• Title/Summary/Keyword: cancer initiation

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Heterogeneous Sequences of Brain Cytoplasmic 200 RNA Formed by Multiple Adenine Nucleotide Insertions

  • Shin, Heegwon;Lee, Jungmin;Kim, Youngmi;Jang, Seonghui;Kim, Meehyein;Lee, Younghoon
    • Molecules and Cells
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    • v.42 no.6
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    • pp.495-500
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    • 2019
  • Brain cytoplasmic 200 RNA (BC200 RNA), originally identified as a neuron-specific non-coding RNA, is also observed in various cancer cells that originate from non-neural cells. Studies have revealed diverse functions of BC200 RNA in cancer cells. Accordingly, we hypothesized that BC200 RNA might be modified in cancer cells to generate cancerous BC200 RNA responsible for its cancer-specific functions. Here, we report that BC200 RNA sequences are highly heterogeneous in cancer cells by virtue of multiple adenine nucleotide insertions in the internal A-rich region. The insertion of adenine nucleotides enhances BC200 RNA-mediated translation inhibition, possibly by increasing the binding affinity of BC200 RNA for eIF4A (eukaryotic translation initiation factor 4A).

Emerging Role of NRF2 Signaling in Cancer Stem Cell Phenotype

  • Steffanus P. Hallis;Jin Myung Kim;Mi-Kyoung Kwak
    • Molecules and Cells
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    • v.46 no.3
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    • pp.153-164
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    • 2023
  • Cancer stem cells (CSCs) are a small population of tumor cells characterized by self-renewal and differentiation capacity. CSCs are currently postulated as the driving force that induces intra-tumor heterogeneity leading to tumor initiation, metastasis, and eventually tumor relapse. Notably, CSCs are inherently resistant to environmental stress, chemotherapy, and radiotherapy due to high levels of antioxidant systems and drug efflux transporters. In this context, a therapeutic strategy targeting the CSC-specific pathway holds a promising cure for cancer. NRF2 (nuclear factor erythroid 2-like 2; NFE2L2) is a master transcription factor that regulates an array of genes involved in the detoxification of reactive oxygen species/electrophiles. Accumulating evidence suggests that persistent NRF2 activation, observed in multiple types of cancer, supports tumor growth, aggressive malignancy, and therapy resistance. Herein, we describe the core properties of CSCs, focusing on treatment resistance, and review the evidence that demonstrates the roles of NRF2 signaling in conferring unique properties of CSCs and the associated signaling pathways.

Monitoring microRNAs Using a Molecular Beacon in CD133+/CD338+ Human Lung Adenocarcinoma-initiating A549 Cells

  • Yao, Quan;Sun, Jian-Guo;Ma, Hu;Zhang, An-Mei;Lin, Sheng;Zhu, Cong-Hui;Zhang, Tao;Chen, Zheng-Tang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.161-166
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    • 2014
  • Lung cancer is the most common causes of cancer-related deaths worldwide, and a lack of effective methods for early diagnosis has greatly impacted the prognosis and survival rates of the affected patients. Tumor-initiating cells (TICs) are considered to be largely responsible for tumor genesis, resistance to tumor therapy, metastasis, and recurrence. In addition to representing a good potential treatment target, TICs can provide clues for the early diagnosis of cancer. MicroRNA (miRNA) alterations are known to be involved in the initiation and progression of human cancer, and the detection of related miRNAs in TICs is an important strategy for lung cancer early diagnosis. As Hsa-miR-155 (miR-155) can be used as a diagnostic marker for non-small cell lung cancer (NSCLC), a smart molecular beacon of miR-155 was designed to image the expression of miR-155 in NSCLC cases. TICs expressing CD133 and CD338 were obtained from A549 cells by applying an immune magnetic bead isolation system, and miR-155 was detected using laser-scanning confocal microscopy. We found that intracellular miR-155 could be successfully detected using smart miR-155 molecular beacons. Expression was higher in TICs than in A549 cells, indicating that miR-155 may play an important role in regulating bio-behavior of TICs. As a non-invasive approach, molecular beacons could be implemented with molecular imaging to diagnose lung cancer at early stages.

Tumour Lysis Syndrome: Implications for Cancer Therapy

  • Mika, Denish;Ahmad, Sabrina;Guruvayoorappan, C.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3555-3560
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    • 2012
  • The tumour lysis syndrome (TLS) is a group of metabolic abnormalities caused by rapid and unexpected release of cellular components into the circulation as a result of massive destruction of rapidly proliferating malignant cells. It usually develops in patients with hematologic malignancies like acute lymphoid leukemia, non-Hodgkin and Burkitt's lymphoma after initiation of chemotherapy or may, rarely, occur spontaneously. Though TLS is seldom observed in relation to solid tumours, there have been reports of connections with examples such as lung, liver, breast, gastric carcinomas. The clinical manifestations of TLS include hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. These indications if untreated lead to life-threatening complications such as acute renal failure, cardiac arrhythmias, seizures, and eventually death due to multiorgan failure. Therefore early detection of TLS is of vital importance. This can be accomplished by identification of high risk patients, implementation of suitable prophylactic measures andmonitoring of the electrolyte levels in patients undergoing chemotherapy.

CHEMOPREVENTIVE EFFECTS OF ETHYL 3-(4'-GERANYLOXY-3-METHOXYPHENYL)-2-PROPENOATE AND FERULIC ACID ON MOUSE COLON CARCINOGENESIS

  • Han, Beom-Seok;Shin, Dong-Whan;Yum, Young-Na;Cho, Jeong-Sik;Yang, Ki-Wha;Nobuo Takasuka;Tetsuyuki Takahashi;Hiroyuki Tsuda
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.74-74
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    • 2002
  • Ethyl 3-(4'-geranyloxy-3-methoxyphenyl)-2-propenoate (EGMP) and ferulic acid (FA) have been shown to inhibit development of aberrant crypt foci (ACF) in the azoxymethane (AOM)-treated rat colon. In the present study, inhibitory effects of EGMP and FA on the post-initiation stage of AOM-induced colon carcinogenesis were studied in male ddY mice.(omitted)

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Combined Effects Methylation of FHIT, RASSF1A and RARβ Genes on Non-Small Cell Lung Cancer in the Chinese Population

  • Li, Wen;Deng, Jing;Tang, Jian-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5233-5237
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    • 2014
  • Epigenetic modifications of tumour suppressor genes are involved in all kinds of human cancer. Aberrant promoter methylation is also considered to play an essential role in development of lung cancer, but the pathogenesis remains unclear.We collected the data of 112 subjects, including 56 diagnosed patients with lung cancer and 56 controls without cancer. Methylation of the FHIT, RASSF1A and RAR-${\beta}$ genes in DNA from all samples and the corresponding gene methylation status were assessed using the methylation-specific polymerase chain reaction (PCR, MSP). The results showed that the total frequency of separate gene methylation was significantly higher in lung cancer compared with controls (33.9-85.7 vs 0 %) (p<0.01).Similar outcomes were obtained from the aberrant methylation of combinations of any two or three genes (p<0.01). There was a tendency that the frequency of combinations of any two or three genes was higher in stage I+II than that in stage III+IV with lung cancer. However, no significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis. Methylation of FHIT, RASSF1A and $RAR{\beta}$ genes may be related to progression of lung oncogenesis.

Benzo[a]pyrene Alters the Expression of Genes in A549 Lung Cancer Cells and Cancer Stem Cells

  • Bak, Yesol;Jang, Hui-Joo;Seo, Ji-Hye;No, Su-Hyun;Chae, Jung-il;Hong, Jintae;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.28 no.3
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    • pp.425-431
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    • 2018
  • Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, is a principal component of cigarette smoke. B[a]P can cause lung carcinogenesis and plays a key role in lung cancer progression. The role of B[a]P has been reported in lung cancer, but its effects on lung cancer stem cells (CSCs) have not been investigated. Emerging evidence indicates that CSCs are associated with carcinogenesis, tumor initiation, relapse, and metastasis. Therefore, targeting CSCs to defeat cancer is a challenging issue in the clinic. This study explored whether B[a]P alters gene expression in lung cancer cells and CSCs. The lung adenocarcinoma A549 cell line was used to investigate the role of B[a]P on lung cancer cells and lung CSCs using microarray and quantitative PCR. B[a]P ($1{\mu}M$) provoked gene expression changes in A549 cancer cells and CSCs by deregulating numerous genes. Gene pathway analysis was performed using GeneMANIA and GIANT. We identified genes that were coexpressed and showed physical interactions. These findings improve our understanding of the mechanism of B[a]P in lung cancer and cancer stem cells and can be an attractive therapeutic target.

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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    • v.14 no.4
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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.

Sleep Disturbance in Prostate Cancer Patients (전립선암환자의 수면장애)

  • Jun, Seong-Sook;Kim, Dong-Hee;Kim, Min-Young
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.17 no.2
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    • pp.169-176
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    • 2010
  • Purpose: This study was done to investigate clinical characteristics and risk factors for sleep disturbance in patients with prostate cancer. Method: Participants were recruited from P hospital outpatient clinic from March 23 to April 20, 2006, and 101 participants completed a questionnaire assessing general and clinical characteristics, sleep quality, physical symptoms and psychological symptoms such as anxiety and depression. The data was analyzed using the SPSS 12.0 program. Results: In this study, 29.7% of the patients reported sleep disturbance. Cancer diagnosis related factors which affected sleep disturbance were onset (55.3%) and aggravation (83.3%). Habitual sleep efficiency of patients with sleep disturbance was as follows: bedtime was 10 PM, wake-up time was 6AM, sleep duration was six hours and twenty minutes. Risk factors for the presence of sleep disturbance included metastasis, the presence of intestinal symptoms, depression and anxiety. Conclusion: Sleep disturbance is a frequent problem associated with prostate cancer and seems to be influenced by aggravation of illness and the presence of physical and psychological symptoms.

A systematic review of the biological mechanisms linking physical activity and breast cancer

  • Hong, Bok Sil;Lee, Kang Pa
    • Korean Journal of Exercise Nutrition
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    • v.24 no.3
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    • pp.25-31
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    • 2020
  • [Purpose] Epidemiological evidence has shown that leisure-time physical activity and structured exercise before and after breast cancer diagnosis contribute to reducing the risk of breast cancer recurrence and mortality. Thus, in this review, we aimed to summarize the physical activity-dependent regulation of systemic factors to understand the biological and molecular mechanisms involved in the initiation, progression, and survival of breast cancer. [Methods] We systematically reviewed the studies on 1) the relationship between physical activity and the risk of breast cancer, and 2) various systemic factors induced by physical activity and exercise that are potentially linked to breast cancer outcomes. To perform this literature review, PubMed database was searched using the terms "Physical activity OR exercise" and "breast cancer", until August 5th, 2020; then, we reviewed those articles related to biological mechanisms after examining the resulting search list. [Results] There is strong evidence that physical activity reduces the risk of breast cancer, and the protective effect of physical activity on breast cancer has been achieved by long-term regulation of various circulatory factors, such as sex hormones, metabolic hormones, inflammatory factors, adipokines, and myokines. In addition, physical activity substantially alters wholebody homeostasis by affecting numerous other factors, including plasma metabolites, reactive oxygen species, and microRNAs as well as exosomes and gut microbiota profile, and thereby every cell and organ in the whole body might be ultimately affected by the biological perturbation induced by physical activity and exercise. [Conclusion] The understanding of integrative mechanisms will enhance how physical activity can ultimately influence the risk and prognosis of various cancers, including breast cancer. Furthermore, physical activity could be considered an efficacious non-pharmacological therapy, and the promotion of physical activity is probably an effective strategy in primary cancer prevention.