• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.591-602
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• 2019

Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.

• Journal of Life Science
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• v.21 no.9
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• pp.1288-1294
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• 2011

Resveratrol, a kind of phytochemical, is presented in grape skins. Resveratorl exerts antiproliferative, anti-cancer and pro-apoptotic activities in cancer cells. Mammalian target of rapamycin (mTOR) is a critical regulator of cellular growth and proliferation, and it is known to be a strategic target for anti-cancer therapeutic uses. mTOR is a major downstream of the PI3K/Akt pathway, which is activated in various cancer cells. It also plays an important role in the survival, proliferation and angiogenesis of cells. Cyclooxygenase-2 (COX-2) is an important protein that mediates inflammatory processes. It plays an important role in various tumors by affecting cell proliferation, mitosis, apoptosis and angiogenesis. In this study, we have investigated the effects of resveratrol on apoptosis through mTOR and COX-2 expression in MCF-7 breast cancer cells. The treatment of resveratrol with different concentrations inhibited proliferation of MCF-7. The data showed that resveratrol induced apoptotic cell death of cancer cells and decreased mTOR and COX-2 expression. These results suggest that resveratrol induces apoptosis of MCF-7 breast cancer cells by inhibiting mTOR and COX-2 expression.

• International Journal of Oncology
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• v.56 no.6
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• pp.1509-1520
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• 2020

The phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in human cancer as it regulates critical cellular functions, such as survival, proliferation and metabolism. In the present study, a novel PI3Kα inhibitor (HS-146) was synthesized and its anticancer effects on MCF-7, MDA-MB-231, SKBR3 and BT-474 human breast cancer cell lines were confirmed. HS-146 was found to be most effective in inhibiting the proliferation of MCF-7 cells and in inducing cell cycle arrest in the G0/G1 phase by downregulating cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)2 and Cdk4, and upregulating p21Waf1/Cip1 protein levels in this cell line. The induction of apoptosis by HS-146 was confirmed by DAPI staining and western blot analysis. Cell shrinkage and nuclear condensation, which are typical morphological markers of apoptosis, were increased by HS-146 in the MCF-7 cells in a concentration-dependent manner, and HS-146 also increased the protein expression levels of cleaved poly(ADP-ribose) polymerase (PARP) and decreased the protein expression levels of Mcl-1 and caspase-7. In addition, HS-146 effectively decreased the phosphorylation levels of downstream PI3K effectors, such as Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β), p70S6K1 and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression were also suppressed by HS-146 under hypoxic conditions, and HS-146 inhibited the migration and invasion of MCF-7 cells in a concentration-dependent manner. On the whole, the findings of the present study suggest that HS-146, a novel PI3Kα inhibitor, may be an effective novel therapeutic candidate that suppresses breast cancer proliferation and metastasis by inhibiting the PI3K/Akt/mTOR pathway.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.331-337
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• 1997

Purpose : To evaluate our experience in the breast-conserving treatment for early breast cancer with special regard to recurrence Pattern and related risk factors. Materials and Method :Two hundred and sixteen patients with AJC stage 1and 11 breast cancer who received breast conserving treatment between January 1991 and December 1994 were evaluated A9e distribution ranged from 23-80 year old with a median a9e of 44. One hundred and seventeen Patients had 71 lesions and 99 Patients had 72 lesions. Axillary lymph nodes were involved in 73 patients. All patients received a breast conserving surgery (wide excision to quadrantectomy) and axillary node dissection followed by radiotherapy. Ninety six patients received chemotherapy before or after radiotherapy. Results : During the follow-up period (3-60 months, median 30 months), local recurrences were noted in six Patients (true: 3, elsewhere; 1, skin: 2). Sixteen patients developed distant metastases as the first sign of recurrence at 8-38 months (median 20 months) after surgery. Among them, three patients simultaneously developed local recurrence with distant metastases. Contralateral breast cancer developed in one Patient and non-mammary cancers developed in three patients. The actuarial 5 year survival rate was $88.4\%\;(stage\;I\;96.7\%,\;stage\;IIa\;95.2\%,\;stage\;IIb\;69.9\%)$. Age, I stage, number of involved axillary lymph nodes. and AJC stage were risk factors for distant metastases in univariate analysis. In the multivariate analysis, the number of involved axillary lymph nodes was the most significant risk factor for metastases. Conclusion : Local recurrence was not common in the early years after radiotherapy. Distant metastases occurred at a steady rate during the first three years and was more common in the Patients with larger tumors, higher number of involved axillary nodes, and younger age.

• Journal of Korean Traditional Oncology
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• v.21 no.2
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• pp.37-50
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• 2016

Ovarian cancer is the tenth most common cancer in Korean female, and the third most common cancer of female reproductive organ after breast cancer and uterine cervical cancer. In spite of develop of conventional treatment, high modality of ovarian cancer comes from difficulty of an early diagnosis. Recent studies revealed that combining conventional and integrative medical treatment can reduce the adverse effect of surgical operation, chemotherapy and radiotherapy. Also it can improve survival rate, quality of life. However there isn't still a systemic clinical protocol for ovarian cancer in Korean medicine. This study will be helpful to establish clinical practice guidelines of Korean Medicine for ovarian cancer. And further studies on integrative ovarian cancer treatment are needed to build the clinical practice guidelines of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4335-4340
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• 2016

Background: Bone metastasis is a single condition but presents with various patterns and severities. Skeletal-related events (SREs) deteriorate overall performance status and reduce quality of life. However, guidelines for early detection and management are limited. This study includes a survey of the prevalence of bone metastasis in cases with common cancers in Thailand as well as a focus on survival patterns and SREs. Materials and Methods: A retrospective cohort analysis was conducted using a database of the Chiang Mai Cancer Registry and the Musculoskeletal Tumor Registry of the OLARN Center, Chiang Mai University. The prevalence of bone metastasis from each type of primary cancer was noted and time-to-event analysis was performed to estimate cancer survival rates after bone metastasis. Results: There were 29,447 cases of the ten most common cancers in Thailand, accounting for 82.2% of the entire cancer registry entries during the study period. Among those cases, there were 2,263 with bone metastases, accounting for 7.68% of entries. Bone metastasis from lung, liver, breast, cervix and prostate are common in the Thai population, accounting for 83.4% of all positive cases. The median survival time of all was 6 months. Of the bone metastases, 48.9% required therapeutic intervention, including treatment of spinal cord and nerve root compression, pathological fractures, and bone pain. Conclusions: The frequency of the top five types of bone metastasis in Thailand were different from the frequencies in other countries, but corresponded to the relative prevalence of the cancers in Thailand and osteophilic properties of each cancer. The results of this study support the establishment of country specific guidelines for primary cancer identification with skeletal lesions of unknown origin. In addition, further clinical studies of the top five bone metastases should be performed to develop guidelines for optimal patient management during palliative care.

• Journal of Korean Neurosurgical Society
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• v.54 no.5
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• pp.399-404
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• 2013

Objective : The authors conducted a retrospective cohort study to determine prognostic factors and treatment outcomes of brain metastases (BM) from breast cancer (BC) after Gamma Knife radiosurgery (GKS). Methods : Pathologic and clinical features, and outcomes were analyzed in a cohort of 62 patients with BM from BC treated by GKS. The Kaplan- Meier method, the log-rank test, and Cox's proportional hazards model were used to assess prognostic factors. Results : Median survival after GKS was 73.0 weeks (95% confidence interval, 46.0-100.1). HER2+ [hazard ratio (HR) 0.441; p=0.045], Karnofsky performance scale (KPS) ${\geq}70$ (RR 0.416; p=0.050) and systemic chemotherapy after GKS (RR 0.282; p=0.001) were found to be a favorable prognostic factor of overall survival. Actuarial local control (LC) rate were $89.5{\pm}4.5%$ and $70.5{\pm}6.9%$ at 6 and 12 months after GKS, respectively. No prognostic factors were found to affect LC rate. Uni- and multivariate analysis revealed that the distant control (DC) rate was higher in patients with; a small number (${\leq}3$) of metastasis (HR 0.300; p=0.045), no known extracranial metastasis (p=0.013, log-rank test), or the HER2+ subtype (HR 0.267; p=0.027). Additional whole brain radiation therapy and metastasis volume were not found to be significantly associated with LC, DC, or overall survival. Conclusion : The treatment outcomes of patients with newly diagnosed BM from BC treated with GKS could be affected primarily by intrinsic subtype, KPS, and systemic chemotherapy. Therapeutic strategy and prognosis scoring system should be individualized based on considerations of intrinsic subtype in addition to traditionally known parameters related to stereotactic radiosurgery.

• Radiation Oncology Journal
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• v.31 no.3
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• pp.138-146
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• 2013

Purpose: To analyze the results of locoregional and systemic therapy in the breast cancer patients with locoregional recurrence (LRR) after mastectomy. Materials and Methods: Seventy-one patients who received radiotherapy for isolated LRR after mastectomy between January 1999 and December 2009 were retrospectively reviewed. Among the 71 patients, 59 (83.1%) underwent wide excision and radiotherapy and 12 (16.9%) received radiotherapy alone. Adjuvant hormonal therapy was given to 45 patients (63.4%). Oncologic outcomes including locoregional recurrence-free survival, disease-free survival (DFS), and overall survival (OS) and prognostic factors were analyzed. Results: Median follow-up time was 49.2 months. Of the 71 patients, 5 (7%) experienced second isolated LRR, and 40 (56%) underwent distant metastasis (DM). The median DFS was 35.6 months, and the 3- and 5-year DFS were 49.1% and 28.6%, respectively. The median OS was 86.7 months, and the 5-year OS was 62.3%. Patients who received hormone therapy together showed better 5-year DFS and OS than the patients treated with locoregional therapy only (31.6% vs. 22.1%, p = 0.036; 66.5% vs. 55.2%, p = 0.022). In multivariate analysis, higher N stage at recurrence was a significant prognostic factor for DFS and OS. Disease free interval (${\leq}30$ months vs. >30 months) from mastectomy to LRR was also significant for OS. The patients who received hormone therapy showed superior DFS and showed trend to better OS. Conclusion: DM was a major pattern of failure after the treatment of LRR after mastectomy. The role of systemic treatment for LRR after mastectomy should be investigated at prospective trials.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5081-5086
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• 2016

Background: Pathological factors, based mainly on immunohistochemistry (IHC) and histological differentiation, are mostly used to differentiate breast cancer (BC) subtypes. Our present aim was to describe the characteristics and survival of a relapsing BC patient cohort based on clinico-pathologic subtypes determined for the primary tumors. Methods: We used a clinico- pathological definition of BC subtypes based on histological grade (HG), estrogen receptor (ER), progesterone receptor (PgR),and epidermal growth factor receptor type 2 (HER2) expression assessed by IHC. We determined variables associated with loco-regional recurrence (LRR), second primaries (SP), systemic recurrence (SR) and post-recurrence survival (PRS). Results: Out of 1,702 patients, 240 (14%) had an event defined as recurrence. Those with recurrent disease were significantly younger than those without,and were initially diagnosed at more advanced stages, with larger tumors, greater lymph nodal involvement and higher HG. With a median follow up of 61 months (1-250), 4.6% of patients without recurrence and 56.6% of patients with an event defined as recurrence had died. The median PRS for the LRR group was 77 months; 75 months for those who developed a SP and 22 months for patients with an SR (p <0.0001). In SR cases, the median PRS was shorter for ER- tumors than for ER+ tumors (15 vs. 26 months, respectively; p = 0.0019, HR 0.44; CI: 0.25-0.44). Conclusions: Subtype, defined through classic histopathologic parameters determined for primary tumors, was found to eb related to type of recurrence and also to prognosis after relapse.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.1
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• pp.57-61
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• 2010

Objective: Second primary malignancy (SPM) that occur in various period and region are important factors that deteriorate long-term survival rate in patients who recovered from oral cancer. Researches such as chemoprevention are being tried to reduce occurrence of SPMs. Only if analysis of clinical features of patients who develop SPM such as period, region and factors precedes, adequate prevention and treatment of SPM is possible. But, there are few researches about clinical features of SPMs that have primary lesion in oral cavity. In this study, we analysis that occurrence rates, regions that happen, risk factors and effect to survival rates of 2nd primary malignancies in oral cancer patients. From this survey, we willing to collect basic data for prevention and early diagnosis of SPMs. Methods: The medical records of 139 patients of oral oncology clinic of National Cancer Center who had up to 2-years follow up records after surgical or radiological treatment due to squamus cell carcinoma of oral cavity were reviewed. In these patients, survey of occurrence rate of SPMs, duration, survival rate and risk factors about occurrence of SPMs such as history of smoking, body mass index, age, sex, stage of primary lesion and history of radiologic treatment were achieved. Results: There are 15 patients who developed SPM in 139 cases. The actual occurrence rate of SPM was 10.79% and SPM were more likely to occur in male patients with 11 male Vs 4 female patients. Median age of these patient is 61.47 within 32 to 74 range. The regions that develop SPM are oral cavities (2 cases), stomach (4 cases), esophagus (2 cases), lung (2 cases) and others (1 case each breast, larynx, cervix, liver and kidney). In addition, metachronous cancers were 11 cases which happened more common than 4cases of synchronous cancers. Surveys of risk factors that relate to development of SPMs, such as sex, age, history of radiologic treatment, body mass index, history of smoking and stage of primary disease were done. Among them, factor of sex is only appear statistically significant (P=0.001), but rest are not significant in statistically. Conclusion: Occurrence rates of SPMs were reported from 10% to 20% by precede study. In this study, occurrence rate of SPMs is 10.79% that is similar to results of precede research. In comparison of 5-yr survival rates of groups that develop SPMs or not, there is statistically significance between two groups. Present treatment modalities of SPMs are surgical operation, radiotherapy, chemotherapy and combination of these modalities. In choosing the treatment modality, we must consider the first treatment modality, region of primary disease, region of SPMs and general conditions of patient. Because development of SPMs have big effect on prognosis, prevention of SPMs must regard to important objective of treatments in patients of SCCa in oral cavity.