• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권5호
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• pp.396-402
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• 2011

Introduction: Epidermal growth factor is a single-chain polypeptide consisting of 53 amino acids with potent mitogenic activity that stimulates the proliferation of a range of normal and neoplastic cells through an interaction with its specific receptor (epidermal growth factor receptor, EGFR). This interaction plays a key role in tumor progression including the induction of tumor cell proliferation. An increased EGFR copy number have been associated with a favorable response to EGFR tyrosine kinase inhibitors therapy. In contrast, K-ras mutations tend to predict a poor response to such therapy. The aim of this study was to determine the correlation between the clinicopathological factors and the up-regulation of EGFR expression and Kras mutations in oral squamous cell carcinoma. Materials and Methods: This study examined the immunohistochemical staining of EGFR, K-ras mutation detection with peptide nucleic acid (PNA)-based real-time polymerase chain reaction (PCR) clamping in 20 specimens from 20 patients with oral squamous cell carcinoma. Results: 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, a high level of EGFR staining was observed. The correlation between immunohistochemical EGFR expression and histological differentiation, as well as the tumor size of the specimens was significant (Pearson correlation analysis, significance [r] >0.5, P<0.05). 2. In PNA-based real-time PCR clamping analysis, a K-ras mutation was not detected in all specimens. Conclusion: These findings suggest that the up-regulation of the EGFR may play a role in the progression and invasion of oral squamous cell carcinoma that is, independent of a K-ras mutation.

• Clinical and Experimental Pediatrics
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• 제61권1호
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• pp.30-34
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• 2018

Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation, is a rare developmental lung abnormality associated with rhabdomyosarcoma, pleuropulmonary blastoma, and mucinous adenocarcinoma of the lung. We report an unusual case of a 10-day-old male newborn with a left lower lobe pulmonary cyst who underwent lobectomy, which revealed type II CPAM complicated by multifocal mucinous adenocarcinoma. KRAS sequencing revealed a somatic mutation in Codon12 ($GGT{\rightarrow}GAT$), suggesting the development of a mucinous adenocarcinoma in the background of mucinous metaplasia. Mucinous adenocarcinoma is the most common lung tumor associated with CPAM, but it generally occurs in older children and adults. Further, all cases in the literature are of type I CPAM. This case in a neonate indicates that malignant transformation can occur very early in type II CPAM.

• Journal of Genetic Medicine
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• 제16권1호
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• pp.1-9
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• 2019

Noonan syndrome (NS) and NS-related disorders (cardio-facio-cutaneous syndrome, Costello syndrome, NS with multiple lentigines, or LEOPARD [lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth and sensory neural deafness] syndrome) are collectively named as RASopathies. Clinical presentations are similar, featured with typical facial features, short stature, intellectual disability, ectodermal abnormalities, congenital heart diseases, chest & skeletal deformity and delayed puberty. During past decades, molecular etiologies of RASopathies have been growingly discovered. The functional perturbations of the RAS-mitogen-activated protein kinase pathway are resulted from the mutation of more than 20 genes (PTPN11, SOS1, RAF1, SHOC2, BRAF, KRAS, NRAS, HRAS, MEK1, MEK2, CBL, SOS2, RIT, RRAS, RASA2, SPRY1, LZTR1, MAP3K8, MYST4, A2ML1, RRAS2). The PTPN11 (40-50%), SOS1 (10-20%), RAF1 (3-17%), and RIT1 (5-9%) mutations are common in NS patients. In this review, the constellation of overlapping clinical features of RASopathies will be described based on genotype as well as their differential diagnostic points and management.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5699-5703
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• 2013

Objective: To investigate the clinical effects of whole brain radiotherapy concomitant with targeted therapy for brain metastasis in non-small cell lung cancer (NSCLC) patients with chemotherapy failure. Materials and Methods: Of the 157 NSCLC patients with chemotherapy failure followed by brain metastasis admitted in our hospital from January 2009 to August 2012, the combination group (65 cases) were treated with EGFR-TKI combined with whole brain radiotherapy while the radiotherapy group (92 cases) were given whole brain radiotherapy only. Short-term effects were evaluated based on the increased MRI in brain 1 month after whole brain radiotherapy. Intracranial hypertension responses, hematological toxicity reactions and clinical effects of both groups were observed. Results: There were more adverse reactions in the combination group than in radiotherapy group, but no significant differences were observed between the two groups in response rate (RR) and disease control rate (DCR) (P>0.05). Medium progression free survival (PFS), medium overall survival (OS) and 1-year survival rate in combination group were 6.0 months, 10.6 months and 42.3%, while in the radiotherapy group they were 3.4 months, 7.7 months and 28.0%, respectively, which indicated that there were significant differences in PFS and OS between the two groups (P<0.05). Additionally, RPA grading of each factor in the combination group was a risk factor closely related with survival, with medium PFS in EGFR and KRAS mutation patients being 8.2 months and 11.2 months, and OS being 3.6 months and 6.3 months, respectively. Conclusions: Whole brain radiotherapy concomitant with target therapy is favorable for adverse reaction tolerance and clinical effects, being superior in treating brain metastasis in NSCLC patients with chemotherapy failure and thus deserves to be widely applied in the clinic.

• 셀메드
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• 제3권1호
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• pp.9.1-9.10
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• 2013

In traditional systems of medicine including homeopathy, the Condurango extract (Con) is often used to cure stomach cancer mainly, without having any scientific validation of its anti-cancer ability. Con has therefore been tested against non-small-cell lung cancer cells (NSCLC) A549 and NCI-H522 (H522) known to contain the KRAS mutation, making them resistant to most chemotherapeutic agents. As cancer cells generally defy cytotoxicity developed by chemopreventive agents and escape cell death, any drug showing the capability of preferentially killing cancer cells through apoptosis is worth consideration for judicious application. A549 and H522 cells were exposed to $0.35{\mu}g/{\mu}l$ and $0.25{\mu}g/{\mu}l$ of Con, respectively, for 48 h and analysed based on various protocols associated with apoptosis and DNA damage, such as MTT assay to determine cell viability, LDH assay, DNA fragmentation assay, comet assay, and microscopical examinations of DNA binding fluorescence stains like DAPI, Hoechst 33258 and acridine orange/ethidium bromide to determine the extent of DNA damage made in drug-treated and untreated cells and the results compared. Changes in mitochondrial membrane potential and the generation of reactive oxygen species were also documented through standard techniques. Con killed almost 50% of the cancer cells but spared normal cells significantly. Fluorescence studies revealed increased DNA nick formation and depolarized membrane potentials after drug treatment in both cell types. Caspase-3 expression levels confirmed the apoptosis-inducing potential of Con in both the NSCLC lines. Thus, overall results suggest considerable anticancer potential of Con against NSCLC in vitro, validating its use against lung cancer by practitioners of traditional medicine including homeopathy.

• 대한병리학회지
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• 제52권6호
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• pp.386-395
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• 2018

Background: Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. Methods: Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. Results: SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p=.003) and distant metastasis (p=.001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p<.001), but not for recurrence-free survival (p=.151). Conclusions: Findings suggested that multiplicity of advanced T category-tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

• 대한임상검사과학회지
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• 제55권1호
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• pp.16-28
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• 2023

폐암은 크게 소세포성 폐암과 비소세포성 폐암으로 구분되며 비소세포성폐암이 차지하는 비율은 약 70%~80%이다. 비소세포성폐암 중 폐선암은 전체 폐암의 약 40%를 차지한다. 최근 유전자 프로파일링 기술이 발전하면서 종양의 발생 및 성장에 중요한 종양 유전자와 종양 억제 유전자의 변이에 대한 연구가 활발히 진행되어 폐암을 유발하는 특정 유전자들이 발견되면서 생존율에 큰 영향을 미치게 되었으며 특히 폐선암은 차세대 염기서열 분석법(next generation sequencing, NGS)을 이용한 동반진단을 통해 표적 치료로 생존을 높이는 데 도움을 얻을 수 있다. 본 연구는 한국인에서 폐선암을 유발하는 유전자 변이 검출을 위해 비소세포성폐암 환자의 파라핀 포매조직(formalin-fixed paraffin-embedded)으로 hematoxylin and eosin 염색을 시행하여 폐선암을 구분하였으며 정확한 폐선암 조직을 분류하기 위해 면역조직화학(immunohistochemistry, IHC)염색을 시행하였다. 그 결과를 바탕으로 NGS를 이용하여 유전자 변이의 종류와 패턴을 분석하였고 폐암을 유발하는 가장 대표적인 원인인 흡연과의 관계를 확인하였다. NGS 결과 단일염기서열변이(single nucleotide variation, SNV), 복제수변이 (copy number variation, CNV), 유전자 재배열을 확인하였으며 폐선암에서 SNV는 TP53 (44.6%), EGFR (35.7%), KRAS (10.7%), PIK3CA (6.2%), CDKN2A (4.4%) 순으로 발생하였고 CNV의 경우 EGFR (14%)이 가장 빈번하게 발생하였다. 또한 ALK, ROS1, RET 과 같은 유전자 재배열을 확인하였다. NGS의 신뢰도를 확인을 위하여 기존에 사용되고 있는 유전자 검사방법인 PCR-EGFR, IHC-ALK (D5F3), FISH-ROS1 검사를 추가적으로 시행하여 NGS 결과와 일치도를 확인하였다. 이 연구는 폐선암 환자에 대한 NGS가 여러 유전자의 돌연변이를 동시에 확인하여 치료 전략에 더욱 긍정적인 이익을 줄 수 있음을 보여준다.