Team:NU Kazakhstan/Modeling

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<center><h3>This is an overview of our project</h3></center>
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Cancer development is a complex process requiring the coordinated interactions of numerous proteins, signal pathways and cell types. Its detection infers that certain characteristics of the tumor are different from corresponding normal tissue and can be seen and measured as biomarkers of tumorigenesis. Detection of disease is not the same as its diagnosis. Identification of disease does not require recognition of symptoms but also detection of specific features that would indicate the presence of certain disease. Diagnosis based on symptoms is not acceptable for cancer because symptoms usually appear when tumor is large enough to be able to detect. Therefore, finding appropriate cancer biomarkers in minimum amount of biological fluids such as serum, urine and exhaled breath and detecting them in patients would improve diagnosis and prove the presence of cancerous cells. Biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal or pathogenic processes. Appropriate biomarkers may be able to define risks and identify early stages of tumor development, assist in tumor detection and diagnosis, verify stratification of patients for treatment, predict outcomes of the disease and help surveillance for disease recurrence. Improved and timely diagnosis of cancer will positively affect treatment outcomes and increase cancer survival rates. Detecting cancer as early as possible will help to reduce the cancer burden (Etzioni et al., 2003). </p></div>
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<p style="line-height:200%;padding-top:10px"><a id="show_id" onclick="document.getElementById('spoiler_id').style.display=''; document.getElementById('show_id').style.display='none';" class="link"><u><b>Screening tools</b></u> are needed that exhibit the combined features of high sensitivity and high specificity for early stages of cancers...</a><span id="spoiler_id" style="display: none"><a onclick="document.getElementById('spoiler_id').style.display='none'; document.getElementById('show_id').style.display='';" class="link"><u><b>Screening tools</b></u></a><br><b>Screening tools for biomarkers</b> are needed that exhibit the combined features of high sensitivity and high specificity for early stages of cancers, and which are widely accepted, affordable, and safe to use. There are various types of cancer biomarkers are known such as protein biomarkers, peptide biomarkers, volatile biomarkers, cell based biomarkers, and circulating free DNA biomarkers. Careful selection of these biomarkers in cancer detection is important in diagnosis. Protein biomarkers such as carcinoembryonic antigen (CEA) has been implicated in various types of human cancer and, therefore, will be used as targets of the proposed study. Their combination in one simple, easy and portable test detection assay or test system would generate a fast diagnostic methodology.
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CEA is a 201 kDa glycoprotein that is involved in a cell adhesion. Its specialized sialofucosylated glycoforms serve as functional L-selectin and E-selectin ligands which are critical to the metastatic dissemination for cancer cells. Serum CEA is currently one of the most relevant and widespread tumor markers of colorectal cancer (Christenson et al., 2011). It is used for prognosis and monitoring in colorectal cancer patients (Sturgeon et al., 2008). The use of CEA for screening and early diagnosis is limited due to a lack of diagnostic sensitivity and specificity (Smith et al., 2002).</span></p></div>
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<p style="line-height:200%;padding-top:10px"><a id="show1_id" onclick="document.getElementById('spoiler3_id').style.display=''; document.getElementById('show1_id').style.display='none';" class="link"><b><u>Biosensors and immunoassays</u></b> as more recent methods for the rapid detection of single-tumor markers...</a><span id="spoiler3_id" style="display: none"><a onclick="document.getElementById('spoiler3_id').style.display='none'; document.getElementById('show1_id').style.display='';" class="link"><b><u>Biosensors and immunoassays</u></b></a><br><b>Biosensors</b> and <b>immunoassays</b> as more recent methods for the rapid detection of single-tumor markers have been well progressed for cancer diagnosis. According to the International Union of Applied and Pure Chemistry, a biosensor is a sensor composed of biological recognition elements (e.g., antibodies, enzymes, or aptamers) whose interaction with their analytes is detected with a transducer. The transducer is a device that converts the chemical or physical signals into something measurable such as an electrical signal (Thevenot et al., 1999).  Biosensors consisting of various types of transducers, such as optical, electrochemical, mass-based or calorimetric were designed for detection of either single or multiple tumor markers. Biosensors for the detection of CEA, IL-6, and autoantibodies to ECPKA are reviewed in Rusling et al. (2010), Tothill et al. (2009), Arya and Bhansali (2011), and Tan et al. (2009). Most of such biosensors use antibodies as biorecognition element. As for DNA aptamers, Wang et al. (2007) selected aptamers against CEA, although the quantitative data on aptamer affinity towards its target were not presented.
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<b>Application of tumor markers for cancer diagnosis</b> is facing great challenges, because most markers are not specific to a particular tumor and no single marker can be used for accurately predicting disease in all of its stages. Panels of cancer biomarkers can improve their diagnostic value in complex biological samples. Therefore, the development of highly sensitive and selective sensors capable of simultaneous detection of multiple analytes has attracted much attention. Compared with the traditional single-analyte immunoassay, the simultaneous multiplexed immunoassay is more efficient in clinical application since it can quantitatively detect a panel of biomarkers in a single run with improved diagnostic specificity (Tian et al., 2012). Moreover, the multiplexed immunoassay can shorten analytical time, enhance detection throughput, and decrease sampling volume and detection costs.
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The approach proposed in this work combines the advantage of using aptamers for recognition of specific cancer biomarkers, magnetic nanoparticles for separation and quantum dots for detection, resulting in a novel, portable, and rapid competitive tool for sensitive and selective multiplexed detection of cancer biomarkers. Since biosensors for biomarker detection involve a biological recognition element, it is necessary to develop an ideal candidate possessing advantages over traditional antibodies, and aptamers can be a good example of it.</p></div> </span>
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<p style="line-height:200%;padding-top:10px"><a id="showit_id" onclick="document.getElementById('spoiler1_id').style.display=''; document.getElementById('showit_id').style.display='none';" class="link"><b><u>Aptamers</u></b> are short single stranded DNAs (ssDNAs) or RNAs that have an ability to bind to...</a><span id="spoiler1_id" style="display: none"><a onclick="document.getElementById('spoiler1_id').style.display='none'; document.getElementById('showit_id').style.display='';" class="link"><b><u>Aptamers</u></b></a><br><b>Aptamers</b> are short single stranded DNAs (ssDNAs) or RNAs that have an ability to bind to various targets with high affinity and specificity and can be developed by way of repetitive cycles of affinity selection and PCR amplification. Being an emerging group of recognition elements, aptamers hold significant advantages over antibodies such as they do not require a host animal for production since in vitro combinatorial biochemistry is applied in this process, exhibit high binding affinities for their targets, and are resistant to biodegradation and denaturation.
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To use aptamers versus antibodies in our experiments will be vital since aptamers have been shown to distinguish intimately related substances from their targets on the basis of minor structural changes, such as a methyl group, a hydroxyl group, and a urea vs. a guanidine group. Moreover, there is one more big advantage of aptamer application in biosensors. The capability to regenerate the function of immobilized aptamers would be the most attractive characteristic of aptamers. Being nucleic acids, aptamers could be exposed to repeated cycles of denaturation and renaturation. Heat, salt concentration, pH of the medium, and chelating agents could work as aptamer regeneration methods (Jayasena, 1999). According to experience of Bruno et al. (2009), the DNA aptamer–MB and aptamet–QD sandwich assay components remain adherent to the inner surface of the polystyrene cuvette for days to weeks and they have much stronger adherence in comparison to antibody–MBs, which fall away from the collection site when the magnetic insert is removed, but a very thin brown film sometimes remain. They explain it with the fact that antibody coated–MBs adhere to polystyrene cuvettes with lesser affinity at neutral pH and most proteins adhere optimally to polystyrene microtiter plates only at elevated pH.           
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Given that aptamer based optical biosensors represent an unexplored field, we expect many exciting opportunities for aptamer based bioelectronic devices.</span></p></div>
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<a id="show2_id" onclick="document.getElementById('spoiler2_id').style.display=''; document.getElementById('show2_id').style.display='none';" class="link"><b><u><div>List of References</div></u></b></a><span id="spoiler2_id" style="display: none"><a onclick="document.getElementById('spoiler2_id').style.display='none'; document.getElementById('show2_id').style.display='';" class="link"><b><u><div>Hide List of References</div></u></b></a><br><ol>
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<li>ARYA S.K., BHANSALI S. (2011) LUNG CANCER AND ITS EARLY DETECTION USING BIOMARKER-BASED BIOSENSORS. CHEMICAL REVIEWS, 111 (11), 6783-6809.</li>
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<li>AZZAZY, H.M., MANSOUR, M.M., KAZMIERCZAK, S.C. 2007. FROM DIAGNOSTICS TO THERAPY: PROSPECTS OF QUANTUM DOTS. CLIN. BIOCHEM. 40, 917-27. </li>
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<li>BAMRUNGSAP S., CHEN T., SHUKOOR M.I., CHEN ZH., SEFAH K., CHEN Y., TAN W. (2012) PATTERN RECOGNITION OF CANCER CELLS USING APTAMER-CONJUGATED MAGNETIC NANOPARTICLES. ACS NANO; 6 (5), 3974-3981.</li>
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<li>BRUNO, J. G., PHILLIPS, T., CARILLO, M. P. CROWELL, R. (2009) PLASTIC – ADHERENT DNA APTAMER – MAGNETIC BEAD AND QUANTUM DOT SANDWICH ASSAY FOR CAMPYLOBACTER DETECTION. J. FLUORESC. 19, 427 – 435.</li>
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<li>CHEN Z, MALHOTRA PS,  THOMAS GR, ET AL (1999) EXPRESSION OF PROINFLAMMATORY AND PROANGIOGENIC CYTOKINES IN PATIENTS WITH HEAD AND NECK CANCER. CLIN CANCER RES; 5,1369-1379.</li>
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<li>CHO-CHUNG YS, CLAIR T. (1993) THE REGULATORY SUBUNIT OF CAMP-DEPENDENT PROTEIN KINASE AS A TARGET FOR CHEMOTHERAPY OF CANCER AND OTHER CELLULAR DYSFUNCTIONAL RELATED DISEASES. PHARMACOLTHER; 60:265–88.</li>
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<li>CHO YS, PARK YG, LEE YN, KIM MK, BATES S, TAN L &amp; CHO-CHUNG YS (2000) EXTRACELLULAR PROTEIN KINASE A AS A CANCER BIOMARKER: ITS EXPRESSION BY TUMOR CELLS AND REVERSAL BY A MYRISTATE-LACKING CALPHA AND RIIBETA SUBUNIT OVEREXPRESSION. PROC NATL ACAD SCI USA 97, 835–840.</li>
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<li>CHO YS, LEE YN, CHO-CHUNG YS. (2002) BIOCHEMICAL CHARACTERIZATION OF EXTRACELLULAR CAMP-DEPENDENT PROTEIN KINASE AS A TUMOR MARKER. BIOCHEM BIOPHYS RES COMMUN; 278:679–84.</li>
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<li>CHRISTENSON, R.H., CERVELLI, D.R., STERNER, J., BACHMANN, L.M., REBUCK, H., GRAY, J., KELLEY, W.E. (2011) ANALYTICAL PERFORMANCE AND CLINICAL CONCORDANCE OF THE CANCER BIOMARKERS CA 15-3, CA 19-9, CA 125 II, CARCINOEMBRYONIC ANTIGEN, AND ALPHA-FETOPROTEIN ON THE DIMENSION VISTA® SYSTEM. CLINICAL BIOCHEMISTRY, 44, 1128-1136.</li>
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<li>CHUNG YC, CHANG YF. (2003) SERUM INTERLEUKIN-6 LEVELS REFLECT THE DISEASE STATUS OF COLORECTAL CANCER. J SURG ONCOL; 83:222-6.</li>
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<li>CVIJIC ME, KITA T, SHIH W, DIPAOLA RS &amp; CHIN KV (2000) EXTRACELLULAR CATALYTIC SUBUNIT ACTIVITY OF THE CAMP-DEPENDENT PROTEIN KINASE IN PROSTATE CANCER. CLIN CANCER RES 6, 2309–2317.</li>
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<li>DE VITA F, ROMANO C, ORDITURA M, ET AL (2001) INTERLEUKIN-6 SERUM LEVEL CORRELATES WITH SURVIVAL IN ADVANCED GASTROINTESTINAL CANCER PATIENTS BUT IS NOT AN INDEPENDENT PROGNOSTIC INDICATOR. J INTERFERON CYTOKINE RES; 21: 45-52.</li>
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<li>DYMICKA-PIEKARSKA V, MATOWICKA-KARNA J, GRYKO M, KEMONACHETNIK I, KEMONA H (2007) RELATIONSHIP BETWEEN SOLUBLE PSELECTIN AND INFLAMMATORY FACTORS (INTERLEUKIN-6 AND C-REACTIVE PROTEIN) IN COLORECTAL CANCER. THROMB RES.; 20:585–590</li>
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<li>ETZIONI, R., URBAN, N., RAMSEY, S., MCINTOSH, M., SCHWARTZ, S., RIED, B., RADICH, J., ANDERSON, G., AND HARTWELL, L. (2003) THE CASE FOR EARLY DETECTION. NATURE REV. CANCER 3, 243– 252.</li>
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<li>GALIZIA G, ORDITURA M, ROMANO C, LIETO E, CASTELLANO P, PELOSIO L, IMPERATORE V, CATALANO G, PIGNATELLI C, DE VITA F (2002) PROGNOSTIC SIGNIFICANCE OF CIRCULATING IL-10 AND IL-6 SERUM LEVELS IN COLON CANCER PATIENTS UNDERGOING SURGERY. CLIN IMMUNOL; 102:169-78.</li>
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<li>IKEGUCHI M, HATADA T, YAMAMOTO M, ET AL. (2009) SERUM INTERLEUKIN-6 AND -10 LEVELS IN PATIENTS WITH GASTRIC CANCER. GASTRIC CANCER;12: 95–100.</li>
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<li>JAYASENA, S. D. (1999) APTAMERS: AN EMERGING CLASS OF MOLECULES THAT RIVAL ANTIBODIES IN DIAGNOSTICS. 45(9), 1628 – 1650.</li>
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<li>KAMINSKA J, NOWACKI MP, KOWALSKA M, RYSINSKA A, CHWALINSKI M, FUKSIEWICZ M, MICHALSKI W, CHECHLINSKA M. (2005) CLINICAL SIGNIFICANCE OF SERUM CYTOKINE MEASUREMENTS IN UNTREATED COLORECTAL CANCER PATIENTS: SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR TYPE I—AN INDEPENDENT PROGNOSTIC FACTOR. TUMOUR BIOL; 26:186–194.</li>
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<li>KINOSHITA T, ITO H, MIKI C (1999) SERUM INTERLEUKIN-6 LEVEL REFLECTS THE TUMOR PROLIFERATIVE ACTIVITY IN PATIENTS WITH COLORECTAL CARCINOMA. CANCER 85:2526–2531.</li>
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<li>KITA T, GOYDOS J, REITMAN E, ET AL. (2004) EXTRACELLULAR CAMP-DEPENDENT PROTEIN KINASE (ECPKA) IN MELANOMA. CANCER LETT; 208: 187–91</li>
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<li>LAUTA VM (2003) A REVIEW OF THE CYTOKINE NETWORK IN MULTIPLE MYELOMA: DIAGNOSTIC, PROGNOSTIC, AND THERAPEUTIC IMPLICATIONS. CANCER; 97:2440-2452.</li>
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<li>NAKASHIMA J, TACHIBANA M, HORIGUCHI Y, ET AL (2000) SERUM INTERLEUKIN 6 AS A PROGNOSTIC FACTOR IN PATIENTS WITH PROSTATE CANCER. CLIN CANCER RES; 6:2702-2706.</li>
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<li>NESTEROVA, M., JOHNSON, N., &amp; CHEADLE, C. (2006 A). AUTOANTIBODY BIOMARKER OPENS A NEW GATEWAY FOR CANCER DIAGNOSIS. BUILDING, 1762, 398-403. DOI:10.1016/J.BBADIS.2005.12.010.</li>
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<li>NESTEROVA MV, JOHNSON N, CHEADLE C, BATES SE, MANI S, STRATAKIS CA, KHAN IU, GUPTA RK &amp; CHO-YUNG YS (2006 B) AUTOANTIBODY CANCER BIOMARKER: EXTRACELLULAR PROTEIN KINASE A. CANCER RES 66, 8971–8974.</li>
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<li>NIKITEAS NI, TZANAKIS N, GAZOULI M, RALLIS G, DANIILIDIS K, THEODOROPOULOS G, KOSTAKIS A, PEROS G (2005) SERUM IL-6, TNFALPHA AND CRP LEVELS IN GREEK COLORECTAL CANCER PATIENTS: PROGNOSTIC IMPLICATIONS. WORLD J GASTROENTEROL; 11:1639–1643.</li>
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<li>OKADA S, OKUSAKA T, ISHII H, ET AL (1998) ELEVATED SERUM INTERLEUKIN-6 LEVELS IN PATIENTS WITH PANCREATIC CANCER. JPN J CLIN ONCOL;28:12-15.</li>
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<li>RUSLING JF, KUMAR CV, GUTKIND JS, PATEL V. (2010) MEASUREMENT OF BIOMARKER PROTEINS FOR POINT-OF-CARE EARLY DETECTION AND MONITORING OF CANCER. ANALYST, 135 (10), 2496-2511.</li>
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<li>SMITH RA, COKKINIDES V, VON ESCHENBACH AC, ET AL. (2002) AMERICAN CANCER SOCIETY GUIDELINES FOR THE EARLY DETECTION OF CANCER. CA CANCER J CLIN; 52(1):8–22.</li>
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<li>STURGEON, CM, DUFFY, MJ, STENMAN, U-H, ET AL. (2008) NATIONAL ACADEMY OF CLINICAL BIOCHEMISTRY LABORATORY MEDICINE PRACTICE GUIDELINES FOR USE OF TUMOR MARKERS IN TESTICULAR, PROSTATE, COLORECTAL, BREAST, AND OVARIAN CANCERS. CLINICAL CHEMISTRY; 54(12): E11–79.</li>
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<li>SZKUDLAREK M., BOSIO R.M., WUA Q., CHIN K.V. (2009) INHIBITION OF ANGIOGENESIS BY EXTRACELLULAR PROTEIN KINASE A. CANCER LETTERS, 283: 68–73.</li>
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<li>TOTHILL, I.E. (2009) BIOSENSORS FOR CANCER BIOMARKER DIAGNOSIS SEMINARS IN CELL AND DEVELOPMENTAL BIOLOGY, 20 (1), 55-62.</li>
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<li>TAN HT, LOW J, LIM SG, CHUNG MC (2009) SERUM AUTOANTIBODIES AS BIOMARKERS FOR EARLY CANCER DETECTION. FEBS JOURNAL;276:6880–904.</li>
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<li>TEMPFER C, ZEISLER H, SLIUTZ G, ET AL (1997) SERUM EVALUATION OF INTERLEUKIN 6 IN OVARIAN CANCER PATIENTS. GYNECOLONCOL; 66:27-30.</li>
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<li>THÉVENOT D.R., TOTH K., DURST R.A., WILSON G.S. (1999) ELECTROCHEMICAL BIOSENSORS: RECOMMENDED DEFINITIONS AND CLASSIFICATION. PURE APPLIED CHEMISTRY, VOL. 71, 2333–2348.</li>
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<li>TIAN, J., ZHOU, L., ZHAO, Y., WANG, Y., PENG, Y., ZHAO, S. 2012. MULTIPLEXED DETECTION OF TUMOR MARKERS WITH MULTICOLOR QUANTUM DOTS BASED ON FLUORESCENCE POLARIZATION IMMUNOASSAY. TALANTA. 92, 72-77. </li>
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<li>UEDA T, SHIMADA E, URAKAWA T (1994) SERUM LEVELS OF CYTOKINES IN PATIENTS WITH COLORECTAL CANCER: POSSIBLE INVOLVEMENT OF INTERLEUKIN-6 AND INTERLEUKIN-8 IN HEMATOGENOUS METASTASIS. J GASTROENTEROL 29:423–429.</li>
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<li>VIVEKANDA, J., KIEL, J. L. (2006) ANTI-FRANCISELLA TULARENSIS DNA APTAMERS DETECT TULEREMIA ANTIGEN FROM DIFFERENT SUBSPECIES BY APTAMER-LINKED IMMOBILIZED SORBENT ASSAY. LABORATORY INVESTIGATION; 86, 610-618.</li>
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<li>WANG, L., LIU, R., YIN, H., WEI, J., QIAN, X., YU, L. (2007) SELECTION OF DNA APTAMER THAT SPECIFIC BINDING HUMAN CARCINOEMBRYONIC ANTIGEN IN VITRO. JOURNAL OF NANJING MEDICAL UNIVERSITY, 21(5):277-281.</li>
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<li>YOSHIDA N, IKEMOTO S, NARITA K, ET AL (2002) INTERLEUKIN-6, TUMOUR NECROSIS FACTOR ALPHA AND INTERLEUKIN-1BETA IN PATIENTS WITH RENAL CELL CARCINOMA. BR J CANCER; 86:1396-1400.</li>
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Latest revision as of 15:21, 27 September 2013

NU_Kazakhstan

This is an overview of our project

Cancer development is a complex process requiring the coordinated interactions of numerous proteins, signal pathways and cell types. Its detection infers that certain characteristics of the tumor are different from corresponding normal tissue and can be seen and measured as biomarkers of tumorigenesis. Detection of disease is not the same as its diagnosis. Identification of disease does not require recognition of symptoms but also detection of specific features that would indicate the presence of certain disease. Diagnosis based on symptoms is not acceptable for cancer because symptoms usually appear when tumor is large enough to be able to detect. Therefore, finding appropriate cancer biomarkers in minimum amount of biological fluids such as serum, urine and exhaled breath and detecting them in patients would improve diagnosis and prove the presence of cancerous cells. Biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal or pathogenic processes. Appropriate biomarkers may be able to define risks and identify early stages of tumor development, assist in tumor detection and diagnosis, verify stratification of patients for treatment, predict outcomes of the disease and help surveillance for disease recurrence. Improved and timely diagnosis of cancer will positively affect treatment outcomes and increase cancer survival rates. Detecting cancer as early as possible will help to reduce the cancer burden (Etzioni et al., 2003).

Screening tools are needed that exhibit the combined features of high sensitivity and high specificity for early stages of cancers...

Biosensors and immunoassays as more recent methods for the rapid detection of single-tumor markers...

Aptamers are short single stranded DNAs (ssDNAs) or RNAs that have an ability to bind to...

List of References