• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2823-2828
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• 2012

Objective: To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. Method: On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Results: Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenograpfts in-situ than in the negative control group(both P<0.01). Moreover, the expression of VEGF-C, VEGF-D and VEGFR-3 proteins and mRNAs were significantly higher in xenografts in-situ (both P<0.01), in conformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. Conclusions: In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3045-3050
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• 2014

Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely related with its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domain multiple 7 (EGFL7) is overexpressed by many tumors, such as colorectal cancer and hepatocellular carcinoma; it is also correlated with progression, metastasis, and a poor prognosis. However, the role of EGFL7 in RCC is not clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture system in vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migration and tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesion kinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7 cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells was significantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylation was abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group was noticeably smaller than those in the 786-0 cell group and their vascular density was also significantly decreased. These data suggest that EGFL7 has an important function in the growth of RCC by facilitating angiogenesis.

• Advances in pediatric surgery
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• 제10권2호
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• pp.145-149
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• 2004

A 12-year-old boy with severe periumbilical pain visited the emergency room. Physical examination, abdominal ultrasonography, colonoscopy and CT, identified a lesion of sigmoid colon. Endoscopic biopsy showed a signet ring cell carcinoma of the sigmoid colon. On explorative laparotomy, cancer invasions of the adjacent structures and metastases on peritoneal wall were noticed. We performed palliative loop-ileostomy. He underwent chemotherapy and radiotherapy for 3 months. The second case was a 16-year-old boy with abdominal pain and hematochezia, transferred to our hospital with the diagnosis of acute appendicitis with periappendiceal abscess. Although he underwent appendectomy, the abdominal pain persisted. Digital rectal examination revealed a lumen-obstructing fungating mass in the rectum. Endoscopic biopsy revealed a adenocarcinoma. Cancer invasion of the adjacent structures and metastases involving the mesentery of the small intestine were found at laparotomy. A palliative procedure, a Hartmann's operation and end-colostomy at the sigmoid colon were performed. The patient died 8 month later due to pneumonia and sepsis. Chemotherapy was not applied.

• 대한임상검사과학회지
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• 제36권2호
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• pp.193-198
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• 2004

PET/CT combines the functional information from a positron emission tomography (PET) exam with the anatomical information from a computed tomography (CT) exam into one single exam. A CT scan uses a combination of x-rays and computers to give the radiologist a non-invasive way to see inside your body. One advantage of CT is its ability to rapidly acquire two-dimensional pictures of your anatomy. Using a computer these 2-D images can be presented in 3-D for in-depth clinical evaluation. A PET scan detects changes in the cellular function - how your cells are utilizing nutrients like sugar and oxygen. Since these functional changes take place before physical changes occur, PET can provide information that enables your physician to make an early diagnosis. The PET exam pinpoints metabolic activity in cells and the CT exam provides an anatomical reference. When these two scans are fused together, your physician can view metabolic changes in the proper anatomical context of your body. PET/CT offers significant advantages including more accurate localization of functional abnormalities, and the distinction of pathological from normal physiological uptake, and improvements in monitoring treatment. A PET/CT scan allows physicians to measure the body's abnormal molecular cell activity to detect cancer (such as breast cancer, lung cancer, colorectal cancer, lymphoma, melanoma and other skin cancers), brain disorders (such as Alzheimer's disease, Parkinson's disease, and epilepsy), and heart disease (such as coronary artery disease).

• Archives of Pharmacal Research
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• 제19권5호
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• pp.342-347
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• 1996

Doxorubicin, one of the clinically most useful anticancer agents, is used alone or in combination with other drugs against a wide variety of tumors, recently. But cancer cells developed resistance to this agent in many ways. This resistance is an important limiting factor of doxorubicin for anticancer drug. We newly established doxorubicin-resistant HCT15/CL02 subline from parental HCT15 human adenocarcinoma colon cancer cells. HCT15/CL02 revealed resistance to doxorubicin about 85-fold of its parental cells, and it also revealed cross-resistance to actinomycin D, etoposide and vinblastine but not to displatin and tamoxifen. And verapamil, a reversal agent of multidrug-resistance (MDR) by P-glycoprotein, elevated the cytotoxicity of doxorubicin against both HCT15 and GCT15/CL02 cells. But the relative resistant rate was not reduced. Verapamil had no effects on the tosicity of cisplatin to the both cell lines. These results indicate that HCT15/CL02 cells have some functionally complex mechanisms for MDR.

• 대한의생명과학회지
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• 제28권4호
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• pp.312-316
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• 2022

We have previously reported that genetically modified tumor cells with 4-1BBL have anti-cancer effects in a CT26 mouse colorectal tumor model. In this study, genetically modified tumor cells with 4-1BBL were evaluated for their potential as candidates for preventive and therapeutic cancer vaccine. To identify the effect of preventive and therapeutic vaccine of genetically modified tumor cells with 4-1BBL, tumor growth pattern of CT26-4-1BBL as a cancer vaccine was examined compared to CT26-beta-gal. In therapeutic vaccination, CT26-WT was inoculated into mice and then vaccinated mice with doxorubicin (Dox)-treated CT26-beta-gal and CT26-4-1BBL (single or three times). Triple vaccination with Dox-treated tumor cell inhibited tumor growth compared to single vaccination. Vaccination with CT26-4-1BBL showed an efficient tumor growth inhibition compared to vaccination with CT26-beta-gal. For preventive vaccination, Dox-treated CT26-beta-gal and CT26-4-1BBL was vaccinated into mice with three times and then administered mice with CT26-WT. Preventive vaccination with CT26-4-1BBL showed no tumor growth. Preventive vaccination with CT26-beta-gal also led to tumor-free mice. These results suggest that genetically modified tumor cells with 4-1BBL can be used as therapeutic or preventive cancer vaccine.

• Journal of Digestive Cancer Research
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• 제4권2호
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• pp.64-76
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• 2016

The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor-&B (NF-κB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-κB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.

• IMMUNE NETWORK
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• 제12권2호
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• pp.66-69
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• 2012

The immunological death induction by EY-6 on the human tumor cell lines was screened. Human colon carcinoma (HCT15, HCT116), gastric carcinoma (MKN74, SNU668), and myeloma (KMS20, KMS26, KMS34) cells were died by EY-6 treatment with dose-dependent manner. CRT expression, a typical marker for the immunological death, was increased on the EY-6-treated colorectal and gastric cancer cells. Interestingly, the effects on the myeloma cell lines were complicated showing cell line dependent differential modulation. Cytokine secretion from the EY-6 treated tumor cells were dose and cell-dependent. IFN-${\gamma}$ and IL-12 secretion was increased in the treated cells (200% to over 1000% of non-treated control), except HCT116, SNU668 and KMS26 cells which their secretion was declined by EY-6. Data suggest the potential of EY-6 as a new type of immuno-chemotherapeutics inducing tumor-specific cell death. Further studies are planned to confirm the efficacy of EY-6 including in vivo study.

• Journal of Nutrition and Health
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• 제27권6호
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• pp.552-562
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• 1994

The study was designed to observe the effect of different dietary fats on the incidence of colorectal tumor and in vivo cell proliferation in colon carcinogenesis. Male Sprague Dawley rats were intrarectally infused with chemical carcinogen(methylnitrosourea, MNU) and fed 16%(w/w) fat diet containing one of dietary fats(beef tallow, corn oil, perilla oil) for 30 weeks. To measure in vivo cell proliferation, the incorporation of 5-bromo-2-deoxyuridine(BrdU) into DNA was localized using the monoclonal anti-BrdU antibody. Large number of tumors were found in the distal colon and tumor incidence was increased in the order of perilla oil(57.7%)$\alpha$-linolenic acid rich in perilla oil could have a protective effect against colon cancer compared to saturated fatty acid or n-6 linoleic acid.

• 생명과학회지
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• 제31권10호
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• pp.929-936
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• 2021

본 연구에서는 시판하는 천연물 library (Selleckchem, L1400)로부터 암세포 항 성장 활성을 보여주는 천연물을 선별하였다. 즉, 인간 대장암 세포주인 HCT116에 50 μM의 각 천연물을 처리한 후 세포 생존율을 측정하였다. 1차 선별과정을 통하여 5종의 천연물(chrysin, diosmetin, emodin, piperlongumine, tanshinone I)을 선별하였다. 5종의 천연물에 의한 NAG-1 단백질의 발현을 확인한 결과 chrysin과 emodin에 의해서 발현이 현저하게 증가하였다. 또한, chrysin과 emodin은 농도의존적으로 세포 생존율을 감소시켰으며, chrysin과 emodin은 항암 단백질인 NAG-1의 발현을 농도 및 시간 의존적으로 증가시켰다. 게다가, chrysin과 emodin 처리에 의해 증가된 PARP cleavage가 NAG-1 siRNA transfection에 의해서 감소됨을 확인함으로써, chrysin과 emodin에 의한 세포사멸과 NAG-1의 발현 증가가 직접적인 관련이 있음을 증명하였다. 따라서, 본 연구결과는 암세포 항 성장 활성을 보여주는 천연물 선별에 대한 기초 데이터를 제공해 주며, chrysin과 emodin에 의한 암세포 항 성장 활성 및 세포사멸의 기전을 이해하는 데 도움을 줄 것으로 판단된다.