Combination of intratumoural micellar paclitaxel with radiofrequency ablation: efficacy and toxicity in rodents.

OBJECTIVES: To determine whether radiofrequency ablation (RFA) is more effective when combined with intratumoural injection (IT) than with intravenous injection (IV) of micelles. MATERIALS AND METHODS: Balb/c mice bearing 4T1 breast cancer were used. The tumour drug accumulation and biodistribution in major organs were evaluated at different time points after IT, IV, IT+RFA and IV+RFA. Periablational drug penetration was evaluated by quantitative analysis and pathologic staining after different treatments. For long-term outcomes, mice bearing tumours were randomised into six groups (n = 7/group): the control, IV, IT, RFA alone, IV+RFA and IT+RFA groups. The end-point survival was estimated for the different treatment groups. RESULTS: In vivo, intratumoural drug accumulation was always much higher for IT than for IV within 48 h (p < 0.001). The IT+RFA group (3084.7 ± 985.5 µm) exhibited greater and deeper drug penetration than the IV+RFA group (686.3 ± 83.7 µm, p < 0.001). Quantitatively, the intratumoural drug accumulation in the IT+RFA group increased approximately 4.0-fold compared with that in the IV+RFA group (p < 0.001). In addition, compared with the IT treatment, the IT+RFA treatment further reduced the drug deposition in the main organs. Survival was longer in the IT+RFA group than in the IV+RFA (p = 0.033) and RF alone (p = 0.003) groups. CONCLUSION: The use of IT+RFA achieved much deeper and greater intratumoural drug penetration and accumulation, resulting in better efficacy, and decreased the systemic toxicity of nanoparticle-delivered chemotherapy. KEY POINTS: • Association of IT+RFA achieved much deeper and greater intratumoural drug penetration than of IV+RFA, leading to better therapeutic efficacy. • Compared with IV or IT chemotherapy alone, the combination with RFA decreased toxicity, especially in the IT+RFA group.

Comparison of anti-atopic dermatitis activities between DHMEQ and tacrolimus ointments in mouse model without stratum corneum.

This study is aimed to further investigate the anti-atopic dermatitis (AD) activities of dehydroxymethylepoxyquinomicin (DHMEQ) ointment and compare its effect with that of tacrolimus ointment based on the previous study that DHMEQ improves AD-like lesions. AD were induced by 2,4-dinitroclilorobenzene/oxazolone (DNCB/OX) repeatedly on the ears of BABL/C mice while medical tape was additionally used to disrupt stratum corneum in order to exacerbate the lesions. The mice were randomly divided into groups, which are normal, vehicle, DHMEQ (0.1%) and tacrolimus (0.1%). Those in the last two groups were externally applied with DHMEQ ointment and tacrolimus ointment, respectively. The results showed that both of them significantly improved dermatitis symptoms of DNCB/OX-induced AD-like lesions, such as redness, itching, weeping, scaling and thickening of the skin, while reducing epidermis thickness, dermis thickness and the number of mast cells as well, which were examined histopathologically. In contrast with DHMEQ, tacrolimus led to a significant decrease in body weight after long-term application. Both DHMEQ and tacrolimus suppress DNCB-induced increase of serum total IgE and attenuate expression of inflammatory factors IL-4, IL-6, IL-13, IL-1ß and interferon (IFN)-γ in the disrupted ear tissues. On the other hand, the mice applied with tacrolimus became obviously irritable, jumping up and down, and inflammatory exudation on the lesioned-skin surface of the mice was remarkably observed. Contrary to the side effects made by tacrolimus, DHMEQ didn't cause any adverse stimulus response. As a conclusion, DHMEQ is safer, milder and more suitable for long-term use than tacrolimus for the treatment of AD-like lesions.

Evidence of transplacental transmission of Encephalitozoon cuniculi genotype II in murine model.

Microsporidia are obligate intracellurar unicellular parasite of wide range of vertebrates. Although ingestion or inhalation of microsporidian spores is the main route of infection, assumed vertical transmission was described in some mammals. The present study was focused on proof of vertical transmission in mice under experimental conditions. Mice were infected with E. cuniculi genotype II intraperitoneally after mating, or perorally followed by mating in acute or chronic phase of infection. Fetuses were delivered by Caesarean section or mice were kept up to the parturition. Some of cubs were immediately after birth transferred to uninfected surrogate mothers. Group of cubs was immunosuppressed. All cubs were examined using polymerase chain reaction for the presence of Encephalitozoon after birth or in their age of 3 or 6 weeks, respectively. All fetuses delivered by Caesarean section, which were intraperitoneally or perorally infected were negative as well as all neonatal mice and youngsters tested in age of 6 weeks. Only immunosuppressed cubs and cubs of immunodeficient mice in age of 21 days were positive for Encephalitozoon cuniculi genotype II. Present results provided the evidence that transplacental transmission of Encephalitozoon cuniculi in mice occurs, but the mechanism of these transport is still unknown.

Role of prokaryotic pprI gene in protecting BALB/c mice from acute radiation injury / 中华放射医学与防护杂志

Objective To investigate the radioresistant effects of pprI gene of Deinococcus radiodurans on BALB/c mice.Methods Male BALB/c mice in SPF level were applied for this work.The pEGFP-c1 plasmid and pEGFP-c1-pprI gene recombinant plasmid were transferred into anterolateral muscle of mice with in vivo electroporation technology.The mice were irradiated by 6 Gy 60Co γ-rays in whole body and the mortality of mice was observed within 30 days after irradiation.In addition,the mouse were irradiated with 4 Gy γ-rays and then the peripheral blood cell number,apoptosis rates of thymocyte cells,spleen cells and bone marrow cells were observed in the days of 1,7,14,28 and 35 after irradiation while the histopathological changes of lung and testis were observed in the days 7 and 28 after γ-ray irradiation.Results The highest gene transfection efficiency of muscle cells was obtained in a Plasmid injection amount of 50 μg/50 μl and electric field strength of 200 V/cm.The acute radiation mortality of pEGFP-c1-pprI gene recombinant plasmid transfer group was 30％,lower than that of irradiation group (60.0％) and pEGFP-c1 plasmid transfer group (63.3％) after 6 Gy γ-ray irradiation (x2 =4.90,6.24,P ＜ 0.05).Compared with the irradiation group and pEGFP-c1 plasmid transfer group,the WBC count of pEGFP-c1-pprI gene recombinant plasmid group in peripheral blood of mice was significantly higher in the days of 1,7,14 and 28 (F =16.26,8.10,6.37,10.74,P ＜0.05),PLT count was significantly higher in days of 7 and 14 (F =7.36,5.71,P ＜ 0.05),meanwhile the lymphocyte percentage was increased significantly on the 7th day (F =18.43,P ＜ 0.05) after irradiation.On the other hand,the apoptosis rates of thymocyte cells and bone marrow cells were significantly decreased in the days of 1,7,14,28 and 35 (F =3.88,14.91,14.14,39.86,5.65,P ＜0.05 and F=53.70,11.75,21.78,41.40,4.54,P ＜0.05) while the apoptosis rate of spleen cells was significantly decreased in the days of 1,7,14 and 28 (F =97.95,56.61,33.55,14.71,P ＜0.05) after irradiation.Finally,the radiation histopathological changes of lung and testis of the pEGFP-c1-pprI gene recombinant plasmid group were slight and easy to recover.Conclusions Transfection of pprI gene of Deinococcus radiodurans by in vivo electroporation has significant protective effect on the acute radiation injury in BALB/c mice,which may have important clinical applications.

Establishment of mouse model of orbital diffuse large B cell lymphoma / 中华实验眼科杂志

Background Recently, the morbidity of orbital lymphoma increased gradually, and we have made deeper research in pathology,therapy and pathogenesis of the disease.There were few reports of mice model of orbital lymphoma up to now for its lower morbidity and culture difficulty.Objective This study was to establish a mouse model of orbital diffuse large B cell lymphoma (DLBCL) by injection of systemic DLBCL cell line pfeiffer.Methods Ten SPF BALB/c mice and 5 nod-SCID mice were radiated firstly using 137Cs,with the absorption dose 3.5 Gy in the BALB/c mice and 2.6 Gy in the nod-SCID mice,and then pfeiffer cells were intraobitally injected in 4eyes of BALB/c mice (orbital injection group) and suncutaneously injectied in 4 eyes of BALB/c mice and 4 eyes of nod-SCID mice (subcutaneous injection group) at the concentration of 1.5×l08/ml.The developing status of tumors were examined once per day and the growth curve was drawn.The tumors and nearby lymph nodes were obtained 54 days after injection for the preparation of 4 μm thickness of serial sections.Hemotoxylin-eosin staining was used to examine the histopathology of the tumors, and immunochemistry was employed to detect the expressions of CD20,CD79α and CD45RO proteins.The tumors were typed based on the expressions of CD10, BCL-6 and mum-1 in the specimens,and the expressions of Ki-67 and survivin were assyed to assess the prognosis of the tumor.All the results were compared with 3 diagnosed human orbital DLBCL sections.The use and care of the mice complied with Chinese Administration Rule of Laboratory Animal.Results The tumor formation rates were 100％ in both the orbital injection group and subcutaneous injection group, and the tumors grew much faster in nod-SCID mice than BALB/c mice.Infiltration of tumor cells in lymph nodes were found in the subcutaneous injection group rather than the orbital injection group.The pathological features were accordant among the orbital injection group, subcutaneous injection group and human orbital DLBCL sections.The number of ＜50％ and ≥50％ CD20+ specimens was 3 and 5,CD79αwas 2 and 6,CD45RO was 8 and 0 in the BALB/c mice;while that in the nod-SCID mice was 1 and 3 in CD20,0 and 4 in CD79α,4 and 0 in CD45RO;the number of human orbital DLBCL specimens was 1 and 2 in CD20,1 and 2 in CD79α,2 and 1 in CD45RO,without significant differences among them (all at P=1.00).No significant differences were seen in Ki-67+ number and survivin+ number among the BALB/c mice, nod-SCID mice and human orbital DLBCL specimens (all at P=1.00).The detection of CD10,BCL-6 and mum-1 expressions indicated that the tumors of BALB/c mice,nod-SCID mice and human orbital DLBCL specimens all were the non-germinal center B cell-like types.Conclusions The orbital and subcutaneous DLBCL mouse models are successfully established by injection of pfeiffer cell line.There are the same findings and features in biological behavior, pathology and immunohistochemistry in orbital,subcutaneous models with human orbitl DLBCL.Nod-SCID mice appear to be more suitable for the growth of lymphoma cells.

ENMD-1068, a protease-activated receptor 2 antagonist, inhibits the development of endometriosis in a mouse model.

OBJECTIVE: Protease-activated receptor 2 plays an important role in the pathogenesis of endometriosis. We studied the effect of ENMD-1068, a protease-activated receptor 2 antagonist, on the development of endometriosis in a noninvasive fluorescent mouse model. STUDY DESIGN: A red fluorescent protein-expressing xenograft model of human endometriosis was created in nude mice. After endometriosis induction, the mice were injected intraperitoneally with either 25 mg/kg or 50 mg/kg ENMD-1068 or with 200 µL of the vehicle control daily for 5 days. The endometriotic lesions that developed in the mice were then counted, measured, and collected. The lesions were assessed for the production of interleukin 6 and monocyte chemotactic protein-1 by enzyme-linked immunosorbent assays and evaluated for the activation of nuclear factor-κB and the expression of vascular endothelial growth factor by immunohistochemical analyses. Cell proliferation and apoptosis were assessed by immunohistochemistry for Ki-67 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, respectively. RESULTS: ENMD-1068 dose-dependently inhibited the development of endometriotic lesions (P < .05) without apparent toxicity to various organs of the treated mice. Consistently, ENMD-1068 dose-dependently inhibited the expression of interleukin 6 and nuclear factor-κB (P < .05) and cell proliferation (P < .05) in the lesions, as well as increased the percentage of apoptotic cells (P < .05). ENMD-1068 reduced the levels of monocyte chemotactic protein-1 and vascular endothelial growth factor in the lesions (P < .05), but not in a dose-dependent manner. CONCLUSION: Our study suggests that ENMD-1068 is effective in suppressing the growth of endometriosis, which might be attributed to the drug's antiangiogenic and antiinflammatory activities.