• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2429-2435
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• 2012

Methyl isocyanate may have a role in cancer etiology, although the link is unclear. There is evidence in the literature that it can induce cancer in animals but the carcinogenic potency is weak. Pheochromocytoma of adrenal medulla and acinar cell tumors of pancreas have been observed in methyl isocyanate exposed animals. Conversely, emerging data from population-based epidemiological studies are contradictory since there is no evidence of such cancers in methyl isocyanate exposed humans. Recently, we reported a high prevalence of breast and lung cancers in such a population in Bhopal. In vitro findings appearing in the latest scientific literature suggest that genomic instability is caused by methyl isocyanate analogs in lung, colon, kidney, ovary epithelial cells, and that hepatocytes may undergo oncogenic transformation, have obvious implications. The conflicting information prompted us to present this update over the last three decades on methyl isocyanate-induced cancers after an extensive literature search using PubMed. While the pertinent literature remains limited, with a scarcity of strong laboratory analyses and field-epidemiological investigations, our succinct review of animal and human epidemiological data including in vitro evidences, should hopefully provide more insight to researchers, toxicologists, and public health professionals concerned with validation of the carcinogenicity of methyl isocyanate in humans.

• Journal of Oral Medicine and Pain
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• 제24권2호
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• pp.145-161
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• 1999

The proto-oncogene bcl-2 confers a survival advantage to cells by blocking programmed cell death (apoptosis). Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. An increased expression of nitric oxide synthetase(NOS) has been observed in human colon cancer cell lines as well as in human gynecological, breast, and CNS tumors. However there have been only a few reports on the expression of bcl-2 and $NOS_2$ in oral white lesions and cancer. The aim of this study was to investigate the relationship between the expression of Bcl-2 and $NOS_2$ and several pathological parameters such as histological types and layers. We reported desregulation of bcl-2 and $NOS_2$ expression during progression from oral white lesion, lichen planus and leukoplakia to squamous cell carcinoma. The obtained results were as follows: 1. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein and $NOS_2$ in formalin-fixed paraffin-embedded tissue sections revealed that bcl-2 expression is restricted to the basal cell layer and $NOS_2$ was mild expressed only in subepithelial inflammatory cells in normal human mucosa. There wasn't specific finding of those in lichen planus and leukoplakia. 2. Bcl-2 immunoreactivity in severe epithelial dysplasia or CIS occurs throughout the epithelium, $NOS_2$ reactivity in most superficial layer were noted. 3. In well-differentiated squamous cell carcinomas, mostly bcl-2 was overexpressed. In moderated and poor squamous cell carcinomas, the expression of $NOS_2$ was increased and that of bcl-2 was decreased. 4. The immunoreactivity of bcl-2 was 12.5% of normal mucosa, 30% of leukoplakia, 44% of lichen planus and 67% of carcinoma in situ. In carcinoma, those were 43%, 50% and 67% according to differentiation, respectively. 5. The immunoreactivity of $NOS_2$ was 25% of normal mucosa, 70% of leukoplakia, 78% of lichen planus and 100% of carcinoma in situ and epithelial dysplasia. In carcinoma, those were higher in moderated(100%) and poor(83%) squamous cell carcinomas than in well differentiated type(71%). 6. The expression of bcl-2 and $NOS_2$ by Western blot was increased highly in lichen planus and leukoplakia. Therefore, the expression of bcl-2 was increased in the white and precancerous lesions and that was decreased by differentiation of carcinoma. However, $NOS_2$ immunoreactivity in carcinoma in situ was lower than those in moderated and poor squamous cell. These findings suggest that the interaction of bcl-2 and $NOS_2$ may be roled importantly in growth and development of carcinoma.

• Journal of Microbiology and Biotechnology
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• 제33권9호
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• pp.1206-1212
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• 2023

The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N⁶-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

• 대한임상검사과학회지
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• 제54권3호
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• pp.217-223
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• 2022

다양한 건강기능식품 중 프로바이오틱스는 전 세계적으로 가장 방대한 시장을 이루고 있으며, 장 건강이 우리 몸의 전반적인 면역작용을 조절하며 질병을 예방하고, 나아가 치료에 도움을 줄 수 있다는 연구결과에 따라 지속적으로 프로바이오틱스에 대한 관심이 증가하고 있다. 본 연구에서는 무화과식초가 가진 항균능을 이용하여 유제품과 드레싱 소스를 개발하여 그 선호도를 조사하고 대장세포에 미치는 영향을 분석하고자 하였다. 일반우유에 5% 무화과식초를 첨가하였을 때 마시는 요거트와 리코타치즈에 대한 가장 만족도가 높았다. 제조된 유제품에서 분리한 균은 Leuconostoc lactis이며 1.0×10⁷~1.0×10⁸ CFU/mL 이상의 세균수가 측정되어 식품의 기준 및 규격의 기준치를 만족하였다. 인체의 소장 상피세포와 흡사하게 증식되는 Caco-2 세포주에서 세포생존율을 관찰한 결과, 유청을 10% 농도로 처리하였을 때 세포생존율이 19% 가량 유의적으로 증가하였다. 농도별로 유청을 처리하였을 때 최대 58%의 항산화능을 보였다. 또한 유청에서 분리된 Leuconostoc lactis는 우수한 부착능이 관찰됨에 따라 장건강에 도움을 주는 유제품임을 확인하였다.

• 생명과학회지
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• 제27권11호
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• pp.1245-1255
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• 2017

암세포는 정상세포와는 다른 metabolism 특히 glycolytic switch를 나타낸다. Glycolytic switch는 암세포가 정상세포와 달리 산소가 충분한 상태에서도 미토콘드리아에 의존하지 않고 glycolysis를 통해 대부분의 ATP 에너지를 생성하는 현상이다. 또한 암세포는 invasion 및 metastasis 능력을 획득하기 위해 epithelial-mesenchymal transition (EMT)를 나타낸다. EMT와 glycolytic switch는 암세포의 생존 및 증식에 관여하는 중요한 현상이지만, 이들 상호작용 및 그 기작에 대한 연구는 아직 밝혀져 있지 않다. Snail은 EMT를 유도하는 주요한 전사인자이다. 본 연구진은 이전 연구에서 Snail이 발생 및 암성장에 관여하는 전사인자인 Dlx-2에 의해 조절됨을 밝혔다. 또한 Wnt가 Dlx-2/Snail cascade을 통하여 EMT 및 glycolytic switch을 유도함을 밝혔다. 본 연구에서는 glycolytic switch가 Wnt에 의한 EMT에 미치는 영향을 규명하고자 하였다. Dlx-2/Snail의 glycolytic switch target 유전자로 phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2)를 발굴하였다. PFKFB2는 fructose-2,6-bisphosphate (F2,6BP)의 합성 및 분해에 관여하는 효소로서 glycolysis에서 중요하게 작용한다. Wnt에 의해 PFKFB2 발현이 Dlx-2/Snail 의존적으로 증가함을 관찰하였다. 또한 PFKFB2를 knockdown한 결과 Wnt에 의한 EMT가 억제되므로 glycolytic switch가 Wnt에 의한 EMT에 관여할 가능성이 높을 것으로 보인다. 뿐만 아니라 PFKFB2 shRNA가 xenograft mouse model에서 tumor 성장 및 metastasis를 억제하는 것으로 나타났다. 또한 Human 암조직에서 정상조직에 비해 PFKFB2의 발현이 높음을 관찰하였다. 따라서 PFKFB2가 Wnt-Dlx-2/Snail-induced EMT 및 metastasis에서 중요한 역할을 할 것으로 예상된다.

• 한국식품저장유통학회지
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• 제31권1호
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• pp.183-196
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• 2024

본 연구에서는 AEEL의 고당으로 유도되는 장 상피세포 보호효과 및 L.brevis의 증식에 대한 영향을 확인하기 위해 수행되었다. AEEL은 우수한 환원력, 라디칼 소거 활성 및 지질과산화물 생성 억제 활성을 나타냈으며 고당, H₂O₂, 및 LPS로 유도된 HT-29 세포에서 우수한 세포 생존율 및 산화적 스트레스 억제 활성을 가지는 것으로 나타났다. 또한, AEEL은 항당뇨 활성을 가진 장내 유익균인 L.brevis의 증식에 효과를 보였으며 탄수화물 가수분해 효소인 α-glucosidase 및 최종당화산물 생성에서도 우수한 억제 활성을 나타냈다. 따라서, AEEL의 주요 생리활성 물질을 확인하기 위해 HPLC 분석한 결과, chlorogenic acid와 rutin 등이 확인되었다. 이러한 결과들을 통해, AEEL이 혈당 상승을 억제하고 고당으로 유도되는 산화스트레스로부터 장 건강을 보호하는 기능성 식품 소재로써 활용될 수 있을 것으로 사료된다.