• Natural Product Sciences
• /
• 제27권2호
• /
• pp.134-139
• /
• 2021

A new cipadesin limonoid, i.e. 3-epi-cipadonoid C (1), and a new tirucallane triterpene, i.e. hispidol B 3-palmitate (3), have been isolated from the seeds and fruit peels extract of Sandoricum koetjape, respectively. Along with these compounds the known limonoid, cipaferen G (2), and two pentacyclic triterpenes, bryonolic (4) and bryononic (5) acids, were also isolated. The strucrures of the new compounds were elucidated by the analysis of NMR and mass spectral data. Compounds 1 - 5 were evaluated as the inhibitor of receptor tyrosine kinases (EGFR, Epidermal Growth Factor Receptor; HER2, HER4, Human Epidermal growth factor Receptor 2, -4; IGFR, Insulin-like Growth Factor Receptor; InsR, Insulin Receptor; KDR, Kinase insert Domain Receptor; PDGFRα, and PDGFRβ, Platelet-Derived Growth Factor Receptor-α and -β). The results showed only 1 and 3 that have weak activity against InsR.

• Journal of Digestive Cancer Research
• /
• 제1권1호
• /
• pp.24-28
• /
• 2013

위암은 최근 50년간 5년 생존율에 있어서 미약하게만 상승되었다. 이에 따라 위암에 대한 분자생물학적 치료에 대한 여러 연구가 진행되고 있다. 이에 진행성, 전이성 위암에서의 분자생물학적 치료에 대해 살펴보고자 한다. 위암의 분자생물학적 치료의 타켓으로는 EGFR (Epidermal growth factor receptor), HER(Human epidermal growth factor receptor), VEGF (Vascular endothelial growth factor receptor)를 들 수 있다. 대표적으로 분자생물학적 치료 중 trastuzumab은 HER2과발현 환자에게 유용하게 사용될 수 있어, 기존 항암화학요법에 복합투여해 볼 수 있다. Trastuzumab와 그 밖의 여러 분자생물학적 제재에 대해 본 연구에서 살펴보고자 한다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제36권3호
• /
• pp.177-185
• /
• 2010

Introduction: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. Materials and Methods: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/ immunofluorescent analyses. Results: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. Conclusion: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제28권3호
• /
• pp.193-201
• /
• 2006

Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

• 대한의생명과학회지
• /
• 제8권4호
• /
• pp.229-234
• /
• 2002

Chlorella is rich in chlorella growth factor (CGF). A review of the literature has described that CGF improves the capability of a Th1-based immunity, anticancer, antioxidant antibacterial activity, growth promotion, wound healing and so on, but has not studied the effect for the metabolism and the proliferation of human skin keratinocyte. The aim of this study was to examine the effect of metabolism and the proliferation of human skin keratinocyte in vitro. CGF was extracted with an autoclaving method which is a modified hot-water extraction method from dried chlorella and conformed by means of absorbance 0.22 at 260 nm. We have measured the extracellular acidification rate (ECAR) of the CGF by Cytosensor$^{\circledR}$ Microphysiometer and evaluated responsiveness depending upon the dosage on the HaCaT cell. The ECAR for the concentrations of 0.15, 1.5, 15, 150 $\mu\textrm{g}$/ml of CGF increased as a 103.6, 128.2, 149.0 and 423.9%, respectively compared to control (0.0 $\mu\textrm{g}$/ml, 100% ECAR). The ECAR for ErbBl tyrosine kinase inhibited by 4-anilinoquinazolines, $C_{16}$H$_{14}$BrN$_3$O$_2$.HCl on tile HaCaT cells with the amounts of 10 $\mu\textrm{g}$/ml of the CCF compared with 100 $\mu\textrm{g}$/ml of rhEGF. The conclusion of the study is that CGF might increase human epidermal keratinocyte proliferation through the interaction between the epidermal growth factor receptor and itself.

• 대한의생명과학회지
• /
• 제12권3호
• /
• pp.249-254
• /
• 2006

It has been reported that liver is a very important organ to xenotransplantation. Pig is known to be a most suitable species in transplantation of human organs. However, the physiological function of pig hepatocytes is not clear elucidated. Epidermal growth factor (EGF) is known to be a mitogen in various cell systems. Thus, we examined the effect of EGF on cell proliferation and its related signal cascades in primary cultured pig hepatocytes. EGF stimulates cell proliferation in a dose (>1ng/ml) dependent manner. EGF-induced increase of $[^3H]-thymidine$ incorporation was blocked by AG 1478 ($10^{-6}M$, an EGF receptor antagonist) genistein and herbymycin A (tyrosine kinase inhibitors, $10^{-6}M$), suggesting the role of activation and tyrosine phosphorylation of EGF receptor. In addition, EGF-induced increase of $[^3H]-thymidine$ incorporation was prevented by neomycin $(10^{-4}M)$, U73122 $(10^{-5}M)$ (phospholipase C [PLC] inhibitors), staurosporine ($(10^{-8}M)$, or bisindolylmaleimide I $(10^{-6}M)$ (protein kinase C [PKC] inhibitors), suggesting the role of PLC and PKC. Moreover, EGF-induced increase of $[^3H]-thymidine$ incorporation was blocked by PD 98059 (a p44/42 mitogen activated protein kinase [MAPK] inhibitor), SB 203580 (a p38 MAPK inhibitor), and SP 600125 (a JNK inhibitor). EGF increased the translocation of PKC from cytosol to membrane fraction and activated p42/44 MAPK, p38 MAPK and JNK. In conclusion, EGF stimulates cell proliferation via PKC and MAPK in cultured pig hepatocytes.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권14호
• /
• pp.5647-5654
• /
• 2015

Gall bladder cancer (GBC) is a gastro-intestinal cancer with high prevalence among north Indian women. Platelet derived growth factor-B (PDGFB) and human epidermal growth factor receptor-2 (HER2) may play roles in the etiology of GBC through the inflammation-hyperplasia-dysplasia-carcinoma pathway. To study the association of PDGFB and HER2 polymorphisms with risk of GBC, 200 cases and 300 controls were considered. PDGFB +286A>G and +1135A>C polymorphisms were investigated with an amplification refractory mutation system and the HER2 $Ile^{655}Val$ polymorphism by restriction fragment length polymorphism. Significant risk associations for PDGFB +286 GG (OR=5.25) and PDGFB +1135 CC (OR=3.19) genotypes were observed for GBC. Gender wise stratification revealed susceptibility for recessive models of PDGFB +1135A>C (OR=3.00) and HER2 $Ile^{655}Val$ (OR=2.52) polymorphisms among female GBC cases. GBC cases with gall stones were predisposed to homozygous +286 GG and +1135 CC genotypes. Significant risk associations were found for ACIle (OR=1.48), GAVal (OR=1.70), GAIle (OR=2.00) haplotypes with GBC cases and GCIle haplotype with female GBC cases (OR=10.37, P=<0.0001). Pair-wise linkage disequilibrium revealed negative associations among variant alleles. On multi-dimensional reduction analysis, a three factor model revealed significant gene-gene interaction for PDGFB +286A>G, PDGFB +1135A>C and HER2 Ile165Val SNPs with GBC. Protein-protein interaction showed significant association of PDGFB and HER2 with the epidermal growth factor receptor signaling pathway.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권3호
• /
• pp.903-907
• /
• 2015

Background: Among human epidermal growth factor receptor 2 (HER2)-positive breast cancer, more than half are also hormone receptor (HR)-positive. Although HR is a predictive factor for the efficacy of hormone therapy, there are still some uncertainties in regard to the effects on patients with HR-positive and HER2-positive metastatic breast cancers due to the potential resistance to hormone therapy caused by co-expression of HR and HER2. There are no clinical trials directly comparing the efficacy of hormonal therapy with chemotherapy. Materials and Methods: To examine the real-world effect of hormone therapy on patients with HR-positive and HER2-positive metastatic breast cancers, a cross-sectional study of a representative sample of the Chinese population was conducted. The study included 113 patients who received first-line and second-line palliative treatment between 2005 and 2010 in the Cancer Institute and Hospital, Chinese Academy of Medical Science. The effect of hormone therapy on overall survival (OS) was studied. Results: The patients who received hormone therapy (n=51) had better overall survival in contrast to those who received chemotherapy with anti-HER2 therapy (n=62) in first- or second-line treatment. The difference was of borderline statistical significance (51.8m vs 31.9m, p=0.065). In addition, the effect of hormone therapy did not differ significantly with other prognostic factors, including age (${\leq}50$ years or >50 years), disease free survival (${\geq}2$ years or < 2 years) and site of metastasis (visceral or bone/soft tissue). On multivariate analysis, administration of hormone therapy was associated with a trend toward a favorable prognosis (p=0.148, HR=0.693, 95%CI 0.422-1.139). Age more than 50 years was the sole independent harmful prognostic factor (p<0.001, HR=2.797, 95%CI 1.676-4.668). Conclusions: Our data suggest that hormonel therapy may improve outcomes of the patients with ER-positive and HER2-positive metastatic breast cancer.

• Tuberculosis and Respiratory Diseases
• /
• 제76권3호
• /
• pp.120-126
• /
• 2014

Background: We investigated whether wogonin and apigenin significantly affect the epidermal growth factor receptor (EGFR) signaling pathway involved in MUC5AC mucin gene expression, and production from cultured airway epithelial cells; this was based on our previous report that apigenin and wogonin suppressed MUC5AC mucin gene expression and production from human airway epithelial cells. Methods: Confluent NCI-H292 cells were pretreated with wogonin or apigenin for 15 minutes or 24 hours and then stimulated with epidermal growth factor (EGF) for 24 hours or the indicated periods. Results: We found that incubation of NCI-H292 cells with wogonin or apigenin inhibited the phosphorylation of EGFR. The downstream signals of EGFR such as phosphorylation of MEK1/2 and ERK1/2 were also inhibited by wogonin or apigenin. Conclusion: The results suggest that wogonin and apigenin inhibits EGFR signaling pathway, which may explain how they inhibit MUC5AC mucin gene expression and production induced by EGF.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권7호
• /
• pp.4115-4119
• /
• 2013

Background: Previous reports have shown that human epidermal receptor (HER)-3 overexpression may be associated with poor prognosis in patients with breast cancer, but results have been conflicting. In this study, we sought to investigate the prognostic significance of HER-3 immunohistochemical expression in patients with metastatic breast cancer. Methods: We retrospectively analyzed HER-3 immunohistochemical expression profiles in 45 paraffin-embedded specimens from patients who had been treated between 1996 and 2006 in the Department of Oncology of the Uludag University School of Medicine, Bursa, Turkey. Membranous or cytoplasmic dominant expression patterns of HER-3 were analyzed using the Rajkumar score and a cytoplasmic 4-point scoring system, respectively. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. Results: The median PFS in the study participants was 9 months (interquartile range: 4.5-13 months), whereas the median OS was 20 months (interquartile range: 7.5-28 months). Categorization of the patient population according to HER-3 positive immunohistochemical expression did not reveal any statistically significant difference in terms of both PFS (p=0.70) and OS (p=0.81). The results of multivariable Cox regression analysis indicated that tumor size was the only independent predictor of PFS, whereas estrogen and progesterone receptor status was independently associated with OS. Conclusions: HER-3 immunohistochemical expression did not correlate with outcomes in Turkish patients with metastatic breast cancer. Although our results suggest that HER-3 expression in cancer specimens is not of prognostic significance, further prospective studies are warranted to confirm these results.