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Chinese Medical Journal ; (24): 1523-1528, 2015.
Article in English | WPRIM | ID: wpr-231744


<p><b>BACKGROUND</b>Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats. In this study, we observed the effect of salubrinal (Sal, Sigma, USA) on liver cells in BD rats and explored its relevant mechanisms.</p><p><b>METHODS</b>Thirty Sprague-Dawley rats were equally randomized into three groups: BD group, Sal group, and DMSO group. The BD models were established by increasing intracranial pressure in a modified, slow, and intermittent way. In the drug groups, Sal was administered 1 h before the induction of BD. After modeling was completed, the blood and liver samples were harvested. CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction. PKR-like ER kinase (PERK), P-eukaryotic translation initiation factor 2α (eIF2α), eIF2α, CHOP and caspase-12 expression was detected using western blotting (WB). CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC). Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer. Hepatic cell apoptosis was detected using TUNEL. The results were analyzed using Quantity-one v4.62 software (Bio-Rad, USA).</p><p><b>RESULTS</b>CHOP and caspase-12 expression and PERK, eIF2α, and P-eIF2α protein expression showed no significant difference between BD group and DMSO group. Compared with BD group, Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P < 0.05). However, eIF2α expression showed no significant difference (P > 0.05). After the Sal treatment, CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P < 0.05). WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment. Sal was associated with improved liver function and decreased hepatic cell apoptosis.</p><p><b>CONCLUSIONS</b>Sal can significantly reduce apoptosis in hepatic cells of BD rats. This protective effect may be achieved via the PERK-eIF2α signaling pathway.</p>

Animals , Apoptosis , Blotting, Western , Brain Death , Metabolism , Caspase 12 , Genetics , Metabolism , Cinnamates , Disease Models, Animal , Endoplasmic Reticulum Stress , Eukaryotic Initiation Factor-2 , Genetics , Metabolism , Immunohistochemistry , Liver , Wounds and Injuries , Male , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Thiourea , Transcription Factor CHOP , Genetics , Metabolism
Article in Chinese | WPRIM | ID: wpr-250270


<p><b>OBJECTIVE</b>To study the relationship between status of methylation of human runt-related transcription factor 3 (RUNX3) gene promoter in papillary thyroid carcinoma (PTC).</p><p><b>METHODS</b>Methylation-specific PCR and immunohistochemical SP technique were used to detect the methylation of RUNX3 gene promoter and expression of its protein in 56 cases of PTC and their matched adjacent non-carcinous epithelium (NCE).</p><p><b>RESULTS</b>In NCE, there was no methylation of RUNX3 gene promoter, while in PTC the methylation rate was 35.7%(20/56), which was related to the tumor TNM stage, pathological grade and lymph node metastasis (P < 0.05). The positive rates of RUNX3 protein expression in NCE and PTC were 100.0% and 60.7%, respectively, with a significant difference (χ(2) = 27.378, P < 0.05). In PTC, the positive rates of RUNX3 protein expression in gradeI and grade II were 70.0% and 37.5%, respectively (P < 0.05); the rates were 46.7% and 76.9% in lymph node metastasis group and no metastasis group, respectively (P < 0.05). Moreover, there was a distinct correlation between methylation of RUNX3 gene promoter and expression of its protein (χ(2) = 21.62, P < 0.01).</p><p><b>CONCLUSIONS</b>Methylation of promoter might be one of the important factors of inactivation of RUNX3 gene, and might play an important role in carcinogenesis and progression of PTC.</p>

Adolescent , Adult , Aged , Carcinoma , Carcinoma, Papillary , Core Binding Factor Alpha 3 Subunit , Genetics , Metabolism , DNA Methylation , Female , Humans , Male , Middle Aged , Promoter Regions, Genetic , RNA, Messenger , Genetics , Thyroid Neoplasms , Metabolism , Pathology , Young Adult
Article in Chinese | WPRIM | ID: wpr-277479


<p><b>OBJECTIVE</b>To study the expressions of Piwil2 protein and mRNA in papillary thyroid carcinoma (PTC) and the relationship between Piwil2 and the invasion and metastasis of PTC.</p><p><b>METHODS</b>Immunohistochemistry and in situ hybridization were used to detect the expression of Piwil2 protein and mRNA in 60 cases of PTC with the matched adjacent non-cancerous epithelium (NCE).</p><p><b>RESULTS</b>The positive rates of Piwil2 protein expression in PTC and NCE were 88.3% (53/60) and 10.0% (6/60) respectively, with significant difference (χ² = 73.654, P < 0.01). The positive rates of Piwil2 mRNA expression in PTC and NCE were 85.0% (51/60) and 6.7% (4/60) respectively, also with significant difference (χ(2) = 74.148, P < 0.01). Up-regulated expressions of Piwil2 protein and mRNA were related to the invasion and metastasis of PTC (P < 0.05).</p><p><b>CONCLUSIONS</b>Piwil2 may play a role in the invasion and metastasis of PTC.</p>

Adolescent , Adult , Aged , Argonaute Proteins , Carcinoma , Carcinoma, Papillary , Child , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Proteins , Genetics , Metabolism , RNA, Messenger , Genetics , Thyroid Neoplasms , Metabolism , Pathology , Young Adult
Acta Pharmaceutica Sinica ; (12): 109-114, 2009.
Article in Chinese | WPRIM | ID: wpr-232588


Folate receptor (FR) is over-expressed in a variety of human cancers and it is seldom expressed or found in normal tissues. Therefore, folate receptor-mediated antitumor drugs can be targeted specially to the FR-positive tumor cells. This strategy improves the selectivity of drugs which may destroy the normal tissues in traditional chemotherapeutics. This review provides the delivery mechanism of FR-mediated antitumor drugs and highlights the novel folate-drug conjugates and their activities.

Animals , Antineoplastic Agents , Chemistry , Pharmacology , Carrier Proteins , Metabolism , Cell Line, Tumor , Drug Carriers , Drug Delivery Systems , Folate Receptors, GPI-Anchored , Folic Acid , Chemistry , Pharmacology , Humans , Neoplasms , Metabolism , Pathology , Receptors, Cell Surface , Metabolism
Acta Pharmaceutica Sinica ; (12): 741-746, 2007.
Article in Chinese | WPRIM | ID: wpr-268586


A series of 4(3H)-quinazolinone derivatives bearing dithiocarbamate side chains have been synthesized through the reaction of 6-bromomethyl-2-methyl-4(3H)-quinazolinone with CS2 and various amines in the presence of anhydrous K3PO4, and their structures were confirmed with ESI-MS, H NMR, elemental analysis or HRMS. The target compounds 8a -8q were tested for their in vitro antitumor activity against human myelogenous leukaemia K562 and human Hela cell lines by means of colorimetric MTT assay. Among the tested compounds, 8q exhibited in vitro inhibitory activity against K562 and Hela cells with IC50 values of 0.5 and 12.0 micromol x L(-01), respectively. Therefore, compound 8q is worthy to be a lead compound for the design and synthesis of new antitumor agents.

Antineoplastic Agents , Pharmacology , Ethylenebis(dithiocarbamates) , Chemistry , Pharmacology , HeLa Cells , Humans , Inhibitory Concentration 50 , K562 Cells , Molecular Structure , Quinazolinones , Chemistry , Pharmacology , Structure-Activity Relationship