• Radiation Oncology Journal
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• v.32 no.4
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• pp.262-265
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• 2014

Tamoxifen and radiotherapy are used in breast cancer treatment worldwide. Radiation recall dermatitis (RRD), induced by tamoxifen, has been rarely reported. Herein, we report a RRD case induced by tamoxifen. A 47-year-old woman had a right quadrantectomy and an axillary lymph node dissection due to breast cancer. The tumor was staged pT2N0; it was hormone receptor positive, and human epidermal growth factor receptor 2 negative. The patient received adjuvant chemotherapy followed by tamoxifen and radiotherapy. After 22 months of tamoxifen, the patient developed a localized heating sensation, tenderness, edema, and redness at the irradiated area of the right breast. The symptoms improved within 1 week without treatment. Three weeks later, however, the patient developed similar symptoms in the same area of the breast. She continued tamoxifen before and during dermatitis, and symptoms resolved within 1 week.

• 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.

• 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.

• Biomedical Science Letters
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• v.25 no.1
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• pp.23-31
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• 2019

The protein kinase $CK2{\alpha}$ (formerly Casein Kinase II) is implicated in tumorigenesis and transformation. However, the mechanisms of $CK2{\alpha}$ activation in breast cancer have yet to be elucidated. This study investigated the mechanisms of $CK2{\alpha}$ activation in estrogen signaling. Estrogen increased reactive oxygen species (ROS) production, $CK2{\alpha}$ activity, and protein expression in estrogen receptor positive ($ER^+$) MCF-7 human breast cancer cells, which were inhibited by the antioxidant N-acetyl-L-cysteine. $H_2O_2$ enhanced $CK2{\alpha}$ activity and protein expression. Human epidermal growth factor (EGF) increased ROS production, $CK2{\alpha}$ activity and protein expression in EGF receptor 2 (HER2)-overexpressing MCF-7 (MCF-7 HER2) cells, but not in MCF-7 cells. Estrogen induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The p38 inhibitor, SB202190, blocked estrogen-induced increases in ROS production, $CK2{\alpha}$ activity and $CK2{\alpha}$ protein expression. The data suggest that ROS/p38 MAPK is the key inducer of $CK2{\alpha}$ activation in response to estrogen or EGF.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9233-9239
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• 2014

Background: We aimed to evaluate the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression discordance in matched pairs of primary breast cancer and lymph node metastasis specimens and determine the effect of discordance on prognosis. Materials and Methods: Among all patients diagnosed with lymph node metastases from 2004 to 2007, primary tumors and paired lymph node metastases were resected from 209 patients. The status of ER, PR, and HER2 expression was analyzed immunohistochemically in 200, 194, and 193 patients, respectively. Discordance was correlated with prognosis. Results: Biomarker discordance between primary tumors and paired lymph node metastases was 25.0% (50/200) for ER status, 28.9% (56/194) for PR status, and 14.0% (27/193) for HER2 status. ER positivity was a significant independent predictor of improved survival when analyzed in primary tumors and lymph node metastases. Patients with PR-positive primary tumors and paired lymph node metastases displayed significantly enhanced survival compared to patients with PR-positive primary tumors and PR-negative lymph node metastases. Patients with ER- and PR-positive primary tumors and paired lymph node metastases who received endocrine therapy after surgery displayed significantly better survival than those not receiving endocrine therapy. Similalry treated patients with PR-negative primary tumors and PR-positive paired lymph node metastases also displayed better survival than those not receiving endocrine therapy. Conclusions: Biomarker discordance was observed in matched pairs of primary tumors and lymph node metastases. Such cases displayed poor survival. Thus, it is important to reassess receptor biomarkers used for lymph node metastases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4113-4117
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• 2012

Breast cancer is a prevalent heterogeneous malignant disease. Gene expression profiling by DNA microarray can classify breast tumors into five different molecular subtypes: luminal A, luminal B, HER-2, basal and normal-like which have differing prognosis. Recently it has been shown that immunohistochemistry (IHC) markers including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2), can divide tumors to main subtypes: luminal A (ER+; PR+/-; HER-2-), luminal B (ER+;PR+/-; HER-2+), basal-like (ER-;PR-;HER2-) and Her2+ (ER-; PR-; HER-2+). Some subtypes such as basal-like subtype have been characterized by poor prognosis and reduced overall survival. Due to the importance of the ER signaling pathway in mammary cell proliferation; it appears that epigenetic changes in the $ER{\alpha}$ gene as a central component of this pathway, may contribute to prognostic prediction. Thus this study aimed to clarify the correlation of different IHC-based subtypes of breast tumors with $ER{\alpha}$ methylation in Iranian breast cancer patients. For this purpose one hundred fresh breast tumors obtained by surgical resection underwent DNA extraction for assessment of their ER methylation status by methylation specific PCR (MSP). These tumors were classified into main subtypes according to IHC markers and data were collected on pathological features of the patients. $ER{\alpha}$ methylation was found in 25 of 28 (89.3%) basal tumors, 21 of 24 (87.5%) Her2+ tumors, 18 of 34 (52.9%) luminal A tumors and 7 of 14 (50%) luminal B tumors. A strong correlation was found between $ER{\alpha}$ methylation and poor prognosis tumor subtypes (basal and Her2+) in patients (P<0.001). Our findings show that $ER{\alpha}$ methylation is correlated with poor prognosis subtypes of breast tumors in Iranian patients and may play an important role in pathogenesis of the more aggressive breast tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6681-6686
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• 2013

Background: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. Methods: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. Results: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). Conclusions: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.74 no.1
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• pp.37-40
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• 2013

Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used for non-small-cell lung cancer patients. Its untoward cutaneous effects are largely well known and developed in many patients treated with EGFR TKIs. However trichomegaly of eyelash is rarely reported. Although trichomegaly is not a drug-limiting side effect, it could be troublesome of continuing the treatment because of cosmetic issue or eyeball irritation by long eyelashes. Therefore clinicians are needed to pay attention to this uncommon effect. We herein describe erlotinib induced trichomegaly of eyelashes in a woman with adenocarcinoma of the lung.

• Journal of Gastric Cancer
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• v.23 no.1
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• pp.224-249
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• 2023

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

• Biomolecules & Therapeutics
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• v.26 no.3
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• pp.322-327
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• 2018

A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.