• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2839-2843
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• 2013

Objective: To investigate the effects of miR-106b on malignant characteristics of gastric cancer cells, and explore possible mechanisms. Methods: Expression of miR-106b, p21 and E2F was determined by real-time PCR. Transfection with miR-106b mimics was conducted, and gastric cancer cells with miR-106b overexpression were obtained. Cells transfected with mimic mutants and those without transfection served as negative and blank controls, respectively. Flow cytometry and transwell assays were adopted to detect the effects of miR-106b overexpression on cell cycle, migration and invasion of gastric cancer cells. Results:. The expression of miR- 106b in gastric cancer cells was significantly higher than that in normal gastric mucosa cells. Furthermore, the expression level of miR-106b rose according to the degree of malignacy among the three GC cell strains (MKN- 45 > SGC-7901 > MKN-28). Overexpression of miR-106b shortened the G0/G1 phase and accelerated cell cycle progression, while reducing p21 and E2F5, without any significant effects on the capacity for migration and invasion of gastric cancer cells. Conclusions: miR-106b may promote cell cycling of gastric cancer cells through regulation of p21 and E2F5 target gene expression.

• Journal of Gastric Cancer
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• 제5권2호
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• pp.101-105
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• 2005

목적: 일반적인 위암의 분류와 맞지 않게 고유근층까지 침범한 위암환자에서 몇몇 경우에는 조기위암의 그것과 유사하게 양호한 술 후 경과를 보이는 경우가 있다. 이에, 고유근층 침범도에 근거해서 고유근층 위선암으로 진단 받은 125예의 환자에 대한 후향적 분석을 시도하였다. 대상 및 방법: 125예의 고유근층 위암환자를 침윤도에 따라 세분류하여 전향적으로 임상병리학적 특징을 검토하고 222예의 점막하층 위암환자와 비교, 검토하였다. 각각의 환자에 대하여 100배 확대 시야에서 고유근층 내의 최대 심달도에 따라서 세분류하였다. 각 환자들은 심달도에 따라서 고유근층의 표층부 1/3까지만 침범한 경우를 mp1암, 그 이상으로 침범한 경우를 mp2암이라고 정의하였다. 결과: mp1암(n=50)인 환자는 mp2암(n=52)과 비교하여 림프절 전이율과 종양의 크기에서 통계적으로 유의하게 차이가 있었다(P=0.01,P=0.029). 5년 생존율에 있어서도 mp1암에서 mp2에서보다 통계적으로 유의하게 양호하였다($95.3\%\;vs.\;77.6\%$, P=0.0282). 림프절 전이가 없는 고유근층 암의 5년 생존율은 림프절 전이가 있는 경우보다 통계적으로 유의하게 양호하였다($93.3\%\;vs.\;78.2\%$, P=0.0192). 림프절 전이율에 있어서 mp1암은 점막하층암보다 유의하게 높았으나($42.5\%\;vs.\;23\%$, P=0.006) 5년 생존율에 있어서는 통계적으로 차이가 없었다. 결론: mp1암과 mp2암 사이에는 명확한 임상적 차이를 보였다. 고유근층암을 침윤도에 따라 세분류하는 것은 좀 더 정확한 예후 예측을 가능하게 할 수 있을 것이며 동시에 적절한 치료 계획을 세울 수 있을 것이다. 특히 mp1암의 임상병리학적 특징과 치료성적이 점막하층암의 그것과 유사하므로 점막하층암 환자에게 시행되는 것과 유사한 치료를 시행할 수 있을 것이다.

• 한국식품영양과학회지
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• 제44권1호
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• pp.44-48
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• 2015

알로에를 첨가한 표고버섯 배양 추출물(ESA)의 항암효과를 검정하기 위하여 인간 유방암 세포주인 MDA-MB-231에 ESA를 처리하여 생육저해 활성과 세포 이동 억제 효과를 확인하였다. MDA-MB-231 세포에 ESA를 처리하여 72시간 후 관찰한 결과 약간의 생육저해 활성을 나타내었으며, 또한 transwell에서 TNF-${\alpha}$가 처리된 세포에 ESA를 처리해 본 결과 migration/invasion 정도를 상당히 저해함을 알 수 있었다. 이러한 세포 이동능의 저해 기작은 웨스턴 블럿 분석을 통해 확인해 본 결과 p-ERK 신호를 통해 일어나며, ICAM-1 단백질의 발현을 억제함으로써 나타나는 것을 알 수 있었다. 따라서 본 실험에서는 알로에 첨가 담자균 배양추출물(ESA)은 인간 유방암세포에 대해 잠재적인 항암효과가 있음을 확인하였다. 이후 표고버섯 외 꽃송이버섯과 상황버섯에서의 알로에 배양액에 대한 항암효과에 대한 연구를 수행하고 있어 그 결과를 보고하고자 한다.

• BMB Reports
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• 제55권2호
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• pp.87-91
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• 2022

Aurora kinase is a family of serine/threonine kinases intimately associated with mitotic progression and the development of human cancers. Studies have shown that aurora kinases are important for the protein kinase C (PKC)-induced invasion of colon cancer cells. Recent studies have shown that aurora kinase A promotes distant metastasis by inducing epithelial-to-mesenchymal transition (EMT) in colon cancer cells. However, the role of aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A on PKC-induced cell invasion, migration, and EMT in human SW480 colon cancer cells. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) changed the expression levels of EMT markers, increasing α-SMA, vimentin, and MMP-9 expression and decreasing E-cadherin expression, with changes in cell morphology. TPA treatment induced EMT in a PKC-dependent manner. Moreover, the inhibition of aurora kinase A by siRNAs and inhibitors (reversine and VX-680) suppressed TPA-induced cell invasion, migration, and EMT in SW480 human colon cells. Inhibition of aurora kinase A blocked TPA-induced vimentin and MMP-9 expression, and decreased E-cadherin expression. Furthermore, the knockdown of aurora kinase A decreased the transcriptional activity of NF-κB and AP-1 in PKC-stimulated SW480 cells. These findings indicate that aurora kinase A induces migration and invasion by inducing EMT in SW480 colon cancer cells. To the best of our knowledge, this is the first study that showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.422-429
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• 2009

Invasion and metastasis is the main cause of cancer mortality. Angiogenesis is a prerequisite for the tumor growth and metastasis. Matrix metalloproteinases (MMPs) are the key enzymes playing in the invasive growth and metastasis of cancer as well as angiogenesis. Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L), has been reported to suppress cancer invasion and angiogenesis. In the present study, we investigated the antiinvasive effects of xanthohumol (1) and its synthetic derivatives, 4'-O-methylxanthohumol SEM ether (2), xanthohumol C (3), and xanthohumol C MOM ether (4) in relation to MMP expression in HT-1080 human fibrosarcoma cells. The compound 1 and its derivative, 3 and 4, significantly inhibited serum-induced HT-1080 cell invasion, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced activity and expression level of MMP-2 and MMP-9 in a concentration-dependant manner. In addition, they inhibited TPA-enhanced expression of MT1-MMP with relatively weak inhibition in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 level. The compound 1 significantly decreased the cell viability, whereas the derivatives, 2 and 3 showed no cytotoxicity, and compound 4 showed slight cytotoxicity in the cells. Furthermore, in a chick chorioallantoic membrane (CAM) assay, the derivatives 3 and 4 dose-dependently suppressed vascular endothelial growth factor (VEGF)-induced angiogenesis, which is similar to that of compound 1. Taken together, the results indicate that compounds 3 and 4 may be valuable anti-angiogenic agents in the treatment of chronic diseases such as cancer and inflammation working through suppression of MMP-2 and MMP-9.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5017-5021
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• 2013

Objective: MicroRNAs (miRNAs) are a small class of non-coding, single-stranded RNAs with a critical role in genesis and maintenance of renal cancer mainly through binding to 3'-untranslated regions (3'UTR) of target mRNAs, which causes a block of translation and/or mRNA degradation. The aim of the present study was to investigate the potential effects of miR-122 in human renal cell carcinomas. Methods: The expression level of miR-122 was quantified by qRT-PCR. MTT, colony formation, invasion and migration assays were used to explore the potential functions of miR-122 in human renal cell carcinoma cells. Results: Cellular growth, invasion and migration in two A498 and 786-O cells were significantly increased after miR-122 transfection. Further experiments demonstrated that overexpression of miR-122 resulted in the increase of phospho-Akt (Ser473) and phospho-mTOR (Ser2448), then activation of mTOR targets, p70S6K and 4E-BP1. Conclusions: The up-regulation of miR-122 may play an important role in the progress of renal cancer through activating PI3K/Akt signal pathway and could be a potential molecular target for anti-cancer therapeutics.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5397-5402
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• 2013

The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because of difficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticancer activities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIE on metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCC cells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasion of the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- and time-dependent manners. Incubation of SK-Hep1 cells with $200-400{\mu}g/mL$ of SIE significantly inhibited cell adhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cells showed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasion capacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9 and MT1-MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, it was suggested that SIE could be used as potential anti-tumor agent.

• Journal of Gynecologic Oncology
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• 제29권6호
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• pp.97.1-97.12
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• 2018

Objective: Women with cervical cancer (CC) found to have positive surgical margins, positive lymph nodes, and/or parametrial invasion receive a survival benefit from postoperative chemoradiotherapy (CRT) vs. radiation therapy (RT) alone. However, older women may not benefit to the same extent, as they are at increased risk of death from non-oncologic causes as well as toxicities from oncologic treatments. This study sought to evaluate whether there was a survival benefit of CRT over RT in elderly patients with cervical cancer. Methods: The National Cancer Database was queried for patients ${\geq}70$ years old with newly diagnosed IA2, IB, or IIA CC and positive margins, parametrial invasion, and/or positive nodes on surgical resection. Statistics included logistic regression, Kaplan-Meier overall survival (OS), and Cox proportional hazards modeling analyses. Results: Altogether, 166 patients met inclusion criteria; 62 (37%) underwent postoperative RT and 104 (63%) underwent postoperative CRT. Younger patients and those living in areas of higher income were less likely to receive CRT, while parametrial invasion and nodal involvement were associated with an increased likelihood (p<0.05 for all). There were no OS differences by treatment type. Subgroup analysis by number of risk factors, as well as each of the 3 risk factors separately, also did not reveal any OS differences between cohorts. Conclusion: In the largest such study to date, older women with postoperative risk factor(s) receiving RT alone experienced similar survival as those undergoing CRT. Although causation is not implied, careful patient selection is paramount to balance treatment-related toxicity risks with theoretical outcome benefits.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.117-122
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• 2012

Aim: To elucidate the effects of hyperthermic $CO_2$ pneumoperitoneum on human gastric AGS cells. Methods: Based on a newly devised in vitro study model, we evaluated the anti-cancer effects of HT-$CO_2$ ($42-44^{\circ}C$ for 2-4h) on human gastric cancer cells, and also the corresponding mechanisms. Results: HT-$CO_2$ ($42-44^{\circ}C$ for 2-4h) severely inhibited cell proliferation as assessed by Cell Counting Kit-8 assay, while inducing apoptosis in a temperature- and time-dependent manner demonstrated by annexin-V/PI flow cytometry and morphological analysis (Hoechst/PI fluorescence). In addition, it was found that HT-$CO_2$ ($42-44^{\circ}C$ for 2-4h) promoted the up-regulation of Bax by western blotting. Significantly, it could also suppress gastric cancer cell invasion and metastasis by in vitro invasion and motility assay. Conclusion: In conclusion, HT-$CO_2$ had an efficacious cytotoxic effect on gastric cancer cells through Bax-induced mitochondrial apoptotic signaling. Our studies indicate that it may serve as a potential therapy for peritoneal carcinomatosis of gastric cancer. Further investigations in vivo using animal models are now urgently needed.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9277-9281
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• 2014

Purpose: To investigate clinicopathological features in patients with recurrent colorectal cancer within 1 year and more than 1 year after curative resection. Materials and Methods: We retrospectively evaluated 103 patients with disease recurrence before versus after 1 year of resection. Thirty-two patients (31%) were diagnosed with recurrence less than 1 year after curative resection for colorectal cancer (early recurrence) and 71 (69%) after more than 1 year (non-early recurrence). Results: The early recurrence group displayed a significantly lower overall survival rate for both colon cancer (p=0, 01) and rectal cancer (p<0.001). Inadequate lymph node dissection was a significant predictor for early relapse. There were no statistically significant differences in clinicopathological variables such as age, sex, primary tumor localization, stage, depth of invasion, lymphovascular invasion and perineural invasion between the early and non-early recurrence groups. However, a K-ras mutation subgroup was significantly associated with early recurrence (p<0.001). Conclusions: Poor survival is associated with early recurrence for patients undergoing resection for non-metastatic colorectal cancer, as well as K-ras mutation.