• Title/Summary/Keyword: colon-target

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In - Silico approach and validation of JNK1 Inhibitors for Colon Rectal Cancer Target

  • Bavya, Chandrasekhar;Thirumurthy, Madhavan
    • Journal of Integrative Natural Science
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    • v.15 no.4
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    • pp.145-152
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    • 2022
  • Colon rectal cancer is one of the frequently diagnosed cancers worldwide. In recent times the drug discovery for colon cancer is challenging because of their speedy metastasis and morality of these patients. C-jun N-terminal kinase signaling pathway controls the cell cycle survival and apoptosis. Evidence has shown that JNK1 promotes the tumor progression in various types of cancers like colon cancer, breast cancer and lung cancer. Recent study has shown that inhibiting, JNK1 pathway is identified as one of the important cascades in drug discovery. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened ChEMBL dataset against JNK1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top compounds to be more specific with JNK1 comparing the affinity with JNK2 and JNK3.The drugs which exhibited higher binding were subjected to Conceptual - Density functional theory. The results showed mainly Entrectinib and Exatecan showed better binding to the target.

The Nursing Needs of Post-Surgical Colon Cancer Patients at Discharge (대장암 수술 환자의 퇴원 시 간호요구도 조사)

  • Ju, Ae-Ra;Yeoum, Soon-Gyo;Park, Kyung-Sook
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.16 no.4
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    • pp.392-401
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    • 2009
  • Purpose: This study was a descriptive survey of nursing needs for post surgical colon cancer patients at discharge. Method: A survey was done utilizing questionnaires about the nursing needs a target sample of 61 patients who had colon cancer surgery during April May 2006 in a general hospital in Seoul. Results: Levels for treatment & prognosis were the highest in all domain, high in order of psychological support & stability, complications & discomfort, diet, daily life style, recovery & health promotion, and support system. Patient factors affecting nursing needs were age, job, duration of colon cancer and handling of stoma. Conclusion: Using discharge education for colon cancer patients based on the results of this study, nurses should focus on the domains of treatment & prognosis, psychological support & stability and complication & discomfort, and should tailor teaching content to be specified for age, job, duration of colon cancer, and handling of stoma.

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Next-generation sequencing analysis of exosomal microRNAs: Fusobacterium nucleatum regulates the expression profiling of exosomal microRNAs in human colorectal cancer cells

  • Yu, Mi Ra;Kim, Hye Jung;Kang, Ji Wan;Kim, Yun Hak;Park, Hae Ryoun
    • International Journal of Oral Biology
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    • v.45 no.3
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    • pp.134-142
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    • 2020
  • Colon cancer is one of the most common malignant tumors, but there are still a few validated biomarkers of colon cancer. Exosome-mediated microRNAs (miRNAs) have been recognized as potential biomarkers in cancers, and miRNAs can regulate a variety of genes. Recently, Fusobacterium nucleatum was discovered in the tissues of human colon cancer patients. Its role in colon cancer was highlighted. F. nucleatum may contribute to the progression of colon cancer through the mechanism of exosome-mediated miRNAs transfer. However, the exosomal miRNAs regulation mechanism by F. nucleatum in colon cancer is not well known. Thus, we performed next-generation sequencing to investigate the overall pattern of exosomal miRNAs expression in the colon cancer cell culture supernatant. We have confirmed the alterations of various exosomal miRNAs. In addition, to investigate the function of exosomal miRNAs, a Kyoto Encyclopedia of Genes and Genomes analysis was performed on the target genes of changed miRNAs. Potential target genes were associated with a variety of signaling pathways, and one of these pathways was related to colorectal cancer. These findings suggested that F. nucleatum can alter exosomal miRNAs released from colorectal cancer cells. Furthermore, exosomal miRNAs altered by F. nucleatum could be potential biomarkers for the diagnosis and therapy of colon cancer.

Gene Expression Profiling of Doxifluridine Treated Liver, Small and Large Intestine in Cynomolgus (Macaca fascicularis) Monkeys

  • Jeong, Sun-Young;Park, Han-Jin;Oh, Jung-Hwa;Kim, Choong-Yong;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.3 no.2
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    • pp.137-144
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    • 2007
  • The mechanism of cytotoxicity of doxifluridine, a prodrug fluorouracil (5-FU), has been ascribed to the misincorporation of fluoropyrimidine into RNA and DNA and to the inhibition of the nucleotide synthetic enzyme thymidylate synthase. Increased understanding of the mechanism of 5-FU has led to the development of strategies that increases its anticancer activity or predicts its sensitivity to patients. Using GeneChip?? Rhesus Macaque Genome arrays, we analyzed gene expression profiles of doxifluridine after two weeks repeated administration in cynomolgus monkey. Kegg pathway analysis suggested that cytoskeletal rearrangement and cell adhesion remodeling were commonly occurred in colon, jejunum, and liver. However, expression of genes encoding extracellular matrix was distinguished colon from others. In colon, COL6A2, COL18A1, ELN, and LAMA5 were over-expressed. In contrast, genes included in same category were down-regulated in jejunum and liver. Interestingly, MMP7 and TIMP1, the key enzymes responsible for ECM regulation, were overexpressed in colon. Several studies were reported that both gene reduced cell sensitivity to chemotherapy-induced apoptosis. Therefore, we suggest they have potential as target for modulation of 5-FU action. In addition, the expression of genes which have been previously known to involve in 5-FU pathway, were examined in three organs. Particularly, there were more remarkable changes in colon than in others. In colon, ECGF1, DYPD, TYMS, DHFR, FPGS, DUT, BCL2, BAX, and BAK1 except CAD were expressed in the direction that was good response to doxifluridine. These results may provide that colon is a prominent target of doxifluridine and transcriptional profiling is useful to find new targets affecting the response to the drug.

Mitochondrial metabolism in cancer stem cells: a therapeutic target for colon cancer

  • Song, In-Sung;Jeong, Yu Jeong;Han, Jin
    • BMB Reports
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    • v.48 no.10
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    • pp.539-540
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    • 2015
  • It has been proposed that the selective elimination of cancer stem cells (CSCs) using targeted therapy could greatly reduce tumor growth, recurrence, and metastasis. To develop effective therapeutic targets for CSC elimination, we aimed to define the properties of CSC mitochondria, and identify CSC-mitochondria-specific targets in colon cancer. We found that colon CSCs utilize mitochondrial oxidative phosphorylation (OXPHOS) to produce ATP. We also found that forkhead box protein 1 (FOXM1)-induced peroxiredoxin 3 (PRDX3) maintains the mitochondrial function, and the FOXM1/PRDX3 mitochondrial pathway maintains survival of colon CSCs. Furthermore, FOXM1 induces CD133 (PROM1/prominin 1) expression, which maintains the stemness of colon CSCs. Together, our findings indicate that FOXM1, PRDX3, and CD133 are potential therapeutic targets for the elimination of CSCs in colon cancer.

Atractylochromene Is a Repressor of Wnt/β-Catenin Signaling in Colon Cancer Cells

  • Shim, Ah-Ram;Dong, Guang-Zhi;Lee, Hwa Jin;Ryu, Jae-Ha
    • Biomolecules & Therapeutics
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    • v.23 no.1
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    • pp.26-30
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    • 2015
  • Wnt/${\beta}$-catenin signaling pathway was mutated in about 90% of the sporadic and hereditary colorectal cancers. The abnormally activated ${\beta}$-catenin increases the cancer cell proliferation, differentiation and metastasis through increasing the expression of its oncogenic target genes. In this study, we identified an inhibitor of ${\beta}$-catenin dependent Wnt pathway from rhizomes of Atractylodes macrocephala Koidzumi (Compositae). The active compound was purified by activity-guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2-(4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC). AC suppressed b-catenin/Tcell factor transcriptional activity of HEK-293 reporter cells when they were stimulated by Wnt3a or inhibitor of glycogen synthase kinase-$3{\beta}$. AC down-regulated the nuclear level of ${\beta}$-catenin through the suppression of galectin-3 mediated nuclear translocation of ${\beta}$-catenin in SW-480 colon cancer cells. Furthermore, AC inhibits proliferation of colon cancer cell. Taken together, AC from A. macrocephala might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

Therapeutic effect of a TM4SF5-specific peptide vaccine against colon cancer in a mouse model

  • Kwon, Sanghoon;Kim, Young-Eun;Park, Jeong-A;Kim, Doo-Sik;Kwon, Hyung-Joo;Lee, Younghee
    • BMB Reports
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    • v.47 no.4
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    • pp.215-220
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    • 2014
  • Molecular-targeted therapy has gained attention because of its high efficacy and weak side effects. Previously, we confirmed that transmembrane 4 superfamily member 5 protein (TM4SF5) can serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC). We recently extended the application of the peptide vaccine, composed of CpG-DNA, liposome complex, and TM4SF5 peptide, to prevent colon cancer in a mouse model. Here, we first implanted mice with mouse colon cancer cells and then checked therapeutic effects of the vaccine against tumor growth. Immunization with the peptide vaccine resulted in robust production of TM4SF5-specific antibodies, alleviated tumor growth, and reduced survival rate of the tumor-bearing mice. We also found that serum levels of VEGF were markedly reduced in the mice immunized with the peptide vaccine. Therefore, we suggest that the TM4SF5-specific peptide vaccine has a therapeutic effect against colon cancer in a mouse model.

Release Properties of BSA from Pectin Heads for Colonic Drug Delivery (Colonic Delivery를 위한 펙틴 비드로부터 BSA의 방출 특성)

  • 최춘순;박상무;송원현;이창문;이기영;김동운;김진철
    • KSBB Journal
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    • v.18 no.2
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    • pp.161-164
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    • 2003
  • Oral drug delivery system using pectin gel was developed for colon-targeting of peptide drug. BSA(bovine serum albumin)-loaded pectin and pectin-alginate beads were prepared for drug release properties in vitro. Morphological studies by electron microscopy indicated that pectin and pectin-alginate beads were spherical in shape and approximately 1.0 mm. In order to find the suitable beads, effects of cross-linking agents (calcium chloride or zinc acetate) and drying temperature of beads were investigated. Drug release decreased with concentration of cross-linking agents and drying temperature. For colonic drug delivery from pectin and pectin-alginate beads, pectin degradable enzymes were added at 5 hrs from the beginning of drug release. After addition of enzymes, drug release was suddenly increased against free enzymes. Therefore, pectin and pectin-alginate beads can be promised as useful drug release carriers for colon-targeted delivery.

Combined EGFR and c-Src Antisense Oligodeoxynucleotides Encapsulated with PAMAM Denderimers Inhibit HT-29 Colon Cancer Cell Proliferation

  • Nourazarian, Ali Reza;Najar, Ahmad Gholamhoseinian;Farajnia, Safar;Khosroushahi, Ahmad Yari;Pashaei-Asl, Roghiyeh;Omidi, Yadollah
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4751-4756
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    • 2012
  • Colon cancer continues to be one of the most common cancers, and the importance and necessity of new therapies needs to be stressed. The most important proto-oncogen factors for colon cancer appear to be epidermal growth factor receptor, EGFR, and c-Src with high expression and activity leading to tumor growth and ultimately to colon cancer progression. Application of c-Src and EGFR antisense agents simultaneously should theoretically therefore have major benefit. In the present study, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were combined in a formulation using PAMAM dendrimers as a carrier. Nano drug entry into cells was confirmed by flow cytometry and fluorescence microscopy imaging and real time PCR showed gene expression of c-Src and EGFR, as well as downstream STAT5 and MAPK-1 with the tumor suppressor gene P53 to all be downregulated. EGFR and c-Src protein expression was also reduced when assessed by western blotting techniques. The effect of the antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay, reduction beijng observed after 48 hours. In summary, nano-drug, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were effectively transferred into HT-29 cells and inhibited gene expression in target cells. Based on the results of this study it appears that the use of antisense EGFR and c-Src simultaneously might have a significant effect on colon cancer growth by down regulation of EGFR and its downstream genes.