Autophagy Inhibition Potentiates the Anticancer Effects of a Bendamustine Derivative NL-101 in Acute T Lymphocytic Leukemia.

Acute T lymphocytic leukemia (T-ALL) is an aggressive hematologic resulting from the malignant transformation of T-cell progenitors. Drug resistance and relapse are major difficulties in the treatment of T-ALL. Here, we report the antitumor potency of NL-101, a compound that combines the nitrogen mustard group of bendamustine with the hydroxamic acid group of vorinostat.

A novel SAHA-bendamustine hybrid induces apoptosis of leukemia cells.

Hybrid anticancer drugs are of great therapeutic interests as they can potentially overcome the deficiencies of conventional chemotherapy drugs and improve the efficacy. Many studies have revealed that the combination of histone deacetylase inhibitors (HDACi) and alkylating agents have synergistic effects. We reported a novel hybrid NL-101, in which the side chain of bendamustine was replaced with the hydroxamic acid of HDACi vorinostat (SAHA).

Synthesis and anticancer evaluation of thiazolyl-chalcones.

Thirty-seven (E)-1-(4-methyl-2-arylaminothiazol-5-yl)-3-arylprop-2-en-1-ones were synthesized via Claisen-Schmidt condensation of 1-(4-methyl-2-(arylamino)thiazol-5-yl)ethanone with the corresponding arylaldehydes. All these thiazolyl-chalcones were characterized and evaluated by MTT assay on human cancer cell lines BGC-823, PC-3, NCI-H460, BEL-7402 in vitro. Compounds 5, 8, 26, 37 and 41 are effective against cancer cell lines with IC(50)s below 10 μM.

Synthesis and anticancer evaluation of alpha-lipoic acid derivatives.

alpha-Lipoic acid derivatives were synthesized and evaluated for their in vitro anticancer activities against NCI-460, HO-8910, KB, BEL-7402, and PC-3 cell lines. The results, for most compounds exhibited dose-dependent inhibitory property and several compounds had good inhibitions at the dose of 100 microg/mL. Compound 17 m was further selected for in vivo evaluation against S180 xenograft in ICR mice, which had 24.

[Effects of cysteinyl receptor agonist and antagonists on rat primary cortical neurons].

Objective: To determine the effect of cysteinyl receptor agonist leukotriene D(4) (LTD(4)) and its antagonists on rat primary neurons.

Methods: In the primarily cultured rat cortical neurons, the neuron injury was evaluated by measuring intracellular calcium, 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) reduction, and propidium iodide (PI) and Hoechst 33258 staining. The in vitro ischemic injury was induced by oxygen-glucose deprivation (OGD) for 1.

Baicalin attenuates oxygen-glucose deprivation-induced injury via inhibiting NMDA receptor-mediated 5-lipoxygenase activation in rat cortical neurons.

The flavonoid baicalin exerts neuroprotective effects but the mechanism is not fully clarified. On the other hand, 5-lipoxygenase (5-LOX) activation is involved in ischemic neuronal injury. In this study, we determined whether baicalin protects rat cortical neurons against oxygen-glucose deprivation (OGD)-induced ischemic-like injury, if so, whether this effect relates to 5-LOX activation.

[Homeostatic conditions affect the protective effect of edaravone on ischemic injury in neurons].

Objective: To determine whether homeostatic conditions (pH, glycine or ion concentration) affect the protective effects of edaravone on ischemic injury in rat cortical neurons.

Methods: In cultured rat cortical neurons, the compositions in the experimental solutions were changed to mimic the disturbance of homeostasis after cerebral ischemia. In vitro ischemic injury was induced by oxygen-glucose deprivation (OGD) for 3 h and reperfusion for 12 h, and the neuron injury was evaluated by 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) reduction assay and lactate dehydrogenase (LDH) release.

Activation of 5-lipoxygenase after oxygen-glucose deprivation is partly mediated via NMDA receptor in rat cortical neurons.

5-Lipoxygenase (5-LOX) is the enzyme metabolizing arachidonic acid to produce pro-inflammatory leukotrienes. We have reported that 5-LOX is translocated to the nuclear envelope after ischemic-like injury in PC12 cells. In the present study, we determined whether 5-LOX is activated (translocation and production of leukotrienes) after oxygen-glucose deprivation (OGD) in primary rat cortical neurons; if so, whether this activation is mediated by NMDA receptor.

Minocycline protects PC12 cells against NMDA-induced injury via inhibiting 5-lipoxygenase activation.

Recently, we have reported that minocycline, a semi-synthetic tetracycline with neuroprotective effects, inhibits the in vitro ischemic-like injury and 5-lipoxygenase (5-LOX) activation in PC12 cells. In the present study, we further determined whether minocycline protects PC12 cells from excitotoxicity via inhibiting 5-LOX activation. We used N-methyl-d-aspartate (NMDA, 200 microM) to induce early (exposure for 6 h) and delayed (exposure for 6 h followed by 24 h recovery) injuries.

Distribution of cysteinyl leukotriene receptor 2 in human traumatic brain injury and brain tumors.

Aim: To determine the distribution of cysteinyl leukotriene receptor 2 (CysLT2), one of the cysteinyl leukotriene receptors, in human brains with traumatic injury and tumors.

Methods: Brain specimens were obtained from patients who underwent brain surgery. CysLT2 in brain tissues was examined using immunohistochemical analysis.

GM1 stabilizes expression of NMDA receptor subunit 1 in the ischemic hemisphere of MCAo/reperfusion rat.

Objective: To determine the protective effect of monosialoganglionside (GM1) and evaluate the influence of GM1 on expression of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) in Sprague-Dawley (SD) rats with focal cerebral ischemia-reperfusion (I/R).

Methods: Left middle cerebral artery (MCA) was occluded by an intraluminal suture for 1 h and the brain was reperfused for 72 h in SD rats when infarct volume was measured, GM1 (10 mg/kg) was given ip (intraperitoneally) at 5 min (group A), 1 h (group B) and 2 h (group C) after MCA occlusion (MCAo). Expression of NMDAR1 was detected by Western blot at various time after reperfusion (4 h, 6 h, 24 h, 48 h and 72 h) in ischemic hemispheres of the rats with or without GM1 administered.

[Reversing effect of histamine on neuron death induced by N-methyl-D-aspartate].

Objective: To determine the effect of histamine on N-methyl-D-aspartate (NMDA) induced neuron death and to elucidate its mechanism.

Methods: The primary cortical cell culture was adopted. Neuron morphology and MTT assay were used to evaluate the drugs effects.

Monosialoganglioside protected ischemic rat hippocampal slices through stabilizing expression of N-methyl-D-aspartate receptor subunit.

Aim: To determine direct protective effect of monosialoganglioside (GM1) on hippocampal slices after oxygen-glucose deprivation and reperfusion (OGD/RP), and investigate the influence on the expression of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) in those hippocampal slices.

Methods: Injury of hippocampal slices and protective effects of GM1 were detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining, toluidine blue staining, and transmission electron microscopy of rat hippocampal slices. Expression of NMDAR1 was detected by Western blot.

[An improved quantitative method for evaluation of ischemic injury and neuroprotection in mouse brain slices].

Objective: To establish a simpler and more accurate method for evaluating in vitro ischemic injury and neuroprotective effects of drugs through improving experimental instrument and quantitative index in mouse brain slices.

Methods: An incubation instrument was developed and its application tested. 2,3,5-triphenyltetrazolium chloride (TTC) was used as a substrate to biosynthesize formazan standard in mouse brain slices, and formazan was isolated, purified and identified.

[Study on protective effect of monosialoganglioside (GM1) on injury induced by oxygen glucose deprivation/reperfusion in rat hippocampal slices].

Aim: To investigate the protective effect of monosialoganglioside (GM1) on injury induced by oxygen glucose deprivation/reperfusion (OGD/Rep) in rat hippocampal slices.

Methods: The protective effects of GM1 on hippocampal slices after OGD/Rep were observed by detecting the light transmittance (LT) changes of rat hippocampal slices and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining of rat hippocampal slices.

Results: (1) In four groups treated with 0 (control), 0.