• BMB Reports
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• 제50권3호
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• pp.117-125
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• 2017

Most of the cancers are still incurable human diseases. According to recent findings, especially targeting cancer stem cells (CSCs) is the most promising therapeutic strategy. CSCs take charge of a cancer hierarchy, harboring stem cell-like properties involving self-renewal and aberrant differentiation potential. Most of all, the presence of CSCs is closely associated with tumorigenesis and therapeutic resistance. Despite the numerous efforts to target CSCs, current anti-cancer therapies are still impeded by CSC-derived cancer malignancies; increased metastases, tumor recurrence, and even acquired resistance against the anti-CSC therapies developed in experimental models. One of the most forceful underlying reasons is a "cancer heterogeneity" due to "CSC plasticity". A comprehensive understanding of CSC-derived heterogeneity will provide novel insights into the establishment of efficient targeting strategies to eliminate CSCs. Here, we introduce findings on mechanisms of CSC reprogramming and CSC plasticity, which give rise to phenotypically varied CSCs. Also, we suggest concepts to improve CSC-targeted therapy in order to overcome therapeutic resistance caused by CSC plasticity and heterogeneity.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2217-2221
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• 2016

Vascular endothelial growth factor 2 (VEGFR2) was initially identified as a receptor of VEGF on endothelial cells with a role in regulating angiogenesis during organism development and tumorigenesis. Previously, in cancer tissue, VEGFR2 has been reported to be expressed in endothelial cells. In our research, we found that VEGFR2 was expressed not only in endothelial cells but also cancer cells in head and neck squamous cell carcinomas (HNSCCs). Knockdown of VEGFR2 in Hep2 cells could arrest the cell cycle in G0/G1, leading to a decrease in proliferation. We also present evidence that MAPK/ERK signal pathways and expression of CDK1 downstream of VEGFR2 might regulate proliferation and cell cycle arrest. Furthermore, we discovered that down-regulate VEGRF2 in Hep2 cells could significantly affect the invasion ability. Taken together, our data suggest that VEGFR2 might regulate proliferation and invasion in HNSCC cancer cells in vivo.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1235-1239
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• 2015

Background: Fragile histidine triad (FHIT) gene is a tumor suppressor gene which involved in breast cancer pathogenesis. Epigenetics alterations in FHIT contributes to tumorigenesis of breast cancer. Objective: Our objective was to study FHIT promoter region hypermethylation in Egyptian breast cancer patients and its association with clinicopathological features. Materials and Methods: Methylation-specific polymerase chain reaction was performed to study the hypermethylation of FHIT promoter region in 20 benign breast tissues and 30 breast cancer tissues. Results: The frequency of hypermethylation of FHIT promoter region was significantly increased in breast cancer patients compared to bengin breast disease patients. The Odd's ratio (95%CI) of development of breast cancer in individuals with FHIT promoter hypermethylation (MM) was 11.0 (1.22-250.8). There were also significant associations between FHIT promoter hypermethylation and estrogen, progesterone receptors negativity, tumor stage and nodal involvment in breast cancer pateints. Conclusions: Our results support an association between FHIT promotor hypermethylation and development of breast cancer in Egyptian breast cancer patients. FHIT promoter hypermethylation is associated with some poor prognostic features of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.875-880
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• 2015

Mediator 19 (Med19) is a component of the mediator complex which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II. Accumulating evidence has shown that Med19 plays important roles in cancer cell proliferation and tumorigenesis. The involvement of Med19 in sensitivity to the chemotherapeutic agent cisplatin was here investigated. We employed RNA interference to reduce Med19 expression in human non-small cell lung cancer (NSCLC) cell lines and analyzed their phenotypic changes. The results showed that after Med19 siRNA transfection, expression of Med19 mRNA and protein was dramatically reduced (p<0.05). Meanwhile, impaired growth potential, arrested cell cycle at G0/G1 phase and enhanced sensitivity to cisplatin were exhibited. Apoptosis and caspase-3 activity were increased when cells were exposed to Med19 siRNA and/or cisplatin. The present findings suggest that Med19 facilitates tumorigenic properties of NSCLC cells and knockdown of Med19 may be a rational therapeutic tool for lung cancer cisplatin sensitization.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.1041-1046
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• 2014

Evidence is growing that the $GABA_B$ receptor, which belongs to the G protein-coupled receptor (GPCR) superfamily, is involved in tumorigenesis. Recent studies have shown that ${\beta}$-arrestin can serve as a scaffold to recruit signaling protein c-Jun N-terminal knase (JNK) to GPCR. Here we investigated whether ${\beta}$-arrestin recruits JNK to the $GABA_B$ receptor and facilitates its activation to affect the growth of cancer cells. Our results showed that ${\beta}$-arrestin expression is decreased in breast cancer cells in comparison with controls. ${\beta}$-arrestin could enhance interactions of the $GABA_BR{\cdot}{\beta}-arrestin{\cdot}JNK$ signaling module in MCF-7 and T-47D cells. Further studies revealed that increased expression of ${\beta}$-arrestin enhances the phosphorylation of JNK and induces cancer cells apoptosis. Collectively, these results indicate that ${\beta}$-arrestin promotes JNK mediated apoptosis via a $GABA_BR{\cdot}{\beta}-arrestin{\cdot}JNK$ signaling module.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.551-560
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• 2014

Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)-${\kappa}B$, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, $Wnt/{\beta}$-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3077-3084
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• 2016

Various beneficial effects have been described for fermented papaya preparation (FPP: SAIDO-PS501) based on its anti-oxidative and anti-inflammatory functions. The present study was designed to determine the effects of FPP on carcinogenesis in vivo, and immunomodulatory function in vitro. Mice were injected with RL male 1 cells subcutaneously or 3-methylcholantherene (MCA) intravenously to induce cancer and orally or intraperitoneally treated with FPP solution. Human peripheral blood mononuclear cells (PBMC) were obtained from healthy volunteers and patients with atopic dermatitis, treated with FPP, and subjected to measurement of cytokine production and changes in Foxp3-expressing regulatory T cell (Treg) stimulated with phytohemagglutinin (PHA). Administration of FPP suppressed tumor size and the incidence of malignancy. In vitro, treatment of PBMC with FPP induced IL-$1{\beta}$, $TNF{\alpha}$ and $IFN{\gamma}$ production. Moreover, FPP suppressed proliferation of PHA-stimulated Foxp3-expressing Treg. These results suggest that FPP has chemotherapeutic properties.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5449-5454
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• 2013

Background: A large variety of familiar and non-familiar lung carcinomas (LC) are caused by long term exposure to chemical carcinogens that are present in tobacco smoke. We aimed to investigate the prevalence of 5 thrombophilic germ-line mutations in patients with lung carcinomas. Materials and Methods:A total of 52 LC patients and 212 healthy controls from same population were analyzed for FV Leiden, factor V H1299R (R2), PAI-1, MTHFR C677T, MTHFR A1298C, ACE I/D, and Apo E genes and compared. Results: Overall, heterozygous and/or homozygous point mutations in FV Leiden Apo E2, PAI-1 and MTHFR C677T genes were associated with LC in the current cohort. There was no meaningful association between LC and ACE I/D gene markers. Conclusions: The current results showed that LC is related to combined thrombophilic gene mutations and individuals with homozygosity of 4G in PAI-1 and MTHFR C677T genes and heterozygosity of FV Leiden, Apo E4 genes have a germ-line risk for LC tumorigenesis.

• Molecules and Cells
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• 제39권9호
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• pp.705-713
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• 2016

The efficiency of Agrobacterium-mediated transformation in plants depends on the virulence of Agrobacterium strains, the plant tissue culture conditions, and the susceptibility of host plants. Understanding the molecular interactions between Agrobacterium and host plant cells is crucial when manipulating the susceptibility of recalcitrant crop plants and protecting orchard trees from crown gall disease. It was discovered that Arabidopsis voltage-dependent anion channel 1 (atvdac1) mutant has drastic effects on Agrobacterium-mediated tumorigenesis and growth developmental phenotypes, and that these effects are dependent on a Ws-0 genetic background. Genetic complementation of Arabidopsis vdac1 mutants and yeast porin1-deficient strain with members of the AtVDAC gene family revealed that AtVDAC1 is required for Agrobacterium-mediated transformation, and there is weak functional redundancy between AtVDAC1 and AtVDAC3, which is independent of porin activity. Furthermore, atvdac1 mutants were deficient in transient and stable transformation by Agrobacterium, suggesting that AtVDAC1 is involved in the early stages of Agrobacterium infection prior to transferred-DNA (T-DNA) integration. Transgenic plants overexpressing AtVDAC1 not only complemented the phenotypes of the atvdac1 mutant, but also showed high efficiency of transient T-DNA gene expression; however, the efficiency of stable transformation was not affected. Moreover, the effect of phytohormone treatment on competence to Agrobacterium was compromised in atvdac1 mutants. These data indicate that AtVDAC1 regulates the competence of Arabidopsis to Agrobacterium infection.

• 대한기관식도과학회지
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• 제4권2호
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• pp.197-204
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• 1998

Human papillomavirus(HPV) is epitheliotrophic virus invading the anogenital tract and the upper aerodigestive tract HRV produces a diversity of benign and maljgnant tumors. In this study, the author determined the frequency of association of human papillomavirus(HPV) and laryngeal carcinomas and investigated the significance of HRV infection of different subtypes in the tumorigenesis of laryngeal carcinoma. Laryngeal squamous cell cancinomas from 34 patients who did not have preexisting papillomas by clinical history were retrieved from formalin-fixed, paraffin-embedded blocks and analyzed for HPV. Nineteen cases were tumors of the true vocal folds, 11 were supraglottic and 4 were transglottic. HPV detection was dane using polymerase chain reaction amplification with HPV L$_1$consensus primer. HPV type was determined by the same method using HPV-6, 11 and 16,-18 type-specific E6 primers. The results were as follows : 1) HPV DNA was detected in 7 cases among the 34 patients(20.6%). According to the type of HPV DNA HPV-11 was detected in 3 cases, HPV-16 was detected in 2 cases and HPV-6 and HPV-18 were detected in 1 case, respectively. 2) These 7 HPV-positive patients were advanced cancinoma cases. From these results, we concluded that HPV was thought to be the etiological factor of laryngeal squamous cell carcinomas.