• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.77-80
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• 2016

Oral squamous cell carcinoma (OSCC) is one of the ten most common causes of cancer death worldwide. Assessment of molecular changes can help detect and control lesions. The aim of this study was evaluation of salivary levels of ErbB2 and CEA in OSCC patients. In this case-control study, 27 OSCC patients and 26 healthy controls participated. After obtaining consent and filling out a questionnaire, unstimulated saliva samples were collected from people in the morning for measurement of the two markers using ELISA. Data were analyzed using Mann Whitney U test in SPSS 19 software with P<0.05 considered significant. Subjects were in the age range of 40 to 65 years. \Salivary level CEA was elevated in OSCC samples ($42.6{\pm}21.1ng/ml$) as compared to those of controls ($22.6{\pm}22.1ng/ml$) (p< 0.01), but no significant variation was noted for ErbB2 ($5.2{\pm}1.8ng/ml$ and $4.93{\pm}2.14ng/ml$, p=0.28). The role of ErbB2 as a tumor marker in patients with OSCC must still be regarded as controversial and needs further studies to clarify any significance for early detection or screening. In contrast the salivary level of CEA may find application for early detection of patients.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.523-532
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• 1999

Background: With the development of the molecular biological methods, studies of the early diagnosis of lung cancer and the detection in the preneoplastic state by using genetic probes in the high risk groups are widely investigated. In lung cancer, squamous cell carcinoma is considered to progress from the normal bronchial mucosa to the preneoplastic state, and finally to the invasive carcinoma. In this study, we investigated the expression of p53 and c-erbB2 in the normal bronchi and the cancer tissues in patients with squamous cell lung cancer to evaluate the possibility of using these immunohistochemical markers as the diagnostic and prognostic parameters of patients with squamous cell lung cancer. Method: The normal and cancerous bronchial tissues of 25 patients with squamous cell carcinoma of the lung, surgically resected from May 1995 to November 1996, were immunohistochemically stained with the monoclonal antibodies to p53(DAKO-p53) and c-erbB2(phamingen 15821A) respectively. We compared the expression status of these markers between the normal bronchial mucosa and the tumor tissue, and also investigated the relationship between the expression status of these markers in tumor tissues and the pathological stage, and the survival time. Results: The pathological stage was as follows; stage I, II were found in 5 patients respectively, stage IIIA was in 8 patients, stage IIIB was in 4 patients, and stage IV was in 3 patients. The expression rate of p53 in the squamous cell lung cancer was 48%, and it was not expressed in the normal bronchial mucosa. The expression status was increased as the pathological stage advanced(p=0.0091 by test of trend). But there were no relationship between the expression of p53 and the median survival time. C-erbB2 did not yield a significantly meaningful result. Conclusion: p53 was not found in the normal bronchial mucosa, but it was expressed in 48% of the tumor tissue. And the expression rate increased as the pathological stage advanced. So it would be helpful to apply the immunochistochemical stain with p53 in the bronchial biopsy specimen in the early diagnosis trial or staging of squamous cell lung cancer.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.162-168
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• 2001

Background: Inverted papilloma(IP) of the nasal cavity and paranasal sinuses is a benign neoplastic condition that can be associated with squamous cell carcinoma (SCC). Several studies have indicated an etiologic role for viruses in the development of inverted papilloma. And it is necessary to find out the significance of a biologic markers such as p53, c-erbB-2 to predict the malignant potential. The purposes of this study are to detect HPV in inverted papilloma of the nasal cavity and paranasal sinus, to examine role of HPV as an etiological agent, to examine the relationship between HPV subtype and malignant transformation of inverted papilloma, and to investigate the relation between expression rate of p53, c-erbB-2 and HPV in recurrent or malignant transformation cases. Material and Methods: Thirty two cases of inverted papilloma(IP) in the nasal cavity and paranasal sinuses were reviewed and classified into 3 groups; simple IP, IP with dysplasia group, IP with squamous cell carcinoma group. Paraffin embedded achival tissue was used in this study. The HPV was detected by in situ hybridzation (ISH) using HPV type 6/11, 16/18, 31/33/35 DNA probes. Expression of p53 and c-erbB-2 was examined by immunohistochemical staining. Results: 1) The HPV was detected in 6(19%) out of 32 cases. 2) The HPV 6/11 was dectected in 4 out of 21 cases of simple IP, HPV 16/18 in 1, HPV 31/33/35 in lout of 8 cases of IP with dysplasia respectively. 3) The positive expression of p53 was 13 cases out of 32 cases; 2 out of 21 cases of simple IP, all of 8 cases of IP with dysplasia and 3 cases of IP with squamous cell carcinoma 4) The positive expression of c-erbB-2 was in 24 out of 32 cases; 16 out of 21 cases of simple IP, 6 out of 8 cases of IP with dysplasia, 2 out of 3 cases of IP with squamous cell ca. 5) The recurrence of IP occurred in lout of 6 cases of positive for HPV, in 4 out of 26 cases negative for HPV. 6) The recurrence of IP occurred only in positive cases for p53. 7) The recurrence of IP occurred in 4(17%) out of 24 cases positive for c-erbB-2, in 1(13%) out of 8 cases negative for c-erbB-2. Conclusion: The p53 expression was associated with Inverted papillomas exhibiting evidence of malignant transformation. Also, there was a correlation between the p53 expression and recurrence.

• BMB Reports
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• v.53 no.3
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• pp.133-141
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• 2020

The epidermal growth factor receptor (EGFR), a member of the ErbB family (EGFR, ErbB2, ErbB3 and ErbB4), plays a crucial role in regulating various cellular responses such as proliferation, differentiation, and survival. As a result, aberrant activation of EGFR, mostly mediated through different classes of genomic alterations occurring within EGFR, is closely associated with the pathogenesis of numerous human cancers including lung adenocarcinoma, glioblastoma, and colorectal cancer. Thus, specific suppression of oncogenic activity of mutant EGFR with its targeted drugs has been routinely used in the clinic as a very effective anti-cancer strategy in treating a subset of tumors driven by such oncogenic EGFR mutants. However, the clinical efficacy of EGFR-targeted therapy does not last long due to several resistance mechanisms that emerge in the patients following the drug treatment. Thus, there is an urgent need for the development of novel therapeutic tactics specifically targeting mutant EGFR with the focus on the unique biological features of various mutant EGFR. Regarding this point, our review specifically emphasizes the recent findings about distinct requirements of receptor dimerization and autophosphorylation, which are critical steps for enzymatic activation of EGFR and signaling cascades, respectively, among wildtype and mutant EGFR and further discuss their clinical significance. In addition, the molecular mechanisms regulating EGFR dimerization and enzymatic activity by a key negative feedback inhibitor Mig6 as well as the clinical use for developing potential novel drugs targeting it are described in this review.

• 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.

• Journal of Nutrition and Health
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• v.38 no.8
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• pp.656-662
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• 2005

Ginger (Zingiber of oficinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. Besides its extensive use as a spice, the rhizome of ginger has also been used in traditional oriental herbal medicine for the management of symptoms such as common cold, digestive disorders, rheumatism, neurologia, colic, and motion-sickness. The oleoresin from rhizomes of ginger contains [6] -gingerol (1- [4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) and its homologs as pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, analgesic, antipyretic, antiheatotoxic, and cardiotonic effects. However, the effect of [6]-gingerol on cell proliferation in breast cancer cell are not currently well known. Therefore, in this study, we examined effect of [6]-gingerol on protein and mRNA expression associated with cell proliferation in MDA-MB-231 human breast. cancer cell lines. We cultured MDA-MB-231 cells in presence of 0, 2.5, 5 and $10{\mu}M$ of [6] -gingerol. [6]-Gingerol inhibited breast cancer cell growth in a dose-depenent manner as determined by MTT assay. ErbB2 and ErbB3 protein and mRNA expression were decreased dose-dependently in cells treated with [6]-gingerol (p<0.05). In addition, phosphorylated Akt levels and total hぉ levels were markedly decreased in cells treated with $2.5{\mu}M$ [6]-gingerol (p<0.05). In conclusion, we have shown that [6]-gingerol inhibits cell proliferation through ErbB2 and ErbB3, reduction in MDA-MB-231 human breast cancer cell lines.

• Biomedical Science Letters
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• v.13 no.3
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• pp.213-221
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• 2007

This study was designed to investigate the correlation between the expression rate of p53 and p21 proteins, c-erbB-2 oncoprotein and $TGF-{\beta}1$ and tumor prognostic factors in colon cancer including the tumor size, histological differentiation and Dukes' stage. The expression rate of p53 protein was 11.4% (4 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation. In other words, the poorer differentiation, the higher the expression rate of p53 protein (P<0.05). The expression rate of p21 protein was 17.1% (6 cases) at well differentiation, 40.0% (14 cases) at moderately differentiation, and 8.6% (3 cases) at poorly differentiation, indicating that, as the histological malignant degeneration progressed, the expression rate of p21 protein decreased distinctively (P<0.05). However, the correlation of the above mentioned proteins with tumor size and Dukes' stage was not recognized. The expression rate of c-cerbB-2 oncoprotein was 11.4% (4 cases) at well differentiation, 54.3% (19 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation, indicating that the poorer differentiation, the higher expression rate of c-erbB-2 oncoprotein (P<0.05). The expression rate of $TGF-{\beta}1$ was 17.1% (6 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 11.4% (4 cases) at poorly differentiation. As Dukes' stage progressed, the expression rate of $TGF-{\beta}1$ was 8.6% (3 cases) in stage A, 20.0% (7 cases) in stage B, 37.1 % (13 cases) in stage C, and 11.4% (4 cases) in stage D. There was a difference in expression rates between Dukes' stages (P<0.05). In 10 cases, p53 protein was positive while p21 protein was negative, and in 6 cases, p53 protein was negative whereas p21 was positive (P<0.05). Therefore, a statistically significant inverse correlation between the expression rate of p53 protein and that of p21 protein was observed. In conclusion, since there was a signigicant correlation between histological differentiation of colon cancer and the expressions of p53 and p21 proteins and c-erbB-2 oncoprotein, and between Dukes' stage and the expression of $TGF-{\beta}1$, it was conformed that the overexpression of p53 and p21 proteins, c-erbB-2 oncoprotein, and $TGF-{\beta}1$ is closely associated with the occurrence of colon cancer and its progress. Accordingly, this study may be greatly beneficial to the presumption of diagnosis, treatment and prognosis of colon cancer patients.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.5
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• pp.405-416
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• 2007

Objective : Lots of papers have revealed that tumor growth related factors such as EGF, EGFR, c-erbB-2 play an important role in tumorigenesis and proliferation. These factors are found in most tumors of ectodermal origin. But, documentations of tumor growth related factors on salivary gland tumors were rare. Therefore, we determined expressions of tumor growth related factors; PCNA, p53, EGF, EGFR, cerbB2(HER-2), Maspin, DMBT-1, N-Ras in representative salivary gland tumors. Materials and methods : A few types of salivary tumors were examined by immunohistochemical assays. Each antibody was applied to specimens of tumors. Specimens were composed of 5 pleomorphic adenomas (PA), 3 mucoepidermoid carcinomas (MEC), 2 adenoid cystic carcinomas (ACC) and 2 squamous cell carcinomas (SCC) from 12 patients. One specimen was selected randomly as negative control. For evaluation of staining intensity, each stained sample was divided into 5 grade; no staining, obscure, weak staining, moderate staining, strong staining. Results : Strong expressions of PCNA were found in all tumors except of PA. EGF was expressed strongly in SCC, ACC sequently. But in both PA and MEC, EGF expression was weak. EGFR and c-erbB-2 expression showed similar patterns in all salivary gland tumor tissues. P53 showed weak expression generally in all salivary gland tumors. DMBT-1 was expressed in SCC rather than in ACC or in MEC. N-Ras showed weak expressions in all salivary gland tumors except of squamous cell carcinoma. Conclusion : Taken together, tumor growth related factors were expressed in salivay tumors as well as mucosal squamous cell carcinoma. Especially EGFR and c-erbB-2 could be candidates as diagnostic markers for estimating clinical grade of salivary gland tumors. But further studies with reliable methods will be needed to confirm the results of this study.

• 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.