insight-association-of-l-arginine-levels-and-two-loci-in-genes-of-the-kallikrein-kinin-system
#14
Pablo García de Frutos, José Martínez-González
No abstract text is available yet for this article.
November 30, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27827323/sequence-variation-at-klk-and-wfdc-clusters-and-its-association-to-semen-hyperviscosity-and-other-male-infertility-phenotypes
#15
Patrícia Isabel Marques, Filipa Fonseca, Ana Sofia Carvalho, Diana A Puente, Isabel Damião, Vasco Almeida, Nuno Barros, Alberto Barros, Filipa Carvalho, Mikel Azkargorta, Felix Elortza, Hugo Osório, Rune Matthiesen, Victor Quesada, Susana Seixas
STUDY QUESTION: Are kallikreins (KLKs), the whey-acidic-protein four-disulfide core domain (WFDCs) and their neighbors, semenogelins (SEMGs), known to play a role in the cascade of semen coagulation and liquefaction, associated with male infertility? SUMMARY ANSWER: Several KLK and SEMG variants are overrepresented among hyperviscosity, asthenozoospermia and oligozoospermia, supporting an effect of abnormal semen liquefaction on the loss of semen quality and in lowering male reproductive fitness...
November 7, 2016: Human Reproduction
https://www.readbyqxmd.com/read/27826093/cytokine-and-estrogen-stimulation-of-endothelial-cells-augment-activation-of-the-prekallikrein-high-molecular-weight-kininogen-complex-implications-for-hereditary-angioedema-hae
#16
Kusumam Joseph, Baby G Tholanikunnel, Allen P Kaplan
BACKGROUND: When the prekallikrein-high molecular weight kininogen complex is bound to endothelial cells, prekallikrein is stoichiometrically converted to kallikrein due to release of heat shock protein-90 (Hsp90). While bradykinin formation is typically initiated by factor XII autoactivation it is also possible to activate factor XII either by kallikrein, thus formed, or plasmin. RATIONALE: Since attacks of hereditary angioedema can be related to infection and/or exposure to estrogen, we questioned whether estrogen or cytokine stimulation of endothelial cells could augment release of Hsp90 and prekallikrein activation...
November 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27824929/tissue-kallikrein-inhibitors-based-on-the-sunflower-trypsin-inhibitor-scaffold-a-potential-therapeutic-intervention-for-skin-diseases
#17
Wenjie Chen, Veronica A Kinsler, Derek Macmillan, Wei-Li Di
Tissue kallikreins (KLKs), in particular KLK5, 7 and 14 are the major serine proteases in the skin responsible for skin shedding and activation of inflammatory cell signaling. In the normal skin, their activities are controlled by an endogenous protein protease inhibitor encoded by the SPINK5 gene. Loss-of-function mutations in SPINK5 leads to enhanced skin kallikrein activities and cause the skin disease Netherton Syndrome (NS). We have been developing inhibitors based on the Sunflower Trypsin Inhibitor 1 (SFTI-1) scaffold, a 14 amino acids head-to-tail bicyclic peptide with a disulfide bond...
2016: PloS One
https://www.readbyqxmd.com/read/27814507/a-functional-genomics-approach-to-understand-variation-in-cytokine-production-in-humans
#18
Yang Li, Marije Oosting, Sanne P Smeekens, Martin Jaeger, Raul Aguirre-Gamboa, Kieu T T Le, Patrick Deelen, Isis Ricaño-Ponce, Teske Schoffelen, Anne F M Jansen, Morris A Swertz, Sebo Withoff, Esther van de Vosse, Marcel van Deuren, Frank van de Veerdonk, Alexandra Zhernakova, Jos W M van der Meer, Ramnik J Xavier, Lude Franke, Leo A B Joosten, Cisca Wijmenga, Vinod Kumar, Mihai G Netea
As part of the Human Functional Genomics Project, which aims to understand the factors that determine the variability of immune responses, we investigated genetic variants affecting cytokine production in response to ex vivo stimulation in two independent cohorts of 500 and 200 healthy individuals. We demonstrate a strong impact of genetic heritability on cytokine production capacity after challenge with bacterial, fungal, viral, and non-microbial stimuli. In addition to 17 novel genome-wide significant cytokine QTLs (cQTLs), our study provides a comprehensive picture of the genetic variants that influence six different cytokines in whole blood, blood mononuclear cells, and macrophages...
November 3, 2016: Cell
https://www.readbyqxmd.com/read/27814401/the-kallikrein-kinin-system-a-novel-mediator-of-il-17-driven-anti-candida-immunity-in-the-kidney
#19
Kritika Ramani, Abhishek V Garg, Chetan V Jawale, Heather R Conti, Natasha Whibley, Edwin K Jackson, Sruti S Shiva, William Horne, Jay K Kolls, Sarah L Gaffen, Partha S Biswas
The incidence of life-threatening disseminated Candida albicans infections is increasing in hospitalized patients, with fatalities as high as 60%. Death from disseminated candidiasis in a significant percentage of cases is due to fungal invasion of the kidney, leading to renal failure. Treatment of candidiasis is hampered by drug toxicity, the emergence of antifungal drug resistance and lack of vaccines against fungal pathogens. IL-17 is a key mediator of defense against candidiasis. The underlying mechanisms of IL-17-mediated renal immunity have so far been assumed to occur solely through the regulation of antimicrobial mechanisms, particularly activation of neutrophils...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27810449/detection-of-high-grade-prostate-cancer-among-plco-participants-using-a-prespecified-four-kallikrein-marker-panel
#20
Eric H Kim, Gerald L Andriole, E David Crawford, Daniel D Sjoberg, Melissa Assel, Andrew J Vickers, Hans Lilja
PURPOSE: To assess the performance of a four-kallikrein panel, with and without microseminoprotein-beta (MSP), to predict high-grade (Gleason 7+, Gleason Grade Group 2+) prostate cancer (PCa) on biopsy in a multiethnic cohort from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. MATERIALS AND METHODS: Levels of free, intact, total prostate-specific antigen (PSA), human kallikrein-2, and MSP were measured blinded to outcome in cryo-preserved serum from men in the intervention arm of PLCO...
October 31, 2016: Journal of Urology
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