8^th European Conference on Predictive, Preventive & Personalized Medicine and Molecular Diagnostics August 20-21, 2018 Rome, Italy

Biography:

V F Semenkov has completed his Doctorate in 1983 at Immunology Institute, Moscow, Russia. He is the Professor at Medical University named N I Pirogov Immunology Department, Moscow. He has published more than 170 papers in reputed journals and now is a member of Scientific Council on Pathophysiology at the Medical University named N I Pirogov

Abstract:

Individual sensitivity to oxidative stress is important biological marker for medical management optimization. Dose of antioxidant used in treatment should be in accordance with that sensitivity. We propose a hypothesis that functions of anti-stress genes consist in regulation of ROS level through production of heat shock proteins p70. In this work AS influence on ROS production in isolated from peripheral blood neutrophils of donors was studied. The neutrophils samples from 50 donors 20-95 years were used. In the study AS was heated at 100ËšC for 30 sec. or was irradiated by UV rays 200-280 nm, 8 W, 10 min. Neutrophils were exposed to heat shock at 42ËšC for 30 sec., 1 min. and 3 min. with following determination of chemiluminescence reaction induced by zymosan. It has been demonstrated that AS can increase or decrease ROS production by neutrophils depending on presence in the serum of proteins with structure changed by heating or UV treatment. It has been also shown that expression of heat shock protein p70 family in neutrophils and lymphocytes of peripheral blood obtained from old donors was reduced in comparison with level of this expression in group of young donors. Shortening of heat shock stress duration for neutrophils was effective for determination of individual sensitivity to oxidative stress. We suppose that action of environment factors on AS proteins can cause an adverse increase of oxidative stress level as result of functional activity reduction of anti-stress genes.

Biography:

Natalie Pankova holds a PhD from the Faculty of Medicine from University of Toronto, where her work was focused on inflammatory disease and retinal degeneration. Additionally she worked on advanced diagnostics and precision medicine strategies, which turned into a career in biotech and drug development, where she was a Director in early stage healthcare startups. She is now Chief Scientific Officer at Shivom, a global genomics blockchain company focused on advancing precision medicine by enriching and improving the currently limited and siloed genomic data. She is also the global lead for the genomic research working group within the government blockchain association.

Abstract:

With the costs of pharmaceutical development sky rocketing, companies are looking for new ways to innovate, obtain insights and cut R&D costs. The use of biomarkers can dramatically improve success rates for drug development and genomics and multi omics data are the next steps in precision medicine and effective drug discovery. However, current data sets are often lacking in information, may be inaccessible and numerous gaps exist that need to be filled and this information needs to be transformed into formats that are useful for pharma companies. Work need to be done to obtain the right genomic data, efficiently combine this data with phenotypic and peripheral health data and properly analyzing it to deliver value. Blockchain technology is a tool that can be used to effectively manage patient data, including genomic sequences, such that data silos can be broken, interoperability and collaboration can be increased and novel insights can be delivered to provide effective solutions. Here, cases will be introduced for the implementation of blockchain in a precision medicine ecosystem and describes how both pharma and patients can benefit from gaining access to such data

Biography:

Somayeh yaslianifard, has completed her Dr Ph.D. Research at Tehran University of Medical Sciences. Tehran. Iran. She has completed her M.sc. research Tarbiat Modares University

Abstract:

Aim: Considerably, about half of the world human population is infected by H. pylori. Current standard therapies against H. pylori are based on the use of one proton pump inhibitor plus two or more antibiotics the efficacy of this treatment has decreased, mainly due to the increase of antibiotic resistance but also to side effects. As regards to the antibiotics resistant and its side effects we tried to follow other therapies. The role of probiotics in the treatment of gastrointestinal infections has increased during some decades. One of the most important groups of probiotics is lactic acid bacteria. The aim of this study was to analyze the efficacy of Lactobacillus rhamnosus on gastric ulcer induced by Helicobacter pylori (ATCC43504).

Materials & Methods: In this experiment the mice were randomly divided into three experimental groups (eight mouse in each group) in group one, mice were inoculated with H. pylori suspension (5*10¹⁰cfu_s/ml) in PBS by gavage twice daily for three consecutive days and animals were treated with lactobacillus rhamnosus segregated from honey + bismuth and omeprazole (10⁶cfu_s/ml) suspended in PBS twice daily for two weeks. In group two after infection will be treatment with clarithromycin (Positive control), in group three, after confirmation of infection, treatment was not used. (Negative control) Four weeks after the last inoculation, we confirmed the infection by determination of H. pylori stool Ag (ELISA) and histopathological examination. One mouse from each group was sacrificed and the tissues removed for histological experiment.

Result & Conclusion: After six weeks, the improvement or existence of inflammation in the biopsies sample of gastric ulcer in each group was investigated. H. pylori infection in mice was determined by the Eliza test and histopathology. Histopathology in the negative control group was normal, while in the H. pylori infected positive control group there was H. pylori colonization and inflammation. Lactobacillus rhamnosus + bismuth and omeprazole 10⁶ CFU/mL treated groups showed significant improved stomach inflammation. Lactobacillus rhamnosus has healing effects on gastric ulcer induced by Helicobacter pylori.

Biography:

Hans-Peter Deigner completed his PhD in Pharmaceutical Chemistry from Heidelberg University; Post-doctoral research at Harvard Medical School, Boston and then became Senior Lecturer at Heidelberg University. He has extensive experience in Biotechnology and Molecular Diagnostics including positions as Sr. Director Biomarker Research/CSO and share-holder of several biotech companies across Europe. From 2004-2006, he took up a chair in Biomedicinal Chemistry, School of Chemical Sciences and Pharmacy (CAP), University of East Anglia, Norwich, UK. Currently, he is Professor in the Faculty of Medical and Life Sciences (MLS), Furtwangen University and Co-director of Institute of Precision Medicine. He also holds an appointment as Visiting Scientist at Fraunhofer Institute IZI, Leipzig, Germany. He is author of more than 90 peer reviewed articles, 40 patents and patent applications. His research interests include “Precision diagnostics, biomarker and quantitative assay development, metabolomics and nanopore-sequencing”.

Abstract:

Metabolomics data are very important for the elucidation of pathobiochemical mechanisms and an integral part of disease-related omics analyses. They further offer opportunities for diagnosis, prognosis and therapy control in numerous neurodegenerative diseases. This paper provides an overview on recent developments in metabolomics across diseases including Alzheimer’s disease, multiple sclerosis (MS) and asphyxia of neonates. Recent publications report a good match of a brain metabolite signature with plasma data in Alzheimer’s patients and indicate a disturbed glucose as well as glutamate-glutamine metabolism in MS patients. In cerebrospinal fluid (CSF) samples of MS patient’s metabolic changes were found to be disease stage dependent. Our focus is on asphyxia diagnostics applying metabolic classifier. In asphyctic neonates, asphyxia was found to be reflected by characteristic plasma metabolite signatures involving e.g. Krebs-cycle metabolites. We have identified metabolites indicating early asphyxia and demonstrate that metabolite quantification offers an ideal tool for characterizing and prognosing neurodegenerative diseases and diagnosing oxygen deprivation.

Biography:

Farihan Farouk Helmy has completed her Dr.PH from Alexandria University, Child Mental Health department and Post-doctoral studies from Alexandria University. She is running a Clinic (Behavioural problems and Autism) in Taif Children Hospital Ministry of health and also working as Assistant Paediatrics Professor in Medical College at Taif University

Abstract:

A three year old female patient born of consanguineous parents presented to the (development and behavioural clinic) Taif Children Hospital, Western Saudi Arabia, her mother complained that her daughter had speech delay, no eye to eye contact, and was performing stereotyped behaviours (hand flapping). The girl developed convulsions at the age of three months and was on anticonvulsant medication since that age her convulsions were controlled on anti-epileptic treatment. Family history revealed that the girl had a male sibling six years old who developed convulsions at the age of four months and is on antiepileptic medications, the boy also suffered from speech delay, absence of social interaction, and repetitive behaviours. On examination the girl had characteristic features of angio-fibromas, hypo-pigmented macules on the trunk and legs and moreover the boy had similar skin features plus hypo-pigmented tufts of hair. Both cases were diagnosed as autistic spectrum disorder, tuberous sclerosis, and mental retardation. The family needed genetic counselling, while both cases needed possible behavioural and educational strategies

Biography:

He was born in 1980 at Erzurum, Turkey. He attended from Ataturk University Medical School, in 1999-2005.  He was completed internal medicine residency at the same ınstitute between 2005 - 2010.  Dr. Cadirci is working at Saglik Bilimleri University Regional Training and Research Hospital Erzurum, Turkey

Abstract:

The use of dietary multivitamin supplements has incresed in developed and developing countries.  The most popular belief which largely depends on the observational trials has been that these multivitamin supplements can prevent cancer.  Some of these trials show a positive effect or ineffectiveness on the cancer risk while some may even increase the risk. 

An important point is that specific populations take dietary supplements, compared to the general healthy population.  This is a significant bias in most of the large trials.  To break down this bias, interventional cohorts can be evaluated.  There are a few interventional cohorts on this topic and these interventional trials results show that most of the multivitamin supplements reduce the total cancer risk and mortality, but it is necessary not to forget that these studies were set up in underdeveloped or developing countries, and most of the participants that have malnutrition were dependent on unidirectional nutrition. 

What is the interaction between these minerals and the dietary supplements?  What is the cut-off values for benefit and harm?  Are these cut-off values the same for the different nations, lifestyle, gender and ages, even different geographic regions where the soils have the different amounts of minerals?  What is the interaction or are there any interactions between the amount of minerals in the soil and these multivitamins supplements?  There are so many questions like the ones above.  To answer these questions, there is a need for more randomized controlled trials, interventional trials, and systematic review and meta-analysis.

Biography:

Elena A Kotenkova completed her PhD from V M Gorbatov Federal Research Center for Food Systems-RAS. She is the Senior Researcher of experimental - clinical research laboratory of bioactive substances of animal origin. She has published more than 60 papers in reputed journals. Her scientific interests are in the fields of “Medicine, nutrition, agricultural and biological sciences, biochemistry and laboratory animal science”.

Abstract:

Meat product for specialized nutrition made of porcine aortas and hearts in ratio 1:3 was tested on thirty male Wistar rats (380±20 g) aged approximately one year, which were randomly divided into three groups: group 1 – negative control (n=10); group 2 – positive control (n=10) and group 3 – experimental animals (n=10). Animals in group 2 and 3 were modeled an alimentary hyperlipidemia by adding cholesterol, fat and vitamin D2 into diet. After modeling, rats in group 2 were fed with standard chow, in group 3 – meat product (8 g/kg b.w.) with standard chow. It was observed that consumption of developed meat product by hyperlipidemic rats during 42 days led to reduction of serum lipids level while compared with positive control group. Serum total cholesterol was decreased by 31.8%, triglycerides – 28.2%, atherogenic fractions of lipoproteins by 2.4 times, atherogenic index by 41.3%. Proteomic study revealed the presence of a number specific proteins in tissues of porcine aorta and heart, such as apolipoprotein A-1, peroxiredoxin-1 (in mixture with transgelin), galectin-1, fatty acid binding protein, a number of heat shock proteins as well as various peptides, which mainly were decomposed after sterilization, presumably, into active peptides with similar biological action. On the other hand, numerous publications also confirmed structural proteins as a good source of bioactive peptides, including peptides with lipid lowering action. Heart tissue is enriched with muscle tissue proteins, while aorta – collagen and elastin, which are a source of Gly-Pro peptides with hypo lipidemic action. Presumably, active peptides could be generated both during meat product processing and digestion processes. Results of both in vivo and proteomic studies indicated developed meat product as a perspective diet component for people with a high risk of atherosclerosis.

Biography:

Bazyleva Ekaterina Vladlenovna completed her Graduation from German School in Moscow in 2014. Currently, she is a student of Medical University of Varna in Bulgaria and pursuing her PhD in Department for Personalized and Precision Medicine at University of World Politics and Law, Moscow, Russia.

Abstract:

Immune reactions triggered by microbial antigens (Ags) can be ignored by tools of immune surveillance (apoptosis or immune suppression), and auto-reactive T- and B-cells can survive for molecular mimicry phenomenon based on the activation of auto-reactive lymphocytes by cross-reactive epitopes of the pathogen. The outcome of the event would result in manifestations of a so-called post-infectious autoimmune syndrome (PIFAS), a new combinatorial biomarker illustrating immune-mediated disorders including latent ones. Wherein the evaluation of triggering role of infection in the pathogenesis of PIFAS is often difficult since the time for provoking the disease to be transformed into PIFAS may begin prior specific manifestations of PIFAS would form. Thus, for autoimmune myocarditis (AIM) to make a bridging link with the infection is established for two-thirds of all the patients, and transformation of primary or infectious phase into PIFAS is initiated by mimicking epitopes of, for instance, CVB3 and/or CMV, herewith presence of auto-reactive CTLs and anti-CM auto-Abs, to release sequestered auto-Ags and to facilitate the induction and/or development of PIFAS is required. Despite a vast armamentarium of approaches to assess PIFAS, there are still no obvious clinical and laboratory criteria to get the syndrome validated. An application of transgenic models to suit the objectives of clinical practice will give an opportunity to reveal the sequence of events between induction and progressing of PIFAS and allow to control induction and progression of PIFAS and thus chronification of the disease to prevent the latter in time.

Biography:

She attended from Istanbul University, Istanbul Medical School, in 1993-1999.  She did her residency at Ankara University Hospital between 2002-2007.  Professor Dr. Ahmet Demikazık was her mentor during her residency.  Dr. Ahmet, one of the most famous oncologists and researchers in Turkey, served as her mentor.  Medical Oncology Section of Ankara University School of Medicine is also one of the largest Medical Oncology Departments in Turkey.  She worked with Professor Dr. Philip R. Taylor as a guest researcher and fellow assistant at National Institutes of Health (NIH), National Cancer Institute (NCI) Division of Cancer Epidemiology & Genetics, Metabolic Epidemiology Branch, 2015-2017.  She improved her skills in epidemiology and clinical research.  She is proud to work with excellent mentors. Dr. Keskin is working at Istanbul Medeniyet University Research Hospital, and she is enrolled in a doctoral program in Epidemiology and Data Management at Istanbul University Cerrahpasa Medical school

Abstract:

The daily taking of a low-dose aspirin has become more common when dealing with cardiovascular and cerebrovascular issues in the past century. Evidence from the re-examination of the case control and cohort studies which were designed primarly to assess different diseases showed that the taking of a daily low dose aspirin in the long term not only decreases the frequencies of these mentioned diseases but also leads to a decrease in the frequency of certain cancers especially colorectal cancer. However, some of the cilinical trials show a positive effect while some decelerated ineffectivenees and even showed a negative effect on some kind of cancers. An important point is that specific populations take the daily low dose aspirin in the long term, compared to the general healthy population. This point may be a significant bias in these large trials. To break down this bias, more interventional cohorts should be set up at diffrent socioeconomic populations in different countries. Most of the participants take different drugs due to different comorbidities. These comorbid diseases can also cause inflammation and the development of various cancers. It has been displayed there is some possible effect of usage of aspirin in cancer chemoprevention, but the mechanisms are not still clear. As a result, taking daily low dose aspirin in cancer primary prevention remains controversial. The latest meta analyses have been very encouraging especially the taking daily low dose long term aspirin to prevent cancer, but the current consensus is: not yet. There is a need for more randomized controlled trials, interventional trials, systematic reviews and meta-analyses.

Biography:

S Suchkov graduated from Astrakhan State Medical University in 1980 and was awarded with MD. In 1985, he completed PhD from I M Sechenov Moscow Medical Academy and Institute of Medical Enzymology. In 2001, he completed his Doctor Degree at the National Institute of Immunology, Russia. From 1989 to 1995, he was Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004, he is a Chair of the Dept. for Clinical Immunology, Moscow Clinical Research Institute (MONIKI). In 1993-1996, he was a Secretary-in-Chief of the Editorial Board, Biomedical Science, an international journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK. At present, he is Professor and Chair, Department for Personalized and Translational Medicine, I M Sechenov First Moscow State Medical University and Department of Clinical Immunology, A I Evdokimov Moscow State Medical and Dental University. He is a member of the Editorial Boards of Open Journal of Immunology, EPMAJ, American J of Cardiovascular Research and Personalized Medicine Universe. He was the Head of the Lab of Clin Immunol at Helmholtz Eye Res Inst in Moscow from 1989 to 1995. He was a Chair in the Dept. for Clin Immunol at Moscow Reg Clin Res Inst from 1995 to 2004. He has been trained at: NIH; Wills Eye Hospital, PA, USA; University of Florida in Gainesville; UCSF, S-F, CA, USA; Johns Hopkins University, Baltimore, MD, USA. He was an Executive Secretary-in-Chief of the Editorial Board, Biomedical Science, an international journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK. At present, he is a Director of the Center for Personalized Medicine, Sechenov University and Chair in the Dept. for Translational Medicine at Moscow Engineering Physical Institute (MEPhI), Russia. He is a member of New York Academy of Sciences, USA; American Chemical Society (ACS), USA; American Heart Association (AHA), USA; EPMA (European Association for Predictive, Preventive and Personalized Medicine), Brussels, EU; ARVO (American Association for Research in Vision and Ophthalmology); ISER (International Society for Eye Research); PMC (Personalized Medicine Coalition), Washington, USA.

Abstract:

Antibodies armed with functionality including catalytic Abs (catAbs) are multivalent immunoglobulin’s (Igs) with a capacity to hydrolyze the antigenic (Ag) substrate. In this sense, proteolytic Abs (Ab-proteases) represents Abs to provide proteolytic effects. Abs against myelin basic protein/MBP with proteolytic activity exhibiting sequence-specific cleavage of MBP is of great value to monitor demyelination whilst in MS. The activity of Ab-proteases was first registered at the subclinical stages 1-2 years prior to the clinical illness. And the activity of the Ab-proteases revealed significant correlation with scales of demyelination and the disability of the patients as well. So, the activity of Ab-proteases and its dynamics tested would confirm a high subclinical and predictive (translational) value of the tools as applicable for personalized monitoring protocols. Of tremendous value are Ab-proteases directly affecting remodeling of tissues with multilevel architectonics (for instance, myelin). By changing sequence specificity one may reach reduction of a density of the negative proteolytic effects within the myelin sheath and thus minimizing scales of demyelination. Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of new catalysts with no natural counterparts. Further studies are needed to secure artificial or edited Ab-proteases as translational tools of the newest generation to diagnose, to monitor, to control and to treat and rehabilitate MS patients at clinical stages and to prevent the disorder at subclinical stages in persons-at-risks to secure the efficacy of regenerative manipulations.

Biography:

Megnanou Rose-Monde is an Associate Professor in Biochemistry at University Félix Houphouët-Boigny, where she has completed her PhD in Biochemistry/Food Sciences. She has more than 30 scientific publications about various biological materials (shea butter, yellow cassava, qp maize, plantain, vegetable-leaves and cow-milk) published in reputed scientific journals. She has skills in statistical analyses (descriptive statistic, ANOVA, ACP, CAH, AFD), microbiology tests (germs numeration and identification), molecular biology techniques (DNA extraction, enzymatic digestion, western blot, etc.) and various biochemical and physicochemical parameters determination.

Abstract:

Traditional shea butter has increasing demand throughout the world which is directly linked to its intrinsic biochemical properties. There are various processes that induced several qualities of shea butter, but author has set up the optimized traditional processes which lead to shea butter in conformity with international standards and presenting interesting nutritive and cosmetic/pharmaceutical potentials. It consists of a creamy fat which is UV-visible and infrared spectra revealed anti-UV compounds, carotenoids and chlorophyll. Tocopherols (3788.44±1.90 ppm), vitamin A equivalent (0,065± 0,001 g/100g), and various fatty acids (oleic, linoleic, linolenic, arachidic, palmitic and stearic) and exaltolide which is an unusual compound of shea butter were also found. pH (06.78±0.30) was nearby neutral and unsaponifiable (17.61±0.01%) content is very high. Above all, its moisture (0.15%), acid (0.280±0.001 mg KOH/g) and peroxide (0.960±0.001 mEgO₂/kg) indexes were at far lower than those (8.36±0.02%, 14.97±0.33 mg KOH/g and 17.92±0.50 mEgO₂/kg, respectively) of ordinary traditional shea butter. These potentials would place the optimized shea butter at the level of valuable organic (Bio) vegetable fat exploitable in preventive and curative medicine. Moreover, it would contribute to improve rural woman-producers living standard.

Biography:

Kruchinina M V has completed her Doctor of Medicine degree at Institute of Internal Medicine SB RAS, Novosibirsk, Russia. From 2009, she is a Leading Researcher at Research Institute of Internal and Preventive Medicine–Branch of Federal State Budget Scientific Institution of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia. She is the author of more than 120 publications, including one monograph, five teaching aids and eight patents. Her areas of scientific interests are metabolomics, microcirculation, rheology, membrane disorders in oncopathology, endocrinological, cerebrovascular, cardiovascular pathology and diagnosis of diffuse liver pathology.

Abstract:

The aim of the work was to evaluate lipid metabolites of blood serum (BS) and red blood cells (RBCs) as potential biomarkers for the diagnosis of colorectal cancer (CRC). BS, RBCs from 95 patients (56+8 years old) with colorectal adenocarcinoma (early stages I-II, n=44; late stages III-IV, n=51) and 28 healthy controls were analyzed by FT mass spectrometry, GC/MS system triple quad Agilent 7000B (USA). The list one of the BS lipid metabolites - amines of fatty acids (FA) (palmitic amide, erucamide, oleamide), saturated FA (C14:0, 16:0, 18:0), polyunsaturated FA (C20:3, 20:4), lysophosphatidylcholines (m>2) (C18:2, 20:2, 20:4, 20:6, 22:6) allowed us to obtain the high level of AUC 0.98 (sensitivity 0,97, specificity 0,99) when comparing early stage CRC patients with controls. Panel two including the following lipids of BS - palmitic amide, erucamide, oleamide, myristic, palmitic, stearic acids, lysophosphatidic acids, LPC(16:0)- showed good opportunities for distinguishing the CRC patients from healthy controls (AUC 0,95 (0,8, 0,96). The combination of the lipids - phosphatidylcholine, phosphatidylserine, lysophosphatidylcholines (18:0, 18:1, 18:2, 20:4, 20:6, 22:6), palmitic acid – differentiated the late stages from the early ones (AUC 0,91 (0,80, 0,92). Differentiating FA of RBCs membranes were polyunsaturated (C20:0, C20:2, C20:3, C20:4, C22:4, C22:5, C22:6), the levels of which were significantly higher in CRC patients, and saturated and monounsaturated (C 12-17:0, C16:1, C 18:1, C18:2), prevailing in healthy controls. The observed shifts correlated with the CRC stages. The lipid metabolites of blood serum and erythrocytes should be considered as the promising biomarkers for CRC diagnosis.

Biography:

Min-kyung Yeo has completed her Medical degree at Chungnam National University, Daejeon, South Korea in 2007 and PhD in 2015 at the same university. She is working as an Assistant Professor in the Department of Pathology at Chungnam National University Hospital, Daejeon, South Korea.

Abstract:

Partitioning defective (Par) proteins regulate cell polarity and differentiation. Par3, Par6β, and protein kinase Cζ (PKCζ), which are PAR complex members, have been shown to be associated with oncogenesis and progression. Herein, we report the expression pattern and clinical relevance of Par3, Par6β, and PKCζ in colorectal adenocarcinoma (CRAC). A total of 393 primary CRACs, 41 primary-metastatic CRAC pairs, 41 adenomas with low-grade dysplasia, and 41 non-tumor colorectal tissue samples were examined by immunohistochemistry and western blot assays for Par3, Par6β, and PKCζ protein expressions. The association Par3, Par6β, and PKCζ expressions and clinicopathological factors, including patient survival, was evaluated. Primary CRACs and adenomas demonstrated higher levels of Par3, Par6β, and PKCζ than in non-tumor colorectal epithelia. The expressions of Par3, Par6β, and PKCζ were higher in primary CRACs as compared to adenomas or in metastatic CRACs. Among primary CRACs, decreased Par3 expression was found to correlate with a high proliferation rate and poor histological differentiation, decreased PKCζ expression was correlated with pathological TNM stage (I-II versus III-IV) and lymph node metastasis, and decreased Par6β and PKCζ expressions were correlated with shortened overall survivals. In metastatic CRACs, decreased PKCζ expression was correlated with a shortened metastasis-free survival. While increased Par3, Par6β, and PKCζ expressions were implicated in tumorigenesis, decreased expressions of Par3, Par6β, and PKCζ were found to be associated with worse clinicopathological factors in CRAC. In particular, the results of our study suggest that PKCζ down-expression is an independent poor prognostic and metastatic factor for CRAC.