• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1471-1477
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• 2015

Background: Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. Materials and Methods: Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. Results: Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2%, respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). Conclusions: In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.

• Journal of Microbiology and Biotechnology
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• 제28권4호
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• pp.542-550
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• 2018

Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from genetically engineered Streptomyces hygroscopicus, was found to have anticancer activity against two human breast cancer cell lines. WK-88-1 produced concentration-dependent inhibition of cell proliferation, cell cycle arrest, and apoptosis in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cell lines. Detailed analysis showed that WK-88-1 downregulated some key cell cycle molecules (CDK1 and cyclin B1) and lead to $G_2/M$ cell cycle arrest. Further studies also showed that WK-88-1 could induce human breast cancer cell apoptosis by downregulating Hsp90 client proteins (Akt, p-Akt, IKK, c-Raf, and Bcl-2), decreasing the ATP level, increasing reactive oxygen species production, and lowering the mitochondrial membrane potential. Meanwhile, we discovered that WK-88-1 significantly decreased the levels of Her-2 and $ER-{\alpha}$ in MCF-7 cells but not in MDA-MB-231 cells. In addition, WK-88-1 significantly increased caspase-3, -8, and -9 activities and the cleavage of PARP in a concentration-dependent manner (with the exception of caspase-3 and PARP in MCF-7 cells). Taken together, our preliminary results suggest that WK-88-1 has the potential to play a role in breast cancer therapy.

• Journal of Gastric Cancer
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• 제20권1호
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• pp.106-114
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• 2020

Breast metastases of extramammary malignant neoplasms are rare, with an incidence of 0.3%-2.7% among all malignant mammary tumors. Breast metastases from gastric carcinoma are very rare (<0.1%), and this event is even rarer during pregnancy. Herein, we describe a 39-year-old Caucasian woman with a history of an Epstein-Barr virus-associated gastric carcinoma (EBVaGC) that was characterized by prominent tumor infiltrating lymphocytes. Three years after undergoing radical surgery, the patient developed bilateral breast nodules during her pregnancy. A breast biopsy was performed, and histology confirmed a diagnosis of EBVaGC; tumor cells showed positivity for cytokeratin 8/18 and E-cadherin, and negativity for cytokeratin 7, cytokeratin 20, cytokeratin 5/6, caudal type homebox 2, androgen receptor, mammaglobin, gross cystic disease fluid protein-15, and estrogen and progesterone receptors. We also discuss the main diagnostic pitfalls. To our knowledge, this is the first report of an EBVaGC with lymphoid stroma that developed breast metastases during pregnancy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6135-6140
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• 2013

Background: Breast cancer is a common malignant tumor which affects health of women and multidrug resistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted to establish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms of MDR. Methods: The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves were measured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electron microscopy. The cell cycle distribution was determined by flow cytometry. Furthermore, expression of proteins related to breast cancer occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice were injected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were observed after paclitaxel treatment. In addition, proteins involved breast cancer and MDR were detected by immunohistochemistry. Results: Compared to MCF-7/S, MCF-7/TAX cells had a higher resistance to paclitaxel, cross-resistance and prolonged doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure. Estrogen receptor (ER) expression was low in drug resistant cells and tumors while expression of human epidermal growth factor receptor 2 (HER2) and Ki-67 was up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP) and glutathione-S-transferase-${\pi}$ (GST-${\pi}$) involved in the MDR phenotype of resistant cells and tumors were all overexpressed. Conclusion: The underlying MDR mechanism of breast cancer may involve increased expression of P-gp, LRP and GST-${\pi}$.

• 대한영상의학회지
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• 제83권1호
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• pp.149-161
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• 2022

목적 3-tesla (이하 T) 자기공명영상에서 비특이 침윤성 유방암의 컴퓨터보조진단 인자들과 병리적 면역조직화학 표지자들과의 상관성을 알아보고자 하였다. 대상과 방법 2018년 1월부터 2019년 4월까지 비특이 침윤성 유방암으로 진단받은 총 94명의 3T 자기공명영상에서 컴퓨터보조진단 시스템을 통해 얻은 혈관조영부피, 최대 조영증강, 조기 및 지연 조영증강 양상과 면역화학인자와 유방암의 분자형 아형과의 상관성을 Dwass, Steel, Critchlow-Fligner 비교 분석과 이분형 로지스틱 회귀 분석을 이용하여 후향적으로 연구하였다. 결과 혈관조영부피가 큰 비특이 침윤성 유방암이 핵등급과 조직학적 등급이 높고, 림프절 전이가 있고, 에스트로겐 수용체/프로게스테론 수용체 음성, 인간 표피성장인자수용체 2/Ki-67 양성이 많았다. Ki-67 양성인 비특이 침윤성 유방암에서 지연기 소실 성분 비율이 높고 지연기 지속 조영증강 비율이 낮았다. 이항회귀분석에서는 컴퓨터보조진단 시스템의 요소 중 혈관조영부피 인자가 독립적으로 핵등급, 조직학적 등급, 림프절 전이, 에스트로겐/프로게스테론 수용체, 인간 표피성장인자수용체 2와 Ki-67과 상관성이 있고, 지연기 소실 및 지속 조영증강 인자가 Ki-67과 상관성이 있었다. 결론 조영증강 유방 MRI 컴퓨터보조진단 시스템 인자 중 혈관조영부피 요소와 지연기 소실/지속 조영증강 비율이 예후 예측 인자로 알려진 면역화학인자들과 연관성이 높아 임상적 예후 예측 인자로서 이용될 수 있을 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5081-5084
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• 2015

Background: Breast cancer is a malignant tumor that starts from cells of the breast and is seen mainly in women. It's the most common cancer in women worldwide and is a major threat to health. The purpose of this study was to fit a Cox proportional hazards model for prediction and determination of years of survival in Iranian patients. Materials and Methods: A total of 366 patients with breast cancer in the Cancer Research Center were included in the study. A Cox proportional hazard model was used with variables such as tumor grade, number of removed positive lymph nodes, human epidermal growth factor receptor 2 (HER2) expression and several other variables. Kaplan-Meier curves were plotted and multi-years of survival were evaluated. Results: The mean age of patients was 48.1 years. Consumption of fatty foods (p=0.033), recurrence (p<0.001), tumor grade (p=0.046) and age (p=0.017) were significant variables. The overall 1- year, 3-year and 5-year survival rates were found to be 93%, 75% and 52%. Conclusions: Use of covariates and the Cox proportional hazard model are effective in predicting the survival of individuals and this model distinguished 4 effective factors in the survival of patients.

• 한국해양바이오학회지
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• 제2권2호
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• pp.81-85
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• 2007

글루코코르티코이드의 다양한 생리학적 과정은 이 호르몬에 의해 활성화된 수용체가 표적 유전자의 전사를 촉진 혹은 억제시킴으로써 일어나게 된다. 본 논문은 렌티바이러스 리포터 시스템을 이용하여 글루코코르티코이드 호르몬에 의한 GR 활성을 핵내에서 GRE에 의해 유도된 리포터 단백질인 mRFP 또는 루시퍼라아제의 발현을 통해 정성, 정량화 하였다. 그 결과 GR이 endogenous 하게 발현되는 HeLa 세포에서 코티졸을 처리하였을 때 활성화된 GR에 의해 GRE-inducible한 RFP와 루시퍼라아제의 발현이 각각 공초점 형광 현미경과 IVIS-200을 이용하여 형광 또는 BLI을 통해 증가함을 확인하였다. 이러한 결과를 통해 렌티바이러스 리포터 시스템을 이용한 연구는 세포 내에서 뿐 만 아니라 향후 생체내에서의 GR signaling을 모니터링하는데 유용하게 사용되어질 수 있을 것이다.

• Pediatric Infection and Vaccine
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• 제28권3호
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• pp.173-180
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• 2021

2020년 4월에 유럽에서 처음으로 소아 다기관 염증 증후군(multisystem inflammatory syndrome in children; MIS-C)이 확인된 이후, MIS-C는 코로나바이러스감염증-19(COVID-19)의 병력이 있는 소아들에게서 발병하는 것으로 알려졌고 대부분의 환자들은 유럽과 미국에서 보고되었다. 이에 국내에서 진단된 MIS-C 사례로, 급성 심근염이 동반되고 정맥내 면역글로불린(intravenous immunoglobulin; IVIG), 스테로이드 및 anakinra로 효과적으로 치료한 증례를 보고하고자 한다. 내원 5주 전 COVID-19 진단받은 병력이 있는 14세 여아가 지속되는 고열, 전신 발진 및 부종, 복통, 그리고 저혈압을 주소로 내원하였다. 혈액검사에서 염증수치 및 심장효소수치 상승을 보였고 감염질환을 비롯하여 다른 질환이 배제되었다. 환자는 MIS-C 진단 하에 IVIG와 고용량 메틸프레드니솔론(methylprednisolone) 요법으로 치료하였으나 심기능이 점차 악화되고 관상동맥 확장증이 확인되었다. 이에 제6병일부터 인터루킨-1 수용체 길항제인 anakinra를 투여하였고 이후 점차 환자의 심기능이 호전되었다. 환자는 제19병일에 퇴원하였고 1개월 후 시행한 심초음파상 심기능 및 관상동맥이 정상화되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7975-7979
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• 2015

Purpose: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). Materials and Methods: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. Results: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI=1.28-13.16, p=0.018) and a lower pathological stage (OR=3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI=1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. Conclusions: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.

• Journal of Gastric Cancer
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• 제19권4호
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• pp.375-392
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• 2019

Preoperative chemo- and radiotherapeutic strategies followed by surgery are currently a standard approach for treating locally advanced gastric and esophagogastric junction cancer in Western countries. However, in a large number of cases, the tumor is extremely resistant to these treatments and the patients are exposed to unnecessary toxicity and delayed surgical therapy. The current clinical trials evaluating the combination of preoperative systemic therapies with modern targeted and immunotherapeutic agents represent a unique opportunity for identifying predictive biomarkers of response to select patients that would benefit the most from these treatments. However, it is of utmost importance that these potential biomarkers are corroborated by extensive preclinical and translational research. The aim of this review article is to present the most promising biomarkers of response to classic chemotherapeutic, anti-HER2, antiangiogenic, and immunotherapeutic agents that can be potentially useful for personalized preoperative systemic therapies in gastric cancer patients.