ALDH Cancer Research Results

ALDH, Aldehyde Dehydrogenase: Click to Expand ⟱

Source:

Type:

ALDH (Aldehyde Dehydrogenase) is a family of enzymes that play a crucial role in various cellular processes, including detoxification, differentiation, and cell survival. In the context of cancer, ALDH has been implicated in several aspects of tumor biology.

ALDH enzymes are involved in the metabolism of aldehydes, which are toxic compounds that can damage cellular components. In cancer cells, ALDH enzymes can help to detoxify these compounds, promoting cell survival and resistance to chemotherapy.

There are 19 different ALDH isoforms, and each has a distinct expression pattern in cancer. Some isoforms, such as ALDH1A1 and ALDH1A3, are more commonly associated with cancer stem cells, while others, such as ALDH2, are more widely expressed in cancer cells.

Highly Expressed: Brain, overian, prostate, pancreatic, liver, stomach, esophageal, head and neck, melanoma, ALL, CML

Scientific Papers found: Click to Expand⟱

3454-

ALA,

Lipoic acid blocks autophagic flux and impairs cellular bioenergetics in breast cancer and reduces stemness

in-vitro,

BC,

MCF-7

(0.5 mM, 1 mM, 2.5 mM, and 5 mM)

in-vitro,

BC,

MDA-MB-231

TumCG↑, Lipoic acid inhibits breast cancer cell growth via accumulation of autophagosomes.
Glycolysis↓, Lipoic acid inhibits glycolysis in breast cancer cells.
ROS↑, Lipoic acid induces ROS production in breast cancer cells/BCSC.
CSCs↓, Here, we demonstrate that LA inhibits mammosphere formation and subpopulation of BCSCs
selectivity↑, In contrast, LA at similar doses. had no significant effect on the cell viability of the human embryonic kidney cell line (HEK-293)
LC3B-II↑, LA treatment (0.5 mM and 1.0 mM) increased the expression level of LC3B-I to LC3B-II in both MCF-7 and MDA-MB231cells at 48 h
MMP↓, LA induced mitochondrial ROS levels, decreased mitochondria complex I activity, and MMP in both MCF-7 and MDA-MB231 cells
mitResp↓, In MCF-7 cells, we found a substantial reduction in maximal respiration and ATP production at 0.5 mM and 1 mM of LA treatment after 48 h
ATP↓,
OCR↓, LA at 2.5 mM decreased OCR
NAD↓, we found that LA (0.5 mM and 1 mM) significantly reduced ATP production and NAD levels in MCF-7 and MDA-MB231 cells
p‑AMPK↑, LA treatment (0.5 mM and 1.0 mM) increased p-AMPK levels;
GlucoseCon↓, LA (0.5 mM and 1 mM) significantly decreased glucose uptake and lactate production in MCF-7, whereas LA at 1 mM significantly reduced glucose uptake and lactate production in MDA-MB231 cells but it had no effect at 0.5 mM
lactateProd↓,
HK2↓, LA reduced hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) expression in MCF-7 and MDA-MB231 cells
PFK↓,
LDHA↓,
eff↓, Moreover, we found that LA-mediated inhibition of cellular bioenergetics including OCR (maximal respiration and ATP production) and glycolysis were restored by NAC treatment (Fig. 6E and F) which indicates that LA-induced ROS production is responsibl
mTOR↓, LA inhibits mTOR signaling and thereby decreased the p-TFEB levels in breast cancer cells
ECAR↓, LA also inhibits glycolysis as evidenced by decreased glucose uptake, lactate production, and ECAR.
ALDH↓, LA decreased ALDH1 activity, CD44+/CD24-subpopulation, and increased accumulation of autophagosomes possibly due to inhibition of autophagic flux of breast cancer.
CD44↓,
CD24↓,

2289-

Ba,

Rad,

Baicalein Inhibits the Progression and Promotes Radiosensitivity of Esophageal Squamous Cell Carcinoma by Targeting HIF-1A

in-vitro,

ESCC,

KYSE150

20uM

TumCP↓, Radiation combined with baicalein could significantly inhibit the proliferation and migration of esophageal cancer cells compared with that of 6 Gy rays alone
TumCMig↓,
Glycolysis↓, 20μM baicalein reduced glycolysis in KYSE150 cells
cycD1/CCND1↓,
CDK4↓,
ECAR↓, Baicalein reduces ECAR and glycoPER
TumCCA↑, baicalein arrested cells in the G1 phase of the cell cycle
HK1↓, HK1 (4QS9),13 ALDH2, GPI and ALDOA are the key enzymes in the process of glycolysis.
ALDH↓,
ALDOA↓,
PKM2↓, protein levels of HIF-1A and PKM2 decreased significantly after baicalein treatment.
Hif1a↓,

6216-

CUR,

Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials

Review,

Var,

TumCG↓, Curcumin can prevent tumor growth, angiogenesis, epithelial–mesenchymal transition, invasion, and metastasis by modulating the expression of tumor-related non-coding RNA (ncRNA)
angioG↓,
EMT↓,
TumCI↓,
TumMeta↓,
*GutMicro↑, curcumin plays a crucial role in regulating the gut microbiota via biotransformation of curcumin and its metabolites.
*BioAv↓, one of the primary drawbacks of taking curcumin alone is its low bioavailability, which appears to be caused by poor absorption, fast metabolism, and excretion
*HO-1↑, Curcumin is an efficient inducer of hemoxygenase-1 and a powerful inhibitor of reactive oxygen-generating enzymes, such as cyclooxygenase (COX), inducible nitric oxygen synthase (iNOS), lipoxygenase, and xanthine dehydrogenase/oxidase
*ROS↓,
*COX2↓,
*iNOS↓,
PKCδ↓, Curcumin is also a powerful inhibitor of protein kinase C (PKC), tyrosine kinase, epidermal growth factor receptor (EGFR), and IB kinase.
EGFR↓,
NF-kB↓, It suppresses NF-κB activation and the expression of oncogenes, such as c-jun, c-fos, c-myc, Akt, PI3K, cyclin-dependent kinase (CDK)
cJun↓,
cFos↓,
cMyc↓,
Akt↓,
PI3K↓,
CDK4↓,
*TNF-α↓, Continuous supplementation with nanocurcumin (two 40 mg capsules/day after a meal) for 3 months suppressed expression of inflammatory tumor necrosis factor-alpha (TNF-α), high sensitive protein with C-reactive protein (CRP), and interleukin-6 (IL-6)
*CRP↓,
*IL6↓,
MMP9↓, curcumin suppressed metastasis to the lung by suppressing NF-κB, MMP-9, COX-2, and vascular endothelial growth factor (VEGF) expression.
VEGF↓,
JAK↓, Curcumin remarkably inhibits JAK/STAT signaling by downregulating pro-inflammatory interleukins, such as IL-1, IL-2, IL-6, IL-8, IL-12, and MCP-1.
STAT↓,
IL1↓,
IL2↓,
IL6↓,
IL8↓,
IL12↓,
MCP1↓,
Apoptosis↑, It promotes apoptosis and ER stress by targeting phosphorylated protein kinase-like ER-resident kinase,
ER Stress↑,
5LO↓, inhibiting lipoxygenase and xanthine oxidase activity
XO↓,
*NRF2↑, The expression of nuclear factors erythroid 2-related factor (Nrf2) and heme oxygenase 1 (HO-1) is boosted by curcumin
*HO-1↑,
*AChE↓, Curcumin also inhibits the key enzyme acetylcholinesterase (AChE) and p300, a positive regulator of the Wnt/β-catenin pathway
*neuroP↑, Curcumin has also been suggested to prevent and cure neurotoxicity by replenishing dopamine and 3,4-dihydroxyphenylacetic acid levels.
*glucose↓, remarkably lowers blood glucose levels and improves insulin resistance by reducing hepatic glucose synthesis, inhibiting inflammatory reactions produced by hyperglycemia,
*GLUT2↑, boosting glucose transporters 2 (GLUT2), 3 (GLUT3), and 4 (GLUT4) gene expression, enhancing glucose uptake, and activating the AMPK signaling pathway.
*GLUT3↑,
*GLUT4↑,
*GlucoseCon↑,
*AMPK↑,
*BMD↑, Supplementation with nanomicelle curcumin (80 mg) alone or in combination with Nigella sativa oil (1000 mg) for 2–6 months increased plasma levels of miRNA-21 in postmenopausal women with low bone mass density.
*MDA↓, (1000 mg/day) for 8 weeks reduced serum levels of malondialdehyde (MDA) and high-sensitivity CRP (hs-CRP) and increased the total antioxidant capacity in 81 healthy postmenopausal women
*eff↑, Loriczova et al. demonstrated that iron (18 mg and 65 mg) supplementation along with curcumin (500 mg) reduces iron-induced systemic inflammation by reducing plasma levels of TNF-α
eff↑, high-dose vitamin C (25–100 g/day) along with oral nutrient supplementation including curcumin (1–3 g/day) had improved QoL and survival
P53↑, Curcumin was also reported to induce p53 and Bax expression in patients with colorectal cancer, causing apoptosis and DNA fragmentation and suppressing TNF-α and Bcl-2.
BAX↑,
DNAdam↑,
Bcl-2↓,
CSCs↓, The combination of curcumin, 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in colorectal liver metastases reduced stem cell markers, such as aldehyde dehydrogenase and CD133.
ALDH↓,
CD133↑,

6238-

CUSP9,

A phase Ib/IIa trial of 9 repurposed drugs combined with temozolomide for the treatment of recurrent glioblastoma: CUSP9v3

Trial,

GBM,

Ten adults with histologically confirmed GBM and recurrent or progressive disease were included.

toxicity↓, CUSP9v3 is safe in patients with recurrent GBM.
TrxR↓, The anti-rheumatoid arthritis drug auranofin inhibits thioredoxin reductase, resulting in increased intracellular reactive oxygen species
ROS↓,
TumCI↓, The anti-hypertensive captopril reduces invasion, migration and adhesion of GBM cell activity through soluble matrix metalloproteinase (MMP)-2 and MMP-9 inhibition.12
TumCMig↓,
TumCA↓,
MMP2↓,
MMP9↓,
COX2↓, celecoxib has long been shown to have anticancer properties related to cyclooxygenase-2 inhibition and has demonstrated encouraging results in combination with low-dose temozolomide
ALDH↓, alcohol deterrent disulfiram is consistently cytotoxic to a wide range of cancer cells and is effective against GBM stem cells through aldehyde dehydrogenase inhibition.15
TumAuto↑, itraconazole likely exerts its anticancer activity due to its multiple pharmacological effects16 with specific data in GBM pointing towards an effect on autophagy
P-gp↓, the antidepressant sertraline was included for its ability to inhibit P-glycoprotein at the blood-brain barrier21
eff↑, Best overall response was stable disease (SD) in 6 patients and progressive disease (PD) in 4 patients

6237-

CUSP9,

CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide

NA,

GBM,

PI3K↓, ARTESUNATE phosphoinositide 3-kinase, Akt, increases ROS, NF-κB activation, TNF-alpha, IL-6, TLR2,
Akt↓,
ROS↑,
NF-kB↓,
TNF-α↓,
TLR2↓,
other↓, APREPITANT 10 hrs NK-1 receptors
TrxR↓, AURANOFIN 10 days thioredoxin, increases ROS, STAT3
STAT3↓,
MMPs↓, CAPTOPRIL 2 hrs ACE, AT1 receptors, MMPs
COX1↓, CELECOXIB 9 hrs COX-1 and -2, carbonic anhydrase -2 and -9
COX2↓,
CA↓,
ALDH↓, DISULFIRAM ALDH, increases ROS
P-gp↓, ITRACONAZOLE P-gp efflux transporters, BCRP, Hedgehog, 5-lipoxygenase
HH↓,
5LO↓,
mTOR↓, RITONAVIR P-gp efflux transporters [weak], Akt, mTOR, cyclin D3, proteasome,
CycD3↓,
Proteasome↓,
other↓, SERTRALINE Akt, mTOR, TCTP
MMP2↓, Captopril inhibited the activity of soluble MMP-2 and MMP-9
MMP9↓,
ALDH↓, Disulfiram potent inhibitor of all isoforms of aldehyde dehydrogenase, ALDH, disulfiram stops ethanol metabolism at the acetaldehyde stage
Copper↓, Since disulfiram chelates Cu++ in the stomach even without adding exogenous Cu

6245-

Cyc,

Blockade of Hedgehog Signaling Inhibits Pancreatic Cancer Invasion and Metastases: A New Paradigm for Combination Therapy in Solid Cancers

vitro+vivo,

PC,

seven mice

HH↓, Hh inhibition with cyclopamine resulted in down-regulation of snail and up-regulation of E-cadherin, consistent with inhibition of epithelial-to-mesenchymal transition,
Snail↓,
E-cadherin↑,
EMT↓,
TumCI↓, striking reduction of in vitro invasive capacity
ChemoSen↑, Combination of gemcitabine and cyclopamine completely abrogated metastases while also significantly reducing the size of “primary” tumors.
TumMeta↓, Cyclopamine abrogates metastases in an orthotopic xenograft model of pancreatic cancer and synergizes with gemcitabine
ALDH↓, Cyclopamine treatment preferentially reduces the ALDH-expressing population in pancreatic cancer cells
eff↑, We believe that our results provide a compelling rationale for exploring Hh inhibitors in human pancreatic cancer, particularly from the standpoint of therapy of metastatic disease.

4914-

DSF,

immuno,

Disulfiram and cancer immunotherapy: Advanced nano-delivery systems and potential therapeutic strategies

Review,

Var,

AntiTum↑, potential as an anti-tumor agent and even as an enhancer of cancer immunotherapy
eff↑, Targeted delivery: through nanotechnology, specific delivery of disulfiram to tumor sites can be achieved to minimize damage to normal tissues and increase drug accumulation in tumor cells
ALDH↓, It works by inhibiting an enzyme called Aldehyde Dehydrogenase (ALDH).
Dose↝, DSF is not only affordable at $20–40 for a daily dose of 250 mg taken orally in the USA, but it is also considered to be safe, allowing for long-term treatment at the same dosage.
RadioS↑, DSF/Cu can enhance the effects of ionizing radiation and induce ICD in breast cancer
angioG↓, inhibition of angiogenesis and metastasis, make it a versatile agent in combating cancer
TumMeta↓,
BioAv↝, limitations associated with its delivery, solubility, and off-target toxicity have prompted the development of innovative strategies to improve its clinical efficacy
ROS↑, DSF effectively treats tumors. Such as increasing the production of ROS, causing DNA damage, and impeding enzyme activity.
DNAdam↑,
P-gp↓, DSF can target P-glycoprotein (P-gp) dysfunction, cancer stem cells (CSCs), and hinder the process of epithelial-mesenchymal transition (EMT).
CSCs↓,
EMT↓,
Imm↑, DSF stimulates the immune system
SOD↓, generation of ROS, inhibition of the superoxide dismutase activity and activation of the mitogen-activated protein kinase (MAPK)
MAPK↓,
NF-kB↓, NF-κB inhibiting activity of DSF could be attributed to their inhibition of the proteasome and degradation other regulatory redox-sensitive proteins.
ChemoSen↑, therapeutic effect of combining DSF with conventional cancer drugs like cisplatin and doxorubicin (DOX) has been proven to be enhanced.
eff↑, combination use of DSF with immunotherapy has shown remarkable success in preclinical and clinical studies.
toxicity↝, The administration of disulfiram necessitates the complete abstinence from alcohol
BioAv↑, researchers use lipid nanoparticles as carriers for disulfiram and used to improve its bioavailability and reduce side effects.
*Inflam↓, DSF has the ability to inhibit inflammation, which has potential applications in treating various inflammatory diseases,
Sepsis↓, Mice with sepsis experienced reduced mortality when administered with DSF-loaded lactoferrin nanoparticles,

5012-

DSF,

Cu,

Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems

ROS↑, DSF’s anticancer mechanism is primarily due to its generating reactive oxygen species, inhibiting aldehyde dehydrogenase (ALDH) activity inhibition, and decreasing the levels of transcriptional proteins
ALDH↓,
TumCP↓, DSF also shows inhibitory effects in cancer cell proliferation, the self-renewal of cancer stem cells (CSCs), angiogenesis, drug resistance, and suppresses cancer cell metastasis.
CSCs↓,
angioG↓,
TumMeta↓,
DNAdam↑, anti-cancer mechanism of DSF/Cu (II) may be mediated by the regulation of reactive oxygen species (ROS), enzyme activity regulation, induction of DNA damage, proteasome inhibition, and transcription factors
Proteasome↓,
SOD1↓, The complex of DSF and Cu (II)has been reported to inhibit the enzyme superoxide dismutase 1 (SOD1), one of the major enzymesthat mitigates oxidative damage in melanoma cells
GSR↓, The inhibition of Glutathione reductase (GSR) inhibition by DSF disrupts glutathione GSH redox cycling, producing an accumulation of oxidized glutathione (GSSG) and a lower GSH/GSSG ratio, producing an increase in ROS level
ox-GSSG↑,
GSH/GSSG↓,
MMP↓, DSF induces the disruption of the mitochondrial membrane potential and cause apoptosis in human melanoma cell lines
Akt↓, induced the apoptosis of erbB2-positive breast cancer cells by inhibiting AKT, cyclin D1, and NFκB signaling
cycD1/CCND1↓,
NF-kB↓,
CSCs↓, In hepatocellular carcinoma, DSF decreases CSCs by inhibiting the p38 mitogen-activated protein kinase (MAPK) pathway [118].
MAPK↓,
angioG↓, Thus, the inhibition of DSF/Cu (II) in CSCs decrease angiogenesis.
DrugR↓, DSF/Cu (II) overcomes drug resistance via targeting the proteasome, epithelial–mesenchymal transition (EMT), P-gp, CSC activity
EMT↓,
Vim↓, By downregulating associated proteins such as Vimentin, DSF/Cu (II) inhibits the EMT, which consequently overcomes the paclitaxel resistance of prostate and lung cancer
BioAv↑, The use of these nanoparticle-based formulations can increase the accumulation of DSF at the target site, thereby reducing the toxic effects on healthy tissues and improving the therapeutic index.
eff↑, In clinical trials, DSF is provided orally, but Cu (II) is critical for the efficacy of DSF

6325-

Eug,

Anticancer Properties of Eugenol: A Review

Review,

Var,

*antiOx↑, long been utilized all over the world as a result of its broad properties like antioxidant, anticancer, anti-inflammatory, and antimicrobial activities. Both eugenol and clove oil display potent antioxidant capabilities.
*AntiCan↑,
*Inflam↓, Eugenol Anti-Inflammatory Agent
TumCD↑, Anticancer effects of eugenol are accomplished by various mechanisms like inducing cell death, cell cycle arrest, inhibition of migration, metastasis, and angiogenesis on several cancer cell lines.
TumCCA↑,
TumCMig↓,
TumMeta↓,
angioG↓,
ChemoSen↑, eugenol might be utilized as an adjunct remedy for patients who are treated with conventional chemotherapy. This combination leads to a boosted effectiveness with decreased toxicity.
chemoP↑,
*BioAv↝, Eugenol is an aromatic pale yellowish liquid that dissolves well in organic solvents and moderately in water.
*BioAv↑, Eugenol is susceptible to oxidation and many biochemical interactions. It is quickly absorbed via diverse organs and processed in the liver when taken orally.
*BioAv↑, encapsulation of eugenol appears to be the finest approach for avoiding early absorption, improving its water solubility, and, therefore, increasing its action.
*BioAv↑, when eugenol is supplied as solid lipid nanoparticles, the quantity of eugenol delivered to infected cells upsurges by at least sixfold
*Bacteria↓, Eugenol is well-known for its antibacterial properties.
*ROS↓, They possess a potent DPPH radical scavenging influence (half maximal inhibitory concentration (IC50) = 11.7 μg/mL for eugenol; 13.2 μg/mL for clove oil) and hinder reactive oxygen species (ROS) generation in human neutrophils
*IL6↓, exposure of rats to eugenol (10.7 mg/kg body weight/day) for 15 days reduced the translation of inflammatory markers (IL-6, COX-2, and TNF-α), lipid peroxidation indices, and protein oxidation [51].
*COX2↓,
*TNF-α↓,
*lipid-P↓,
*SOD1↑, Pretreatment with eugenol was capable of dramatically enhancing SOD1, CAT, Gpx1, and GST levels as well as decreasing inflammation triggered via lung exposure to LPS.
*Catalase↑,
*GPx1↑,
*GSTs↑,
ROS↑, Eugenol triggered cell apoptosis in these cancerous cells through a process reliant on elevated ROS production and decreased the mitochondrial membrane potential, indicating that it might possess apoptosis-triggering characteristics
MMP↓,
Apoptosis↑,
COX2↓, Lung cancer in vitro low concentrations to 1000 μM reduces cyclooxygenase-2 activity, promotes cell cycle arrest at S-phase
TumCCA↑,
E2Fs↓, Breast cancer in vitro and in vivo 2 µM down regulating E2F1
PI3K↓, inhibition of the PI3K/Akt pathway and prevention of MMP (matrix metalloproteinase) action, an in-laboratory study using lung cancer
Akt↓,
MMPs↓,
CSCs↓, CSC markers like Oct4, CD44, EpCAM, and Notcht1, whose expression is reliant on β-catenin, were considerably reduced,
OCT4↓,
CD44↓,
EpCAM↓,
NOTCH1↓,
TumVol↓, Eugenol works through the synthesis of ROS [82], which leads to DNA synthesis inhibition, hence postponing cancer progress. A 40% decrease was documented in tumor size via eugenol activity
Casp3↑, Elevated caspase-3, p53, and PARP cleavage levels are associated with eugenol-triggered apoptosis in HOS cells
P53↑,
cl‑PARP↑,
MMP2↓, Eugenol-treated cells demonstrated substantially reduced expression of MMP2 and MMP9 and an insignificant rise in the expression of TIMP1 in HER2-positive and triple-negative breast cancer cells.
MMP9↓,
TIMP1↑,
ALDH↓, Eugenol is thought to help cisplatin suppress breast cancer stem cells by hindering the action of aldehyde dehydrogenases (ALDH) and ALDH-positive cancer beginning cells, as well as inhibiting the NF-B signaling pathway.
NF-kB↓,
*toxicity↓, Overall, the toxic effect of eugenol on mammals is low, and the US Environmental Protection Agency has categorized eugenol as category 3. The oral LD50 value is >1930 mg kg−1 in rodents

6330-

Eug,

Molecular Mechanisms of Action of Eugenol in Cancer: Recent Trends and Advancement

Review,

Var,

TumCD↑, investigations reveal eugenol inducing cytotoxicity, inhibiting phases of the cell cycles, programmed cell death, and auto-phagocytosis in studied cancer lines; thus, portraying eugenol as a promising anticancer molecule.
TumCCA↑,
AntiCan↑,
Apoptosis↑, The suggested techniques can be enlisted as induction of apoptosis, cell cycle arrest, reducing angiogenesis, interplaying dual roles as an oxidant and pro-oxidant, inhibiting inflammation, and stopping cellular invasion and metastasis.
angioG↓,
TumCI↓,
TumMeta↓,
ChemoSen↑, Combining cisplatin (30 µM) with eugenol (1 µM) potentiated its chemotherapeutic activity by inhibiting aldehyde dehydrogenases (ALDH) enzyme activity, impeding the nuclear factor kappa B (NF-κB) and signaling cascade by reducing binding affinity of
ALDH↓,
NF-kB↓,
IL6↓, downregulating IL-6 and IL-8 mRNA (messenger ribonucleic acid).
IL8↓,
BAX↑, Increased Bcl-2/Bax ratio, elevated levels of proapoptotic protein Bax, increased expression of cleaved caspases-3 and -9, cleaved poly (ADP-ribose) polymerase (PARP) on the higher side
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
Bcl-2↓, epression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) accounted for the apoptotic potential for the combination of eugenol and cisplatin.
MMP2↓, repression of the expression level of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) explained the inhibition of the invasive tendency of the TNBCs by combination therapy
MMP9↓,
EMT↓, Reduced epithelial-to-mesenchymal transition (EMT) was evident from reduced expressions of N-cadherin and Snail1 and higher E-cadherin expression.
N-cadherin↓,
Snail↓,
E-cadherin↑,
SOX2↓, Inhibition of pluripotency was evident by reduced expression of biomarker Sox-2 [(sex determining region Y)-box 2]
ROS↑, (MCF-7) (IC50: 22.75 𝜇M) and MDA-MB-231 (IC50: 15.09 𝜇M) breast cancer cells with increasing ROS levels which inhibited cell cycle at G2/M phase, that leads to clastogenesis in vitro.
PCNA↓, downregulated the proliferation of the cell nuclear antigen (PCNA) associated with deceased mitochondria membrane potential (ΔΨm) and upregulation of Bcl-2 associated X protein (Bax)
MMP1↓,
Cyt‑c↑, release of cytochrome-c and lactate dehydrogenase was also observed at a concentration of eugenol of more than 0.9 mM.
LDH↑,
CSCs↓, Downregulation of cancer stem cell markers octamer-binding transcription factor 4 (oct4), Notch1 (Neurogenic locus notch homolog protein 1), epithelial cellular adhesion molecule (EpCAM), and CD44 was observed in the stem cells
OCT4↓,
NOTCH1↓,
EpCAM↓,
CD44↓,
HER2/EBBR2↓, A therapeutic dose (80 μM) of eugenol was shown to cease the proliferating of human epidermal growth factor of receptor 2 (HER-2) positive MCF-10AT cell lines by 32.8%.
VEGF↓, The expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 1 (VEGFR1), and MMPs are all reduced by eugenol, while that of reversion-inducing-cysteine-rich protein with kazal motifs (RECK) and TIMP-2 is in
TIMP2↑,
eff↑, Eugenol-loaded chitosan nanopolymers (IC50: 7.5 µM) convincingly induce apoptosis and inhibition of metastasis in rat C6 glioma cells.
Ca+2↑, Eugenol (100–300 µM) stimulated PLC-dependent Ca2+ discharge from the endoplasmic reticulum and promoted Ca2+ influx
TumVol↓, Eugenol significantly reduced tumors (nearly 40%) and delayed the time to the endpoint (by 19%) in B16 melanoma xenografts.
DNAdam↑, EUG MCF-7 cells ↑ DNA fragmentation, ↓ intracellular glutathione level, ↑ intracellular H2O2 and lipid peroxidation, ↑ apoptosis 1–4 mM
GSH↓,
H2O2↑,
lipid-P↑,

4949-

PEITC,

Phenethyl Isothiocyanate Exposure Promotes Oxidative Stress and Suppresses Sp1 Transcription Factor in Cancer Stem Cells

in-vitro,

Cerv,

HeLa

ROS↑, Cruciferous vegetable-derived phenethyl isothiocyanate (PEITC) selectively induces reactive oxygen species (ROS), leading to apoptosis of cancer cells, but not healthy cells.
selectivity↑,
CSCs↓, PEITC treatments resulted in a reduced number of ALDHhi hCSCs in a concentration-dependent manner
Sp1/3/4↓, PEITC suppressed the cancer-associated transcription factor (Sp1) and a downstream multidrug resistance protein (P-glycoprotein)
P-gp↓,
ALDH↓, PEITC inhibits ALDH2 in the liver
GSH↓, The electrophilic property of PEITC has been shown to covalently interact with nucleophilic glutathione (GSH), leading to ROS-induction in cells
TumCP↓, Phenethyl Isothiocyanate Treatment Suppressed HeLa Cancer Stem Cells Proliferation and Increased Early Apoptosis
Apoptosis↑,

4956-

PEITC,

Inhibition of cancer growth in vitro and in vivo by a novel ROS-modulating agent with ability to eliminate stem-like cancer cells

vitro+vivo,

Lung,

A549

 IC50 value from 11.6 μM for PEITC down to 4.1 μM for LBL21

GSH↓, synthetic analog of PEITC with superior in vitro and in vivo antitumor effects. Mechanistic study showed that LBL21 induced a rapid depletion of intracellular glutathione (GSH), leading to abnormal ROS accumulation
ROS↑,
mtDam↑, and mitochondrial dysfunction, evident by a decrease in mitochondrial respiration and transmembrane potential.
mitResp↓,
MMP↓,
CSCs↓, Importantly, LBL21 exhibited the ability to abrogate stem cell-like cancer side population (SP) cells in non-small cell lung cancer A549
OCT4↓, with a downregulation of stem cell markers including OCT4, ABCG2, SOX2 and CD133.
ABC↓,
SOX2↓,
CD133↓,
CD44↓, LBL21 caused a significant decrease in various CSC biomarkers CD44, CD133, OCT4, ABCG2, SOX2, ALDH2 and NANOG in mRNA expression levels
ALDH↓,
Nanog↓,
TumCG↓, LBL21 substantially suppressed tumor growth in A549 xenograft mice

4957-

PEITC,

Phenethyl Isothiocyanate (PEITC) from Cruciferous Vegetables Targets Human Cancer Stem-Like Cells

vitro+vivo,

Cerv,

HeLa

10 µM PEITC-

 human cervical HeLa CSC (hCSC) in vitro and on attenuation of tumorigenicity in hCSC-transplanted mice.

CSCs↓, PEITC attenuated proliferation of sphere-culture-enriched (ANOVA, p蠄 0.001), aldehyde dehydrogenase (ALDH1)bright, CD44high⁄+/CD24low⁄–, Hoechst 33342-excluded hCSC in a concentration- and time-dependent manner.
ALDH↓,
CD44↓,
CD24↓,
cl‑PARP↑, PEITC up-regulated cleaved poly (ADP-ribose) polymerase (p蠄 0.05) and induced death receptors, DR4 (p蠄 0.01) and DR5 (p蠄 0.001), of tumor necrotic factor-related apoptosis-inducing ligand signaling.
DR4↑,
DR5↑,

4959-

PEITC,

Phenethyl isothiocyanate hampers growth and progression of HER2-positive breast and ovarian carcinoma by targeting their stem cell compartment

in-vitro,

Ovarian,

CSCs↓, Isothiocyanates elicit anticancer effects by targeting cancer stem cells (CSCs).
ALDH↓, We found that PEITC significantly impaired the SFE of HER2-positive human cancer cells by decreasing their ALDH-positive compartments
CSCsMark↓, The anti-CSC activity of PEITC was demonstrated by a reduced expression/activation of established cancer-stemness biomarkers
eff↑, , in combination with trastuzumab, by significantly reducing spontaneous tumor development in d16HER2 transgenic mice.

5216-

PI,

doxoR,

Piperine enhances doxorubicin sensitivity in triple-negative breast cancer by targeting the PI3K/Akt/mTOR pathway and cancer stem cells

vitro+vivo,

BC,

MDA-MB-231

ChemoSen↑, synergistic interaction between DOX and PIP on MDA-MB-231 cells.
necrosis↑, combination regimen to enhance necrosis while downregulating PTEN and curbing PI3K levels as well as p-Akt, mTOR, and ALDH-1 immunoreactivities.
PTEN↓,
PI3K↓,
p‑Akt↓,
mTOR↓,
ALDH↓,
TumVol↓, Combining PIP to DOX reduces tumor size and improves survival of tumor-bearing mice
OS↑, combining PIP to DOX improved survival rates in mice compared to their DOX-treated counterparts (Fig. 4B).
cardioP↑, PIP protects against DOX-induced cardiotoxicity
cl‑PARP↑, PIP enhances apoptosis via PARP cleavage in EAC-tumor bearing mice

2687-

RES,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

NA,

Review,

AD,

NF-kB↓, RES affects NF-kappaB activity and inhibits cytochrome P450 isoenzyme (CYP A1) drug metabolism and cyclooxygenase activity.
P450↓,
COX2↓,
Hif1a↓, RES may inhibit also the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) and thus may have anti-cancer properties
VEGF↓,
*SIRT1↑, RES induces sirtuins, a class of proteins involved in regulation of gene expression. RES is also considered to be a SIRT1-activating compound (STACs).
SIRT1↓, In contrast, decreased levels of SIRT1 and SIRT2 were observed after treatment of BJ cells with concentrations of RES
SIRT2↓,
ChemoSen⇅, However, the effects of RES remain controversial as it has been reported to increase as well as decrease the effects of chemotherapy.
cardioP↑, RES has been shown to protect against doxorubicin-induced cardiotoxicity via restoration of SIRT1
*memory↑, RES has been shown to inhibit memory loss and mood dysfunction which can occur during aging.
*angioG↑, RES supplementation resulted in improved learning in the rats. This has been associated with increased angiogenesis and decreased astrocytic hypertrophy and decreased microglial activation in the hippocampus.
*neuroP↑, RES may have neuroprotective roles in AD and may improve memory function in dementia.
STAT3↓, RES was determined to inhibit STAT3, induce apoptosis, suppress the stemness gene signature and induced differentiation.
CSCs↓,
RadioS↑, synergistically increased radiosensitivity. RES treatment suppressed repair of radiation-induced DNA damage
Nestin↓, RES decreased NESTIN
Nanog↓, RES was determined to suppress the expression of NANOG
TP53↑, RES treatment activated TP53 and p21Cip1.
P21↑,
CXCR4↓, RES downregulated nuclear localization and activity of NF-kappa-B which resulted in decreased expression of MMP9 and C-X-C chemokine receptor type 4 (CXCR4), two proteins associated with metastasis.
*BioAv↓, The pharmacological properties of RES can be enhanced by nanoencapsulation. Normally the solubility and stability of RES is poor.
EMT↓, RES was determined to suppress many gene products associated with EMT such as decreased vimentin and SLUG expression but increased E-cadherin expression.
Vim↓,
Slug↓,
E-cadherin↑,
AMPK↑, RES can induce AMPK which results in inhibition of the drug transporter MDR1 in oxaliplatin-resistant (L-OHP) HCT116/L-OHP CRCs.
MDR1↓,
DNAdam↑, RES induced double strand DNA breaks by interfering with type II topoisomerase.
TOP2↓, The DNA damage was determined to be due to type II topoisomerase poisoning.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt.
Akt↓,
Wnt↓, RES was shown to decrease WNT/beta-catenin pathway activity and the downstream targets c-Myc and MMP-7 in CRC cells.
β-catenin/ZEB1↓,
cMyc↓,
MMP7↓,
MALAT1↓, RES also decreased the expression of long non-coding metastasis associated lung adenocarcinoma transcript 1 (RNA-MALAT1) in the LoVo and HCT116 CRC cells.
TCF↓, Treatment of CRC cells with RES resulted in decreased expression of transcription factor 4 (TCF4), which is a critical effector molecule of the WNT/beta-catenin pathway.
ALDH↓, RES was determined to downregulate ALDH1 and CD44 in HNC-TICs in a dose-dependent fashion.
CD44↓,
Shh↓, RES has been determined to decrease IL-6-induced Sonic hedgehog homolog (SHH) signaling in AML.
IL6↓, RES has been shown to inhibit the secretion of IL-6 and VEGF from A549 lung cancer cells
VEGF↓,
eff↑, Combined RES and MET treatment resulted in a synergistic response in terms of decreased TP53, gammaH2AX and P-Chk2 expression. Thus, the combination of RES and MET might suppress some of the aging effects elicited by UVC-induced DNA damage
HK2↓, RES treatment resulted in a decrease in HK2 and increased mitochondrial-induced apoptosis.
ROS↑, RES was determined to shut off the metabolic shift and increase ROS levels and depolarized mitochondrial membranes.
MMP↓,

4667-

RES,

CUR,

SFN,

Physiological modulation of cancer stem cells by natural compounds: Insights from preclinical models

Review,

Var,

CSCs↓, phytochemicals such as resveratrol, curcumin, sulforaphane, and others suppress CSC-associated pathways as well as sensitize CSCs to chemotherapy and radiotherapy
ChemoSen↑,
RadioS↑,
ALDH↓, deplete ALDH+ or CD44+ CSC pools, which ultimately decrease tumor initiation and recurrence.
CD44↓,
Wnt↓, graphical abstract
β-catenin/ZEB1↓,
NOTCH↓,
HH↓,
NF-kB↓,

4900-

Sal,

Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

Review,

BC,

CSCs↓, Salinomycin, a monocarboxylic polyether antibiotic isolated from Streptomyces albus, can precisely kill cancer stem cells (CSCs), particularly BCSCs, by various mechanisms, including apoptosis, autophagy, and necrosis.
Apoptosis↑,
TumAuto↑,
necrosis↑,
TumCP↓, salinomycin can inhibit cell proliferation, invasion, and migration in BC and reverse the immune-inhibitory microenvironment to prevent tumor growth and metastasis.
TumCI↓,
TumCMig↓,
TumCG↓,
TumMeta↓,
eff↑, Salinomycin is over 100 times more effective against BCSCs than paclitaxel, the traditional chemotherapy drug for the treatment of BC
Bcl-2↓, downregulation of Bcl-2 expression, and decreases their migration capacity, which is accompanied by downregulation of c-Myc and Snail expression
cMyc↓,
Snail↓,
ALDH↓, salinomycin reduces aldehyde dehydrogenase activity and the expression of MYC, AR, and ERG; it induces oxidative stress and inhibits nuclear factor (NF)-κB activity
Myc↓,
AR↓,
ROS↑, Salinomycin also induces autophagy by increasing intracellular ROS level, which is accompanied by MAPK signaling pathway activation
NF-kB↓,
PTCH1↓, significantly reduces tumor growth, which is accompanied by decreased PTCH, SMO, Gli1, and Gli2 expression
Smo↓,
Gli1↓,
GLI2↓,
Wnt↓, Figure 2
mTOR↓,
GSK‐3β↓,
cycD1/CCND1↓,
survivin↓,
P21↑,
p27↑,
CHOP↑,
Ca+2↑, cytosolic
DNAdam↑,
Hif1a↓,
VEGF↓,
angioG↓,
MMP↓, salinomycin can affect the cell membrane potential and reduce the level of ATP to induce mitophagy and mitoptosis.
ATP↓,
p‑P53↑, Salinomycin increases DNA breaks in BC cells as well as the expression of phosphorylated p53 and γH2AX in Hs578T cells.
γH2AX↑,
ChemoSen↑, Table 3 Synergistic anticancer co-action of salinomycin with other agents in BC.

4995-

Sal,

Salinomycin possesses anti-tumor activity and inhibits breast cancer stem-like cells via an apoptosis-independent pathway

vitro+vivo,

BC,

MDA-MB-231

ALDH↓, Salinomycin reduces ALDH1 activity and downregulates Nanog, Oct4 and Sox2.
Nanog↓,
OCT4↓,
SOX2↓,
CSCs↓, Salinomycin targets BCSCs via an apoptosis-independent pathway.
tumCV↓, Salinomycin suppressed cell viability, concomitant with the downregulation of cyclin D1 and increased p27kip1 nuclear accumulation.
cycD1/CCND1↓,
P21↑,
TumCG↓, MDA-MB-231-derived xenografts revealed that salinomycin administration elicited a significant reduction in tumor growth with a marked downregulation of ALDH1 and CD44 levels, but seemingly without the induction of apoptosis.
CD44↓,
Apoptosis∅,

4909-

Sal,

Salinomycin: Anti-tumor activity in a pre-clinical colorectal cancer model

vitro+vivo,

CRC,

AntiTum↑, salinomycin alone or in combination with FOLFOX exerts superior antitumor activity compared to FOLFOX therapy in a patient-derived mouse xenograft model of colorectal cancer
Apoptosis↑, Salinomycin induces apoptosis of human colorectal cancer cells, accompanied by accumulation of dysfunctional mitochondria and reactive oxygen species
mtDam↑,
ROS↑, Accumulation of dysfunctional mitochondria and increased production of reactive oxygen species upon salinomycin treatment
SOD1↓, These effects are associated with expressional down-regulation of superoxide dismutase-1 (SOD1) in response to salinomycin treatment.
ChemoSen↑, salinomycin alone or in combination with 5-fluorouracil and oxaliplatin exerts increased antitumoral activity compared to common chemotherapy.
CSCs↑, Anti-stem cell activity of salinomycin in TIC cultures
ALDH↓, Strikingly, exposure to 5-FU and oxaliplatin resulted in a more pronounced reduction of the ALDH1+ population compared to salinomycin treatment
TumCG↓, Salinomycin inhibits tumor growth in a patient-derived xenograft model
TumCP↓, Salinomycin inhibits proliferation, induces cell death and abolishes ATP production of human colorectal cancer cells
TumCD↑,
ATP↓,

1730-

SFN,

Sulforaphane: An emergent anti-cancer stem cell agent

Review,

Var,

BioAv↓, When exposed to high temperatures during meal preparation, myrosinase can be degraded, lose its function, and subsequently compromise the synthesis of SFN.
BioAv↑, eating raw cruciferous vegetables, instead of heating them can significantly improve the biodisponibility of SFN and its subsequent beneficial effects.
GSTA1↑, induction of Phase II enzymes [glutathione S-transferase (GST)
P450↓, (cytochrome P450, CYP) inhibition
TumCCA↑, herb-derived agent can also promote cell cycle arrest and apoptosis by regulating different signaling pathways including Nuclear Factor erythroid Related Factor 2 (Nrf2)-Keap1 and NF-κB.
HDAC↓, modulate the activity of some epigenetic factors, such as histone deacetylases (HDAC),
P21↑, upregulation of p21 and p27,
p27↑,
DNMT1↓, SFN was able to decrease the expression of DNMT1 and DNMT3 in LnCap prostate cancer cells
DNMT3A↓,
cycD1/CCND1↑, reduce methylation in Cyclin D2 promoter, thus inducing Cyclin D2 gene expression in those cells
DNAdam↑, SFN induced DNA damage, enhanced Bax expression and the release of cytochrome C followed by apoptosis
BAX↑,
Cyt‑c↑,
Apoptosis↑,
ROS↑, SFN increased reactive oxygen species (ROS), apoptosis-inducing factor (AIF)
AIF↑,
CDK1↑,
Casp3↑, activation of caspase-3, -8, and -9
Casp8↑,
Casp9↑,
NRF2↑, SFN significantly activated the major antioxidant marker Nrf2 and decreased NFκB, TNF-α, IL-1β
NF-kB↓,
TNF-α↓,
IL1β↓,
CSCs↓, SFN, have attracted attention due to their anti-CSC effect
CD133↓,
CD44↓,
ALDH↓,
Nanog↓,
OCT4↓,
hTERT/TERT↓,
MMP2↓,
EMT↓, SFN was reported to inhibit EMT and metastasis in the NSCLC, the cell lines H1299
ALDH1A1↓, ALDH1A1), Wnt3, and Notch4, other CSC-related genes inhibited by SFN treatment
Wnt↓,
NOTCH↓, SFN can inhibit aberrantly activated embryonic pathways in CSCs, including Sonic Hedgehog (SHH), Wnt/β-catenin, Cripto-1 (CR-1), and Notch.
ChemoSen↑, These results suggest that the antioxidant properties of SFN do not impact the cytotoxicity of antineoplastic drugs, but on the contrary, seems to improve it.
*Ki-67↓, Ki-67 and HDAC3 levels significantly decreased in benign breast tissues, and there was also a reduction in HDAC activity in blood cells
*HDAC3↓,
*HDAC↓,

5337-

TFdiG,

Theaflavin 3,3'-digallate suppresses metastasis and reduces insulin-like growth factor-1-induced cancer stemness and invasiveness in human melanoma cells

in-vitro,

Melanoma,

A375

in-vitro,

Melanoma,

A2058

TumCMig↓, TF3 significantly inhibited cell migration, invasion, and matrix metalloproteinase (MMP) activity in A 375 and A2058 melanoma cells.
TumCI↓,
MMPs↓,
ALDH↓, It also suppressed sphere formation, self-renewal capacity, and aldehyde dehydrogenase 1 (ALDH1) activity.
CSCs↓, TF3 downregulated key cancer stemness and drug resistance markers, including ABCB1, ABCG2, CD44, and CXCR4.
ABCG2↓,
CD44↓,
CXCR4↓,
TumCG↓, In vivo, TF3 significantly inhibited tumor growth, reduced angiogenic marker expression, and suppressed lung metastasis.
angioG↓,
TumMeta↓,

Showing Research Papers: 1 to 22 of 22

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 22

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

Sepsis↓, 1,
Total Targets: 199

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, Catalase↑, 1, GPx1↑, 1, GSTs↑, 1, HO-1↑, 2, lipid-P↓, 1, MDA↓, 1, NRF2↑, 1, ROS↓, 2, SOD1↑, 1,

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1, glucose↓, 1, GlucoseCon↑, 1, GLUT2↑, 1, SIRT1↑, 1,

Cell Death ⓘ

iNOS↓, 1,

Proliferation, Differentiation & Cell State ⓘ

HDAC↓, 1, HDAC3↓, 1,

Migration ⓘ

Ki-67↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 1,

Barriers & Transport ⓘ

GLUT3↑, 1, GLUT4↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 2, CRP↓, 1, IL6↓, 2, Inflam↓, 2, TNF-α↓, 2,

Synaptic & Neurotransmission ⓘ

AChE↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, BioAv↑, 3, BioAv↝, 1, eff↑, 1,

Clinical Biomarkers ⓘ

BMD↑, 1, CRP↓, 1, GutMicro↑, 1, IL6↓, 2, Ki-67↓, 1,

Functional Outcomes ⓘ

AntiCan↑, 1, memory↑, 1, neuroP↑, 2, toxicity↓, 1,

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 42

Scientific Paper Hit Count for: ALDH, Aldehyde Dehydrogenase

4 Phenethyl isothiocyanate
3 salinomycin
2 Curcumin
2 CUSP9
2 Disulfiram
2 Eugenol
2 Resveratrol
2 Sulforaphane (mainly Broccoli)
1 Alpha-Lipoic-Acid
1 Baicalein
1 Radiotherapy/Radiation
1 Cyclopamine
1 immunotherapy
1 Copper and Cu NanoParticles
1 Piperine
1 doxorubicin
1 Aflavin-3,3′-digallate

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:676  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

ALDH Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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