• 한국식품영양과학회지
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• 제23권2호
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• pp.340-347
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• 1994

원발성 위암환자로 확진받은 환자들의 암조직과 암조직 주위의 정상점막 조직을 대조군으로 사용하여, $TGF-{\alpha}$와 이에 대한 결합력을 갖고 있는 EGF-Receptor에 대한 mRNA를 면역세포화학적 방법과 in situ hybridization방법을 결합하여 규명하였다. 성장한 세포에서 발견되지 않는 $TGF-{\alpha}$가 위암환자의 조직학적으로는 정상적으로 간주되는 위점막 조직에서 발견된 점으로 미루어 $TGF-{\alpha}$가 암의 분화에 적극적으로 개입하고 있다는 증거가 된다. EMB-11 항체를 사용한 면역세포 화학적 방법에 의해 macrophage를 발견하고, macrophage cell에서 $TGF-{\alpha}$와 EGF-R mRNA가 발현됨을 규명할 수 있었다. 또한 단클론 항체를 이용해 EGF-R에 해당하는 단백질을 발견하였다. CEA를 이용한 면역세포화학 실험에서 정상으로 간주되는 위점막 조직에서 암 세포를 규명하였다. 특히, macrophage cell의 활동이 암의 증식과 더불어 증가하고 있다는 점을 관찰할 수 있었다. 위암과 검사 방법으로서 본 실험에서 사용된 면역세포화학적 기법과 in situ hybridization방법을 사용하여 생검을 통한 조직을 대상으로 성장인자에 대한 검사를 함으로써 정확한 위암의 발생과 진행에 대한 판단을 내리는데 이용할 수 있고 실용성이 있다고 사료된다.

• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.131-138
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• 2017

This study was conducted to investigate stimulatory effect of epidermal growth factor (EGF) on nuclear maturation and the expression level of EGF-receptor (EGFR), GM-130 (a marker of Golgi apparatus), transport protein Sec61 subunit beta ($Sec61{\beta}$), and coatomer protein complex subunit gamma 2 (COPG2) in porcine oocytes. The cumulus-oocyte complexes were collected from follicle with 3-6 mm in diameter. They were incubated in medium with/without EGF for 22 h (IVM I) and subsequently incubated hormone-free medium with/without EGF for 22 h (IVM II). Nuclear maturation state was checked by aceto-orcein stain. Protein expression of EGFR, GM-130, $Sec61{\beta}$, and COPG2 were measured by immunofluorescence. In results, nuclear maturation of oocytes in EGF non-treated oocytes were significantly lower than EGF-treated groups at IVM I or IVM II stage (P<0.05), whereas maturational rate in EGF treatment groups at both of IVM stage was higher in among the all treatment groups (P<0.05). EGFR, GM-130, $Sec61{\beta}$ and COPG2 were expressed in the cytoplasm of oocytes. Especially, GM-130 and EGFR were strongly expressed, but $Sec61{\beta}$ and COPG2 were weakly expressed in cortical area of cytoplasm. The protein level of GM-130, $Sec61{\beta}$, and COPG2 were significantly higher in the EGF-treated groups (P<0.05). However EGFR was no difference between non EGF-treated groups and control. In conclusion, EGF plays an important role in the systems for oocyte maturation with endoplasmic reticulum and Golgi apparatus. In addition, the protein levels of $Sec61{\beta}$ and COPG2 could be changed by EGF in the porcine oocytes during maturation.

• Journal of Ginseng Research
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• 제46권3호
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• pp.348-356
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• 2022

Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin exerts its neuronal and non-neuronal in vitro and in vivo effects through LPA receptor subtypes. However, it is unknown whether gintonin can bind to the plasma membrane of cells and can transactivate the epidermal growth factor (EGF) receptor. In the present study, we examined whether gintonin-biotin conjugates directly bound to LPA receptors and transactivated the EGF receptor. Methods: We designed gintonin-biotin conjugates through gintonin biotinylation and examined whether gintonin-biotin conjugate binding sites co-localized with the LPA receptor subtype binding sites. We further examined whether gintonin-biotin transactivated the EGF receptor via LPA receptor regulation via phosphor-EGF and cell migration assays. Results: Gintonin-biotin conjugates elicit [Ca²⁺]_i transient similar to that observed with unbiotinylated gintonin in cultured PC3 cells, suggesting that biotinylation does not affect physiological activity of gintonin. We proved that gintonin-biotin conjugate binding sites co-localized with the LPA1/6 receptor binding sites. Gintonin-biotin binding to the LPA1 receptor transactivates the epidermal growth factor (EGF) receptor through phosphorylation, while the LPA1/3 receptor antagonist, Ki16425, blocked phosphorylation of the EGF receptor. Additionally, an EGF receptor inhibitor AG1478 blocked gintonin-biotin conjugate-mediated cell migration. Conclusions: We observed the binding between ginseng-derived gintonin and the plasma membrane target proteins corresponding to the LPA1/6 receptor subtypes. Moreover, gintonin transactivated EGF receptors via LPA receptor regulation. Our results suggest that gintonin directly binds to the LPA receptor subtypes and transactivates the EGF receptor. It may explain the molecular basis of ginseng physiology/pharmacology in biological systems.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9615-9619
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• 2014

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which is more likely to be her-2/neu amplified. While the her-2/neu status has been utilised to predict prognosis, the published data are inconsistent. The present meta-analysis was conducted to determine whether the her-2/neu status predicts outcomes. Papers were selected from the PubMed database based on defined inclusion and exclusion criteria. Parameters such as total patients, follow-up time and outcome statistics (i.e. overall survival (OS), relapse-free survival (RFS) were collected. The analysis included 6 studies with 2,838 IBC patients. The summary hazards ratio (HR) estimating the association of OS with HER-2-positive disease was 0.96 (95% confidence interval (95%CI: 0.85-1.10)), with similar findings for RFS (HR=0.81, 95%CI: 0.61-1.09). No obvious statistical heterogeneity was detected. This meta-analysis suggests that HER-2-positive status is not an independent adverse prognostic factor for survival among IBC patient cases.

• Journal of Ginseng Research
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• 제43권4호
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• pp.550-561
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• 2019

Background: Gastric ulcer (GU) is a common gastrointestinal disease that can be induced by many factors. Finding an effective treatment method that contains fewer side effects is important. 20 (S)-ginsenoside Rg3 is a kind of protopanaxadiol and has shown superior antiinflammatory and antioxidant effects in many studies, especially cancer studies. In this study, we examined the treatment efficacy of 20 (S)-ginsenoside Rg3 on GU. Methods: Three kinds of GU models, including an alcohol GU model, a pylorus-ligated GU model, and an acetic acid GU model, were used. Mouse endothelin-1 (ET-1) and nitric oxide (NO) levels in blood and epidermal growth factor (EGF), superoxide dismutase, and NO levels in gastric mucosa were evaluated. Hematoxylin and eosin staining of gastric mucosa and immunohistochemical staining of ET-1, inducible nitric oxide synthase (NOS2), and epidermal growth factor receptors were studied. Ulcer index (UI) scores and UI ratios were also analyzed to demonstrate the GU conditions in different groups. Furthermore, Glide XP from $Schr{\ddot{o}}dinger$ was used for molecular docking to clarify the interactions between 20 (S)-ginsenoside Rg3 and EGF and NOS2. Results: 20 (S)-ginsenoside Rg3 significantly decreased the UI scores and UI ratios in all the three GU models, and it demonstrated antiulcer effects by decreasing the ET-1 and NOS2 levels and increasing the NO, superoxide dismutase, EGF, and epidermal growth factor receptor levels. In addition, high-dose 20 (S)-ginsenoside Rg3 showed satisfactory gastric mucosa protection effects. Conclusion: 20 (S)-ginsenoside Rg3 can inhibit the formation of GU and may be a potential therapeutic agent for GU.

• Genomics & Informatics
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• 제18권4호
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• pp.35.1-35.7
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• 2020

Identifying the patterns of gene expression in breast cancers is essential to understanding their pathophysiology and developing anticancer drugs. Breast cancer is a heterogeneous disease with different subtypes determined by distinct biological features. Luminal breast cancer is characterized by a relatively high expression of estrogen receptor (ER) and progesterone receptor (PR) genes, which are expressed in breast luminal cells. In ~25% of invasive breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed; these cancers are categorized as the HER2 type. Triple-negative breast cancer (TNBC), in which the cancer cells do not express ER/PR or HER2, shows highly aggressive clinical outcomes. TNBC can be further classified into specific subtypes according to genomic mutations and cancer immunogenicity. Herein, we discuss the brief history of TNBC classification and its implications for promising treatments.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2007년도 제48회 학술심포지움 및 추계국제학술대회
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• pp.95.2-95.2
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• 2007

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• 미생물학회지
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• 제54권4호
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• pp.320-324
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• 2018

발효대두 청국장에는 대두단백질이 발효에 의해 분해 형성된 다양한 펩타이드류가 들어 있다. 청국장 추출물이 처리된 유방암세포의 microarray data와 잘 알려진 유방암 전이 마커를 합쳐서 새로운 연결망이 제조되었으며 이를 이용해 전이 마커와 발현 차이가 있는 단백질 사이의 상호작용을 체크하였다. 연결망 분석을 통해 PLAU (plasminogen activator, urokinase, uPA)와 ERBB2 (epidermal growth factor receptor 2)를 실제 전이 가능성을 보여주는 유전자로 선택하였다. MCF7 암세포를 청국장추출물로 처리하고 PLAU와 ERBB2 발현정도를 측정하였다. 청국장 추출물은 PLAU와 ERBB2 발현을 상당히 억제하였다. 청국장 추출물을 처리한 암세포에서 염증 마커인 NO의 생산이 감소하였다. 인간 유방암세포에서 PLAU와 ERBB2 발현을 특이적으로 감소시키는 펩타이드를 찾아내는 것은 흥미로운 일일 것이다.

• 셀메드
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• 제3권2호
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• pp.10.1-10.8
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• 2013

Cancer is one of the major dreaded diseases causing high mortality. Lung cancer is second in position of all cancer related deaths and mainly divided into two morphologic sub-types: small-cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is an aggressive neoplasm which hardly responds to any conventional chemotherapy. Epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinase that is mainly over-expressed in NSCLC. EGFR is mainly involved in the pathogenesis and progression of different carcinoma. In vivo and in vitro studies suggest that EGFR and EGF like peptides are often over-expressed in human NSCLC and these proteins are able to induce cell transformation. The conventional therapies mostly inhibit the EGFR activity and expression level in human NSCLC with the use of some EGFR-inhibitors like HKI-272, EKB569, CL-387785 etc. and some synthetic chemotherapeutic drugs like erlotinib, gefitinib, plumbagin, docetaxel, cisplatin etc., alone or in combination of two or more drugs. These therapies selectively act by competitive inhibition of the binding of adenosine triphosphate to the tyrosine kinase domain of the EGFR, resulting in inhibition of the EGFR signaling pathway. But these chemotherapeutic drugs have some cytotoxic activities to the normal cells and have some adverse side-effects. Recent studies on some traditional alternative therapies including some herbal and plant extracts, active ingredients like curcumin, different homeopathic drugs, etc. can target EGFR-signalling in NSCLC with less toxic side-effects are being currently developed.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6221-6225
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• 2012

Background: To determine the frequency of HER-2 overexpression in colorectal cancer (CRC) patients, and to explore the relationship between clinicopathological prognostic factors and their effects on survival, based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis. Materials and Methods: The study included 80 patients with a histologically proven diagnosis of CRC that received adjuvant FOLFOX-4 chemotherapy at our department between March 2006 and September 2010. Patient data were analyzed retrospectively. Results: The median follow-up period and age of the patients were 24 months and 59 years, respectively. In immunohistochemical staining, 3+ staining was found in 2 patients (2.5%) while 2+ was in 13 (16%). FISH for HER-2 was performed for all of these 15 patients; samples which were 3+ showed positivity but the ones with 2+ were negative. There was no significant correlation between HER-2 expression and age, gender, tumor localization, histological subtype, grade, lymphovascular and perineural invasion, or pTN stage (P>0.05), even when the patients with HER-2 overexpression were analyzed separately. There was also no significant relationship between progression-free survival (PFS) and overall survival (OS), and HER-2 expression, gender, tumor localization, obstruction-perforation, bleeding, histological type, grade, lymphovascular and perineural invasion, or pT staging (P>0.05); however, there was a significant relationship between lymph node involvement, and PFS and OS (P<0.05). Conclusions: Evaluation of HER-2 overexpression in a more comprehensive, multi-center, prospective trial with standardized methods will be an appropriate approach.