scholarly journals Radiation-Guided Peptide Delivery in a Mouse Model of Nasopharyngeal Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Pei-cheng Lin ◽  
Jun-yan He ◽  
Yu-yin Le ◽  
Kai-xin Du ◽  
Wei-feng Zhu ◽  
...  

Purpose.This study aimed to evaluate the characteristics of the HVGGSSV peptide, exploring radiation-guided delivery in a mouse model of nasopharyngeal carcinoma.Methods.Mice with CNE-1 nasopharyngeal carcinoma were assigned to two different groups treated with Cy7-NHS and Cy7-HVGGSSV, respectively. Meanwhile, each mouse received a single dose of 3 Gy radiation. Biological distribution of the recombinant peptide was assessed on anin vivosmall animal imaging system.Results.The experimental group showed maximum fluorescence intensity in irradiated tumors treated with Cy7-labeled HVGGSSV, while untreated (0 Gy) control tumors showed lower intensity levels. Fluorescence intensities of tumors in the right hind limbs of experimental animals were7.84×107±1.13×107,1.35×108±2.66×107,4.05×108±1.75×107,5.57×108±3.47×107, and9.26×107±1.73×107photons/s/cm2higher compared with left hind limb values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence intensities of tumor in the right hind limbs of the experimental group were1.66×108±1.71×107,1.51×108±3.23×107,5.38×108±1.96×107,5.89×108±3.57×107, and1.62×108±1.69×107photons/s/cm2higher compared with control group values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence was not specifically distributed in the control group. Compared with low fluorescence intensity in the heart, lungs, and tumors, high fluorescence distribution was found in the liver and kidney at 48 h.Conclusions.HVGGSSV was selectively bound to irradiated nasopharyngeal carcinoma, acting as a targeting transport carrier for radiation-guided drugs that are mainly metabolized in the kidney and liver.

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hui Hua ◽  
Jiawei Cheng ◽  
Wenbo Bu ◽  
Juan Liu ◽  
Weiwei Ma ◽  
...  

Aim. To determine whether 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is effective in combating ultraviolet A- (UVA-) induced oxidative photodamage of hairless mice skin in vivo and human epidermal keratinocytes in vitro. Methods. In in vitro experiments, the human keratinocyte cell line (HaCaT cells) was divided into two groups: the experimental group was treated with ALA-PDT and the control group was left untreated. Then, the experimental group and the control group of cells were exposed to 10 J/m2 of UVA radiation. ROS, O2− species, and MMP were determined by fluorescence microscopy; p53, OGG1, and XPC were determined by Western blot analysis; apoptosis was determined by flow cytometry; and 8-oxo-dG was determined by immunofluorescence. Moreover, HaCaT cells were also treated with ALA-PDT. Then, SOD1 and SOD2 were examined by Western blot analysis. In in vivo experiments, the dorsal skin of hairless mice was treated with ALA-PDT or saline-PDT, and then, they were exposed to 20 J/m2 UVA light. The compound 8-oxo-dG was detected by immunofluorescence. Conclusion. In human epidermal keratinocytes and hairless mice skin, UVA-induced oxidative damage can be prevented effectively with ALA-PDT pretreatment.


2020 ◽  
Vol 76 (03) ◽  
pp. 6356-2020 ◽  
Author(s):  
KATARZYNA PONIEDZIAŁEK-KEMPNY ◽  
BARBARA GAJDA ◽  
IWONA RAJSKA ◽  
LECHOSŁAW GAJDA ◽  
ZDZISŁAW SMORĄG

The aim of the study was to examine the in vivo viability of in vitro-produced (IVP) porcine embryos obtained from oocytes matured with thymosin. The research material for this study consisted of immature pig oocytes obtained from ovaries after slaughter and ejaculated semen obtained from one boar. The immature oocytes were cultured in vitro until the metaphase II stage in a medium supplemented with thymosin (TMS). The presumptive zygotes obtained were cultured in vitro for 4-40 hours. The presumptive zygotes and 2-4-cell embryos were evaluated in vivo after transferring them to synchronized recipients. After the transfer of embryos from the experimental group into 2 recipients (50 embryos into each gilt) and the transfer of 50 embryos from the control group into 1 recipient, both gilts that had received embryos obtained by in vitro fertilization of oocytes matured with TMS became pregnant and delivered a total of 16 live piglets. After the transfer of embryos from the control group, no pregnancy was achieved. In conclusion, the results of our preliminary study suggest that the maturation of pig oocytes with thymosin supports the in vivo survival of in vitro produced embryos. It is important to note, that this was the first birth of piglets obtained after transfer of IVP embryos in Poland.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Junya Suzuki ◽  
Yuuki Shimizu ◽  
Kazuhito Tsuzuki ◽  
Zhongyue Pu ◽  
Shukuro Yamaguchi ◽  
...  

Introduction: Implantation of adipose-derived regenerative cells (ADRC) is a promising novel strategy to augment angiogenesis and blood perfusion recovery in ischemic diseases with no other therapeutic option. However, there is a clinical concern underlying therapeutic angiogenesis that implantation of ADRC may promote tumor growth and metastasis via remote angiogenesis. Accordingly, we tested whether therapeutic angiogenesis with ADRC against hindlimb ischemia (HLI) would affect remote tumor growth and angiogenesis in a tumor-bearing mouse ischemic hindlimb model. Methods and results: B16F10-Luc (murine melanoma cells expressing luciferase, 1x106 cells/animal) were implanted to C57BL/6J mice’s (male, 8-10 weeks old, n=10) back. Mice were subjected to unilateral HLI surgery one day after tumor implantation. Then, mice were randomly assigned to the control group or the ADRC group (n=5 for each). ADRC (1x106 cells/animal) or PBS were implanted/injected into ischemic hindlimb muscles one day after the surgery. Blood perfusion recovery in HLI by laser Doppler perfusion imaging system and tumor size by a caliper were measured every week up to 21 days after surgery. At POD 21, tumor weight and luciferase activity in primary tumors obtained by in vivo bioluminescence imaging system were also evaluated. Immunohistochemistry by CD31 or LYVE1 staining was performed to detect feeder arteries or outflow lymphatic vessels in tumors. The results demonstrated that better blood perfusion recovery and more capillary density in HLI was observed in the ADRC group than in the control group (p<0.05, respectively). However, there were no significant differences in terms of tumor volume (p=0.95), tumor weight (p=0.88) and luciferase activity of primary tumor (p=0.92) between those two groups. No sign of distant metastasis was detected by macroscopic and pathological examination, and by in vivo bioluminescence imaging system in both groups. Further study also revealed that capillary density of peritumoral blood vessels or lymphatic vessels was not augmented by ADRC implantation into remote HLI. Conclusions: Our data indicated that therapeutic angiogenesis with ADRC implantation against HLI did not promote remote tumor growth, angiogenesis and metastasis.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Guifeng Wang ◽  
Ning Ma ◽  
Feng He ◽  
Shosuke Kawanishi ◽  
Hatasu Kobayashi ◽  
...  

Taurine (2-aminoethane-sulfonic acid) is a type of amino acids and has numerous physiological and therapeutic functions, including anti-inflammation. However, there are few studies on the anticancer action of taurine. Our previous studies have demonstrated that taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells in vitro. In this study, we have investigated whether taurine has an anticancer effect, using azoxymethane (AOM)/sulfate sodium (DSS)- induced mouse model for colon carcinogenesis. All mice, except those in control group, received a single intraperitoneal injection of AOM and DSS in the drinking water for 7 days twice, with 1-week interval. After the first DSS treatment, mice were given distilled water (model group) or taurine in the drinking water (taurine group) ad libitum. No tumor was observed in the control group. Taurine significantly suppressed AOM+DSS-induced tumor formation. Histopathological examination revealed AOM/DSS treatment induced colon cancer in all mice (8/8, 100%), and taurine significantly inhibited the progression of colon cancer (4/9, 44.4%). Taurine significantly attenuated cell proliferation in cancer tissues detected by Ki-67 staining. Taurine significantly increased the levels of an apoptosis marker cleaved caspase-9 and tumor suppressor protein PTEN. This is the first study that demonstrated that taurine significantly reduced carcinogenicity in vivo using AOM/DSS-induced colon cancer mouse model.


2002 ◽  
Vol 06 (01) ◽  
pp. 23-29 ◽  
Author(s):  
Junya Sonobe ◽  
Kazuhisa Bessho ◽  
Shinji Kaihara ◽  
Yasunori Okubo ◽  
Tadahiko Iizuka

The purpose of this study was to investigate the effectiveness of human bone morphogenetic protein-2 (BMP-2) expressing adenoviral vector in vivo. The day before vector injection, immunosuppressant FK506 was given subcutaneously to each rat at doses of 12 mg/kg (Group I), 6 mg/kg (Group II) and 3 mg/kg (Group III). FK506 was not administered to the six rats of the control group. Twenty-five liters of AXCAOBMP-2 (3.93 × 109pfu/ml) were injected into the right calf muscle of all rats. On day 21 after vector injection, all groups were investigated radiologically, histologically, and biochemically. Osteoinduction was seen in the AxCAOBMP-2-injected groups with immunosuppression. However, no bone formation was observed in the control group. These findings suggest that AxCAOBMP-2 has the potential of osteoinduction under transient immunosuppression. AxCAOBMP-2 may be useful for future clinical application in bone reconstruction, if host immunity response can be regulated.


2020 ◽  
Vol 21 (18) ◽  
pp. 6494
Author(s):  
Enrico P. Spugnini ◽  
Manuel Scimeca ◽  
Bruno Amadio ◽  
Giancarlo Cortese ◽  
Maurizio Fanciulli ◽  
...  

We describe an original electroporation protocol for in vivo plasmid DNA transfection. The right hind limbs of C57 mice are exposed to a specifically designed train of permeabilizing electric pulses by transcutaneous application of tailored needle electrodes, immediately after the injection of pEGFP-C1 plasmid encoding GFP (Green Fluorescente Protein). The electroporated rodents show a greater GFP expression than the controls at three different time points (4, 10, and 15 days). The electroporated muscles display only mild interstitial myositis, with a significant increase in inflammatory cell infiltrates. Finally, mild gait abnormalities are registered in electroporated mice only in the first 48 h after the treatment. This protocol has proven to be highly efficient in terms of expression levels of the construct, is easy to apply since it does not require surgical exposure of the muscle and is well tolerated by the animals because it does not cause evident morphological and functional damage to the electroporated muscle.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Başak Akça ◽  
Aysun Ankay Yılbaş ◽  
Filiz Üzümcügil ◽  
Berkem Büyükakkuş ◽  
Elham Bahador Zırh ◽  
...  

Abstract Background Intraarticular injections are widely used to provide pain relief after arthroscopic procedures and minimize the use of opioids. Dexmedetomidine has been proven to potentiate pain relief and postpone the demand for the first analgesic drug when it is used intraarticularly following arthroscopic knee procedures. However, the effects of dexmedetomidine on articular structures have not yet been evaluated. Our aim was to determine the effects of intraarticular dexmedetomidine injection on articular structures such as cartilage and synovium. Design Animal study. Methods Twenty adult rats (Sprague-Dawley) were enrolled in the study. Following appropriate aseptic and anesthetic conditions, dexmedetomidine (100 mcg/ml) (0.25 ml) was injected into the right knee joint (the study group) and normal saline solution (0.25 ml) into the left knee joint (the control group) of the rats. Four rats were sacrificed from each group on days 1, 2, 7, 14, and 21, and knee joint samples were obtained. Histologists evaluated the articular and periarticular regions and the synovium using histological sections, and a five-point scale was used to grade the inflammatory changes in a blinded manner. Results The groups were found to be similar in terms of median congestion scores, edema and inflammation scores, subintimal fibrosis, neutrophil activation and cartilage structure at each of the time intervals. Conclusion In our placebo-controlled, in vivo trial, the intraarticular use of dexmedetomidine seemed to be safe with respect to the studied histopathological parameters. However, complementary studies investigating the histopathological effects, analgesic dosage and adverse effects of dexmedetomidine on damaged articular structure models are needed.


2016 ◽  
Vol 13 (10) ◽  
pp. 7623-7627
Author(s):  
Zhenyu Jin ◽  
Ki Yong Hong ◽  
Kyung Won Minn ◽  
Hak Chang ◽  
Ung Sik Jin

Capsular contracture is the most common complication after insertion of silicone implants during breast implant surgery. The discovery that myofibroblasts play an important role in the formation of hypertrophic scars led to the development of pharmacological drugs such as zafirlukast, which prevents capsular contracture by resisting the above mechanism. As a result, the author sought to investigate the effect of the anti-leukotriene montelukast on capsular contracture. Ten white female New Zealand rabbits, each weighing approximately 3 kg, were used as subjects. Through bilateral incision of the midback area, the prostheses were inserted on the subpanniculus carnosus plane. Once the silicone prostheses had been inserted, the right implant was injected with 10 mL of montelukast (10 µg/mL), and the left implant was injected with 10 mL of normal saline. Eight weeks after the procedure, the capsular pressure was measured via tonometry using a circular glass piece weighing 42.7 g. The tissue samples were then extracted, and their thicknesses were measured using hematoxylin-eosin stain and Masson trichrome stain. The average pressure was 4.23±0.99 mmHg in the control group and 3.71±0.51 mmHg in the experimental group, a statistically significant difference (p = 0.02). The average capsular thickness was 947.938±300 µm in the control group and 709.672±274 µm in the experimental group, a statistically significant difference (p = 0.028). The author confirmed that montelukast injections during silicone prosthesis insertion decreased the formation of capsular contracture.


Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2241-2246 ◽  
Author(s):  
Michael P. Reilly ◽  
Uma Sinha ◽  
Pierrette André ◽  
Scott M. Taylor ◽  
Yvonne Pak ◽  
...  

AbstractHeparin-induced thrombocytopenia (HIT) is a major cause of morbidity and mortality resulting from the associated thrombosis. Extensive studies using our transgenic mouse model of HIT have shown that antibodies reactive with heparin-platelet factor 4 complexes lead to FcγRIIA-mediated platelet activation in vitro as well as thrombocytopenia and thrombosis in vivo. We tested PRT-060318 (PRT318), a novel selective inhibitor of the tyrosine kinase Syk, as an approach to HIT treatment. PRT318 completely inhibited HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Transgenic HIT model mice were treated with KKO, a mouse monoclonal HIT-like antibody, and heparin. The experimental group received orally dosed PRT318, whereas the control group received vehicle. Nadir platelet counts of PRT318-treated mice were significantly higher than those of control mice. When examined with a novel thrombosis visualization technique, mice treated with PRT318 had significantly reduced thrombosis. The Syk inhibitor PRT318 thus prevented both HIT immune complex-induced thrombocytopenia and thrombosis in vivo, demonstrating its activity in HIT.


2013 ◽  
Vol 110 (4) ◽  
pp. 625-631 ◽  
Author(s):  
Virginie Alexandre ◽  
Patrick C. Even ◽  
Christiane Larue-Achagiotis ◽  
Jean-Marc Blouin ◽  
François Blachier ◽  
...  

Lactose malabsorption is associated with rapid production of high levels of osmotic compounds, such as organic acids and SCFA in the colon, suspected to contribute to the onset of lactose intolerance. Adult rats are lactase deficient and the present study was conducted to evaluatein vivothe metabolic consequences of acute lactose ingestion, including host–microbiota interactions. Rats received diets of 25 % sucrose (S25 control group) or 25 % lactose (L25 experimental group). SCFA and lactic acid were quantified in intestinal contents and portal blood. Expression of SCFA transporter genes was quantified in the colonic mucosa. Carbohydrate oxidation (Cox) and lipid oxidation (Lox) were computed by indirect calorimetry. Measurements were performed over a maximum of 13 h. Time, diet and time × diet variables had significant effects on SCFA concentration in the caecum (P< 0·001,P= 0·004 andP= 0·007, respectively) and the portal blood (P< 0·001,P= 0·04 andP< 0·001, respectively). Concomitantly, expression of sodium monocarboxylate significantly increased in the colonic mucosa of the L25 group (P= 0·003 att= 6 h andP< 0·05 att= 8 h). During 5 h after the meal, the L25 group's changes in metabolic parameters (Cox, Lox) were significantly lower than those of the S25 group (P= 0·02). However, after 5 h, L25 Cox became greater than S25 (P= 0·004). Thus, enhanced production and absorption of SCFA support the metabolic changes observed in calorimetry. These results underline the consequences of acute lactose malabsorption and measured compensations occurring in the host's metabolism, presumably through the microbiota fermentations and microbiota–host interactions.


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