Dose Cancer Research Results
Dose, Dosage: Click to Expand ⟱
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Drug dosage vs efficacy, and actual dosage number of research papers.
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Scientific Papers found: Click to Expand⟱
HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
selectivity↑, it doesn’t affect the normal cells but strongly toxic to cancer cells
ATP↓, 3-BP killed 95% of Panc-2 cells at 15 μM concentration and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
mtDam↑, Electron microscopy data revealed that 3-BP severely damaged mitochondrial membrane in cancer cells.
Dose↝, We further examined therapeutic effect of 3-BP in syngeneic mouse pancreatic cancer model by treating animals with 10, 15 and 20 mg/kg dose. 3-BP at 15 & 20 mg/kg dose level significantly reduced tumor growth by approximately 75-80% in C57BL/6 female
TumCG↓, 3-BP inhibit in vivo pancreatic tumor growth in C57BL/6 mouse model
Casp3↑, observed enhanced expression of active caspase-3 in tumor tissues exhibited apoptotic death.
Glycolysis↓, Notably, metabolomic data also revealed severe inhibition in glycolysis, NADP, ATP and lactic acid production in cancer cells treated with 40 μM 3-BP.
NADPH↓,
ATP↓,
ROS↑, 3-BP treatment produces increased levels of reactive oxygen species (ROS), which causes DNA damage with reduction of free glutathione levels [11].
DNAdam↑,
GSH↓,
Bcl-2↓, Further, treatment with 40 µM of 3-BP suppressed BCL2L1 expression and causing activation of mitochondrial caspases
Casp↑,
lactateProd↓, Metabolic inhibition of glucose consumption and lactic acid production in cancer cells treated with 3-BP
eff↑, novel microencapsulated formulation of 3BP (ME3BP-7), which is effective against a variety of PDAC cells in vitro and remains stable in serum.
TumCG↓, Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity.
TumMeta↓,
toxicity↝,
Glycolysis↓, The anticancer effects of 3BP were initially attributed to inhibition of glycolysis (Ganapathy-Kanniappan et al., 2009;
toxicity↓, Our previous work demonstrated that microencapsulation of 3BP reduces its toxicity (Chapiro et al., 2014).
Dose↝, we were only able to reliably deliver multiple doses of the drug intravenously (i.v.), and the number of injections and time periods over which we could administer the drug were limited.
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CRC, |
DLD1 |
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HCT116 |
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eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,
ATP↓, Advanced cancers (2-3cm) developed and were treated with the alkylating agent 3-bromopyruvate, a lactate/pyruvate analog shown here to selectively deplete ATP and induce cell death.
TumCD↑,
toxicity↓, In all 19 treated animals advanced cancers were eradicated without apparent toxicity or recurrence.
eff↑, These findings attest to the feasibility of completely destroying advanced, highly glycolytic cancers.
tumCV↓, The chemical agent 3-BrPA depletes ATP stores and inhibits HCC cell viability
Dose↝, administered eight treatments on successive days with 1 ml of 2 mM 3-BrPA, also in 1· PBS, pH 7.5. Injection
of 3-BrPA was into the tumor.
TumCG↓, In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal
toxicity↓, In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA.
BioAv↝, It is possible that in the microencapsulated formulation, 3-BrPA, is more bioavailable for uptake into tumor cells and less available to the normal cells that apparently mediate its toxicity
GAPDH↓, 3-Bromopyruvate (3-BrPA), a highly potent small-molecular inhibitor of the enzyme GAPDH, represents the only available antiglycolytic drug candidate that is able to enter cancer cells selectively through the monocarboxylate transporter 1 (MCT1; refs.
toxicity↑, However, due to its alkylating properties, 3-BrPA is associated with significant toxicity when delivered systemically in therapeutic doses, which has impeded the clinical development and use of this drug in patients with cancer
Dose↝, Encapsulation of 3-BrPA in β-CD was achieved by portionwise addition of 3-BrPA (166 mg, 1 mmol/L) to a stirring solution of β-CD (1,836 mg in 30 mL DI water). The resulting solution was sonicated for 1 hour at room temperature and then shaken overnig
ATP↓, ability of microencapsulated 3-BrPA (β-CD-3-BrPA) to achieve dose-dependent ATP depletion and cell death, two human pancreatic cancer cell lines were employed.
eff↑, both PDAC cell lines were more sensitive to the drugs when hypoxic (Fig. 2)
TumCI↓, MiaPaCa-2 and Suit-2 cells showed a reduction in invasion at drug concentrations as low as 12.5 µmol/L.
MMP9↓, marked reduction in the secretion of MMP-9 was detected in both cell lines.
toxicity↓, No organ toxicities or tissue damage was observed in animals treated with β-CD–3-BrPA
toxicity↑, 3-Bromopyruvate (3BP), a small alkylating
agent, acts as an anti-metabolite to vital substrates in cancer metabolism and exhibits antitumor activity
across various cancer types, but the unformulated 3BP can cause high toxicity
eff↝, This study explores the efficacy of the 3BP clinical derivative KAT/3BP, currently in phase 1 for patients with hepatocellular carcinoma, in lymphoma models.
eff↑, AT/3BP exhibited synergistic activity when combined with lymphoma therapies, including bendamustine and R-CHOP.
Glycolysis↓, At acidic extracellular pH, 3BP enters cancer cells via monocarboxylic acid-1 (MCT-1) and inhibits glycolysis
through hexokinase II (HK-2) covalent modification
HK2↓, with HK-2 inhibition and dissociation from mitochondria, apoptosis-inducing factor (AIF) release, and apoptosis induction (9).
AIF↑,
Apoptosis↑,
NK cell↑, In the latter, tumor growth was in vivo reversed, with an increase in the number of circulating CD4+, CD8+, and NK-
cells
toxicity↑, unformulated 3BP administrations are associated with severe toxicities, including deaths (22,23)
toxicity↓, However, improvements have been made in developing novel 3BP formulations based on
liposomes, polyethylene glycol (PEG), PEGylated liposomes (stealth liposomes), perillyl alcohol
formulations, and others (12,22,24
Dose↝, KAT-101 and KAT-201 are two clinical 3BP derivatives formulated for oral or intratumoral (IT) administration, respectively (National Cancer Institute Thesaurus Codes C193479 and
C193479), now entering the early clinical evaluation of patients with h
AntiTum↑, KAT/3BP has in vivo antitumor activity in a syngeneic mouse model.
other↝, Since the use of ALA-based drugs for tumor diagnosis or therapy depends on preferential PpIX tumor accumulation, we begin this review with an overview of PpIX biosynthesis from ALA and end with the prospect of combining the diagnostic and therapeutic
ROS↑, These components individually are not harmful but become cytotoxic when combined due to the generation of reactive oxygen species (ROS) via type I and II photochemical reactions.
other↝, ALA was known to cause endogenous PpIX accumulation in human lymphocytes in the 1970s [15].
mtDam↑, which causes direct mitochondrial structural damage and Ca2+ release [24].
Ca+2↑,
ER Stress↑, ALA-PDT is known to damage the endoplasmic reticulum (ER) and cause Ca2+ release, triggering apoptosis through ER-stress signaling [25].
Apoptosis↑,
TumAuto↑, Lastly, ALA-PDT is also known to induce autophagy, the degradation of cellular components by lysosomes.
other↝, ALA administration exhibits red fluorescence and photosensitizing activity upon light activation.
Dose↝, Although blue and red light-emitting diode (LED) illuminators are commonly used as the light source to activate ALA and MAL for PDT of AK lesions, natural daylight is emerging as an attractive and convenient alternative.
Imm↑, ALA-PDT not only directly kills tumor cells but also elicits potent immune responses with important implications in the long-term therapeutic outcome.
*cognitive↑,
*Dose↝, 100mg nightly
*5HT↑,
*BioAv↑, By combining 5-HTP with carbidopa (CBD), increased bioavailability for brain penetration and decreased peripheral side effects would be expected, due to reduced peripheral decarboxylation of 5-HTP to 5-HT
*Dose↝, he tolerability and subjective effects of oral 5-HTP at 100, 200 and 300 mg combined with CBD and the pharmacokinetic properties of the 5-HTP/CBD-challenge.
*toxicity↝, Frequent occurrence of nausea and vomiting limits the applicability of this challenge at 5-HTP doses above 100 mg.
*cognitive↑, Improved recognition of positive emotions with TRP in older participants supports the use of a TRP-rich diet to compensate for age related decline in social-cognitive processes.
*Dose↝, they took cellulose capsules containing either 200 mg 5-HTP (extracted from Griffonia simplicifolia) or placebo (cellulose and mannitol) with a 200 ml mixture of fruit juice (15–20%) and water.
*toxicity↝, Ingestion of 5-HTP in dogs can result in a potentially life-threatening syndrome resembling serotonin syndrome in humans, which requires prompt and aggressive care
*5HT↑, The reported mechanism of action of 5-HTP is through an increase of serotonin concentrations within the CNS,1
*Dose↝, The lowest dose at which signs developed was 23.6 mg/kg (10.7 mg/lb); death was reported for 3 dogs at 128, 131.9, and 287 mg/kg (58.2, 60, and 157.7 mg/lb), respectively
TrxR↓, TrxR is viable target in clinical trials using the anti-rheumatic drug, auranofin (AF).
Dose↝, 4 mg/kg once daily resulting in 18 μM gold in the plasma and 50% inhibition of TrxR activity in DMS273 SCLC tumors.
RadioS↑, effective inhibitor of TrxR and suggest that AF could be used as an adjuvant in radio-chemotherapy protocols to enhance therapeutic efficacy.
ChemoSen↑,
ROS↑, We also demonstrated the suppressing TrxR with AF can sensitize breast cancer stem cells to ROS induced differentiation and cytotoxicity.16
Diff↑,
toxicity↓, These results suggest that this dosing regimen is nontoxic to kidneys, liver, and bone marrow as well as demonstrating a trend toward a survival advantage in tumor bearing animals.
AntiTum↑, Over the last twenty years, AF has also been repurposed as an antitumor, antiviral, and antibacterial drug.
Bacteria↓,
TrxR↓, ability to inhibit thioredoxin reductase (TrxR) and disrupt redox homeostasis, leading to selective cytotoxicity in cancer cells.
ChemoSen↑, synergistic effects observed when AF is combined with chemotherapeutics, targeted therapies, or immune modulators.
Dose↝, Patients received AF orally twice daily on days 1–28. atients received AF orally, 6 mg in the morning and 6 mg in the evening.
ROS↑, AF induces oxidative stress and apoptosis in cancer cells by disrupting redox homeostasis, while sirolimus inhibits mTOR signaling.
Apoptosis↑,
mTOR↓,
*BioAv↝, intramuscularly administered gold is greater than 95% bioavailable, whereas only 20 to 30% of an orally administered dose of auranofin is absorbed.
*Dose↝, 50mg intramuscular injection of GST, serum gold concentrations rise sharply, peaking between 4 and 8 mg/L in approximately 2 hours and declining to an average of 3 mg/L by 7 days.
*Half-Life↑, Both compounds are retained within the body for prolonged periods.
*BioAv↝, In human subjects, parenterally administered gold is widely distributed among bodily tissues, showing a predilection for tissues of the reticuloendothelial system as well as the kidney and adrenal cortex.
*other↝, auranofin but animal studies have shown comparatively less affinity for the liver, kidney and spleen.
Dose↝, 6mg dose(equivalent to 1.74mg of gold) radioactive
Half-Life↝, plasma terminal half-life was 17days
TrxR↓, mechanism of action of auranofin was correlated with thioredoxin reductase inhibition,
other↝, but other modes of action such as interference with mitochondrial protein import and NADH kinase were also described and discussed
IL6↑, Conversely, auranofin stimulated IL-6 and IL-8 secretion in monocytes,
IL8↑,
NK cell⇅, NK activation was only observed at low doses of auranofin, while high doses inhibited NK activity
COX2↓, suppression of pro-inflammatory factors such as COX-2 (cyclooxygenase-2), NOS (nitric oxide synthase), NF-κB (nuclear factor-κB), and TrxR, as well as on the activation of peroxyredoxin-1 and Nrf2 (nuclear factor erythroid 2-related factor 2) [19].
NOS2↓,
NRF2↑,
Prx↑,
Half-Life↑, plasma half-lives of 15–25 days [24]
Dose↝, To avoid frequently occurring diarrhea, oral doses of 3–6 mg per day, or below, should also be considered when repurposing auranofin for the treatment of other human diseases.
ROS↑, Imbalances in this system lead to the accumulation of cytotoxic ROS.
NF-kB↓, Auranofin can bind to IKK, which ultimately leads to NF-κB inhibition
TrxR↓, AF treatment decreased TrxR activity and clonogenic survival in small cell lung cancer (SCLC) cell lines (DMS273 and DMS53) as well as the lung atypical (neuroendocrine tumor) NET cell line H727.
eff↑, AF treatment also significantly sensitized DMS273 and H727 cell lines in vitro to sorafenib, a multi-kinase inhibitor that was shown to decrease intracellular glutathione.
Dose↝, AF was administered intraperitoneally at 2 mg/kg or 4 mg/kg (IP) once (QD) or twice daily (BID) for 1 to 5 days in mice with DMS273 xenografts.
OS↑, When this daily AF treatment was extended for 14 days a significant prolongation of median survival from 19 to 23 days (p=0.04, N=30 controls, 28 AF) was observed without causing changes in animal bodyweight, CBCs, bone marrow toxicity, blood urea ni
eff↑, We also demonstrated that suppressing TrxR with AF can sensitize breast cancer stem cells to ROS induced stem cell transitions associated with EMT and cytotoxicity associated with 2-deoxyglucose treatment.
*Imm↑, AR possesses various biological functions, including potent immunomodulation, antioxidant, anti-inflammation and antitumor
activities.
*antiOx↑,
*Inflam↓,
AntiTum↑,
eff↑, characteristics of increasing curative effect and reducing the toxicity of chemotherapeutic drugs [11 , 118].
chemoP↑,
Dose↝, main bioactive compounds responsible for the anti-cancer effects of AR mainly include formononetin,
AS-IV and APS. S
TumCMig↓, AS-IV could inhibit the migration and proliferation of non-small cell lung cancer (NSCLC
TumCP↓,
Akt↓, h via inhibition of the Akt/GSK-3β/β-catenin
signaling axis.
GSK‐3β↓,
MMP2↓, downregulating the expression of matrix metalloproteases (MMP)-2 and -9
MMP9↓,
EMT↓, AS-IV could inhibit TGF-B1 induced EMT through inhibition of PI3K/AKT/NF-KB
PI3K↓,
Akt↓,
NF-kB↓,
Inflam↓,
TGF-β1↓,
TNF-α↓,
IL6↓,
Fas↓, reduced FAS/FasL
FasL↓,
NOTCH1↓, decressing notch1
JNK↓, inactivating JNK pathway [145]
TumCG↓, The results showed that the AR water extract could inhibit the growth of colorectal cancer in vivo without apparent toxicity and side effect, which suggests that AR is a potential therapeutic drug for colorectal cancer
*Dose↝, the mean maximum plasma concentration (Cmax) values of AGS-IV were 2.12, 3.59, 3.71 and 5.17 μg ml−1 after single doses of 200, 300, 400 and 500 ml of AI, respectively.
Half-Life↝, mean values of elimination half-life (t1/2) were 2.14, 2.59, 2.62 and 2.69 h, respectively.
*toxicity↓, AI was safe and well tolerated, and the adverse events, such as raised total bilirubin and rash, were mild and resolved spontaneously. AI was safe and well tolerated in this study,
fatigue↓, meta-analysis showed that the addition of Astragalus membranaceus to the control group was effective in reducing cancer-related fatigue
QoL↑, The current evidence is supportive of the efficacy of Astragalus membranaceus in patients with cancer-related fatigue and their quality of life,
Dose↝, Wang et al. study 16 showed that both doses of 500 mg and 250 mg were effective in improving fatigue.
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BT549 |
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MDA-MB-231 |
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TumCD↑, Our findings provide additional support for proteotoxic stress as a mechanism by which AgNPs selectively kill TNBCs
selectivity↑,
*toxicity↝, Failure to separate dissolved silver cations (Ag+) from AgNPs before toxicity testing likely contributes to the lack of a definitive answer. Ag+ is highly toxic and has a distinct cytotoxic mechanism of action compared to AgNPs;
Dose↝, doses in the range of 4–6 mg/kg delivered systemically for multiple weeks induced therapeutic responses
OS↑, 40 patients were injected intravenously with 1.8 mg of AgNPs for 3 consecutive days (combined with standard COVID-19 treatments), and the group receiving AgNPs had significantly greater survival rate
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MCF-7 |
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MCF10 |
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BT549 |
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ROS↑, AgNPs is known to cause dose-dependent toxicities, including induction of oxidative stress and DNA damage, which can lead to cell death.
DNAdam↑,
selectivity↑, We show that AgNPs are highly cytotoxic toward TNBC cells at doses that have little effect on nontumorigenic breast cells or cells derived from liver, kidney, and monocyte lineages.
TumCG↓, reduce TNBC growth and improve radiation therapy.
RadioS↑,
Dose↝, s 23±14 nm: particles were diluted to 40 μg/mL. 25 μg/mL AgNP dilution for 24 hours. zeta potential of AgNPs in water at pH 7 was approximately −36 mV, indicating good colloidal stability.
selectivity↑, Depending on AgNP dose, all three TNBC cell lines were 5- to 10-fold more sensitive to AgNP exposure than the nontumorigenic breast cells.
other↝, this study demonstrate that the cytotoxicity was dependent on exposure of cells to intact AgNPs and not due to Ag+ ions
eff↓, toxicity of AgNPs was significantly reduced in MDA-MB-231, MCF-7, and MCF-10A cells following pretreatment with GSH
eff↑, Selective depletion of GSH by BSO resulted in increased AgNP toxicity in all cell lines.
γH2AX↑, AgNPs significantly increased γH2AX in these cells compared to radiation alone.
Dose↓, Strikingly, an AgNP dose of as little as 1 μg/mL resulted in a dose enhancement of IR treatment (approximately 2-fold at the 2 Gy dose) f
eff↑, Moreover, intratumoral injection of AgNPs with or without radiation treatment can inhibit the growth of TNBC xenografts in mice
ROS↑, significant increase in ROS and lipid peroxidation (LPO), along with a decrease in MMP and glutathione (GSH) levels.
lipid-P↑,
MMP↓,
GSH↓,
TumCCA↑, significant increase in ROS and lipid peroxidation (LPO), along with a decrease in MMP and glutathione (GSH) levels.
Apoptosis↑,
Necroptosis↑,
TumCD↑, AgNPs-induced cell death in HeLA cells suggested the anticancer potential of ND-AgNPs.
Dose↝, ND-AgNPs at 10, 25, and 50 µg/ml concentration
*Inflam↓, Qualitative analysis showed a reduction in pro-inflammatory proteins and in the COX-2 pathway.
*COX2↓,
*ROS↓, Its in vitro mechanism of action shows potential to eliminate free radicals
*Dose↝, The method of synthesizing nanoparticles (NPs) influences parameters such as size, shape, topography, stability, concentration, purity and release of Ag + ions, which in turn influences their anti-inflammatory activity
*eff↑, In vitro studies have compared the ingestion of AgNPs at low concentrations (0.012 % per kg) with gold standard drugs (glucocorticoids; 0.1 % per kg) and observed higher efficacy of NPs in promoting therapeutic effect
*toxicity↓, another study has shown that chronic in vivo application of AgNPs at the minimum concentration necessary to promote therapeutic effect does not cause toxic effects
*IL4↑, AgNPs and mitoxantrone increased levels of anti-inflammatory cytokines (IL4, IL5, IL10, IL13, and IFNα) and decreased pro-inflammatory cytokines (IL1, IL6, IL12, IL18, IFNY and TNFα).
*IL5↑,
*IL10↑,
*IL1↓,
*IL6↓,
*TNF-α↓,
*NF-kB↓, AgNPs selectively inhibit COX-2 and the NF-kB pathway.
*MDA↓, AgNPs reduce biomarkers of oxidative stress [55], such as malondialdehyde (MDA) and cell membrane peroxidation [19,31] and increase intracellular GSH
*GSH↑,
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AntiCan↑, The PGE-AgNPs showed a dose-dependent response against human liver cancer cells (HepG2) (IC50; 70 μg/mL) indicating its greater efficacy in killing cancer cells.
Dose↝, surface charge of synthesized AgNPs was highly negative (−26.6 mV) and particle size distribution was ranging from ∼35 to 60 nm and the average particle size was about 48 nm determined by dynamic light scattering (DLS)
*antiOx↑, literature suggests that AgNPs display considerable antioxidant activity in vitro
*AntiDiabetic↑, Antidiabetic potential of biosynthesized AgNPs
*Bacteria↓, Synergistic antibacterial potential of AgNPs with standard antibiotics
*toxicity∅, concluding no detectable toxicity
*Dose↝, 10 ppm oral silver particle dosing [36 subjects] and 32 ppm oral silver particle dosing [24 subjects]). 100 μg/day for 10 ppm, and 480 μg/day for 32 ppm silver
*Dose↝, corresponding to ionic silver comprising some 84.3% of the total silver content in the product
administered orally to patients.
*BioAv↝, Peak serum silver concentration was detected in 42% of subjects in the 14-day 10 ppm dosing showing a mean of 1.6±0.4 mcg/L
*BioAv↝, The 32 ppm dose mean concentration was detected in 92% of subjects at 6.8±4.5 mcg/L
*H2O2∅, No statistically significant change in markers of hydrogen peroxide production or
peroxiredoxin protein expression were detected.
*IL8∅, Analysis of IL-8, IL-1α, IL-1β, MCP1 and NQO1 also showed no statistical difference between the active silver and placebo solutions.
*IL1α∅,
*IL1β∅,
*MCP1∅,
*NQO1∅,
*BioAv↓, miniscule (<1%) amounts of 10-nm gold nanoparticles permeate across the gut to enter systemic vascular circulation from the intestine in rodents.51 We assert that silver metallic particle absorption is similar
*Dose↝, 0.005mg/kg/day limit based on Argyria (0.5mg/day for 220lb adult) for 70 years
*AntiAg↑, Potentially, materials exhibiting antiplatelet activity may be applied in devices that prevent arterial thrombotic events like ischemic stroke, coronary heart disease, and ischemic gangrene.
*AntiThr↑,
*Dose↝, All four types of AgNPs were spherical in shape with the primary size close to 10 nm
*AntiAg↑, n the present study we show that nanosilver has an innate antiplatelet property and effectively prevents integrin-mediated platelet responses, both in vivo and in vitro, in a concentration-dependent manner
*Bacteria↓, We have recently reported synthesis of highly stable, uniformly sized silver nanoparticles endowed with enhanced antibacterial properties.
*Dose↝, Nanoparticles were spherical in shape, 10-15nm in diameter and monodispersed
*Dose↝, The extent of inhibition was the same irrespective of whether platelets were aspirinized or not. More than 80% (n $ 10) inhibition in amplitude was recorded at a nanoparticle concentration of 50 uM, which also reduced the slope of agregation/min
*Dose↝, (2!8 mg/kg body weight) in two different mice strains led to significant inhibition of platelet aggregation in mouse whole blood (studied by electronic impedance) in a dose-dependent manner
*toxicity↝, a dose of nanosilver up to 300 mg/kg was nontoxic to rodents.
OS↑, remission
Dose↓, Electron microscopy of AgNP solution revealed bimodal nanoparticle size
distribution: 3 and 12 nm.
BioAv↝, basal **silver ion** concentrations of 32 ng/g, rising to 46 ng/g 1 hour after ingesting 60 mL of AgNP solution.
toxicity↓, no toxicities were observed and he had complete radiographic resolution of his cancer
Remission↑,
other↝, patient serum was analyzed and intact nanoparticles were not identified. Thus, we could not isolate the circulating AgNP form
other↝, Analysis of urine showed no AgNP or detectable nanoparticle fragments
other↝, AgNP solution was also exposed to simulated gastric fluid, in which they aggregated into larger nanoparticles according to UV-Vis absorption.
Dose↝, GDH: based on repeat setup, estimated PPM is 20PPM assuming 67% effecient. 1.2mg/60mL (he took 160mL/day
BioAv↝, GDH: chatAI computed the estimated bioavailability at 7%
Dose↝, Values found were between 3.2 and 3.9 molecules sugar/nm2.
eff↑, glucose and citrate coated nanoparticles show a similar toxicity, galactose and mannose functionalized nanoparticles were significant less toxic towards both cell lines.
ROS↑, suggesting that the toxicity is mainly caused by oxidative stress related to ROS formation
eff↝, Many authors have argued that in fact the toxicity of nanosilver is only caused by the ionic form [24]
eff↑, Trojan-horse mechanism has been often discussed in literature as a responsible for toxicity of silver nanoparticles.
eff↝, although mannose and glucose-functionalized nanoparticles present similar cellular uptakes, observed toxicities were considerably different.
eff↑, Actually, in this study, glucose-capped nanoparticles present the highest toxicity as well as protein carbonylation, despite their moderate cellular uptake, compared with other nanoparticles.
eff↝, Observed toxicity was strongly correlated with intracellular oxidative stress, measured as protein carbonylation, but not to cellular uptake.
*hepatoP↑, AgNPs + RV treatment significantly reduced pro-inflammatory cytokines, NF-κB activation, presepsin, PCT, 8-OHDG, and VEGF levels compared with the CLP group, indicating attenuation of sepsis-induced liver injury.
*Inflam↓,
*NF-kB↓,
*VEGF↓,
*SIRT1↑, Both RV and AgNPs + RV treatments increased SIRT1 levels, suggesting a potential role of SIRT1 activation in mediating the protective effects.
*ROS↓, alleviating sepsis-induced liver injury by modulating inflammation, oxidative stress, and endothelial dysfunction, potentially mediated through SIRT1 activation.
*Dose↝, 30 mg/kg of AgNPs + RV was given intraperitoneally to the rats
*Catalase↑, AgNPs + RV treatment exhibited a robust effect in bolstering CAT activity
*MDA↓, AgNPs + RV treatment effectively ameliorates sepsis-induced oxidative stress and inflammation in rat livers by reducing MDA, MPO, and NO levels
*MPO↓,
*NO↓,
*ALAT↓, AgNPs + RV effectively reduced the ALT and AST levels, returning them to values similar to those observed in the Sham group
*AST↓,
*antiOx↑, corroborates the antioxidant potential of RV and AgNPs observed in earlier studies
*Dose↝, The treated group received a single oral dose of 5.5 mg/kg of Ag NPs. 5 to 12 nm
*eff↑, Ag NPs treatment in septic mice significantly decreased liver enzyme activities, total protein, and serum albumin.
*RenoP↑, Ag NPs significantly enhanced kidney function, as indicated by a significant decrease in the levels of creatinine, urea, and uric acid.
*antiOx↑, Ag NPs showed a powerful antioxidant effect via the considerable reduction of malondialdehyde and nitric oxide levels and the increase in antioxidant content.
*MDA↓,
*NO↓,
*hepatoP↑, hepatoprotective effect of Ag NPs may be attributed to their antioxidant properties
*toxicity↝, The Ag NPs dose is 1/10 of LD50, which is 5.5 mg/kg.
*GSH↑, GSH, SOD, GST, and CAT of the septic group. Meanwhile, the Ag NPs-treated mice showed a significant (p < 0.05) increase in all four parameters.
*SOD↑,
*GSTs↑,
*Catalase↑,
*AntiAg↑, Garlic has been known to have antiplatelet properties.
*toxicity↓, The results suggest that AGE is relatively safe and poses no serious hemorrhagic risk for closely monitored patients on warfarin oral anticoagulation therapy.
*cardioP↑, ts positive effects may be beneficial to people with a high-risk background or who are taking cardiovascular medications
*Dose↝, formulated by soaking sliced raw garlic in aqueous ethanol solution for up to 20 mo at room temperature. The extract was filtered and concentrated under reduced pressure at low temperature
*AntiAg↑, Garlic and its components are known to possess antiplatelet activity
BioAv↝, Though garlic components leave the body quickly, a slow build-up of the active ingredients may take place.
Dose↝, Each capsule contained oil equivalent to I g of raw garlic. oil extract of garlic was encapsulated. 2 capsules of
garlic three times a day (i.e. 6 capsules/day) for a period of 1 month.
Inflam↓, , anti-inflammatory, anti-cancer, and immune-modulatory activities
AntiCan↑,
ROS↑, allicin treatment led to the accumulation of ROS
MAPK↑, activation of MAPK/JNK
JNK↑,
TumAuto↑, of autophagy in non small cell lung cancer (NSCLC) cells.
other↑, autophagy at a low dose of allicin is cytoprotective
Dose↝, whereas a high dose of allicin leads to autophagic cell death.
MALAT1↓, allicin could considerably induce oxidative stress and autophagy to suppress osteosarcoma growth via inactivating the MALAT1-miR-376a-Wnt/β-catenin axis,
Wnt↓,
β-catenin/ZEB1↓,
ROS↑, apoptosis and autophagy pathway in A549 cells by ROS accumulation and facilitating S/G2-M phase arrest in both normoxia as well as hypoxia
HIF-1↓,
E-cadherin↑,
N-cadherin↓,
antiOx↓, ROS trigger cell death when its generation reached toxic threshold level by overcoming the antioxidant capacity of the cell and inducing irreversible oxidative modifications of lipid, protein or DNA [30, 48]
Dose↝, 10μg/ml (LD) and 40μg/ml (HD) allicin for 24hr
*ROS↓, scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age.
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑,
*antiOx↑, LA has long been touted as an antioxidant
*NRF2↑, activate Phase II detoxification via the transcription factor Nrf2
*MMP9↓, lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*VCAM-1↓,
*NF-kB↓,
*cognitive↑, it has been used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits, and has been implicated as a modulator of various inflammatory signaling pathways
*Inflam↓,
*BioAv↝, LA bioavailability may be dependent on multiple carrier proteins.
*BioAv↝, observed that approximately 20-40% was absorbed [
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies
*H2O2∅, Neither species is active against hydrogen peroxide
*neuroP↑, chelation of iron and copper in the brain had a positive effect in the pathobiology of Alzheimer’s Disease by lowering free radical damage
*PKCδ↑, In addition to PKCδ, LA activates Erk1/2 [92, 93], p38 MAPK [94], PI3 kinase [94], and Akt [94-97].
*ERK↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, In skeletal muscle, LA is proposed to recruit GLUT4 from its storage site in the Golgi to the sarcolemma, so that glucose uptake is stimulated by the local increase in transporter abundance.
*GlucoseCon↑,
*BP↝, Feeding LA to hypertensive rats normalized systolic blood pressure and cytosolic free Ca2+
*eff↑, Clinically, LA administration (in combination with acetyl-L-carnitine) showed some promise as an antihypertensive therapy by decreasing systolic pressure in high blood pressure patients and subjects with the metabolic syndrome
*ICAM-1↓, decreased demyelination and spinal cord expression of adhesion molecules (ICAM-1 and VCAM-1)
*VCAM-1↓,
*Dose↝, Considering the transient cellular accumulation of LA following an oral dose, which does not exceed low micromolar levels, it is entirely possible that some of the cellular effects of LA when given at supraphysiological concentrations may be not be c
mt-ROS↑, DHLA but not ALA was able to scavenge cytosolic o2- in HT-29 cells whereas both compounds increased O2 -generation inside mitochondria
Apoptosis↑,
Casp3↑, increased caspase-3-like activity (start after 300uM, figure 2A)
DNAdam↑, and was associated with DNA-fragmentation
Bcl-xL↓, down-regulation of the anti-apoptotic protein bcl-X
Dose↝, The margin between these apparent opposing effects of ROS-production and ROS-scavenging seems to be above 100 uM since at lower concentrations of DHLA no apoptosis-induction was observed.
Strength↑, improved physical performance (total physical activity, mean movement velocity and total travelled distance).
*Casp3↓, Interestingly, l-carnitine treatment also decreases caspase-3 mRNA content therefore suggesting a modulation of apoptosis.
cachexia↓, concluded that l-carnitine supplementation may be a good approach for a multi-targeted therapy for the treatment of cancer-related cachexia.
*Dose↝, It is a natural compound free from toxicity up to 6 g/day in human subjects with cancer10 and up to 9 g/day i.v. in patients with acute cardiac infarction.
*cachexia↓, The results of this process favored L-carnitine supplementation in patients with cancer-related cachexia.
*Apoptosis↓, inhibiting apoptosis or reversing inflammatory processes.
*Inflam↓,
QoL↑, This treatment increased plasma-free carnitine concentrations and significantly improved fatigue, which was assessed using the functional assessment of cancer therapy, fatigue, and quality of life questionnaire, as well as quality-of-life measu
Dose↝, placebo-controlled trial, in which 2 g per day of LC was administrated orally for four weeks among eligible patients.
Weight↑, advanced pancreatic cancer received either LC (4 g/day orally) or a placebo for 12 weeks. The results showed that body mass index, nutritional status (body cell mass and body fat), and quality-of-life parameters increased
OS↝, There was an insignificant increase in overall survival, a decline in length of hospital stays, and decrease in fatigue among the LC-treated patients.
fatigue↓,
eff↝, some dietary factors, such as food intake restriction and intake of LC and certain micronutrients (vitamin C, vitamin B6, and iron, which are required as cofactors for endogenous LC biosynthesis) may have some effects on the efficacy of LC sup
fatigue↝, There is little evidence that L-carnitine supplementation improves cancer-related fatigue, low fertility, or overall physical health
*Dose↝, f you choose to take L-carnitine supplements, the Linus Pauling Institute recommends acetyl-L-carnitine at a daily dose of 0.5 to 1 g.
NP/CIPN↓, Acetyl-L-carnitine (ALCAR) may help reduce the severity of chemotherapy-induced peripheral neuropathy.
fatigue↓, carnitine supplementation has been tested in preliminary studies concerning human cachexia, resulting in improved fatigue and quality of life.
QoL↑,
*GSH↑, l-carnitine treatment improved the tumor-induced decrease in muscular glutamate and glutathione levels and the increased plasma glutamate levels in tumor-bearing rodents
Dose↝, Significant improvements in fatigue were also observed in a randomized phase III clinical trial, in which l-carnitine (4 g/day) was orally given to patients with advanced cancer
*Dose↝, n a 2003 meta-analysis of 21 clinical trials, a total of 1,204 adults with mild cognitive impairment or mild Alzheimer’s disease took supplements containing 1.5 to 3.0 g/day acetyl-L-carnitine or placebo for 3 to 12 months.
*cognitive↑, Clinical and psychometric assessment scores were better, and improvements determined by clinicians were greater in supplement users than in the placebo groups [30].
EGFR↓, Almonertinib (HS-10296) is an oral, potent, high selective third generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) for sensitizing mutations and EGFR T790M mutation.
OS↑, Almonertinib demonstrated progression-free survival benefit in EGFR T790M positive NSCLC patients
Dose↝, received almonertinib 110 mg orally once daily until disease progression.
BBB↑, Both almonertinib and bevacizumab are capable of crossing the blood–brain barrier with comparable central nervous system effectiveness.
Dose↝, present five cases to further evaluate the effectiveness and tolerability of almonertinib in combination with bevacizumab for patients with EGFRm NSCLC and LM.
eff↓, For the first time, we report that almonertinib plus bevacizumab can not only effectively improve the neurological symptoms caused by LM but also prolong the survival time of patients with limited and controllable side effects, which provided a novel
OS↑,
TumCD↑, Treatment with a combination of apigenin and curcumin increased the expression levels of genes related to cell death in HeLa cells 1.29- to 27.6-fold.
eff↑, combination of curcumin and apigenin showed a synergistic anti-tumor effect
TumAuto↑, autophagic cell death, as well as ER stress-associated paraptosis
ER Stress↑,
Paraptosis↑,
GRP78/BiP↓, GRP78 expression was down-regulated, and massive cytoplasmic vacuolization was observed in HeLa cells
Dose↝, combined use of 0.09 μg/μl curcumin and 0.06 μg/μl apigenin showed a synergistic anti-tumor effect
| - |
Human, |
AD, |
NA |
|
|
|
- |
in-vitro, |
AD, |
NA |
|
|
|
*cognitive↑, benefits of aromatherapy on the cognitive function of patients with AD utilizing various aromatic essential oils
*Dose↝, The mice were exposed to a mixture of lemon and rosemary oil at nighttime as well as to a mixture of lavender and orange oil in the daytime for 2 months.
*Aβ↓, brain levels of Aβ and abnormally phosphorylated tau were considerably lower in the aromatherapy group, while the levels of BDNF were marginally higher.
*tau↓,
*BDNF↑,
*motorD↑, fig 1
AntiCan↑, The artemisinin class of anti-malarial drugs has shown significant anti-cancer activity in pre-clinical models.
Dose↝, maximum tolerated dose (MTD) . maximum tolerated dose (MTD) a
Dose↝, MTD of intravenous artesunate is 18 mg/kg
*Half-Life↝, Artemisinin was found to induce its own metabolism with a mean induction time of 1.9 h, whereas the enzyme elimination half-life was estimated to 37.9 h.
BioAv↝, Artemisinin produces a rapid onset of enzyme induction, resulting in a decrease in its own bioavailability over time.
*Half-Life↓, Plasma artemisinin concentrations reach a peak within 2–3 h after oral intake and decline with a short half-life of 1.5–2 h
BioAv↑, Artemisinin is believed to pass through the gut membrane relatively easily [3, 4], although high oral clearance values are indicative of high first-pass metabolism of the compound, resulting in low bioavailability
*Dose↝, either a daily single dose of 500 mg oral artemisinin for 5 days, or single oral doses of 100/100/250/250/500 mg on each of the first 5 days.
Showing Research Papers: 1 to 50 of 401
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 401
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
antiOx↓, 1, Ferroptosis↓, 1, GSH↓, 3, lipid-P↑, 1, MDA↑, 1, NRF2↑, 1, Prx↑, 1, ROS↑, 11, mt-ROS↑, 1, TrxR↓, 4, xCT↑, 1,
Mitochondria & Bioenergetics ⓘ
AIF↑, 1, ATP↓, 5, MMP↓, 1, mtDam↑, 2,
Core Metabolism/Glycolysis ⓘ
GAPDH↓, 1, Glycolysis↓, 3, HK2↓, 3, lactateProd↓, 1, NADPH↓, 1,
Cell Death ⓘ
Akt↓, 2, Apoptosis↑, 6, Bcl-2↓, 1, Bcl-xL↓, 1, Casp↑, 1, Casp3↑, 2, Fas↓, 1, FasL↓, 1, Ferroptosis↓, 1, JNK↓, 1, JNK↑, 1, MAPK↑, 1, Necroptosis↑, 1, Paraptosis↑, 1, TumCD↑, 4,
Kinase & Signal Transduction ⓘ
AMPKα↑, 1,
Transcription & Epigenetics ⓘ
other↑, 1, other↝, 8, tumCV↓, 1,
Protein Folding & ER Stress ⓘ
ER Stress↑, 2, GRP78/BiP↓, 1,
Autophagy & Lysosomes ⓘ
p‑Beclin-1↑, 1, TumAuto↑, 4,
DNA Damage & Repair ⓘ
DNAdam↑, 3, γH2AX↑, 1,
Cell Cycle & Senescence ⓘ
TumCCA↑, 1,
Proliferation, Differentiation & Cell State ⓘ
Diff↑, 1, EMT↓, 1, FOXO3↑, 1, GSK‐3β↓, 1, mTOR↓, 1, NOTCH1↓, 1, PI3K↓, 1, TumCG↓, 5, Wnt↓, 1,
Migration ⓘ
Ca+2↑, 1, E-cadherin↑, 1, MALAT1↓, 1, MMP2↓, 1, MMP9↓, 2, N-cadherin↓, 1, TGF-β1↓, 1, TumCI↓, 1, TumCMig↓, 1, TumCP↓, 1, TumMeta↓, 1, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature ⓘ
EGFR↓, 1, HIF-1↓, 1,
Barriers & Transport ⓘ
BBB↑, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, IL6↓, 1, IL6↑, 1, IL8↑, 1, Imm↑, 1, Inflam↓, 2, NF-kB↓, 2, NK cell↑, 1, NK cell⇅, 1, TNF-α↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↑, 1, BioAv↝, 5, ChemoSen↑, 2, Dose↓, 2, Dose↝, 31, eff↓, 3, eff↑, 14, eff↝, 5, Half-Life↑, 1, Half-Life↝, 2, RadioS↑, 2, selectivity↑, 4,
Clinical Biomarkers ⓘ
EGFR↓, 1, IL6↓, 1, IL6↑, 1, NOS2↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 3, AntiTum↑, 3, cachexia↓, 1, chemoP↑, 1, fatigue↓, 3, fatigue↝, 1, NP/CIPN↓, 1, OS↑, 5, OS↝, 1, QoL↑, 3, Remission↑, 1, Strength↑, 1, toxicity↓, 7, toxicity↑, 3, toxicity↝, 1, TumVol↓, 1, TumW↓, 1, Weight↑, 1,
Infection & Microbiome ⓘ
Bacteria↓, 1,
Total Targets: 115
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 5, Catalase↑, 2, GSH↑, 4, GSTs↑, 1, H2O2∅, 2, MDA↓, 3, MPO↓, 1, NQO1∅, 1, NRF2↑, 1, ROS↓, 3, SOD↑, 1,
Metal & Cofactor Biology ⓘ
IronCh↑, 1,
Core Metabolism/Glycolysis ⓘ
ALAT↓, 1, AMPK↑, 1, GlucoseCon↑, 1, SIRT1↑, 1,
Cell Death ⓘ
Akt↑, 1, Apoptosis↓, 1, Casp3↓, 1, MAPK↑, 1,
Transcription & Epigenetics ⓘ
AntiThr↑, 1, other↝, 1,
Proliferation, Differentiation & Cell State ⓘ
ERK↑, 1, PI3K↑, 1, PTEN↓, 1,
Migration ⓘ
AntiAg↑, 4, MMP9↓, 1, PKCδ↑, 1, VCAM-1↓, 2,
Angiogenesis & Vasculature ⓘ
NO↓, 2, VEGF↓, 1,
Barriers & Transport ⓘ
BBB↑, 1, GLUT4↑, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, ICAM-1↓, 1, IL1↓, 1, IL10↑, 1, IL1α∅, 1, IL1β∅, 1, IL4↑, 1, IL5↑, 1, IL6↓, 1, IL8∅, 1, Imm↑, 1, Inflam↓, 5, MCP1∅, 1, NF-kB↓, 3, TNF-α↓, 1,
Synaptic & Neurotransmission ⓘ
5HT↑, 2, BDNF↑, 1, tau↓, 1,
Protein Aggregation ⓘ
Aβ↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1, BioAv↑, 1, BioAv↝, 6, Dose↝, 23, eff↑, 3, Half-Life↓, 1, Half-Life↑, 1, Half-Life↝, 1,
Clinical Biomarkers ⓘ
ALAT↓, 1, AST↓, 1, BP↝, 1, IL6↓, 1,
Functional Outcomes ⓘ
AntiDiabetic↑, 1, cachexia↓, 1, cardioP↑, 1, cognitive↑, 5, hepatoP↑, 2, motorD↑, 1, neuroP↑, 1, RenoP↑, 1, toxicity↓, 3, toxicity↝, 5, toxicity∅, 1,
Infection & Microbiome ⓘ
Bacteria↓, 2,
Total Targets: 76
Scientific Paper Hit Count for: Dose, Dosage
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
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