• Journal of Genetic Medicine
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• v.19 no.1
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• pp.1-6
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• 2022

Radiation therapy (RT) is a very important treatment for cancer that irradiates a large amount of radiation to lead cancer cells and tissues to death. The progression of RT in the aspect of personalized medicine has greatly advanced over the past few decades in the field of technical precision responding anatomical characteristics of each patient. However, the consideration of biological heterogeneity that makes different effect in individual patients has not actually applied to clinical practice. There have been numerous discovery and validation of biomarkers that can be applied to improve the efficiency of radiotherapy, among which those related to genomic information are very promising developments. These genome-based biomarkers can be applied to identify patients who can benefit most from altering their therapeutic dose and to select the best chemotherapy improving sensitivity to radiotherapy. The genomics-based biomarkers in radiation oncology focus on mutational changes, particularly oncogenes and DNA damage response pathways. Although few have translated into clinically viable tools, there are many promising candidates in this field. In this review the prominent mutation-based biomarkers and their potential for clinical translation will be discussed.

• Journal of Digestive Cancer Research
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• v.1 no.2
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• pp.95-99
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• 2013

MicroRNA (miRNA) dysregulations are associated with various types of human cancers, and miRNAs can function as tumor suppressors and oncogenes. Emerging evidence has shown that miRNA pathway is also altered during colorectal tumorigenesis. The detection of cancer-related miRNAs in stool samples may become useful diagnostic marker for colorectal cancer, because miRNAs in stool samples has high stability, and maintains a high portion of its original level. Recent studies reported that stool-based miRNAs can offer more sensitivity and specificity than currently used stool-based screening methods for CRC. In addition, unlike fecal occult blood test, sampling on consecutive dates and special dietary restrictions are not required. In this review, the authors discuss stool-based miRNA for the early diagnosis of CRC and perspectives on future application.

• Korean Journal of Food Science and Technology
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• v.36 no.1
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• pp.141-146
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• 2004

Fungal products indirectly mediate anti-tumor effects in vitro and in vivo. To investigate whether Lentinus edodes might possess direct anti-tumor substance, L. edodes was extracted and tested on human papillomavirus (HPV) 16 oncogenes-associated animal tumor cells (TC-1) and in an animal tumor model. Only water extract displayed direct anti-proliferative effects in TC-1 tumor cells in vitro. This inhibition was dose-dependent, and inhibitory concentration ($IC_{50}$) was $800\;{\mu}g/mL$. Fungal extracts also showed growth inhibition to human cervical cancer cells (CaSki and HeLa) similarly to TC-1 tumor cells. When fungal extracts were added at a high dose (1.5 mg/mL), cell growth was inhibited within 6 hr following extract treatment. Cell growth inhibition was blocked by heat treatment, but not by low pH, which is indicative of heat sensitivity of this anti-proliferative substance. Cell growth suppression was mediated by apoptosis, as determined by Annexin V and propidium iodide staining. When challenged with TC-1 cells, direct intratumoral injection of fungal extracts resulted in some positive effect on tumor growth inhibition, as compared to oral delivery. Results suggest that heat labile substance of L. edodes suppresses growth of HPV oncogenes-associated tumor cells through apoptosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.6
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• pp.483-490
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• 2001

There were many controversies in the cause and progress of tumorigenesis. Recently, studies on the mutation of genes related to the tumor have extensively been performed due to development of molecular biology. Structural and morphological changes of chromosomes, which are related to the abnormal activation of oncogenes or inactivation of tumor suppression genes, transform the normal cells into the tumor cells. p53 and Rb are well known tumor suppressor genes, while oncogenes include c-myc, bcl-2 and ras, etc. When exposed to cell damaging agents, p53 inhibits cell growth by inducing transcription of p21. Especially p73, which is homo-logy of p53, frequently deleted in melanoma, neuroblastoma, colon cancer, and breast cancer, when over produced, p73 activates the transcription of p21, bax-1 and inhibits cell growth by inducing apoptosis. For study on mRNA expression of p21 and p73, normal oral keratinocytes, and cell lines of primary and metastatic oral squamous cell carcinoma were cultured and then electrophoresis and RT-PCR(reverse transcription-polymerase chain reaction) were performed. 1. The mRNA of p21 and p73 in normal oral keratinocyte expressed lower than that of primary squamous cell carcinoma. 2. The mRNA of p21 in metastatic oral squamous carcinoma cell lines was expressed as various patterns compared with that of normal oral keratinocyte. 3. In the metastatic oral squamous cell lines, the mRNA of HN8 expressed higher than that of HN12 or HN19. 4. The mRNA of p73 in primary oral squamous cell lines expressed 4-5 times higher than that of normal keratinocyte. 5. In metastatic oral squamous cell lines, there was no significant expression of p73 mRNA compared with that of normal oral keratinocyte. From the results obtained in this study, mRNA expression of p73 in primary oral squamous cell lines was remarkable, while mRNA expression of p21 and p73 in metastatic oral squamous cell lines were statistically insignificant.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.4
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• pp.355-362
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• 2000

Neoplastic growth is characterized by alterations of oncogenes and antioncogenes. The interaction between activated oncogenes and functional deletion of antioncogene appears to be the driving force directing normal cells to uncontrolled growth resulting in tumor. In addition to those genes mentioned, other genes controlling the entry of cells into the cell cycle have recently been implicated in cancer development. The overexpression of the cyclin D1 gene, which has been mapped to 11q13, either by gene rearrangement or amplification has been noted in various malignant tumors. The product of the cyclin D1 gene forms a complex with cyclin-dependent protein kinases(CDK4) that governs a key transition in the cell cycle. The relationships between the overexpression of cyclin D1 assessed by immunihistochemistry and the amplification of the cyclin D1 gene by differential polymerase chain reaction(DPCR) using primers for dopamin D2 receptor gene in 13 cases of squamous cell carcinomas of the oral cavity have been studied. The semiquantitative assay of cyclin D1 amplification has been made by cyclin D1/dopamin D2 receptor(CD/DR) ratio. The results were as follows; 1. In the normal tissue and the tumor, the CD/DR ratios were 0.82 and 1.36 respectively. This implicates 1.65-fold amplification of cyclin D1 gene in tumor compared to that in normal tissue. 2. The tumor tissue which showed overexpression of cyclin D1 by immunohistochemistry revealed 2-fold amplification of cyclin D1 compared to the normal tissue. 3. The tumor tissue which showed mild expression of cyclin D1 by immunihistochemistry revealed 1.7-fold amplification of cyclin D compared to the normal tissue. 4. The cyclin D1 was overexpressed in the tumor tissue at the rate of 38%. Above results suggest that cyclin D1 has close correlation with the development of carcinoma in the oral cavity. But further studies were needed to elucidate the carcinogeneic mechanisms by comparative studies among cyclin D1, pRb and p53.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.28 no.1
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• pp.245-259
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• 1998

Cellular transforming genes have been identified in a number of different tumor cell lines and tumor types. A significant number of these oncogenes belong to the ras gene family. The ras gene family consists of three closely related genes:H-ras, K-ras and N-ras which code for a related 21 kDa protein. Mutations in codon 12, 13 and 61 of one of the three ras genes convert these genes into acute oncogenes. The presence of H-ras gene mutations has important prognostic implications in various tumors. Each genomic DNA was isolated from tumors induced by implantation with DMBA, or by treatment with DMBA -implantation/irradiation. When genome DNA was transfected into NIH 3T3 cells and investigated by two-step PCR-RFLP, the fOllowing results were concluded: 1. Transformation foci developed in two groups when the genome DNA of two experimental groups were transfected into NIH 3T3 cells. 2. Transformation efficiency was 0.01-0.02 foci/㎍DNA in the experimental group with the DMBA-implantation, 0.01-0.03 foci/㎍lgDNA in the experimental group with the DMBA-implantation/irradiation according to results of transfection assay. 3. When the point mutation of H-ras gene was investigated by a two-step PCR-RFLP, there was 13.9％ (5/36) in the experimental group with the DMBA implantation, 15.4 ％ (6/39) in the experimental group with the DMBA -implantation/irradiation. 4. The point mutation in codon 12 and 61 of H-ras was 5.6％(2/36) and 8.3％(3/36) in the experimental group with the DMBA implantation. 5. The point mutation in codon 12 and 61 of H-ras gene was 7.7％(3/39) in the experimental group with the DMBA -implantation/irradiation.

• YAKHAK HOEJI
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• v.44 no.4
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• pp.340-346
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• 2000

Cervical cancer is one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papilloma viruses (HPV types 16 and 18) and cervical cancer has been well known. An extract of natural products, named as Somatid, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. This Somatid inhibited the proliferation of human cervical cancer cell lines (C-33A, SiHa, CaSki) and HaCaT keratinocytes in a dose response manner, In vitro binding assay and ELISA showed that Somatid inhibited the in vitro biding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, Somatid inhibited the in vitro binding of E7 and Rb which is essential tumor suppressor for the control of cell cycle. The levels of mRNA for E6 and E7 were also decreased by Somatid. Our data suggested that Somatid inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus can be used as a putative anti-HPV agent for the treatment of cervical carcinomas caused by HPV.

• Journal of Applied Biological Chemistry
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• v.57 no.2
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• pp.103-111
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• 2014

A1E is an extract from traditional Asian medicinal plants that has therapeutic activities against cancers, metabolic disease, and other intractable conditions. However, its mechanism of action on cervical cancer has not been studied. In order to ascertain if A1E would have pronounced anti-cervical cancer effect, cervical cancer cells were incubated with A1E and apoptosis was detected by nuclear morphological changes, annexin V-FITC/PI staining, cell cycle analysis, western blotting, Reverse-transcription polymerase chain reaction, and measurement of mitochondrial membrane potential. Expression of human papiloma virus E6 and E7 oncogenes was down-regulated in A1E-treated cervical cancer cells, while p53 and retinoblastoma protein levels were enhanced. A1E also perturbed cell cycle progression at sub-G1 and altered cell cycle regulatory factors in SiHa cervical cancer cells. A1E activated apoptotic intrinsic pathway markers such as caspase-9, caspase-3 and poly ADP-ribose polymerase, and down-regulated expression of Bcl-2 and Bcl-xl. A1E induced mitochondrial membrane potential collapse and cytochrome c release, and inhibited phosphatidylinositol 3-kinase (PI3K)/Akt, key factors involved in cell survival signaling. Taken all these results, A1E induced apoptosis via activation of the intrinsic pathway and inhibition of the PI3K/Akt survival-signaling pathway in SiHa cervical cancer cells. In conclusion, A1E exerts anti-proliferative action growth inhibition on cervical cancer cells through apoptosis which demonstrates its anti-cervical cancer properties.

• Korean Journal of Food Science and Technology
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• v.32 no.6
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• pp.1389-1395
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• 2000

Cervical cancer has been one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papillomaviruses (HPV types 16 and 18) and cervical cancer has been well known. An extract of natural products, Rhus, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. This Rhus inhibited the proliferation of human cervical cancer cell lines (C-33A, SiHa, Caski) and HaCaT keratinocytes in a dose response manner. In vitro binding assay and ELISA showed that Rhus inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, Rhus inhibited the in vitro binding of E7 and Rb which essential tumor suppressor for the control of cell cycle. The level of mRNA for E6 was also decreased by Rhus while that of E7 mRNA was not changed. Our data suggested that Rhus inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus can be used as a putative anti-HPV agent for the treatment of cervical carcinomas by HPV.

• Journal of Life Science
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• v.29 no.6
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• pp.645-652
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• 2019

Non-small cell lung cancer (NSCLC) has the infamous distinction of being the leading cause of global cancer-related death over the past decade, and novel molecular targets are urgently required to change this status. We previously conducted a microarray analysis to investigate the association of transcription factor activating enhancer-binding protein 2C (TFAP2C) with NSCLC and revealed its oncogenic roles in NSCLC development. In this study, to identify new biomarkers for NSCLC, we focused on several oncogenes from the microarray analysis that are transcriptionally regulated by TFAP2C. Here, the cell division cycle 20 (CDC20) and tribbles pseudokinase 3 (TRIB3) were subsequently found as potential potent oncogenes as they are positively regulated by TFAP2C. The results showed that the mRNA and protein levels of CDC20 and TRIB3 were down-regulated in two NSCLC cell lines (NCI-H292 and NCI-H838), which were treated with TFAP2C siRNA, and that the overexpression of either CDC20 or TRIB3 was responsible for promoting cell viability in both NSCLC cell lines. In addition, apoptotic levels of NCI-H292 and NCI-H838 cells treated with TFAP2C siRNA were found to be suppressed by the overexpression of either CDC20 or TRIB3. Together, these results suggest that CDC20 and TRIB3 are positively related to NSCLC tumorigenesis and that they should be considered as potential prognostic markers for developing an NSCLC therapy.