• 제목/요약/키워드: Tumor initiation

검색결과 137건 처리시간 0.022초

LINC00562 drives gastric cancer development by regulating miR-4636-AP1S3 axis

  • Lin Xu;Daiting Liu;Xun Wang
    • The Korean Journal of Physiology and Pharmacology
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    • 제27권3호
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    • pp.197-208
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    • 2023
  • Dysregulation of certain long non-coding RNAs may facilitate tumor initiation and progression. However, numerous carcinogenesis-related long noncoding RNAs have not been characterized. The goal of this study was to elucidate the role of LINC00562 in gastric cancer (GC). The expression of LINC00562 was analyzed using real-time quantitative PCR and Western blotting. The proliferative capacity of GC cells was determined using Cell Counting Kit-8 and colony-formation assays. The migration of GC cells were evaluated using wound-healing assays. The apoptosis of GC cells was assessed by measuring the expression levels of apoptosis-related proteins (Bax and Bcl-2). Xenograft models in nude mice were constructed for in vivo functional analysis of LINC00562. The binding relationship between miR-4636 and LINC00562 or adaptor protein complex 1 sigma 3 (AP1S3), obtained from public databases, was confirmed using dual-luciferase and RNA-binding protein immunoprecipitation experiments. LINC00562 was expressed in GC cells at high levels. Knockdown of LINC00562 repressed GC cell growth and migration, promoted apoptosis in vitro, and inhibited tumor growth in nude mouse models. LINC00562 directly targeted miR-4636, and miR-4636 depletion restored the GC cell behavior inhibited by LINC00562 absence. AP1S3, an oncogene, binds to miR-4636. MiR-4636 downregulation increased AP1S3 level, restoring GC cell malignant behaviors inhibited by AP1S3 downregulation. Thus, LINC00562 exerts carcinogenic effects on GC development by targeting miR-4636-mediated AP1S3 signaling.

Inhibition of Cell Growth and Induction of Apoptosis by Euonymus Alatus (Thunb.) Sieb in Human Leiomyomal Smooth Muscle Cells

  • Kim Yi-Geun;Han Ji-Young;Park Young-Soo;Kim Dong-Il;Lee Tae-Kyun
    • 대한한의학회지
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    • 제25권4호
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    • pp.108-120
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    • 2004
  • Objective : Euonymus alatus (Thunb.) Sieb (EA) is a traditional Korean herbal medicine, commonly used to treat tumors in Korea and China for centuries. Several earlier studies have indicated that EA exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we evaluated the molecular mechanism of EA in a human uterine leiomyomal smooth muscle cell (ULSMC) line. Methods : This study was evaluated by: (a), morphological changes by using acridine orange/ethidium bromide staining; (b), DNA fragmentation by TdT-mediated dUTP nick end labeling (TUNEL); and (c), sub-G1 cell analysis. Results : This study observed that EA treatment caused apoptotic cell death and depletion of intracellular glutathione (GSH) and that reduction of mitochondrial membrane potential was found to be involved in the initiation of apoptosis by EA. Conclusion : This results show that EA exerted clear cytotoxic effects and strongly inhibited the proliferation of ULSMC.

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Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways

  • Pandurangan, Ashok Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권4호
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    • pp.2201-2205
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    • 2013
  • Colorectal cancer (CRC) is one of the most common cancers in many parts of the world. Its development is a multi-step process involving three distinct stages, initiation that alters the molecular message of a normal cell, followed by promotion and progression that ultimately generates a phenotypically altered transformed malignant cell. Reports have suggested an association of the phosphoinositide-3-kinase (PI3K)/Akt pathway with colon tumorigenesis. Activation of Akt signaling and impaired expression of phosphatase and tensin homolog (PTEN) (a negative regulator of Akt) has been reported in 60-70% of human colon cancers and inhibitors of PI3K/Akt signaling have been suggested as potential therapeutic agents. Around 80% of human colon tumors possess mutations in the APC gene and half of the remainder feature ${\beta}$-catenin gene mutations which affect downstream signaling of the PI3K/Akt pathway. In recent years, there has been a great focus in targeting these signaling pathways, with natural and synthetic drugs reducing the tumor burden in different experiment models. In this review we survey the role of PI3K/Akt/mTOR and Wnt signaling in CRC.

Lung Cancer in Malabar Cancer Center in Kerala - A Descriptive Analysis

  • Bhaskarapillai, Binukumar;Kumar, Saina Sunil;Balasubramanian, Satheesan
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권9호
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    • pp.4639-4643
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    • 2012
  • The burden of lung cancer in terms of mortality is the highest among all types of cancers globally. The present study aimed to evaluate lifestyle related habits, clinico-pathological profile and treatment details of lung cancer patients who were registered at Malabar Cancer Centre (MCC), Kerala, during the calendar year 2010. A retrospective evaluation was made from medical records to gather data from 281 registered lung cancer cases in 241 males and 40 females, with a male to female ratio of 6.03: 1. Approximately 89% of the cases were above 50 years of age. Among males about 91% of the cases were smokers and 62% of them had a chronic smoking habit. Adenocarcinomas, squamous cell carcinomas, non-small cell carcinomas and small cell cancers accounted for 10.7, 13.9, 17.0 and 5.7% respectively. Out of 281 cases around 67% were diagnosed with distant metastasis and the remainder had regional lymph node involvement. However, no statistically significant difference was observed for secondary site of tumor according to gender. As majority of the cases reported at MCC were in an advanced stage of the disease, histology of the secondary site from supraclavicular lymph nodes or liver was taken for diagnosis. Initiation of population based screening for early detection of cancer, and primary and secondary prevention strategies for reducing the prevalence of tobacco consumption are high priorities to reduce the lung cancer burden in Kerala.

Downregulated microRNAs in the colorectal cancer: diagnostic and therapeutic perspectives

  • Hernandez, Rosa;Sanchez-Jimenez, Ester;Melguizo, Consolacion;Prados, Jose;Rama, Ana Rosa
    • BMB Reports
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    • 제51권11호
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    • pp.563-571
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    • 2018
  • Colorectal cancer (CRC), the third most common cancer in the world, has no specific biomarkers that facilitate its diagnosis and subsequent treatment. The miRNAs, small single-stranded RNAs that repress the mRNA translation and trigger the mRNA degradation, show aberrant levels in the CRC, by which these molecules have been related with the initiation, progression, and drug-resistance of this cancer type. Numerous studies show the microRNAs influence the cellular mechanisms related to the cell cycle, differentiation, apoptosis, and migration of the cancer cells through the post-transcriptionally regulated gene expression. Specific patterns of the upregulated and down-regulated miRNA have been associated with the CRC diagnosis, prognosis, and therapeutic response. Concretely, the downregulated miRNAs represent attractive candidates, not only for the CRC diagnosis, but for the targeted therapies via the tumor-suppressing microRNA replacement. This review shows a general overview of the potential uses of the miRNAs in the CRC diagnosis, prognosis, and treatment with a special focus on the downregulated ones.

Depletion of PDCD4 Accelerates Stress Granule Assembly Through Sensitization of Stress Response Pathways

  • Kim, Jeeho;Chang, In Youb;Lee, Wooje;Ohn, Takbum
    • 통합자연과학논문집
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    • 제12권4호
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    • pp.127-132
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    • 2019
  • Programmed cell death 4 (PDCD4) is a novel tumor suppressor that function in the nucleus and the cytoplasm and appears to be involved in the regulation of transcription and translation. Stress granules (SGs) are cytoplasmic foci at which untranslated mRNAs accumulate when cells exposed to environmental stresses. Since PDCD4 has implicated in translation repression through direct interaction with eukaryotic translation initiation factor 4A (eIF4A), we here investigated if PDCD4 has a functional role in the process of SG assembly under oxidative stresses. Using immunofluorescence microscopy, we found that PDCD4 is localized to SGs under oxidative stresses. Next, we tested if knockdown of PDCD4 has an effect on the assembly of SG using PDCD4-specific siRNA. Interestingly, SG assembly was accelerated and this effect was caused by sensitization of phosphorylation of eIF2α and dephosphorylation of eIF4E binding protein (4E-BP). These results suggest that PDCD4 has an effect on SG dynamics and possibly involved in cap-dependent translation repression under stress conditions.

적포도의 주 항산화물질, 레스베라트롤의 항암작용: 아폽토시스 의한 인체 암세포 사멸 유도 (Anticarcinogenic Activity of Resveratrol, a Major Antioxidant Presnet in Red Wine : Induction of Apoptosis in Human Cancer Cells)

  • 허연진;김정환;서효정;공구;서영준
    • 한국환경성돌연변이발암원학회지
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    • 제19권1호
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    • pp.56-62
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    • 1999
  • Resveratrol (3,5,4'-trihydroxy-trans-stilbene) has been considered to be as one of major antioxidants present in grapes responsible for beneficial effects of red wine consumption on coronary heart disease. This triphenolic stilbene has been suggested as a potential cancer chemopreventive agent based on its striking inhiitory effects on diverse cellular events associated with tumor initiation, promotion, and progression. The compound has strong antioxidative and anti-inflammatory activities which amy contribute to its chemopreventive/chemoprotective properties. In the present work, we have found that resveratrol reduces viability and DNA synthesis capability of cultured human promyelocytic leukemia (HL-60) cells. Likewise, the viability of human breast cancer cell line, MCF-7 was reduced by resveratrol treatment. The growth inhibitory and antiproliferative properties of resveratrol appear to be associated with its induction of apoptotic cell death as determined by morphological and ultrastructural changes, agarose gel electrphoretic analysis of internucleosomal DNA fragmentation, and in situ terminal end-labeling of fragmented DNA (TUNEL). This compound also inhibited the phorbol ester-induced expression of cyclooxygenase-2 (COX-2) protein in immortalized human mammary epithelial MCF-10A cells. These results suggest that resveratrol has the promising cancer therapeutic/chemopreventive potential.

Possible Protective Effects of Quercetin and Sodium Gluconate Against Colon Cancer Induction by Dimethylhydrazine in Mice

  • Saleem, TH;Attya, AM;Ahmed, EA;Ragab, SMM;Abdallah, MA Ali;Omar, HM
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권14호
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    • pp.5823-5828
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    • 2015
  • Micronutrients in food have been found to have chemopreventive effects, supporting the conclusions from epidemiologie studies that consumption of fresh fruits and vegetables reduces cancer risk. The present study was carried out to evaluate the role of querctin (Q) and sodium gluconate (GNA) supplementation separately or in combination in ameliorating promotion of colon tumor development by dimethyl-hydrazine (DMH) in mice. Histopathological observation of colons in mice treated with DMH showed goblet cell dysplasia with inflammatory cell infiltration. This pathological finding was associated with significant alteration in oxidative stress markers in colon tissues and carcinoembryonic antigen (CEA) levels in plasma. Mice co-treated with GNA and Q showed mild changes of absorptive and goblet cells and inflammatory cell infiltration in lamina properia, with improvement in oxidative stress markers. In conclusion, findings of the present study indicate significant roles for reactive oxygen species (ROS) in pathogenesis of DMH-induced colon toxicity and initiation of colon cancer. Also, they suggest that Q, GNA or the combination of both have a positive beneficial effect against DMH induced colonic cancer induction in mice.

Effects of Hwangryun-Hae-Dok-tang on TNF-${alpha}$ and IL-4 Stimulated TARC, eotaxin, RANTES in the Human Bronchial Epithelial A549 Cells

  • Choi, Jong-Min;Kim, Hee-Taek
    • 동의생리병리학회지
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    • 제20권6호
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    • pp.1649-1653
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    • 2006
  • Allergic diseases are the result of Th2-dominated responses to single or multiple environmental allergens. Th2 cytokines regulate these mechanisms of allergic disease at many levels, including initiation, progression, and persistence. The effect of hwangryun-Hae-Dok-Tang (HRHDT) on tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-4 (IL-4) stimulated inflammation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay, thymus and activation-regulated chemokine (TARC), eotaxin, regulated on activation normal T cells expressed and secreted (RANTES) immunoassay on the human bronchial epithelial microglial cells. From the present study, the crude extract of Hwangryun-Hae-Dok-tang suppressed the TNF-${\alpha}$ and IL-4 stimulated TARC, eotaxin, and RANTES production in the human bronchial epithelial A549 cells. Based on the present results, Hwangryun-Hae-Dok-tang may be useful in the treatment asthmatic allergy by inhibiting TARC, eotaxin, and RANTES chemokines.

Chemopreventive Effects of Ginseng on Rat Carcinogenesis

  • Wanibuchi Hideki;Ichihara Toshio;Morimura Keiichirou;Fukushima Shoji
    • 고려인삼학회:학술대회논문집
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    • 고려인삼학회 2002년도 학술대회지
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    • pp.277-287
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    • 2002
  • The chemopreventive effects of ginseng on rat carcinogenesis models were investigated, In the present study, the inhibitory effects of white and red ginseng on tumor development were examined using medium-term liver, initiation and medium-term multi-organ carcinogenicity bioassay systems. No modifying potential of the ginsengs was evident in terms of the numbers or areas of glutathione S-transferase placental form (GST -P)-positive foci, which is a marker of preneoplastic lesion in rat livers. However, white ginseng, but not red ginseng was found to decrease the incidences of adenocarcinoma of the small intestine and colon in the medium-term multi-organ carcinogenesis model. These results indicate that white ginseng may have inhibitory effects on progression stage of rat intestinal carcinogenesis, but the influence is not strong. Ginseng is unlikely to have promoting or inhibitory effects in other organs under the present type of experimental conditions. Possible application on ginseng for chemoprevention of colon cancer in humans, can be concluded given the lack of obvious adverse effects.

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