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Incidence of microsatellite instability-high hepatocellular carcinoma among Japanese patients and response to pembrolizumab.

Pembrolizumab was quickly approved in many countries for the treatment of patients with unresectable or metastatic, microsatellite instability-high (MSI-H) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. We aimed to determine the incidence of MSI-H tumors in Japanese patients with advanced hepatocellular carcinoma (HCC).

1667 related Products with: Incidence of microsatellite instability-high hepatocellular carcinoma among Japanese patients and response to pembrolizumab.



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Clinical Effectiveness of Levetiracetam Compared to Fosphenytoin in the Treatment of Benzodiazepine Refractory Convulsive Status Epilepticus.

To determine whether levetiracetam is an alternative to fosphenytoin to control Benzodiazepine Refractory Status Epilepticus (BRSE) in pediatric population and also to compare the acute drug related side-effects and ventilation requirement among the both arms of anti-epileptic drug therapy.

2582 related Products with: Clinical Effectiveness of Levetiracetam Compared to Fosphenytoin in the Treatment of Benzodiazepine Refractory Convulsive Status Epilepticus.

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Hydrogen sulfide renal protective effects: possible link between hydrogen sulfide and endogenous carbon monoxide in a rat model of renal injury.

Hydrogen sulfide (HS), along with nitric oxide (NO) and carbon monoxide (CO), proved to have renoprotective effects in various renal diseases. Therefore, this study investigated the renoprotective effect of HS, in a renal injury model, and its crosstalk with other gasotransmitters such as CO. Thirty-two adult rats were divided into four groups: control, gentamicin (GEN)-treated, GEN + sodium hydrosulfide (NaHS), and GEN + NaHS + zinc protoporphyrin (ZnPP) groups. GEN was used to induce renal injury, NaHS is a water-soluble HS, and ZnPP is a selective heme oxygenase-1 (HO-1) inhibitor used to inhibit CO synthesis in vivo. NaHS improved kidney functions in the GEN group as evidenced by significantly lower levels of renal injury markers: serum urea, creatinine, uric acid, urinary albumin excretion, and urinary albumin/creatinine. Moreover, NaHS administration to the GEN-treated group significantly lowered renal levels of NO and tumor necrosis factor-α with an increase in total antioxidant, HO-1, and interleukin-10 levels. Furthermore, NaHS administration downregulated the GEN-induced overexpression of the renal inducible nitric oxide synthase (iNOS) and upregulated the suppression of endothelial nitric oxide synthase (eNOS) with improvement in the histological examination and periodic acid Schiff (PAS) staining. However, this improvement in kidney function produced by NaHS was reduced by combination with ZnPP but still improved as compared with the GEN-treated group. The renoprotective effects of HS can be through its effects on renal tissue antioxidants, pro-inflammatory and anti-inflammatory cytokines, and expression of eNOS and iNOS which can be partially dependent on CO pathway via induction of HO-1 enzyme.

1657 related Products with: Hydrogen sulfide renal protective effects: possible link between hydrogen sulfide and endogenous carbon monoxide in a rat model of renal injury.

Kidney cancer test tissue Goat Anti-Human, Mouse Re Amplite™ Fluorimetric H Goat Anti-Mouse, Rat Rena Renal disease spectrum ti Amplite™ Intracellular Rabbit Anti-Renalase Poly Rabbit Anti-Renalase Poly Advanced Airway Intubatio Potassium hydrogen carbon Rabbit Anti-Renalase Poly Rabbit Anti-Renalase Poly

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Poly(Lactic-co-Glycolic Acid) Nanoparticle Delivery of Peptide Nucleic Acids In Vivo.

Many important biological applications of peptide nucleic acids (PNAs) target nucleic acid binding in eukaryotic cells, which requires PNA translocation across at least one membrane barrier. The delivery challenge is further exacerbated for applications in whole organisms, where clearance mechanisms rapidly deplete and/or deactivate exogenous agents. We have demonstrated that nanoparticles (NPs) composed of biodegradable polymers can encapsulate and release PNAs (alone or with co-reagents) in amounts sufficient to mediate desired effects in vitro and in vivo without deleterious reactions in the recipient cell or organism. For example, poly(lactic-co-glycolic acid) (PLGA) NPs can encapsulate and deliver PNAs and accompanying reagents to mediate gene editing outcomes in cells and animals, or PNAs alone to target oncogenic drivers in cells and correct cancer phenotypes in animal models. In this chapter, we provide a primer on PNA-induced gene editing and microRNA targeting-the two PNA-based biotechnological applications where NPs have enhanced and/or enabled in vivo demonstrations-as well as an introduction to the PLGA material and detailed protocols for formulation and robust characterization of PNA/DNA-laden PLGA NPs.

2699 related Products with: Poly(Lactic-co-Glycolic Acid) Nanoparticle Delivery of Peptide Nucleic Acids In Vivo.

MarkerGeneTM Live Dead As C Peptide ELISA Kit, Rat Rabbit Anti-IAA (Indole-3 Nucleic Acid Isolation En GELRED NUCLEIC ACID STAIN Stat3 Peptide Inhibitor, (FREE SAMPLE) GELRED NUCL Indole 7 carboxylic acid (1R,3S)-1-(1,3-Benzodioxo OliGloTM TAMRA Universal GelGreen Nucleic Acid Sta Indazole 6 carboxylic aci

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Evaluation of the INCREMENT-CPE, Pitt Bacteremia and qPitt Scores in Patients with Carbapenem-Resistant Enterobacteriaceae Infections Treated with Ceftazidime-Avibactam.

The aim of this study was to evaluate the predictive performance of the INCREMENT-CPE (ICS), Pitt bacteremia score (PBS) and qPitt for mortality among patients treated with ceftazidime-avibactam for carbapenem-resistant Enterobacteriaceae (CRE) infections.

1416 related Products with: Evaluation of the INCREMENT-CPE, Pitt Bacteremia and qPitt Scores in Patients with Carbapenem-Resistant Enterobacteriaceae Infections Treated with Ceftazidime-Avibactam.

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Chronic harmine treatment has a delayed effect on mobility in control and socially defeated rats.

Depression is characterized by behavioral, cognitive and physiological changes, imposing a major burden on the overall wellbeing of the patient. Some evidence indicates that social stress, changes in growth factors (e.g., brain-derived neurotrophic factor (BDNF)), and neuroinflammation are involved in the development and progression of the disease. The monoamine oxidase A inhibitor drug harmine was suggested to have both antidepressant and anti-inflammatory properties and may, therefore, be a potential candidate for treatment of depression.

2299 related Products with: Chronic harmine treatment has a delayed effect on mobility in control and socially defeated rats.

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Chrysin attenuates traumatic brain injury-induced recognition memory decline, and anxiety/depression-like behaviors in rats: Insights into underlying mechanisms.

Cortical and hippocampal neuronal apoptosis and neuroinflammation are associated with behavioral deficits following traumatic brain injury (TBI).

1937 related Products with: Chrysin attenuates traumatic brain injury-induced recognition memory decline, and anxiety/depression-like behaviors in rats: Insights into underlying mechanisms.

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Role of the tumor microenvironment in regulating the anti-metastatic effect of KISS1.

KISS1, a metastasis suppressor gene, has been shown to block metastasis without affecting primary tumor formation. Loss of KISS1 leads to invasion and metastasis in multiple cancers, which is the leading cause of cancer morbidity and mortality. The discovery of KISS1 has provided a ray of hope for early clinical diagnosis and for designing effective treatments targeting metastatic cancer. However, this goal requires greater holistic understanding of its mechanism of action. In this review, we go back into history and highlight some key developments, from the discovery of KISS1 to its role in regulating multiple physiological processes including cancer. We discuss key emerging roles for KISS1, specifically interactions with tissue microenvironment to promote dormancy and regulation of tumor cell metabolism, acknowledged as some of the key players in tumor progression and metastasis. We finally discuss strategies whereby KISS1 might be exploited clinically to treat metastasis.

1459 related Products with: Role of the tumor microenvironment in regulating the anti-metastatic effect of KISS1.

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The synergistic anti-proliferative effect of the combination of diosmin and BEZ-235 (dactolisib) on the HCT-116 colorectal cancer cell line occurs through inhibition of the PI3K/Akt/mTOR/NF-κB axis.

One of the most lethal malignancies worldwide is colorectal cancer (CRC). Alterations in various signalling pathways, including PI3K-mTOR and NF-κB, have been reported in CRC with subsequent dysregulation of proliferation, apoptosis, angiogenesis and, questionably, autophagy processes. BEZ-235 (dactolisib) is a dual PI3K-mTOR inhibitor with potent anti-tumour activity. However, the observed toxicity of BEZ-235 necessitated the termination of its clinical trials. Hence, we aimed to evaluate the potential long-lasting anti-carcinogenic effects of adding diosmin (DIO, a natural NF-κB inhibitor) to BEZ-235 in HCT-116 CRC cells. The median inhibitory concentrations (IC50s) of BEZ-235 and/or DIO were evaluated in the HCT-116 CRC cell line. Caspase-3 activity was assessed colorimetrically, and p-Akt, NF-κB, CD1, VEGF and LC3B levels were assessed by ELISA. Additionally, LC3-II and P62 gene expression were assessed using qRT-PCR. The observed CIs (combination indices) and DRIs (dose reduction indices) confirmed the synergistic effect of DIO and BEZ-235. Co-administration of both drugs either in combination-1 (1 μM for BEZ-235, 250 μM for DIO) or in combination-2 (0.51 μM for BEZ-235 + 101.99 μM for DIO) inhibited the PI3K/Akt/mTOR/NF-κB axis, leading to the induction of apoptosis (via active caspase-3), and the inhibition of proliferation marker (CD1), angiogenesis marker (VEGF), autophagy protein (LC3B) and altered effects on LC3-IIandP62 gene expression. Our results reveal the synergistic chemotherapeutic effects of DIO combined with BEZ-235 in the HCT-116 CRC cell line and encourage future preclinical and clinical studies of this combination with reduced BEZ-235 concentrations to avoid its reported toxicity.

2409 related Products with: The synergistic anti-proliferative effect of the combination of diosmin and BEZ-235 (dactolisib) on the HCT-116 colorectal cancer cell line occurs through inhibition of the PI3K/Akt/mTOR/NF-κB axis.

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Posture related in-vitro characterization of a flow regulated MEMS CSF valve.

Overdrainage in upright position is one of the most prevalent issues in treating hydrocephalus with a cerebrospinal fluid (CSF) shunt. Anti-siphon devices (ASDs) are employed to reduce this problem. A novel microelectromechanical system (MEMS)-based valve, termed Chronoflow device, aims to regulate CSF drainage indifferently of the body posture. With this study, the suitability of this MEMS-based valve is evaluated regarding its use for the treatment of hydrocephalus, particularly for the prevention of overdrainage and blockage. In total, four Chronoflow devices were tested. An established in-vitro hardware-in-the-loop (HIL) test bed was used to investigate the valves regarding their pressure-flow characteristics, their behaviors towards CSF dynamics, and their capabilities to prevent CSF overdrainage in upright position. Additionally, a contamination test was conducted to evaluate the susceptibility of the device to blockage due to particles. All valves tested regulated the drainage rate at similar nominal flows and independently of posture. The pressure-flow relation measured, however, was notably higher than numerically calculated. Regarding the CSF dynamics, the first three valves tested led to a decreased steady-state intracranial pressure in supine position and showed stable drainage rate in upright position. During the transitional phase from supine to upright and vice versa, the valves continuously adjusted the outflow resistance, which resulted in a stable transitional phase preventing overdrainage. Yet, the fourth valve showed continuous overdrainage in upright position due to an increased nominal flow. However, after several test iterations the nominal flow decreased and stabilized at a level similar to that of the first three valves tested. The contamination test showed that most particles initially adhere to the pillars and spread throughout the cavity of the valve as the concentration of particles increases, thereby affecting the displacement of the membrane. The devices generally provide a stable flow regulation and prevent overdrainage in upright position. Specifically, their drainage behaviors during the posture changes are very effective. However, they also showed high hysteresis and sensitivity towards particle contamination, which resulted in initial increased and altering nominal flows after many test iterations. This result suggests that the MEMS design presented lacks robustness. Yet, an upstream filter and specific coatings on the fluid pathway may increase significantly its reliability.

1427 related Products with: Posture related in-vitro characterization of a flow regulated MEMS CSF valve.

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