• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.835-840
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• 2013

Accumulating evidence has shown that microRNAs are involved in cancer development and progression. However, it remains unknown about the potential role of miR-19a in the pathogenesis of gastric cancer. Here, we report that suppressor of cytokine signaling 1 (SOCS1) is a novel target of miR-19a in gastric cancer cells and that miR-19a expression is inversely correlated with SOCS1 expression in gastric cancer cells and a subset of gastric cancer tissues. Ectopic expression of miR-19a dramatically promoted proliferation and tumorigenicity of gastric cancer cells both in vitro and in vivo. Moreover, we showed that silencing of SOCS1 promoted cell growth and colony formation resembling that of miR-19a overexpression, whereas re-introduction of SOCS1 (without the 3'-UTR) attenuated the pro-tumorigenic functions. Taken together, our findings suggest that the SOCS1 gene is a direct target of miR-19a, which functions as an oncogenic miRNA in gastric cancer by repressing the expression of tumor suppressor SOCS1.

• IMMUNE NETWORK
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• 제6권1호
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• pp.13-19
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• 2006

Background: Granulocyte colony stimulating factor (G-CSF) is known as a cytokine central to the hematopoiesis of blood cells and to modulate their cellular functions. Besides granulocytes and their precursors, monocytes/macrophages and endothelial cells are direct target cells of G-CSF action. G-CSF influences immune cells in an anti inflammatory way. Methods: To evaluate whether G-CSF has a potential for preventing or ameliorating diseases characterized by mucosal inflammation, we used a mouse model with trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. To the mice model G-CSF was administrated daily by intraperitoneal injection. Macroscopic evaluation and immunohistochemical analysis of colonic tissues were performed. Results: Re combinant human G-CSF significantly inhibited LPS-induced TNF-${\alpha}$ mRNA expression in THP-1 cells. As for in vivo relevance, G-CSF dramatically reduced the weight loss of mice, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, G-CSF suppressed the expression of tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and intercellular adhesion molecule-1 in TNBS colitis. Conclusion: Current results demonstrate that G-CSF may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

• 대한의생명과학회지
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• 제19권4호
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• pp.295-302
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• 2013

Some of the pituitary adenomas are invasive and spread into neighboring tissues. In previous studies, the invasion of pituitary adenomas is thought to be associated with epithelial-mesenchymal transition (EMT). In addition to that, we thought that mesenchymal stem cells (MSCs) exist in relevant microenvironment in pituitary adenoma. However, it has been little known about the existence of MSCs from pituitary adenoma. So we investigated whether mesenchymal stem-like cells (MSLCs) can be isolated from the pituitary adenoma specimen. We isolated and cultured candidate MSLCs from the fresh pituitary adenoma specimen with the same protocols used in culturing bone marrow derived MSCs (BM-MSCs). The cultured candidate MSLCs were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with MSCs. Candidate MSLCs were exposed to mesenchymal differentiation conditions to determine the mesenchymal differentiation potential of these cells. To evaluate the tumorigenesis of candidate MSLCs from pituitary adenoma, we implanted these cells into the brain of athymic nude mice. We isolated cells resembling BM-MSCs named pituitary adenoma stroma mesenchymal stem-like cells (PAS-MSLCs). PAS-MSLCs were spindle shaped and had adherent characteristics. FACS analysis identified that the PAS-MSLCs had a bit similar surface markers to BM-MSCs. Isolated cells expressed surface antigen, positive for CD105, CD75, and negative for CD45, NG2, and CD90. We found that these cells were capable of differentiation into adipocytes, osteocytes and chondrocytes. Tumor was not developed in the nude mice brains that were implanted with the PAS-MSLCs. In this study, we showed that MSLCs can be isolated from a pituitary adenoma specimen which is not tumorigenic.

• Clinical and Experimental Pediatrics
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• 제60권11호
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• pp.365-372
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• 2017

Purpose: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot. Results: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group. Conclusion: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.

• Journal of Chest Surgery
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• 제30권12호
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• pp.1214-1218
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• 1997

폐전이 골 연부조직 육종에 대한 폐절제 및 합병치료의 성적을 분석하였다. 1986년부터 1996년까지 14례 (남자 11례, 여자 3례)에서 15회의 폐절제술을 시행하였는데, 1례에서는 폐전이 육종의 재발로 2회의 폐절제술을 시행하였다. 절제된 폐전이 육종의 수는 1∼5개였다. 폐전이 육종의 병리조직학적 소견상 4례는 골육종 이었으며, 10례는 연부조직 육종이었다 폐절제술후 평균 생존기간은 29.2개월이었으며, Kaplan-Meier식에 의 한 5년생존율은 33.2%였다. 14례중 3례의 종양 자유기간이 3년이상으로 평균 생존기간은 52.6개월이었으며, 3년 이하의 11례는 추적기간중 모두 사망하여 이들의 평균 생존기간은 17.3개월이었다. 결론적으로 폐전이 육종에 대한 폐절제술은 뚜렷한 수명 연장 효과가 있을 것으로 생각된다.

• 대한수의학회지
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• 제54권3호
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• pp.171-177
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• 2014

Garlic and mugwort have long been used in traditional medicine to prevent various diseases. Several in vitro studies have reported protective efficacies of garlic and mugwort in cases of gastric cancer. In the present study, we investigated the cancer preventive effects of garlic and mugwort mixture extract (GME) in a Helicobacter (H.) pylori-associated gastric carcinogenesis mouse model. To induce gastric cancer, C57BL/6 mice were treated with N-methyl-N-nitrosourea and H. pylori. Various concentrations of GME (0, 100, 500, and 1,000 ppm) were then fed to the mice for 38 weeks, after which the tumor tissues were examined for histopathology, mucin histochemistry and ${\beta}$-catenin. The incidence of gastric tumors was significantly lower in the highest dose GME-treated mice (46.7%) than control mice (85.7%) (p < 0.05). The multiplicity and size of tumors were also significantly reduced by GME feeding in a dose-dependent manner (p < 0.01). Furthermore, GME suppressed the H. pylori-associated chronic inflammation measured by histologic grading of H. pylori density, chronic gastritis, glandular atrophy and intestinal metaplasia in non-tumorous gastric mucosae. Our data suggest that GME suppresses gastric tumorigenesis via suppression of H. pylori-associated chronic inflammation.

• 대한두경부종양학회지
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• 제15권1호
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• pp.3-8
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• 1999

Objective: The expression of Ki67, a proliferation marker, and p27, a cyclin dependent kinases(CDKs) inhibitor, has been studied in various human neoplasms. This study was carried out to determine whether these markers are useful in distinguishing benign from malignant lesions of the thyroid or predicting biologic behavior of malignant lesions. Material and Methods: Using immunohistochemical techniques with monoclonal antibodies to Ki67 and p27, we analyzed the expression of Ki67 and p27 in various thyroid disorders(25 follicular adenomas, 47 follicular carcinomas, 16 papillary carcinomas, 20 adenomatous goiters and 40 normal thyroid tissues). The labeling indices(LIs) were determined by counting cells expressing these markers in 1000 cells per immunostained slide. Results: Neoplastic thyroid diseases showed higher expression of Ki67 and lower expression of p27 than non-neoplastic diseases(p<0.05). The expression of p27 was significantly different between follicular adenomas($LI=55.4{\pm}5.7$) and follicular carcinomas($LI=23.2{\pm}10.2$). There was, however, no significant correlation between the degree of Ki67 and p27labeling indices and types of carcinoma or clinical aggressiveness of diseases. Conclusion: The degree of Ki67 and p27 expression was useful in distinguishing between benign from malignant thyroid lesions, particulary between follicular adenoma and follicular carcinoma, but was not directly proportional to the tumor aggressiveness.

• 생명과학회지
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• 제21권6호
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• pp.912-922
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• 2011

Cancer-testis (CT) antigen은 다양한 종양과 정상 고환에서 제한적으로 발현되고, 암환자에서 체액성 면역과 세포성 면역반응을 일으키는 종양항원이다. 지금까지 MAGE, NY-ESO-1, GAGE, BAGE, LAGE, SSX2, NY-SAR-35를 포함하여 100개 이상의 CT antigen들이 동정되었고, 이러한 CT antigen들은 백신을 이용한 면역치료에 있어서 중요한 요소로 작용할 것으로 사료된다. CT antigen은 여러 가지 방법들을 통해 확인할 수 있고, X 염색체에 암호화 되어있는 CT-X gene과 X 염색체에 암호화 되어있지 않은 non-X CT gene으로 나눌 수 있다. 또한 몇몇의 종양에서 비정상적으로 활성화되지 않거나 발현되지 않는 CT antigen도 존재한다. 생식세포 조직과 종양에서 CT-X gene의 생물학적 역할이 아직 명확하게 규명되지 않았지만, 현재 여러 종류의 CT antigen을 이용한 암백신 치료법이 시도되고 있다. 본 논문은 암의 면역치료를 위한 CT antigen의 최근 연구동향과 앞으로의 연구방향에 대해 서술하고자 한다.

• 대한임상검사과학회지
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• 제43권3호
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• pp.113-119
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• 2011

This study was designed to determine the effects of larval extracts from Protaetia brevitarsis seulensis shade dried larva from Korea and China on liver tissues of hepatic injury groups. The experimental groups are divided into five groups; Normal, carbon tetrachloride single injection ($CCl_4$), Pb-CHI ($CCl_4$ + P. brevitarsis shade dried larva from China), Pb-KOR ($CCl_4$ + P. brevitarsis shade dried larva from Korea) and SIL ($CCl_4$ + 0.35% silymarin) groups. Sprague Dawley rats were oral injected with $CCl_4$ at a dose l mg/kg (20% in corn oil) for induction of liver damage for 4 weeks. Each experimental group was fed with a dose 50 mg/kg of larval extracts based on medicinal preparations from 3 weeks to 4 weeks after $CCl_4$ treatment. At the end of 4 weeks, we evaluated the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transferase (GPT), alkaline phosphatase (ALP) and blood urea nitrogen (BUN) in serum and the cytokine levels of tumor necrosis factor-${\alpha}$) (TNF-${\alpha}$) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the cells isolated from spleen and liver. The histological analysis was also conducted. The $CCl_4$ injection reduced body weight, induced congestion of middle lobe and hepatocytic degeneration, resulting in disintegration of hepatic cords, and increased biochemical markers of blood related to hepatic injury. On the other hand, the Pb-CHI and Pb-KOR group decreased the levels of biochemical markers in blood and cytokine levels in spleen and liver. Especially, the Pb-KOR group facilitated the recovery of biochemical values of blood related to hepatic injury, hepatic lesions and fibrosis. Taken together, larval extract from P. brevitarsis might prevent acute hepatotoxicity and enhance the recovery of liver fibrosis and cirrhosis induced by $CCl_4$, and the ingredients could be a promising candidate for the prevention and treatment of hepatic disorders.

• 동의생리병리학회지
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• 제24권3호
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• pp.463-469
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• 2010

This research is performed to obtain positive evidences of Mori cortex, a kind of oriental medicinal herbs, in the cellular levels. The extracts of M. cortex have shown anti-inflammatory effects against cutaneous inflammation and clinical effects on pulmonary asthma and congestion in oriental medicine. Thus BV2 cells were chosen because microglia are considered as the main immunocompetent cells in the central nervous system. Lipopolysaccharide (LPS)-induced microglial activation of cultured BV2 cells and subsequent release of nitric oxide (NO) and Prostaglandin E2 (PGE2) were effectively suppressed by methylene chloride extract of Morus alba L. (MEMA). From the inflammation-mediated mRNA and protein analyses, we showed that inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-$1{\beta}$ (IL-$1{\beta}$) and tumor necrosis alpha (TNF-${\alpha}$) induced by LPS were markedly decreased by MEMA treatment. From the observation of nuclear factor-kB (NF-${\kappa}B$) which is controlling and mediating inflammation through COX-2 and iNOS, there showed that p65, a subunit of NF-${\kappa}B$, was increased in nuclear and $I{\kappa}B$, a competitor of NF-${\kappa}B$, was recovered in cytosol after MEMA treatment. These are corresponding with results of iNOS, COX-2, IL-$1{\kappa}$ and TNF-${\alpha}$, and confirm some suppressive effect against transcriptional activation of NF-${\kappa}B$. In conclusion, the anti-inflammatory action of M. cortex against BV2 microglia cells is expected to protect nerve tissues through suppression of neuronal inflammation in various neurodegenerative diseases.