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Prognostic significance of microsatellite alterations at 1p36 in cholangiocarcinoma

World Journal of Gastroenterology 2006年第27期12卷 4377-4382页

作者： Temduang Limpaiboon Sumonta Tapdara Patcharee Jearanaikoon Banchob Sripa vajarabhongsa bhudhisawasdi Department of Clinical Chemistry Center for Research and Development of Medical Diagnostic LaboratoriesFaculty of Associated Medical SciencesKhon Kaen UniversityKhon Kaen 40002Thailand Department of Pathology Liver Fluke and Cholangiocarcinoma Research CenterFaculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Surgery Liver Fluke and Cholangiocarcinoma Research CenterFaculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand

AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellite alterations and clinicopathological parameters. METHODS： Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer. RESULTS： Sixty-eight out of 90 cases （75.6%） showed LOH in one or more loci. LOH was found most frequently at DIS199 （40.0%）, DIS507 （34.6%）, DIS2845 （30.5%）, and DIS2734 （30.1%）. MSI was found in 34 of 90 cases （37.8%） at one or more loci. Fine mapping at lp36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion （P = 0.017）, whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without （P = 0.031）. LOH at D1S2845 showed a significant correlation with nerve invasion （P = 0.029）. Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis （P = 0.0026）. CONCLUSION： Allelic loss plays a major role in microsatellite alterations at chromosome lp36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.

关键词： Cholangiocarcinoma Liver fluke Chromosome 1p36 Loss of heterozygosity Microsatellite instability

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Amplification of chromosome 21q22.3 harboring trefoil factor family genes in liver fluke related cholangiocarcinoma is associated with poor prognosis

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World Journal of Gastroenterology 2006年第26期12卷 4143-4148页

作者： Kanuengnuch Muenphon Temduang Limpaiboon Patcharee Jearanaikoon Chawalit Pairojkul Banchob Sripa vajarabhongsa bhudhisawasdi Department of Clinical Chemistry Center for Research and Development of Medical Diagnostic Laboratories Faculty of Associated Medical SciencesKhon Kaen UniversityKhon Kaen 40002Thailand Department of Pathology Liver Fluke and Cholangiocarcinoma Research Center Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Surgery Liver Fluke and Cholangiocarcinoma Research Center Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand

AIM： To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes （TFF） in cholangiocarcinoma （CCA） patients and analyze the correlation between allelic imbalances and clinicopathological parameters. METHODS： Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes （TFF1, TFF2, and TFF3） using a standard curve and SYBR Green I dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by χ^2-tests. Kaplan-Meier method was used to analyze survival. RESULTS： The frequencies of amplification at D21S1890, D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%, respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis （mean： 51.7 wk vs 124.82 wk, P = 0.012）. Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF, blood vessel invasion, and staging were associated with poor prognosis. CONCLUSION： D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients.

关键词： Cholangiocarcinoma Amplification on chromosome 21 Trefoil factor family Quantitative PCR Liver fluke

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Amplification of D22S283 as a favorable prognostic indicator in liver fluke related cholangiocarcinoma

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World Journal of Gastroenterology 2006年第27期12卷 4338-4344页

作者： Jongkonnee Thanasai Temduang Limpaiboon Patcharee Jearanaikoon vajarabhongsa bhudhisawasdi Narong Khuntikeo Banchob Sripa Masanao Miwa Graduate School Faculty of Medical TechnologyMahidol UniversityBangkok 10700Thailand Department of Clinical Chemistry Centre for Research and Development of Medical Diagnostic LaboratoriesFaculty of Associated Medical SciencesKhon Kaen UniversityKhon Kaen 40002Thailand Department of Surgery Liver Fluke and Cholangiocarcinoma Research CenterFaculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Pathology Liver Fluke and Cholangiocarcinoma Research CenterFaculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Biochemistry and Molecular Oncology Institute of Basic Medical SciencesUniversity of TsukubaIbaraki 3058575Japan

AIM： To analyze the DNA copy number of target genes NF2, TIMP3, ST13, TOB2, BIK, and TP and the reference microsatellite markers D22S283, D22S423, and D22S274 mapped on 22q12-qter in liver fluke related cholangiocarcinoma （CCA） and define its correlation with clinical parameters. METHODS： Quantitative real time PCR （qPCR） was used for determining allelic imbalances in 65 liver fluke related CCA tissues. Statistical correlations between allelic imbalances and clinicopathological parameters, i.e. age, sex, tumor stage, histological type, blood vessel invasion, nerve invasion and lymphatic invasion were evaluated by means of the X^2 test. Cox regression analysis was used for determining patient＇s survival. RESULTS： Amplifications of the TP （22q13.33）, TOB2 （22q13.2-13.31）, D22S283 （22q12.3）, TIMP3 （22q12.3） and NF2 （22q12.2） were found in 35 （53.8%）, 28 （43.1%）, 27 （41.5%）, 24 （36.9%）, and 24 （36.9%）, respectively. Losses at the D22S423 （22q13.1-13.2）and BIK （22q13.31） were detected in 26 （40%） and 23 （35.4%）, respectively. Significant correlations were observed between lymphatic invasion and allelic losses of BIK （P = 0.025） and D22S283 （P = 0.041）. Univariate and multivariate Cox regression analysis revealed D22S283 amplification as an independent predictor of good prognosis （P = 0.006, death hazard ratio = 0.411, 95% CI = 0.217-0.779） and blood vessel invasion as an independent poor prognostic factor （P = 0.042, death hazard ratio = 1.911, 95% CI = 1.022-3.571） in CCA patients. CONCLUSION： This study provides evidence for the involvement of gene amplification and deletion on chromosome 22q in liver fluke related CCA, This is the first report of D22S283 amplification as an independent indicator of favorable prognosis in liver fluke related CCA.

关键词： Liver fluke related cholangiocarcinoma Chromosome 22q D22S283 Allelic imbalance Quantitative real time PCR

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Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

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World Journal of Gastroenterology 2005年第18期11卷 2748-2753页

作者： Nisana Tepsiri Liengchai Chaturat Banchob Sripa Wises Namwat Sopit Wongkham vajarabhongsa bhudhisawasdi Wichittra Tassaneeyakul Department of Biochemistry Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Department of Pharmacology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Department of Pathology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Department of Microbiology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Department of Surgery Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand

AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase PI (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined. METHODS: Five human CCA cell lines (KKU-100, KKU-M055, KKU-M156, KKU-M214 and KKU-OCA17) were treated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC_(50) values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC_(50) values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC_(50) values (＜5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC_(50) values of etoposide, doxorubicin and pirarubicin (r=0.86-0.98, P＜0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of dr

关键词： Cholangiocarcinoma Chemotherapeutic agents Drug sensitivity Drug resistance Multidrug resistance protein MRP

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Establishment and characterization of an opisthorchiasis-associated cholangiocarcinoma cell line (KKU-100)

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World Journal of Gastroenterology 2005年第22期11卷 3392-3397页

作者： Banchob Sripa Saman Leungwattanawanit Takayuki Nitta Chaisiri Wongkham vajarabhongsa bhudhisawasdi Anucha Puapairoj Chongrak Sripa Masanao Miwa Department of Pathology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Liver Fluke and Cholangiocarcinoma Research Center Khon Kaen University Khon Kaen 40002 Thailand Department of Pathology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Institute of Basic Medical Science University of Tsukuba Ibaraki 305-8575 Tsukuba Japan Department of Biochemistry Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Liver Fluke and Cholangiocarcinoma Research Center Khon Kaen University Khon Kaen 40002 Thailand Department of Surgery Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Liver Fluke and Cholangiocarcinoma Research Center Khon Kaen University Khon Kaen 40002 Thailand Department of Pathology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand Puapairoj Liver Fluke and Cholangiocarcinoma Research Center Khon Kaen University Khon Kaen 40002 Thailand

AM: To establish and characterize a new cholangiocarcinoma cell line from a patient living in the Opisthorchis viverrini (O. viverrini) endemic area of Northeast Thailand. METHODS: Fresh liver biopsy and bile specimens were obtained from a 65-year-old Thai woman with cholangiocarcinoma of the ports hepatis. After digestion, the cells were cultured in Ham's F12 media. The established cell line was then characterized for growth kinetics, cell morphology, imm-unocytochemistry and cytogenetics. Tumorigenicity of the cell line was determined by heterotransplanting in nude mice. RESULTS: The primary tumor was a poorly differentiated tubular adenocarcinoma. Examination of the bile revealed malignant cells with O. viverrin eggs. The cholangiocarcinoma cell line KKU-100 was established 4 mo after the primary culture-population doubling time was 72 h. KKU-100 possesses compact and polygonal-shaped epithelial cells. Immunocytochemically, this cell line exhibited cytokeratin, EMA, CEA, and CA125, but not a-fetoprotein (AFP), CA19-9, desmin, c-met, or p53. Such protein expressions parallel those of the primary tumor. Cytogenetic analysis identified aneuploidy karyotypes with a modal chromosome number of 78 and marked chromosomal structural changes. Inoculation of KKU-100 cells into nude mice produced a transplantable, poorly differentiated aden-ocarcinoma, similar to the original tumor. CONCLUSION: KKU-100 is the first egg-proven, Opisthorchis- associated cholangiocarcinoma cell line, which should prove useful for further investigations of the tumor biology of this cancer.

关键词： Cholangiocarcinoma Cell line Establishment Characterization Opisthorchiasis

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Orotate phosphoribosyl transferase mRNA expression and the response of cholangiocarcinoma to 5-fluorouracil

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World Journal of Gastroenterology 2012年第30期18卷 3955-3961页

作者： Chariya Hahnvajanawong Jariya Chaiyagool Wunchana Seubwai vajarabhongsa bhudhisawasdi Nisana Namwat Narong Khuntikeo Banchob Sripa Ake Pugkhem Wichittra Tassaneeyakul Department of Microbiology Center of Excellence for Innovation in Chemistryand Liver Fluke and Cholangiocarcinoma Research CenterFaculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Forensic Medicine Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Surgery Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Biochemistry Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Pathology Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Pharmacology Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand

AIM:To determine whether expression of certain enzymes related to 5-fluorouracil(5-FU)metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma(CCA).METHODS:The histoculture drug response assay(HDRA)was performed using surgically resected CCA *** cell viability was determined morphologically with hematoxylin and eosin-and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained *** mRNA expression of thymidine phosphorylase(TP),orotate phosphoribosyl transferase(OPRT),thymidylate synthase(TS),and dihydropyrimidine dehydrogenase(DPD)was determined with realtime reverse transcriptase-polymerase chain *** levels of gene expression and the sensitivity to 5-FU were ***:Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital,Khon Kaen University from 2007 to *** was used to determine the response of these CCA tissues to *** on the dose-response curve,200μg/mL 5-FU was selected as the test *** percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to *** the relationship between TP,OPRT,TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined,only OPRT mRNA expression was significantly correlated with the response to *** mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group(0.41±0.25 vs 0.22±0.12,P<0.05).CONCLUSION:OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of *** OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients.

关键词： Histoculture drug response assay 5-fluorouracil Cholangiocarcinoma Orotate phosphoribosyl transferase Chemosensitivity

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Compliance with enhanced recovery after surgery predicts long-term outcome after hepatectomy for cholangiocarcinoma

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World Journal of Gastrointestinal Surgery 2023年第3期15卷 362-373页

作者： Chaowasaporn Jongkatkorn Vor Luvira Chalisa Suwanprinya Kantaruthai Piampatipan Natwutpong Leeratanakachorn Theerawee Tipwaratorn Attapol Titapun Tharatip Srisuk Suapa Theeragul Apiwat Jarearnrat Vasin Thanasukarn Ake Pugkhem Narong Khuntikeo Chawalit Pairojkul Supot Kamsa-Ard vajarabhongsa bhudhisawasdi Department of Surgery Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Surgery Saraburi HospitalSaraburi 18000Thailand Department of Pathology Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Epidemiology and Biostatistics Faculty of Public HealthKhon Kaen UniversityKhon Kaen 40002Thailand

BACKGROUND Enhanced recovery after surgery(ERAS)program has been proved to improve postoperative outcome for many surgical procedures,including liver *** was limited evidence regarding the feasibility and benefit of ERAS in patients who underwent liver resection for *** To evaluate the feasibility of ERAS in patients who underwent liver resection for cholangiocarcinoma and its association with patient *** We retrospectively analyzed 116 cholangiocarcinoma patients who underwent hepatectomy at Srinagarind Hospital,Khon Kaen University between January 2015 and December *** primary outcome was the compliance with *** determine the association between ERAS compliance and patient *** patients were categorized into those adhering more than and equal to 50%(ERAS≥50),and below 50%(ERAS<50)of all *** on type of surgical procedure,preoperative and postoperative care,tumor location,postoperative laboratory results,and survival time were *** compliance with ERAS was measured by the percentage of ERAS items *** Kaplan-Meier curve was used for survival *** The median percentage of ERAS goals achieved was 40%(±12%).Fourteen patients(12.1%)were categorized into the ERAS≥50 group,and 102 patients were in the ERAS<50 *** hospital stay was significantly shorter in the ERAS≥50 group[8.9 d,95%confidence interval(CI):7.3-10.4 d]than in the ERAS<50 group(13.7 d,95%CI:12.2-15.2 d)(P=0.0217).No hepatobiliary-related complications or in-hospital mortality occurred in the ERAS≥50 *** survival was significantly higher in the ERAS≥50 *** median survival of the patients in the ERAS<50 group was 1257 d(95%CI:853.2-1660.8 d),whereas that of the patients in the ERAS≥50 group was not *** Overall ERAS compliance for patients who underwent liver resection for cholangiocarcinoma is *** ERAS compliance could predict in-hospital,short-term,an

关键词： Enhanced recovery program after surgery Cholangiocarcinoma Hepatectomy Survival Enhanced recovery after surgery Outcome

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Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion

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World Journal of Gastroenterology 2005年第30期11卷 4644-4649页

作者： Somchai Pinlaor Banchob Sripa Ning Ma Yusuke Hiraku Puangrat Yongvanit Sopit Wongkham Chawalit Pairojkul vajarabhongsa bhudhisawasdi Shinji Oikawa Mariko Murata Reiji Semba Shosuke Kawanishi Department of Parasitology Department of Pathology Department of Anatomy Department of Environmental and Molecular Medicine Department of Biochemistry Department of Surgery

AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesis. The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma. METHODS： We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α （HIF-1α） with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma. RESULTS： Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1α expression was correlated with inducible niltric oxide synthase （iNOS） expression （r = 0.369 and P = 0.025） and 8-oxodG formation （r = 0.398 and P = 0.015）. Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion （r = 0.386 and P = 0.018）. Moreover, 8- nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion （P = 0.042 and P = 0.026, respectively）. These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis. CONCLUSION： The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.

关键词： 8-Nitroguanine 8-Oxo-7,8-dihydro-2'-deoxyguanosine Hypoxia-inducible factor-1α Cholangiocarcinoma Tumor invasion

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Pathway analysis of metabolic genes and serum metabolites in HCC reveal aberrations associated with fatty acid and lipid metabolism

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Cancer Biology & Medicine 2018年第S1期15卷 12-13页

作者： Yotsawat Pomyen Anuradha Budhu Jittiporn Chaisaingmongkol Hien Dang Siritida Rabibhadana Benjarath Pupacdi Marshonna Forgues vajarabhongsa bhudhisawasdi Nirush Lertprasertsuke Chirayu Auewarakul Thaniya Sricharunrat Kannika Phornphutkul Suleeporn Sangrajrang Chulabhorn Mahidol Mathuros Ruchirawat Xinwei Wang The Liver Carcinogenesis Section Laboratory of Human CarcinogenesisCenter for Cancer ResearchNational Cancer InstituteBethesdaMarylandUSA Chulabhorn Research Institute BangkokThailand Khon Kaen University Khon KaenThailand Chiang Mai University Chiang MaiThailand Chulabhorn Hospital BangkokThailand Rajavej Hospital and Lampang Cancer Center Chiang MaiThailand National Cancer Institute BangkokThailand

Objective:Hepatocellular carcinoma(HCC)is among the deadliest cancers in *** Thailand Initiative in Genomics and Expression Research for Liver Cancer(TIGER-LC)cohort was established to discover molecular markers that can be used for early detection and diagnosis and to understand possible molecular mechanisms underlying the disease.

关键词： Pathway analysis metabolic

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Global tissue and serum metabolomics reveals altered tumor biochemical activity in molecular subtypes of hepatocellular carcinoma and cholangiocarcinoma

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Cancer Biology & Medicine 2018年第S1期15卷 13-14页

作者： Xinwei Wang Thaniya Mathuros Ruchirawat Anuradha Budhu Yotsawat Pomyen Jittiporn Chaisaingmongkoll Hien Dang Siritida Rabibhadana Benjarath Pupacdi Marshonna Forgues vajarabhongsa bhudhisawasdi Nirush Lertprasertsuke Anon Chotirosniramit Chawalit Pairojkul Chirayu Auewarakul Thaniya Sricharunrat Kannika Phornphutkul Suleeporn Sangrajrang Chulabhorn Mahidol The Liver Carcinogenesis Section Laboratory of Human CarcinogenesisCenter for Cancer ResearchNational Cancer InstituteBethesdaMDUSA Chulabhorn Research Institute BangkokThailand Khon Kaen University Khon KaenThailand Chiang Mai University Chiang MaiThailand Chulabhorn Hospital BangkokThailand Rajavej Hospital and Lampang Cancer Center Chiang MaiThailand

Objective:Cancer metabolite profiling(or cancer metabolomics),the global view of the biochemical end products of cellular processes,is a promising approach to identify biomarkers and tumor subgroups,and to understand ... 详细信息

关键词： Global tissue metabolomics

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