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Protein and Prognostic Biomarkers |
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Protein and Prognostic Biomarkers

Research Article

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Serum c-kit Protein Detection as a Reliable Biomarker for the Diagnosis of Gastrointestinal Stromal Tumors: A Case-Control Study

Kakavetsi V, Apostolopoulos P, Karameris A, Dimakis A, Tsimbouris P, Zalonis A, Karamountzos A, Adamopoulos A, Vafiadis I, Ladas S and Alexandrakis G

DOI:

DOI: 10.4172/2155-9929.S6-001

Background: In the last decade, the diagnostic approach of Gastrointestinal Stromal Tumors (GIST) has drastically changed with the utilization of tissue-specific biomarkers, such as c-Kit. However, a serum biomarker aiding in differential GIST diagnosis prior to surgery would provide added benefit in the daily clinical practice. Thus, the aim of the study was to investigate whether detection of c-Kit protein in the serum could be used as a reliable diagnostic biomarker.

Methods: Twenty-seven patients with histologically confirmed GIST (16 men; age 41-80 years), 27 healthy controls (14 men; age 45-76 years) and 24 patients with submucosal tumors other than GIST (10 men; age 25-85 years) were enrolled in the study. Detection of serum c-Kit protein in blood samples of all patients prior to any treatment-related intervention and of healthy participants was accomplished using flow cytometry. The sensitivity and specificity of the assay were estimated.

Results: Of the 27 patients with GIST, 25 were serum c-Kit positive. In the control group of 27 healthy participants, all except one were serum c-Kit negative, while among the 24 patients with tumors either than GIST, 22 were serum c-Kit negative and 2 were positive. Based on these results, the sensitivity of the assay was 92.6%, while the specificity was 96.3% when compared with the healthy volunteers and 91.7% in comparison with the non-GIST group.

Conclusion: c-Kit protein detection with flow cytometry could represent a reliable sensitive and specific serum bioassay for differential GIST diagnosis.

Research Article

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The ACTN3 Gene is a Potential Biomarker for the Risk of Non-Contact Sports Injury in Female Athletes

Kyoko Iwao-Koizumi, Tomoko Ota, Mariko Hayashida, Yasukazu Yonetani, Ken Nakata, Kenji Kinoshita, Yoshio Koyanagi and Shigenori Murata

DOI:

DOI: 10.4172/2155-9929.S6-002

Sports injuries can become serious impairments for all athletes. Most notably, female athletes are at higher risk than men for sports injury, for example, anterior cruciate ligament (ACL) disorder. However, there is currently no genetic marker to determine if a female athlete harbors a predisposition for muscle trauma. Hence, we performed single nucleotide polymorphism genotyping of the α-actinin-3 (ACTN3), angiotensin-converting enzyme (ACE), and uncoupling proteins (UCP1, UCP2, and UCP3) in 99 young female athletes who had been injured during a sports activity, and we compared the occurrence of muscle traumas with the genotypes using the chi-square test. For the ACTN3 577R allele, the subjects who had non-contact muscle injury had a marked increase in frequency (p-value=0.0015; odds ratio=2.52). The significant increase in non-contact muscle injury related to ACTN3 577R alleles suggests that ACTN3 is likely to be involved in muscle strain and that non-contact muscle injury might occur due to the presence of this allele. It is crucially important for young female athletes to understand their risk for injury, as they might be able to modify their training program to avoid injury, depending on their specific genetic markers.

Research Article

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Analysis of 32 Blood-Based Protein Biomarkers for their Potential to Diagnose Colorectal Cancer

Kim YC Fung, Leanne Purins, Ilka K Priebe, Celine Pompeia, Gemma V Brierley, Bruce Tabor1, Trevor Lockett, Peter Gibbs, Jeannie Tie, Paul McMurrick, James Moore, Andrew Ruszkiewicz, Antony Burgess, Edouard Nice and Leah J Cosgrove

DOI:

DOI: 10.4172/2155-9929.S6-003

Colorectal cancer (CRC) is largely viewed as a preventable disease but the prevalence is increasing worldwide. Although many faecal and blood-based biomarkers have been proposed as potential diagnostic markers, none have been successful in large cohort studies. In this study, ELISA was used to evaluate 32 candidate protein biomarkers in a single cohort of CRC patients (n=95) and age/sex matched controls (n=50). Of these, 12 markers differed statistically between cases and controls. Receiver operating characteristic analysis identified IL8, Mac2BP, TIMP1, and OPN as the best performing markers for overall CRC diagnosis. However, further analysis determined that IL6, TGFB1, TIMP2 and IGF2 were most accurate at identifying early stage disease. We also assessed the correlation between markers and determined that the strongest correlations existed between VEGFA and TGFB1 (r=0.65, p<0.0001), M30 and M65 (r=0.59, p<0.001), and between TGFB1 and TIMP1 (r=0.55, p<0.0001). This analysis provides a consistent baseline for identifying a potential panel of diagnostic protein biomarkers in blood. Our results highlight protein biomarker combinations that reflect the disease process and which may provide the sensitivity and specificity required a reliable diagnosis of CRC.

Research Article

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Evaluation of CGB, GNRH1, MET and KRT19 Genes Expression Profile as a Circulating Tumor Cells Marker in Blood of Cancer Patients

Anna Szczerba, Krystyna Adamska, Wojciech Warchol, Mirosław Andrusiewicz, Ewa Nowak-Markwitzand Anna Jankowska

DOI:

DOI: 10.4172/2155-9929.S6-004

The aim of this study was to evaluate human chorionic gonadotropin beta subunit (CGB), gonadotropin releasing hormone type 1 (GNRH1), hepatocyte growth factor receptor (MET) and keratin 19 (KRT19) genes expression profile as a circulating tumor cells (CTC) marker in blood of cancer patients. Expression level of studied genes was assessed in peripheral blood of 122 patients with different types of cancers and 86 healthy volunteers using reverse transcription real time quantitative polymerase chain reaction (RT-qPCR). The result of the experiments demonstrated that in blood of cancer patients the level of MET transcripts showed positive correlation with KRT19 and negative correlation with GNRH1. In the control group negative correlation between CGB and GNRH1 was documented. What is more the level of CGB, MET and KRT19 expression was significantly higher in blood of cancer patients. Even though the analysis proved that studied genes are expressed in blood of both cancer patients and healthy volunteers, their expression level was highly heterogeneous. In order to interpret the results, the obtained data was log-transformed and fitted to multiplied normal distribution model using the maximal likelihood method. The results of this analysis showed elevated expression of CGB, MET and KRT19 together with extremely high levels of GNRH1 in blood of cancer patients which might indicate the presence of circulating tumor cells and increased risk of metastasis.

Research Article

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Presence of Phosphorylated Tau Protein in the Skin of AlzheimerÃ?â??Ã?´s Disease Patients

Rodríguez-Leyva Ildefonso, Chi-Ahumada Erika, Calderón–Garcidueñas Ana Laura, Medina-Mier Verónica, Santoyo Martha E, Martel-Gallegos Guadalupe, Zarazúa Sergio , Carrizales Juan and Jiménez-Capdeville María E

DOI:

DOI: 10.4172/2155-9929.S6-005

Background: The presence of misfolded proteins in the brain is the hallmark of neurodegenerative diseases. Protein aggregates could have systemic expression and might be found in several tissues including the skin. Objective: To demonstrate the presence of phosphorylated Tau (p-Tau) in the skin cells of patients with Alzheimer´s Disease (AD). Material and methods: Antibodies against p-Tau (PHF, phosphorylated at S296 and AT8, phosphorylated at S202) were assayed in biopsied tissue from the retro-auricular area in 49. subjects: 20 with AD, 12 with nondegenerative dementia and 17 age-matched controls. Light and confocal microscopies were employed to localize Tau protein by immunohistochemistry and their presence in the skin was confirmed through Western blots. Results: The skin biopsy taken from AD patients presented significantly higher levels of p-Tau (AT8: hyperphosphorylated at Ser 202) when compared both to control subjects and patients with non-degenerative dementia (p<0.001). Conclusion: This study demonstrates the presence of p-Tau in skin biopsies by immunoreactivity. This procedure could be used to support the clinical diagnosis of AD in living patients.

Research Article

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Differential Expression of Serum Ceruloplasmin and Alpha2-HS Glycoprotein among Nasopharyngeal Carcinoma Patients

Saied Reza Doustjalali, Munira Bhuiyan, Karim Al-Jashamy, Mohammed Irfan, Magdi El Sersi, Khin Thant Zin, Nyan Htain Linn, Wai Ma Lin, Vinothini Appalanaidu, Samiah Yasmin Abdul Kadir, Jeyaseelan Nadankutty, Rohaini Mohamad, Viswanathan Neelakantan, Hafiza Arzuman, Wong A-Chin, Htet Htet, Ahmad Yusuf, Harmiza Harun, Ali Yaldrum, Aida Nur Ashikin Abdu

The two-dimensional gel electrophoresis (2-DE) approach was used to evaluate the simultaneous expression of serum proteins in patients with nasopharyngeal carcinoma (NPC) and to detect differentially expressed proteins which could be used as specific and sensitive biomarkers for early diagnosis of the disease. We have subjected unfractionated whole sera of ten newly diagnosed Malaysian Chinese patients with World Health Organization (WHO) type III NPC to 2-DE and image analysis. The results obtained were then compared to that generated from sera of ten normal healthy controls of the same ethnic group and range of age. Our data showed higher expression of ceruloplasmin (CPL) and lower expression of α2-HS glycoprotein (AHS) in the serum high abundance 2-DE protein profiles of NPC patients as compared to that of the normal healthy controls. The ceruloplasmin (CPL) and α2-HS glycoprotein (AHS) spots were identified by mass spectrometric analysis and Mascot database search. In conclusions, this information may help in early diagnosis of nasopharyngeal carcinoma.

Commentary

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In-vitro "Depletion" of Mitochondrial Cytochrome C Oxidase Subunit II Affects the Patterns of Gene Expression across Multiple Cancer Pathways

Mai A Masri, Nuha M. Elhassan, Hiba S. Mohamed, Christina Wasunna, Abukashawa S and Muntaser E. Ibrahim

There is mounting molecular evidence to suggest mitochondrial malfunctions as a key element in turning-on the vicious circle of oncogenesis in the human body. Cytochrome c oxidase II (MT-CO2) encoded by mitochondrial DNA, and implicated in a number of tumors, has been shown to bind directly to cytochrome c and is speculated to regulate apoptosis through this affinity for cytochrome c. In an attempt to understand the effect of MT-CO2 depletion on the cell function we employ RNA interference and low density arrays encompassing six cancer pathways to gain insights on the potential effect on gene expression caused by siRNA specific to MT-CO2. The results show that MTCO2 knock- down initiated differential expression in eleven genes involved in different pathways including cell cycle, signaling, apoptosis and Angiogenesis, indicating that mtDNA and sMT-CO2 in particular may be key players in the stability of the genome and its functions during tumoregensis.

Commentary

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Simulation of Intestinal Gaseous Environment in Order to Verify the Capability of Nanostructured Chemoresistive Sensors to Detect Colorectal Tumor Markers (Benzene, 1-Iodo-Nonane, Decanal)

Cesare Malagu and Nicolo Landini

Studies have proven that neoplasia development and growth are linked to the production and spreading in the body of chemicals, originated from different sources. In the studied case of colorectal cancer (CRC), the main sources of these chemicals (together with the decay of these compounds into smaller products), are:
• Products from lipid bilayer peroxidation, generated for instance from contact with free radicals;
• Metabolites expelled as discard products from cancerous/benignant cells;
• Alteration of the microbiota in the intestine, leading to the variation in concentration of the metabolites produced from these microorganisms;
• Vascular endothelial growth factor (VEGF) produced from the tumor itself to stimulate angiogenesis and increase the vascularization in its direct surroundings.

Together with some published studies, from the same team, on the other three families of markers, in this work the goal is to study the first group, the peroxidation products, taking as markers the volatile organic compounds (VOCs), already known in literature, 1-iodo-nonane and decanal (highly reactive aldehydes maintaining the hydrophobic tails from the phospholipids), and benzene as sub-product (due to the fact that the main marker itself may turn into other chemicals due to various reactions, some of which are benzene itself and his bis-benzene compounds). These chemicals have been mixed with different concentrations of interferes, commonly produced in the digestive system from various sources (O2, N2, H2, CH4, H2S, NO, NO2, SO2), thus to define which sensors (or sensor arrays) aremost sensitive, and selective, to the presence of the above indicated markers.

Nanostructured chemoresistive sensors, widely studied as environmental and industrial real-time monitoring devices, have been used in this work as an opening to a new field of application, the biomedical, with the final goal to provide a new technology to medics and biologists in order to screen the occurrence, and study the degenerative processes, of neoplasms.

Research Article

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Expression of Steroid Receptors and Cytokeratin 18 in Breast Cancer after Neoadjuvant Chemotherapy

Vladimir Sergeevich Chernyy, Lydmila Fedorovna Gulyaeva and Vadim Viktorovich Kozlov

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CIP2A as a Potential Stratification Marker and Target for Tumor Responsiveness to DNA Damaging Therapies

Johannes Routila and Jukka Westermarck

DNA damaging therapies such as irradiation therapy and chemotherapy are used in the treatment of numerous cancer types both definitively and in combination with surgery. However, many cancer types show intrinsic resistance to DNA damaging therapies resulting in failure in tumor eradication and relapse after therapy. Thus it would be very useful to identify novel diagnostic strategies to predict for tumor radio tolerance. Head and neck squamous cell carcinoma (HNSCC) is a common cancer type characterized with great heterogeneity and lack of predictive markers for tumor radio resistance. Recent literature has revealed Cancerous inhibitor of PP2A, CIP2A, as a novel potential diagnostic marker for HNSCC, and other tumors, that show high radio resistance. In particular, we recently identified a functional link between stem cell factor Oct4 and CIP2A in HNSCC cells and demonstrated their potential role in predicting for HNSCC tumor response to radiotherapy. CIP2A´s role in mediating radio resistance in vivo has also been recently confirmed by using genetic mouse model. This raises an interesting possibility that diagnostic evaluation of CIP2A in combination with other factors indicative for cancer cell stemness, could be a novel useful diagnostic approach for stratification of HNSCC patients based on their tumor radio resistance. CIP2A could also serve as a target protein for therapeutic radiosensitation.

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Citations: 2054

Molecular Biomarkers & Diagnosis received 2054 citations as per Google Scholar report

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