Antitumor effects of apoptin expressed by the dual cancer-specific oncolytic adenovirus - a review.

Apoptin is a small molecular weight protein derived from chicken anemia virus, which can induce the apoptosis of transformed cells and tumor cells and leave primary and nontransformed cells unharmed. Apoptin's cell localization depends on its own phosphorylation state and cell type. In tumor cells, phosphorylated apoptin enters the nucleus and induces apoptosis. While, in normal cells apoptin mainly exists in the cytoplasm. Apoptin, as a disordered protein in cells, interacts with many proteins in cell signal pathways to induce apoptosis of tumor cells. The specific mechanism of apoptosis induced by apoptin has not been completely elucidated. Therefore, apoptin has become a potential anticancer agent. This review summarizes the research results of apoptin in our laboratory and reveals the specific antitumor mechanism of apoptin expressed by oncolytic virus vector on a variety of tumor cells and mouse models.

Identification of four novel ADAMs with potential roles in spermatogenesis and fertilization.

The ADAM (A Disintegrin And Metalloprotease) family is known to have important roles in various developmental systems, e.g., myogenesis and neurogenesis. In this study, we searched for ADAMs that may function in spermatogenesis or fertilization, and have cloned and sequenced four new mouse ADAM cDNAs: ADAM 24, ADAM 25, ADAM 26 and ADAM 27. The deduced amino acid sequences show that all four contain the complete domain organization common to ADAM family members. Messenger RNA for each of the four ADAMs was found only in the testis. The conserved zinc-dependent metalloprotease active site HEXGHXXGXXHD was found in the metalloprotease domain of three of the novel ADAMs, suggesting that they are testis-specific proteases, to which we give the alternative names: testase 1, ADAM 24; testase 2, ADAM 25; and testase 3, ADAM 26. Using RNA extracted from testes of pre-pubertal males of increasing age (8-40days), we found that adult levels of transcription, assessed in Northern blots, are reached by day 20 (ADAM 27), day 25 (ADAMs 24 and 25) and in the range day 25-50 (ADAM 26). These results suggest that each ADAM is transcribed in spermatogenic cells in a regulated pattern at a specific developmental stage.

Insertion of poly(ethylene glycol) derivatized phospholipid into pre-formed liposomes results in prolonged in vivo circulation time.

Transfer of MPEG(1900)-DSPE from micellar phase to pre-formed liposomes imparts long in vivo circulation half-life to an otherwise rapidly cleared lipid composition. MPEG(1900)-DSPE transfers efficiently and quickly in a time and temperature dependent manner. There is negligible content leakage and a strong correlation between assayed mol% MPEG(1900)-DSPE, liposome diameter increase, and pharmacokinetic parameters such as distribution phase half-life. Since a biological attribute (liposome clearance rate) can be modified by the insertion process, it suggests a simple and economical way to impart site-specific targeting to a variety of liposome delivery systems. This method is also a convenient way to measure the 'brush' thickness of such conjugates directly.

[Synthesis and analgesic activity of the derivatives of 3-methyl fentanyl].

Six analogues of 1-substituted-3-methylfentanyl were synthesized. All of them are liquid compounds. Preliminary pharmacological results showed that some compounds of 1-beta-substituted vinylethyl-3-methyl derivatives of fentanyl have strong analgesic activity with typical morphine-like action.

[Synthesis and pharmacological activities of the 1-substituted 4-methoxycarbonyl fentanyl derivatives].

Five derivatives of 4-methoxycarbonyl fentanyl were synthesized, four of them carry in the molecules some radicals that may alkylate opiate receptors. Their analgesic activities were measured and the irreversible inhibitory effects of all compounds on the electrically elicited contraction of MVD were investigated. The analgesic test showed that the compounds in this series possess analgesic activity with typical morphine--like action. The isolated tissue experiment indicated that these new compounds were all capable of binding with opiate receptors, and that compounds 2, 4 and 5 were determined to be a new irreversible ligand of opiate receptors.

[Synthesis and analgesic activity of 1-substituted derivatives of 4-methoxycarbonyl-4-N-propionylanilinepiperidine].

In this paper, the synthesis and analgesic activities of a series of 1-substituted derivatives of N-[1-(2-phenylethyl)-4-methoxycarbonyl-4-piperidinyl]-N-propionylanil ine (4-methoxycarbonyl fentanyl) are reported. Preliminary pharmacological results showed that most compounds in this series exhibited typical morphine-like action and that replacement of beta-phenyl group in the 1-position of piperidine ring of 4-methoxycarbonyl fentanyl by some substituents e.g., some substituted vinyl groups, heterocyclic (or alcyclic) radicals, alkyl groups or N-methyl-anilino groups, can keep strong analgesic activity. Especially, some substituted vinyl groups were found to be effective groups which could replace 1-beta-phenyl group of 4-methoxycarbonyl fentanyl. Compounds N-[1-(3, 4-dimethyl-3-pentenyl)-4-methoxycarbonyl-4-piperidinyl]-N- propionylaniline(1321) and N-[1-(4-methyl-3-pentenyl)-4-methoxycarbonyl-4-piperidinyl]-N- propionylaniline(1302) exhibited higher analgesic activity than that of 4-methoxycarbonyl fentanyl.

[Endometrioid carcinoma of the ovary: clinicopathologic analysis in 87 cases].

From Jan. 1972 through Dec. 1984, 87 cases of endometrioid carcinoma of ovary were treated in our hospital, accounting for 23.5% of all cases of epithelial ovarian cancer admitted during the same period. Histologically they could be subdivided into 4 types, i. e. endometrioid carcinoma, clear cell carcinoma, adenocanthoma, and adenosquamous carcinoma. The 5-year survival rates for each type of tumors were 51.2, 0, 100 and 0% respectively. The 5- and 10-year survival rates were 90.1 and 90.1% for stage I, patients, 23.3 and 23.3% for stage II, 4.6 and 0% for stage III, and nil for stage IV. For improving the survival rate and reducing the incidence of recurrence, postoperative long term hormonal therapy should be considered.

[Long-term follow-up of the ovarian malignant teratoma].

Sixty-six patients with ovarian malignant teratoma have been treated in our hospital from Jan. 1954 to Dec. 1990. Two histological types were covered: (1) some malignant tissue came from mature teratoma; (2) embryonic tissue immature ovarian teratoma. During the process of long-term follow up, 38 cases survived, 28 died. With life table calculation, the 5, 10, 15, 20, 25 and 30 year survival rates of the malignant teratoma were 61.5 +/- 6.1; 57.8 +/- 6.2; 57.8 +/- 6.2; 52.8 +/- 7.4; 52.8 +/- 7.4; and 52.8 +/- 7.4%, respectively. The prognosis was related to the age of patient, the size of the tumor, the histological grade and especially, to the clinical staging. The treatment method of this teratoma was discussed as well.

[The effects of the cyclopentyl ethinyl estriol on the cardiovascular function of postmenopausal women].

The cardiovascular function of postmenopausal women before and after oral supplement of cyclopentyl ethinyl estriol (CEE3) were evaluated with 3-dimensional ultrasound and Doppler technique. The results are as follows: there were no changes of HR, SBP, DBP, MBP and E2 in postmenopausal women before and after the oral supplement of CEE3. Ves and SVR were obviously reduced (P < 0.001). SV, CO, EF, Vmax V and A were obviously increased (P < 0.001). There were no changes in Ved, E and E/A. The results showed that CEE3 could reinforce the cardiac function and increase cardiac output and also reduce the resistance in peripheral blood vessels in postmenopausal women. It is assumed that the cardioprotective effect of hormone replacement therapy in postmenopausal women may be due not only to changes in lipid profile but also to direct effects of estrogens on central and peripheral hemodynamic parameters.

Birth weight and subsequent risk of obesity: a systematic review and meta-analysis.

This report describes the association between birth weight (BW) and obesity. Screening of 478 citations from five electronic databases resulted in the inclusion of 33 studies, most of medium quality. The meta-analysis included 20 of these published studies. The 13 remaining articles did not provide sufficient dichotomous data and were systematically reviewed, revealing results consistent with the meta-analysis. Our results revealed that high BW (>4000 g) was associated with increased risk of obesity (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.91-2.24) compared with subjects with BW ≤ 4000 g. Low BW (<2500 g) was associated with decreased risk of obesity (OR, 0.61; 95% CI, 0.46-0.80) compared with subjects with BW ≥ 2500 g. However, when two studies exhibited selection bias were removed, the results indicated no significant association between low BW and obesity (OR, 0.77; 95% CI, 0.58-1.04). Sensitivity analyses showed that differences in the study design, sample size and quality grade of the study had an effect on the low BW/obesity association, which low BW was not associated with the risk of obesity in cohort studies, studies with large sample sizes and studies with high quality grades. Pooled results were similar when normal birth weight (2500-4000 g) was used as the reference category. Subgroup analyses based on different growth and developmental stages (pre-school children, school children and adolescents) also revealed that high BW was associated with increased risk of obesity from childhood to early adulthood. No significant evidence of publication bias was present. These results suggest that high BW is associated with increased risk of obesity and may serve as a mediator between prenatal influences and later disease risk.

Testase 1 (ADAM 24) a plasma membrane-anchored sperm protease implicated in sperm function during epididymal maturation or fertilization.

Plasma membrane-anchored proteases have key roles in cell signaling, migration and refashioning the cell surface and its surroundings. We report the first example of a plasma membrane-anchored protease on mature sperm, testase 1 (ADAM 24). Unlike other studied sperm ADAMs (fertilin alpha and beta, cyritestin) whose metalloprotease domains are removed during sperm development, we found testase 1 retains an active metalloprotease domain, suggesting it acts as a protease on mature sperm. Testase 1 is a glycoprotein (molecular mass 88 kDa), localized to the equatorial region of the plasma membrane of cauda epididymal sperm. Typically, proteolytic removal of the pro-domain is an initial activation step for ADAM proteases. The pro-domain of the testase 1 precursor (108 kDa) is proteolytically removed as sperm transit the caput epididymis to produce processed (mature) testase 1 (88 kDa). Testase 1 is unique among all studied ADAMs in that its proteolytic processing occurs on the sperm plasma membrane instead of at an intracellular site (the Golgi). Using GST-fusion proteins and a synthetic testase 1 C-terminal peptide, we found that the cytoplasmic tail of testase 1 could be phosphorylated in vitro by protein kinase C (PKC). Thus testase 1 apparently has a cytoplasmic PKC phosphorylation site(s). Protein kinase C is known to stimulate other ADAMs' protease activity. Because events of the acrosome reaction include PKC activation, we speculate that testase 1 protease function could be important in sperm penetration of the zona pellucida after sperm PKC is activated during the acrosome reaction.

Free phenytoin monitoring in serum and saliva of epileptic patients in China.

Twenty-three serum samples and 13 saliva samples from 14 Chinese epileptic patients treated with phenytoin (DPH) were obtained to study the correlations between total, free serum, and saliva DPH concentrations. The binding of DPH to serum protein was assessed by equilibrium dialysis, and total and free DPH concentrations were analyzed with a domestic fluorescence polarization immunoassay reagent by the TDx system. A strong correlation existed between the total and free concentrations (r = 0.90, n = 20, p < 0.001). The mean value for the DPH free fraction was 11.13 +/- 3.65%. The mean value for the saliva fraction was 9.40 +/- 2.60%. This is the first attempt to monitor free DPH concentrations in serum in Chinese patients.

Poly(methacrylic acid)-induced liposome aggregation for measuring drug entrapment.

This report characterizes a procedure for rapidly and accurately determining the entrapment of vincristine or other water-soluble drugs in polyethylene glycol-derivatized liposomes. Rapid liposome aggregation with poly(methacrylic acid) and pelleting by mild centrifugation separates liposome-associated vincristine from unentrapped drug. After collecting the supernatant fraction, the pellet is resuspended and solubilized in isopropyl alcohol. Quantitative uv spectrophotometry determines vincristine mass in both fractions. The mean accuracy (recovery) is 100.6% over an entrapped drug range from 70 to 99%. Within and between day precision of the method has a relative standard deviation of 0.76% for a single measurement.