Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVLQFIP)

• DOT Name: Keratin, type I cytoskeletal 18 (KRT18)
• Synonyms: Cell proliferation-inducing gene 46 protein; Cytokeratin-18; CK-18; Keratin-18; K18
• Gene Name: KRT18
• Related Disease:
  Bladder cancer
  Gastric neoplasm
  Acute liver failure
  Adenocarcinoma
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cholangiocarcinoma
  Chronic kidney disease
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Cystic fibrosis
  Esophageal squamous cell carcinoma
  Fatty liver disease
  Head-neck squamous cell carcinoma
  Hepatitis
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Liver cancer
  Lung cancer
  Melanoma
  Metastatic malignant neoplasm
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-alcoholic steatohepatitis
  Non-insulin dependent diabetes
  Obesity
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Chronic obstructive pulmonary disease
  Small-cell lung cancer
  Squamous cell carcinoma
  Type-1 diabetes
  Advanced cancer
  Castration-resistant prostate carcinoma
  Cirrhosis, familial
  Gastric cancer
  Liver cirrhosis
  Non-small-cell lung cancer
  Type-1/2 diabetes
• UniProt ID: K1C18_HUMAN
• Pfam ID: PF00038
• Sequence:
  MSFTTRSTFSTNYRSLGSVQAPSYGARPVSSAASVYAGAGGSGSRISVSRSTSFRGGMGS
  GGLATGIAGGLAGMGGIQNEKETMQSLNDRLASYLDRVRSLETENRRLESKIREHLEKKG
  PQVRDWSHYFKIIEDLRAQIFANTVDNARIVLQIDNARLAADDFRVKYETELAMRQSVEN
  DIHGLRKVIDDTNITRLQLETEIEALKEELLFMKKNHEEEVKGLQAQIASSGLTVEVDAP
  KSQDLAKIMADIRAQYDELARKNREELDKYWSQQIEESTTVVTTQSAEVGAAETTLTELR
  RTVQSLEIDLDSMRNLKASLENSLREVEARYALQMEQLNGILLHLESELAQTRAEGQRQA
  QEYEALLNIKVKLEAEIATYRRLLEDGEDFNLGDALDSSNSMQTIQKTTTRRIVDGKVVS
  ETNDTKVLRH
• Function: Involved in the uptake of thrombin-antithrombin complexes by hepatic cells. When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to the plasma membrane. Together with KRT8, is involved in interleukin-6 (IL-6)-mediated barrier protection.
• Tissue Specificity: Expressed in colon, placenta, liver and very weakly in exocervix. Increased expression observed in lymph nodes of breast carcinoma.
• KEGG Pathway:
  Estrogen sig.ling pathway (hsa04915)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Definitive	Altered Expression	[1]
Gastric neoplasm	DISOKN4Y	Definitive	Biomarker	[2]
Acute liver failure	DIS5EZKX	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[9]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[13]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[8]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[15]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[16]
Hepatitis	DISXXX35	Strong	Altered Expression	[17]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[18]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[19]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[20]
Liver cancer	DISDE4BI	Strong	Biomarker	[21]
Lung cancer	DISCM4YA	Strong	Altered Expression	[22]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[23]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[24]
Neoplasm	DISZKGEW	Strong	Altered Expression	[12]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[25]
Non-alcoholic steatohepatitis	DIST4788	Strong	Biomarker	[26]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[27]
Obesity	DIS47Y1K	Strong	Biomarker	[28]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[29]
Prostate cancer	DISF190Y	Strong	Biomarker	[30]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[30]
Stomach cancer	DISKIJSX	Strong	Biomarker	[31]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[32]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[33]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[34]
Type-1 diabetes	DIS7HLUB	Disputed	Altered Expression	[35]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[36]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Altered Expression	[37]
Cirrhosis, familial	DISGG52B	Limited	Autosomal recessive	[38]
Gastric cancer	DISXGOUK	Limited	Biomarker	[31]
Liver cirrhosis	DIS4G1GX	Limited	Altered Expression	[39]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[22]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[40]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Keratin, type I cytoskeletal 18 (KRT18) decreases the response to substance of Arsenic trioxide.	[86]

48 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[43]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[44]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[45]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[46]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[47]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[48]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[49]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[50]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[51]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[42]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[52]
Selenium	DM25CGV	Approved	Selenium increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[53]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[54]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Keratin, type I cytoskeletal 18 (KRT18).	[55]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[56]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[58]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[59]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[60]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[61]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[62]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[61]
Docetaxel	DMDI269	Approved	Docetaxel increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[63]
Ardeparin	DMYRX8B	Approved	Ardeparin increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[64]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[61]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[65]
Vinorelbine	DMVXFYE	Approved	Vinorelbine increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[63]
Griseofulvin	DMK54YG	Approved	Griseofulvin increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[66]
Estramustine	DMWTAOI	Approved	Estramustine increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[63]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[67]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[56]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[68]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[69]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[56]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[70]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[71]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[73]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[74]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[75]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[76]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[77]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[78]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[80]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[81]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[61]
Flavone	DMEQH6J	Investigative	Flavone decreases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[50]
SU 6656	DMF1P6W	Investigative	SU 6656 increases the expression of Keratin, type I cytoskeletal 18 (KRT18).	[85]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Keratin, type I cytoskeletal 18 (KRT18).	[57]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Keratin, type I cytoskeletal 18 (KRT18).	[72]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Keratin, type I cytoskeletal 18 (KRT18).	[79]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the phosphorylation of Keratin, type I cytoskeletal 18 (KRT18).	[83]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
acrolein	DMAMCSR	Investigative	acrolein increases the metabolism of Keratin, type I cytoskeletal 18 (KRT18).	[82]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TINGENIN B	DMEV7FY	Investigative	TINGENIN B increases the cleavage of Keratin, type I cytoskeletal 18 (KRT18).	[84]

References

• [1] Significance of suppressor of cytokine signaling-3 expression in bladder urothelial carcinoma in relation to proinflammatory cytokines and tumor histopathological grading.Asian Pac J Cancer Prev. 2015;16(1):307-14. doi: 10.7314/apjcp.2015.16.1.307.
• [2] Detection of circulating gastric cancer cells in peripheral blood using real time quantitative RT-PCR.Hepatogastroenterology. 2008 May-Jun;55(84):1131-5.
• [3] Anti-Apoptotic Effects of Recombinant Human Hepatocyte Growth Factor on Hepatocytes Were Associated with Intrahepatic Hemorrhage Suppression Indicated by the Preservation of Prothrombin Time.Int J Mol Sci. 2019 Apr 12;20(8):1821. doi: 10.3390/ijms20081821.
• [4] In vivo and in vitro evidence for transforming growth factor-beta1-mediated epithelial to mesenchymal transition in esophageal adenocarcinoma.Cancer Res. 2006 Oct 1;66(19):9583-90. doi: 10.1158/0008-5472.CAN-06-1842.
• [5] Fluorescence Self-Quenching from Reporter Dyes Informs on the Structural Properties of Amyloid Clusters Formed in Vitro and in Cells.Nano Lett. 2017 Jan 11;17(1):143-149. doi: 10.1021/acs.nanolett.6b03686. Epub 2016 Dec 8.
• [6] Downregulation of cytokeratin 18 enhances BCRP-mediated multidrug resistance through induction of epithelial-mesenchymal transition and predicts poor prognosis in breast cancer.Oncol Rep. 2019 May;41(5):3015-3026. doi: 10.3892/or.2019.7069. Epub 2019 Mar 15.
• [7] Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K.EMBO Mol Med. 2014 Dec;6(12):1542-60. doi: 10.15252/emmm.201404402.
• [8] Evaluation of serum HGF and CK18 levels in patients with esophageal cancer.Genet Mol Res. 2016 Aug 29;15(3). doi: 10.4238/gmr.15038583.
• [9] Histogenesis of primary liver carcinomas: strengths and weaknesses of cytokeratin profile and albumin mRNA detection.Hum Pathol. 1996 Jun;27(6):599-604. doi: 10.1016/s0046-8177(96)90169-0.
• [10] Keratin 18 and heat-shock protein in chronic kidney disease.Adv Clin Chem. 2013;62:123-49. doi: 10.1016/b978-0-12-800096-0.00003-2.
• [11] Transcriptional deregulation of the keratin 18 gene in human colon carcinoma cells results from an altered acetylation mechanism.Nucleic Acids Res. 2002 Aug 1;30(15):3312-22. doi: 10.1093/nar/gkf462.
• [12] KRT18 is correlated with the malignant status and acts as an oncogene in colorectal cancer.Biosci Rep. 2019 Aug 13;39(8):BSR20190884. doi: 10.1042/BSR20190884. Print 2019 Aug 30.
• [13] Molecular cytogenetic analysis of cytokeratin 20-labeled cells in primary tumors and bone marrow aspirates from colorectal carcinoma patients.Cancer. 1997 May 1;79(9):1664-70.
• [14] An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion.BMC Med Genet. 2011 May 6;12:62. doi: 10.1186/1471-2350-12-62.
• [15] Serum cytokeratin-18 and its relation to liver fibrosis and steatosis diagnosed by FibroScan and controlled attenuation parameter in nonalcoholic fatty liver disease and hepatitis C virus patients.Eur J Gastroenterol Hepatol. 2019 May;31(5):633-641. doi: 10.1097/MEG.0000000000001385.
• [16] Cytokeratin 18 expression in squamous cell carcinoma of the head and neck.Eur Arch Otorhinolaryngol. 1996;253(4-5):227-33. doi: 10.1007/BF00171132.
• [17] Serum Cytokeratin 18 M30 Levels in Chronic Hepatitis B Reflect Both Phase and Histological Activities of Disease.Mediators Inflamm. 2017;2017:3480234. doi: 10.1155/2017/3480234. Epub 2017 Jul 30.
• [18] Serum keratin-18 fragments as cell death biomarker in association with disease progression and prognosis in hepatitis B virus-related cirrhosis.J Viral Hepat. 2019 Jul;26(7):835-845. doi: 10.1111/jvh.13100. Epub 2019 May 3.
• [19] High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype.Transl Oncol. 2019 Feb;12(2):256-268. doi: 10.1016/j.tranon.2018.10.010. Epub 2018 Nov 12.
• [20] Denaturing temperature selection may underestimate keratin mutation detection by DHPLC.Hum Mutat. 2006 May;27(5):444-52. doi: 10.1002/humu.20311.
• [21] Cytokeratin 8/18 as a new marker of mouse liver preneoplastic lesions.Toxicol Appl Pharmacol. 2010 Jan 1;242(1):47-55. doi: 10.1016/j.taap.2009.09.013. Epub 2009 Sep 29.
• [22] Cytokeratin 18 knockdown decreases cell migration and increases chemosensitivity in non-small cell lung cancer.J Cancer Res Clin Oncol. 2016 Dec;142(12):2479-2487. doi: 10.1007/s00432-016-2253-x. Epub 2016 Sep 6.
• [23] Cross-species application of cDNA microarrays to profile gene expression using UV-induced melanoma in Monodelphis domestica as the model system.Genomics. 2004 Apr;83(4):588-99. doi: 10.1016/j.ygeno.2003.10.007.
• [24] Micrometastases in sentinel nodes of gastric cancer.Br J Cancer. 2003 Aug 18;89(4):676-80. doi: 10.1038/sj.bjc.6601183.
• [25] MACK-3 (combination of hoMa, Ast and CK18): A promising novel biomarker for fibrotic non-alcoholic steatohepatitis.Liver Int. 2019 Jul;39(7):1315-1324. doi: 10.1111/liv.14084. Epub 2019 Mar 18.
• [26] Effect of PNPLA3 polymorphism on diagnostic performance of various noninvasive markers for diagnosing and staging nonalcoholic fatty liver disease.J Gastroenterol Hepatol. 2020 Jun;35(6):1057-1064. doi: 10.1111/jgh.14894. Epub 2019 Dec 9.
• [27] Elevated serum cytokeratin-18 concentration in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease.Ann Clin Biochem. 2019 Jan;56(1):141-147. doi: 10.1177/0004563218796259. Epub 2018 Aug 27.
• [28] Novel Ultrasonographic Fatty Liver Indicator Can Predict Hepatitis in Children With Non-alcoholic Fatty Liver Disease.Front Pediatr. 2019 Jan 8;6:416. doi: 10.3389/fped.2018.00416. eCollection 2018.
• [29] Isolation of tissue-type plasminogen activator, cathepsin H, and non-specific cross-reacting antigen from SK-PC-1 pancreas cancer cells using subtractive hybridization.FEBS Lett. 1996 Apr 29;385(1-2):72-6. doi: 10.1016/0014-5793(96)00352-3.
• [30] Prostate-Derived Ets Factor (PDEF) Inhibits Metastasis by Inducing Epithelial/Luminal Phenotype in Prostate Cancer Cells. Mol Cancer Res. 2018 Sep;16(9):1430-1440.
• [31] Cytokeratin-18 fragments predict treatment response and overall survival in gastric cancer in a randomized controlled trial.Tumour Biol. 2018 Mar;40(3):1010428318764007. doi: 10.1177/1010428318764007.
• [32] Increased Circulating Autoantibodies Levels of IgG, IgA, IgM Against Cytokeratin 18 and Cytokeratin 19 in Chronic Obstructive Pulmonary Disease.Arch Med Res. 2017 Jan;48(1):79-87. doi: 10.1016/j.arcmed.2017.01.007.
• [33] Comparative proteomics of pulmonary tumors with neuroendocrine differentiation.J Proteome Res. 2006 Mar;5(3):643-50. doi: 10.1021/pr050460x.
• [34] Squamous cell carcinoma arising in mature cystic teratoma of the ovary: an immunohistochemical analysis of its tumorigenesis.Histopathology. 2007 Jul;51(1):98-104. doi: 10.1111/j.1365-2559.2007.02727.x. Epub 2007 Jun 1.
• [35] Omentin-1 and NAMPT serum concentrations are higher and CK-18 levels are lower in children and adolescents with type 1 diabetes when compared to healthy age, sex and BMI matched controls.J Pediatr Endocrinol Metab. 2018 Sep 25;31(9):959-969. doi: 10.1515/jpem-2018-0353.
• [36] Prognostic value and clinicopathological significance of serum- and tissue-based cytokeratin 18 express level in breast cancer: a meta-analysis.Biosci Rep. 2018 Mar 21;38(2):BSR20171145. doi: 10.1042/BSR20171145. Print 2018 Apr 27.
• [37] Downregulation of cytokeratin 18 is associated with paclitaxelresistance and tumor aggressiveness in prostate cancer.Int J Oncol. 2016 Apr;48(4):1730-6. doi: 10.3892/ijo.2016.3396. Epub 2016 Feb 17.
• [38] Chronic hepatitis, hepatocyte fragility, and increased soluble phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved arginine mutant. J Cell Biol. 1995 Dec;131(5):1303-14. doi: 10.1083/jcb.131.5.1303.
• [39] Diagnostic value of serum cytokeratin-18 in children with chronic liver disease.J Paediatr Child Health. 2020 Jan;56(1):41-46. doi: 10.1111/jpc.14488. Epub 2019 May 4.
• [40] Cytokeratin-18 and enhanced liver fibrosis scores in type 1 and type 2 diabetes and effects of two different insulins.J Investig Med. 2018 Mar;66(3):661-668. doi: 10.1136/jim-2017-000609. Epub 2017 Nov 21.
• [41] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [42] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
• [43] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [44] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [45] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [46] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [47] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [48] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [49] Application of cDNA microarray to the study of arsenic-induced liver diseases in the population of Guizhou, China. Toxicol Sci. 2001 Jan;59(1):185-92.
• [50] Identification of biomarkers for the initiation of apoptosis in human preneoplastic colonocytes by proteome analysis. Int J Cancer. 2004 Mar 20;109(2):220-9. doi: 10.1002/ijc.11692.
• [51] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [52] Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells. Int J Oncol. 2014 Jul;45(1):448-58.
• [53] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [54] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [55] New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids. Arch Toxicol. 2021 Aug;95(8):2691-2718. doi: 10.1007/s00204-021-03092-2. Epub 2021 Jun 20.
• [56] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [57] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [58] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [59] Genotoxic, cytotoxic, and apoptotic effects of Hypogymnia physodes (L.) Nyl. on breast cancer cells. Environ Toxicol. 2014 May;29(7):804-13. doi: 10.1002/tox.21809. Epub 2012 Aug 21.
• [60] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [61] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [62] The stability of cytokeratin 18 in human liver cells during colchicine-induced microtubule disruption. Food Chem Toxicol. 2001 Jan;39(1):85-9. doi: 10.1016/s0278-6915(00)00113-7.
• [63] Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006 Jun 5;94(11):1592-8. doi: 10.1038/sj.bjc.6603129.
• [64] Heparin and aspirin attenuate placental apoptosis in vitro: implications for early pregnancy failure. Am J Obstet Gynecol. 2005 Jan;192(1):23-30. doi: 10.1016/j.ajog.2004.09.029.
• [65] Nevirapine restores androgen signaling in hormone-refractory human prostate carcinoma cells both in vitro and in vivo. Prostate. 2009 May 15;69(7):744-54. doi: 10.1002/pros.20923.
• [66] Formation of Mallory body-like inclusions and cell death induced by deregulated expression of keratin 18. Mol Biol Cell. 2002 Oct;13(10):3441-51. doi: 10.1091/mbc.01-10-0510.
• [67] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [68] Novel retinoic acid metabolism blocking agents have potent inhibitory activities on human breast cancer cells and tumour growth. Br J Cancer. 2007 Apr 23;96(8):1204-15. doi: 10.1038/sj.bjc.6603705. Epub 2007 Mar 27.
• [69] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [70] Comparative mechanisms of PAH toxicity by benzo[a]pyrene and dibenzo[def,p]chrysene in primary human bronchial epithelial cells cultured at air-liquid interface. Toxicol Appl Pharmacol. 2019 Sep 15;379:114644.
• [71] Epigenetic reader BRD4 inhibition as a therapeutic strategy to suppress E2F2-cell cycle regulation circuit in liver cancer. Oncotarget. 2016 May 31;7(22):32628-40. doi: 10.18632/oncotarget.8701.
• [72] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [73] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [74] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [75] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [76] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [77] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [78] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [79] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [80] Deguelin suppresses pancreatic tumor growth and metastasis by inhibiting epithelial-to-mesenchymal transition in an orthotopic model. Oncogene. 2013 Aug 22;32(34):3980-91. doi: 10.1038/onc.2012.413. Epub 2012 Sep 17.
• [81] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.
• [82] Toxicity of smoke extracts towards A549 lung cells: role of acrolein and suppression by carbonyl scavengers. Chem Biol Interact. 2010 Feb 12;183(3):416-24.
• [83] Hyperphosphorylation of intermediate filament proteins is involved in microcystin-LR-induced toxicity in HL7702 cells. Toxicol Lett. 2012 Oct 17;214(2):192-9. doi: 10.1016/j.toxlet.2012.08.024. Epub 2012 Sep 1.
• [84] The plant-derived triterpenoid tingenin B is a potent anticancer agent due to its cytotoxic activity on cancer stem cells of breast cancer in?vitro. Chem Biol Interact. 2016 Dec 25;260:248-255. doi: 10.1016/j.cbi.2016.10.001. Epub 2016 Oct 5.
• [85] A small molecule inhibitor of SRC family kinases promotes simple epithelial differentiation of human pluripotent stem cells. PLoS One. 2013;8(3):e60016. doi: 10.1371/journal.pone.0060016. Epub 2013 Mar 20.
• [86] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.