• Journal of Pathology and Translational Medicine
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• v.52 no.6
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• pp.396-403
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• 2018

Background: In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer. Methods: We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012. Results: Patients were divided into two groups according to multiplicity (single, n=4,744; multiple, n=1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p<.001). Patients with multiple masses tended to have luminal A molecular subtype (p<.001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p=.016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p=.019 and p=.032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p=.031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p=.025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS. Conclusions: Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1-2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.

• Clinical and Experimental Reproductive Medicine
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• v.24 no.2
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• pp.261-265
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• 1997

The objective of this study was to examine the effect of EGF to the in vivo development of mouse IVF/IVC embryo. The 2-cell embryos were cultured in medium (5-6 embryos/25 ${\mu}l$/drop) w/wo EGF (10 ng/ml) and day 4 blastocysts recovered from each treatment group were transferred into the uteri of recipients of pseudopregnant day 3. The results obtained in this experiment were summarized as follows: 1. When the effect of EGF to the in vitro development and cell number of blastocysts produced from the culture of 2-cell embryos in w/wo EGF was determined, those results of EGF treatment group showed not significant difference compared with control. 2. However, when the effect of EGF to the in vivo development of blastocysts recovered from each treatment group was examined, production of the normal fetus against transferred embryos in EGF treatment group (51.2%) was very higher than that in control group (31.1%), although total implantation was not significantly different between treatment group (control: 64.4%, EGF: 69.8%). Therefore, this result suggested that EGF can affect to the in vivo development of IVF/IVC embryos through the improvement of embryo quality, although EGF treated embryos showed not significant development rate compared with control.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.415-424
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• 2018

Purpose: Triple-positive breast cancer is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity. Several systemic breast cancer therapies target hormonal and HER2 responsiveness. We compared clinical outcomes of triple-positive disease with those of HER2-enriched and luminal HER2-negative disease and investigated the clinical efficacy of anti-HER2 therapy for triple-positive disease. Methods: We retrospectively compared overall and recurrence-free survival among cases included in the Korean Breast Cancer Society (KBCS) and Seoul St. Mary's Hospital breast cancer registries and the therapeutic efficacy of trastuzumab for triple-positive and HER2-enriched cases. Results: KBCS registry data (2006-2010; median follow-up, 76 months) indicated that patients with triple-positive breast cancer had intermediate survival between those with luminal A and HER2-enriched subtypes (p<0.001). Trastuzumab did not improve overall survival among patients with triple-positive breast cancer (p=0.899) in contrast to the HER2-enriched subtype (p=0.018). Seoul St. Mary's Hospital registry data indicated similar recurrence-free survival outcomes (p<0.001) and a lack of improvement with trastuzumab among patients with triple-positive breast cancer (median follow-up, 33 months; p=0.800). Multivariate analysis revealed that patients with triple-positive breast cancer had better overall survival than those with HER2-enriched disease and similar survival as those with the luminal A subtype (triple-positive: hazard ratio, 1.258, p=0.118; HER2-enriched: hazard ratio, 2.377, p<0.001). Conclusion: Our findings showed that anti-HER2 therapy was less beneficial for treatment of triple-positive breast cancer than for HER2-enriched subtypes of breast cancer, and the triple-positive subtype had a distinct prognosis.

• Journal of Breast Disease
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• v.6 no.2
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• pp.52-59
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• 2018

Purpose: This study aimed to determine whether clinicopathological factors are potentially associated with successful breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) and develop a nomogram for predicting successful BCS candidates, focusing on those who are diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors during the pre-NAC period. Methods: The training cohort included 239 patients with an HR-positive, HER2-negative tumor (${\geq}3cm$), and all of these patients had received NAC. Patients were excluded if they met any of the following criteria: diffuse, suspicious, malignant microcalcification (extent >4 cm); multicentric or multifocal breast cancer; inflammatory breast cancer; distant metastases at the time of diagnosis; excisional biopsy prior to NAC; and bilateral breast cancer. Multivariate logistic regression analysis was conducted to evaluate the possible predictors of BCS eligibility after NAC, and the regression model was used to develop the predicting nomogram. This nomogram was built using the training cohort (n=239) and was later validated with an independent validation cohort (n=123). Results: Small tumor size (p<0.001) at initial diagnosis, long distance from the nipple (p=0.002), high body mass index (p=0.001), and weak positivity for progesterone receptor (p=0.037) were found to be four independent predictors of an increased probability of BCS after NAC; further, these variables were used as covariates in developing the nomogram. For the training and validation cohorts, the areas under the receiver operating characteristic curve were 0.833 and 0.786, respectively; these values demonstrate the potential predictive power of this nomogram. Conclusion: This study established a new nomogram to predict successful BCS in patients with HR-positive, HER2-negative breast cancer. Given that chemotherapy is an option with unreliable outcomes for this subtype, this nomogram may be used to select patients for NAC followed by successful BCS.

• BMB Reports
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• v.51 no.12
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• pp.660-665
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• 2018

Human epidermal growth factor receptor 2 (HER2) inhibitors, such as trastuzumab and lapatinib are used to treat HER2-positive breast and gastric cancers. However, as with other targeted therapies, intrinsic or acquired resistance to HER2 inhibitors presents unresolved therapeutic problems for HER2-positive gastric cancer. The present study describes investigations with AUY922, a heat shock protein 90 (HSP90) inhibitor, in primary lapatinib-resistant (ESO26 and OE33) and lapatinib-sensitive gastric cancer cells (OE19, N87, and SNU-216) harboring HER2 amplification/over-expression. In order to investigate whether AUY922 could overcome intrinsic and acquired resistance to HER2 inhibitors in HER2-positive gastric cancer, we generated lapatinib-resistant gastric cancer cell lines (OE19/LR and N87/LR) by continuous exposure to lapatinib in vitro. We found that activation of HER2 and protein kinase B (AKT) were key factors in inducing intrinsic and acquired lapatinib-resistant gastric cancer cell lines, and that AUY922 effectively suppressed activation of both HER2 and AKT in acquired lapatinib-resistant gastric cancer cell lines. In conclusion, AUY922 showed a synergistic anti-cancer effect with lapatinib and sensitized gastric cancer cells with intrinsic resistance to lapatinib. Dual inhibition of the HSP90 and HER2 signaling pathways could represent a potent therapeutic strategy to treat HER2-positive gastric cancer with intrinsic and acquired resistance to lapatinib.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.35 no.4
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• pp.75-94
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• 2022

Objectives : To identify the active ingredient of Poncirus Trifoliata Immaturus and to explore the mechanism expected to potentially act on dermatitis accompanied by pruritus. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of Poinciri Fructus Immaturus. We found the target protein of the selected active ingredient, disease(dermatitis accompanied by pruritus) and fexofenadine. Then we established the network between the proteins which Poinciri Fructus Immaturus and fexofenadine intersected with disease respectively, and the coregene was also extracted. After that, the active pathways in the human body involving the groups and coregenes were searched. Results : Total of 7 active ingredients were selected, and 202 target proteins were collected. There were 756 proteins related to inflammatory skin disease accompanied by pruritus, and 75 proteins were related to fexofenadine. 42 proteins crossed by Poinciri Fructus Immaturus with a disease, and 31 proteins crossed by fexofenadine with a disease. 12 proteins were found as a coregene from the proteins that cross Poinciri Fructus Immaturus and disease. Coregenes are involved in 'Nitric-oxide synthase regulator activity', 'Epidermal growth factor receptor signaling pathway'. 2 groups that extracted are invloved in 'Fc receptor signaling pathway', 'Central carbon metabolism in cancer', 'Phosphatidylinositol 3-kinase complex, class IB', and 'omega-hydroxylase P450 pathway'. Conclusion : It is expected that Poinciri Fructus Immaturus will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied by pruritus in the future. And it is also expected to have a synergy effect with fexofenadine on skin disease.

• Journal of Chest Surgery
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• v.56 no.1
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• pp.25-32
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• 2023

Background: We reviewed the clinical outcomes of patients with oligometastatic (OM) non-small cell lung cancer (NSCLC) who received multimodal therapy including lung surgery. Methods: We retrospectively analyzed 117 patients with OM NSCLC who underwent complete resection of the primary tumor from 2014 to 2017. Results: The median follow-up duration was 2.91 years (95% confidence interval, 1.48-5.84 years). The patients included 73 men (62.4%), and 76 patients (64.9%) were under the age of 65 years. Based on histology, 97 adenocarcinomas and 14 squamous cell carcinomas were included. Biomarker analysis revealed that 53 patients tested positive for epidermal growth factor receptor, anaplastic lymphoma kinase, or ROS1 mutations, while 36 patients tested negative. Metastases were detected in the brain in 74 patients, the adrenal glands in 12 patients, bone in 5 patients, vertebrae in 4 patients, and other locations in 12 patients. Radiation therapy for organ metastasis was performed in 81 patients and surgical resection in 27 patients. The 1-year overall survival (OS) rate in these patients was 82.8%, and the 3- and 5-year OS rates were 52.6% and 37.2%, respectively. Patients with positive biomarker test results had 1-, 3-, and 5-year OS rates of 98%, 64%, and 42.7%, respectively. These patients had better OS than those with negative biomarker test results (p=0.031). Patients aged ≤65 years and those with pT1-2 cancers also showed better survival (both p=0.008). Conclusion: Surgical resection of primary lung cancer is a viable treatment option for selected patients with OM NSCLC in the context of multimodal therapy.

• Journal of Digestive Cancer Research
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• v.5 no.2
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• pp.125-129
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• 2017

A 38-year-old man presented with abdominal discomfort and was diagnosed as type 3 advanced gastric cancer with multiple liver and lung metastases (Stage IV). Endoscopic forcep biopsy revealed moderately differentiated adenocarcinoma, which stained positive HER2 (Human epidermal growth factor receptor) on immunohistochemistry. We started chemotherapy with FP (5-Fluorouracil plus Cisplatin) plus trastuzumab. After 6 cycles of FP plus trastuzumab chemotherapy, there were partial response in the liver, lung and lymph nodes metastasis. Especially, metastatic lung lesions showed remarkable improvement. Chemotherapy with FP plus trastuzamab was effective for HER2 positive advanced cancer with multiple liver and lung metastases. Through active research on target therapy about advanced gastric cancer, we expect to improve the survival rate and quality of life of patients with advanced gastric cancer who can not undergo curative resection.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.142-148
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• 1995

Background: Despite modern diagnostic, staging, and therapeutic advances, esp. with molecular biologic techniques, the 5-year survival rate of all cases of lung cancer does not exceed 15%. Also, the incidence of lung cancer of both sex in Korea is increasing year by year and the lung cancer is one of the leading causes of cancer death. Therefore, it is strongly needed to develop the new combination of treatment modalities including neoadjuvant chemotherapy and to identify tumor specific characteristics with staging or prognostic markers. Here we present the clinical significance of several biologic tumor markers to use as a prognostic markers in patients with non-small cell lung cancers. Method: The survival has correlated with the expressibility of proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor(EGFR), p53 and/or blood group antigen A(BGAA) using immunohistochemistry in 46 patients with non-small cell lung cancers. Results: 1) The expression rates of PCNA, EGFR, p53 and BGAA were 80.6%, 61.3%, 45.9% and 64.3%, respectively and those were not correlated to cell types or clinical stges. 2) The expression of BGAA was correlated with better survival in median survival and in 2-year survival rate and that of PCNA was correlated with worse survival in median survival and 2-year survival rate. 3) The expression of EGFR or p53 was not valuable to predict prognosis in non-small cell lung cancers. 4) With simultaneous applications of PCNA, EGFR and p53 immunostain, the patients with 2 or more negative expressions showed better prognosis than the patients with 2 or more positive expressions. Conclusion: It is suggested that the expression of blood group antigen may be a positive prognostic factor and that of PCNA may be a negative prognostic factor. Also, the combination of expressions of PCNA, EGFR and p53 may be used as a negative prognostic factor.

• KSBB Journal
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• v.23 no.3
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• pp.205-212
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• 2008

The efficient soluble expression of human epidermal growth factor (hEGF) was achieved by using functional fusion partners in cytoplasm and periplasm of Escherichia coli (E. coli). hEGF was over-expressed in inactive inclusion body form in cytoplasm of E. coli due to improper disulfide bond formation and hydrophobic interaction, yielding about 5.9 mg/L in flask culture. Six functional fusion partners were introduced by linking to N-terminal part of hEGF gene for the high-level expression of soluble and active hEGF in cytoplasm and peri plasm region. Three fusion partners for cytoplasmic expression such as acidic tail of synuclein (ATS), thioredoxin (Trx) and lipase, and three fusion partners for periplasmic expression such as periplasmic cystein oxidoreductases (DsbA and DsbC) and maltose binding protein (MBP) were investigated. hEGF fused with ATS and DsbA showed over 90% of solubility in cytoplasm and periplasm, respectively. Especially DsbA was found to be an efficient fusion partner for soluble and high-level expression of hEGF, yielding about 18.1 mg/L and three-fold higher level compared to that of insoluble non-fusion hEGF in cytoplasm. Thus, heterologous proteins containing complex disulfide bond and many hydrophobic amino acids can effectively be produced as an active form in E. coli by introducing a suitable peptide or protein.