scholarly journals SELECTED ASPECTS OF ALLO- AND XENOGRAFT MODEL APPLICATIONS FOR DEVELOPING NOVEL ANTI-CANCER VACCINES AND ONCOLYTIC VIRUSES

2019 ◽  
Vol 21 (2) ◽  
pp. 221-230
Author(s):  
T. S. Nepomnyashchikh ◽  
E. V. Gavrilova ◽  
R. A. Maksyutov
Keyword(s):  
Cancer Vaccines ◽  
Xenograft Model ◽  
Oncolytic Viruses ◽  
Anti Cancer

scholarly journals Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma

2021 ◽  
Vol 22 (7) ◽  
pp. 3578
Author(s):  
Federico Armando ◽  
Adnan Fayyad ◽  
Stefanie Arms ◽  
Yvonne Barthel ◽  
Dirk Schaudien ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Virus Infection ◽  
Tumor Growth ◽  
Canine Distemper Virus ◽  
Xenograft Model ◽  
Histiocytic Sarcoma ◽  
Oncolytic Viruses ◽  
Canine Distemper ◽  
Murine Xenograft Model ◽  
The Impact

Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.

scholarly journals Immunotherapy in Glioblastoma: A Clinical Perspective

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3721
Author(s):  
Nicolas Desbaillets ◽  
Andreas Felix Hottinger
Keyword(s):  
Cancer Vaccines ◽  
Adoptive Cell Transfer ◽  
Oncolytic Viruses ◽  
Clinical Perspective ◽  
Immune Microenvironment ◽  
Medical Need ◽  
Great Hope ◽  
Car T ◽  
Cancer Types ◽  
Proof Of Efficacy

Glioblastoma is the most frequent and the most aggressive brain tumor. It is notoriously resistant to current treatments, and the prognosis remains dismal. Immunotherapies have revolutionized the treatment of numerous cancer types and generate great hope for glioblastoma, alas without success until now. In this review, the rationale underlying immune targeting of glioblastoma, as well as the challenges faced when targeting these highly immunosuppressive tumors, are discussed. Innovative immune-targeting strategies including cancer vaccines, oncolytic viruses, checkpoint blockade inhibitors, adoptive cell transfer, and CAR T cells that have been investigated in glioblastoma are reviewed. From a clinical perspective, key clinical trial findings and ongoing trials are discussed for each approach. Finally, limitations, either biological or arising from trial designs are analyzed, and strategies to overcome them are presented. Proof of efficacy for immunotherapy approaches remains to be demonstrated in glioblastoma, but our rapidly expanding understanding of its biology, its immune microenvironment, and the emergence of novel promising combinatorial approaches might allow researchers to finally fulfill the medical need for GBM patients.

scholarly journals To Infection and Beyond: The Multi-Pronged Anti-Cancer Mechanisms of Oncolytic Viruses

Viruses ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 43 ◽  
Author(s):  
Kevin Cassady ◽  
Kellie Haworth ◽  
Josh Jackson ◽  
James Markert ◽  
Timothy Cripe
Keyword(s):  
Oncolytic Viruses ◽  
Anti Cancer

scholarly journals Anti-Cancer Effect of Ginsenoside F2against Glioblastoma Multiforme in Xenograft Model in SD Rats

2012 ◽  
Vol 36 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Ji-Yon Shin ◽  
Jung-Min Lee ◽  
Heon-Sub Shin ◽  
Sang-Yong Park ◽  
Jung-Eun Yang ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Xenograft Model ◽  
Sd Rats ◽  
Anti Cancer

scholarly journals Anti-Cancer Effects of CKD-581, a Potent Histone Deacetylase Inhibitor against Diffuse Large B-Cell Lymphoma

2020 ◽  
Vol 21 (12) ◽  
pp. 4377
Author(s):  
Soo Jin Kim ◽  
U Ji Kim ◽  
Hae Yong Yoo ◽  
Yong June Choi ◽  
Keon Wook Kang
Keyword(s):  
B Cell ◽  
Histone Deacetylase ◽  
Cell Lymphoma ◽  
Hdac Inhibitors ◽  
Xenograft Model ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Mouse Xenograft Model ◽  
Anti Cancer ◽  
Large B Cell

Double-hit lymphoma (DHL) and double-expressor lymphoma (DEL) are aggressive forms of lymphoma that require better treatments to improve patient outcomes. CKD-581 is a new histone deacetylase (HDAC) inhibitor that exhibited a better safety profile in clinical trials compared to other HDAC inhibitors. Here, we demonstrate that CKD-581 inhibited the class I–II HDAC family via histone H3 and tubulin acetylation. CKD-581 treatment also up-regulated the phosphorylation of histone H2AX (γH2AX, DNA double-strand break marker), and reduced levels of MYC and anti-apoptotic proteins such as BCL-2, BCL-6, BCL-XL, and MCL-1 in DH/DE-diffuse large B cell lymphoma (DLBCL) cell lines. Ultimately, CKD-581 also induced apoptosis via poly(ADP ribose) polymerase 1 (PARP1) cleavage. In a DLBCL SCID mouse xenograft model, CKD-581 exhibited anti-cancer effects comparable with those of rituximab (CD20 mAb). Our findings suggest that CKD-581 could be a good candidate for the treatment of DLBCL.

scholarly journals Hitting the Target but Missing the Point: Recent Progress towards Adenovirus-Based Precision Virotherapies

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3327
Author(s):  
Tabitha G. Cunliffe ◽  
Emily A. Bates ◽  
Alan L. Parker
Keyword(s):  
Viral Genome ◽  
Recent Progress ◽  
Oncolytic Viruses ◽  
Transformed Cells ◽  
Immunogenic Cell Death ◽  
Full Potential ◽  
Immune Mediated ◽  
Efficacious Treatment ◽  
Anti Cancer ◽  
Improvement In Survival

More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for efficacious treatment. Transformative amongst those are immunotherapies, which have proven effective agents for treating immunogenic forms of cancer, although immunologically “cold” tumour types remain refractive. Oncolytic viruses, such as those based on adenovirus, have great potential as anti-cancer agents and have seen a resurgence of interest in recent years. Amongst their many advantages is their ability to induce immunogenic cell death (ICD) of infected tumour cells, thus providing the alluring potential to synergise with immunotherapies by turning immunologically “cold” tumours “hot”. Additionally, enhanced immune mediated cell killing can be promoted through the local overexpression of immunological transgenes, encoded from within the engineered viral genome. To achieve this full potential requires the development of refined, tumour selective “precision virotherapies” that are extensively engineered to prevent off-target up take via native routes of infection and targeted to infect and replicate uniquely within malignantly transformed cells. Here, we review the latest advances towards this holy grail within the adenoviral field.

scholarly journals Spironolactone, a Classic Potassium-Sparing Diuretic, Reduces Survivin Expression and Chemosensitizes Cancer Cells to Non-DNA-Damaging Anticancer Drugs

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1550 ◽  
Author(s):  
Tomomi Sanomachi ◽  
Shuhei Suzuki ◽  
Keita Togashi ◽  
Asuka Sugai ◽  
Shizuka Seino ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Kinase Inhibitors ◽  
Xenograft Model ◽  
Growth Factor Receptor ◽  
Survivin Expression ◽  
Mouse Xenograft Model ◽  
Anti Cancer ◽  
Underlying Mechanisms

Spironolactone, a classical diuretic drug, is used to treat tumor-associated complications in cancer patients. Spironolactone was recently reported to exert anti-cancer effects by suppressing DNA damage repair. However, it currently remains unclear whether spironolactone exerts combinational effects with non-DNA-damaging anti-cancer drugs, such as gemcitabine and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Using the cancer cells of lung cancer, pancreatic cancer, and glioblastoma, the combinational effects of spironolactone with gemcitabine and osimertinib, a third-generation EGFR-TKI, were examined in vitro with cell viability assays. To elucidate the underlying mechanisms, we investigated alterations induced in survivin, an anti-apoptotic protein, by spironolactone as well as the chemosensitization effects of the suppression of survivin by YM155, an inhibitor of survivin, and siRNA. We also examined the combinational effects in a mouse xenograft model. The results obtained revealed that spironolactone augmented cell death and the suppression of cell growth by gemcitabine and osimertinib. Spironolactone also reduced the expression of survivin in these cells, and the pharmacological and genetic suppression of survivin sensitized cells to gemcitabine and osimertinib. This combination also significantly suppressed tumor growth without apparent adverse effects in vivo. In conclusion, spironolactone is a safe candidate drug that exerts anti-cancer effects in combination with non-DNA-damaging drugs, such as gemcitabine and osimertinib, most likely through the suppression of survivin.

scholarly journals Disrupting Androgen Receptor Functionality with Xanthones from the Mangosteen (Garcinia mangostana) Fruit

Proceedings ◽  
2020 ◽  
Vol 40 (1) ◽  
pp. 50
Author(s):  
Jeremy J. Johnson
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Xenograft Model ◽  
Pharmacokinetic Studies ◽  
Garcinia Mangostana ◽  
Optimal Dosing ◽  
Anti Cancer

The Southeast Asian mangosteen (Garcinia mangostana) contains a class of phytochemicals known as xanthones that possess extensive biological activity. Applications of xanthones, including the most prominent, alpha-mangostin, have been shown to possess anti-cancer, anti-oxidant, and anti-proliferation properties. To confirm the anti-cancer activity of xanthones we have evaluated 9 xanthones for decreasing cellular proliferation of cancer cells. These xanthones include alpha-mangostin, gartanin, 9-hydroxycalabaxanthone, garcinone C, garcinone D, and others. Using this approach, we have focused on understanding the ability of xanthones to disrupt androgen receptor in prostate cancer cells with a combination of cell free and cell-based assays. In addition, we have performed pharmacokinetic studies in mice with alpha-mangostin to characterize the optimal dosing strategy. Taken together, we have identified individual xanthones as capable of disrupting kinases, including CDK4, using cell free biochemical models and cell-based animal models. These results have been further validated in an in vivo xenograft model. Taken together, we have begun to describe the anti-cancer potential of xanthones for prostate cancer.

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