[Questions and reflections in the diagnosis and treatment of younger breast cancer in China].

Compared with the median age of breast cancer onset in western countries at 62-64 years, the median age in China is around 16 years earlier. There are nearly fifty thousand new breast cancer patients younger than 40 years in China every year. The tumor characteristics, diagnosis and treatment methods, and psychosocial needs of these young patients are often different from elder breast cancer patients. Currently, the international clinical guidelines for young breast cancer are mainly formulated by western countries, which often do not address the unique clinical needs from young breast cancer patients in China. There are many questions and problems in the diagnosis and treatment of young breast cancer in China that do not have standard answer and are urgently in need of expert consensus to guide clinical decision-making.

CC chemokine ligand 21 enhances the immunogenicity of the breast cancer cell line MCF-7 upon assistance of TLR2.

CC chemokine ligand 21 (CCL21) is a known attractant for CCR7-positive (CCR7+) cells, but its additional role in the immunogenicity of CCR7+ cells remains poorly understood. This study explored the effects of CCL21-CCR7 ligation on cancer immunogenicity and related antitumor immune response, in the presence and absence of mitomycin C (MMC) treatment. CCL21-CCR7 binding upregulated human leukocyte antigen class I-restricted tumor antigen presentation with increased expression of human leukocyte antigen class I and transporter associated with antigen processing-1. In addition, CCL21 restrained the tumor-derived immunosuppressive factors FasL and transforming growth factor-ß. Consequently, CCL21 facilitated cancer-educated lymphocytes reaction in vitro. In the tumor-bearing mouse, CCL21 inhibited tumor growth and prolonged mouse survival via lymphocytes, especially in CCR7+ cancer cells. Furthermore, Toll-like receptor 2 activation of lymphocytes assisted the tumor-suppression functions of CCL21, in vitro and in vivo. This study implies that CCL21 improved the immunogenicity of the CCR7+ breast cancer cell line even with MMC treatment and triggered antitumor response by lymphocytes. These findings provide a new insight into the research and application of CCL21-associated antitumor response.

[Effects of beta-agkistrodotoxin on synaptic transmission in toad sympathetic ganglia].

The effects of beta-agkistrodotoxin (beta-AgTX) on synaptic transmission of the toad sympathetic ganglia were investigated by intracellular recording techniques. Superfusion of beta-AgTX (30 microgram/ml, 5-15 min) reversibly inhibited the cholinergic fast excitatory postsynaptic potential (f-EPSP, n = 16) and the fast components of acetylcholine (ACh) potential induced by micropressure administration of ACh (n = 24). Comparison of beta-AgTX effect in the same cell group showed significantly different inhibition rates on f-EPSP (77.2 +/- 27.7%) and ACh potential (25.5 +/- 17.5%) (n = 6, P less than 0.01, F test). During application of beta-AgTX (30 or 50 micrograms/ml) for 15-30 min, no detectable change was found in non-cholinergic late slow EPSPs (n = 22). The results suggest that beta-AgTX selectively inhibits the cholinergic transmission of the toad sympathetic ganglia by both presynaptic and postsynaptic mechanism.

[Preparation and in vitro activity of monoclonal antibody-pharmorubicin immunoconjugates].

Bifunctional agent adipic dihydrate was used to form hydrazon bond between polyglutamic acid (PGA) and pharmorubicin (PAR). Under controlled condition, a relatively high rate of conjugation was obtained with no self-condensation. The value of PGA/PAR was in positive portion with the molecular weight (MW) of PGA: per 8-11 glutamic acid monomer linking one pharmorubicin. When PGA of MW 14,300 was used as carrier, the ratio of PGA/PAR was 1:11. After conjugating with anti-hepatoma monoclonal antiboty (McAb), an immunoconjugate of McAb:PGA:PAR being 1:2:22 was obtained. The immunoconjugate retained the binding activity to targeted cell compared with the purified and the oxidized antibody. Pharmacological studies in vitro showed lower cytotoxicity of the immunoconjugate than the free drug, but selective cytotoxicity directed by antibody was observed. Consequently, the immunoconjugate McAb-PGA-PAR with high ratio of drug/McAb as well as moderate targeting cytotoxity in vitro was successfully prepared. That makes it possible for the preparation of cell-targeted drug which is expected to be benificial to tumor treatment.

[Determination of liquid-crystalline transition temperature of temperature-sensitive liposomes of futraful by 1HNMR].

1HNMR was employed to determine the liquid-crystalline transition temperature (TC) of the temperature-sensitive liposomes of futraful. It is a method with high sensitivity, high accuracy and furnishing more information. The 1HNMR spectra were made and studied. The rate of peak height increase of phospholipid correlates to the thermotropic phase transition of liposomes. The study shows that the TC of DPPC-liposomes and DSPC-liposomes is 36 degrees C and 48 degrees C, respectively. The TC of DPPC-DSPC-liposomes correlates with the proportion of the amount of DPPC and DSPC. The TC is not affected by futraful. The temperature-sensitive liposomes of futraful with TC of 41 degrees C were prepared which consisted of 60% DPPC and 40% DSPC.

[Studies on oral sustained-release microspheres of nifedipine].

Nifedipine has been incorporated into Eudragit RL microspheres by the emulsion solvent-evaporation process using an acetone/liquid paraffin system. The drug in the Eudragit RL microspheres was present in either molecular dispersion or amorphous state. The drug release profile from microspheres conformed to the Higuchi equation. The microspheres were stable under different storage conditions for six months with respect to drug content, dispersing state and release profile. The in vivo results in eight healthy volunteers showed that the relative bioavailability of the nifedipine sustained-release microspheres against commercial retard tablet as a control was 102.5%, and the microsphere formulation was bioequivalent to the retard tablet. Significant in vitro and in vivo correlation was also found for the microspheres.

[Studies on CDDP-albumin microspheres for hepatic arterial chemoembolization].

An optimum procedure was established by orthogonal test for preparing cis-platin albumin microspheres (CDDP-AMS) with emulsion-heating stabilization method. The factors which affect particle size and release rate in vitro were studied. The particle size focusing on 58.8-256 microns, the mean size was 148.46 microns, drug content was 51.16% (w/w). The dissolution profiles of the CDDP-AMS followed Higuchi kinetics. In rabbits the distribution and elimination half times of platinum were prolonged 3.36 times and 1.23 times vs injection group, respectively, after hepatic arterial chemoembolization with CDDP-AMS. The highest serum concentration of platinum is 30 percent of that of the injection group. The platinum concentration was increased in liver (P < 0.01) and decreased in kidney (P < 0.05) vs that of injection group.

[Studies on transdermal delivery system of isosorbide dinitrate].

A transdermal delivery system of isosorbide dinitrate (ISDN-TDS) and an HPLC method for the measurement of ISDN were developed. The system is composed of backing, drug reservoir, control membrane, contact adhesive and protective layer. The influences of drug reservoir, solvent, control membrane, viscosity and penetration enhancer azone on the release of ISDN were investigated. The cumulative released amount of ISDN/time profile indicated that ISDN was permeated through excised skin in a zero-order kinetic in 48 h. The release of ISDN from ISDN-TDS can last 72 h at least. The mean permeation rate is 13.76 micrograms.h-1/cm2. Releasing ISDN from ISDN-TDS was more stable than that from Frandol tape-s whose release profile was found to follow a linear Q vs t1/2 relationship with a release flux of 114.39 micrograms.h-1/cm2.

Design and synthesis of amidino-tyrosine derivatives as non-peptide fibrinogen receptor antagonists.

The design, synthesis and antiaggregation activity of amidino-tyrosine derivatives based on Arg-Gly-Asp (RGD) tripeptide sequence as non-peptide fibrinogen receptor antagonists is described. Optimization of the spacer and the substituent at the C-terminal is reported.

Experimental study on topical antimicrobial agents in burns.

Numerous organic silver salts have been tested against a virulent strain of Pseudomonas aeruginosa which had been deliberately applied to the scalded tails of mice and deeper scald wounds on the backs of rabbits. Silver pipemidate was found to be more effective than silver sulphadiazine in treating these infected wounds.