• Natural Product Sciences
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• v.27 no.2
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• pp.134-139
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• 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
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• v.1 no.1
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• pp.24-28
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• 2013

The five-year survival for patients with gastric cancer improved only modestly over the last 50 years. So, several studies about molecular target chemotherapy were investigated. We reviewed about molecular target chemotherapy for advanced unresectable and metastatic gastric cancer, which has developed recently. EGFR (Epidermal growth factor receptor), HER (Human epidermal growth factor receptor), VEGF (Vascular endothelial growth factor receptor) can be the target of therapy for gastric cancer. Patients with advanced gastric adenocarcinoma who are potential candidates for trastuzumab should have their tumors assayed for the presence of HER2 overexpression utilizing tumor-specific criteria and/or gene amplification. We suggest the addition of trastuzumab to chemotherapy in patients with HER2-positive tumors (as defined by 3+ immunohistochemical staining or FISH positivity), as long as they do not have a contraindication to trastuzumab. Except for trastuzumab, we summarized several studies for molecular target agents which were not validated yet.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.3
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• pp.193-201
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• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.2
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• pp.110-122
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• 2005

Adenoid cystic carcinoma (ACC) of salivary glands has a protracted clinical course with perineural invasion, delayed onset of hematogenous metastasis, and poor responses to classical cytotoxic chemotherapic agents. Most deaths from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the dissemination of metastatic cells is important for the design of more effective therapy of salivary cancer. I determined in vitro expression of epidermal growth factor receptor (EGFR) and its downstream effectors and vascular endothelial growth factor receptor (VEGFR)-2 on a human salivary ACC cell line (ACC2). I also evaluated the expression of EGF and VEGF signaling molecules and metastasis-related proteins on human salivary ACC cells orthotopically growing in nude mice. In Western blot and immunohistochemical analyses, EGFR and VEGFR-2 were presented and phosphorylated in ACC2 cells. In human parotid cancer xenografts in nude mice, EGF and VEGF signaling molecules, IL-8, and MMP-9 were expressed at markedly higher levels than in normal parotid tissues. Moreover, tumor-associated endothelial cells of this orthotopic parotid tumor expressed phosphorylated VEGFR-2 and phosphorylated Akt, which is a cell-survival protein. These data show that those biomarkers can be molecular targets for therapy of salivary ACC, which has a propensity for delayed lung metastasis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.4
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• pp.334-340
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• 1998

Stimulatory effects of epidermal growth factor (EGF) and transforming growth $factor-{\alpha}$($TGF-{\alpha}$) on the growth of squamous cancer cell lines established from human oral cancer tissue with moderate differentiation were studied in vitro. After culturing in serum-free media for 24 hours, growth factors-EGF only, $TGF-{\alpha}$ only and EGF, $TGF-{\alpha}$ together-were added to the media and numbers of cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and compared with the control at 96, 144 hours. Each of EGF and $TGF-{\alpha}$ showed statistically significant stimulatory effects on the growth of cells respectively. Dose-dependent relationship of the stimulatory effects were not clearly demonstrated. The effects of EGF were higher than those of $TGF-{\alpha}$ and combinative administration showed higher effects than those of single uses. In conclusion, EGF may play an important and major role in differentiation and growth of human oral squamous cancer cells. $TGF-{\alpha}$, produced from cells activated by EGF, also can stimulate the cell growth and could be an alternative ligand for EGF receptor.

• Biomedical Science Letters
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• v.8 no.4
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• pp.229-234
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• 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.

• Radiation Oncology Journal
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• v.34 no.1
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• pp.1-9
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• 2016

Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5647-5654
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• 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.

• Tuberculosis and Respiratory Diseases
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• v.76 no.3
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• pp.120-126
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• 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.

• Korean Journal of Veterinary Research
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• v.43 no.2
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• pp.211-218
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• 2003

Human ovarian cancerous cells survive in a way that they trigger the nucleotide excision repair (NER) or double-strand DNA repair (dsDNA) repair mechanism to show resistance to anticancer drugs and activate many kinds of repair protein, thus removing damaged DNAs. Two experiments on the PA-1 human ovarian teratocareinoma cell line that hardly has any expression of epidermal growth factor receptor (EGFR) were conducted in the study; first, EGF-R was transfected and its receptor was obtained. The receptor was investigated in terms of its mutual relations with many kinds of protein concerning NER or dsDNA repair. Second, it was examined what kind impact cisplatin and adriamycin had on the effects of EGF-R over the PA-1 cell line lacking EGF-R. When being administered with cisplatin and adriamycin, Hey and Hey C2 cell lines showed a high level of resistance while PA-1 cell line a high level of sensitivity. Hey and Hey C2 cell lines that are resistant against anticancer drugs exhibited a high level of EGF-R expression while PA-1 cell line that is sensitive to them did a much lower level of the expression. When PA-1 cell line was transfected for the expression of DNA adduct and EGF-R, it showed a higher level of resistance compared to the control group. There was no difference in the expression of DNA repair proteins (DNA- dependent protein kinase, Ku70, and Ku80) between Hey and the PA-1 cell lines. The results indicate that the Hey cell line that is resistant against cisplatin and adriamycin works along the signaling system responding to the changes of EGF-R while the PA-1 cell line that is sensitive to both of them does to the lack of EGF-R.