• 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.

• Asian-Australasian Journal of Animal Sciences
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• 제22권6호
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• pp.900-905
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• 2009

We analyzed succession of the bacterial communities during composting of animal manure in three individual facilities. Polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) targeting for the bacterial 16S rRNA gene were used to clarify the changes of bacterial community throughout each composting process. Our study revealed that the bacterial community structures differed during the composting process. The bacterial community in composting of facility A showed little change throughout the process. In the compost sample from facility B, its community had a small shift as the temperature increased. In compost from facility C, the temperature dynamically changed; it was shown that various bacterial communities appeared and disappeared as follows: in the initial phase, the members of phylum Bacteroidetes dominated; in the thermophilic phase, some bacteria belonging to phylum Firmicutes increased; towards the end, the community structure consisted of three phyla, Bacteroidetes, Firmicutes, and Proteobacteria. This study provides some information about the bacterial community actually present in field-scale composting with animal manure.

• BMB Reports
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• 제48권3호
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• pp.147-152
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• 2015

Small interfering RNA (siRNA) functions through pairing with specific mRNA sequences and results in the mRNA's degradation. It is a potential therapeutic approach for many diseases caused by altered gene expression. The delivery of siRNA is still a major problem due to its rapid degradation in the circulation. Various strategies have been proposed to help with the cellular uptake of siRNA and short or small hairpin RNA (shRNA). Here, we reviewed recently published data regarding local applications of siRNA. Compared with systemic delivery methods, local delivery of siRNA/shRNA has many advantages, such as targeting the specific tissues or organs, mimicking a gene knockout effect, or developing certain diseases models. The eye, brain, and tumor tissues are 'hot' target tissues/organs for local siRNA delivery. The siRNA can be delivered locally, in naked form, with chemical modifications, or in formulations with viral or non-viral vectors, such as liposomes and nanoparticles. This review provides a comprehensive overview of RNAi local administration and potential future applications in clinical treatment.

• Journal of Plant Biotechnology
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• 제37권3호
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• pp.243-249
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• 2010

Molecular farming is production of pharmaceutically and industrially important proteins in plants. Plants and plant cell culture systems have been used as bio-factory to produce recombinant proteins such as monoclonal antibodies, enzymes, vaccines, hormones, interleukins, commercial enzymes and etc. The terms molecular farming, biofarming, molecular pharming, phytomanufacturing, recombinant or plant-made industrials, planta-pharma, plant bioreactors, plant biofactory, and pharmaceutical gardening are used interchangeably. Molecular farming can provide safe and inexpensive pharmaceutical proteins as well as commercial ones. In spite of several advantages of molecular farming such as safety and inexpensive cost, there are also a couple of drawbacks in the existing technology. One of them is low expression level of target gene in plants, which has been improved by optimizing gene-based codon usage, screening of strong promoters, expression of transcription factors, subcellular targeting of target proteins, chloroplast transformation, and transient expression using viral expression system (magnifection). Some plant-based commercial proteins have already been in markets and more than twenty plant-based pharmaceuticals have been in clinical trials, from that we can expect that several plant-based pharmaceutical proteins will be seen in the markets in the near future.

• International Journal of Industrial Entomology and Biomaterials
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• 제11권1호
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• pp.71-74
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• 2005

A LIM protein gene homologue of the CRP (cysteine­rich protein) family in the whiter-spotted flower chafer, Protaetia brevitarsis, was cloned. The P. brevitarsis LIM protein cDNA encodes a 92 amino acid polypep­tide with a predicted molecular mass of 10,030 Da and a pI of 8.57. The P. brevitarsis LIM protein contains the cysteine-rich consensus sequence of LIM domain and the glycine-rich consensus sequence observed in the cysteine-rich protein family 1 (CRPl). The potential nuclear targeting signal is retained. The deduced amino acid sequence of the P. brevitarsis LIM protein cDNA showed 92$\%$ identity to another beetle, Apriona germari LIM protein. Northern blot analysis showed that P. brevitarsis LIM protein is highly expressed in epidermis and midgut, but not in the fat body.

• 한국미생물·생명공학회지
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• 제23권5호
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• pp.536-543
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• 1995

Multicopy integration vector is a very useful vector system in that they can be integrated into chromosomal DNA in several copies and stably maintained under non-selective conditions. To develop a multicopy integration vector system in the yeast Yarrowia lipolytica, P-type ribosomal DNA was cloned from Y lipolytica. A HindIII-BglII fragment of the cloned rDNA and a promoterless URA3 gene were inserted into pGEM1, generating multicopy integration vectors, pMIYL-1 and pMIYL-2. The rDNA fragment is for targeted homologous recombination between the vector and the chromosomal DNA of Y. lipolytica, and the promoterless URA3 gene is a defective selection marker for inducing multicopy integration. pMIYL-1 and pMIYL-2 have an unique restriction enzyme site, KpnI, and two unique restriction enzyme sites, KpnI and EcoRI, repectively, which can be used for targeting of the vectors into the rDNA of Y. lipolytica chromosomal DNA. After transformation of the vectors into Y. lipolytica, copy number and stability were analyzed by Southern hybridization. The vectors were found to be present in less than 5 copies per cell and were stably maintained during growth in non-selective media.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.127-131
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• 2013

Trastuzumab is the first molecular targeting drug to increase the overall survival rate in advanced gastric cancer. However, it has also been found that a high intrinsic or primary trastuzumab resistance exists in some proportion of gastric cancer patients. In order to explore the mechanism of resistance to trastuzumab, firstly we investigated the expression of MUC1 (membrane-type mucin 1) in gastric cancer cells and its relationship with drug-resistance. Then using gene-silencing, we transfected a siRNA of MUC1 into drug-resistant cells. The results showed the MKN45 gastric cell line to be resistant to trastuzumab, mRNA and protein expression of MUC1 being significantly upregulated. After transfection of MUC1 siRNA, protein expression of MUC1 in MKN45cells was significantly reduced. Compared with the junk transfection and blank control groups, the sensitivity to trastuzumab under MUC1 siRNA conditions was significantly increased. These results imply that HER2-positive gastric cancer cell MKN45 is resistant to trastuzumab and this resistance can be cancelled by silencing expression of the MUC1 gene.

• 대한의생명과학회지
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• 제26권3호
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• pp.238-243
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• 2020

Tuberculosis is a global public health problem and manifests itself as a difference in the genetic susceptibility of the host, along with the properties of Mycobacterium tuberculosis (MTB). The single nucleotide polymorphisms (SNPs) and candidate genes proposed in the Genome-wide association study (GWAS) on tuberculosis in a recently published Chinese population were reported. In this study, we investigated whether the genetic polymorphism of candidate genes related to tuberculosis is reproduced when targeting Koreans. The CLCN6 (rs12404124, rs198391, rs535107), DOK7 (rs1203104, rs1203103) and HLA-DRA (rs1051336) gene polymorphisms showed statistically significant results. In addition, it was also found whether it acts as an expression quantitative trait loci (eQTL) that can influence gene expression. This study confirmed that the genetic polymorphism of the three genes (CLCN6, DOK7, HLA-DRA) affects the development of tuberculosis and will help to understand the genetic specificity of tuberculosis and the interaction between pathogens and hosts.

• BMB Reports
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• 제51권2호
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• pp.79-84
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• 2018

Niemann-Pick type C disease (NP-C) is a fatal neurodegenerative disorder caused by a deficiency of NPC1 gene function, which leads to severe neuroinflammation such as astrogliosis. While reports demonstrating neuroinflammation are prevalent in NP-C, information about the onset and progression of cerebellar astrogliosis in this disorder is lacking. Using gene targeting, we generated vascular endothelial growth factor (VEGF) conditional null mutant mice. Deletion of VEGF in cerebellar Purkinje neurons (PNs) led to a significant increase of astrogliosis in the brain of NP-C mice in addition to the loss of PNs, suggesting PN-derived VEGF as an important factor in NP-C pathology. Moreover, replenishment of VEGF in neurons improved brain pathology in NP-C mice. Overall, our data provide a new pathological perspective on cerebellar astrogliosis in NP-C and suggest the importance of VEGF as a therapeutic target for this disease.

• Genomics & Informatics
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• 제6권2호
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• pp.84-86
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• 2008

The Tetrahymena group I intron has been shown to employ a trans-splicing reaction and has been modified to specifically target and replace human telomerase reverse transcriptase (hTERT) RNA with a suicide gene transcript, resulting in the induction of selective cytotoxicity in cancer cells that express the target RNA, in animal models as well as in cell cultures. In this study, we evaluated the target RNA specificity of trans-splicing phenomena by the group I intron in mice that were intraperitoneally inoculated with hTERT-expressing human cancer cells to validate the anti-cancer therapeutic applicability of the group I intron. To this end, an adenoviral vector that encoded for the hTERT-targeting group I intron was constructed and systemically injected into the animal. 5'-end RACE-PCR and sequencing analyses of the trans-spliced cDNA clones revealed that all of the analyzed products in the tumor tissue of the virus-infected mice resulted from reactions that were generated only with the targeted hTERT RNA. This study implies the in vivo target specificity of the trans-splicing group I intron and hence suggests that RNA replacement via a trans-splicing reaction by the group I intron is a potent anti-cancer genetic approach.