Details of the Drug Combination

General Information of Drug Combination (ID: DCFU2WL)

Drug Combination Name
Altretamine Mitomycin
Indication
Disease Entry Status REF
Astrocytoma Investigative [1]
Component Drugs Altretamine   DMKLAYG Mitomycin   DMH0ZJE
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SNB-19
Zero Interaction Potency (ZIP) Score: 26.48
Bliss Independence Score: 30.43
Loewe Additivity Score: 28.33
LHighest Single Agent (HSA) Score: 26.93

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Altretamine
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Approved [2]
Altretamine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Breaker [6]
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Indication(s) of Mitomycin
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [3]
Gastrointestinal cancer 2C11 Approved [3]
Pancreatic adenocarcinoma N.A. Approved [4]
Solid tumour/cancer 2A00-2F9Z Approved [5]
Urinary bladder cancer N.A. Approved [4]
Urinary bladder neoplasm N.A. Approved [4]
Urinary system neoplasm N.A. Approved [4]
Urinary tract disease GC2Z Approved [4]
Bladder disease DC11-DC1Z Investigative [4]
Colon cancer 2B90.Z Investigative [4]
Mitomycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Binder [13]
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Mitomycin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [14]
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Mitomycin Interacts with 274 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [15]
Alternative prion protein (PRNP) OTE85L1Q APRIO_HUMAN Increases Expression [16]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Increases Expression [16]
HLA class I histocompatibility antigen, C alpha chain (HLA-C) OTV38BUJ HLAC_HUMAN Decreases Expression [16]
Bone morphogenetic protein 4 (BMP4) OTPZMDFH BMP4_HUMAN Decreases Expression [16]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Increases Expression [16]
Early growth response protein 1 (EGR1) OTCP6XGZ EGR1_HUMAN Increases Expression [16]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [16]
DNA ligase 1 (LIG1) OTEEQS43 DNLI1_HUMAN Decreases Expression [16]
Nuclear transcription factor Y subunit alpha (NFYA) OTWFFOVH NFYA_HUMAN Increases Expression [16]
Ephrin type-A receptor 2 (EPHA2) OTI6QNX2 EPHA2_HUMAN Decreases Expression [16]
Replication factor C subunit 4 (RFC4) OTWALD2R RFC4_HUMAN Decreases Expression [16]
Matrix metalloproteinase-14 (MMP14) OT9C197Z MMP14_HUMAN Decreases Expression [16]
Activated RNA polymerase II transcriptional coactivator p15 (SUB1) OTK71JYU TCP4_HUMAN Increases Expression [16]
Small ribosomal subunit protein eS1 (RPS3A) OTUEP7CL RS3A_HUMAN Increases Expression [16]
Microtubule-associated protein RP/EB family member 1 (MAPRE1) OTCVQD60 MARE1_HUMAN Increases Expression [16]
Histone-binding protein RBBP7 (RBBP7) OTLB56HX RBBP7_HUMAN Increases Expression [16]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [17]
TP53-regulated inhibitor of apoptosis 1 (TRIAP1) OTEAUJXN TRIA1_HUMAN Increases Expression [18]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Increases Expression [18]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [18]
Heat shock cognate 71 kDa protein (HSPA8) OTJI2RCI HSP7C_HUMAN Increases Expression [18]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Increases Expression [18]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [18]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [18]
Quinone oxidoreductase PIG3 (TP53I3) OTSCM68G QORX_HUMAN Increases Expression [18]
DNA damage-binding protein 2 (DDB2) OTO8HVVB DDB2_HUMAN Increases Expression [18]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Decreases Expression [19]
Succinate dehydrogenase assembly factor 1, mitochondrial (SDHAF1) OTDG5VW7 SDHF1_HUMAN Decreases Expression [8]
Serine/threonine-protein kinase Sgk1 (SGK1) OT301T1U SGK1_HUMAN Decreases Expression [8]
E3 ubiquitin-protein ligase TRIM38 (TRIM38) OT6SP1M9 TRI38_HUMAN Decreases Expression [8]
Torsin-1A (TOR1A) OTYCLGJU TOR1A_HUMAN Decreases Expression [8]
Telomerase reverse transcriptase (TERT) OT085VVA TERT_HUMAN Decreases Expression [20]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Increases Phosphorylation [21]
Transcription factor EC (TFEC) OTUST8MR TFEC_HUMAN Decreases Expression [8]
Regulator of G-protein signaling 16 (RGS16) OTBKZASI RGS16_HUMAN Decreases Expression [8]
E3 ubiquitin-protein ligase RNF113A (RNF113A) OTR6N7HU R113A_HUMAN Decreases Expression [8]
HMG box-containing protein 1 (HBP1) OTDPGGDV HBP1_HUMAN Decreases Expression [8]
Kinesin-like protein KIF20A (KIF20A) OTXOQHE0 KI20A_HUMAN Decreases Expression [8]
Myelin protein zero-like protein 1 (MPZL1) OTJSUUHR MPZL1_HUMAN Decreases Expression [8]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [21]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [22]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [23]
Thymidine kinase, cytosolic (TK1) OTY5JFM1 KITH_HUMAN Increases Mutagenesis [24]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [23]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [23]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [25]
Fibroblast growth factor 2 (FGF2) OT7YUJ9F FGF2_HUMAN Increases Expression [22]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Activity [26]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [27]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [28]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [27]
CD59 glycoprotein (CD59) OTSUMQDH CD59_HUMAN Increases Mutagenesis [29]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [30]
Beta-galactosidase (GLB1) OTB0TKAG BGAL_HUMAN Increases Activity [23]
rRNA 2'-O-methyltransferase fibrillarin (FBL) OTRODIE5 FBRL_HUMAN Affects Localization [31]
Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2) OTIN6G20 CPT2_HUMAN Decreases Expression [8]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [32]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [33]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [33]
GTP cyclohydrolase 1 (GCH1) OTOZ6NSL GCH1_HUMAN Decreases Expression [8]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Expression [34]
Replication factor C subunit 1 (RFC1) OT3L5PK3 RFC1_HUMAN Decreases Expression [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [35]
RNA-binding protein 34 (RBM34) OTX3LUGI RBM34_HUMAN Decreases Expression [8]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Expression [32]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [23]
LIM/homeobox protein Lhx2 (LHX2) OTK61NP8 LHX2_HUMAN Decreases Expression [8]
DNA mismatch repair protein Msh6 (MSH6) OT46FP09 MSH6_HUMAN Decreases Expression [8]
RecQ-like DNA helicase BLM (BLM) OTEJOAJX BLM_HUMAN Decreases Expression [8]
Ataxin-1 (ATXN1) OTQF0HNR ATX1_HUMAN Decreases Expression [8]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [34]
Ras-related protein Rap-2b (RAP2B) OTD2NDQP RAP2B_HUMAN Decreases Expression [8]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Increases Secretion [35]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [36]
Transcription factor E2F1 (E2F1) OTLKYBBC E2F1_HUMAN Decreases Expression [8]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Increases Expression [37]
Protein kinase C zeta type (PRKCZ) OTN2FE42 KPCZ_HUMAN Increases Cleavage [35]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Increases Expression [33]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Decreases Expression [28]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [38]
Tripartite motif-containing protein 26 (TRIM26) OTS0DJIP TRI26_HUMAN Decreases Expression [8]
E3 ubiquitin-protein ligase TRIM32 (TRIM32) OTJOV0PG TRI32_HUMAN Decreases Expression [8]
Chromatin assembly factor 1 subunit A (CHAF1A) OTXSSY4H CAF1A_HUMAN Decreases Expression [8]
Chromatin assembly factor 1 subunit B (CHAF1B) OTOMK4KH CAF1B_HUMAN Decreases Expression [8]
Interleukin-18 (IL18) OTBB2A8O IL18_HUMAN Decreases Expression [37]
Protein BTG3 (BTG3) OT9ANHVT BTG3_HUMAN Decreases Expression [8]
Histone RNA hairpin-binding protein (SLBP) OTVYYQRT SLBP_HUMAN Decreases Expression [8]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [35]
Transforming growth factor-beta-induced protein ig-h3 (TGFBI) OTR443C5 BGH3_HUMAN Decreases Expression [38]
Neutral amino acid transporter B(0) (SLC1A5) OTE2H26Q AAAT_HUMAN Decreases Expression [8]
Protein MCM10 homolog (MCM10) OTV0O3JN MCM10_HUMAN Decreases Expression [8]
Partner and localizer of BRCA2 (PALB2) OT6DNDBG PALB2_HUMAN Decreases Expression [8]
Leucine-rich repeat-containing protein 47 (LRRC47) OTSE8NAO LRC47_HUMAN Decreases Expression [8]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [34]
Cytochrome c oxidase assembly factor 7 (COA7) OTRQJYL6 COA7_HUMAN Decreases Expression [8]
Mitochondrial potassium channel (CCDC51) OTOJNHNA MITOK_HUMAN Decreases Expression [8]
Integrator complex subunit 15 (INTS15) OT3O4INM INT15_HUMAN Decreases Expression [8]
Krueppel-like factor 6 (KLF6) OTQY9S7F KLF6_HUMAN Decreases Expression [8]
Cell division control protein 6 homolog (CDC6) OTX93FE7 CDC6_HUMAN Decreases Expression [8]
Growth/differentiation factor 15 (GDF15) OTWQN50N GDF15_HUMAN Increases Expression [8]
Protein orai-3 (ORAI3) OTUP3OH3 ORAI3_HUMAN Decreases Expression [8]
Protein pelota homolog (PELO) OTF3WLIM PELO_HUMAN Decreases Expression [8]
TIMELESS-interacting protein (TIPIN) OT9PZHXV TIPIN_HUMAN Decreases Expression [8]
Fanconi anemia group D2 protein (FANCD2) OTVEB5LF FACD2_HUMAN Increases Ubiquitination [21]
tRNA pseudouridine(38/39) synthase (PUS3) OT6WG6M2 PUS3_HUMAN Decreases Expression [8]
Transmembrane protein 185B (TMEM185B) OTGNYS0J T185B_HUMAN Decreases Expression [8]
Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2) OT3Q11WQ I20L2_HUMAN Decreases Expression [8]
GrpE protein homolog 1, mitochondrial (GRPEL1) OT8O00YJ GRPE1_HUMAN Decreases Expression [8]
Forkhead box protein J2 (FOXJ2) OTPT639J FOXJ2_HUMAN Decreases Expression [8]
Homologous-pairing protein 2 homolog (PSMC3IP) OT9UB5UO HOP2_HUMAN Decreases Expression [8]
rRNA methyltransferase 2, mitochondrial (MRM2) OTRYA1HU MRM2_HUMAN Decreases Expression [8]
Frizzled-1 (FZD1) OTZATHVS FZD1_HUMAN Decreases Expression [8]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Affects Response To Substance [11]
Tripartite motif-containing protein 2 (TRIM2) OT0V1YVC TRIM2_HUMAN Affects Response To Substance [11]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Affects Response To Substance [11]
Fanconi-associated nuclease 1 (FAN1) OT1LM1HZ FAN1_HUMAN Increases Response To Substance [39]
Replication factor C subunit 3 (RFC3) OT1MS7AO RFC3_HUMAN Affects Response To Substance [11]
CD9 antigen (CD9) OT2184XU CD9_HUMAN Affects Response To Substance [11]
KN motif and ankyrin repeat domain-containing protein 1 (KANK1) OT2E7A6W KANK1_HUMAN Affects Response To Substance [11]
Aldehyde oxidase (AOX1) OT2FZP6H AOXA_HUMAN Affects Response To Substance [11]
Mitochondrial fission 1 protein (FIS1) OT2HL10J FIS1_HUMAN Affects Response To Substance [11]
Cytoplasmic aconitate hydratase (ACO1) OT2VUR7L ACOHC_HUMAN Affects Response To Substance [11]
Syncytin-2 (ERVFRD-1) OT3064D7 SYCY2_HUMAN Affects Response To Substance [11]
Protein FAM171A1 (FAM171A1) OT33BHEP F1711_HUMAN Affects Response To Substance [11]
Sister chromatid cohesion protein PDS5 homolog A (PDS5A) OT34P56Z PDS5A_HUMAN Affects Response To Substance [11]
Excitatory amino acid transporter 3 (SLC1A1) OT3B9M6W EAA3_HUMAN Affects Response To Substance [11]
Syntabulin (SYBU) OT3FQV7N SYBU_HUMAN Affects Response To Substance [11]
Fatty acid CoA ligase Acsl3 (ACSL3) OT3MWER1 ACSL3_HUMAN Affects Response To Substance [11]
Prelamin-A/C (LMNA) OT3SG7ZR LMNA_HUMAN Affects Response To Substance [11]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Increases Response To Substance [40]
Pyridoxal kinase (PDXK) OT40AJ5J PDXK_HUMAN Affects Response To Substance [11]
Proteinase-activated receptor 1 (F2R) OT4WVWBO PAR1_HUMAN Affects Response To Substance [11]
Diamine acetyltransferase 1 (SAT1) OT52AU22 SAT1_HUMAN Affects Response To Substance [11]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Increases Response To Substance [41]
Neprilysin (MME) OT5Q39P8 NEP_HUMAN Affects Response To Substance [11]
Lymphokine-activated killer T-cell-originated protein kinase (PBK) OT5Z27TW TOPK_HUMAN Affects Response To Substance [11]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2) OT6MFOWF TGM2_HUMAN Affects Response To Substance [11]
G-protein-signaling modulator 2 (GPSM2) OT6RPMRM GPSM2_HUMAN Affects Response To Substance [11]
Dual specificity protein phosphatase 4 (DUSP4) OT6WAO12 DUS4_HUMAN Affects Response To Substance [11]
Interferon-induced GTP-binding protein Mx1 (MX1) OT6X8G5T MX1_HUMAN Increases Response To Substance [42]
Plasminogen activator inhibitor 2 (SERPINB2) OT72QLZB PAI2_HUMAN Affects Response To Substance [11]
Transcriptional regulator ATRX (ATRX) OT77RSQW ATRX_HUMAN Affects Response To Substance [11]
Monocarboxylate transporter 7 (SLC16A6) OT7BIIZX MOT7_HUMAN Affects Response To Substance [11]
Ras-related protein Rab-17 (RAB17) OT7NBUGQ RAB17_HUMAN Affects Response To Substance [11]
Stanniocalcin-2 (STC2) OT86YP8G STC2_HUMAN Affects Response To Substance [11]
Pirin (PIR) OT8ALXHU PIR_HUMAN Affects Response To Substance [11]
Myelin proteolipid protein (PLP1) OT8CM9CX MYPR_HUMAN Affects Response To Substance [11]
Protein-S-isoprenylcysteine O-methyltransferase (ICMT) OT8CNKBO ICMT_HUMAN Affects Response To Substance [11]
G0/G1 switch protein 2 (G0S2) OT8FL49L G0S2_HUMAN Affects Response To Substance [11]
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform (PPP2R5E) OT8GPFT5 2A5E_HUMAN Decreases Response To Substance [43]
cAMP-dependent protein kinase inhibitor alpha (PKIA) OT8M5GVO IPKA_HUMAN Affects Response To Substance [11]
Melanoma-associated antigen 12 (MAGEA12) OT8ULELL MAGAC_HUMAN Affects Response To Substance [11]
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform (PPP2R2A) OT9297OG 2ABA_HUMAN Decreases Response To Substance [43]
Tissue factor pathway inhibitor (TFPI) OTA0FX16 TFPI1_HUMAN Affects Response To Substance [11]
Acyl-coenzyme A thioesterase 2, mitochondrial (ACOT2) OTAKUO27 ACOT2_HUMAN Affects Response To Substance [11]
Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) OTAYZZE6 AL3A1_HUMAN Affects Response To Substance [44]
Long-chain-fatty-acid--CoA ligase 1 (ACSL1) OTB06ESI ACSL1_HUMAN Affects Response To Substance [11]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Affects Response To Substance [11]
Cochlin (COCH) OTBEHD89 COCH_HUMAN Affects Response To Substance [11]
ETS domain-containing protein Elk-3 (ELK3) OTBM9BHT ELK3_HUMAN Affects Response To Substance [11]
High mobility group protein HMGI-C (HMGA2) OTBMBHHL HMGA2_HUMAN Affects Response To Substance [11]
Protein PRRC2C (PRRC2C) OTBX3MXM PRC2C_HUMAN Affects Response To Substance [11]
Melanocyte protein PMEL (PMEL) OTCDDHHM PMEL_HUMAN Affects Response To Substance [11]
BMP and activin membrane-bound inhibitor homolog (BAMBI) OTCEJ8W5 BAMBI_HUMAN Affects Response To Substance [11]
Creatine kinase U-type, mitochondrial (CKMT1A) OTCINHH5 KCRU_HUMAN Affects Response To Substance [11]
Sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1) OTCJ458Q AT1A1_HUMAN Affects Response To Substance [11]
CD166 antigen (ALCAM) OTCO4LP7 CD166_HUMAN Affects Response To Substance [11]
Cytochrome c oxidase copper chaperone (COX17) OTCP4LH2 COX17_HUMAN Affects Response To Substance [11]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Decreases Response To Substance [45]
Collagen alpha-3(IX) chain (COL9A3) OTCUJOEK CO9A3_HUMAN Affects Response To Substance [11]
A-kinase anchor protein 12 (AKAP12) OTCVRDDX AKA12_HUMAN Affects Response To Substance [11]
Dystrophin (DMD) OTD21T5J DMD_HUMAN Affects Response To Substance [11]
Dickkopf-related protein 3 (DKK3) OTDU94EY DKK3_HUMAN Affects Response To Substance [11]
dTDP-D-glucose 4,6-dehydratase (TGDS) OTEOFLOS TGDS_HUMAN Affects Response To Substance [11]
Calmegin (CLGN) OTEWVFQV CLGN_HUMAN Affects Response To Substance [11]
Ras association domain-containing protein 1 (RASSF1) OTEZIPB7 RASF1_HUMAN Increases Response To Substance [46]
Protocadherin Fat 1 (FAT1) OTF174DH FAT1_HUMAN Affects Response To Substance [11]
Midkine (MDK) OTF24HKC MK_HUMAN Affects Response To Substance [11]
Serine/arginine-rich splicing factor 1 (SRSF1) OTF61HOV SRSF1_HUMAN Affects Response To Substance [11]
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform (PPP2R5C) OTF7CGO2 2A5G_HUMAN Increases Response To Substance [43]
G antigen 7 (GAGE7) OTF8BTR9 GAGE7_HUMAN Affects Response To Substance [11]
Serglycin (SRGN) OTFAVSX0 SRGN_HUMAN Affects Response To Substance [11]
Catenin alpha-1 (CTNNA1) OTFC725Z CTNA1_HUMAN Affects Response To Substance [11]
Sortilin (SORT1) OTFCQ4B1 SORT_HUMAN Affects Response To Substance [11]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Affects Response To Substance [11]
Myelin basic protein (MBP) OTFZCEDB MBP_HUMAN Affects Response To Substance [11]
Tudor domain-containing protein 3 (TDRD3) OTG83E2C TDRD3_HUMAN Affects Response To Substance [11]
Enhancer of filamentation 1 (NEDD9) OTGCFN4M CASL_HUMAN Affects Response To Substance [11]
Squalene synthase (FDFT1) OTGDISIT FDFT_HUMAN Affects Response To Substance [11]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Response To Substance [47]
Sigma intracellular receptor 2 (TMEM97) OTH76ZWK SGMR2_HUMAN Affects Response To Substance [11]
Transmembrane protein 156 (TMEM156) OTH7YJID TM156_HUMAN Affects Response To Substance [11]
Probable JmjC domain-containing histone demethylation protein 2C (JMJD1C) OTHAWK8C JHD2C_HUMAN Affects Response To Substance [11]
Unconventional myosin-X (MYO10) OTHB78ZQ MYO10_HUMAN Affects Response To Substance [11]
Tribbles homolog 2 (TRIB2) OTHSX3MX TRIB2_HUMAN Affects Response To Substance [11]
Actin-binding LIM protein 1 (ABLIM1) OTHXEK3E ABLM1_HUMAN Affects Response To Substance [11]
DNA damage-inducible transcript 4 protein (DDIT4) OTHY8SY4 DDIT4_HUMAN Affects Response To Substance [11]
Protein S100-A11 (S100A11) OTI57KDN S10AB_HUMAN Affects Response To Substance [11]
Protein S100-A10 (S100A10) OTI71243 S10AA_HUMAN Affects Response To Substance [11]
Melanoma-associated antigen 6 (MAGEA6) OTI8S0O2 MAGA6_HUMAN Affects Response To Substance [11]
Runt-related transcription factor 3 (RUNX3) OTITK1XD RUNX3_HUMAN Increases Response To Substance [48]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Affects Response To Substance [11]
Nuclear receptor-interacting protein 1 (NRIP1) OTIZOJQV NRIP1_HUMAN Affects Response To Substance [11]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Affects Response To Substance [11]
Trefoil factor 3 (TFF3) OTJJDRTU TFF3_HUMAN Affects Response To Substance [11]
Collagen alpha-2(IV) chain (COL4A2) OTJK1LKN CO4A2_HUMAN Affects Response To Substance [11]
Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) OTJQL0I3 HEY1_HUMAN Affects Response To Substance [11]
E3 ubiquitin-protein ligase MYLIP (MYLIP) OTL0PFGV MYLIP_HUMAN Affects Response To Substance [11]
Hematopoietically-expressed homeobox protein HHEX (HHEX) OTLIUVYX HHEX_HUMAN Affects Response To Substance [11]
Glycylpeptide N-tetradecanoyltransferase 2 (NMT2) OTLNA39Z NMT2_HUMAN Affects Response To Substance [11]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Increases Response To Substance [49]
Protein S100-A4 (S100A4) OTLRGFSQ S10A4_HUMAN Affects Response To Substance [11]
Tyrosine-protein kinase Fyn (FYN) OTLSLVZS FYN_HUMAN Affects Response To Substance [11]
Bridging integrator 3 (BIN3) OTMIWWDW BIN3_HUMAN Affects Response To Substance [11]
Transcription factor AP-2-alpha (TFAP2A) OTMYT3NK AP2A_HUMAN Affects Response To Substance [11]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Affects Response To Substance [11]
Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2) OTNE3T6Z CHIC2_HUMAN Affects Response To Substance [11]
Inositol monophosphatase 2 (IMPA2) OTNFB9YN IMPA2_HUMAN Affects Response To Substance [11]
Neural cell adhesion molecule L1 (L1CAM) OTNWAQ4Y L1CAM_HUMAN Affects Response To Substance [11]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Affects Response To Substance [50]
Kynurenine--oxoglutarate transaminase 3 (KYAT3) OTO4U2QK KAT3_HUMAN Affects Response To Substance [11]
Beta-secretase 2 (BACE2) OTO5YQVK BACE2_HUMAN Affects Response To Substance [11]
Histone deacetylase 9 (HDAC9) OTO8O0LF HDAC9_HUMAN Affects Response To Substance [11]
SH3 domain-binding protein 5 (SH3BP5) OTOOEGUJ 3BP5_HUMAN Affects Response To Substance [11]
Glutathione S-transferase Mu 4 (GSTM4) OTOTF8DU GSTM4_HUMAN Affects Response To Substance [11]
Ras-related protein Rab-20 (RAB20) OTP9OOVS RAB20_HUMAN Affects Response To Substance [11]
Tumor protein D52 (TPD52) OTPKSK43 TPD52_HUMAN Affects Response To Substance [11]
DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) OTPL0AI1 ABC3C_HUMAN Affects Response To Substance [11]
Kazrin (KAZN) OTPM7BYM KAZRN_HUMAN Affects Response To Substance [11]
DNA-binding protein inhibitor ID-4 (ID4) OTPMJ39I ID4_HUMAN Affects Response To Substance [11]
Centrosomal protein of 57 kDa (CEP57) OTPOHLIX CEP57_HUMAN Affects Response To Substance [11]
Epithelial membrane protein 2 (EMP2) OTPS2H0L EMP2_HUMAN Affects Response To Substance [11]
Dermatan-sulfate epimerase (DSE) OTQ108VJ DSE_HUMAN Affects Response To Substance [11]
Adhesion G-protein coupled receptor G1 (ADGRG1) OTQBB8NT AGRG1_HUMAN Affects Response To Substance [11]
Cyclic GMP-AMP phosphodiesterase SMPDL3A (SMPDL3A) OTQDYH8E ASM3A_HUMAN Affects Response To Substance [11]
MAPK/MAK/MRK overlapping kinase (MOK) OTQK7M9V MOK_HUMAN Affects Response To Substance [11]
High mobility group protein HMG-I/HMG-Y (HMGA1) OTQUSHPX HMGA1_HUMAN Affects Response To Substance [11]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Affects Response To Substance [11]
Dr1-associated corepressor (DRAP1) OTRWLF6D NC2A_HUMAN Affects Response To Substance [11]
Latent-transforming growth factor beta-binding protein 2 (LTBP2) OTS88GSD LTBP2_HUMAN Affects Response To Substance [11]
Terminal nucleotidyltransferase 5A (TENT5A) OTSYF511 TET5A_HUMAN Affects Response To Substance [11]
Lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF) OTT5JX1F LITAF_HUMAN Affects Response To Substance [11]
DNA repair protein RAD51 homolog 3 (RAD51C) OTUD6SY5 RA51C_HUMAN Increases Response To Substance [51]
Calcium-dependent secretion activator 2 (CADPS2) OTV1FW0M CAPS2_HUMAN Affects Response To Substance [11]
Matrilin-2 (MATN2) OTVDR68G MATN2_HUMAN Affects Response To Substance [11]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Increases Response To Substance [49]
Ensconsin (MAP7) OTVSSJ33 MAP7_HUMAN Affects Response To Substance [11]
Protein artemis (DCLRE1C) OTW3KB1I DCR1C_HUMAN Decreases Response To Substance [12]
Sorbin and SH3 domain-containing protein 1 (SORBS1) OTWH8762 SRBS1_HUMAN Affects Response To Substance [11]
Protein mago nashi homolog (MAGOH) OTWRYTOX MGN_HUMAN Affects Response To Substance [11]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Affects Response To Substance [11]
Acylamino-acid-releasing enzyme (APEH) OTX258QE ACPH_HUMAN Affects Response To Substance [11]
Hematopoietic lineage cell-specific protein (HCLS1) OTX7WGYN HCLS1_HUMAN Affects Response To Substance [11]
S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) OTX8L3M5 SAHH2_HUMAN Affects Response To Substance [11]
Long-chain fatty acid transport protein 3 (SLC27A3) OTXB60L7 S27A3_HUMAN Affects Response To Substance [11]
Metallothionein-1E (MT1E) OTXJKU4Y MT1E_HUMAN Affects Response To Substance [11]
Arginine vasopressin-induced protein 1 (AVPI1) OTXSBR60 AVPI1_HUMAN Affects Response To Substance [11]
Neuroendocrine protein 7B2 (SCG5) OTXSJMT1 7B2_HUMAN Affects Response To Substance [11]
Carbamoyl-phosphate synthase , mitochondrial (CPS1) OTXV8NSR CPSM_HUMAN Affects Response To Substance [11]
Peripheral myelin protein 22 (PMP22) OTXWYWCZ PMP22_HUMAN Affects Response To Substance [11]
Kinesin-like protein KIF23 (KIF23) OTY850JC KIF23_HUMAN Affects Response To Substance [11]
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B) OTY94WRA HM20B_HUMAN Affects Response To Substance [11]
Protein Niban 1 (NIBAN1) OTYOLI12 NIBA1_HUMAN Affects Response To Substance [11]
LIM and calponin homology domains-containing protein 1 (LIMCH1) OTYPC4XA LIMC1_HUMAN Affects Response To Substance [11]
Galectin-3 (LGALS3) OTYQT0ZI LEG3_HUMAN Affects Response To Substance [11]
L-dopachrome tautomerase (DCT) OTYVNTBG TYRP2_HUMAN Affects Response To Substance [11]
Epithelial discoidin domain-containing receptor 1 (DDR1) OTYW1SH8 DDR1_HUMAN Affects Response To Substance [11]
Tissue factor pathway inhibitor 2 (TFPI2) OTZCRWOR TFPI2_HUMAN Affects Response To Substance [11]
Suppressor of tumorigenicity 7 protein (ST7) OTZG8RC6 ST7_HUMAN Affects Response To Substance [11]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Response To Substance [49]
CTD small phosphatase-like protein (CTDSPL) OTZJ0CZK CTDSL_HUMAN Affects Response To Substance [11]
C-X-C motif chemokine 5 (CXCL5) OTZOUPCA CXCL5_HUMAN Affects Response To Substance [11]
Eukaryotic translation initiation factor 5B (EIF5B) OTZTT22W IF2P_HUMAN Affects Response To Substance [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 274 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCREBQH DU-145 Investigative [1]
Adenocarcinoma DCJ841J A549 Investigative [1]
Childhood T acute lymphoblastic leukemia DCPRV7D CCRF-CEM Investigative [1]
Large cell lung carcinoma DCM67U0 NCI-H460 Investigative [1]
Lung adenocarcinoma DC5UENX MDA-MB-231 Investigative [1]
Melanoma DCPRSGJ SK-MEL-2 Investigative [1]
Melanoma DCO5FUW UACC-257 Investigative [1]
Renal cell carcinoma DCKBZIU SN12C Investigative [1]
Carcinoma DC7KBGK MCF7 Investigative [52]
Invasive ductal carcinoma DCCO0E6 BT-549 Investigative [52]
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⏷ Show the Full List of 10 DrugCom(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7112).
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7089).
4 Mitomycin FDA Label
5 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
6 Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agen... Cancer Chemother Pharmacol. 2008 Dec;63(1):19-26.
7 Influence of chemotherapeutic agents and cytokines on the expression of 5-fluorouracil-associated enzymes in human colon cancer cell lines. J Gastroenterol. 2006 Feb;41(2):140-50.
8 Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
9 TCDD as a biological response modifier for Mitomycin C: oxygen tension affects enzyme activation, reactive oxygen species and cell death. Life Sci. 2006 Feb 23;78(13):1499-507. doi: 10.1016/j.lfs.2005.07.021. Epub 2005 Oct 14.
10 Expression of X-linked inhibitor of apoptosis protein and its effect on chemotherapeutic sensitivity of bladder carcinoma. J Huazhong Univ Sci Technolog Med Sci. 2007 Jun;27(3):285-7. doi: 10.1007/s11596-007-0317-5.
11 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
12 Differences in sensitivity to DNA-damaging Agents between XRCC4- and Artemis-deficient human cells. J Radiat Res. 2011;52(4):415-24. doi: 10.1269/jrr.10168.
13 Assessment of cell viability, lipid peroxidation and quantification of DNA fragmentation after the treatment of anticancerous drug mitomycin C and ... Exp Toxicol Pathol. 2010 Sep;62(5):503-8.
14 In vivo expansion of MDR1-transduced cells accompanied by a post-transplantation chemotherapy regimen with mitomycin C and methotrexate. J Gene Med. 2010 Jul;12(7):596-603.
15 Mitomycin C induces multidrug resistance in glaucoma surgery. Graefes Arch Clin Exp Ophthalmol. 2008 Feb;246(2):297-304. doi: 10.1007/s00417-007-0695-1. Epub 2007 Oct 13.
16 Genomic and proteomic profiling of responses to toxic metals in human lung cells. Environ Health Perspect. 2003 May;111(6):825-35.
17 Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac. World J Gastroenterol. 2005 Mar 28;11(12):1829-32.
18 Differential expression of TP53 associated genes in Fanconi anemia cells after mitomycin C and hydroxyurea treatment. Mutat Res. 2008 Oct 30;656(1-2):1-7.
19 Oxidative stress mechanisms do not discriminate between genotoxic and nongenotoxic liver carcinogens. Chem Res Toxicol. 2015 Aug 17;28(8):1636-46.
20 Trace levels of mitomycin C disrupt genomic integrity and lead to DNA damage response defect in long-term-cultured human embryonic stem cells. Arch Toxicol. 2015 Jan;89(1):33-45. doi: 10.1007/s00204-014-1250-6. Epub 2014 May 18.
21 Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms. Oncotarget. 2015 Sep 22;6(28):25770-83. doi: 10.18632/oncotarget.4514.
22 Effects of mitomycin-C on normal dermal fibroblasts. Laryngoscope. 2006 Apr;116(4):514-7. doi: 10.1097/01.MLG.0000205590.62824.0A.
23 Mitomycin induces alveolar epithelial cell senescence by down-regulating GSK3 signaling. Toxicol Lett. 2021 Nov 1;352:61-69. doi: 10.1016/j.toxlet.2021.09.015. Epub 2021 Oct 5.
24 DNA polymerase kappa protects human cells against MMC-induced genotoxicity through error-free translesion DNA synthesis. Genes Environ. 2017 Jan 7;39:6. doi: 10.1186/s41021-016-0067-3. eCollection 2017.
25 In vitro effect of cyclosporin A, mitomycin C and prednisolone on cell kinetics in cultured human umbilical vein endothelial cells. Thromb Res. 2005;115(3):219-28. doi: 10.1016/j.thromres.2004.09.001.
26 Chloramphenicol-induced mitochondrial stress increases p21 expression and prevents cell apoptosis through a p21-dependent pathway. J Biol Chem. 2005 Jul 15;280(28):26193-9. doi: 10.1074/jbc.M501371200. Epub 2005 May 19.
27 Dexamethasone reduces mitomycin C-related inflammatory cytokine expression without inducing further cell death in corneal fibroblasts. Wound Repair Regen. 2010 Jan-Feb;18(1):59-69. doi: 10.1111/j.1524-475X.2009.00551.x. Epub 2009 Dec 11.
28 The growth-inhibition effect of tamoxifen in the combination chemotherapeutics on the human cholangiocarcinoma cell line QBC939. Mol Biol Rep. 2010 Jul;37(6):2693-701. doi: 10.1007/s11033-009-9801-2. Epub 2009 Sep 13.
29 Comparison of the mutagenic potential of 17 physical and chemical agents analyzed by the flow cytometry mutation assay. Mutat Res. 2006 Dec 1;602(1-2):14-25. doi: 10.1016/j.mrfmmm.2006.07.009. Epub 2006 Oct 11.
30 Development of an integrated assay in human TK6 cells to permit comprehensive genotoxicity analysis in vitro. Mutat Res Genet Toxicol Environ Mutagen. 2020 Jan;849:503129. doi: 10.1016/j.mrgentox.2019.503129. Epub 2019 Dec 27.
31 Specific inhibition of rRNA transcription and dynamic relocation of fibrillarin induced by mercury. Exp Cell Res. 2000 Aug 25;259(1):225-38. doi: 10.1006/excr.2000.4923.
32 Influence of antitumor drugs on the expression of Fas system in SW480 colon cancer cells. Eur J Gastroenterol Hepatol. 2006 Oct;18(10):1071-7. doi: 10.1097/01.meg.0000231750.68513.6c.
33 Curcumin enhances the mitomycin C-induced cytotoxicity via downregulation of MKK1/2-ERK1/2-mediated Rad51 expression in non-small cell lung cancer cells. Toxicol Appl Pharmacol. 2011 Sep 15;255(3):327-38. doi: 10.1016/j.taap.2011.07.012. Epub 2011 Jul 24.
34 Mitomycin-C induces the apoptosis of human Tenon's capsule fibroblast by activation of c-Jun N-terminal kinase 1 and caspase-3 protease. Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3545-52. doi: 10.1167/iovs.04-1358.
35 Mitomycin C induces apoptosis in a caspases-dependent and Fas/CD95-independent manner in human gastric adenocarcinoma cells. Cancer Lett. 2000 Oct 1;158(2):125-32. doi: 10.1016/s0304-3835(00)00489-4.
36 Mdm2 as a sensitive and mechanistically informative marker for genotoxicity induced by benzo[a]pyrene and dibenzo[a,l]pyrene. Toxicol Sci. 2008 Apr;102(2):232-40. doi: 10.1093/toxsci/kfm305. Epub 2007 Dec 20.
37 Mitomycin C induces apoptosis via Fas/FasL dependent pathway and suppression of IL-18 in cervical carcinoma cells. Cancer Lett. 2006 Jun 8;237(1):33-44. doi: 10.1016/j.canlet.2005.05.043. Epub 2005 Jul 12.
38 Mitomycin C induces apoptosis in cultured corneal fibroblasts derived from type II granular corneal dystrophy corneas. Mol Vis. 2008 Jun 30;14:1222-8.
39 FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair. Nat Genet. 2012 Jul 8;44(8):910-5. doi: 10.1038/ng.2347.
40 O(6)-methylguanine DNA-methyltransferase (MGMT) overexpression in melanoma cells induces resistance to nitrosoureas and temozolomide but sensitizes to mitomycin C. Toxicol Appl Pharmacol. 2006 Mar 1;211(2):97-105. doi: 10.1016/j.taap.2005.06.009. Epub 2005 Jul 22.
41 Mutation of the BRCA1 SQ-cluster results in aberrant mitosis, reduced homologous recombination, and a compensatory increase in non-homologous end joining. Oncotarget. 2015 Sep 29;6(29):27674-87. doi: 10.18632/oncotarget.4876.
42 MxA overexpression reveals a common genetic link in four Fanconi anemia complementation groups. J Clin Invest. 1997 Dec 1;100(11):2873-80. doi: 10.1172/JCI119836.
43 PP2A-B56? complex is involved in dephosphorylation of -H2AX in the repair process of CPT-induced DNA double-strand breaks. Toxicology. 2015 May 4;331:57-65. doi: 10.1016/j.tox.2015.03.007. Epub 2015 Mar 12.
44 Human aldehyde dehydrogenase 3A1 inhibits proliferation and promotes survival of human corneal epithelial cells. J Biol Chem. 2005 Jul 29;280(30):27998-8006. doi: 10.1074/jbc.M503698200. Epub 2005 May 19.
45 Sensitization of human renal cell carcinoma cells to cis-diamminedichloroplatinum(II) by anti-interleukin 6 monoclonal antibody or anti-interleukin 6 receptor monoclonal antibody. Cancer Res. 1995 Feb 1;55(3):590-6.
46 Methylation of Ras association domain family protein 1, isoform A correlated with proliferation and drug resistance in hepatocellular carcinoma cell line SMMC-7721. J Gastroenterol Hepatol. 2007 May;22(5):683-9. doi: 10.1111/j.1440-1746.2006.04676.x.
47 [Establishment of MRP-overexpression subline of bladder carcinoma and its MDR phenotype]. Zhonghua Zhong Liu Za Zhi. 2000 Jul;22(4):273-5.
48 Tumor suppressor gene Runx3 sensitizes gastric cancer cells to chemotherapeutic drugs by downregulating Bcl-2, MDR-1 and MRP-1. Int J Cancer. 2005 Aug 10;116(1):155-60. doi: 10.1002/ijc.20919.
49 Concise prediction models of anticancer efficacy of 8 drugs using expression data from 12 selected genes. Int J Cancer. 2004 Sep 10;111(4):617-26. doi: 10.1002/ijc.20289.
50 [Effect of adenovirus-mediated mutant exogenous P27kip1 gene expression on the chemosensitivities of cholangiocarcinoma cell line]. Zhonghua Wai Ke Za Zhi. 2006 Oct 1;44(19):1349-52.
51 Mutation of the RAD51C gene in a Fanconi anemia-like disorder. Nat Genet. 2010 May;42(5):406-9. doi: 10.1038/ng.570. Epub 2010 Apr 18.
52 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.