• BMB Reports
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• 제41권9호
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• pp.626-634
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• 2008

Novel cancer biomarkers are required to achieve early diagnosis and optimized therapy for individual patients. Cancer is a disease of the genome, and tumor tissues are a rich source of cancer biomarkers as they contain the functional translation of the genome, namely the proteome. Investigation of the tumor tissue proteome allows the identification of proteomic signatures corresponding to clinico-pathological parameters, and individual proteins in such signatures will be good biomarker candidates. Tumor tissues are also a rich source for plasma biomarkers, because proteins released from tumor tissues may be more cancer specific than those from non-tumor cells. Two-dimensional difference gel electrophoresis (2D-DIGE) with novel ultra high sensitive fluorescent dyes (CyDye DIGE Fluor satulation dye) enables the efficient protein expression profiling of laser-microdissected tissue samples. The combined use of laser microdissection allows accurate proteomic profiling of specific cells in tumor tissues. To develop clinical applications using the identified biomarkers, collaboration between research scientists, clinicians and diagnostic companies is essential, particularly in the early phases of the biomarker development projects. The proteomics modalities currently available have the potential to lead to the development of clinical applications, and channeling the wealth of produced information towards concrete and specific clinical purposes is urgent.

• 센서학회지
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• 제22권2호
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• pp.144-149
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• 2013

In this research, we developed a biosensor to detect lung cancer-specific biomarker using Anodic Aluminum Oxide (AAO) chip based on interference and nano surface plasmon resonance (nanoSPR). The nano-porous AAO chip was fabricated $2{\mu}m$ of pore-depth by two-step anodizing method for surface uniformity. NanoSPR has sensitivity to the refractive index (RI) of the surrounding medium and also provides simple and label-free detection when specific antibodies are immobilized to the Au-deposited surface of nano-porous AAO chip. To detect the lung cancer-specific biomarker, antibodies were immobilized on the surface of the chip by Self Assembled Monolayer (SAM) method. Since then lung cancer-specific biomarker was applied atop the antibodies immobilized layer. The specific reaction of the antigen-antibody contributed to the change in the refractive index that cause shift of resonance spectrum in the interference pattern. The Limit of Detection (LOD) was 1 fg/ml by using our nano-porous AAO biosensor chip.

• Molecules and Cells
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• 제43권4호
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• pp.384-396
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• 2020

Breast cancer is one of the most common life-threatening malignancies and the top cause of cancer deaths in women. Although many conventional therapies exist for its treatment, breast cancer still has many handicaps to overcome. Cancer stem cells (CSCs) are a well-known cause of tumor recurrences due to the ability of CSCs for self-renewal and differentiation into cell subpopulations, similar to stem cells. To fully treat breast cancer, a strategy for the treatment of both cancer cells and CSCs is required. However, current strategies for the eradication of CSCs are non-specific and have low efficacy. Therefore, surface biomarkers to selectively treat CSCs need to be developed. Here, 34 out of 641 surface biomarkers on CSCs were identified by proteomic analysis between the human breast adenocarcinoma cell line MCF-7 and MCF-7-derived CSCs. Among them, carcinoembryonic antigen-related cell adhesion molecules 6 (CEACAM6 or CD66c), a member of the CEA family, was selected as a novel biomarker on the CSC surface. This biomarker was then experimentally validated and evaluated for use as a CSC-specific marker. Its biological effects were assessed by treating breast cancer stem cells (BCSCs) with short hairpin (sh)-RNA under oxidative cellular conditions. This study is the first to evaluate the biological function of CD66c as a novel biomarker on the surface of CSCs. This marker is available as a moiety for use in the development of targeted therapeutic agents against CSCs.

• BMB Reports
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• 제41권9호
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• pp.615-625
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• 2008

Over a last decade, intense interest has been focused on biomarker discovery and their clinical uses. This interest is accelerated by the completion of human genome project and the progress of techniques in proteomics. Especially, cancer biomarker discovery is eminent in this field due to its anticipated critical role in early diagnosis, therapy guidance, and prognosis monitoring of cancers. Among cancers, lung cancer, one of the top three major cancers, is the one showing the highest mortality because of failure in early diagnosis. Numerous potential DNA biomarkers such as hypermethylations of the promoters and mutations in K-ras, p53, and protein biomarkers; carcinoembryonic antigen (CEA), CYFRA21-1, plasma kallikrein B1 (KLKB1), Neuron-specific enolase, etc. have been discovered as lung cancer biomarkers. Despite extensive studies thus far, few are turned out to be useful in clinic. Even those used in clinic do not show enough sensitivity, specificity and reproducibility for general use. This review describes what the cancer biomarkers are for, various types of lung cancer biomarkers discovered at present and predicted future advance in lung cancer biomarker discovery with proteomics technology.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1865-1868
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• 2016

Background: The number of patients with oral cancer in India is increasing gradually (especially in younger people). Although the diagnostic modalities and therapeutic management of oral cancer are improving, the treatment outcome and prognosis of oral cancer remain poor. The absence of definite early warning symptoms for most head and neck cancers suggests that sensitive and specific biomarkers are likely to be important in screening for high-risk patients. Aims: To analyze serum adenosine deaminase (ADA) levels in oral squamous cell carcinoma (OSCC) cases who reported to our institute. Materials and Methods: A prospective study was performed on 100 histopathologically proven cases of OSCC (study group) and 100 normal healthy individuals (control group). Independent sample and one sample t-tests and one way ANOVA followed by Tuckey's POST HOC test were conducted for analysis. Results: Statistically significant increase in serum ADA levels was observed in OSCC cases compared to the control group. Also serum ADA level increased significantly with the histopathological grade. Conclusions: Serum ADA levels in OSCC may be a useful diagnostic and prognostic biomarkers in clinical practice and our findings suggest that a large-scale study is warranted to confirm clinical utility as a prognostic and diagnostic biomarker.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2297-2299
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• 2016

Background: Early detection of malignant transformation with expression biomarkers has significant potential to improve the survival rate of patients as such biomarkers enable prediction of progression and assess sensitivity to chemotherapy. The expression of interferon inducible transmembrane protein 1 (IFITM1) has been associated with early invasion events in several carcinomas, including head and neck cancers, and hence has been proposed as a novel candidate biomarker. As the incidence of oral squamous cell carcinoma (OSCC) is highest in the Indian population, we sought to investigate: 1) the expression pattern of IFITM1 in OSCC tissue samples obtained from Indian patients of Dravidian origin; and 2) the possibility of using IFITM1 expression as a potential biomarker. Materials and Methods: Total RNA extracted from thirty eight OSCC biopsy samples was subjected to semi-quantitative RT-PCR with IFITM1 and GAPDH specific primers. Results: Of the thirty eight OSCC samples that were analyzed, IFITM1 overexpression was identified in fifteen (39%). Seven expressed a low level, while the remainder expressed high level of IFITM1. Conclusions: The overexpression of IFITM1 in OSCC samples indicates that IFITM1 may be explored for the possibility of use as a high confidence diagnostic biomarker in oral cancers. To the best of our knowledge, this is the first time that IFITM1 overexpression is being reported in Indian OSCC samples.

• 대한의생명과학회지
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• 제29권4호
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• pp.336-343
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• 2023

Lung cancer is one of the cancers with high mortality and incidence rates worldwide. Although, various anticancer research efforts are underway to completely treat cancer, the challenge against it remains in the inability to eliminate cancer stem cells (CSCs), leading to difficulties in curing the cancer and resulting in recurrence. As a result, there is a growing interest in the discovery of new biomarkers and therapeutic molecules that can simultaneously target both cancer cells and CSCs. From this point of view, we focused on fibronectin leucine rich transmembrane protein 3 (FLRT3), one of the genes known to be present in human lung cells and the discovery from our previous cancer proteomic analysis study. This study aimed to evaluate the potential of FLRT3 as a specific therapeutic biomarker for lung cancer and Lung Cancer-derived-Stem Cells (LCSC). Also, to estimate the biological function of FLRT3 in cancer and LCSC, short hairpin RNA (shRNA) was generated and showed the ability of the decreased-cell migration and cell proliferation of lung cancer through ERK signaling pathway when FLRT3 was knock-downed. In conclusion, our study is the first to report that FLRT3 has the potential as therapeutic biomarker for the treatment of lung cancer and LCSC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5563-5568
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• 2012

Based on our previous report on gastric cancer which documented ATP4A and ATP4B mRNA down-regulation in gastric tumors relative to normal gastric tissues, we hypothesized that epigenetic mechanisms could be responsible. ATP4A and ATP4B mRNA expression in gastric cancer cell lines AGS, SNU638 and NUGC-3 was examined using reverse transcriptase PCR (RT-PCR). AGS cells were treated with TSA or 5'-AzaDC and methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis were performed. MSP analysis was on DNA from paraffin embedded tissues sections and plasma. Expression analysis revealed downregulation of ATP4A and ATP4B genes in gastric cancer cell lines relative to normal gastric tissue, while treatment with 5'-AzaDC re-activated expression of both. Search for CpG islands in their putative promoter regions did not indicate CpG islands (CGI) but only further downstream in the bodies of the genes. Methylation specific PCR (MSP) in the exon1 of the ATP4B gene and exon7 in ATP4A indicated methylation in all the gastric cancer cell lines tested. MSP analysis in tumor tissue samples revealed methylation in the majority of tumor samples, 15/19, for ATP4B and 8/8 for ATP4A. There was concordance between ATP4B and ATP4A down-regulation and methylation status in the tumour samples tested. ATP4B methylation was detectable in cell free DNA from gastric cancer patient's plasma samples. Thus ATP4A and ATP4B down-regulation involves DNA methylation and methylated ATP4B DNA in plasma is a potential biomarker for gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9607-9610
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• 2014

Breast cancer, a leading cause of death among women in most countries worldwide, is rapidly increasing in incidence in Vietnam. One of biomarkers is the disruption of the genetic material including epigenetic changes like DNA methylation. With the aim of finding hypermethylation at CpG islands of promoter of BRCA1 gene, belonged to the tumor suppressor gene family, as the biomarker for breast cancer in Vietnamese population, sensitive methyl specific PCR (MSP) was carried out on 115 samples including 95 breast cancer specimens and 20 normal breast tissues with other diseases which were obtained from Ho Chi Minh City Medical Hospital, Vietnam. The result indicated that the frequency of BRCA1 hypermethylation reached 82.1% in the cases (p<0.001). In addition, the DNA hypermethylation of this candidate gene increased the possibility to be breast cancer with high incidence via calculated odd ratios (p<0.05). In conclusion, hypermethylation of this candidate gene could be used as the promising biomarker application with Vietnamese breast cancer patients.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2012년도 제42회 동계 정기 학술대회 초록집
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• pp.549-549
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• 2012

Early detection of cancer biomarkers in the blood is of vital importance for reducing the mortality and morbidity in a number of cancers. From this point of view, immunosensors based on nanowire (NW) and carbon nanotube (CNT) field-effect transistors (FETs) that allow the ultra-sensitive, highly specific, and label-free electrical detection of biomarkers received much attention. Nevertheless 1D nano-FET biosensors showed high performance, several challenges remain to be resolved for the uncomplicated, reproducible, low-cost and high-throughput nanofabrication. Recently, two-dimensional (2D) graphene and reduced GO (RGO) nanosheets or films find widespread applications such as clean energy storage and conversion devices, optical detector, field-effect transistors, electromechanical resonators, and chemical & biological sensors. In particular, the graphene- and RGO-FETs devices are very promising for sensing applications because of advantages including large detection area, low noise level in solution, ease of fabrication, and the high sensitivity to ions and biomolecules comparable to 1D nano-FETs. Even though a limited number of biosensor applications including chemical vapor deposition (CVD) grown graphene film for DNA detection, single-layer graphene for protein detection and single-layer graphene or solution-processed RGO film for cell monitoring have been reported, development of facile fabrication methods and full understanding of sensing mechanism are still lacking. Furthermore, there have been no reports on demonstration of ultrasensitive electrical detection of a cancer biomarker using the graphene- or RGO-FET. Here we describe scalable and facile fabrication of reduced graphene oxide FET (RGO-FET) with the capability of label-free, ultrasensitive electrical detection of a cancer biomarker, prostate specific antigen/${\alpha}$ 1-antichymotrypsin (PSA-ACT) complex, in which the ultrathin RGO channel was formed by a uniform self-assembly of two-dimensional RGO nanosheets, and also we will discuss about the immunosensing mechanism.