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Anticancer activity of Δ^(9)-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft

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Asian Pacific Journal of Tropical Biomedicine 2022年第8期12卷 323-332页

作者： surang leelawat Kawin leelawat Thaniya Wannakup Worawan Saingam Nanthaphong Khamthong Fameera Madaka Athip Maha Patamaporn Pathompak Lukman Sueree Thanapat Songsak Medicinal Cannabis Research Institute College of PharmacyRangsit UniversityPathum Thani 12000Thailand Department of Surgery Bumrungrad International HospitalBangkok 10110Thailand Drug and Herbal Product Research and Development Center College of PharmacyRangsit UniversityPathum Thani 12000Thailand College of Oriental Medicine Rangsit UniversityPathum Thani 12000Thailand Department of Pharmacognosy College of PharmacyRangsit UniversityPathum Thani 12000Thailand

Objective:To investigate the effects of Δ^(9)-tetrahydrocannabinol,the principal psychoactive compound of Cannabis sativa,and cannabinol,a Δ^(9)-tetrahydrocannabinol degradative product,on human non-small cell lung cancer ***:Δ^(9)-Tetrahydrocannabinol and cannabinol were tested for anticancer activity in human non-small cell lung cancer(A549)*** effects on cell proliferation,apoptosis,and phosphorylation profiles were *** effects of Δ^(9)-tetrahydrocannabinol and cannabinol on tumor growth were also investigated using a xenograft nude mouse *** and targeted phosphorylation were verified by ***:Δ^(9)-Tetrahydrocannabinol and cannabinol significantly inhibited cell proliferation and increased the number of apoptotic cells in a concentration-dependent *** Δ^(9)-tetrahydrocannabinol-and cannabinol-treated cells had lower levels of phosphorylated protein kinase B[AKT(S473)],glycogen synthase kinase 3 alpha/beta,and endothelial nitric oxide synthase compared to the *** study of xenograft mice revealed that tumors treated with 15 mg/kg Δ^(9)-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly smaller than those of the control *** tumor progression rates in mice treated with 15 mg/kg Δ^(9)-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly slower than in the control ***:These findings indicate that Δ^(9)-tetrahydrocannabinol and cannabinol inhibit lung cancer cell growth by inhibiting AKT and its signaling pathways,which include glycogen synthase kinase 3 alpha/beta and endothelial nitric oxide synthase.

关键词： Cannabis Δ9-Tetrahydrocannabinol Cannabinol Non-small cell lung cancer AKT Cannabis sativa Glycogen synthase kinase 3 alpha/beta Endothelial nitric oxide synthase

Circulating hTERT mRNA as a tumor marker in cholangiocarcinoma patients

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World Journal of Gastroenterology 2006年第26期12卷 4195-4198页

作者： Kawin leelawat surang leelawat Thawee Ratanachu-Ek Somboon Trubwongchareon Jerasak Wannaprasert Saad Tripongkaruna Suchart Chantawibul Panadda Tepaksorn Department of Surgery Rajavithi Hospital Bangkok10400Thailand Department of BiochemistryFaculty of ScienceMahidol UniversityBangkok10400Thailand Faculty of Pharmacy Rangsit University Patumthani12000Thailand Department of Surgery Rajavithi Hospital Bangkok10400Thailand Medical Biotechnology Center National Institute of Health 13000Thailand

AIM： To investigate human telomerase reverse transcriptase （hTERT） mRNA in the serum of cholangiocarcinoma patients. METHODS： The serum of thirty three cholangiocarcinoma patients, forty one benign biliary tract disease patients and ten healthy volunteers were collected and analyzed for the expression of hTERT mRNA by real-time reverse transcriptase-polymerase chain reaction （RT-PCR）. We then examined the correlation between values of serum hTERT mRNA and the pathological staging of cholangiocarcinoma. RESULTS： hTERT mRNA was detected in 28 of 33 （84.85%） of serum obtained from cholangiocarcinoma patients and 9 of 41 （21.9%） of serum obtained from benign biliary tract disease patients, hTERT mRNA was not detected in any serum obtained from healthy volunteers, on the other hand the common tumor marker, CA19-9 was detected in 20 of 33 （60.6%） of serum obtained from cholangiocarcinoma patients and 8 of 41 （19.5%） of serum obtained from benign biliary tract disease patients. However, no correlation was found between the present of serum hTERT mRNA and tumor staging. CONCLUSION： These results indicate that the detection of circulating hTERT mRNA was identified in almost all cholangiocarcinoma patients. It offers a novel tumor marker, which can be used as a complementary study for diagnosis of cholangiocarcinoma .

关键词： Cholangiocarcinoma Telomerase hTERT Real-time reverse transcriptase-polymerase chain reaction

Disaster Recovery and Reconstruction Following the 2011 Great East Japan Earthquake and Tsunami: A Business Process Management Perspective

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International Journal of Disaster Risk Science 2015年第3期6卷 310-314页

作者： Natt leelawat Anawat Suppasri Fumihiko Imamura Department of Industrial Engineering and Management Graduate School of Decision Science and TechnologyTokyo Institute of Technology International Research Institute of Disaster Science Tohoku University

The Tohoku Regional Bureau(TRB) of the Ministry of Land, Infrastructure, Transport and Tourism(MLIT) performed various actions in response to the 2011 Great East Japan Earthquake and Tsunami. The total disaster recovery and reconstruction period is expected to last for 10 years, of which the first five years are regarded as the concentrated reconstruction period. As of 2013, a majority of the mega projects that involved restoration actions have been completed, which indicates a more effective rate of completion compared with the MLIT projects performed in normal non-disaster situations. This short article explains the management process of the recovery and reconstruction utilized by the TRB—an interorganizational process—from a business process management(BPM) perspective and creates a simple organization construction diagram of the entire process. The study focused on the transactions and actor roles to identify their strengths. The findings indicate the utilization of different operational procedures in some parts of the process, the importance of liaison role, as well as some obstacles. The lessons learned from this analysis can assist managers and researchers in designing and managing restoration processes for future disasters.

关键词： Business process management Disaster reconstruction Disaster recovery 2011 Great East Japan Earthquake and Tsunami

Receptor-binding cancer antigen expressed on SiSo cells can be detected in metastatic lymph nodes from gastrointestinal cancers

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World Journal of Gastroenterology 2005年第38期11卷 6014-6017页

作者： Kawin leelawat surang Engprasert Supathip Tujinda Cheepsumon Suthippintawong Munechika Enjoji Manabu Nakashima Takeshi Watanabe Vijittra Leardkamolkarn Department of Surgery Department of Pharmacognosy Department of Pathology Department of Medical Bioregulation Department of Anatomy

AIM： To investigate the expression of receptor-binding cancer antigen expressed on SiSo cells （RCAS1） in metastatic lymph nodes from gastrointestinal cancer. METHODS： Metastatic lymph nodes from gastrointestina cancer were detected for RCAS1 by immunohistochemica staining and mRNA in situ hybridization.RESULTS： A total of 102 metastatic lymph nodes from bile duct, gastric, colon, and pancreatic cancer were investigated for RCAS1 expression. The immunoreactivity of RCAS1 was identified in 100% of metastatic lymph nodes. Both local and distant metastatic lymph nodes showed RCAS1 expression. On the contrary, specimens of non-cancerous lymph nodes were negative for RCAS1. The result of mRNA in situ hybridization was also confirmed by the finding of immunohistochemical staining. RCAS1 mRNA was detected in all tumor cells that metastasized to lymph nodes. CONCLUSION： All metastatic lymph nodes express RCAS1 in tumor cells at both protein and mRNA levels, and RCAS1 should be used as a complementary factor for identification of metastatic lymph nodes from gastrointestinal cancers.

关键词： RCAS1 Gastrointestinal cancer Lymph node metastasis

Frontiers in antibiotic alternatives for Clostridioides difficile infection

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World Journal of Gastroenterology 2021年第42期27卷 7210-7232页

作者： Matthew Phanchana Phurt Harnvoravongchai Supapit Wongkuna Tanaporn Phetruen Wichuda Phothichaisri Supakan Panturat Methinee Pipatthana Sitthivut Charoensutthivarakul surang Chankhamhaengdecha Tavan Janvilisri Department of Molecular Tropical Medicine and Genetics Faculty of Tropical MedicineMahidol UniversityBangkok 10400Thailand Department of Biology Faculty of ScienceMahidol UniversityBangkok 10400Thailand Department of Biochemistry Faculty of ScienceMahidol UniversityBangkok 10400Thailand School of Bioinnovation and Bio-based Product Intelligence Faculty of ScienceMahidol UniversityBangkok 10400Thailand

Clostridioides difficile(***)is a gram-positive,anaerobic spore-forming bacterium and a major cause of antibiotic-associated *** are naturally resistant to *** infection(CDI)owing to the protection provided by healthy gut *** the gut microbiota is disturbed,*** can colonize,produce toxins,and manifest clinical symptoms,ranging from asymptomatic diarrhea and colitis to *** the steady-if not risingprevalence of CDI,it will certainly become more problematic in a world of antibiotic overuse and the post-antibiotic *** is naturally resistant to most of the currently used antibiotics as it uses multiple resistance ***,current CDI treatment regimens are extremely limited to only a few antibiotics,which include vancomycin,fidaxomicin,and ***,one of the main challenges experienced by the scientific community is the development of alternative approaches to control and treat *** this Frontier article,we collectively summarize recent advances in alternative treatment approaches for *** the past few years,several studies have reported on natural product-derived compounds,drug repurposing,highthroughput library screening,phage therapy,and fecal microbiota *** also include an update on vaccine development,pre-and probiotics for CDI,and toxin antidote *** measures tackle CDI at every stage of disease pathology via multiple *** also discuss the gaps and concerns in these *** next epidemic of CDI is not a matter of if but a matter of ***,being well-equipped with a collection of alternative therapeutics is necessary and should be prioritized.

关键词： Bacteriophage Pharmaceutical Clostridioides difficile Alternative therapy Drug resistance Fecal microbiota

Prospective study of MMP7 serum levels in the diagnosis of cholangiocarcinoma

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World Journal of Gastroenterology 2010年第37期16卷 4697-4703页

作者： Kawin leelawat Siriluck Narong Jerasak Wannaprasert Thawee Ratanashu-ek Department of Surgery Rajavithi Hospital College of Medicine Department of Surgery Rangsit University

AIM: To determine whether the serum level of matrix metalloproteinase-7 (MMP7) has the potential to diagnosis cholangiocarcinoma from benign biliary tract diseases. METHODS: This study was performed according to the PRoBE (a prospective-specimen-collection, retrospectiveblinded-evaluation) design. A total of 187 patients with obstructive jaundice were consecutively enrolled. After the diagnostic status of these patients was ascertained, their levels of serum MMP7 were assayed and compared with serum carbohydrate antigen 19-9 (CA19-9). This was conducted in a blinded case (cholangiocarcinoma)control (benign biliary tract disease) setup. RESULTS: MMP7 and CA19-9 serum levels were significantly elevated in cholangiocarcinoma patients (P < 0.001). The area under the curve (AUC) from a receiver operating characteristic (ROC) curve analysis for thediagnosis of cholangiocarcinoma, using MMP7 was more accurate than CA19-9 (AUC = 0.84, 95% CI: 0.778-0.903 for MMP7 and AUC = 0.79, 95% CI: 0.708-0.868 for CA19-9). The sensitivity and specificity of serum MMP7 (cut-off value of 5.5 ng/mL) was 75% and 78%, respectively, while the sensitivity and specificity of serum CA19-9 (cut-off value of 100 U/mL) was 68% and 87%, respectively. CONCLUSION: Serum values of MMP7 and CA19-9 appear to be useful biomarkers for differentiating cholangiocarcinoma from benign biliary tract obstructive diseases.

关键词： Carbohydrate antigen 19-9 Cholangiocarcinoma Matrix metalloproteinase-7 Sensitivity Specificity Tumor marker

Strong expression of CD133 is associated with increased cholangiocarcinoma progression

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World Journal of Gastroenterology 2011年第9期17卷 1192-1198页

作者： Kawin leelawat Taweesak Thongtawee Siriluck Narong Somboon Subwongcharoen Sa-ad Treepongkaruna Department of Surgery Rajavithi Hospital College of Medicine Rangsit University

AIM:To determine the role of CD133 in cholangiocarcinoma progression. METHODS:CD133 protein expression was evaluated by immunohistochemistry in 34 cholangiocarcinoma *** addition,proliferation,chemoresistance and invasive properties of CD133-enriched(CD133 + ) and CD133-depleted(CD133 )RMCCA1 cholangiocarcinoma cells were studied and compared. RESULTS:Strong CD133 expression was observed in 67.6%(23/34)of the cholangiocarcinoma specimens. Strong expression of CD133 was significantly associated with nodal metastasis(P=0.009)and positive surgical margin status(P=0.011).In the in vitro study, both the CD133 + and CD133 cells had similar proliferation abilities and resistance to chemotherapeutic ***,the CD133 + cells had a higher invasive ability compared with CD133 cells. CONCLUSION:CD133+cells play an important role in the invasiveness of *** of the CD133+cells may be a useful approach to improve treatment against cholangiocarcinoma.

关键词： CD133 Cholangiocarcinoma Immunohistochemistry Invasion Metastasis

γ-aminobutyric acid B2 receptor:A potential therapeutic target for cholangiocarcinoma in patients with diabetes mellitus

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World Journal of Gastroenterology 2023年第28期29卷 4416-4432页

作者： Charupong Saengboonmee Supannika Sorin Sakkarn Sangkhamanon surang Chomphoo Somsiri Indramanee Wunchana Seubwai Kanyarat Thithuan Ching-Feng Chiu Seiji Okada Marie-Claude Gingras Sopit Wongkham Department of Biochemistry Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Center for Translational Medicine Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Cholangiocarcinoma Research Institute Khon Kaen UniversityKhon Kaen 40002Thailand Department of Pathology Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Anatomy Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Forensic Medicine Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Graduate Institute of Metabolism and Obesity Sciences Taipei Medical UniversityTaipei 11031Taiwan Division of Hematopoiesis Joint Research Center for Human Retrovirus InfectionKumamoto UniversityKumamoto 860-0811Japan Human Genome Sequencing Center Department of Human and Molecular GeneticsBaylor College of MedicineHoustonTX 77030United States Michael E.DeBakey Department of Surgery Baylor College of MedicineHoustonTX 77030United States

BACKGROUND The association between diabetes mellitus(DM)and the increased risk and progression of cholangiocarcinoma(CCA)has been reported with unclear underlying *** studies showed thatγ-aminobutyric acid(GABA)B2 receptor(GABBR2)was upregulated in CCA cells cultured in high glucose(HG)*** of GABA receptors in CCA progression have also been studied,but their association with DM and hyperglycemia in CCA remains *** To investigate the effects of hyperglycemia on GABBR2 expression and the potential use of GABBR2 as a CCA therapeutic *** CCA cells,KKU-055 and KKU-213A,were cultured in Dulbecco Modified Eagle’s Medium supplemented with 5.6 mmol/L(normal glucose,NG)or 25 mmol/L(HG)glucose and assigned as NG and HG cells,***2 expression in NG and HG cells was investigated using real-time quantitative polymerase chain reaction and western *** and localization of GABBR2 in CCA cells were determined using ***2 expression in tumor tissues from CCA patients with and without DM was studied using immunohistochemistry,and the correlations of GABBR2 with the clinicopathological characteristics of patients were analyzed using univariate *** of baclofen,a GABA-B receptor agonist,on CCA cell proliferation and clonogenicity were tested using the MTT and clonogenic ***-kinases arrays were used to screen the affected signaling pathways after baclofen treatment,and the candidate signaling molecules were validated using the public transcriptomic data and western *** GABBR2 expression in CCA cells was induced by HG in a dose-and time-dependent *** tissues from patients with DM and hyperglycemia also showed a significantly higher GABBR2 expression compared with tumor tissues from those with euglycemia(P<0.01).High GABBR2 expression was significantly associated with a poorer non-papillary histological subtype but with smaller sizes of CCA tumors(P<0.0

关键词： Baclofen Cholangiocarcinoma Diabetes mellitus Drug repurposing Hyperglycemia Gamma-aminobutyric acid

Establishment and characterization of a cholangiocarcinoma cell line (RMCCA-1) from a Thai patient

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World Journal of Gastroenterology 2006年第40期12卷 6500-6506页

作者： Panthip Rattanasinganchan Kawin leelawat Sa-ard Treepongkaruna Chintana Tocharoentanaphol Somboon Subwongchareon Tuangporn Suthiphongchai Rutaiwan Tohtong Department of Biochemistry Faculty of Science Mahidol University Bangkok 10400 Thailand Department of Biochemistry Faculty of Science Mahidol University Bangkok 10400 ThailandDepartment of Surgery Rajavithi Hospital Bangkok 10400 ThailandCancer Cytogenetic Unit Chulabhorn Cancer Center Chulabhorn Research Institute Patumthani 12000 Thailand Department of Surgery Rajavithi Hospital Bangkok 10400 Thailand Cancer Cytogenetic Unit Chulabhorn Cancer Center Chulabhorn Research Institute Patumthani 12000 Thailand

AIM: To establish and characterize a new cell line derived from peripheral cholangiocarcinoma of a Thai ***: The peripheral cholangiocarcinoma specimen surgically obtained from the patient was aseptically processed by washing and mincing before culturing in Ham’s F12 medium containing 10% fetal bovine serum. After 3 mo, when the cell line has become homogeneous and stabilized, several features were investigated, including growth characteristics, immunofluorescence staining for cytokeratins, expression of tumor markers, chromosomal analysis by G-banding and multicolour fluorescence in situ hybridization (mFISH), in vitro migration and invasion characteristics. RESULTS: The RMCCA-1 cell line has been established. These cells proliferated as a monolayer with a population doubling time of 48 h. Immunofluorescence staining showed positive staining for human cytokeratin 7 and 19 verifying the biliary epithelial origin. RMCCA-1 secreted carbohydrate antigen 19-9 (CA19-9), but insignificant levels of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP). Chromosome analysis identified aneuploidy karyotypes with a modal chromosome number of 59. RMCCA-1 exhibited a low level of in vitro invasiveness, but a high degree of motility. The cell line exhibited a significant number of chromosomal aberrations as shown by mFISH and G-banding ***: A new cell line derived from peripheral cholangiocarcinoma of a Thai patient has been established. This cell line shows a low level of in vitro invasiveness, but a high degree of motility. It will serve as a valuable tool for further studies on tumor biology, molecular pathogenesis, metastatic mechanism and response to therapeutic drugs of cholangiocarcinoma.

关键词： Cholangiocarcinoma Cell line Establishment mFISH Invasion Migration