C-terminal domain of p16(INK4a) is adequate in inducing cell cycle arrest, growth inhibition and CDK4/6 interaction similar to the full length protein in HT-1080 fibrosarcoma cells.

The tumor suppressor p16(INK4a) has earned widespread attention in cancer studies since its discovery as an inhibitor of cyclin-dependent kinases (CDKs) 4/6. Structurally, it consists of four complete ankyrin repeats, believed to be involved in CDK4 interaction. According to the previous disparities concerning the importance of domains and inactivating mutations in p16, we aimed to search for the domain possessing the functional properties of the full length protein.

Cyclooxygenase 2 plays a role in Emdogain-induced proliferation.

Background And Objective: Enamel matrix proteins are involved in the development and regeneration of root cementum and in its attachment to dentin; however, the mechanisms through which this occurs have yet to be elucidated. The present study was therefore carried out to evaluate the mitogenic and proliferative responses of human periodontal fibroblast (HPLF) cells to Emdogain (EMD), and the potential role of cyclooxygenase 2 (COX-2) in this process.

Material And Methods: We investigated the effects of EMD on 5-bromo-2'-deoxyuridine (BrdU) incorporation, colchicine freezing of mitosis, XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and Trypan Blue dye exclusion, with or without celecoxibe, a selective cyclooxygenase-2 (COX-2) inhibitor; we also evaluated the expression of COX-2 mRNA and COX-2 protein in response to EMD.

Whole sheep ovary cryopreservation: evaluation of a slow freezing protocol with dimethylsulphoxide.

Purpose: To evaluate a slow freezing method for whole ovary cryopreservation by evaluating effects of added cryoprotectant.

Methods: Sheep ovaries were isolated during surgery, flushed with either Ringer-Acetate or dimethylsulphoxide and cryopreserved by slow freezing. After rapid thawing, viability was assessed by ovarian in vitro perfusion, cell culture, histology and fluorescent live-dead assay.

Influence of CYP2C9 polymorphism on metabolism of valproate and its hepatotoxin metabolite in Iranian patients.

Sodium valproate (VPA) has 16 known metabolites in humans. The 2-ene-VPA has anti-convulsant efficacy and 4-ene-VPA is reported to contribute in VPA hepatotoxicity. The formation of 4-ene-VPA is catalyzed by cytochrome P450 2C9 (CYP2C9).

Protection by pentoxifylline of malathion-induced toxic stress and mitochondrial damage in rat brain.

Objective: The objective of this study was to investigate the possible protective effects of pentoxifylline as a phosphodiesterase-5 inhibitor on malathion-induced oxidative damage to rat brain mitochondria.

Methods: Rats received malathion (200 mg/kg/day) and pentoxifylline (PTX, 50 mg/kg/day) in combination or alone. Alpha-tocopherol (AT, 15 mg/kg/day) was used as a positive standard.

Neuronal apoptosis inhibitory protein, NAIP, is an inhibitor of procaspase-9.

Ability of the full length NAIP and its BIR3 domain in inhibition of the proteases of the intrinsic apoptosis pathway was investigated. Activity of endogenous executioner caspases was drastically reduced by both recombinant NAIP-BIR3 (NBIR3) and the full length protein. Western blotting experiments showed that the full length NAIP and its BIR3 domain inhibited the cleavage of procaspase-3 by apoptosome activated caspase-9.

The expression of p38, ERK1 and Bax proteins has increased during the treatment of newly diagnosed acute promyelocytic leukemia with arsenic trioxide.

Background: Promising reports exist regarding the use of arsenic trioxide (ATO) as first-line treatment in acute promyelocytic leukemia (APL). Although the in vitro effect of ATO is extensively studied, the in vivo mechanism(s) of ATO action is mostly unknown.

Patients And Methods: Newly diagnosed APL patients were involved and received ATO (0.

Correlation between inducible nitric oxide synthase and cyclooxygenase-2 expression in human colorectal adenocarcinoma: a cross-sectional study.

Cyclooxygenase-2 (COX-2) enzyme is believed to play a role in tumor angiogenesis, differentiation, and apoptosis. The inducible isoform of nitric oxide synthase (iNOS) also has the potential ability to damage DNA and conceivably contribute to tumor formation by a rise in nitric oxide production. Seventeen patients diagnosed with colorectal adenocarcinoma, who underwent surgical resection of the tumor, were enrolled in the study.

The effect of full length and mature NAG-1 protein overexpression on cytotoxicity of celecoxib, tamoxifen and doxorubicin in HT1080.

Background And The Purpose Of The Study: Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is involved in inflammation, apoptosis/survival and tumorigenesis as well as resistance to chemotherapy. NAG-1 protein is synthesized as pro-peptide, cleaved and secreted as mature protein. Regulation of NAG-1 is not completely discovered and increased level of NAG-1 has been reported in many cancers.

Primary WWOX phosphorylation and JNK activation during etoposide induces cytotoxicity in HEK293 cells.

Background And The Purpose Of The Study: Etoposide is an antineoplastic agent used in multiple cancers. It is known that etoposide induce cell death via interaction with topoisomerase II; however, the etopoisde cellular response is poorly understood. Upon etoposide induced DNA damage, many stress signaling pathways including JNK are activated.

Neurodegenerative, with expression ATF-2 by p38 in cortical neurons.

DNA damage, as an important initiator of neuronal cell death, has been implicated in numerous neurodegenerative conditions. We previously delineated several pathways that control embryonic cortical neuronal cell death evoked by the DNA-damaging agent, camptothecin. The topisomerase-1 inhibitor, camptothecin, has been shown to induce cortical neuronal cell death in a reproducible and synchronistic manner.

Physiological genomics identifies estrogen-related receptor alpha as a regulator of renal sodium and potassium homeostasis and the renin-angiotensin pathway.

Estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor highly expressed in the kidney, an organ playing a central role in blood pressure regulation through electrolyte homeostasis and the renin-angiotensin system. Physiological analysis revealed that, relative to wild-type mice, ERRalpha null mice are hypotensive despite significant hypernatremia, hypokalemia, and slight hyperreninemia. Using a combination of genome-wide location analysis and expression profiling, we demonstrate that ERRalpha regulates the expression of channels involved in renal Na(+) and K(+) handling (Scnn1a, Atp1a1, Atp1b1) and altered in Bartter syndrome (Bsnd, Kcnq1).

Cellular cytotoxicity and in-vivo biodistribution of docetaxel poly(lactide-co-glycolide) nanoparticles.

Docetaxel (DTX) is one of the most effective antineoplastic drugs. However, its current clinical administration, formulated in tween80, causes serious side effects. This study is focused on preparation and evaluation of poly(lactide-co-glycolide) nanoparticles (NPs) containing DTX to remove tween80.

The time course of Akt and ERK activation on XIAP expression in HEK 293 cell line.

The cell growth is controlled by the interaction of survival and cell growth arrest pathways as well as apoptosis mechanisms which determine the outcome of cell faith as proliferation or apoptosis. In this study, we have studied the activity of survival pathways, i.e.

Genome-wide identification of direct target genes implicates estrogen-related receptor alpha as a determinant of breast cancer heterogeneity.

Estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor, the expression of which correlates with negative prognosis in breast cancer. ERRalpha shares functional features with the estrogen receptor alpha (ERalpha) and its activity is modulated by the ERBB2 signaling pathway. Using genome-wide binding sites location analyses in ERalpha-positive and ERalpha-negative breast cancer cell lines, we show that ERRalpha and ERalpha display strict binding site specificity and maintain independent mechanisms of transcriptional activation.

Correlation of cyclooxygenase 2 expression and inflammatory cells infiltration in colorectal cancer.

This study want to determine correlation of cyclooxygenans 2 (Cox-2) expression and inflammatory reaction in colorectal carcinoma. Archival H and E slides of 150 patients with primary colorectal carcinoma were reviewed to confirm pathological feature and to select suitable tissue blocks for immunohistochemical staining with mouse monoclonal antibody against human Cox-2 and various inflammatory cells. After scoring, statistical analysis were carried out with SPSS software, chi2 methods and bivariate pearson correlation analysis.

Simulation of different truncated p16(INK4a) forms and in silico study of interaction with Cdk4.

Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex.

Viability and function of the cryopreserved whole ovary: in vitro studies in the sheep.

Background: Cryopreservation of whole ovaries followed by vascular transplantation may improve long-term function in comparison to conventional cryopreservation of ovarian cortex and avascular transplantation. The aim of this study was to assess methods for the evaluation of viability and function of frozen-thawed whole ovaries.

Methods: Ewe ovaries were flushed with either cryoprotectant (propandiol: FROZEN-PROH) or Ringer Acetate (FROZEN-RA) followed by slow freezing.

ATP depletion as a consequence of hypoxia enhances tamoxifen antiproliferative effects in T47D breast carcinoma cells.

Tamoxifen causes a mitochondrial transmembrane potential dysfunction and ATP depletion, which may play a role in tamoxifen cytotoxicity. Administration of oligomycin-2 deoxy glucose (2DG) enhanced tamoxifen antiproliferative effects, which may be due to exacerbated ATP depletion following tamoxifen and oligomycin-2DG coadministration. Sodium nitroprusside (SNP) did not significantly change tamoxifen responsiveness at 0.

Tolerance to the anticonvulsant effect of morphine in mice: blockage by ultra-low dose naltrexone.

The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a mouse model of clonic seizures induced by pentylenetetrazole, and whether ultra-low doses of the opioid receptor antagonist naltrexone which selectively block G(s) opioid receptors were capable of preventing the observed tolerance. The results showed that the morphine anticonvulsant effect could be subject to tolerance after repeated administration. Both the development and expression of tolerance were inhibited by ultra-low doses of naltrexone, suggesting the possible involvement of G(s)-coupled opioid receptors in the development of tolerance to the anticonvulsant effect of morphine.

The role of glutathione-S-transferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N-acetylcysteine.

Oxidative stress has a proven role in pathophysiology of acute respiratory distress syndrome. The antioxidant drugs, especially N-acetylcysteine (NAC) have been used for years to overcome oxidative stress effects in patients. In the present study we have investigated the effects of NAC treatment (IV NAC in 150mg/kg at the first day followed by 50mg/kg/day for three days) on 27 ICU patients with ALI/ARDS considering the glutathione-S-transferase genetic variations, as an important enzyme contributing in oxidative stress pathways.

Docetaxel-albumin conjugates: preparation, in vitro evaluation and biodistribution studies.

Docetaxel (DTX) is one of the most active chemotherapeutic agents for treating metastatic breast cancer. Its aqueous solubility is very low, hence the available formulation of DTX for clinical use consists of high concentrations of tween80, which has been associated with several hypersensitivity reactions. To reduce the systemic toxicity of DTX as well as to avoid the use of tween80, in this study DTX was chemically conjugated with human serum albumin via a succinic spacer.

Monocyte chemotactic protein-1 (MCP-1), its receptor, and macrophages in the perifollicular stroma during the human ovulatory process.

Objective: To evaluate the expression and localization of the macrophage-specific chemokine monocyte chemotactic protein-1 (MCP-1), CC chemokine receptor 2 (CCR2), and macrophages (CD68) in the perifollicular stroma of different phases of the human ovulatory process and its relation to macrophage influx.

Design: Experimental study on patient-controlled material.

Setting: University hospital.