• KSBB Journal
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• v.31 no.1
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• pp.52-57
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• 2016

Mutant p53 (R280K) is highly expressed in MDA-MB-231 triple-negative human breast cancer cells. Currently, we reported the role of mutant p53-R280K in mediating the survival of MDA-MB-231 cells in vitro. The present study was undertaken to determine whether mutant p53-R280K affects breast cancer cell growth in vivo. To this end, we used small interfering RNA to knockdown the level of mutant p53-R280K in MDA-MB-231 cells. Silencing of mutant p53-R280K in MDA-MB-231 cells causes substantial tumor regression of established xenografts in vivo. In xenograft model for breast cancer, silencing of mutant p53-R280K in MDA-MB-231 cells significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in mutant p53-R280K silenced tumors compared to control. Our data indicate that mutant p53-R280K has an important role in mediating tumor growth of MDA-MB-231 cells in vivo. Taken together, this study suggests that endogenous mutant p53-R280K could be used as a therapeutic target for breast cancer cells harboring this TP53 missense mutation.

• Radiation Oncology Journal
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• v.35 no.4
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• pp.332-339
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• 2017

Purpose: This study aimed to evaluate the prognostic effects of lymphovascular invasion (LVI) in triple-negative breast cancer (TNBC) patients who underwent surgical resection. Materials and Methods: A total of 63 non-metastatic TNBC patients who underwent surgical resection were retrospectively investigated from 2007 to 2016 in Inje University Busan Paik Hospital. Pathological tests revealed that 12 patients (19.0%) had LVI. Approximately 61.9% (n = 39) of the patients' samples stained positive for p53. Additional chemotherapy and radiotherapy (RT) were performed in 53 (84.1%) and 47 (74.6%) patients, respectively. Results: The median follow-up period was 39.5 months (range, 5.9 to 123.0 months). The pathological T stage (p = 0.008), N stage (p = 0.014), and p53 positivity (p = 0.044) were associated with LVI. Overall, the 3-year disease-free survival (DFS) rate and overall survival (OS) rate were 85.4% and 90.2%, respectively. Ten patients (15.9%) experienced relapse. LVI (n = 12) was associated with relapses (p = 0.016). p53 positivity was correlated with poor DFS (p = 0.048). Furthermore, LVI was related to poor DFS (p = 0.011) and OS (p = 0.001) and considered as an independent prognostic factor for DFS (p = 0.039). The 3-year DFS of patients with LVI (n = 12) was only 58.3%. Adjuvant RT minimized the negative prognostic effect of LVI on DFS (p = 0.068 [with RT] vs. p = 0.011 [without RT]). Conclusion: LVI was related to the detrimental effects of disease progression and survival of TNBC patients. Thus, a more effective treatment strategy is needed for TNBC patients with LVI.

• Journal of Preventive Medicine and Public Health
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• v.38 no.1
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• pp.9-15
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• 2005

Objectives : To analyze medical expenses by cancer site and survival time among cancer patients in their last year of life. Method : The study subjects were 45,394 people that had died of cancers in 2002, were registered by the Korea Central Cancer Registry and received National Health Insurance benefit in the last year (360 days) of life. Personal identification data, general characteristics, dates of death and cancer incidence, and site of cancer were collected from the National Statistical Office and the Korea Central Cancer Registry, and merged with the data of the individual medical expenses of the Health Insurance Review Agency. Results : Average monthly cost curves were U-shaped with high costs near the time of diagnosis and death, and lower costs in between. Medical expenses in the last year of life were around 30.3, 16.7, 13.0, and 12.1 million won among leukemia, lymphoma, ovarian cancer, and breast cancer patients, respectively. Digestive organ cancers including stomach, esophagus, liver, pancreas, and colorectal cancers had relatively low medical expenses. Medical expenses in the last year of life were inverse U-shaped with high expenses near one year of survival. Average monthly cost in the 12 months before death among the patients who had survived $10{\sim}15$ years were more than two-fold greater than the cost before diagnosis among those who had survived for less than one year. Conclusions : Leukemia was the most expensive cancer. It is possible that once diagnosed as cancer, medical expenses do not return to the level before diagnosis. Further research will be needed to understand the magnitude and change of the medical expenses among cancer patients with long term follow up data.

• Archives of Plastic Surgery
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• v.38 no.6
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• pp.808-814
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• 2011

Purpose: Despite wide clinical use of breast implants, there is continued concern about the lifespan of these devices. The causes of explantation were infection, deflation of implant and patient's want. The deflation of saline-filled breast implant was related to strength and durability of implant shell. The purpose of this study is to evaluate the clinical durability of saline-filled breast implant through the analysis of duration until deflation occurred, causes, incidence and influencing factors. Methods: Retrospective analyses were conducted on clinical records for 19 cases of deflation of saline-filled breast implant from 201 cases of breast reconstruction with saline-filled implant between May 1995 and June 2011. The authors had been analyzed the causes of deflation, survival duration, symptom, sign, nipple excision, volume of implant, saline filling, method of reoperation, breast cancer stage and combined capsular contracture. Results: The causes of deflation were attributed to the cases that cannot be evaluated the causes in 15 cases, fall down in 1 case, mammography in 2 cases, accidental needle injury in 1 case. Mean survival duration was 4 years and 5 months. The duration of survival was less than 1 year for 5 cases, 1 year to 10 years for 10 cases, more than 10 years for 4 cases. The volume between 201 and 250 cc of deflated breast implant was rated as high by 14.0 percent. The deflation rate of underfilled implants was 11.4 percent, adequate filled implants was 9.3 percent. None of overfilled implant was deflated. The deflation of smooth surface implant was 5 of 152 cases. Textured implant was 14 of 49 cases. The capsular contracture of non-deflated breast implant was 28 of 182 cases and that of deflated breast implant was 6 of 19 cases. Conclusion: The patients who underwent saline-filled breast implant implantation should be informed that their implant could deflate. The analysis of clinical durability and causes of deflation in breast implant was important for the prediction and prevention of reopeation. The authors could suppose the causes of deflation of saline-filled breast implant through history, duration of survival, inspection of the shell of implant.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4683-4688
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• 2014

Background: Breast conservation treatment (BCT) has long been recognised to provide survival outcomes equivalent to mastectomy for the treatment of breast cancer. However, published reports of BCT rates in Asian communities are lower than those from Western countries. This study sought to investigate the eligibility and utilisation of BCT in a predominantly Asian population. Materials and Methods: All patients treated surgically by a single surgeon at a private medical facility between 2009 and 2011 were included in the study. Patients were deemed to have successful BCT if they underwent breast conserving surgery with pathologic clear margins and completed all recommended adjuvant treatment. Those who did not complete adjuvant treatment were excluded from the analysis. Results: Data from a total of 161 patients who underwent treatment during the study period were analysed. The mean age was 48.8 years. One hundred and six patients (65.8%) were of Chinese ethnicity, 12 were Indian (7.5%), 11 were Malay (6.8%), 18 were Caucasian (11.2%) and 14 (8.7%) were of other Asian ethnicity. One hundred and thirty-eight women (85.7%) underwent BCT. Of the 23 (14.3%) who underwent mastectomy, 8 (5.4%) elected to undergo a mastectomy despite being eligible for BCT. In total, it was assessed that 146 of 161 patients (90.7%) were eligible for BCT and utilisation was 94.5%. Conclusions: In this study, eligibility, utilisation of BCT and eventual successful breast conservation rates are similar to published rates in Western communities. Additional research is needed to investigate the reasons for the lower published BCT rates in Asian countries and determine ways to improve them.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5471-5476
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• 2015

2-deoxy-D-Glucose (2DG) causes cytotoxicity in cancer cells by disrupting thiol metabolism. It is an effective component in therapeutic strategies. It targets the metabolism of cancer cells with glycolysis inhibitory activity. On the other hand, MLN4924, a newly discovered investigational small molecule inhibitor of NAE (NEDD8 activating enzyme), inactivates SCF E3 ligase and causes accumulation of its substrates which triggers apoptosis. Combination of these components might provide a more efficient approach to treatment. In this research, 2DG and MLN4924 were co-applied to breast cancer cells (MCF-7 and SKBR-3) and cytotoxic and apoptotic activity were evaluated the by Micro culture tetrazolium test (MTT), TUNEL and ELISA methods. Caspase3 and Bcl2 genes expression were evaluated by real time Q-PCR methods. The results showed that MLN4924 and MLN4924/2DG dose-dependently suppressed the proliferation of MCF7 and SKBR-3 cells. Cell survival of breast cancer cells exposed to the combination of 2DG/MLN4924 was decreased significantly compared to controls (p<0.05), while 2DG and MLN4924 alone had less pronounced effects on the cells. The obtained results suggest that 2DG/MLN4924 is much more efficient in breast cancer cell lines with enhanced cytotoxicity via inducing a apoptosis cell signaling gene, caspase-3.

• Korean Journal of Radiology
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• v.24 no.7
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• pp.626-639
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• 2023

Objective: To investigate the association of clinical, pathologic, and magnetic resonance imaging (MRI) variables with progressive disease (PD) during neoadjuvant chemotherapy (NAC) and distant metastasis-free survival (DMFS) in patients with triple-negative breast cancer (TNBC). Materials and Methods: This single-center retrospective study included 252 women with TNBC who underwent NAC between 2010 and 2019. Clinical, pathologic, and treatment data were collected. Two radiologists analyzed the pre-NAC MRI. After random allocation to the development and validation sets in a 2:1 ratio, we developed models to predict PD and DMFS using logistic regression and Cox proportional hazard regression, respectively, and validated them. Results: Among the 252 patients (age, 48.3 ± 10.7 years; 168 in the development set; 84 in the validation set), PD was occurred in 17 patients and 9 patients in the development and validation sets, respectively. In the clinical-pathologic-MRI model, the metaplastic histology (odds ratio [OR], 8.0; P = 0.032), Ki-67 index (OR, 1.02; P = 0.044), and subcutaneous edema (OR, 30.6; P = 0.004) were independently associated with PD in the development set. The clinical-pathologic-MRI model showed a higher area under the receiver-operating characteristic curve (AUC) than the clinical-pathologic model (AUC: 0.69 vs. 0.54; P = 0.017) for predicting PD in the validation set. Distant metastases occurred in 49 patients and 18 patients in the development and validation sets, respectively. Residual disease in both the breast and lymph nodes (hazard ratio [HR], 6.0; P = 0.005) and the presence of lymphovascular invasion (HR, 3.3; P < 0.001) were independently associated with DMFS. The model consisting of these pathologic variables showed a Harrell's C-index of 0.86 in the validation set. Conclusion: The clinical-pathologic-MRI model, which considered subcutaneous edema observed using MRI, performed better than the clinical-pathologic model for predicting PD. However, MRI did not independently contribute to the prediction of DMFS.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3571-3574
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• 2014

Background: Brain metastasis occurs when cancerous cells come from a known (or sometimes an unknown) primary tumor to the brain and implant and grow there. This event is potentially lethal and causes neurologic symptoms and signs. These patients are treated in order to decrease their neurologic problems, increase quality of life and overall survival. Materials and Methods: In this study we evaluated clinical characteristics of 206 patients with brain metastases referred to our center from 2004 to 2011. Results: The mean age was 53.6 years. The primary tumors were breast cancer (32%), lung cancer (24.8%), lymphoma (4.4%), sarcoma (3.9%), melanoma (2.9%), colorectal cancer (2.4%) and renal cell carcinoma (1.5%). In 16.5% of the patients, brain metastasis was the first presenting symptom and the primary site was unknown. Forty two (20.4%) patients had a single brain metastasis, 18 patients (8.7%) had two or three lesions, 87 (42.2%) patients had more than three lesions. Leptomeningeal involvement was seen in 49 (23.8%) patients. Thirty five (17%) had undergone surgical resection. Whole brain radiation therapy was performed for all of the patients. Overall survival was 10.1 months (95%CI; 8.65-11.63). One and two year survival was 27% and 12% respectively. Conclusions: Overall survival of patients who were treated by combination of surgery and whole brain radiation therapy was significantly better than those who were treated with whole brain radiation therapy only [13.8 vs 9.3 months (p=0.03)]. Age, sex, primary site and the number of brain lesions did not show significant relationships with overall survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2179-2183
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• 2014

Background: In vitro, in vivo and clinical studies have demonstrated anti-cancer effects of deuterium depleted water (DDW). The nature of this agents action, cytotoxic or cytostatic, remains to be elucidated. We here aimed to address the point by examining effects on different cell lines. Materials and Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) -based cytotoxicity analysis was conducted for human breast, stomach, colon, prostate cancer and glioblastoma multiforme cell lines as well as human dermal fibroblasts. The cell lines were treated with decreasing deuterium concentrations of DDW alone, paclitaxel alone and both. One way analysis of variance (ANOVA) was used for statistical analysis. Results: Treatment with different deuterium concentrations of DDW alone did not impose any significant inhibitory effects on growth of cell lines. Paclitaxel significantly decreased the survival fractions of all cell lines. DDW augmented paclitaxel inhibitory effects on breast, prostate, stomach cancer and glioblastoma cell lines, with influence being more pronounced in breast and prostate cases. Conclusions: DDW per se does not appear to have inhibitory effects on the assessed tumor cell lines as well as normal fibroblasts. As an adjuvant, however, DDW augmented inhibitory effects of paclitaxel and thus it could be considered as an adjuvant to conventional anticancer agents in future trials.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3211-3217
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• 2014

Background: The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Materials and Methods: Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose ($D_0$), quasi-threshold dose ($D_q$) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM). Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. Results: The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Conclusions: Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA-MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.