Compounds > elafin
Page last updated: 2024-11-13

elafin

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Description

Elafin: A secretory proteinase inhibitory protein that was initially purified from human SKIN. It is found in a variety mucosal secretions and is present at high levels in SPUTUM. Elafin may play a role in the innate immunity (IMMUNITY, INNATE) response of the LUNG. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID44201346
MeSH IDM0485533

Synonyms (10)

Synonym
trappin-2
elafin
human elafin
tiprelestat
human elafin (elastase-specific inhibitor, skin-derived antileukoproteinase, peptidase inhibitor 3)
820211-82-3
78i8295690 ,
unii-78i8295690
tiprelestat [inn]
DTXSID00231519

Research Excerpts

Overview

Elafin is a human protease inhibitor that is down-regulated in the stricturing intestine of Crohn's disease patients. Elafin has been found in the female reproductive tract.

ExcerptReferenceRelevance
"Elafin is a human protease inhibitor that is down-regulated in the stricturing intestine of Crohn's disease patients."( Elafin Reverses Intestinal Fibrosis by Inhibiting Cathepsin S-Mediated Protease-Activated Receptor 2.
Bunnett, NW; Chupina Estrada, A; Fontenot, L; Ho, W; Jensen, DD; Koon, HW; Mattai, SA; Nelson, B; Rieder, F; Shih, DQ; Wang, J; Xie, Y, 2022)		2.89
"Elafin is a natural antimicrobial molecule that plays an important role as an anti-inflammatory agent in mucosal surfaces and has been found in the female reproductive tract."( Upregulation of elafin expression in the fallopian tube of ectopic tubal pregnancies compared to the normal tubes.
Asadikalameh, Z; Asemi-Rad, A; Ghasemi, M; Heidari, Z; Mahmoudzadeh-Sagheb, H; Moudi, B; Sheibak, N; Zakizadeh, F, 2020)		1.63
"Elafin is an antimicrobial and anti-inflammatory protein. "( Elafin inhibits obesity, hyperglycemia, and liver steatosis in high-fat diet-treated male mice.
Fontenot, L; Koon, HW; Law, IKM; Li, Z; Mattai, SA; Mukhopadhyay, R; Ortiz, C; Shih, DQ; Wang, J; Xie, Y, 2020)		3.44
"Elafin is a serine protease inhibitor critical for host defence. "( Elafin promotes tumour metastasis and attenuates the anti-metastatic effects of erlotinib via binding to EGFR in hepatocellular carcinoma.
Gao, S; He, W; Li, B; Li, K; Liao, Y; Liu, W; Qiu, J; Qiu, Y; Shi, Y; Wang, C; Wang, Y; Yang, Z; Yuan, Y; Zhang, H; Zhang, Y; Zuo, D, 2021)		3.51
"Elafin is a serine protease inhibitor that has various epithelial cell regulatory and immunomodulatory effects including inactivation of neutrophil elastases. "( Expression of Elafin in Dermatitis Herpetiformis.
Nousari, CH; Ollague, JE, 2018)		2.28
"Elafin is a natural antimicrobial molecule and a member of the antileukoproteinase (Trappin) family. "( Elafin expression in mucosa of fallopian tubes is altered by hydrosalpinx.
Carson, DD; Engel, BJ; Fuhrich, DG; Neto, EP; Savaris, RF, 2014)		3.29
"Elafin is a serine protease inhibitor produced by epithelial and immune cells with anti-inflammatory properties. "( A functional variant of elafin with improved anti-inflammatory activity for pulmonary inflammation.
Dallet-Choisy, S; Glasgow, AM; McAuley, DF; McNally, P; Moreau, T; O'Kane, C; Quinn, DJ; Small, DM; Taggart, CC; Weldon, S; Zani, ML, 2015)		2.17
"Elafin is a natural antimicrobial molecule member of the antileukoproteinase (Trappin) family that is normally expressed in the mucosa of human fallopian tubes and neutrophils. "( Expression of elafin in fallopian tubes of ectopic pregnancies is reduced.
Fuhrich, DG; Grudzinski, M; Savaris, RF, )		1.93
"Elafin is an endogenous serine protease inhibitor. "( Elafin is downregulated during breast and ovarian tumorigenesis but its residual expression predicts recurrence.
Albarracin, C; Bondy, M; Caruso, JA; Hunt, KK; Karakas, C; Keyomarsi, K; Liu, J; Sahin, A; Yi, M; Zhang, J, 2014)		3.29
"Elafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. "( Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial.
Alam, SR; Dweck, MR; Goodman, K; Harkess, R; Henriksen, PA; Krishan, A; Lewis, SC; Mills, NM; Milne, L; Mirsadraee, S; Moore, C; Newby, DE; Oatey, K; Pessotto, R; Semple, S; Stirrat, C; Thomas, S; Wiedow, O; Zamvar, V, 2015)		2.22
"Elafin is a potent reversible inhibitor of the pro-inflammatory proteases leukocyte elastase and protease 3. "( Biodistribution and pharmacokinetics of the (99m)Tc labeled human elastase inhibitor, elafin, in rats.
Culman, J; Haenisch, S; Kaschwich, M; Lützen, U; Marx, M; Preuss, S; Tjiong, A; Wiedow, O; Zhao, Y; Zuhayra, M, 2016)		2.1
"Elafin is an inducible elastase inhibitor expressed by keratinocytes, and is known to be involved in pathogenesis of neutrophilic skin disorders such as psoriasis."( Deposition of elafin in the involved vascular wall of neutrophil-mediated cutaneous vasculitis.
Chen, KR; Fujimoto, N; Kobayashi, T; Muto, J; Ono, K; Suzuki, S; Tajima, S; Wachi, H, 2016)		1.52
"Elafin is a low molecular weight protein with antileukoproteinase, anti-inflammatory, antibacterial and immunomodulating properties. "( Anti-inflammatory Elafin in human fetal membranes.
Jacobsson, B; Menon, R; Noda, N; Polettini, J; Stalberg, C, 2017)		2.23
"Elafin is a neutrophil serine protease inhibitor expressed in lung and displaying anti-inflammatory and anti-bacterial properties. "( Elafin, an elastase-specific inhibitor, is cleaved by its cognate enzyme neutrophil elastase in sputum from individuals with cystic fibrosis.
Butler, MW; Greene, CM; Guyot, N; Levine, RL; McElvaney, NG; McNally, P; O'Neill, SJ; Taggart, CC; Weldon, S, 2008)		3.23
"Elafin is a component of cervicovaginal secretions in pregnancy, and levels are diminished in bacterial vaginosis. "( Elafin (SKALP/Trappin-2/proteinase inhibitor-3) is produced by the cervix in pregnancy and cervicovaginal levels are diminished in bacterial vaginosis.
Calder, AA; Duthie, L; Kelly, RW; Riley, SC; Stock, SJ; Tremaine, T, 2009)		3.24
"Elafin is a protease inhibitor that also displays antimicrobial activity."( Human gammadelta T cells produce the protease inhibitor and antimicrobial peptide elafin.
Kabelitz, D; Marischen, L; Schröder, JM; Wesch, D; Wiedow, O, 2009)		1.3
"Elafin is a 6-kDa innate immune protein present at several epithelial surfaces including the pulmonary epithelium. "( Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases.
Bergsson, G; Butler, MW; Greene, CM; Guyot, N; Kessler, E; Levine, RL; McElvaney, NG; O'Neill, SJ; Taggart, CC; Weldon, S, 2010)		2.13
"Pre-elafin/trappin-2 is a human innate defense molecule initially described as a potent inhibitor of neutrophil elastase. "( Structural and antimicrobial properties of human pre-elafin/trappin-2 and derived peptides against Pseudomonas aeruginosa.
Bellemare, A; Bourbonnais, Y; Gagné, SM; Morin, S; Vernoux, N, 2010)		1.17
"Elafin is an endogenous human protein composed of an N-terminal transglutaminase substrate motif and a C-terminal WAP (whey acidic protein)-domain with antiproteolytic properties. "( Therapeutic potential of human elafin.
Shaw, L; Wiedow, O, 2011)		2.1
"Elafin is an endogenous inhibitor of neutrophil-derived elastases with numerous anti-inflammatory functions that include modulation of inflammatory cytokine release as well as innate and adaptive immunity."( Role of the endogenous elastase inhibitor, elafin, in cardiovascular injury: from epithelium to endothelium.
Alam, SR; Henriksen, PA; Newby, DE, 2012)		1.36
"Elafin is an elastase-specific inhibitor with increased transcription in normal mammary epithelial cells compared to mammary carcinoma cells. "( Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer.
Fang, B; Hunt, KK; Keyomarsi, K; Liu, Y; Mills, GB; Su, CH; Wingate, H; Yi, M; Yokota, T; Zhang, F; Zhang, M, 2013)		3.28
"Pre-elafin is a tight-binding inhibitor of neutrophil elastase and myeloblastin; two enzymes thought to contribute to tissue damage in lung emphysema. "( Characterization of human pre-elafin mutants: full antipeptidase activity is essential to preserve lung tissue integrity in experimental emphysema.
Bellemare, A; Bouchard, D; Bourbonnais, Y; Doucet, A; Gagné, S; Janelle, MF; Tremblay, GM, 2007)		1.19
"Elafin is an endogenous serine protease inhibitor and is transcriptionally down-regulated in most tumor cell lines."( Differential regulation of elafin in normal and tumor-derived mammary epithelial cells is mediated by CCAAT/enhancer binding protein beta.
Bui, T; Hunt, KK; Keyomarsi, K; Liu, Y; Yi, M; Yokota, T, 2007)		1.36

Effects

ExcerptReferenceRelevance
"Elafin has a primary structure with two functional domains; a transglutaminase substrate domain at the N-terminus and a protease inhibitor domain at the C-terminus. "( Accumulation of elafin in actinic elastosis of sun-damaged skin: elafin binds to elastin and prevents elastolytic degradation.
Hirose, S; Kuroda, K; Muto, J; Tajima, S; Wachi, H, 2007)		2.13
"Elafin has been reported to be abundantly expressed in human epithelial ovarian carcinoma (EOC), however, its functions are poorly understood. "( Elafin selectively regulates the sensitivity of ovarian cancer cells to genotoxic drug-induced apoptosis.
Hellström, I; Hellström, KE; Wei, H, 2012)		3.26

Actions

ExcerptReferenceRelevance
"Elafin and HBD3 increase in chorioamnionitis and levels of the alpha-defensins, HNP1-3, increase in maternal plasma and amniotic fluid in women affected by microbial invasion of the uterus."( Innate immune defences in the human uterus during pregnancy.
Bocking, AD; Challis, JR; Kelly, RW; King, AE; Sallenave, JM, )		0.85

Treatment

ExcerptReferenceRelevance
"Elafin treatment of xenograft mice of melanoma cells led to significantly smaller tumor sizes compared with those of untreated control mice."( The protease inhibitor, elafin, induces p53-dependent apoptosis in human melanoma cells.
Choi, J; Chung, YH; Kim, CM; Koh, SS; Lee, Y; Lim, DS; Park, EC; Yu, KS, 2010)		1.39

Toxicity

ExcerptReferenceRelevance
" No severe adverse events were observed."( Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis.
Bonifacio, KM; Brunner, PM; Coats, I; Cohen, SR; Cueto, I; Dutt, R; Finney, R; Fuentes-Duculan, J; Garcet, S; Gilleaudeau, P; Guttman-Yassky, E; Khattri, S; Krueger, JG; Kunjravia, N; Li, X; Oliva, M; Suárez-Fariñas, M; Sullivan-Whalen, M; Zheng, X, 2017)		0.46

Compound-Compound Interactions

ExcerptReferenceRelevance
"This study evaluated the effects of an mTOR inhibitor everolimus alone or in combination with letrozole on MCF-7/Aro (MCF-7 cells stably transfected with CYP19) in vitro and in vivo."( Everolimus in combination with letrozole inhibit human breast cancer MCF-7/Aro stem cells via PI3K/mTOR pathway: an experimental study.
Hou, G; Liu, J; Liu, Y; Zhang, J; Zhang, S; Zhang, X, 2014)		0.4
"To assess safety and efficacy of mammalian target of rapamycin (mTOR) inhibition in combination with liposomal doxorubicin and bevacizumab in patients with advanced metaplastic TNBC."( Targeting the PI3K/AKT/mTOR Pathway for the Treatment of Mesenchymal Triple-Negative Breast Cancer: Evidence From a Phase 1 Trial of mTOR Inhibition in Combination With Liposomal Doxorubicin and Bevacizumab.
Albarracin, C; Basho, RK; Chavez-MacGregor, M; Gilcrease, M; Helgason, T; Herbrich, SM; Hess, KR; Hong, D; Ibrahim, NK; Janku, F; Karp, DD; Koenig, KB; Kurzrock, R; Litton, JK; Meric-Bernstam, F; Moulder, SL; Murray, JL; Murthy, RK; Subbiah, V; Valero, V, 2017)		0.46

Dosage Studied

ExcerptRelevanceReference
" In conclusion, the blood and organ-specific kinetic data provide a basis for planning of adequate dosing regimens and the high accumulation of intact elafin in the kidney favors clinical developments targeting inflammatory kidney diseases, such as chronic allograft nephropathy after kidney transplantation."( Biodistribution and pharmacokinetics of the (99m)Tc labeled human elastase inhibitor, elafin, in rats.
Culman, J; Haenisch, S; Kaschwich, M; Lützen, U; Marx, M; Preuss, S; Tjiong, A; Wiedow, O; Zhao, Y; Zuhayra, M, 2016)		0.86
" Ustekinumab had clear clinical and molecular effects, but clinical outcomes might have been obscured by a profound "placebo" effect, most likely due to background topical glucocorticosteroids and possibly insufficient dosing for AD."( Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis.
Bonifacio, KM; Brunner, PM; Coats, I; Cohen, SR; Cueto, I; Dutt, R; Finney, R; Fuentes-Duculan, J; Garcet, S; Gilleaudeau, P; Guttman-Yassky, E; Khattri, S; Krueger, JG; Kunjravia, N; Li, X; Oliva, M; Suárez-Fariñas, M; Sullivan-Whalen, M; Zheng, X, 2017)		0.46
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (286)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's1 (0.35)18.2507
2000's56 (19.58)29.6817
2010's196 (68.53)24.3611
2020's33 (11.54)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 36.07

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index36.07 (24.57)
Research Supply Index5.72 (2.92)
Research Growth Index6.91 (4.65)
Search Engine Demand Index48.45 (26.88)
Search Engine Supply Index2.05 (0.95)

This Compound (36.07)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials12 (4.11%)5.53%
Reviews31 (10.62%)6.00%
Case Studies2 (0.68%)4.05%
Observational6 (2.05%)0.25%
Other241 (82.53%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (3)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Levels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients With Metastatic (Stage IV) Breast Cancer: A Phase 2 Randomized, Open-Label Study [NCT05826964]Phase 2500 participants (Anticipated)Interventional2023-06-12Recruiting
Safety and Tolerability of Escalating Doses of Subcutaneous Elafin (Tiprelestat) Injection in Healthy Normal Subjects [NCT03522935]Phase 130 participants (Actual)Interventional2019-03-18Completed
An Open-Label, Phase Ib Dose Escalation Trial of Oral Combination Therapy With MSC1936369B and SAR245409 in Subjects With Locally Advanced or Metastatic Solid Tumors [NCT01390818]Phase 1146 participants (Actual)Interventional2011-05-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT01390818 (25) [back to overview]Accumulation Ratio (Racc) for AUCtau of Pimasertib (MSC1936369B): Day 15
NCT01390818 (25) [back to overview]Accumulation Ratio (Racc) for AUCtau of SAR245409: Day 15
NCT01390818 (25) [back to overview]Accumulation Ratio (Racc) for Cmax of Pimasertib (MSC1936369B): Day 15
NCT01390818 (25) [back to overview]Accumulation Ratio (Racc) for Cmax of SAR245409: Day 15
NCT01390818 (25) [back to overview]Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (0-inf) of SAR245409: Day 1
NCT01390818 (25) [back to overview]Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of Pimasertib (MSC1936369B) at Day 1
NCT01390818 (25) [back to overview]Number of Subjects Experiencing Any Treatment-Emergent Adverse Events (TEAEs)
NCT01390818 (25) [back to overview]Number of Subjects With Dose Limiting Toxicities (DLT)
NCT01390818 (25) [back to overview]Apparent Terminal Half-Life (t1/2) of SAR245409
NCT01390818 (25) [back to overview]Apparent Volume of Distribution of Total Pimasertib During the Terminal Phase Following Oral Administration (Vz/f) of Pimasertib
NCT01390818 (25) [back to overview]Apparent Volume of Distribution of Total SAR245409 During the Terminal Phase Following Oral Administration (Vz/f)
NCT01390818 (25) [back to overview]Area Under the Concentration-Time Curve (AUC) During a Dosing Interval (Tau) of Pimasertib (MSC1936369B)
NCT01390818 (25) [back to overview]Area Under the Concentration-Time Curve (AUC) During a Dosing Interval (Tau) of SAR245409
NCT01390818 (25) [back to overview]Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Last Sampling Time (0-24 Hours) of Pimasertib (MSC1936369B)
NCT01390818 (25) [back to overview]Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Last Sampling Time (0-24 Hours) of SAR245409
NCT01390818 (25) [back to overview]Half-Life (t1/2) of MSC1936369B (Pimasertib)
NCT01390818 (25) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Pimasertib (MSC1936369B)
NCT01390818 (25) [back to overview]Maximum Observed Plasma Concentration (Cmax) for SAR245409
NCT01390818 (25) [back to overview]Number of Subjects With Complete Tumor Response (CR), Partial Tumor Response (PR), or Stable Disease (SD)
NCT01390818 (25) [back to overview]pERK Concentrations in PBMCs
NCT01390818 (25) [back to overview]pS6 Concentrations in Peripheral Blood Mononuclear Cells (PBMCs)
NCT01390818 (25) [back to overview]Time to Reach Maximum Plasma Concentration (Tmax) of Pimasertib (MSC1936369B)
NCT01390818 (25) [back to overview]Time to Reach Maximum Plasma Concentration (Tmax) of SAR245409
NCT01390818 (25) [back to overview]Total Body Clearance (CL/f) of Pimasertib (MSC1936369B)
NCT01390818 (25) [back to overview]Total Body Clearance (CL/f) of SAR245409

Accumulation Ratio (Racc) for AUCtau of Pimasertib (MSC1936369B): Day 15

Accumulation ratio (Racc) for AUCtau, calculated as Day 15 dosing interval AUCtau per Day 1 dosing interval AUCtau. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

Interventionratio (Geometric Mean)
Pimasertib (MSC1936369B) 15mg1.523
Pimasertib (MSC1936369B) 30mg1.269
Pimasertib (MSC1936369B) 60mg1.174
Pimasertib (MSC1936369B) 90mg1.364
Pimasertib (MSC1936369B) 45mg Twice Daily2.176
Pimasertib (MSC1936369B) 60mg Twice DailyNA
TNBC: Pimasertib 60mg Once Daily1.368
NSCLC: Pimasertib 60mg Once Daily1.155
CRC: Pimasertib 60mg Once Daily1.245
MEL: Pimasertib 60mg Once Daily1.283

[back to top]

Accumulation Ratio (Racc) for AUCtau of SAR245409: Day 15

Accumulation ratio (Racc) for AUCtau, calculated as Day 15 dosing interval AUCtau divided by Day 1 dosing interval AUCtau. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

Interventionratio (Geometric Mean)
SAR245409 30mg1.189
SAR245409 50mg1.004
SAR245409 70mg0.9450
SAR245409 90mgNA
SAR245409 30mg Twice DailyNA
SAR245409 50mg Twice Daily1.800
TNBC: SAR245409 70mg Once Daily1.256
NSCLC: SAR245409 70mg Once Daily0.9887
CRC: SAR245409 70mg Once Daily1.187
MEL: SAR245409 70mg Once Daily1.022

[back to top]

Accumulation Ratio (Racc) for Cmax of Pimasertib (MSC1936369B): Day 15

Accumulation ratio (Racc) for Cmax, calculated as Day 15 Cmax/Day 1 Cmax. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

Interventionratio (Geometric Mean)
Pimasertib (MSC1936369B) 15mg1.525
Pimasertib (MSC1936369B) 30mg1.066
Pimasertib (MSC1936369B) 60mg1.106
Pimasertib (MSC1936369B) 90mg1.308
Pimasertib (MSC1936369B) 45mg Twice Daily1.467
Pimasertib (MSC1936369B) 60mg Twice DailyNA
TNBC: Pimasertib 60mg Once Daily1.203
NSCLC: Pimasertib 60mg Once Daily1.059
CRC: Pimasertib 60mg Once Daily1.247
MEL: Pimasertib 60mg Once Daily1.393

[back to top]

Accumulation Ratio (Racc) for Cmax of SAR245409: Day 15

Accumulation ratio (Racc) for Cmax, calculated as Day 15 Cmax divided by Day 1 Cmax. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

InterventionRatio (Geometric Mean)
SAR245409 30mg1.041
SAR245409 50mg0.8133
SAR245409 70mg0.8962
SAR245409 90mgNA
SAR245409 30mg Twice DailyNA
SAR245409 50mg Twice Daily1.336
TNBC: SAR245409 70mg Once Daily1.070
NSCLC: SAR245409 70mg Once Daily0.8950
CRC: SAR245409 70mg Once Daily0.9611
MEL: SAR245409 70mg Once Daily0.9942

[back to top]

Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (0-inf) of SAR245409: Day 1

"Area under the concentration-time curve from time 0 extrapolated to infinity, calculated as AUC0-t + last observed concentration (Clast)/terminal rate constant (λz), using the Linear up/Log down method.~Terminal rate constant (λz). The regression analysis (determination of λz) was to contain as many data points as possible (but excluding Cmax) and had to include concentration data from at least 3 different time points, consistent with the assessment of a straight line (the terminal elimination phase) on the log-transformed scale." (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1 for DE cohorts

Interventionhr*ng/mL (Geometric Mean)
SAR245409 30mg716.5
SAR245409 50mg1165
SAR245409 70mg1504
SAR245409 90mgNA
SAR245409 30mg Twice DailyNA
SAR245409 50mg Twice Daily331.2
TNBC: SAR245409 70mg Once Daily1974
NSCLC: SAR245409 70mg Once Daily1445
CRC: SAR245409 70mg Once Daily1261
MEL: SAR245409 70mg Once Daily1142

[back to top]

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of Pimasertib (MSC1936369B) at Day 1

"Area under the concentration-time curve from time 0 extrapolated to infinity, calculated as AUC0-t + last observed concentration (Clast)/terminal rate constant (λz), using the Linear up/Log down method.~Terminal rate constant (λz)." (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1 for DE cohorts

Interventionhr*ng/mL (Geometric Mean)
Pimasertib (MSC1936369B) 15mg451.6
Pimasertib (MSC1936369B) 30mg770.9
Pimasertib (MSC1936369B) 60mg1607
Pimasertib (MSC1936369B) 90mg2202
Pimasertib (MSC1936369B) 45mg Twice Daily503.1
TNBC: Pimasertib 60mg Once Daily1869
NSCLC: Pimasertib 60mg Once Daily1830
CRC: Pimasertib 60mg Once Daily1857
MEL: Pimasertib 60mg Once Daily1113

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Number of Subjects Experiencing Any Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a subject administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as those AEs that started between first dose of study drug and up to 30 days after last dose. (NCT01390818)
Timeframe: Baseline up to 30 Days after last dose; assessed up to 4 years

Interventionsubjects (Number)
Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily3
Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily3
Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily3
Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily4
Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily4
Pimasertib (MSC1936369B) 30mg and SAR245409 70mg Once Daily3
Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily19
Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily14
Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily3
Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily3
MSC1936369B (Pimasertib) 45mg and SAR245409 50mg Twice Daily4
TNBC: Pimasertib 60mg and SAR245409 70mg Once Daily26
NSCLC: Pimasertib 60mg and SAR245409 70mg Once Daily24
CRC: Pimasertib 60mg and SAR245409 70mg Once Daily18
MEL: Pimasertib 60mg and SAR245409 70mg Once Daily15

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Number of Subjects With Dose Limiting Toxicities (DLT)

DLT was defined as any of the following toxicities experienced during the first cycle of treatment at any dose level (DL) and judged not to be related to the underlying disease or any concomitant medication by the Investigator and/or the Sponsor: A treatment emergent adverse event (TEAE) of potential clinical significance such that further dose escalation (DE) would have exposed subjects to unacceptable risk. Any Grade greater than or equal to (>=) 3 non-hematological toxicity, except for: Grade 3 diarrhea, nausea and vomiting with a duration less than or equal to (<=) 48 hours despite adequate supportive care and Alopecia. Grade 4 neutropenia of > 5 days duration or febrile neutropenia. Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia. Any treatment interruption > 2 weeks due to AEs not related to the underlying disease or concomitant medication at any dose level and any severe, life-threatening impairing daily functions complication or abnormality. (NCT01390818)
Timeframe: Day 1 up to Day 16 in cycle 1

Interventionsubjects (Number)
Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily0
Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily0
Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily0
Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily0
Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily0
Pimasertib (MSC1936369B) 30mg and SAR245409 70mg Once Daily0
Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily0
Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily2
Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily1
Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily2
Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily1

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Apparent Terminal Half-Life (t1/2) of SAR245409

(NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionhour (Median)
Day 1 (n=6, 9, 31, 2, 2, 3, 20, 19, 13, 14)Day 15 (n=6, 8, 22, 1, 1, 2, 10, 15, 8, 10)
CRC: SAR245409 70mg Once Daily4.0706.170
MEL: SAR245409 70mg Once Daily3.1203.065
NSCLC: SAR245409 70mg Once Daily3.3004.050
SAR245409 30mg3.0553.700
SAR245409 30mg Twice DailyNANA
SAR245409 50mg3.3004.570
SAR245409 50mg Twice Daily3.310NA
SAR245409 70mg3.3904.560
SAR245409 90mgNANA
TNBC: SAR245409 70mg Once Daily3.7552.840

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Apparent Volume of Distribution of Total Pimasertib During the Terminal Phase Following Oral Administration (Vz/f) of Pimasertib

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Apparent volume of distribution during the terminal phase, calculated by CL/f/λz. Terminal rate constant (λz). The regression analysis (determination of λz) was to contain as many data points as possible (but excluding Cmax) and had to include concentration data from at least 3 different time points, consistent with the assessment of a straight line (the terminal elimination phase) on the log-transformed scale.Data was not available for 'Pimasertib (MSC1936369B) 60mg Twice Daily' arm as no subjects were considered evaluable because of limited number of samples collected to characterize the terminal phase rate constant needed for the calculation of Vz/f. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,
Interventionliter (Geometric Mean)
Day 1 (n=6, 9, 23, 13, 3, 0, 22, 22, 14, 13)Day 15 (n=6, 9, 13, 9, 0, 0, 16, 16, 9, 12)
CRC: Pimasertib 60mg Once Daily216.2230.6
MEL: Pimasertib 60mg Once Daily322.0273.8
NSCLC: Pimasertib 60mg Once Daily226.9250.9
Pimasertib (MSC1936369B) 15mg294.3188.7
Pimasertib (MSC1936369B) 30mg240.2261.8
Pimasertib (MSC1936369B) 45mg Twice Daily394.1NA
Pimasertib (MSC1936369B) 60mg282.8396.4
Pimasertib (MSC1936369B) 90mg283.0302.4
TNBC: Pimasertib 60mg Once Daily223.8226.3

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Apparent Volume of Distribution of Total SAR245409 During the Terminal Phase Following Oral Administration (Vz/f)

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Apparent volume of distribution during the terminal phase, calculated by CL/f/λz. Terminal rate constant (λz). The regression analysis (determination of λz) was to contain as many data points as possible (but excluding Cmax) and had to include concentration data from at least 3 different time points, consistent with the assessment of a straight line (the terminal elimination phase) on the log-transformed scale. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionlitre (Geometric Mean)
Day 1 (n=5, 9, 31, 2, 1, 3, 20, 17, 12, 12)Day 15 (n=6, 8, 25, 1, 1, 2, 17, 17, 10, 13 )
CRC: SAR245409 70mg Once Daily353.6475.9
MEL: SAR245409 70mg Once Daily270.3293.4
NSCLC: SAR245409 70mg Once Daily251.4247.1
SAR245409 30mg174.8165.7
SAR245409 30mg Twice DailyNANA
SAR245409 50mg223.4257.2
SAR245409 50mg Twice Daily658.0NA
SAR245409 70mg238.5355.9
SAR245409 90mgNANA
TNBC: SAR245409 70mg Once Daily175.2132.8

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Area Under the Concentration-Time Curve (AUC) During a Dosing Interval (Tau) of Pimasertib (MSC1936369B)

(NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionhr*ng/mL (Geometric Mean)
Day 1 (n= 6, 10, 26, 13, 3, 3, 24, 23, 17,13)Day 15 (n=6, 9, 15, 9, 3, 0, 16, 17, 10, 13)
CRC: Pimasertib 60mg Once Daily17721988
MEL: Pimasertib 60mg Once Daily10931506
NSCLC: Pimasertib 60mg Once Daily17541889
Pimasertib (MSC1936369B) 15mg426.8650.4
Pimasertib (MSC1936369B) 30mg742.1902.0
Pimasertib (MSC1936369B) 45mg Twice Daily354.9773.1
Pimasertib (MSC1936369B) 60mg15471617
Pimasertib (MSC1936369B) 60mg Twice Daily1252NA
Pimasertib (MSC1936369B) 90mg21162552
TNBC: Pimasertib 60mg Once Daily18822136

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Area Under the Concentration-Time Curve (AUC) During a Dosing Interval (Tau) of SAR245409

(NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionhr*ng/mL (Geometric Mean)
Day 1 (n=6, 11, 36, 3, 3, 3, 24, 23, 17, 15)Day 15 (n=6, 8, 25, 1, 1, 3, 17, 17, 10, 13)
CRC: SAR245409 70mg Once Daily15421365
MEL: SAR245409 70mg Once Daily948.41074
NSCLC: SAR245409 70mg Once Daily14801437
SAR245409 30mg746.9887.9
SAR245409 30mg Twice Daily634.0NA
SAR245409 50mg12651168
SAR245409 50mg Twice Daily298.6537.5
SAR245409 70mg16011362
SAR245409 90mg3032NA
TNBC: SAR245409 70mg Once Daily21152390

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Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Last Sampling Time (0-24 Hours) of Pimasertib (MSC1936369B)

Area under the concentration-time curve from time 0 to the last quantifiable concentration. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionhour*nanogram per millilitre (hr*ng/mL) (Geometric Mean)
Day 1 (n=6, 10, 25, 13, 4, 3, 25, 23, 18, 15)Day 15 (n=6, 9,15,9, 3, 1, 16, 17, 10, 13)
CRC: Pimasertib 60mg Once Daily17091988
MEL: Pimasertib 60mg Once Daily10931506
NSCLC: Pimasertib 60mg Once Daily17541889
Pimasertib (MSC1936369B) 15mg426.8625.3
Pimasertib (MSC1936369B) 30mg734.4902.0
Pimasertib (MSC1936369B) 45mg Twice Daily326.1773.1
Pimasertib (MSC1936369B) 60mg15471617
Pimasertib (MSC1936369B) 60mg Twice Daily1252NA
Pimasertib (MSC1936369B) 90mg21162552
TNBC: Pimasertib 60mg Once Daily17812136

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Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Last Sampling Time (0-24 Hours) of SAR245409

Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time (0-24 hours) at which the concentration is at or above the lower limit of quantification. Unit of assessment was hour*nanogram per milliliter (hr*ng/mL). (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionhr*ng/mL (Geometric Mean)
Day 1 (n=6, 11, 36, 3, 3, 4, 26, 23, 18, 15)Day 15 (n=6, 8, 25, 1, 1, 3, 17, 17, 10, 13)
CRC: SAR245409 70mg Once Daily14791365
MEL: SAR245409 70mg Once Daily854.9968.8
NSCLC: SAR245409 70mg Once Daily14081437
SAR245409 30mg683.6861.0
SAR245409 30mg Twice Daily634.0NA
SAR245409 50mg12481125
SAR245409 50mg Twice Daily226.2537.5
SAR245409 70mg15661334
SAR245409 90mg3032NA
TNBC: SAR245409 70mg Once Daily19762232

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Half-Life (t1/2) of MSC1936369B (Pimasertib)

(NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionhour (Median)
Day 1 (n=6, 9, 23, 13, 4, 3, 22, 22, 15, 13)Day 15 (n=6, 9, 14, 9, 2, 1, 16, 16, 9, 12)
CRC: Pimasertib 60mg Once Daily4.7705.210
MEL: Pimasertib 60mg Once Daily4.2404.325
NSCLC: Pimasertib 60mg Once Daily4.3705.250
Pimasertib (MSC1936369B) 15mg6.2505.855
Pimasertib (MSC1936369B) 30mg4.6705.410
Pimasertib (MSC1936369B) 45mg Twice Daily3.320NA
Pimasertib (MSC1936369B) 60mg4.8406.755
Pimasertib (MSC1936369B) 60mg Twice Daily4.640NA
Pimasertib (MSC1936369B) 90mg4.8005.590
TNBC: Pimasertib 60mg Once Daily4.8405.210

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Maximum Observed Plasma Concentration (Cmax) for Pimasertib (MSC1936369B)

(NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionnanogram/millilitre (ng/mL) (Geometric Mean)
Day 1 (n=6, 10, 26, 13, 4, 3, 25, 23, 18, 15)Day 15 (n=6, 9,15,9, 3, 1, 16, 17, 13, 10)
CRC: Pimasertib 60mg Once Daily245.6307.7
MEL: Pimasertib 60mg Once Daily234.0338.9
NSCLC: Pimasertib 60mg Once Daily295.4327.6
Pimasertib (MSC1936369B) 15mg86.06131.3
Pimasertib (MSC1936369B) 30mg188.2212.8
Pimasertib (MSC1936369B) 45mg Twice Daily83.72143.1
Pimasertib (MSC1936369B) 60mg246.1234.2
Pimasertib (MSC1936369B) 60mg Twice Daily232.5NA
Pimasertib (MSC1936369B) 90mg406.9516.4
TNBC: Pimasertib 60mg Once Daily323.1320.5

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Maximum Observed Plasma Concentration (Cmax) for SAR245409

(NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionnanogram per millilitre (ng/mL) (Geometric Mean)
Day 1 (n=6, 11, 36, 3, 3, 4, 26, 23, 18, 15)Day 15 (n=6, 6, 25, 1, 1, 3, 17, 17, 10, 13)
CRC: SAR245409 70mg Once Daily239.6178.9
MEL: SAR245409 70mg Once Daily212.5226.6
NSCLC: SAR245409 70mg Once240.6235.5
SAR245409 30mg192.0199.8
SAR245409 30mg Twice Daily130.2NA
SAR245409 50mg295.7224.1
SAR245409 50mg Twice Daily64.22117.2
SAR245409 70mg256.9222.9
SAR245409 90mg224.5NA
TNBC: SAR245409 70mg Once Daily323.6326.0

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Number of Subjects With Complete Tumor Response (CR), Partial Tumor Response (PR), or Stable Disease (SD)

CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD= At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (NCT01390818)
Timeframe: From the date of randomisation every 6 weeks up to assessed up to 4 years

,,,,,,,,,,,,,,
Interventionsubjects (Number)
Stable diseaseProgressive diseaseComplete ResponsePartial ResponseNot Evaluable
CRC: Pimasertib 60mg and SAR245409 70mg Once Daily19001
MEL: Pimasertib 60mg and SAR245409 70mg Once Daily74111
NSCLC: Pimasertib 60mg and SAR245409 70mg Once Daily106013
Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily30000
Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once Daily21000
Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once Daily20010
Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once Daily31000
Pimasertib (MSC1936369B) 30mg and SAR245409 70mg Once Daily20000
Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily21000
Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily10000
Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once Daily11002
Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once Daily49000
Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily02000
Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily63020
TNBC: Pimasertib 60mg and SAR245409 70mg Once Daily78001

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pERK Concentrations in PBMCs

"pERK Concentrations in PBMCs was measured during DDI Evaluation period and Cycle 1 for DE cohorts. DDI evaluation period is a 4-day period that was performed within 1 week prior to Day 1 Cycle 1. In DDI evaluation period, On Day 1, SAR245409 was be administered alone, and on Day 3, Pimasertib was administered alone. No data were planned to be collected for Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily, Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily, Pimasertib (MSC1936369) 30mg and SAR245409 70mg Once Daily and Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily reporting arms." (NCT01390818)
Timeframe: DDI Evaluation: Day 1 and 3 (predose, 2, 4, 8 and 24 hours (hr) postdose); Day 2 and 4 (24 hr postdose); C1D1 and C1D15 (predose, 2, 4, 8, 24 hr postdose); C1D2 and C1D16 (24 hr postdose); C1D19 (predose, 2 hr postdose)

,,,,,,
Interventionfluorescence intensity (Mean)
DDI Day 1: Predose (n= 1, 0, 0, 0, 0, 0, 1)DDI Day 1: 2 hr post-dose (n=1,0,0,0,0.0,1)DDI Day 1: 4 hr post-dose ((n=1,0,0,0,0,0,1)DDI Day 1: 8 hr post-dose(n= 1, 0, 0, 0, 0, 0, 1)DDI Day 1: 24 hr post-dose (n=1,0,0,0,0,0,0)DDI Day 2: 24 hr post-dose ((n= 0,0,0,0,0,0,1)DDI Day 3: Pre-dose (n= 1, 0, 0, 0, 0, 0, 1)DDI Day 3: 2 hr post-dose (n=1,0,0,0,0,0,1)DDI Day 3: 4 hr post-dose (n-1,0,0,0,0,0,1)DDI Day 3: 8 hr post-dose(n= 1, 0, 0, 0, 0, 0, 1)DDI Day 3: 24 hr post-dose (n=1,0,0,0,0,0,0)DDI Day 4: 24 hr post-dose (n=0,0,0,0,0,0,1)C1D1: Pre dose (n=1,1,1,1,1,1,1)C1D1: 2hr postdose(n= 1,1,1,1,1,1,1)C1D1: 4hr postdose(n= 1,1,1,1,1,1,1)C1D1: 8hr postdose(n= 1,1,1,1,1,1,1)C1D1: 24hr postdose(n= 1,1,1,1,0,0,0)C1D2: 24hr postdose(n= 0,0,0,0,1,1,1)C1D15: pre-dose(n= 1,1,1,1,1,0,1)C1D15: 2hr postdose (n= 1,1,1,1,1,0,1)C1D15: 4hr postdose (n= 1,1,1,1,1,0,1)C1D15: 8hr postdose (n= 1,1,1,1,1,0,1)C1D15: 24hr postdose (n= 1,1,1,1,0,0,0)C1D16: 24hr postdose (n= 0,0,0,0,1,0,1)C1D19: pre-dose (n= 1,1,1,1,1,0,1)C1D19: 2hr postdose (n= 1,0,0,0,0,0,0)
Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily6.778.746.107.4210.84NA9.463.126.740.816.18NA5.562.372.850.676.23NA3.792.161.871.924.97NA6.541.60
Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once DailyNANANANANANANANANANANANA6.962.782.913.404.59NA5.292.832.503.385.33NA4.47NA
Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once DailyNANANANANANANANANANANANA3.451.331.370.942.15NA2.261.341.342.080.94NA2.61NA
Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once DailyNANANANANANANANANANANANA3.251.541.241.966.26NA1.411.600.941.104.70NA5.44NA
Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once DailyNANANANANANANANANANANANA3.351.401.961.27NA3.451.931.551.201.74NA2.362.07NA
Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once DailyNANANANANANANANANANANANA1.970.951.111.12NA1.26NANANANANANANANA
Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily10.5510.176.509.36NA8.328.9415.820.6815.68NA1.067.421.041.010.82NA1.052.030.940.810.99NA0.995.72NA

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pS6 Concentrations in Peripheral Blood Mononuclear Cells (PBMCs)

"pS6 Concentrations in PBMCs was measured during DDI Evaluation period and Cycle 1 for DE cohorts. DDI evaluation period is a 4-day period that was performed within 1 week prior to Day 1 Cycle 1. In DDI evaluation period, On Day 1, SAR245409 was be administered alone, and on Day 3, Pimasertib was administered alone. No data were planned to be collected for Pimasertib (MSC1936369B) 60mg and SAR245409 30mg Twice Daily, Pimasertib (MSC1936369B) 45mg and SAR245409 50mg Twice Daily, Pimasertib (MSC1936369) 30mg and SAR245409 70mg Once Daily and Pimasertib (MSC1936369B) 60mg and SAR245409 90mg Once Daily reporting arms." (NCT01390818)
Timeframe: DDI Evaluation: Day 1 and 3 (predose, 2, 4, 8 and 24 hours (hr) postdose); Day 2 and 4 (24 hr postdose); Cycle 1 Day 1 (C1D1) and C1D15 (predose, 2, 4, 8, 24 hr postdose); C1D2 and C1D16 (24 hr postdose); C1D19 (predose, 2 hr postdose)

,,,,,,
Interventionfluorescence intensity (Mean)
DDI Day 1: Pre-dose (n= 1, 0, 0, 0, 0, 0, 1)DDI Day 1: 2hr post-dose (n= 1,0,0,0,0,0,1)DDI Day 1: 4hr post-dose (n= 1,0,0,0,0,0,1)DDI Day 1: 8 hr post-dose(n= 1, 0, 0, 0, 0, 0, 1)DDI Day 1: 24hr post-dose (n= 1,0,0,0,0,0,0)DDI Day 2: 24hr post-dose (n= 0,0,0,0,0,0,1)DDI Day 3: Pre-dose (n= 1, 0, 0, 0, 0, 0, 1)DDI Day 3: 2hr post-dose (n= 1,0,0,0,0,0,1)DDI Day 3: 4hr post-dose (n= 1,0,0,0,0,0,1)DDI: Day 3: 8 hr post-dose(n= 1, 0, 0, 0, 0, 0, 1)DDI:Day 3: 24hr post-dose (n= 1,0,0,0,0,0,0)DDI Day 4: 24hr post-dose (n= 0,0,0,0,0,0,1)C1D1: Pre dose (n= 1,1,1,1,1,1,1)C1D1: 2hr postdose (n= 1,1,1,1,1,1,1)C1D1: 4hr postdose (n= 1,1,1,1,1,1,1)C1D1: 8hr postdose (n= 1,1,1,1,1,1,1)C1D1: 24hr postdose(n= 1,1,1,1,0,0,0)C1D2: 24hr postdose (n= 0,0,0,0,1,1,1)C1D15: pre-dose (n= 1,1,1,1,1,0,1)C1D15: 2hr postdose (n= 1,1,1,1,1,0,1)C1D15: 4hr postdose (n= 1,1,1,1,1,0,1)C1D15: 8hr postdose (n= 1,1,1,1,1,0,1)C1D15: 24hr postdose (n= 1,1,1,1,0,0,0)C1D16: 24hr postdose (n= 0,0,0,0,1,0,1)C1D19: pre-dose (n= 1,1,1,1,1,0,1)C1D19: 2hr postdose (n= 1,0,0,0,0,0,0)
Pimasertib (MSC1936369B) 15mg and SAR245409 30mg Once Daily61.0236.1589.1454.5488.80NA57.5155.9336.761.0887.60NA51.3231.0825.713.0246.16NA43.4826.4141.340.5369.93NA68.484.34
Pimasertib (MSC1936369B) 15mg and SAR245409 50mg Once DailyNANANANANANANANANANANANA96.9856.4150.1184.5774.15NA67.6948.2392.6777.62114.39NA125.77NA
Pimasertib (MSC1936369B) 30mg and SAR245409 30mg Once DailyNANANANANANANANANANANANA83.5224.4846.951.2872.14NA81.2943.7053.3745.970.76NA90.02NA
Pimasertib (MSC1936369B) 30mg and SAR245409 50mg Once DailyNANANANANANANANANANANANA47.0923.8929.8519.7553.47NA1.2015.020.9636.0670.46NA82.06NA
Pimasertib (MSC1936369B) 60mg and SAR245409 50mg Once DailyNANANANANANANANANANANANA50.175.7218.216.21NA24.6633.4321.1119.6830.08NA24.3630.58NA
Pimasertib (MSC1936369B) 60mg and SAR245409 70mg Once DailyNANANANANANANANANANANANA4.180.920.721.18NA1.61NANANANANANANANA
Pimasertib (MSC1936369B) 90mg and SAR245409 70mg Once Daily33.7829.8430.2844.88NA28.8614.9034.061.0340.40NA1.0436.031.040.940.96NA1.000.981.061.030.88NA0.9849.62NA

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Time to Reach Maximum Plasma Concentration (Tmax) of Pimasertib (MSC1936369B)

(NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionhour (Median)
Day 1 (n= 6, 10, 25, 13, 4, 3, 25, 23, 18, 15 )Day 15 (n= 6, 9, 15, 9, 3, 1, 16, 17, 13, 10)
CRC: Pimasertib 60mg Once Daily1.4901.500
MEL: Pimasertib 60mg Once Daily1.0501.030
NSCLC: Pimasertib 60mg Once Daily1.5201.530
Pimasertib (MSC1936369B) 15mg1.7501.275
Pimasertib (MSC1936369B) 30mg0.7651.000
Pimasertib (MSC1936369B) 45mg Twice Daily1.4852.000
Pimasertib (MSC1936369B) 60mg2.0202.000
Pimasertib (MSC1936369B) 60mg Twice Daily1.550NA
Pimasertib (MSC1936369B) 90mg1.5001.550
TNBC: Pimasertib 60mg Once Daily1.5001.505

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Time to Reach Maximum Plasma Concentration (Tmax) of SAR245409

The time to reach maximum plasma concentration (Tmax) of SAR245409 was calculated. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionhours (Median)
Day 1 (n=6, 11, 36, 3, 3, 4, 26, 23, 18, 15)Day 15 (n=6, 8, 25, 1, 1, 3, 17, 17, 10, 13)
CRC: SAR245409 70mg Once Daily2.0001.750
MEL: SAR245409 70mg Once Daily1.5001.050
NSCLC: SAR245409 70mg Once Daily2.0001.530
SAR245409 30mg1.5101.265
SAR245409 30mg Twice Daily2.050NA
SAR245409 50mg1.1501.750
SAR245409 50mg Twice Daily1.5401.550
SAR245409 70mg1.5001.970
SAR245409 90mg1.500NA
TNBC: SAR245409 70mg Once Daily1.5002.030

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Total Body Clearance (CL/f) of Pimasertib (MSC1936369B)

The total body clearance of drug from plasma following oral administration (Cl/f) and the total body clearance of drug from plasma following intravenous administration was calculated by dividing the Dose with area under the plasma concentration time curve from time zero to infinity (AUC0 inf)=Dose/AUC0- inf. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionlitre per hour (L/hr) (Geometric Mean)
Day 1 (n=6, 10, 26, 13, 3, 0, 22, 22, 14, 13)Day 15 (n=6, 9, 15, 9, 3, 1, 16, 17, 10, 13)
CRC: Pimasertib 60mg Once Daily30.7530.20
MEL: Pimasertib 60mg Once Daily53.9439.81
NSCLC: Pimasertib 60mg Once Daily32.7531.73
Pimasertib (MSC1936369B) 15mg33.2223.06
Pimasertib (MSC1936369B) 30mg38.9033.30
Pimasertib (MSC1936369B) 45mg Twice Daily89.4958.22
Pimasertib (MSC1936369B) 60mg37.9937.11
Pimasertib (MSC1936369B) 60mg Twice DailyNANA
Pimasertib (MSC1936369B) 90mg40.8835.28
TNBC: Pimasertib 60mg Once Daily32.1228.11

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Total Body Clearance (CL/f) of SAR245409

The total body clearance of drug from plasma following oral administration (Cl/f) and the total body clearance of drug from plasma following intravenous administration was calculated by dividing the dose with area under the plasma concentration time curve from time zero to infinity (AUC 0-inf)=Dose/AUC 0-inf. (NCT01390818)
Timeframe: Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

,,,,,,,,,
Interventionlitre per hour (Geometric Mean)
Day 1 (n=5, 9, 31, 2, 1, 3, 20, 17, 12, 12)Day 15 (n=6, 8, 25, 1, 1, 3, 17, 17, 10, 13)
CRC: SAR245409 70mg Once Daily55.5151.24
MEL: SAR245409 70mg Once Daily61.2965.16
NSCLC: SAR245409 70mg Once Daily48.4048.69
SAR245409 30mg41.8033.78
SAR245409 30mg Twice DailyNANA
SAR245409 50mg42.9342.81
SAR245409 50mg Twice Daily151.492.90
SAR245409 70mg46.5451.38
SAR245409 90mgNANA
TNBC: SAR245409 70mg Once Daily35.4329.28

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SubstanceRelationship StrengthStudiesTrialsClassesRoles
aminolevulinic acid
Aminolevulinic Acid: A compound produced from succinyl-CoA and GLYCINE as an intermediate in heme synthesis. It is used as a PHOTOCHEMOTHERAPY for actinic KERATOSIS.. 5-aminolevulinic acid : The simplest delta-amino acid in which the hydrogens at the gamma position are replaced by an oxo group. It is metabolised to protoporphyrin IX, a photoactive compound which accumulates in the skin. Used (in the form of the hydrochloride salt)in combination with blue light illumination for the treatment of minimally to moderately thick actinic keratosis of the face or scalp.		3.59114-oxo monocarboxylic acid;
amino acid zwitterion;
delta-amino acid		antineoplastic agent;
dermatologic drug;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
photosensitizing agent;
plant metabolite;
prodrug;
Saccharomyces cerevisiae metabolite
cadaverine
[no description available]		2.0610alkane-alpha,omega-diamineDaphnia magna metabolite;
Escherichia coli metabolite;
mouse metabolite;
plant metabolite
chlorine
chloride : A halide anion formed when chlorine picks up an electron to form an an anion.		2.0410halide anion;
monoatomic chlorine		cofactor;
Escherichia coli metabolite;
human metabolite
glycine
[no description available]		2.1110alpha-amino acid;
amino acid zwitterion;
proteinogenic amino acid;
serine family amino acid		EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor;
fundamental metabolite;
hepatoprotective agent;
micronutrient;
neurotransmitter;
NMDA receptor agonist;
nutraceutical
histamine
[no description available]		2.2510aralkylamino compound;
imidazoles		human metabolite;
mouse metabolite;
neurotransmitter
phosphorylcholine
Phosphorylcholine: Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction.. phosphocholine : The phosphate of choline; and the parent compound of the phosphocholine family.		2.0710phosphocholinesallergen;
epitope;
hapten;
human metabolite;
mouse metabolite
4-nonylphenol
4-nonylphenol: structure in first source; see also record for nonylphenol. 4-nonylphenol : A member of the class of phenols that is phenol which is para-substituted with a nonyl group.		2.0510phenolsenvironmental contaminant
chlorpropamide
Chlorpropamide: A sulfonylurea hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. (From Martindale, The Extra Pharmacopoeia, 30th ed, p277). chlorpropamide : An N-sulfonylurea that is urea in which a hydrogen attached to one of the nitrogens is substituted by 4-chlorobenzenesulfonyl group and a hydrogen attached to the other nitrogen is substituted by propyl group. Chlorpropamide is a hypoglycaemic agent used in the treatment of type 2 (non-insulin-dependent) diabetes mellitus not responding to dietary modification.		2.0310monochlorobenzenes;
N-sulfonylurea		hypoglycemic agent;
insulin secretagogue
fluorouracil
Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. 5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth.		2.0710nucleobase analogue;
organofluorine compound		antimetabolite;
antineoplastic agent;
environmental contaminant;
immunosuppressive agent;
radiosensitizing agent;
xenobiotic
ha14-1
ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate: a BH3 mimetic; synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia		2.03101-benzopyran
letrozole
[no description available]		2.110nitrile;
triazoles		antineoplastic agent;
EC 1.14.14.14 (aromatase) inhibitor
2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first source		3.3260chromones;
morpholines;
organochlorine compound		autophagy inhibitor;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
geroprotector
monodansylcadaverine
monodansylcadaverine: inhibits cross linkage of fibrin. monodansylcadaverine : A sulfonamide obtained by formal condensation of the sulfo group of 5-(dimethylamino)naphthalene-1-sulfonic acid with one of the amino groups of cadaverine.		2.0610aminonaphthalene;
primary amino compound;
sulfonamide;
tertiary amino compound		EC 2.3.2.13 (protein-glutamine gamma-glutamyltransferase) inhibitor;
fluorochrome;
protective agent
pd 98059
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one: inhibits MAP kinase kinase (MEK) activity, p42 MAPK and p44 MAPK; structure in first source. 2-(2-amino-3-methoxyphenyl)chromen-4-one : A member of the class of monomethoxyflavones that is 3'-methoxyflavone bearing an additional amino substituent at position 2'.		2.0410aromatic amine;
monomethoxyflavone		EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
geroprotector
prednisone
Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.. prednisone : A synthetic glucocorticoid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system. Prednisone is a prodrug that is converted by the liver into prednisolone (a beta-hydroxy group instead of the oxo group at position 11), which is the active drug and also a steroid.		2.051011-oxo steroid;
17alpha-hydroxy steroid;
20-oxo steroid;
21-hydroxy steroid;
3-oxo-Delta(1),Delta(4)-steroid;
C21-steroid;
glucocorticoid;
primary alpha-hydroxy ketone;
tertiary alpha-hydroxy ketone		adrenergic agent;
anti-inflammatory drug;
antineoplastic agent;
immunosuppressive agent;
prodrug
glutamine
Glutamine: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.. L-glutamine : An optically active form of glutamine having L-configuration.. glutamine : An alpha-amino acid that consists of butyric acid bearing an amino substituent at position 2 and a carbamoyl substituent at position 4.		2.0610amino acid zwitterion;
glutamine family amino acid;
glutamine;
L-alpha-amino acid;
polar amino acid zwitterion;
proteinogenic amino acid		EC 1.14.13.39 (nitric oxide synthase) inhibitor;
Escherichia coli metabolite;
human metabolite;
metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
lysine
Lysine: An essential amino acid. It is often added to animal feed.. lysine : A diamino acid that is caproic (hexanoic) acid bearing two amino substituents at positions 2 and 6.. L-lysine : An L-alpha-amino acid; the L-isomer of lysine.		2.0610aspartate family amino acid;
L-alpha-amino acid zwitterion;
L-alpha-amino acid;
lysine;
organic molecular entity;
proteinogenic amino acid		algal metabolite;
anticonvulsant;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
methionine
Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.. methionine : A sulfur-containing amino acid that is butyric acid bearing an amino substituent at position 2 and a methylthio substituent at position 4.		2.0210aspartate family amino acid;
L-alpha-amino acid;
methionine zwitterion;
methionine;
proteinogenic amino acid		antidote to paracetamol poisoning;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical
cytarabine
[no description available]		2.0510beta-D-arabinoside;
monosaccharide derivative;
pyrimidine nucleoside		antimetabolite;
antineoplastic agent;
antiviral agent;
immunosuppressive agent
pyrroles
1H-pyrrole : A tautomer of pyrrole that has the double bonds at positions 2 and 4.. pyrrole : A five-membered monocyclic heteroarene comprising one NH and four CH units which forms the parent compound of the pyrrole group of compounds. Its five-membered ring structure has three tautomers. A 'closed class'.. azole : Any monocyclic heteroarene consisting of a five-membered ring containing nitrogen. Azoles can also contain one or more other non-carbon atoms, such as nitrogen, sulfur or oxygen.		2.1510pyrrole;
secondary amine
pyrazolanthrone
pyrazolanthrone: JNK (c-Jun N-terminal kinase) inhibitor; structure in first source. anthra[1,9-cd]pyrazol-6(2H)-one : A member of the class of anthrapyrazoles that is anthra[1,9-cd]pyrazole substituted at position 6 by an oxo group. An inhibitor of c-Jun N-terminal kinase.		2.0410anthrapyrazole;
aromatic ketone;
cyclic ketone		antineoplastic agent;
c-Jun N-terminal kinase inhibitor;
geroprotector
catechin
Catechin: An antioxidant flavonoid, occurring especially in woody plants as both (+)-catechin and (-)-epicatechin (cis) forms.. catechin : Members of the class of hydroxyflavan that have a flavan-3-ol skeleton and its substituted derivatives.. rac-catechin : A racemate comprising equimolar amounts of (+)- and (-)-catechin. (+)-catechin : The (+)-enantiomer of catechin and a polyphenolic antioxidant plant metabolite.		2.2510catechinantioxidant;
plant metabolite
thiazoles
[no description available]		2.49201,3-thiazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
oleanolic acid
[no description available]		2.0510hydroxy monocarboxylic acid;
pentacyclic triterpenoid		plant metabolite
trinitrobenzenesulfonic acid
Trinitrobenzenesulfonic Acid: A reagent that is used to neutralize peptide terminal amino groups.. 2,4,6-trinitrobenzenesulfonic acid : The arenesulfonic acid that is benzenesulfonic acid with three nitro substituents in the 2-, 4- and 6-positions.		2.4110arenesulfonic acid;
C-nitro compound		epitope;
explosive;
reagent
deoxycytidine
[no description available]		2.5220pyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
amiloride
Amiloride: A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705). amiloride : A member of the class of pyrazines resulting from the formal monoacylation of guanidine with the carboxy group of 3,5-diamino-6-chloropyrazine-2-carboxylic acid.		2.0410aromatic amine;
guanidines;
organochlorine compound;
pyrazines		diuretic;
sodium channel blocker
sabinene
sabinene: RN given refers to cpd without isomeric designation. sabinene : A thujene that is a bicyclic monoterpene isolated from the essential oils of various plant species.		2.1510thujeneplant metabolite
lanthanum
[no description available]		2.0410f-block element atom;
lanthanoid atom;
scandium group element atom
technetium
Technetium: The first artificially produced element and a radioactive fission product of URANIUM. Technetium has the atomic symbol Tc, and atomic number 43. All technetium isotopes are radioactive. Technetium 99m (m=metastable) which is the decay product of Molybdenum 99, has a half-life of about 6 hours and is used diagnostically as a radioactive imaging agent. Technetium 99 which is a decay product of technetium 99m, has a half-life of 210,000 years.		2.1310manganese group element atom
trolamine salicylate
Arthritis: Acute or chronic inflammation of JOINTS.		2.3110
daunorubicin
Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.. anthracycline : Anthracyclines are polyketides that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.. daunorubicin : A natural product found in Actinomadura roseola.		2.0510aminoglycoside antibiotic;
anthracycline;
p-quinones;
tetracenequinones		antineoplastic agent;
bacterial metabolite
paclitaxel
Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).		2.0710taxane diterpenoid;
tetracyclic diterpenoid		antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent
substance p
[no description available]		2.0410peptideneurokinin-1 receptor agonist;
neurotransmitter;
vasodilator agent
lovastatin
Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.. lovastatin : A fatty acid ester that is mevastatin carrying an additional methyl group on the carbobicyclic skeleton. It is used in as an anticholesteremic drug and has been found in fungal species such as Aspergillus terreus and Pleurotus ostreatus (oyster mushroom).		2.1110delta-lactone;
fatty acid ester;
hexahydronaphthalenes;
polyketide;
statin (naturally occurring)		anticholesteremic drug;
antineoplastic agent;
Aspergillus metabolite;
prodrug
mifepristone
Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary CUSHING SYNDROME.		3.42113-oxo-Delta(4) steroid;
acetylenic compound;
tertiary amino compound		abortifacient;
contraceptive drug;
hormone antagonist;
synthetic oral contraceptive
imiquimod
Imiquimod: A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial CARCINOMA, BASAL CELL; and ACTINIC KERATOSIS.. imiquimod : An imidazoquinoline fused [4,5-c] carrying isobutyl and amino substituents at N-1 and C-4 respectively. A prescription medication, it acts as an immune response modifier and is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis.		3.5911imidazoquinolineantineoplastic agent;
interferon inducer
gemcitabine
gemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.		2.5220organofluorine compound;
pyrimidine 2'-deoxyribonucleoside		antimetabolite;
antineoplastic agent;
antiviral drug;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
environmental contaminant;
immunosuppressive agent;
photosensitizing agent;
prodrug;
radiosensitizing agent;
xenobiotic
mevastatin
mevastatin: antifungal metabolite from Penicillium brevicopactum; potent inhibitory activity to sterol synthesis; structure. mevastatin : A carboxylic ester that is pravastatin that is lacking the allylic hydroxy group. A hydroxymethylglutaryl-CoA reductase inhibitor (statin) isolated from Penicillium citrinum and from Penicillium brevicompactum, its clinical use as a lipid-regulating drug ceased following reports of toxicity in animals.		2.11102-pyranones;
carboxylic ester;
hexahydronaphthalenes;
polyketide;
statin (naturally occurring)		antifungal agent;
apoptosis inducer;
EC 3.4.24.83 (anthrax lethal factor endopeptidase) inhibitor;
fungal metabolite;
Penicillium metabolite
thiazolyl blue
thiazolyl blue: RN & II refers to bromide. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide : The bromide salt of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium.		2.0810organic bromide saltcolorimetric reagent;
dye
epigallocatechin gallate
epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis). (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin.		2.2510flavans;
gallate ester;
polyphenol		antineoplastic agent;
antioxidant;
apoptosis inducer;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent;
plant metabolite
triazoles
Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.		2.51201,2,3-triazole
avarol
avarol: RN given refers to parent cpd; extract from Dysidea avara(sea sponge)		2.0310
illimaquinone
illimaquinone: structure given in first source; isolated from the Red Sea sponge Smenospongia; inhibits the RNase H. activity of HIV-1 reverse transcriptase		2.0310monohydroxy-1,4-benzoquinones;
prenylquinone		metabolite
glycidyl nitrate
glycidyl nitrate: a nitric oxide donor; structure in first source. peptidoglycan : A peptidoglycosaminoglycan formed by alternating residues of beta-(1->4)-linked N-acetylglucosamine and N-acetylmuramic acid {2-amino-3-O-[(S)-1-carboxyethyl]-2-deoxy-D-glucose} residues. Attached to the carboxy group of the muramic acid is a peptide chain of three to five amino acids.		2.9810
artesunic acid
[no description available]		2.0310
sivelestat
sivelestat: inhibitor of neutrophil elastase; structure given in first source		2.1110N-acylglycine;
pivalate ester
peroxynitrous acid
Peroxynitrous Acid: A potent oxidant synthesized by the cell during its normal metabolism. Peroxynitrite is formed from the reaction of two free radicals, NITRIC OXIDE and the superoxide anion (SUPEROXIDES).		2.1110nitrogen oxoacid
perifosine
[no description available]		2.0710ammonium betaine;
phospholipid		EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
methyl 5-aminolevulinate
methyl 5-aminolevulinate: esterified form of aminolevulinic acid used as PHOTOCHEMOTHERAPY. methyl 5-aminolevulinate : The methyl ester of 5-aminolevulinic acid. A prodrug, it is metabolised to protoporphyrin IX, a photosensitizer, and is used in the photodynamic treatment of non-melanoma skin cancer (including basal cell carcinoma). Topical application (often as the hydrochloride salt) results in an accumulation of protoporphyrin IX in the skin lesions to which the cream has been applied. Subsequent illumination with red light results in the generation of toxic singlet oxygen that destroys cell membranes and thereby kills the tumour cells.		3.5911delta-amino acid esterantineoplastic agent;
dermatologic drug;
photosensitizing agent;
prodrug
cyc 202
seliciclib : 2,6-Diaminopurine carrying benzylamino, (2R)-1-hydroxybutan-2-yl and isopropyl substituents at C-6, C-2-N and N-9 respectively. It is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors.		2.03102,6-diaminopurinesantiviral drug;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
platycodin d
platycodin D: triterpenoid saponin from a root of Platycodon grandiflorum; RN refers to (2beta,3beta,16alpha)-isomer; structure given in first source		2.110triterpenoid saponinmetabolite
sb 203580
[no description available]		2.0410imidazoles;
monofluorobenzenes;
pyridines;
sulfoxide		EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent
erlotinib hydrochloride
[no description available]		2.3110hydrochloride;
terminal acetylenic compound		antineoplastic agent;
protein kinase inhibitor
carboplatin
[no description available]		2.4110
n-acetylneuraminic acid
N-Acetylneuraminic Acid: An N-acyl derivative of neuraminic acid. N-acetylneuraminic acid occurs in many polysaccharides, glycoproteins, and glycolipids in animals and bacteria. (From Dorland, 28th ed, p1518). N-acetylneuraminic acid : An N-acylneuraminic acid where the N-acyl group is specified as acetyl.		2.1110N-acetylneuraminic acidsantioxidant;
bacterial metabolite;
EC 3.2.1.18 (exo-alpha-sialidase) inhibitor;
human metabolite;
mouse metabolite
elastin
[no description available]		7.4720oligopeptide
betadex
beta-Cyclodextrins: Cyclic GLUCANS consisting of seven (7) glucopyranose units linked by 1,4-glycosidic bonds.		2.2110cyclodextrin
tretinoin
Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).. retinoic acid : A retinoid consisting of 3,7-dimethylnona-2,4,6,8-tetraenoic acid substituted at position 9 by a 2,6,6-trimethylcyclohex-1-en-1-yl group (geometry of the four exocyclic double bonds is not specified).. all-trans-retinoic acid : A retinoic acid in which all four exocyclic double bonds have E- (trans-) geometry.		2.1510retinoic acid;
vitamin A		anti-inflammatory agent;
antineoplastic agent;
antioxidant;
AP-1 antagonist;
human metabolite;
keratolytic drug;
retinoic acid receptor agonist;
retinoid X receptor agonist;
signalling molecule
bromochloroacetic acid
Keratins: A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.. bromochloroacetic acid : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by bromine while a second is replaced by chlorine. A low-melting (27.5-31.5degreeC), hygroscopic crystalline solid, it can be formed during the disinfection (by chlorination) of water that contains bromide ions and organic matter, so can occur in drinking water as a byproduct of the disinfection process.		2.45202-bromocarboxylic acid;
monocarboxylic acid;
organochlorine compound
isomethyleugenol
Methylation: Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)		2.2110isomethyleugenol
piperine
piperine : A N-acylpiperidine that is piperidine substituted by a (1E,3E)-1-(1,3-benzodioxol-5-yl)-5-oxopenta-1,3-dien-5-yl group at the nitrogen atom. It is an alkaloid isolated from the plant Piper nigrum.		2.3110benzodioxoles;
N-acylpiperidine;
piperidine alkaloid;
tertiary carboxamide		food component;
human blood serum metabolite;
NF-kappaB inhibitor;
plant metabolite
sesquiterpenes
[no description available]		2.7230
curcumin
Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.. curcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa.		2.2110aromatic ether;
beta-diketone;
diarylheptanoid;
enone;
polyphenol		anti-inflammatory agent;
antifungal agent;
antineoplastic agent;
biological pigment;
contraceptive drug;
dye;
EC 1.1.1.205 (IMP dehydrogenase) inhibitor;
EC 1.1.1.21 (aldehyde reductase) inhibitor;
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor;
EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor;
EC 1.8.1.9 (thioredoxin reductase) inhibitor;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
flavouring agent;
food colouring;
geroprotector;
hepatoprotective agent;
immunomodulator;
iron chelator;
ligand;
lipoxygenase inhibitor;
metabolite;
neuroprotective agent;
nutraceutical;
radical scavenger
u 0126
U 0126: protein kinase kinase inhibitor; structure in first source		2.1110aryl sulfide;
dinitrile;
enamine;
substituted aniline		antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
osteogenesis regulator;
vasoconstrictor agent
mtt formazan
MTT formazan: a blue MEM-insoluble mitochondrial byproduct; used to determine viability of cells with active mitochondrial dehydrogenase enzymes		2.0610
alpha-chymotrypsin
Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.		2.0810
cathepsin g
Cathepsin G: A serine protease found in the azurophil granules of NEUTROPHILS. It has an enzyme specificity similar to that of chymotrypsin C.		3.5820
sphingosine
sphing-4-enine : A sphingenine in which the C=C double bond is located at the 4-position.. sphingenine : A 2-aminooctadecene-1,3-diol having (2S,3R)-configuration.. sphingoid : Sphinganine, its homologs and stereoisomers, and the hydroxy and unsaturated derivatives of these compounds.. 2-aminooctadec-4-ene-1,3-diol : A 2-aminooctadecene-1,3-diol having its double bond at position 4.		2.1110sphing-4-eninehuman metabolite;
mouse metabolite
dinoprostone
prostaglandin E2 : Prostaglandin F2alpha in which the hydroxy group at position 9 has been oxidised to the corresponding ketone. Prostaglandin E2 is the most common and most biologically potent of mammalian prostaglandins.		2.4920prostaglandins Ehuman metabolite;
mouse metabolite;
oxytocic
apigenin
Chamomile: Common name for several daisy-like plants (MATRICARIA; TRIPLEUROSPERMUM; ANTHEMIS; CHAMAEMELUM) native to Europe and Western Asia, now naturalized in the United States and Australia.		2.0510trihydroxyflavoneantineoplastic agent;
metabolite
calcitriol
dihydroxy-vitamin D3: as a major in vitro metabolite of 1alpha,25-dihydroxyvitamin D3, produced in primary cultures of neonatal human keratinocytes		2.1510D3 vitamins;
hydroxycalciol;
triol		antineoplastic agent;
antipsoriatic;
bone density conservation agent;
calcium channel agonist;
calcium channel modulator;
hormone;
human metabolite;
immunomodulator;
metabolite;
mouse metabolite;
nutraceutical
misoprostol
Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties.. misoprostol : A diastereoisomeric mixture composed of approximately equal amounts of a double racemate of four of the sixteen possible diastereoisomers of methyl (13E)-11,16-dihydroxy-16-methyl-9-oxoprost-13-en-1-oate that is racemic prostaglandin E1 which is lacking the hydroxy group at position 15, but which has an additional hydroxy group at position 16. It is a synthetic prostaglandin E1 analogue, used in the treatment of gastric and duodenal ulcers. A weak abortifacient, it is also used for cervical ripening prior to surgical termination of pregnancy. The (11R,16S)-diastereoisomer is the pharmacologically active form.		3.5111
sphingosine 1-phosphate
sphingosine 1-phosphate: RN given refers to (R-(R*,S*-(E)))-isomer; RN for cpd without isomeric designation not available 8/89. sphingosine 1-phosphate : A phosphosphingolipid that consists of sphingosine having a phospho group attached at position 1		2.1110sphingoid 1-phosphatemouse metabolite;
signalling molecule;
sphingosine-1-phosphate receptor agonist;
T-cell proliferation inhibitor;
vasodilator agent
sirolimus
Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.. sirolimus : A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent.		6.4771antibiotic antifungal drug;
cyclic acetal;
cyclic ketone;
ether;
macrolide lactam;
organic heterotricyclic compound;
secondary alcohol		antibacterial drug;
anticoronaviral agent;
antineoplastic agent;
bacterial metabolite;
geroprotector;
immunosuppressive agent;
mTOR inhibitor
casein kinase ii
Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.		2.0510
su 11248
[no description available]		2.1510monocarboxylic acid amide;
pyrroles		angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
immunomodulator;
neuroprotective agent;
vascular endothelial growth factor receptor antagonist
involucrin
involucrin: soluble precursor protein of cross-linked envelope characteristic of epidermal s. corneum synthesized by keratinocytes in natural & cultured human epithelia; see also related records for prekeratin & stratum corneum basic protein precursor		2.110
everolimus
[no description available]		5.5141cyclic acetal;
cyclic ketone;
ether;
macrolide lactam;
primary alcohol;
secondary alcohol		anticoronaviral agent;
antineoplastic agent;
geroprotector;
immunosuppressive agent;
mTOR inhibitor
beta-escin
[no description available]		2.5820
formazans
Formazans: Colored azo compounds formed by the reduction of tetrazolium salts. Employing this reaction, oxidoreductase activity can be determined quantitatively in tissue sections by allowing the enzymes to act on their specific substrates in the presence of tetrazolium salts.		2.0610
mocetinostat
mocetinostat: undergoing phase II clinical trials for treatment of cancer. mocetinostat : A benzamide obtained by formal condensation of the carboxy group of 4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzoic acid with one of the amino groups of benzene-1,2-diamine. It is an orally active and isotype-selective HDAC inhibitor which exhibits antitumour activity (IC50 = 0.15, 0.29, 1.66 and 0.59 muM for HDAC1, HDAC2, HDAC3 and HDAC11).		2.4820aminopyrimidine;
benzamides;
pyridines;
secondary amino compound;
secondary carboxamide;
substituted aniline		antineoplastic agent;
apoptosis inducer;
autophagy inducer;
cardioprotective agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
hepatotoxic agent
ccx282-b
CCX282-B: antagonist of CCR9 chemokine receptor		3.2110
abt-737
[no description available]		2.0810aromatic amine;
aryl sulfide;
biphenyls;
C-nitro compound;
monochlorobenzenes;
N-arylpiperazine;
N-sulfonylcarboxamide;
secondary amino compound;
tertiary amino compound		anti-allergic agent;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
crizotinib
Crizotinib: A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER.. crizotinib : A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)		2.06103-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amineantineoplastic agent;
biomarker;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
sodium salicylate
[no description available]		2.0410organic molecular entity
chitosan
[no description available]		2.2110
oxymatrine
oxymatrine: structure in first source; has anti-apoptosis effects		2.110
piperidines
Piperidines: A family of hexahydropyridines.		2.3110
interleukin-8
Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.		5.5140
vasoactive intestinal peptide
Vasoactive Intestinal Peptide: A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE).		2.0410
transforming growth factor beta
Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.		4.5770
agar
Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis.. agar : A complex mixture of polysaccharides extracted from species of red algae. Its two main components are agarose and agaropectin. Agarose is the component responsible for the high-strength gelling properties of agar, while agaropectin provides the viscous properties.		2.4110
cyclin d1
Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.		2.2510
nitrophenols
Nitrophenols: PHENOLS carrying nitro group substituents.		2.0810
transforming growth factor alpha
Transforming Growth Factor alpha: An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.		2.5220
cyclosporine
Cyclosporine: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).		7.4920
lactoferrin
Lactoferrin: An iron-binding protein that was originally characterized as a milk protein. It is widely distributed in secretory fluids and is found in the neutrophilic granules of LEUKOCYTES. The N-terminal part of lactoferrin possesses a serine protease which functions to inactivate the TYPE III SECRETION SYSTEM used by bacteria to export virulence proteins for host cell invasion.		3.7120
muramidase
Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.		3.5110
metallothionein
Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals.		2.2110
leptin
Leptin: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.		2.2510
ConditionIndicatedRelationship StrengthStudiesTrials
Graft-Versus-Host Disease
[description not available]		09.68212
Graft vs Host Disease
The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.		09.68212
Cancer of the Retina
[description not available]		02.4110
Eye Cancer, Retinoblastoma
[description not available]		02.4110
Retinoblastoma
A malignant tumor arising from the nuclear layer of the retina that is the most common primary tumor of the eye in children. The tumor tends to occur in early childhood or infancy and may be present at birth. The majority are sporadic, but the condition may be transmitted as an autosomal dominant trait. Histologic features include dense cellularity, small round polygonal cells, and areas of calcification and necrosis. An abnormal pupil reflex (leukokoria); NYSTAGMUS, PATHOLOGIC; STRABISMUS; and visual loss represent common clinical characteristics of this condition. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2104)		02.4110
Carcinoma, Non-Small Cell Lung
[description not available]		02.8230
Cancer of Lung
[description not available]		02.4110
Carcinoma, Non-Small-Cell Lung
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.		02.8230
Lung Neoplasms
Tumors or cancer of the LUNG.		02.4110
Heritable Pulmonary Arterial Hypertension
[description not available]		02.4110
Pulmonary Hypertension
[description not available]		08.1950
Pulmonary Arterial Hypertension
A progressive rare pulmonary disease characterized by high blood pressure in the PULMONARY ARTERY.		07.7620
Hypertension, Pulmonary
Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.		03.1950
Familial Primary Pulmonary Hypertension
Familial or idiopathic hypertension in the PULMONARY CIRCULATION which is not secondary to other disease.		02.4110
Constriction, Pathological
[description not available]		02.7220
Colitis, Granulomatous
[description not available]		03.3660
Cirrhosis
[description not available]		02.4110
Constriction, Pathologic
The condition of an anatomical structure's being constricted beyond normal dimensions.		02.7220
Crohn Disease
A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.		03.3660
Fibrosis
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.		07.4110
Intestinal Obstruction
Any impairment, arrest, or reversal of the normal flow of INTESTINAL CONTENTS toward the ANAL CANAL.		02.7220
Innate Inflammatory Response
[description not available]		06.77200
Inflammation
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.		06.77200
Intestinal Diseases
Pathological processes in any segment of the INTESTINE from DUODENUM to RECTUM.		08.5210
Preterm Birth
[description not available]		08.1440
Pregnancy
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.		06.51151
Premature Birth
CHILDBIRTH before 37 weeks of PREGNANCY (259 days from the first day of the mother's last menstrual period, or 245 days after FERTILIZATION).		03.1440
Female Genital Neoplasms
[description not available]		02.610
Cancer of Ovary
[description not available]		03.2150
Genital Neoplasms, Female
Tumor or cancer of the female reproductive tract (GENITALIA, FEMALE).		02.610
Ovarian Neoplasms
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.		03.2150
Acute Disease
Disease having a short and relatively severe course.		07.9371
Sensitivity and Specificity
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)		02.8230
Diabetes Mellitus, Adult-Onset
[description not available]		02.610
Diabetes Mellitus, Type 2
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.		02.610
Diabetic Retinopathy
Disease of the RETINA as a complication of DIABETES MELLITUS. It is characterized by the progressive microvascular complications, such as ANEURYSM, interretinal EDEMA, and intraocular PATHOLOGIC NEOVASCULARIZATION.		02.610
Benign Neoplasms
[description not available]		04.7560
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		04.7560
Benign Neoplasms, Brain
[description not available]		03.1950
Fetal Macrosomia
A condition of fetal overgrowth leading to a large-for-gestational-age FETUS. It is defined as BIRTH WEIGHT greater than 4,000 grams or above the 90th percentile for population and sex-specific growth curves. It is commonly seen in GESTATIONAL DIABETES; PROLONGED PREGNANCY; and pregnancies complicated by pre-existing diabetes mellitus.		02.3110
Compensatory Hyperinsulinemia
A GLUCOSE-induced HYPERINSULINEMIA, a marker of insulin-resistant state. It is a mechanism to compensate for reduced sensitivity to insulin.		02.3110
Diabetes Mellitus, Gestational
[description not available]		02.3110
Brain Neoplasms
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.		03.1950
Hyperinsulinism
A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.		02.3110
Diabetes, Gestational
Diabetes mellitus induced by PREGNANCY but resolved at the end of pregnancy. It does not include previously diagnosed diabetics who become pregnant (PREGNANCY IN DIABETICS). Gestational diabetes usually develops in late pregnancy when insulin antagonistic hormones peaks leading to INSULIN RESISTANCE; GLUCOSE INTOLERANCE; and HYPERGLYCEMIA.		02.3110
Desmoid
[description not available]		03.1710
Carcinogenesis
The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.		03.7330
Adenomatous Polyposis Coli, Familial
[description not available]		03.1710
Invasiveness, Neoplasm
[description not available]		04.3970
Adenomatous Polyposis Coli
A polyposis syndrome due to an autosomal dominant mutation of the APC genes (GENES, APC) on CHROMOSOME 5. The syndrome is characterized by the development of hundreds of ADENOMATOUS POLYPS in the COLON and RECTUM of affected individuals by early adulthood.		03.1710
Fibromatosis, Aggressive
A childhood counterpart of abdominal or extra-abdominal desmoid tumors, characterized by firm subcutaneous nodules that grow rapidly in any part of the body but do not metastasize. The adult form of abdominal fibromatosis is FIBROMATOSIS, ABDOMINAL. (Stedman, 25th ed)		03.1710
Colitis Gravis
[description not available]		03.1950
Colitis, Ulcerative
Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.		03.1950
Hyperoxia
An abnormal increase in the amount of oxygen in the tissues and organs.		02.5920
Chronic Lung Injury
[description not available]		02.5720
Ectopic Pregnancy
[description not available]		02.2510
Pregnancy, Tubal
The most common (		02.520
Pregnancy, Ectopic
A potentially life-threatening condition in which EMBRYO IMPLANTATION occurs outside the cavity of the UTERUS. Most ectopic pregnancies (		02.2510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		03.680
Liver Steatosis
[description not available]		07.2510
Hyperglycemia, Postprandial
Abnormally high BLOOD GLUCOSE level after a meal.		02.5220
Fatty Liver
Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.		02.2510
Hyperglycemia
Abnormally high BLOOD GLUCOSE level.		07.5220
Obesity
A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).		08.5120
Cardiometabolic Syndrome
A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components not only include metabolic dysfunctions of METABOLIC SYNDROME but also HYPERTENSION, and ABDOMINAL OBESITY.		02.2510
Palmoplantaris Pustulosis
[description not available]		03.6180
Psoriasis
A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.		03.6180
Metabolic Syndrome
A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state.		07.2510
Cancer of Cervix
[description not available]		02.8830
Uterine Cervical Neoplasms
Tumors or cancer of the UTERINE CERVIX.		02.8830
Carcinoma, Anaplastic
[description not available]		02.5720
Carcinoma
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for cancer.		02.5720
Cancer of Nasopharynx
[description not available]		02.3110
Nasopharyngeal Neoplasms
Tumors or cancer of the NASOPHARYNX.		02.3110
Hematologic Malignancies
[description not available]		0421
Hematologic Neoplasms
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.		0421
Polyarthritis
[description not available]		02.3110
Arthritis, Degenerative
[description not available]		02.4920
Arthritis
Acute or chronic inflammation of JOINTS.		02.3110
Osteoarthritis
A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.		02.4920
Hepatocellular Carcinoma
[description not available]		08.0640
Cancer of Liver
[description not available]		03.0640
Metastase
[description not available]		03.3760
Carcinoma, Hepatocellular
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.		03.0640
Liver Neoplasms
Tumors or cancer of the LIVER.		03.0640
Neoplasm Metastasis
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.		03.3760
Exanthem
[description not available]		02.3110
Exanthema
Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology.		02.3110
Infections, Pseudomonas
[description not available]		02.9940
Pseudomonas Infections
Infections with bacteria of the genus PSEUDOMONAS.		02.9940
Adenocarcinoma Of Kidney
[description not available]		02.520
Carcinoma, Renal Cell
A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.		02.520
Angioma
A vascular anomaly due to proliferation of blood or lymphatic vessels that forms a tumor-like mass. Vessels in the angioma may or may not be dilated.		02.1510
Angiogenesis, Pathologic
[description not available]		02.7830
Hemangioma
A vascular anomaly due to proliferation of BLOOD VESSELS that forms a tumor-like mass. The common types involve CAPILLARIES and VEINS. It can occur anywhere in the body but is most frequently noticed in the SKIN and SUBCUTANEOUS TISSUE. (from Stedman, 27th ed, 2000)		02.1510
Rheumatoid Arthritis
[description not available]		02.4820
Sclerosis, Systemic
[description not available]		02.5820
Arthritis, Rheumatoid
A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.		02.4820
Scleroderma, Systemic
A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA.		02.5820
Infections, Chlamydia
[description not available]		02.4920
Chlamydia Infections
Infections with bacteria of the genus CHLAMYDIA.		02.4920
Bladder Cancer
[description not available]		02.520
Urinary Bladder Neoplasms
Tumors or cancer of the URINARY BLADDER.		02.520
Bowel Diseases, Inflammatory
[description not available]		02.830
Inflammatory Bowel Diseases
Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.		02.830
Arteriosclerosis, Coronary
[description not available]		04.4822
Complication, Intraoperative
[description not available]		04.4822
Carditis
[description not available]		03.5311
Injury, Myocardial Reperfusion
[description not available]		04.4822
Coronary Artery Disease
Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.		04.4822
Myocarditis
Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.		03.5311
Duhring Disease
[description not available]		02.1710
Dermatitis Herpetiformis
Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis.		07.1710
Drug-Induced Stevens Johnson Syndrome
[description not available]		02.5920
Stevens-Johnson Syndrome
Rare cutaneous eruption characterized by extensive KERATINOCYTE apoptosis resulting in skin detachment with mucosal involvement. It is often provoked by the use of drugs (e.g., antibiotics and anticonvulsants) or associated with PNEUMONIA, MYCOPLASMA. It is considered a continuum of Toxic Epidermal Necrolysis.		02.5920
Breast Cancer
[description not available]		05.49140
Breast Neoplasms
Tumors or cancer of the human BREAST.		05.49140
Bacterial Infections, Gram-Positive
[description not available]		02.2110
Gram-Positive Bacterial Infections
Infections caused by bacteria that retain the crystal violet stain (positive) when treated by the gram-staining method.		02.2110
Bronchopulmonary Dysplasia
A chronic lung disease developed after OXYGEN INHALATION THERAPY or mechanical ventilation (VENTILATION, MECHANICAL) usually occurring in certain premature infants (INFANT, PREMATURE) or newborn infants with respiratory distress syndrome (RESPIRATORY DISTRESS SYNDROME, NEWBORN). Histologically, it is characterized by the unusual abnormalities of the bronchioles, such as METAPLASIA, decrease in alveolar number, and formation of CYSTS.		02.1710
Lung Injury, Ventilator-Induced
[description not available]		02.5220
Adenocarcinoma, Basal Cell
[description not available]		02.7930
Carcinoma, Ductal, Pancreatic
[description not available]		02.2110
Adenocarcinoma
A malignant epithelial tumor with a glandular organization.		02.7930
Carcinoma, Pancreatic Ductal
Carcinoma that arises from the PANCREATIC DUCTS. It accounts for the majority of cancers derived from the PANCREAS.		02.2110
Sexually Transmitted Diseases
Diseases due to or propagated by sexual contact.		02.2110
HIV Coinfection
[description not available]		05.81140
HIV Infections
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).		05.81140
Right Ventricular Dysfunction
[description not available]		02.2110
Skin Ulcer
An ULCER of the skin and underlying tissues.		02.2110
DRESS Syndrome
[description not available]		02.2110
Anasarca
[description not available]		02.2110
Eosinophilia, Tropical
[description not available]		02.2110
Pyrexia
[description not available]		02.2110
Petechiae
Pinhead size (3 mm) skin discolorization due to hemorrhage.		02.2110
Edema
Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.		02.2110
Eosinophilia
Abnormal increase of EOSINOPHILS in the blood, tissues or organs.		02.2110
Fever
An abnormal elevation of body temperature, usually as a result of a pathologic process.		02.2110
Purpura
Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. When the size of the discolorization is		02.2110
Chronic Illness
[description not available]		02.520
Eczema, Atopic
[description not available]		03.9721
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		02.520
Dermatitis, Atopic
A chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. In infants it is known as infantile eczema.		03.9721
Actinic Keratosis
[description not available]		03.5911
Keratosis, Actinic
White or pink lesions on the arms, hands, face, or scalp that arise from sun-induced DNA DAMAGE to KERATINOCYTES in exposed areas. They are considered precursor lesions to superficial SQUAMOUS CELL CARCINOMA.		03.5911
Atherogenesis
[description not available]		04.1630
Atherosclerosis
A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.		04.1630
B-Cell Chronic Lymphocytic Leukemia
[description not available]		02.0810
Leukemia, Lymphocytic, Chronic, B-Cell
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.		02.0810
Genital Herpes
[description not available]		07.0810
Herpes Genitalis
Infection of the genitals (GENITALIA) with HERPES SIMPLEX VIRUS in either the males or the females.		02.0810
Colorectal Cancer
[description not available]		03.9140
Colorectal Neoplasms
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.		03.9140
Disease Exacerbation
[description not available]		03.1850
Cancer of Stomach
[description not available]		02.9940
Stomach Neoplasms
Tumors or cancer of the STOMACH.		02.9940
Genome Instability
[description not available]		02.0810
Carcinoma, Epidermoid
[description not available]		02.5220
Cancer of Head
[description not available]		02.7930
Carcinoma, Squamous Cell
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)		02.5220
Head and Neck Neoplasms
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)		02.7930
Germinoblastoma
[description not available]		02.0810
Symptom Cluster
[description not available]		02.0810
Central Nervous System Neoplasm
[description not available]		02.0810
Local Neoplasm Recurrence
[description not available]		03.0140
Erythema
Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes.		02.0810
Lymphoma
A general term for various neoplastic diseases of the lymphoid tissue.		02.0810
Syndrome
A characteristic symptom complex.		07.0810
Central Nervous System Neoplasms
Benign and malignant neoplastic processes that arise from or secondarily involve the brain, spinal cord, or meninges.		02.0810
Salpingitis
Inflammation of the uterine salpinx, the trumpet-shaped FALLOPIAN TUBES, usually caused by ascending infections of organisms from the lower reproductive tract. Salpingitis can lead to tubal scarring, hydrosalpinx, tubal occlusion, INFERTILITY, and ectopic pregnancy (PREGNANCY, ECTOPIC)		03.4811
Acute Myelogenous Leukemia
[description not available]		03.6930
Leukemia, Myeloid, Acute
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.		03.6930
Breathlessness
[description not available]		03.0110
Experimental Lung Inflammation
Inflammation of any part, segment or lobe, of the lung parenchyma.		03.730
Cough
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. It is a protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions, or to prevent aspiration of foreign materials into the lungs.		03.0110
Dyspnea
Difficult or labored breathing.		03.0110
Pneumonia
Infection of the lung often accompanied by inflammation.		03.730
Disease Resistance
The capacity of an organism to defend itself against pathological processes or the agents of those processes. This most often involves innate immunity whereby the organism responds to pathogens in a generic way. The term disease resistance is used most frequently when referring to plants.		02.4820
Infections, Helicobacter
[description not available]		02.4820
Gastritis
Inflammation of the GASTRIC MUCOSA, a lesion observed in a number of unrelated disorders.		02.4620
Helicobacter Infections
Infections with organisms of the genus HELICOBACTER, particularly, in humans, HELICOBACTER PYLORI. The clinical manifestations are focused in the stomach, usually the gastric mucosa and antrum, and the upper duodenum. This infection plays a major role in the pathogenesis of type B gastritis and peptic ulcer disease.		02.4820
Pocket, Periodontal
[description not available]		02.4820
Pericementitis
[description not available]		02.0810
Periodontal Pocket
An abnormal extension of a gingival sulcus accompanied by the apical migration of the epithelial attachment and bone resorption.		02.4820
Periodontitis
Inflammation and loss of connective tissues supporting or surrounding the teeth. This may involve any part of the PERIODONTIUM. Periodontitis is currently classified by disease progression (CHRONIC PERIODONTITIS; AGGRESSIVE PERIODONTITIS) instead of age of onset. (From 1999 International Workshop for a Classification of Periodontal Diseases and Conditions, American Academy of Periodontology)		02.0810
Osteogenic Sarcoma
[description not available]		02.110
Osteosarcoma
A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)		02.110
Cell Transformation, Neoplastic
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.		02.0810
Premature Rupture of Fetal Membranes
[description not available]		03.4320
Labor, Premature
[description not available]		05.131
Fetal Membranes, Premature Rupture
Spontaneous tearing of the membranes surrounding the FETUS any time before the onset of OBSTETRIC LABOR. Preterm PROM is membrane rupture before 37 weeks of GESTATION.		03.4320
Anoxemia
[description not available]		02.7830
Lymph Node Metastasis
[description not available]		02.5120
Muscle Tissue Neoplasms
[description not available]		02.0810
Hypoxia
Sub-optimal OXYGEN levels in the ambient air of living organisms.		02.7830
Glial Cell Tumors
[description not available]		02.4820
Glioma
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)		02.4820
Pneumothorax, Primary Spontaneous
[description not available]		03.4811
Emphysema, Mediastinal
[description not available]		03.4811
Pneumothorax
An accumulation of air or gas in the PLEURAL CAVITY, which may occur spontaneously or as a result of trauma or a pathological process. The gas may also be introduced deliberately during PNEUMOTHORAX, ARTIFICIAL.		03.4811
Cystadenocarcinoma, Serous
A malignant cystic or semicystic neoplasm. It often occurs in the ovary and usually bilaterally. The external surface is usually covered with papillary excrescences. Microscopically, the papillary patterns are predominantly epithelial overgrowths with differentiated and undifferentiated papillary serous cystadenocarcinoma cells. Psammoma bodies may be present. The tumor generally adheres to surrounding structures and produces ascites. (From Hughes, Obstetric-Gynecologic Terminology, 1972, p185)		02.4820
AIDS Seroconversion
[description not available]		02.110
Genetic Predisposition
[description not available]		02.4720
Inflammatory Response Syndrome, Systemic
[description not available]		02.110
Acute Respiratory Distress Syndrome
[description not available]		05.4751
Respiratory Distress Syndrome
A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA.		05.4751
Systemic Inflammatory Response Syndrome
A systemic inflammatory response to a variety of clinical insults, characterized by two or more of the following conditions: (1) fever		02.110
Cancer of Colon
[description not available]		02.7730
Colonic Neoplasms
Tumors or cancer of the COLON.		02.7730
Cancer of Prostate
[description not available]		02.520
Prostatic Neoplasms
Tumors or cancer of the PROSTATE.		02.520
Encephalopathy, Toxic
[description not available]		02.110
Cognition Disorders
Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment.		02.110
Asthma, Bronchial
[description not available]		02.110
Infections, Picornaviridae
[description not available]		02.4920
Asthma
A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).		02.110
Celiac Sprue
[description not available]		03.7130
Celiac Disease
A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION.		08.7130
Cervix Diseases
[description not available]		02.110
Cystic Fibrosis of Pancreas
[description not available]		03.6930
Cystic Fibrosis
An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.		08.6930
Adenovirus Infections
[description not available]		02.110
Adenoviridae Infections
Virus diseases caused by the ADENOVIRIDAE.		02.110
Chronic Kidney Diseases
[description not available]		02.1110
Acute Kidney Failure
[description not available]		02.1110
Albuminuria
The presence of albumin in the urine, an indicator of KIDNEY DISEASES.		02.1110
Renal Insufficiency, Chronic
Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)		02.1110
Acute Kidney Injury
Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.		02.1110
Carcinoma, Ductal, Breast
An invasive (infiltrating) CARCINOMA of the mammary ductal system (MAMMARY GLANDS) in the human BREAST.		02.110
Atypical Ductal Hyperplasia
[description not available]		02.110
Cystadenoma
A benign neoplasm derived from glandular epithelium, in which cystic accumulations of retained secretions are formed. In some instances, considerable portions of the neoplasm, or even the entire mass, may be cystic. (Stedman, 25th ed)		02.110
Carcinoma, Intraductal, Noninfiltrating
A noninvasive (noninfiltrating) carcinoma of the breast characterized by a proliferation of malignant epithelial cells confined to the mammary ducts or lobules, without light-microscopy evidence of invasion through the basement membrane into the surrounding stroma.		02.110
Astrocytoma, Grade IV
[description not available]		02.4720
Glioblastoma
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.		02.4720
Diathesis
[description not available]		02.1110
Bacterial Vaginitides
[description not available]		02.4820
Vaginosis, Bacterial
Polymicrobial, nonspecific vaginitis associated with positive cultures of Gardnerella vaginalis and other anaerobic organisms and a decrease in lactobacilli. It remains unclear whether the initial pathogenic event is caused by the growth of anaerobes or a primary decrease in lactobacilli.		02.4820
Hormone-Dependent Neoplasms
[description not available]		03.0310
Colitis
Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.		07.4920
Pulmonary Arterial Remodeling
[description not available]		02.1110
Neuroblastoma
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)		02.1110
Malignant Melanoma
[description not available]		02.7730
Melanoma
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)		02.7730
Uveal Neoplasms
Tumors or cancer of the UVEA.		02.1310
Genital Tract Infections
[description not available]		02.1310
Kidney, Polycystic
[description not available]		02.1310
Ciliopathies
Genetic disorders caused by defects in genes related to the primary CILIUM; BASAL BODY; or CENTROSOME. Primary features may include obesity, SKELETAL DYSPLASIA; POLYDACTYLY and malformations that primarily involve the liver, eye or kidneys.		02.1310
Polycystic Kidney Diseases
Hereditary diseases that are characterized by the progressive expansion of a large number of tightly packed CYSTS within the KIDNEYS. They include diseases with autosomal dominant and autosomal recessive inheritance.		02.1310
Angiitis
[description not available]		03.4220
Vasculitis
Inflammation of any one of the blood vessels, including the ARTERIES; VEINS; and rest of the vasculature system in the body.		08.4220
HIV
Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.		08.4220
Atheroma
[description not available]		03.0610
ER-Negative PR-Negative HER2-Negative Breast Cancer
[description not available]		03.5311
Triple Negative Breast Neoplasms
Breast neoplasms that do not express ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and do not overexpress the NEU RECEPTOR/HER-2 PROTO-ONCOGENE PROTEIN.		03.5311
HPV Infection
[description not available]		02.1510
Carcinoma, Squamous Cell of Head and Neck
[description not available]		02.1510
Squamous Cell Carcinoma of Head and Neck
The most common type of head and neck carcinoma that originates from cells on the surface of the NASAL CAVITY; MOUTH; PARANASAL SINUSES, SALIVARY GLANDS, and LARYNX. Mutations in TNFRSF10B, PTEN, and ING1 genes are associated with this cancer.		02.1510
Papillomavirus Infections
Neoplasms of the skin and mucous membranes caused by papillomaviruses. They are usually benign but some have a high risk for malignant progression.		02.1510
Parasitemia
The presence of parasites (especially malarial parasites) in the blood. (Dorland, 27th ed)		02.520
Cerebral Malaria
[description not available]		07.1510
Uterine Prolapse
Downward displacement of the UTERUS. It is classified in various degrees: in the first degree the UTERINE CERVIX is within the vaginal orifice; in the second degree the cervix is outside the orifice; in the third degree the entire uterus is outside the orifice.		02.0410
Disease, Pulmonary
[description not available]		04.8550
Lung Diseases
Pathological processes involving any part of the LUNG.		04.8550
Granulomatosis, Wegener's
[description not available]		02.0510
Granulomatosis with Polyangiitis
A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (VASCULITIS) leading to damage in any number of organs. The common features include granulomatous inflammation of the RESPIRATORY TRACT and KIDNEYS. Most patients have measurable autoantibodies (ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES) against MYELOBLASTIN.		02.0510
Experimental Radiation Injuries
[description not available]		02.0510
Retinal Degeneration
A retrogressive pathological change in the retina, focal or generalized, caused by genetic defects, inflammation, trauma, vascular disease, or aging. Degeneration affecting predominantly the macula lutea of the retina is MACULAR DEGENERATION. (Newell, Ophthalmology: Principles and Concepts, 7th ed, p304)		02.0510
B cepacia Infection
[description not available]		02.0510
Sinus Infections
[description not available]		02.0510
Sinusitis
Inflammation of the NASAL MUCOSA in one or more of the PARANASAL SINUSES.		07.0510
Bacterial Pneumonia
[description not available]		02.9710
Pneumonia, Bacterial
Inflammation of the lung parenchyma that is caused by bacterial infections.		02.9710
Airflow Obstruction, Chronic
[description not available]		02.4720
Cryptogenic Fibrosing Alveolitis
[description not available]		02.0510
Smoking Cessation
Discontinuing the habit of SMOKING.		02.4620
Pulmonary Disease, Chronic Obstructive
A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.		02.4720
Idiopathic Pulmonary Fibrosis
A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change.		02.0510
Diffuse Large B-Cell Lymphoma
[description not available]		02.0510
Lymphoma, Large B-Cell, Diffuse
Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.		02.0510
Chromosomal Instability
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.		02.9710
Microsatellite Instability
The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.		02.9710
Leucocythaemia
[description not available]		02.0510
Leukemia
A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)		02.0510
Fallopian Tube Diseases
Diseases involving the FALLOPIAN TUBES including neoplasms (FALLOPIAN TUBE NEOPLASMS); SALPINGITIS; tubo-ovarian abscess; and blockage.		02.0610
Cancer of Skin
[description not available]		02.0610
Skin Neoplasms
Tumors or cancer of the SKIN.		02.0610
Carcinoma, Transitional Cell
A malignant neoplasm derived from TRANSITIONAL EPITHELIAL CELLS, occurring chiefly in the URINARY BLADDER; URETERS; or RENAL PELVIS.		02.4720
Acute Hypercapnic Respiratory Failure
[description not available]		02.7630
Respiratory Insufficiency
Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)		02.7630
Neointima
The new and thickened layer of scar tissue that forms on a PROSTHESIS, or as a result of vessel injury especially following ANGIOPLASTY or stent placement.		02.0610
B Virus Infection
[description not available]		02.0610
Cancer of Kidney
[description not available]		02.0610
Kidney Neoplasms
Tumors or cancers of the KIDNEY.		02.0610
Leishmaniasis, American
[description not available]		02.0610
Trypanosomiasis
Infection with protozoa of the genus TRYPANOSOMA.		02.0610
Leishmaniasis, Cutaneous
An endemic disease that is characterized by the development of single or multiple localized lesions on exposed areas of skin that typically ulcerate. The disease has been divided into Old and New World forms. Old World leishmaniasis is separated into three distinct types according to epidemiology and clinical manifestations and is caused by species of the L. tropica and L. aethiopica complexes as well as by species of the L. major genus. New World leishmaniasis, also called American leishmaniasis, occurs in South and Central America and is caused by species of the L. mexicana or L. braziliensis complexes.		02.0610
Vascular Diseases
Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.		02.9810
Attachment Loss, Periodontal
[description not available]		02.0710
Adult Periodontitis
[description not available]		02.4820
Dental Plaque
A film that attaches to teeth, often causing DENTAL CARIES and GINGIVITIS. It is composed of MUCINS, secreted from salivary glands, and microorganisms.		02.0710
Hemorrhage, Gingival
[description not available]		02.0710
Gingival Hemorrhage
The flowing of blood from the marginal gingival area, particularly the sulcus, seen in such conditions as GINGIVITIS, marginal PERIODONTITIS, injury, and ASCORBIC ACID DEFICIENCY.		02.0710
Acne Rosacea
[description not available]		02.9810
Rosacea
A cutaneous disorder primarily of convexities of the central part of the FACE, such as FOREHEAD; CHEEK; NOSE; and CHIN. It is characterized by FLUSHING; ERYTHEMA; EDEMA; RHINOPHYMA; papules; and ocular symptoms. It may occur at any age but typically after age 30. There are various subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous, and ocular (National Rosacea Society's Expert Committee on the Classification and Staging of Rosacea, J Am Acad Dermatol 2002; 46:584-7).		02.9810
Blood Clot
[description not available]		02.9910
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.		02.9910
Thrombosis
Formation and development of a thrombus or blood clot in the blood vessel.		02.9910
Aggressive Periodontitis
Inflammation and loss of PERIODONTIUM that is characterized by rapid attachment loss and bone destruction in the presence of little local factors such as DENTAL PLAQUE and DENTAL CALCULUS. This highly destructive form of periodontitis often occurs in young people and was called early-onset periodontitis, but this disease also appears in old people.		02.0710
Gingivitis
Inflammation of gum tissue (GINGIVA) without loss of connective tissue.		02.0710
Epithelial Ovarian Cancer
[description not available]		02.0710
Epithelial Neoplasms
[description not available]		02.0710
Carcinoma, Ovarian Epithelial
A malignant neoplasm that originates in cells on the surface EPITHELIUM of the ovary and is the most common form of ovarian cancer. There are five histologic subtypes: papillary serous, endometrioid, mucinous, clear cell, and transitional cell. Mutations in BRCA1, OPCML, PRKN, PIK3CA, AKT1, CTNNB1, RRAS2, and CDH1 genes are associated with this cancer.		02.0710
Infections, Rhabdoviridae
[description not available]		02.0710
Bacterial Disease
[description not available]		03.3920
Fungal Diseases
[description not available]		02.9910
Viral Diseases
[description not available]		02.9910
Bacterial Infections
Infections by bacteria, general or unspecified.		03.3920
Mycoses
Diseases caused by FUNGI.		02.9910
Virus Diseases
A general term for diseases caused by viruses.		02.9910
Co-infection
[description not available]		02.0710
Lung Injury, Acute
[description not available]		02.0810
Acute Lung Injury
A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological).		07.0810
Dermatoses
[description not available]		03.3720
Skin Diseases
Diseases involving the DERMIS or EPIDERMIS.		03.3720
Acute Confusional Senile Dementia
[description not available]		02.0310
Alzheimer Disease
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)		02.0310
Emphysema
A pathological accumulation of air in tissues or organs.		02.4420
Skin Aging
The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight.		03.3520
Hyperplasia
An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.		02.0310
Granulocytic Leukemia
[description not available]		02.0310
Leukemia, Myeloid
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.		02.0310
Anaplastic Astrocytoma
[description not available]		02.0410
Astrocytoma
Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082)		02.0410
Abortion, Tubal
[description not available]		02.0410
Abortion, Spontaneous
Expulsion of the product of FERTILIZATION before completing the term of GESTATION and without deliberate interference.		02.0410