Effect of PAIP1 on the metastatic potential and prognostic significance in oral squamous cell carcinoma / 国际口腔科学杂志·英文版

Poly Adenylate Binding Protein Interacting protein 1 (PAIP1) plays a critical role in translation initiation and is associated with the several cancer types. However, its function and clinical significance have not yet been described in oral squamous cell carcinoma (OSCC) and its associated features like lymph node metastasis (LNM). Here, we used the data available from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to analyze PAIP1 expression in oral cancer. The publicly available data suggests that PAIP1 mRNA and protein levels were increased in OSCC. The high PAIP1 expression was more evident in samples with advanced stage, LNM, and worse pattern of invasion. Moreover, the in vitro experiments revealed that PAIP1 knockdown attenuated colony forming, the aggressiveness of OSCC cell lines, decreasing MMP9 activity and SRC phosphorylation. Importantly, we found a correlation between PAIP1 and pSRC through the analysis of the IHC scores and CPTAC data in patient samples. Our findings suggest that PAIP1 could be an independent prognostic factor in OSCC with LNM and a suitable therapeutic target to improve OSCC patient outcomes.

Antitumor effect of TW-37, a BH3 mimetic in human oral cancer / 한국실험동물학회지

TW-37 is a small molecule B cell lymphoma-2 (Bcl-2) homology 3 mimetic with potential anticancer activities. However, the in vivo anti-cancer effect of TW-37 in human oral cancer has not been properly studied yet. Here, we attempted to confirm antitumor activity of TW37 in human oral cancer. TW-37 significantly inhibited cell proliferation and increased the number of dead cells in MC-3 and HSC-3 human oral cancer cell lines. TW-37 enhanced apoptosis of both cell lines evidenced by annexin V/propidium iodide double staining, sub-G1 population analysis and the detection of cleaved poly (ADP-ribose) polymerase and caspase-3. In addition, TW-37 markedly downregulated the expression of Bcl-2 protein, while not affecting Bcl-xL or myeloid cell leukemia-1. In vivo, TW-37 inhibited tumor growth in a nude mice xenograft model without any significant liver and kidney toxicities. Collectively, these data reveal that TW-37 may be a promising small molecule to inhibit human oral cancer.

Clinical Efficacy of Pravastatin(Mevalotin(R)) in Patients with Hypercholesterolemia

An open clinical trial was performed to test the efficacy and side effects of Pravastatin(Mevlotin(R)), HMG-CoA reductase inhibitor, administering 5mg twice daily for 12weeks in 30 patients of hypercholesterolemia in out patient clinics, Pusan National University Hospital. The total cholesterol, triglyceride and HDL-cholesterol were measured with enzyme methods and LDL-cholesterol was calculated indirectly by Friedewald formula. The result obtained were as follows: 1) The degree of change at the end points compared with baseline pretreatment levels were 26.1% fall in serum total cholesterol.36.6% fall in LDL-cholesterol, 20.8% fall in triglyceride and 14, 6% rise in HDL-cholesterol. And the rate of improvement more than moderate degree were 90.0% in total cholesterol(the fall of 10% or more), 53.3% in triglyceride (the fall 20% or more) and 33.3% in HDL-cholesterol(the rise of 7mg% or more). 2) The total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL cholesterol ratios were decreased significantly from 6, 4+/-0.7 to 4.2+/-0.5(34.4%) and from 4.5+/-0.7 to 2.5 +/-0.4(44.4%) respectively. 3) The greatest fall in serum total cholesterol and LDL-cholesterol were observed in 2 weeks after administrating drug and thereafter fell gradually and maintained until 12 weeks of endpoint, but HDL-cholesterol showed significant rise from the 4 weeks of administration. On the other hand triglyceride showed remarkable fall in the measured values from the 4 weeks but statistical significance was observed only in 10 and 12 weeks after administration owing to wide individual variation of values. 4) There observed the tendency that the higher the initial pretreatment levels the greater the degree of fall in total cholesterol and triglyceride. 5) Neither side effects nor abnormal laboratory findings were shown during the period of observation. The results suggest that Pravastatin will be a useful and safe drug in the treatment of hyperlipidemia.

Evaluation of the Efficacy and Tolerability of Isradipine in the Treatment of Mild to Moderate Hypertension

An open clinical trial was conducted to evaluate the efficacy and tolerability of isradipine in 30 cases (male 16, female 14 cases, average age 52.6+/-7.94) of mild to moderate essential hypertension using 1.25-2.5mg twice a day for 8 weeks of active treatment. Blood pressure was significantly reduced from 168.5+/-14.33/108.3+/-6.37mmHg, 163.7+/-9.74/105.5+/-7.1mmHg to 141.0+/-13.69/92.0+/-9.27mmHg, 138.8+/-13.46/92.3+/-11.16mmHg in sitting and standing position respectively. The extent of reduction was 27.5/16.3mmHg in sitting position and 29.9/13.2mmHg in standing position. This comprised the mean response rate in terms of reduction of DBP of 10mmHg or more being 90% and the normalization rate, deficed as DBP lowering to 90mmHg or below, being 70%. Heart rate, hematology and blood chemistry including blood sugar and lipids were not changed significantly after treatment with isradipine. No significantl side effect was observed except 2 cases of mild transient facial flushing and nausea during the treatment, so could proceed the trial without drug discontinuation in all 30 cases. The results suggest that isradipine is one of the useful and safe drugs in the treatment of mild to moderate essential hypertension.

Clinical Effects of Isosorbide 5-Mononitrate(Elantan(R)) on Angina Pectoris

An open trial was carried out to investigate the efficacy and tolerance of isosorbide 5-mononitrate(Elantan(R)) in 30 patients diagnosed as angina pectoris at Pusan national university hospital. Drugs were given 20mg two times daily for 2 to 3 weeks and the results were assessed in terms of effects on anginal pain and untoward side effects experienced during administration of medication. Treament resulted in an overall improvement in 25 patients(83.4%), complete abolition of anginal attacks in 17 patients(56.7%) and reduction in frequency of attacks in 8 patients(26.7%). So called "Nitrated headache" was observed in 5 patients(16.6%) but improved with proceeding of administration in 3 patients. This trial indicates that isosorbide 5-mononitrate should be efficacious as well as tolerated in patients with coronary heart disease.