• Asian-Australasian Journal of Animal Sciences
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• 제20권3호
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• pp.334-339
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• 2007

Reactive oxygen species (ROS) generate during electrical activation of oocytes which has detrimental effects on embryo survival when overwhelmed. The present study was designed to investigate the ability of L-ascorbic acid, a novel water soluble antioxidant, to reduce the ROS level in developing embryos and their subsequent effects on embryo development in vitro. The compact cumulus oocyte complexes (COCs) were cultured in tissue culture medium (TCM)-199 supplemented with 10 ng/ml epidermal growth factor, 4 IU/ml pregnant mare serum gonadotropin (PMSG), and human chorionic gonadotropin (hCG) and 10% (v/v) porcine follicular fluid (pFF) for 44 h. After maturation culture, the denuded oocytes were activated with a single DC pulse of 2.0 kV/cm in 0.3 M mannitol solution containing 0.5 mM of HEPES, 0.1 mM of $CaCl_2$ and 0.1 mM of $MgCl_2$ for $30{\mu}s$ using a BTX Electro-cell Manipulator. The activated oocytes were cultured in modified North Carolina State University-23 (mNSCU-23) medium for 168 h. The level of $H_2O_2$ in each embryo was measured by the dichlorohydrofluorescein diacetate (DCHFDA) method at 48 h after activation. The blastocyst formation rate was significantly higher when culture medium was supplemented with 50 and $100{\mu}M$ L-ascorbic acid (31.2 and 38.7%, respectively) compared to non-supplemented (16.1%) group. Accordingly, significantly more cells in blastocyst were found for 50 and $100{\mu}M$ L-ascorbic acid (50.0 and 56.4, respectively) compared to 0 and $200{\mu}M$ L-ascorbic acid (36.5 and 39.8, respectively). L-ascorbic acid reduces the $H_2O_2$ level in developing embryos in a dose-dependant manner. The $H_2O_2$ level (pixels/ embryos) was 191.5, 141.0, 124.0 and 163.3 for 0, 50, 100 and $200{\mu}M$ L-ascorbic acid, respectively. So, we recommend to supplement 50 or $100{\mu}M$ L-ascorbic acid in porcine in vitro culture medium.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5539-5544
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• 2014

Background: To evaluate the location of tumor relapse and imaging modality for detection according to the breast cancer subtype: luminal A, luminal B, HER2 positive luminal B, nonluminal HER2 positive, and triple negative. Materials and Methods: A total of 1244 patients with breast cancer with known estrogen receptor (ER), progesterone receptor (PR), Ki-67 and human epidermal growth factor receptor 2 (HER2), who underwent breast surgery from 2009 to 2012 were analyzed. Patients were classified into the following categories: luminal A (n=458), luminal B (n=241), HER2 positive luminal B (n=227), nonluminal HER2 positive (n=145) and triple negative (n=173). A total of 105 cases of relapse were detected in 102 patients: locoregional recurrence (n=46), recurrence in the contralateral breast (n=28) and distant metastasis (n=31). Comparison of proportions was used to determine the difference between subtypes. Results: Relapse rates by subtypes are as follows: luminal A 23 of 458 (5.02%), luminal B 19 of 241(7.88%), HER2 positive luminal B 15 of 227 (6.61%), nonluminal HER2 postive 19 of 145 (13.10%) and triple negative 29 of 173(16.76%). Luminal A tumors had the lowest rate of recurrence and had significantly lower recurrence rate in comparison with nonluminal HER2 postive (p=0.0017) and triple negative subtypes (p<0.0001). Compared with all other subtypes except nonluminal HER2 positive, triple negative tumors had the highest rate of tumor recurrence (p<0.01). Triple negatives were most likely to develop contralateral recurrence against all subtypes (p<0.05). Detection rate of locoregional and contralateral tumor recurrence were 28.3% on mammography (n=17/60). Conclusions: Luminal A tumors are associated with a low risk of recurrence while triple negative lesions have a high risk. In case of triple negative tumors, the contralateral breast has much more recurrence as compared with all other subtype. In terms of detection rates, breast USG was the best modality for detecting tumor recurrence, compared with other modalities (p<0.05). Subtyping of breast tumors using a molecular gene expression panel can identify patients who have increased risk of recurrence and allow prediction of locations of tumor recurrence for each subtype.

• 한국응용과학기술학회지
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• 제31권1호
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• pp.120-129
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• 2014

나이를 먹으면 피부의 구조와 생리적 기능이 계속적인 감퇴를 일으켜서 노화된다. 외적요인에 의한 노화는 장기간에 걸친 자외선의 노출로 인한 광노화와 바람, 열, 담배 등이 원인으로 내인성 노화를 촉진시키거나 그 자체도 피부노화를 유발한다. 팔미토일 올리고 펩타이드 또는 세라마이드 올리고 펩타이드는 콜라겐 생산을 자극함으로써 피부의 상층부를 재생하며 아세틸 헥사펩타이드는 피하근육과 피부를 유연하게 하여 주름을 완화하는 성분으로 보톡스 대체 항주름 성분으로 대표적인 고기능성 뷰티성분이다. 대조군과 아세틸 헥사펩타이드 함유 7%, 14%, 20% 성분을 실험 군 A, B, C로 나눠서 주름의 변화, 모공의 변화, 수분량 변화, 과각질의 변화를 분석하였다. 아세틸 헥사펩타이드 함유 성분 분석 결과 통계적으로 주름과 모공, 수분에는 대조군에 비해 영향을 준 것으로 보이며, 과각질의 제거에서는 대조군과 실험군의 값에서 비슷한 결과를 얻을 수 있어 피시험자의 자가 평가의 만족도에서 주름과 모공, 수분에는 대조군에 비해 영향을 준 것으로 보이며, 과각질의 제거에서는 대조군과 실험군의 값에서 비슷한 결과를 얻었다.

• 대한병리학회지
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• 제52권6호
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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.

• Journal of Breast Cancer
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• 제21권4호
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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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• 제6권2호
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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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• 제51권12호
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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.

• 한방안이비인후피부과학회지
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• 제35권4호
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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 Digestive Cancer Research
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• 제5권2호
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• pp.125-129
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• 2017

ToGA 연구 결과를 바탕으로 하여, HER2 강양성을 보이는 진행성 위암의 경우에는 Trastuzumab을 기존의 항암제에 병합하여 치료하였을 때 더 좋은 반응과 생존율 향상을 기대할 수 있겠다. 이에 저자들은 HER2 강양성을 보이는 간과 폐와 림프절 전이 등 다발성 전이가 있는 진행성 위암 환자에서 Trastuzumab과 5-Fluorouracil (5-FU)과 Cisplatin 병합 항암요법을 함께 사용하여 큰 부작용 없이 간과 폐, 림프절에 다발성 전이 병변들의 크기가 감소하여 부분 관해를 보인 환자의 증례를 문헌고찰과 함께 보고하는 바이다.

• Korean Journal of Radiology
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• 제20권1호
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• pp.58-68
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• 2019

Objective: To compare digital breast tomosynthesis (DBT) and conventional full-field digital mammography (FFDM) in the detectability of breast cancers in patients with dense breast tissue, and to determine the influencing factors in the detection of breast cancers using the two techniques. Materials and Methods: Three blinded radiologists independently graded cancer detectability of 300 breast cancers (288 women with dense breasts) on DBT and conventional FFDM images, retrospectively. Hormone status, histologic grade, T stage, and breast cancer subtype were recorded to identify factors affecting cancer detectability. The Wilcoxon signed-rank test was used to compare cancer detectability by DBT and conventional FFDM. Fisher's exact tests were used to determine differences in cancer characteristics between detectability groups. Kruskal-Wallis tests were used to determine whether the detectability score differed according to cancer characteristics. Results: Forty breast cancers (13.3%) were detectable only with DBT; 191 (63.7%) breast cancers were detected with both FFDM and DBT, and 69 (23%) were not detected with either. Cancer detectability scores were significantly higher for DBT than for conventional FFDM (median score, 6; range, 0-6; p < 0.001). The DBT-only cancer group had more invasive lobular-type breast cancers (22.5%) than the other two groups (i.e., cancer detected on both types of image [both-detected group], 5.2%; cancer not detected on either type of image [both-non-detected group], 7.3%), and less detectability of ductal carcinoma in situ (5% vs. 16.8% [both-detected group] vs. 27.5% [both-non-detected group]). Low-grade cancers were more often detected in the DBT-only group than in the both-detected group (22.5% vs. 10%, p = 0.026). Human epidermal growth factor receptor-2 (HER-2)-negative cancers were more often detected in the DBT-only group than in the both-detected group (92.3% vs. 70.5%, p = 0.004). Cancers surrounded by mostly glandular tissue were detected less often in the DBT only group than in the both-non-detected group (10% vs. 31.9%, p = 0.016). DBT cancer detectability scores were significantly associated with cancer type (p = 0.012), histologic grade (p = 0.013), T and N stage (p = 0.001, p = 0.024), proportion of glandular tissue surrounding lesions (p = 0.013), and lesion type (p < 0.001). Conclusion: Invasive lobular, low-grade, or HER-2-negative cancer is more detectable with DBT than with conventional FFDM in patients with dense breasts, but cancers surrounded by mostly glandular tissue might be missed with both techniques.