• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9071-9075
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• 2014

Background: microRNAs are small non-coding RNA that control gene expression by mRNA degradation or translational inhibition. These molecules are known to play essential roles in many biological and physiological processes. miR-205 may be differentially expressed in head and neck cancers; however, there are conflicting data and localization of expression has yet to be determined. Materials and Methods: miR-205 expression was investigated in 48 cases of inflammatory, benign and malignant tumor tissue array of the neck, oronasopharynx, larynx and salivary glands by Locked Nucleic Acid in situ hybridization (LNA-ISH) technology. Results: miR-205 expression was significantly differentially expressed across all of the inflammatory, benign and malignant tumor tissues of the neck. A significant increase in miR-205 staining intensity (p<0.05) was observed from inflammation to benign and malignant tumors in head and neck tissue array, suggesting that miR-205 could be a biomarker to differentiate between cancer and non-cancer tissues. Conclusions: LNA-ISH revealed that miR-205 exhibited significant differential cytoplasmic and nuclear staining among inflammation, benign and malignant tumors of head and neck. miR-205 was not only exclusively expressed in squamous epithelial malignancy. This study offers information and a basis for a comprehensive study of the role of miR-205 that may be useful as a biomarker and/or therapeutic target in head and neck tumors.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.246-252
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• 2008

Tumor tissue is usually contaminated by normal tissue components, which reduces the sensitivity of analysis for exploring genetic alterations. Although microdissection has been adopted to minimize the contamination of tumor DNA with normal cell components, there is a concern over the amount of microdissected DNA not enough to be applied to array-CGH reaction. To amplify the extracted DNA, several whole genome amplification (WGA) methods have been developed, but objective comparison of the array-CGH outputs using different types of WGA methods is still scarce. In this study, we compared the performance of non-amplified microdissected DNA and DNA amplified in 2 WGA methods such as degenerative oligonucleotide primed (DOP)-PCR, and multiple strand displacement amplification (MDA) using Phi 29 DNA polymerase. Genomic DNA was also used to make a comparison. We applied those 4 DNAs to whole genome BAC array to compare the false positive detection rate (FPDR) and sensitivity in detecting copy number alterations under the same hybridization condition. As a result microdissected DNA method showed the lowest FPDR and the highest sensitivity. Among WGA methods, DOP-PCR amplified DNA showed better sensitivity but similar FPDR to MDA-amplified method. These results demonstrate the advantage and applicability of microdissection for array-CGH analysis, and provide useful information for choosing amplification methods to study copy number alterations, especially based on precancerous and microscopically invaded lesions.

• 대한구강악안면병리학회지
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• 제42권6호
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• pp.189-198
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• 2018

A 31 years old female had been suffered from a bony swelling in right premolar region of the mandible for 12 years, recently grown rapidly. A fistula tract developed on the right anterior mandibular border, but the lesion was relatively asymptomatic. In the radiological examination, the tumor mass was irregularly mixed with radiolucent and radiopaque areas, forming multiple cystic spaces. Under the diagnosis of calcifying odontogenic cyst, the mandibular mass was resected and examined pathologically. After decalcification, the dissected tumor mass showed multiple small cystic spaces and calcifying fibrous tissue, mimicking calcifying odontogenic cyst or ameloblastoma. Histological observation showed many calcifying cementoid materials and ossifying trabeculae. The cystic spaces were turned out to be dilated vascular channels lined by endothelial cells, containing plasma fluid. However, the main lesion was diagnosed as cemento-ossifying fibroma (COF), and the atypical vascular channels were greatly dilated and gradually expanded the whole tumor mass. The present COF was examined through immunohistochemical (IHC) array, and investigated for tumor cell characteristics, exhibiting abnormal ossification and aneurysmal cystic changes. IHC array disclosed that the tumor cells grew progressively in the lack of apoptosis, and that they showed lower expression of RUNX2 than BMP-2, RANKL, and OPG, and increases of protein expression in $HIF-1{\alpha}$, VEGF-A, and CMG2. These data suggested that the reduced expression of RUNX2, osteoblast differentiation factor, be relevant to abnormal ossification of COF, and that the consistent expressions of angiogenesis factors be relevant to de novo angiogenesis in COF, subsequently resulted in aneurysmal cystic changes.

• 대한의용생체공학회:의공학회지
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• 제20권2호
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• pp.213-220
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• 1999

본 연구는 쥐의 뇌, 심장, 간, 근육 및 근육부위의 종양조직과 인간의 뇌 조직과 뇌 종양 조직의 광학적 흡수계수를 500nm~900nm 범위의 파장에서 측정하고 비교분석하였다. 광학적 흡수계수는 물질마다 가지고 있는 고유한 성질을 나타내므로 생체조직의 광학계수를 측정하면, 생체 조직의 고유한 특성을 나타낼 수 있다. Spectrograph monometer와 PDA를 이용하여, 동결절편으로 제작한 시편에 대하여 실험하였다. 실험결과, 쥐 조직과 인체의 뇌 조직의 흡수계수는 정상적인 일반 조직과 종양 조직에서 차이가 분명하게 있음을 알 수 있었다. 정상 뇌 조직의 흡수계수는 파장이 변화함에 따라 0.1~0.2$cm^{-1}$사이의 비교적 균일한 값을 보이는데 반하여, 뇌종양 조직의 흡수계수는 파장에 따라서 크게는 약 0.4~0.5$cm^{-1}$정도의 변화가 있다. 본 실험 결과들은 다양한 조직에서의 광학계수 중에서 흡수계수를 측정함으로써, 생체조직의 흡수계수의 변화를 감지하여 질병진단의 지표로 삼을 수 있다.

• 대한두경부종양학회지
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• 제24권2호
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• pp.155-161
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• 2008

Head and neck squamous cell carcinoma(HNSCC) still has poor outcome, and laryngeal cancer is the most frequent subtype of HNSCC. Therefore, there is a need to develop novel treatments to improve the outcome of patients with HNSCC. It is critical to gain further understanding on the molecular and chromosomal alteration of HNSCC to identify novel therapeutic targets but genetic etiology of squamous cell carcinoma of the larynx is so complex that target genes have not yet been clearly identified. Array based CGH(array-CGH) allows investigation of general changes in target oncogenes and tumor suppressor genes, which should, in turn, lead to a better understanding of the cancer process. In this study, We used genomic wide array-CGH in tissue specimens to map genomic alterations found in laryngeal squamous cell carcinomas. As results, gains of MAP2, EPHA3, EVI1, LOC389174, NAALADL2, USP47, CTDP1, MASP1, AHRR, and KCNQ5, with losses of SRRM1L, ANKRD19, FLJ39303, ZNF141, DSCAM, GPR27, PROK2, ARPP-21, and B3GAT1 were observed frequently in laryngeal squamous cell carcinoma tissue specimens. These data about the patterns of genomic alterations could be a basic step for understanding more detailed genetic events in the carcinogenesis and also provide information for diagnosis and treatment in laryngeal squamous cell carcinoma. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes which were gained or lost clones.

• 한국음향학회지
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• 제8권4호
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• pp.5-12
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• 1989

초음파 hyperthermia를 이용한 암 치료는 정상세포에 열적 손상을 주지 않으면서 종양 부위만을 적당한 온도로 가열하여야 하며 따라서 종양세포와 정상세포에 대한 정확한 초음파 세기 조절이 필요하게 된다. 본 연구에서 초음파 hyperthermia용 변환기로써 촛점 거리와 집속 범위를 전자적으로 조절할 수 있는 육각환 변환기를 설계, 제작하였으며 위상조 절회로를 이용하여 초음파 hyperthermia 시스템을 구성, 그 음향 특성을 측정하였으며 모의 생체 실험을 수행하였다. 실험 결과 촛점 부근에서 초음파 에너지가 집속되는 것을 확인하였으며 초음과 hyperthermia 시스템으로써의 유용성을 확인하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1771-1774
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• 2014

The rhabdomyosarcoma (RMS) is the most common type of soft tissue tumor in children and adolescents; yet only a few screens for oncogenic mutations have been conducted for RMS. To identify novel mutations and potential therapeutic targets, we conducted a high-throughput Sequenom mass spectrometry-based analysis of 238 known mutations in 19 oncogenes in 17 primary formalin-fixed paraffin-embedded RMS tissue samples and two RMS cell lines. Mutations were detected in 31.6% (6 of 19) of the RMS specimens. Specifically, mutations in the NRAS gene were found in 27.3% (3 of 11) of embryonal RMS cases, while mutations in NRAS, HRAS, and PIK3CA genes were identified in 37.5% (3 of 8) of alveolar RMS (ARMS) cases; moreover, PIK3CA mutations were found in 25% (2 of 8) of ARMS specimens. The results demonstrate that tumor profiling in archival tissue samples is a useful tool for identifying diagnostic markers and potential therapeutic targets and suggests that these HRAS/ PIK3CA mutations play a critical role in the genesis of RMS.

• 대한방사선치료학회:학술대회논문집
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• 대한방사선치료학회 2005년도 춘계학술대회 초록집
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• pp.23-26
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• 2005

재발한 vulva tumor의 근접 치료에 있어서 정상조직의 장애와 tumor volume내의 dose uniformity는 치료성적에 매우 중요한 요인이다. 이를 개선하기 위하여 modified MUPIT applicator를 제작하여 modified MUPIT applicator의 적용에 대한 유용성을 평가하고자 한다. modified MUPIT applicator는 template, cylinder, interstitial needle로 구성되었으며, tumor volume을 정하기 위하여 CT를 시행하였다. CT image를 이용하여 interstitial needle의 삽입 위치를 확인하고 수술실에서 template 를 치료 부위에 고정을 시키고 cylinder를 vaginal cavity에 삽입한 후 interstitial needle을 tumor volume 내에 삽입 하였다. tumor volume내에서 interstitial needle의 정확한 위치를 확인하기 위하여 CT를 시행하였으며 orthogonal film을 이용하여 computer planning을 실시하였다. daily tumor dose는 600 cGy, BID로 3000 cGy를 조사하였으며 치료 시 rectal dose를 평가하기 위하여 TLD를 이용하여 anal verge를 기준으로 5개 지점에서 rectal dose를 측정하였다. rectal dose는 34.1 cGy, 57.1 cGy, 103.8 cGy, 162.7 cGy, 165.7 cGy로 측정되었으며 EBRT(whole pelvis RT), ICR과 overlap되는 지점은 34.1 cGy, 57.1 cGy로 매우 우수하게 평가되었다. 결론적으로 자체 제작한 modified MUPIT applicator 사용하여 interstitial brachytherapy를 시행함으로써 EBRT로 cover하기 어려운 환자의 tumor volume내에서 irregularity를 효율적으로 극복할 수 있었고 우수한 rectal dose 분포를 통하여 rectal complication의 발생 확률을 현저히 감소시킬 수 있었다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권6호
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• pp.550-555
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• 2011

Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. LOH patterns can be generated through allelotyping using polymorphic microsatellite markers; however, owing to the limited number of available microsatellite markers and the requirement for large amounts of DNA, only a modest number of microsatellite markers can be screened. Hybridization to single nucleotide polymorphism (SNP) arrays using Affymetarix GeneChip Mapping 10 K 2.0 Array is an efficient method to detect genome-wide cancer LOH. We determined the presence of LOH in oral SCCs using these arrays. DNA was extracted from tissue samples obtained from 10 patients with tongue SCCs who presented at the Hospital of Tokyo Dental College. We examined the presence of LOH in 3 of the 10 patients using these arrays. At the locus that had LOH, we examined the presence of LOH using microsatellite markers. LOH analysis using Affymetarix GeneChip Mapping 10K Array showed LOH in all patients at the 1q31.1. The LOH regions were detected and demarcated by the copy number 1 with the series of three SNP probes. LOH analysis of 1q31.1 using microsatellite markers (D1S1189, D1S2151, D1S2595) showed LOH in all 10 patients (100). Our data may suggest that a putative tumor suppressor gene is located at the 1q31.1 region. Inactivation of such a gene may play a role in tongue tumorigenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1715-1720
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• 2013

Background: The discovery that microRNAs (miRNAs) regulate proliferation, invasion and metastasis provides a principal molecular basis of tumor heterogeneity. Microvessel distribution is an important characteristic of solid tumors, with significant hypoxia occurring in the center of tumors with low blood flow. The distribution of miR-374a in breast tumors was examined as a factor likely to be important in breast cancer progression. Methods: Breast tissue samples from 40 patients with breast cancer were classified into two groups: a highly invasive and metastatic group (HIMG) and a low-invasive and metastatic Group (LIMG). Samples were collected from the center and edge of each tumor. In each group, six specimens were examined by microRNA array, and the remaining 14 specimens were used for real-time RT-qPCR, Western blot and immunohistochemical analyses. Correlation analysis was performed for the miRNAs and target proteins. Follow-up was carried out during 28 months to 68 months after surgery, and survival data were analyzed. Results: In the LIMG, the relative content of miR-374a was lower in the center of the tumor than at its edge; in the HIMG, it was lower at the edge of the tumor, and miR-374a levels were lower in breast cancer tissues than in normal tissues. There was no difference between VEGF-A and VCAM-1 mRNA levels at the edge and center of the tumor; however, we observed a significant difference between VEGF-A and VCAM-1 protein expression levels in these two regions. There was a negative correlation between miR-374a and target protein levels. The microvessel density (MVD) was lower in the center of the tumor than at its edge in HIMG, but the LIMG vessels were uniformly distributed. There was a significant positive correlation between MVD and the number of lymph node metastases (Pearson correlation, r=0.912, P<0.01). The median follow-up time was 48.5 months. LIMG had higher rate of disease-free survival (100%, P=0.013) and longer median survival time (66 months) than HIMG, which had a lower rate of 75% and shorter median survival time (54 months). Conclusions: Our data demonstrated miR-374a to be differentially distributed in breast cancer; VEGF-A and VCAM-1 mRNA had coincident distribution, and the distribution of teh respective proteins was uneven and opposite to that for the miR-374a. These data might explain the differences in the distribution of MVD in breast cancer and variation in breast cancer prognosis.