• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1609-1615
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• 2016

Breast cancer is one of among all cancers with increased incidence, high mortality rate, and high economic and social costs. The the most common type of cancer among females worldwide, breast cancer is actually the uncontrolled proliferation of cells which attain malignancy. Recently it has shown that breast cancer contributes 11% among all types of cancer diagnosed globally on an annual basis and it is one of the leading causes of death among women. The human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine-protein kinase erbB-2 normally involved in the proliferation and division of breast cells. In some abnormal cases the HER2 gene does not work correctly and makes too many copies of itself. HER2-positive (HER2+) breast cancers constitute an aggressive type of breast cancer and tend to grow faster and are more likely to spread. However, therapies that specifically target HER2, such as Herceptin$^{(R)}$ (traztuzumab), are very effective. HER2 targeted therapies, has significantly improved the therapeutic outcome for patients with HER2 positive breast cancer.

• Bulletin of the Korean Chemical Society
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• v.30 no.8
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• pp.1827-1831
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• 2009

Ligand molecules that can recognize and interact with cancer cell surface marker proteins with high affinity and specificity should greatly aid the development of novel cancer diagnostics and therapeutics. HER-2/ErbB2/Neu (HER-2), a member of the epidermal growth factor receptor family, is specifically overexpressed on the surface of breast cancer cells and serves as both a useful biomarker and a therapeutic target for breast cancer. In this study, we aimed to isolate RNA aptamers that specifically bind to a HER-2-overexpressing human breast cancer cell line, SK-BR-3, using Cell-SELEX strategy. The selected aptamers showed strong affinity to SK-BR-3, but not to MDAMB- 231, a HER-2-underexpressing breast cancer cell line. In addition, we confirmed the specific targeting of HER-2 receptor by aptamers using an unrelated mouse cell line overexpressing human HER-2 receptor. The HER-2-targeting RNA aptamers could become a useful reagent for the development of breast cancer diagnostics and therapeutics.

• Journal of Preventive Medicine and Public Health
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• v.28 no.2 s.50
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• pp.487-496
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• 1995

This study was performed for the comparison of the therapeutic efficiency between 6-month (2HERZ/4HER) and 9-month (9HER) short-course chemotherapy under the programe conditions for pulmonary tuberculosis in terms of sputum AFB negative conversion rate, remedial interruption rate and cost effectiveness analysis. Two hundreds and ninty three patients treated with 9HER and 641 treated with 2HERZ/4HER had been discharged from 22 health centers in Seoul from May 1, 1993 to April 30, 1994. Seven hundreds and seventeen was subsequently analysed excluding 217 patients due to remedial interruption. The results : 1. Bacteriological negative conversion rate in 9HER regimen and 2HERZ/4HER regimen was 97.8% and 96.4% respectively(p>0.05). But the early treatment period, negative conversion rate in 2HERZ/4HER regimen was very higher than in 9HER regimen(p<0.01). 2. Remedial interruption rate for 9HER regimen and 2HERZ/4HER regimen was 34.1% and 13.6% respectively. The primary reason for the interruption was transfering to other clinics and this interruption was high within 3months. 3. Cost effectiveness for 2HERZ/4HER regimen was higher than 9HER regimen. The difference cost effectiveness ratio was 2.33 at the first sputum test and 1.69 at the last sputum test.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7695-7700
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• 2015

Background: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. Materials and Methods: This study was conducted from 2008-2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results. Results: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3%) and 246 were CISH negative (73.7%). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9% concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90% and 53.8%, respectively. Conclusions: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing.

• BMB Reports
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• v.45 no.12
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• pp.719-723
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• 2012

A close association between the obesity hormone leptin and breast cancer progression has been suggested. The present study investigated the molecular mechanism for enhanced leptin expression in breast cancer cells and its functional significance in breast cancer aggressiveness. We examined whether leptin expression level is affected by the oncoprotein human epidermal growth factor receptor2 (HER2), which is overexpressed in ~30% of breast tumors. Here, we report, for the first time, that HER2 induces transcriptional activation of leptin in MCF10A human breast epithelial cells. We also showed that p38 mitogen-activated protein kinase signaling was involved in leptin expression induced by HER2. We showed a crucial role of leptin in the invasiveness of HER2-MCF10A cells using an siRNA molecule targeting leptin. Taken together, the results indicate a molecular link between HER2 and leptin, providing supporting evidence that leptin represents a target for breast cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8395-8400
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• 2014

In Saudi Arabia, cancer of breast is ranked the most frequent neoplasm and second source of cancer death in the female population. Breast cancer (BC) fast diagnosis, prognosis and medication management necessitate, these days, immunohistochemistry (IHC) assessment of hormone receptors and HER2 expression profile. The present report defines the IHC profile of ER, PR and HER2 in Saudi female breast neoplasms of ductal and lobular types and associations ER, PR and HER2 expression patterns with various clinicopathological factors (age, type of tumor, size, laterality, histological grade, and involvement of axillaries lymph nodes). Ninety nine cases of breast tumors were recruited from the pathology department archive of King Abdulaziz University Hospital, Kingdom of Saudi Arabia. ER, PR and HER2 expression was assessed using IHC staining. Ductal carcinomas with a variety of histological grades constituted 88 (88.8%) of total cases. Seventy four (77.8%), 59 (62.1%), and 35 (36.8%) of ductal carcinomas showed positive staining for ER, PR and HER2, in that order. Remaining breast cancer cases were four (4%) lobular carcinomas and two (2%) mixed form of ductal and lobular types, which were ER+, PR+, and HER2-. Breast cancer expression pattern of ER, PR and HER2 in Saudi female is different from that of Tunisian and Jordanian female populations and closer to the expression pattern of Egyptian, Lebanese, Iraqi and western country females. Furthermore, the present study found two IHC patterns of breast cancer ER+/PR-/HER2+ (5%) and ER+/PR-/HER2- (11.1%), which had not been reported in other Arabic studies. Thus the rates of IHC expression patterns in breast cancer show some variation among Arabic female populations.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2891-2896
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• 2012

Background: HER2/neu, a member of EGFR family, is over expressed in some tumors. The purpose of this study was to determine the salivary level and tissue expression of HER2/neu in patients with head and neck squamous cell carcinoma (HNSCC) and any correlation with clinicopathologic parameters. Methods: An enzyme-linked immunosorbent assay (ELISA) was used to evaluate the salivary level and immunohistochemistry (IHC) to assess tissue expression of HER2/neu in 28 patients with HNSCC and 25 healthy controls. Results: The salivary levels of HER2/neu in HNSCC patients was not significantly higher than in the healthy controls (p>0.005). There was no apparent correlation in salivary HER2/neu level with clinicopathological features such as age, sex, grade, tumor size and nodal status. All HNSCC specimens were positive (membranous or/and cytoplasmic) for HER2/neu, except one sample. Only one HNSCC specimen was stained in cytoplasm purely. All control specimens were membranous and cytoplasmic positive for HER2/neu. There was a significant difference between cytoplasmic staining in case and control groups (p-value<0.05). Conclusion: In our cases, no overexpression of HER2/neu was observed. Thus, our findings suggested that the use of Her-2 as a salivary marker of HNSCC cannot be recommended.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9355-9360
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• 2014

Background: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. In this study, we evaluate the efficacy of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting HER2 expression profile in OSCC model in rat. Results: DOX-MTX- nanoparticle complexes caused significant decrease in mRNA level of HER2 compared to untreated cancers (p<0.05) and this finding was more pronounced with the IV mode (p<0.000). Surprisingly, HER2 mRNA was not affected in DOX treated as compared to the control group (p>0.05). On the other hand, in the DOX-MTX NP treated group, fewer tumors characterized with advanced stage and decreased HER2 paralleled improved clinical outcome (P<0.05). Moreover, the effectiveness of the oral route in the group treated with nanodrug accounted for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Furthermore, there was no significant difference in mRNA level of HER2 (p>0.05). Conclusions: Influence of HER2 gene expression is a new feature and mechanism of action observed only in dual action DOX-MTX-NPs treated groups. Down-regulation of HER2 mRNA as a promising marker and prognosticator of OSCC adds to the cytotoxic benefits of DOX in its new formulation. Both oral and IV application of this nanodrug could be used, with no preferences in term of their safety or toxicity. As HER2 is expressed abundantly by a wide spectrum of tumors, i DOX-MTX NPs may be useful for a wide-spectrum of lesions. However, molecular mechanisms underlying HER2 down regulation induced by DOX-MTX NPs remain to be addressed.

• Biomedical Science Letters
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• v.21 no.1
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• pp.23-31
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• 2015

Recently, specific antibodies have been used extensively to diagnose and treat various diseases. It is essential to assess the efficacy and specificity of antibodies, especially the in vivo environment. Anti-HER-2/neu mAb was evaluated as a possible transporting agent for radioimmunotherapy. The monoclonal antibody was successfully radio-labeled with $^{131}I$. In vitro binding assays were performed to confirm its targeting ability using another radio-iodine, $^{125}I$. Binding percentage of $^{125}I$ labeled anti-HER-2/neu mAb in HER-2/neu expressing CT-26 cells was found to be 4.5%, whereas the binding percentage of $^{125}I$ labeled anti-HER-2/neu mAb in wild-type CT-26 was only 0.45%. In vivo images were obtained and analyzed through $\gamma$-camera and an optical fluorescent modality, IVIS-200. $\gamma$-camera images showed that $^{131}I$ labeled anti-HER-2/neu mAb accumulated in HER-2/neu CT-26 tumors. Optical imaging based on near infrared fluorescence labeled anti-HER-2/neu mAb showed higher fluorescence intensities in HER-2/neu CT-26 tumors than in wild-type CT-26 tumors. Anti-HER-2/neu mAb was found to specifically bind to its receptor expressing tumor. Our study demonstrates that in vivo imaging technique is a useful method for the evaluation of an antibody's therapeutic and diagnostic potentials.

• Journal of English Language & Literature
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• v.64 no.2
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• pp.239-252
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• 2018

Many critics on William Faulkner's As I Lay Dying have read Addie Bundren as the disrupter of patriarchal power. By raising a question about the usefulness of language, which is the symbolic power of patriarchy and having an affair with the preacher Whitfield outside her wedlock, Addie directly challenges patriarchal power. From a quite different vantage point, however, we can read Addie as the faithful protector of the norm of whiteness in the South in light of the social hierarchy. As a former school teacher, Addie is from middle class before her marriage. By her marriage to Anse, who is a lower-class white, Addie has class anxiety that her social status in the stratum of whiteness could be degraded from a middle to a lower-class white, "white trash," which means that she is not white enough to be considered as the normative whiteness. Especially, Addie's anxiety increases due to the fact that her lazy husband is reluctant to work and relies on her neighbors, causing her family to be entrapped at the bottom in the stratum of whiteness. Therefore, she decides to take revenge on her husband after giving birth to her second child Darl by asking Anse to bury her dead body in her familial burial site in Jefferson. By rendering her family to suffer the hardship during her funeral procession, not only does she succeed in taking revenge on Anse on the surface, she regains her social status as a middle-class white by being buried in Jefferson fundamentally.