scholarly journals Myxoma Virus Infection Promotes NK Lysis of Malignant Gliomas In Vitro and In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66825 ◽  
Author(s):  
Henry Ogbomo ◽  
Franz J. Zemp ◽  
Xueqing Lun ◽  
Jiqing Zhang ◽  
Danuta Stack ◽  
...  
Keyword(s):  
Virus Infection ◽  
Malignant Gliomas ◽  
Myxoma Virus

scholarly journals Multi-responsive nanofibers composite gel for local drug delivery to inhibit recurrence of glioma after operation

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yufu Zhu ◽  
Jun Jia ◽  
Gang Zhao ◽  
Xuyang Huang ◽  
Lansheng Wang ◽  
...  
Keyword(s):  
Malignant Gliomas ◽  
Postoperative Recurrence ◽  
Local Drug Delivery ◽  
Recurrent Glioma ◽  
Mixed Solution ◽  
Composite Gel ◽  
Poly Propylene ◽  
Responsive Hydrogels

Abstract Background The postoperative recurrence of malignant gliomas has presented a clinical conundrum currently. Worse, there is no standard treatment for these recurrent tumours. Therefore, novel promising methods of clinical treatment are urgently needed. Methods In this study, we synthesized reactive oxygen species (ROS)-triggered poly(propylene sulfide)60 (PPS60) mixed with matrix metalloproteinases (MMPs)-responsive triglycerol monostearate (T) lipids and TMZ. The mixed solution could self-assemble at 50 ℃ to generate hydrogels with MMPs- and ROS-responsiveness. We explored whether the T/PPS + TMZ hydrogel could achieve the MMP- and ROS-responsive delivery of TMZ and exert anti-glioma regrowth effects in vitro and in vivo. These results demonstrated that the T/PPS + TMZ hydrogel significantly improved the curative effect of TMZ to inhibit postsurgical recurrent glioma. Results The results confirmed the responsive release of TMZ encapsulated in the T/PPS + TMZ hydrogel, and the hydrogel showed excellent performance against glioma in an incomplete glioma operation model, which indicated that the T/PPS + TMZ hydrogel effectively inhibited the growth of recurrent glioma. Conclusion In summary, we successfully developed injectable MMPs- and ROS-responsive hydrogels that could achieve the sustained release of TMZ in the surgical cavity to inhibit local recurrent glioma after surgery. Graphic abstract

scholarly journals EXTH-70. ENHANCEMENT OF ANTITUMOR ACTIVITY BY USING 5-ALA–MEDIATED SONODYNAMIC THERAPY TO INDUCE APOPTOSIS AND NECROSIS IN A MOUSE GLIOMA MODEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi97-vi97
Author(s):  
Satoshi Suehiro ◽  
Takanori Ohnishi ◽  
Akihiro Inoue ◽  
Daisuke Yamashita ◽  
Masahiro Nishikawa ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
High Intensity Focused Ultrasound ◽  
Control Group ◽  
Normal Brain ◽  
Sonodynamic Therapy ◽  
Cytotoxic Effects

Abstract OBJECTIVE High invasiveness of malignant gliomas frequently causes local tumor recurrence. To control such recurrence, novel therapies targeted toward infiltrating glioma cells are required. Here, we examined cytotoxic effects of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas both in vitro and in vivo. METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology. Flow cytometric analysis indicated that 5-ALA-SDT induced apoptotic cell death. The 5-ALA-SDT generated higher ROS than in the control group, and inhibition of ROS generation completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

scholarly journals Astrocytes derived from p53-deficient mice provide a multistep in vitro model for development of malignant gliomas.

1995 ◽  
Vol 15 (8) ◽  
pp. 4249-4259 ◽  
Author(s):  
A M Yahanda ◽  
J M Bruner ◽  
L A Donehower ◽  
R S Morrison
Keyword(s):  
Genomic Instability ◽  
Malignant Transformation ◽  
Nude Mice ◽  
Malignant Gliomas ◽  
Early Event ◽  
Wild Type ◽  
Early Passage ◽  
Wild Type P53

Loss or mutation of p53 is thought to be an early event in the malignant transformation of many human astrocytic tumors. To better understand the role of p53 in their growth and transformation, we developed a model employing cultured neonatal astrocytes derived from mice deficient in one (p53 +/-) or both (p53 -/-) p53 alleles, comparing them with wild-type (p53 +/+) cells. Studies of in vitro and in vivo growth and transformation were performed, and flow cytometry and karyotyping were used to correlate changes in growth with genomic instability. Early-passage (EP) p53 -/- astrocytes achieved higher saturation densities and had more rapid growth than EP p53 +/- and +/+ cells. The EP p53 -/- cells were not transformed, as they were unable to grow in serum-free medium or in nude mice. With continued passaging, p53 -/- cells exhibited a multistep progression to a transformed phenotype. Late-passage p53 -/- cells achieved saturation densities 50 times higher than those of p53 +/+ cells and formed large, well-vascularized tumors in nude mice. p53 +/- astrocytes exhibited early loss of the remaining wild-type p53 allele and then evolved in a manner phenotypically similar to p53 -/- astrocytes. In marked contrast, astrocytes retaining both wild-type p53 alleles never exhibited a transformed phenotype and usually senesced after 7 to 10 passages. Dramatic alterations in ploidy and karyotype occurred and were restricted to cells deficient in wild-type p53 following repeated passaging. The results of these studies suggest that loss of wild-type p53 function promotes genomic instability, accelerated growth, and malignant transformation in astrocytes.

In vitro and in vivo Sensitivity of a Non-Mouse-Adapted Influenza A (Beijing) Virus Infection to Amantadine and Ribavirin

Chemotherapy ◽  
1995 ◽  
Vol 41 (6) ◽  
pp. 455-461 ◽  
Author(s):  
Robert W. Sidwell ◽  
Kevin W. Bailey ◽  
Min Hui Wong ◽  
John H. Huffman
Keyword(s):  
Virus Infection ◽  
Influenza A

scholarly journals Chloroquine Administration Does Not Prevent Nipah Virus Infection and Disease in Ferrets

2009 ◽  
Vol 83 (22) ◽  
pp. 11979-11982 ◽  
Author(s):  
Jackie Pallister ◽  
Deborah Middleton ◽  
Gary Crameri ◽  
Manabu Yamada ◽  
Reuben Klein ◽  
...  
Keyword(s):  
Virus Infection ◽  
Nipah Virus ◽  
Disease Outbreaks ◽  
Mortality Rates ◽  
Hendra Virus ◽  
Malaria Therapy ◽  
Sporadic Disease

ABSTRACT Hendra virus and Nipah virus, two zoonotic paramyxoviruses in the genus Henipavirus, have recently emerged and continue to cause sporadic disease outbreaks in humans and animals. Mortality rates of up to 75% have been reported in humans, but there are presently no clinically licensed therapeutics for treating henipavirus-induced disease. A recent report indicated that chloroquine, used in malaria therapy for over 70 years, prevented infection with Nipah virus in vitro. Chloroquine was assessed using a ferret model of lethal Nipah virus infection and found to be ineffective against Nipah virus infection in vivo.

scholarly journals The Ability of Zika virus Intravenous Immunoglobulin to Protect From or Enhance Zika Virus Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Amelia K. Pinto ◽  
Mariah Hassert ◽  
Xiaobing Han ◽  
Douglas Barker ◽  
Trevor Carnelley ◽  
...  
Keyword(s):  
Virus Infection ◽  
Polyclonal Antibody ◽  
Zika Virus ◽  
Virus Disease ◽  
Polyclonal Antibodies ◽  
Antibody Therapeutics ◽  
The World ◽  
Flavivirus Infection

The closely related flaviviruses, dengue and Zika, cause significant human disease throughout the world. While cross-reactive antibodies have been demonstrated to have the capacity to potentiate disease or mediate protection during flavivirus infection, the mechanisms responsible for this dichotomy are still poorly understood. To understand how the human polyclonal antibody response can protect against, and potentiate the disease in the context of dengue and Zika virus infection we used intravenous hyperimmunoglobulin (IVIG) preparations in a mouse model of the disease. Three IVIGs (ZIKV-IG, Control-Ig and Gamunex®) were evaluated for their ability to neutralize and/or enhance Zika, dengue 2 and 3 viruses in vitro. The balance between virus neutralization and enhancement provided by the in vitro neutralization data was used to predict the IVIG concentrations which could protect or enhance Zika, and dengue 2 disease in vivo. Using this approach, we were able to define the unique in vivo dynamics of complex polyclonal antibodies, allowing for both enhancement and protection from flavivirus infection. Our results provide a novel understanding of how polyclonal antibodies interact with viruses with implications for the use of polyclonal antibody therapeutics and the development and evaluation of the next generation flavivirus vaccines.

scholarly journals Systemic Delivery of mLIGHT-Armed Myxoma Virus Is Therapeutic for Later-Stage Syngeneic Murine Lung Metastatic Osteosarcoma

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 337
Author(s):  
John D. Christie ◽  
Nicole Appel ◽  
Liqiang Zhang ◽  
Kenneth Lowe ◽  
Jacquelyn Kilbourne ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Ex Vivo ◽  
Tumor Burden ◽  
Myxoma Virus ◽  
Oncolytic Viruses ◽  
Systemic Delivery ◽  
Clinical Cancer Research ◽  
Critical Issues

Cancers that metastasize to the lungs represent a major challenge in both basic and clinical cancer research. Oncolytic viruses are newly emerging options but successful delivery and choice of appropriate therapeutic armings are two critical issues. Using an immunocompetent murine K7M2-luc lung metastases model, the efficacy of MYXV armed with murine LIGHT (TNFSF14/CD258) expressed under virus-specific early/late promoter was tested in an advanced later-stage disease K7M2-luc model. Results in this model show that mLIGHT-armed MYXV, delivered systemically using ex vivo pre-loaded PBMCs as carrier cells, reduced tumor burden and increased median survival time. In vitro, when comparing direct infection of K7M2-luc cancer cells with free MYXV vs. PBMC-loaded virus, vMyx-mLIGHT/PBMCs also demonstrated greater cytotoxic capacity against the K7M2 cancer cell targets. In vivo, systemically delivered vMyx-mLIGHT/PBMCs increased viral reporter transgene expression levels both in the periphery and in lung tumors compared to unarmed MYXV, in a tumor- and transgene-dependent fashion. We conclude that vMyx-mLIGHT, especially when delivered using PBMC carrier cells, represents a new potential therapeutic strategy for solid cancers that metastasize to the lung.

scholarly journals Linear polysialoside outperforms dendritic analogs for inhibition of influenza virus infection in vitro and in vivo

Biomaterials ◽  
2017 ◽  
Vol 138 ◽  
pp. 22-34 ◽  
Author(s):  
Sumati Bhatia ◽  
Daniel Lauster ◽  
Markus Bardua ◽  
Kai Ludwig ◽  
Stefano Angioletti-Uberti ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection

scholarly journals Autophagy Contributes to Host Immunity and Protection against Zika Virus Infection via Type I IFN Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yuyi Huang ◽  
Yujie Wang ◽  
Shuhui Meng ◽  
Zhuohang Chen ◽  
Haifan Kong ◽  
...  
Keyword(s):  
Virus Infection ◽  
Cell Line ◽  
Zika Virus ◽  
Fetal Brain ◽  
Host Immunity ◽  
Type I ◽  
Type I Ifn ◽  
Zikv Infection

Recent studies have indicated that the Zika virus (ZIKV) has a significant impact on the fetal brain, and autophagy is contributing to host immune response and defense against virus infection. Here, we demonstrate that ZIKV infection triggered increased LC3 punctuation in mouse monocyte-macrophage cell line (RAW264.7), mouse microglial cell line (BV2), and hindbrain tissues, proving the occurrence of autophagy both in vitro and in vivo. Interestingly, manual intervention of autophagy, like deficiency inhibited by 3-MA, can reduce viral clearance in RAW264.7 cells upon ZIKV infection. Besides, specific siRNA strategy confirmed that autophagy can be activated through Atg7-Atg5 and type I IFN signaling pathway upon ZIKV infection, while knocking down of Atg7 and Atg5 effectively decreased the ZIKV clearance in phagocytes. Furthermore, we analyzed that type I IFN signaling could contribute to autophagic clearance of invaded ZIKV in phagocytes. Taken together, our findings demonstrate that ZIKV-induced autophagy is favorable to activate host immunity, particularly through type I IFN signaling, which participates in host protection and defense against ZIKV infection.

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