• Radiation Oncology Journal
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• v.36 no.4
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• pp.285-294
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• 2018

Purpose: To determine the necessity of postmastectomy radiotherapy (PMRT) and which regions would be at risk for recurrence, we evaluated local and regional recurrence in breast cancer patients with 1-3 positive nodes and a tumor size of <5 cm. Materials and Methods: We retrospectively analyzed data of 133 female breast cancer patients with 1-3 positive nodes, and a tumor size of <5 cm who were treated with mastectomy followed by adjuvant systemic therapy between 2007 and 2016. The median follow-up period was 57 months (range, 12 to 115 months). Most patients (82.7%) were treated with axillary lymph node dissection. Adjuvant chemotherapy, endocrine therapy, and trastuzumab therapy were administered to 124 patients (93.2%), 112 (84.2%), and 33 (24.8%), respectively. The most common chemotherapy regimen was anthracycline and cyclophosphamide followed by taxane (71.4%). Results: Three patients (2.3%), 8 (6.0%), and 12 (9.0%) experienced local, regional, and distant failures, respectively. The 5-year cumulative risk of local recurrence, regional recurrence, distant metastasis, and disease-free survival was 3.1%, 8.0%, 11.7%, and 83.4%, respectively. There were no statistically significant clinicopathologic factors associated with local recurrence. Lymphovascular invasion (univariate p = 0.015 and multivariate p = 0.054) was associated with an increased risk of regional recurrence. Conclusion: Our study showed a very low local recurrence in patients with 1-3 positive nodes and tumor size of <5 cm who were treated with mastectomy and modern adjuvant systemic treatment. The PMRT volume need to be tailored for each patient's given risk for local and regional recurrence, and possible radiation-related toxicities.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.265-276
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• 2000

Purpose : Between January 1983 and December 1988, 218 female Patients with known breast cancer and positive axillary nodes were treated with adjuvant radiotherapy and chemotherapy following radical mastectomy. Treatment results were retrospectively analysed at the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University of College of Medicine. Materials and Methods : The patients were classified into 3 groups; group I included II patients treated with adjuvant chemotherapy alone; in group 2, 52 patients treated with radiotherapy alone; and in group 3, n patients treated with combined chemo-radiotherapy. The mean age was 44 years and ranged from 27 to 70. The median follow-up time was 51 months. Results :Seven-year relapse free and overall survival rates were 56$\%$ and 67$\%$; in group 1, 50$\%$ and 56$\%$ in group 2, 51$\%$ and 65$\%$ and in group 3, 62$\%$ and 75$\%$ respectively. This difference was not statistically significant(p<0.05). The loco-regional failure rates were 13$\%$ and distant failure rates were 33$\%$. There was less risk of loco-regional failure in group 2 and 3 which included radiotherapy (p<0.05). But there was no significantly difference in the rates of distant failure( p>0.05). By univariate analysis, the only significant prognostic factor affecting relapse-free survival was the percentage of positive axillary nodes; and the overall survival significantly correlated with the primary tumor site, the number or percentage of positive axillary nodes, and stage. But in multivariate analysis, the only significant prognostic factor was treatment modality. By univariate analysis of prognostic factors affecting the rates of overall failure and distant failure, the significant prognostic factors was the percentage of positive axillary nodes; and the risk of the loco-regional failure significantly correlated with the treatment modality. Conclusion :In conclusion, these results suggest a potential for decreasing the risk of loco-regional failure with the addition of postoperative radiotherapy to chemotherapy in the premenopausal patients, and in the patients with number or percentage of positive nodes more than 4 or 1/3. The results of this study suggest that the combined chemo-radiotherapy as adjuvant treatment following radical mastectomy was the most effective modaliw in groups of 2$\~$5 cm sized tumor, stage IIB, and in patients with more than 4 or 1/3 of number or percentage of positive nodes.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.163-168
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• 2009

Purpose: This study was a retrospective evaluation of the efficacy of stereotactic radiosurgery (SRS) in patients with >4 metastases to the brain. Materials and Methods: Between January 2004 and December 2006, 68 patients with $\geq$4 multiple brain metastases were included and reviewed retrospectively. Twenty-nine patients received SRS and 39 patients received whole brain radiotherapy (WBRT). Patients with small cell lung cancers and melanomas were excluded. The primary lesions were non-small cell lung cancer (69.0%) and breast cancer (13.8%) in the SRS group and non-small cell lung cancer (64.1%), breast cancer (15.4%), colorectal cancer (12.8%), esophageal cancer (5.1%) in the WBRT group. SRS involved gamma-knife radiosurgery and delivered 10~20 Gy (median, 16 Gy) in a single fraction with a 50% marginal dose. WBRT was delivered daily in 3 Gy fractions, for a total of 30 Gy. After completion of treatment, a follow-up brain MRI or a contrast-enhanced brain CT was reviewed. The overall survival and intracranial progression-free survival were compared in each group. Results: The median follow-up period was 5 months (range, 2~19 months) in the SRS group and 6 months (range, 4~23 months) in the WBRT group. The mean number of metastatic lesions in the SRS and WBRT groups was 6 and 5, respectively. The intracranial progression-free survival and overall survival in the SRS group was 5.1 and 5.6 months, respectively, in comparison to 6.1 and 7.2 months, respectively, in the WBRT group. Conclusion: SRS was less effective than WBRT in the treatment of patients with >4 metastases to the brain.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10393-10396
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• 2015

Background: Endometral carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in women after breast, colorectal and lung cancers Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates cellular response to hypoxia HIF-1 plays important roles in the development and progression of cancer through activation of various genes that are involved in crucial aspects of cancer biology, including angiogenesis, energy metabolism, vasomotor function, erythropoiesis, and cell survival. In this study, we aimed to investigate the association between HIF-1 1772 C/T polymorphisms and endometrial cancer. Materials and Methods: 75 patients with endometrial carcinoma and 75 patients whose underwent hysterectomy for non tumoral indication selected for evaluation of HIF-1 1772 C/T polymorphisms by PCR-RFLP and sequencing. Results: For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with endometrial cancer risk. Conclusions: Our results suggest that the C1772T polymorphism of the HIF-1a may be associated with endometrial cancers.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.529-537
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• 2019

Lung cancer is the most common cause of cancer deaths worldwide and several molecular signatures have been developed to predict survival in lung cancer. Increasing evidence suggests that proliferation and migration to promote tumor growth are associated with dysregulated ion channel expression. In this study, by analyzing high-throughput gene expression data, we identify the differentially expressed $K^+$ channel genes in lung cancer. In total, we prioritize ten dysregulated $K^+$ channel genes (5 up-regulated and 5 down-regulated genes, which were designated as K-10) in lung tumor tissue compared with normal tissue. A risk scoring system combined with the K-10 signature accurately predicts clinical outcome in lung cancer, which is independent of standard clinical and pathological prognostic factors including patient age, lymph node involvement, tumor size, and tumor grade. We further indicate that the K-10 potentially predicts clinical outcome in breast and colon cancers. Molecular signature discovered through $K^+$ gene expression profiling may serve as a novel biomarker to assess the risk in lung cancer.

• Journal of Integrative Natural Science
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• v.16 no.3
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• pp.81-95
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• 2023

Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.457-468
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• 2022

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.369-377
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• 1999

A new series of highly water soluble platinum(II) complexes {Pt(II)[1,3-bis(phenylthio) propane](trans- -1,2-diaminocyclohexane) (PC-1) and Pt(II)[1,3-bis-(phenythio)propane] cis-1,2-diaminocyclohexane(PC-2)} were synthesized, and characterized by their elemental analysis and by various spectroscopic techniques[infrared(IR), 13C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II) complexes was tested against P-388 and L-1210 mouse lymphocytic leukemia cell lines, PC-14 / P, PC-14/ADM and PC-14 / CDDP human pulmonary adenocarcinima, DU-145 human prostate carcinoma, HT-1376 human bladder carcinoma, ZR-75-1 human breast carcinoma, MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 showed active against L-1210, P-388 leukemia, human lung, stomach, prostate, bladder and breast cancer cell lines, and the antitumor activity of these compounds were comparable or superior to those of PC-2 and displatin. The nephrotoxicities of PC-1 and PC-2 were found quite less than that of cisplatin using MTT and [3H] thymidine uptake in rabbit proximal tubule cells and human kidney cortical cells. Based on these results, this novel platinum (II) complex compound (PC-1) represents a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.4
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• pp.346-349
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• 2005

Metastatic tumours to oral soft tissue are uncommon and accounts for approximately 1% of malignant oral neoplasms. Because of its rarity and clinical appearance of benign nature, the diagnosis of a metastatic lesion in the oral soft tissue may be challenging, both to clinicians and pathologists. We analyzed the clinical data of 9 patients who had metastatic carcinoma to oral soft tissues. The metastatic site to oral soft tissue was the gingiva in all cases. The most common primary site was lung (6 cases) followed by liver (2 cases) and breast (1 case). The clinical appearance resembled gingiva hyperplasia, pyogenic granuloma or gingival swelling. In one case, the metastatic gingiva lesion was found before detection of primary cancer. The mean survival time after diagnosis of metastatic lesion was 3 months. Although this metastatic lesion is rare, oral and maxillofacial surgeon should recognized that benign inflammatory lesion may be the metastatic malignant lesion or the first sign of undiagnosed underlying malignancy.

• Nutrition Research and Practice
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• v.10 no.4
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• pp.393-397
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• 2016

BACKGROUND/OBJECFTIVES: Artemisinin, a natural product isolated from Gaeddongssuk (artemisia annua L.) and its main active derivative, dihydroartemisinin (DHA), have long been used as antimalarial drugs. Recent studies reported that artemisinin is efficacious for curing diseases, including cancers, and for improving the immune system. Many researchers have shown the therapeutic effects of artemisinin on tumors such as breast cancer, liver cancer and kidney cancer, but there is still insufficient data regarding glioblastoma (GBM). Glioblastoma accounts for 12-15% of brain cancer, and the median survival is less than a year, despite medical treatments such as surgery, radiation therapy, and chemotherapy. In this study, we investigated the anti-cancer effects of DHA and transferrin against glioblastoma (glioblastoma multiforme, GBM). MATERIALS/METHODS: This study was performed through in vitro experiments using C6 cells. The toxicity dependence of DHA and transferrin (TF) on time and concentration was analyzed by MTT assay and cell cycle assay. Observations of cellular morphology were recorded with an optical microscope and color digital camera. The anti-cancer mechanism of DHA and TF against GBM were studied by flow cytometry with Annexin V and caspase 3/7. RESULTS: MTT assay revealed that TF enhanced the cytotoxicity of DHA against C6 cells. An Annexin V immune-precipitation assay showed that the percentages of apoptosis of cells treated with TF, DHA alone, DHA in combination with TF, and the control group were $7.15{\pm}4.15%$, $34.3{\pm}5.15%$, $66.42{\pm}5.98%$, and $1.2{\pm}0.15%$, respectively. The results of the Annexin V assay were consistent with those of the MTT assay. DHA induced apoptosis in C6 cells through DNA damage, and TF enhanced the effects of DHA. CONCLUSION: The results of this study demonstrated that DHA, the derivative of the active ingredient in Gaeddongssuk, is effective against GBM, apparently via inhibition of cancer cell proliferation by a pharmacological effect. The role of transferrin as an allosteric activator in the GBM therapeutic efficacy of DHA was also confirmed.