• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5709-5714
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• 2014

Background: An association between alcohol/tobacco use and risk of metastasis in breast cancer has been clearly shown. Materials and Methods: The present study explored, in 48 samples of tissue from mammary ductal carcinoma (taken from Mexican women with an average age of $58.2{\pm}10.9$ years), the association of risk of metastasis with the status of hormonal receptors and the c-erbB2 protein (by immunohistochemistry) as well as clinical, histopathological and sociodemographic factors. Results: Of 48 patients, 41.6% (20/48) presented with metastasis, 43.8% were positive for the estrogen receptor (RE+), 31.3% for the progesterone receptor (RP+) and 47.7% for c-erbB2 (c-erbB2+). The following combinations were found: RE+/RP+/c-erbB2+ 8.3%, RE+/RP+ 22.9%, RE+/RP- 20.8%, RE-/RP+ 8.3%, RE-/RP-/c-erbB2- 22.9% and RE-/RP- 47.8%. There were 12 patients who used alcohol/tobacco, of which 91.6% did not present metastasis and 81.9% were RE-/RP-. Compared to the RE-/RP-/c-erbB2+, the RE+/RP+/c-erbB2+ group had a 15-fold greater risk for metastasis (95%CI, 0.9-228.8, p=0.05). The carriers of the double negative hormonal receptors had a 4.7 fold greater probability of being (or having been) smokers or drinkers (95%CI, 1.0-20.4, p = 0.03). Conclusions: There was a clear protective effect of using alcohol and/or tobacco, in the cases included in the present study of mammary ductal carcinoma, associated with double negative hormonal receptors. However, this association could be due to a protective factor not measured (Neyman bias) or to a bias inherent in the rate of hospitalization (Berkson fallacy). This question should be explored in a broad prospective longitudinal study.

• Nutrition Research and Practice
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• v.7 no.2
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• pp.89-95
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• 2013

Dietary inorganic sulfur is the minor component in our diet, but some studies suggested that inorganic sulfur is maybe effective to treat cancer related illness. Therefore, this study aims to examine the effects of inorganic sulfur on cell proliferation and gene expression in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured the absence or presence of various concentrations (12.5, 25, or 50 ${\mu}mol/L$) of inorganic sulfur. Inorganic sulfur significantly decreased proliferation after 72 h of incubation (P < 0.05). The protein expression of $ErbB_2$ and its active form, $pErbB_2$, were significantly reduced at inorganic sulfur concentrations of 50 ${\mu}mol/L$ and greater than 25 ${\mu}mol/L$, respectively (P < 0.05). The mRNA expression of $ErbB_2$ was significantly reduced at an inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05). The protein expression of $ErbB_3$ and its active form, $pErbB_3$, and the mRNA expression of $pErbB_3$ were significantly reduced at inorganic sulfur concentrations greater than 25 ${\mu}mol/L$ (P < 0.05). The protein and mRNA expression of Akt were significantly reduced at an inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05), but pAkt was not affected by inorganic sulfur treatment. The protein and mRNA expression of Bax were significantly increased with the addition of inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05). In conclusion, cell proliferation was suppressed by inorganic sulfur treatment through the ErbB-Akt pathway in MDA-MB-231 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2385-2390
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• 2015

Background: Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC. Objectives: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC. Materials and Methods: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records. Results: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC. Conclusions: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6219-6225
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• 2014

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.233-237
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• 2015

Background: Lung cancer is the leading cause of cancer death in Brunei Darussalam, accounting for almost 20% of the total. The epidermal growth factor receptor (EGFR) is a member of the erbB family of tyrosine kinase receptor proteins, which includes c-erbb2(HER2/neu), erb-B3, and erb-B4. EGFR overexpression is found in a third of all epithelial cancers, often associated with a poor prognosis. Materials and Methods: Protein expression of EGFR in 27 cases of lung cancer tissue samples and 9 cases of normal lung tissue samples was evaluated using an immunohistochemical approach. Results: The results demonstrated significant increase and overexpression of EGFR in Bruneian lung cancer tissue samples in comparison to normal lung tissue. However, there was no significant relationship between clinicopathologic variables (age and sex) of patients and EGFR protein expression. Conclusions: EGFR is overexpressed in Bruneian lung cancer patient tissue samples in comparison to normal lung tissue samples. This may indicate that EGFR protein over expression plays an important role in the genesis of this type of cancer in Brunei Darussalam.

• Interdisciplinary Bio Central
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• v.4 no.2
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• pp.3.1-3.7
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• 2012

Epidermal growth factor receptor (EGFR) is a member of the ErbB family (ErbB1-4) of receptor tyrosine kinases (RTKs). EGFR controls numerous physiological functions, including cell proliferation, migration, differentiation and survival. Importantly, aberrant signaling by EGFR has been linked to human cancers in which EGFR and its various ligands are frequently overexpressed or mutated. EGFR coordinates activation of multiple downstream factors and is subject of various regulatory processes as it mediates biology of the cell it resides in. Therefore, many studies have been devoted to understanding EGFR biology and targeting the protein for the goal of controlling tumor in clinical settings. Endocytic regulation of EGFR offers a promising area for targeting EGFR activity. Upon ligand binding, the activated receptor undergoes endocytosis and becomes degraded in lysosome, thereby terminating the signal. En route to lysosome, the receptor becomes engaged in activating various signaling pathways including PI-3K, MAPK and Src, and endocytosis may offer both spatial and temporal regulation of downstream target activation. Therefore, endocytosis is an important regulator of EGFR signaling, and increasing emphasis is being placed on endocytosis in terms of cancer treatment and understanding of the disease. In this review, EGFR signaling pathway and its intricate regulation by endocytosis will be discussed.

• Proceedings of the Zoological Society Korea Conference
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• 1999.10b
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• pp.178.2-178
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• 1999

No Abstract, See Full Text

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

• 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.

• Nutrition Research and Practice
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• v.5 no.4
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• pp.288-293
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• 2011

In this study, we investigated the effects of the ethanol extract of aerial parts of Raphanus sativus L. (ERL) on breast cancer cell proliferation and gene expression associated with cell proliferation and apoptosis in MDA-MB-231 human breast cancer cells. The MDA-MB-231 cells were cultured in the presence or absence of various concentrations (100, 200, or 300 ${\mu}g$/mL) of ERL. ERL significantly decreased cell proliferation after 48 h of incubation (P < 0.05). The protein and mRNA expression of $ErbB_2$ were decreased significantly in a dose-dependent manner (P < 0.05). The protein expression of $ErbB_3$ was decreased significantly at an ERL concentration of 300 ${\mu}g$/mL (P < 0.05), and mRNA expression of $ErbB_3$ was decreased significantly in a dose-dependent manner (P < 0.05). The protein expression of Akt was decreased significantly at the ERL concentration of 200 ${\mu}g$/mL (P < 0.05), and the protein expression of pAkt was decreased significantly in a dose-dependent manner (P < 0.05). The mRNA expression of Akt was decreased significantly at the ERL concentration of 200 ${\mu}g$/mL ERL (P < 0.05). The protein and mRNA expression of Bax were increased significantly at ERL concentrations of 200 ${\mu}g$/mL or higher (P < 0.05). The protein expression of $Bcl_2$ was increased significantly at ERL concentrations of 100 ${\mu}g$/mL or higher (P < 0.05), and mRNA expression of $Bcl_2$ was increased significantly at an ERL concentration of 300 ${\mu}g$/mL (P < 0.05). In conclusion, we suggest that Raphanus sativus, L. inhibits cell proliferation via the ErbB-Akt pathway in MDA-MB-231 cells.