Publications by authors named "Katya Chobotova"

7 Publications

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Bromelain's activity and potential as an anti-cancer agent: Current evidence and perspectives.

Cancer Lett 2010 Apr 22;290(2):148-56. Epub 2009 Aug 22.

University of Oxford, UK.

The medicinal qualities of pineapple are recognized in many traditions in South America, China and Southeast Asia. These qualities are attributed to bromelain, a 95%-mixture of proteases. Medicinal qualities of bromelain include anti-inflammatory, anti-thrombotic, fibrinolytic and anti-cancer functions. Existing evidence derived from clinical observations as well as from mouse- and cell-based models suggests that bromelain acts systemically, affecting multiple cellular and molecular targets. In recent years, studies have shown that bromelain has the capacity to modulate key pathways that support malignancy. It is now possible to suggest that the anti-cancer activity of bromelain consists in the direct impact on cancer cells and their micro-environment, as well as in the modulation of immune, inflammatory and haemostatic systems. This review will summarize existing data relevant to bromelain's anti-cancer activity and will suggest mechanisms which account for bromelain's effect, in the light of research involving non-cancer models. The review will also identify specific new research questions that will need to be addressed in order for a full assessment of bromelain-based anti-cancer therapy.
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http://dx.doi.org/10.1016/j.canlet.2009.08.001DOI Listing
April 2010

Aging and cancer: converging routes to disease prevention.

Authors:
Katya Chobotova

Integr Cancer Ther 2009 Jun;8(2):115-22

Wolfson College, University of Oxford, Oxford, United Kingdom.

An integrative approach to the combined challenges of aging, cancer and stress is a necessary part of a global vision of wellness. Recent research into the mechanisms of aging, cancer and stress has established the biological links between these processes. Understanding these links is an important stepping-stone for developing approaches and therapies that ensure wellness throughout all stages of aging. This paper will consider the most recent developments in research into the molecular mechanisms common to aging and cancer and will discuss the effectiveness of natural approaches for preventing disease. Metabolic regulators as well as nutrient and energy sensors are involved in the processes of aging and cancer, and these are open to external manipulation and control. It is now becoming possible to demonstrate how nutrition, physical activity and stress control can lead to disease-free aging.
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http://dx.doi.org/10.1177/1534735409335505DOI Listing
June 2009

Producing human mechano growth factor (MGF) in Escherichia coli.

Protein Expr Purif 2008 Mar 7;58(1):70-7. Epub 2007 Nov 7.

A.N. Bakh Institute of Biochemistry, Russian Academy of Sciences, Leninskii prosp., 33, Moscow 119071, Russia.

MGF is a product of a unique muscle-specific splice variant of IGF1 gene (insulin-like growth factor). Its peculiar feature is a specific E-peptide, a 16 a.a. strand at the C-terminus. MGF increases cellular proliferation and inhibits terminal differentiation of myoblasts necessary for the secondary myotube formation. Previous analysis of physiological effects of MGF was performed using indirect methods such as RT-PCR based examination of the transcript contents in normal tissues, adenovirus-mediated DNA delivery and synthetic E-domain administration. Here, we describe isolation and purification of recombinant MGF thus allowing for the first time the possibility of direct examining MGF effects. The recombinant MGF of directly examining--was expressed in Escherichia coli as inclusion bodies (about 100-200mg/l), purified and refolded. Biological activity of refolded MGF was analyzed in vitro in proliferation assays with normal human myoblasts. As a result of our work, it has become possible to generate a standard MGF control with characterized activity and a ready-to use MGF test-system neither of which have been previously described. Our data open opportunities for the future works on MGF characterization and to the development of a powerful and highly specific therapeutic agent potentially applicable for muscle growth up-regulation, post-trauma muscle repair, age and hereditary myodystrophy mitigation and in sport medicine.
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http://dx.doi.org/10.1016/j.pep.2007.10.023DOI Listing
March 2008

Heparin-binding epidermal growth factor and its receptors mediate decidualization and potentiate survival of human endometrial stromal cells.

J Clin Endocrinol Metab 2005 Feb 23;90(2):913-9. Epub 2004 Nov 23.

Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.

Heparin-binding epidermal growth factor (HB-EGF) has pleiotropic biological functions in many tissues, including those of the female reproductive tract. It facilitates embryo development and mediates implantation and is thought to have a function in endometrial receptivity and maturation. The mature HB-EGF molecule manifests its activity as either a soluble factor (sol-HB-EGF) or a transmembrane precursor (tm-HB-EGF) and can bind two receptors, EGFR and ErbB4/HER4. In this study, we identify factors that modulate expression of HB-EGF, EGFR, and ErbB4 in endometrial stromal cells in vitro. We demonstrate that levels of sol- and tm-HB-EGF, EGFR, and ErbB4 are increased by cAMP, a potent inducer of decidualization of the endometrial stroma. We also show that production of sol- and tm-HB-EGF is differentially modulated by TNF alpha and TGF beta. Our data suggest that HB-EGF has a function in endometrial maturation in mediating decidualization and attenuating TNF alpha- and TGF beta-induced apoptosis of endometrial stromal cells.
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http://dx.doi.org/10.1210/jc.2004-0476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626580PMC
February 2005

Expression and function of interleukin-11 and its receptor alpha in the human endometrium.

Mol Hum Reprod 2003 Feb;9(2):75-80

Department of Obstretrics and Gynaecology, University of Oxford, Women's Centre, Level 3, John Radcliffe Hospital, UK.

The interleukin-11 (IL-11) receptor alpha has an important function in decidualization of mouse endometrial stroma but the function of IL-11 and its receptor in the human endometrium remains unknown. The mRNA for IL-11 and its receptor alpha in human endometrial tissue samples were analysed by semi-quantitative RT-PCR and RNase protection assays respectively. The proteins were detected in frozen endometrial tissue samples by immunofluorescence. The effect of heparin-binding epidermal growth factor (HB-EGF) on secretion of IL-11 by cultured endometrial stromal cells was assessed by enzyme-linked immunosorbent assay. The proliferative potential of IL-11 in endometrial stromal cells was assessed by [(3)H]thymidine uptake. IL-11 and its receptor alpha mRNAs and proteins were detected in the endometrium throughout the cycle. Distinct patterns of localization of the ligand and receptor were observed. HB-EGF induced IL-11 secretion by cultured stromal cells, and IL-11 induced [(3)H]thymidine uptake by these cells. Our data suggest that IL-11-receptor interactions may perform different functions in the human endometrium at different stages of the cycle, and that secretion of IL-11 is modulated by local growth factors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626582PMC
http://dx.doi.org/10.1093/molehr/gag012DOI Listing
February 2003

The mitogenic potential of heparin-binding epidermal growth factor in the human endometrium is mediated by the epidermal growth factor receptor and is modulated by tumor necrosis factor-alpha.

J Clin Endocrinol Metab 2002 Dec;87(12):5769-77

Nuffield Department of Obstetrics and Gynecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom OX3 9DU.

Heparin-binding epidermal growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, is implicated in a variety of biological processes, including reproduction. Previous studies describe increased levels of HB-EGF in the human endometrium during the midsecretory stage of the menstrual cycle, suggesting a function for HB-EGF in implantation of the human blastocyst. Here we have investigated the expression and function of the soluble and transmembrane forms of HB-EGF in the human endometrium. We show that the expression of the transmembrane form of HB-EGF in the human endometrium is modulated according to the stage of the menstrual cycle. We present data demonstrating that both the soluble and transmembrane forms of HB-EGF induce DNA synthesis in human endometrial stromal cells. Furthermore, TNFalpha has a cooperative effect on HB-EGF, EGF, TGFalpha, and betacellulin-induced DNA synthesis in stromal cells, suggesting roles for the EGF family and TNFalpha in regeneration and maturation of human endometrium. Induction of DNA synthesis by HB-EGF and its modulation by TNFalpha in endometrial stromal cells are mediated by the EGF receptor and not the HB-EGF receptor ErbB4. Our data suggest key functions for HB-EGF, TNFalpha, and the EGF receptor in endometrial maturation, via autocrine/paracrine and juxtacrine pathways, in preparation for embryo implantation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1635788PMC
http://dx.doi.org/10.1210/jc.2002-020069DOI Listing
December 2002

Heparin-binding epidermal growth factor and its receptor ErbB4 mediate implantation of the human blastocyst.

Mech Dev 2002 Dec;119(2):137-44

Nuffield Department of Obstetrics and Gynaecology, The Women's Centre, Level 3, John Radcliffe Hospital, University of Oxford, Headington, Oxford, OX3 9DU, UK.

The mechanisms that mediate implantation of the human embryo remain poorly understood and represent a fundamental problem in reproductive biology. Candidate molecules that mediate and facilitate implantation have been identified in animal studies, and include heparin binding epidermal growth factor. Here we demonstrate a potential function for the transmembrane form of heparin-binding epidermal growth factor in mediating blastocyst attachment to the endometrium, in two different novel in vitro models for human implantation. Furthermore, we demonstrate specific localisation of the heparin-binding epidermal growth factor receptor ErbB4, on the surface of the trophectoderm in peri-implantation human blastocysts. Our data lead the way for further dissection of the molecular mechanisms of implantation of the human embryo, and have implications for infertility, in vitro fertilization and contraception.
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http://dx.doi.org/10.1016/s0925-4773(02)00342-8DOI Listing
December 2002