• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7597-7602
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• 2014

Background: Amplification and overexpression of human epidermal growth factor receptor 2 (HER2/neu) oncogene has considerable prognostic value in breast and gastric cancers. This study aimed to evaluate the frequency, overexpression pattern, clinical significance, and concordance between the results for protein expression and gene amplification of HER-2/neu in gastric and gastro-esophageal junction carcinomas. Materials and Methods: In this study, 101 gastric tissue samples which were included in tissue microarray were immunohistochemically examined for overexpression of HER2/neu. Chromogenic in situ hybridization (CISH) was used for HER-2/neu amplification. The correlation of HER2/neu amplification with clinicopathological parameters was also assessed. In addition, concordance between CISH and IHC was detected. Results: This study demonstrated a significant difference in the overexpression of HER2/neu in gastric tumors. The overexpression of HER2/neu was significantly higher in intestinal type, poorly differentiated grade, large size ($5cm{\leq}$) and positive nodal involvement tumors (p-value=0.041, 0.015, 0.038 and 0.071, respectively). Also, amplification of HER2/neu according to CISH test, had a significant positive correlation with tumor size and tumor type (p-value=0.018 and 0.058, respectively).Concordance between CISH and IHC was 76.9% in 101 evaluable samples. Conclusions: IHC/CISH differences were attributed to basolateral membranous immunoreactivity of glandular cells resulting in incomplete membranous reactivity and/or a higher rate of tumor heterogeneity in gastric cancers compared to breast cancers. Therefore, this can be a potential marker for targeted therapy of malignant gastric tumors.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4863-4867
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• 2015

Background: Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports. Materials and Methods: Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results. Results: The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively. Conclusions: The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1993년도 제27차 학술대회 초록집
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• pp.85-85
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• 1993

후두 편평세포암은 종양세포의 생물학적 특성과 발생부위별 미세환경이 다르기 때문에 임상적 병기만으로 예후를 추정하는 것은 다소 문제점이 있다. 이에 저자들은 종양세포의 유전정보에 의한 증식능이 예후와 연관성이 있는지 규명하고자 EGFR, p53 단백 및 pRB의 표현양상을 후두 편평세포암 40례의 임상적 특성과 비교 검토하여 다음과 같은 성적을 얻었다. 1. p53 단백의 양성 표현율은 임상적 병기, 원발병소의 병기, 경부 림프전이절의 병기, 병리조직학적 분화도, 재발이나 원격전이 흑은 이차암이 있었던 경우와 연관성이 높았다. 2. pRB의 음성 표현율은 침습성이 강한 성문상분, 임상적 병기, 원발병소의 병기, 병리 조직학적 분화도, 재발이나 원격전이 혹은 이차암, 치료에 실패한 경우와 연관성이 높았다. 3. 3년생존율은 p53의 양성표현율과 관계가 있었다. 4. EGFR은 특별한 상관관계가 없었다. 이상의 결과로 보아 p53 단백과 pRB의 암억제유전자 단백의 면역조직화학적 염색을 통한 표현양상은 후두 편평세포암의 생물학적인 특성을 잘 반영하고 있을 뿐만 아니라 종양 즉 인자들과 밀접한 상관관계가 있어 후두 편평세포암의 악성도를 예측하는데 도움을 주는 예후인자로서 적용시킬 수 있을 것으로 생각된다.

• IMMUNE NETWORK
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• 제21권4호
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• pp.31.1-31.16
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• 2021

Gastric cancer (GC) is the fourth most common cause of cancer-related death globally. The classification of advanced GC (AGC) according to molecular features has recently led to effective personalized cancer therapy for some patients. Specifically, AGC patients whose tumor cells express high levels of human epidermal growth factor receptor 2 (HER2) can now benefit from trastuzumab, a humanized monoclonal Ab that targets HER2. However, patients with HER2^negative AGC receive limited clinical benefit from this treatment. To identify potential immune therapeutic targets in HER2^negative AGC, we obtained 40 fresh AGC specimens immediately after surgical resections and subjected the CD45⁺ immune cells in the tumor microenvironment to multi-channel/multi-panel flow cytometry analysis. Here, we report that HER2 negativity associated with reduced overall survival (OS) and greater tumor infiltration with neutrophils and non-classical monocytes. The potential pro-tumoral activities of these cell types were confirmed by the fact that high expression of neutrophil or non-classical monocyte signature genes in the gastrointestinal tumors in The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases associated with worse OS on Kaplan-Meir plots relative to tumors with low expression of these signature genes. Moreover, advanced stage disease in the AGCs of our patients associated with greater tumor frequencies of neutrophils and non-classical monocytes than early stage disease. Thus, our study suggests that these 2 myeloid populations may serve as novel therapeutic targets for HER2^negative AGC.

• 대한치과보철학회지
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• 제59권4호
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• pp.379-394
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• 2021

목적: 이전 연구에서 치은섬유아세포 혹은 성견 구개 연조직에 trichloroacetic acid (TCA)를 적용하는 것이 세포주기진행 유전자 발현의 변화를 일으키는 것으로 밝혀졌다. 이에 따라 본 연구에서는, hydrophobically modified glycol chitosan (HGC)기반의 나노방출제어시스템을 이용한 TCA 및 상피세포성장인자(EGF)의 순차적 방출시스템에서 이 효과를 검증하기 위하여 다양한 세포주기진행 유전자들의 발현을 규명하였다. 재료 및 방법: TCA와 EGF를 담지하는 HGC기반 나노방출제어시스템을 제작하였다. 실험군은 대조군(CON); TCA-담지형 나노방출제어시스템 투여군(EXP1); TCA- 및 EGF-담지형 나노방출제어시스템 투여군(EXP2)으로 정의되었다. 24시간 및 48시간 배양 시 37개 세포주기 유전자들의 발현을 분석하였다. 영향인자로서의 유전자 및 상관관계에 대해서도 분석하였다. 결과: Cyclins (CCNDs), cell division cycles (CDCs), cyclin-dependent kinases (CDKs), E2F transcription factors (E2Fs), extracellular signal-regulated kinases (ERKs)와 같은 다수의 유전자들과 기타 다른 세포주기 유전자들의 발현이 EXP1과 EXP2에서 상향조절되었다. E2F4, E2F5, GADD45G와 같은 세포주기차단 유전자들의 발현도 상향조절되었으나, 또다른 세포주기차단 유전자인 SMAD4의 발현은 하향조절되었다. 다중회귀분석에서 CCNA2, CDK4 그리고 ANAPC4가 ERK 유전자 발현에 가장 영향력 있는 유전자로 선정되었다. 결론: HGC기반 순차적 나노방출제어시스템을 이용한 TCA 및 EGF의 적용은 다양한 세포주기진행 유전자들의 발현을 상향조절함이 밝혀졌고, 이를 토대로 한 구강연조직증대시스템 개발의 가능성이 확보되었다.

• 한국가축번식학회지
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• 제27권2호
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• pp.169-177
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• 2003

본 연구는 착상전 이배체 단위발생 돼지난자를 체외 배양시 우태아혈청 (FBS), 우혈청 알부민 (BSA) 및 상피세포성장인자 (EGF)를 배양액에 첨가하였을 때 배반포, 총 세포수, 세포사멸 및 세포사멸에 관여하는 유전자의 발현을 조사하고자 수행하였다. 0.4% BSA를 배양액에 첨가하였을 때 2세포기 단위발생 난자의 배반포까지의 발달율이 증가되었다(P<0.01). FBS는 배반포의 총세포수를 감소시 켰고 세포사멸을 증가하였다(P<0.01). 그리고 EGF는 BSA가 존재하는 조건하에서 배반포의 총세포수를 증가하였는데 EGF와 BSA가 각각 단독으로 존재할 때는 이런 작용이 없었다. 세포사멸도 이와 이슷한 경향을 보였는데 EGF와 BSA가 각각 존재할 때에는 비처리군과 차이가 없었지만 함께 존재할 때에는 세포사멸을 감소시켰다. RT-PCR의 결과에 의하면 EGF는 BSA가 존재하는 배양액에서 Bcl-xL 유전자의 상대적 발현량을 증가시키고 Bak 유전자의 상대적 발현량에는 영향을 주지 않는 과정을 통하여 세포사멸을 감소시키는것 같다. 반면에 FBS는 Bcl-xL의 발현량을 감소시키고 Bak 유전자의 상대적 발현량을 증가시킨다. 이러한 결과는 세포사멸에 관여하는 유전자의 발현은 배양액의 첨가물에 따라 유의적으로 영향을 받으며, 체외배양시 배아의 초기발달에 관여함을 시사한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7071-7076
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• 2015

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including lung malignancies. Gefitinib and erlotinib are two available therapeutics that act as specific inhibitors of tyrosine kinase (TK) domains. We performed a case-control study with formalin-fixed paraffin-embedded tissue blocks (FFPE) from tissue biopsies of 167 non-small cell lung carcinoma (NSCLC) patients and 167 healthy controls. The tissue biopsies were studied for mutations in exons 18-21 of the EGFR gene. This study was performed using PCR followed by DNA sequencing. We identified 63 mutations in 33 men and 30 women. Mutations were detected in exon 19 (delE746-A750, delE746-T751, delL747-E749, delL747-P753, delL747-T751) in 32 patients, exon 20 (S786I, T790M) in 16, and exon 21 (L858R) in 15. No mutations were observed in exon 18. The 63 patients with EFGR mutations were considered for upfront therapy with oral tyrosine kinase inhibitor (TKI) drugs and have responded well to therapy over the last 15 months. The control patients had no mutations in any of the exons studied. The advent of EGFR TKI therapy has provided a powerful new treatment modality for patients diagnosed with NSCLC. The study emphasizes the frequency of EGFR mutations in NSCLC patients and its role as an important predictive marker for response to oral TKI in the south Indian population.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7529-7534
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• 2015

Background: The epidermal growth factor (EGF) plays important roles in non-small cell lung cancer (NSCLC) susceptibility and functional polymorphism in the EGF (+61A/G) gene has been linked to increased risk of NSCLC. This study aimed to evaluate the role of the EGF +61A/G polymorphism in risk of NSCLC adenocarcinoma (ADC) occurrence and survival in an Indian population. Materials and Methods: This casecontrol study included 100 histopathologically confirmed NSCLC (ADC) patients and 100 healthy controls. EGF (A61G) was genotyped by AS-PCR to elucidate putative associations with clinical outcomes. The association of the polymorphism with the survival of NSCLC patients was estimated by Kaplan-Meier curves. Results: It was found that EGF 61AG heterozygous and GG homozygous genotype is significantly associated with increased risk of NSCLC (ADC) occurrence compared to AA genotype, [OR 2.61 (1.31-5.18) and 3.25 (1.31-8.06), RR 1.51(1.15-2.0) and 1.72 (1.08-2.73) and RD 23.2 (6.90-39.5) and 28.53(7.0-50.1) for heterozygous AG (p=0.005) and homozygous GG (p=0.009)]. Patients homozygous for the G allele exhibited a significantly poor overall survival. The median survival time for patients with EGF 61 AA, AG, and GG genotypes was 10.5, 7.4, and 7.1 months (p=0.02), respectively. NSCLC (ADC) patients with GG + AG exhibited 7.3 months median survival compared to the AA genotype (p=0.009). Conclusions: The present study revealed that the EGF A61G genotype may be a novel independent prognostic marker to identify patients at higher risk of occurrence and an unfavourable clinical outcome.

• Radiation Oncology Journal
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• 제22권2호
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• pp.77-90
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• 2004

종양 발생 과정에 관여되고 있는 분자 생물학적 기전을 직접 공격해 보자고 하는 치료 방침은 암 치료에 있어서 아주 유망한 치료방법의 하나로 인정되고 있다. Epidermal growth factor receptor (EGFR) 수용체에 여러 ligands가 결합하게 되면 발암 단계에서부터 암의 진행 과정과 전이 과정 그리고 방사선에 대한 저항성과 관련된 여러 가지중요한 신호전달체계를 활성화시킨다. 특히 진행된 두경부 암 환자들에서 EGFR이 과발현 된 경우에는 매우 불량한 예후를 나타내고 있기 때문에 이러한 signaling pathway의 selective targeting을 위한 많은 임상 시도가 이루어지고 있다. 현재까지 알려진 표적치료 항암제로는 크게 EGFR에 대한 monoclonal antibody와 tyrosin kinase Inhibitors로 대별될 수 있는데 이와 같은 약제들은 여러 xenograft에서 고무적인 실험 결과들이 입증되어 곧 바로 임상 현장에서 적용되고 있다. 그러나 기대와는 달리 EGFR Inhibitor 단독으로 치료한 초기 임상연구 결과들을 보면 극히 소수의 환자에서만 미미한 효과를 나타내고 있고, 방사선 치료와의 병용치료에서도 괄목할만한 항암 효과를 보여주지 않고 있다. 그럼에도 불구하고 많은 실험적 데이터로부터 여러 가지 생물학적 이점이 밝혀져 있고 또 미래 지향적인 치료법의 하나로 각광을 받고 있기 때문에 현재 많은 연구자들은 어떤 환자 군에서 이러한 표적 치료가 도움이 될 것이며, 방사선 치료 또는 항암 치료와는 어떤 방식으로 조합할 것인지, 또 그 순서는 어떻게 할 것이며, 또 환자 선정에 있어 reliable marker는 무엇인지, 어떻게 체내에서 신호 전달체계의 효과적인 차단을 확인할 수 있겠는지, 또한 multiple targ리ed therapy가 필 요하도록 하는 targeted agent에 대 한 Intrinsic 또는 acquired resistance의 기전은 무엇인지 등등, 현재 당면하고 있는 많은 문제점을 규명하고자 노력하고 있다. 특히 EGFR-signaling pathway를 표적으로 하는 표적 지향적 방사선 치료를 위한 translation research의 적절한 모델이 되고 있는 두경부 암 환자에서 이러한 제반 문제점을 해결하기 위해서는 더 많은 임상 연구와 함께 well-Integrated laboratory clinical research program이 필요할 것으로 생각된다 또한 EGFR antagonist 외에도 anglogenlc pathway나 cell-cycle pathway를 표적으로 하는 새로운 약제들이 계속 개발되고 있고 이에 관한 연구가 활발히 진행 중이다. 따라서 이 고찰에서는 두경부 암 환자에서 이러한 약제들을 방사선 치료와 병용하였을 때의 임상 연구 결과들을 재검토해 보고 부가적으로 EGFR blockade에 따르는 내성 문제 그리고 방사선 치료를 병용하면서 여러 표적을 동시에 차단시키는 multiple-targeted therapy의 개발 현황을 간략히 소개하고자 한다

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9739-9745
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• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.