[Remodeling of tumor stroma combined with photothermal therapy in the treatment of triple-negative breast cancer].

Objective: Polyethylene glycol-modified gold nanostar particles (GNS-PEG) were constructed to investigate whether the degradation of extracellular matrix in triple-negative breast cancer could improve the tumor delivery of GNS-PEG and enhance the efficacy of photothermal therapy. Methods: GNS-PEG were constructed and characterized for physicochemical properties as well as photothermal properties. At the cellular level, the cytotoxicity of halofuginone (HF) and the effect of photothermal therapy were detected. Mouse model of triple negative breast cancer was established by subcutaneous inoculation of 4T1 cells in BALB/c nude mice. Five injections of HF were given via tail vein (HF group), and tumor sections were stained with Masson stain and immunohistochemical staining for transforming growth factor ß1 (TGFß1), α-smooth muscle actin (α-SMA) and CD31 to observe the effect of tumor stromal degradation. Five injections of HF via tail vein followed by GNS-PEG (HF+ GNS-PEG group) were applied to determine the content of gold in tumor tissues by inductively coupled plasma mass spectrometry. The tumor sites of the mice in the GNS-PEG and HF+ GNS-PEG groups were irradiated with NIR laser and the temperature changes were recorded with an IR camera. The tumour growth and weight changes of mice in each group were observed. Ki-67 immunohistochemical staining, TdT-mediated dUTP nick-end labeling and HE staining were performed on tumor tissue sections from each group to observe tumor proliferation, apoptosis and necrosis. HE staining was performed on heart, liver, spleen, lung and kidney tissues from each group to observe the morphological changes of cells. Results: GNS-PEG nanoparticles showed a multi-branched structure with a particle size of 73.5±1.4 nm. The absorption peak of GNS was 810 nm, which is in the near infrared region. The photothermal conversion rate of GNS-PEG was up to 79.3%, and the photothermal effect could be controlled by the laser energy. HF has a concentration-dependent cytotoxicity, with a cell survival rate being as low as (22.8±2.6)% at HF concentration of up to 1 000 nmol/L. The photothermal effect of GNS-PEG was significant in killing tumor cells, with a cell survival rate of (32.7±5.2)% at the concentration of 25 pmol/L. The collagen area fraction, TGFß1 integrated optical density and α-SMA integrated optical density in the tumor tissues of mice in the HF group were (2.1±0.2)%, 3.1±0.4 and 5.2±1.9, respectively, which were lower than those of the control group (all P<0.01), and the vessel diameter was 8.6±2.9 µm, which was higher than that of the control group (P<0.05). In the HF+ GNS-PEG group, the concentration of gold in tissues was 52.4 µg/g, higher than that in the GNS-PEG group (15.9 µg/g, P<0.05). After laser irradiation, the temperature of the tumor site in the HF+ GNS-PEG group was significantly higher than that in the GNS-PEG group. At the 4th minute, the temperatures of the tumor site in the GNS-PEG and HF+ GNS-PEG groups were 51.5 ℃ and 57.7 ℃ respectively; the tumor volume in the HF+ GNS-PEG group was effectively suppressed. The body weights of the mice in each group did not change significantly during the monitoring period. No significant abnormalities were observed in the main organs of the mice in the GNS-PEG group, but some hepatocytes in the HF and HF+ GNS-PEG groups showed edema and degeneration. Conclusion: The remodeling of extracellular matrix in triple-negative breast cancer could significantly improve the intratumoral delivery of GNS-PEG and thus achieve better photothermal therapy effect.

[Clinical and experimental study on Ligusticum wallichii mixture in preventing and treating bronchial asthma].

UNLABELLED: To investigate the significance of Ligusticum wallichii Mixture (LWM) and its possible therapeutical mechanism in bronchial asthma, clinical and experimental studies were carried out. RESULTS: LWM inhibited bronchospasm induced by histamine and acetylcholine in guinea pigs; the plasma level of TXB2 was decreased remarkably and the incubation period from antigen inhalation to asthma attack could be delayed by LWM; the incidence of asthma and its mortality were reduced in guinea pigs, compared with control, P < 0.01. In addition, the prolonged period of induced asthma attack was negatively correlated to the plasma level of TXB2 in guinea pigs (P < 0.01). It was observed that the plasma level of TXB2 was decreased, the forced expiratory volume in 1 sec (FEV1%) was elevated significantly in asthmatic patients after they were treated by LWM. Moreover, the total effective rate was significantly better than that in the control (92% : 62%). It indicated that: (1) The effects of airway allergic inflammation (AAI) might be the important pathological basis for the bronchial asthma, (2) TXA2 might be an important inflammatory mediator in asthma which could be taken as an useful biochemical parameter for evaluating clinical effects, (3) LWM could relax tracheal smooth muscle, improve pulmonary function, inhibit the synthesis and release of TXA2 with no side effects.

[The main factors influencing the toxicity of Chinese materia medica].

This paper discusses the main factors influencing the toxicity of Chinese materia medica in respect of compatibility, dosage, processing, drug form, decoction preparation and channel of administration, then proceeds to expound the different ways these factors influence the toxicity of Chinese materia medica, mainly increasing, reducing, producing and accumulating toxicity, and thus provides theoretical basis for clinical rational administration of Chinese materia medica.