Hyperthermia potentiates oncolytic herpes viral killing of pancreatic cancer through a heat shock protein pathway

Eisenberg, David P.; Carpenter, Stephen M.; Adusumilli, Prasad S.; Chan, Mei-Ki; Hendershott, Karen; Yu, Zhenkun; Fong, Yuman

doi:10.1016/j.surg.2010.05.005

Cited by 23 publications

(24 citation statements)

References 58 publications

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“…OV therapy with several viruses, including adenoviruses (28,33,41), herpesviruses (17,36,52,61,71), and reoviruses (18,(29)(30), has recently shown promise in several PDA tumor models. However, there are several advantages of using VSV as an anticancer therapy.…”

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confidence: 99%

Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma

Murphy

Besmer

Moerdyk-Schauwecker

et al. 2012

J Virol

108

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bVesicular stomatitis virus (VSV) is a promising oncolytic agent against a variety of cancers. However, it has never been tested in any pancreatic cancer model. Pancreatic ductal adenocarcinoma (PDA) is the most common and aggressive form of pancreatic cancer. In this study, the oncolytic potentials of several VSV variants were analyzed in a panel of 13 clinically relevant human PDA cell lines and compared to conditionally replicative adenoviruses (CRAds), Sendai virus and respiratory syncytial virus. VSV variants showed oncolytic abilities superior to those of other viruses, and some cell lines that exhibited resistance to other viruses were successfully killed by VSV. However, PDA cells were highly heterogeneous in their susceptibility to virus-induced oncolysis, and several cell lines were resistant to all tested viruses. Resistant cells showed low levels of very early VSV RNA synthesis, indicating possible defects at initial stages of infection. In addition, unlike permissive PDA cell lines, most of the resistant cell lines were able to both produce and respond to interferon, suggesting that intact type I interferon responses contributed to their resistance phenotype. Four cell lines that varied in their permissiveness to VSV-⌬M51 and CRAd dl1520 were tested in mice, and the in vivo results closely mimicked those in vitro. While our results demonstrate that VSV is a promising oncolytic agent against PDA, further studies are needed to better understand the molecular mechanisms of resistance of some PDAs to oncolytic virotherapy.

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confidence: 99%

Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma

Murphy

Besmer

Moerdyk-Schauwecker

et al. 2012

J Virol

108

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“…The fact that HF10 reduces apoptosis may be related to its ability to spread throughout the tumor instead of being confined only to the injection site. Eisenberg et al 55 reported that virus-related apoptosis in pancreatic cancer cell lines, which is induced by Hsp72, was reduced in hyperthermia; if virus-related apoptosis is reduced, in vitro viral titers and cytotoxicity will be increased. These observations suggest that if viral infection causes apoptosis, the amount of infectious particles will gradually decrease.…”

Section: X400 X400mentioning

confidence: 99%

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

et al. 2011

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Oncolytic viruses are a promising method of cancer therapy, even for advanced malignancies. HF10, a spontaneously mutated herpes simplex type 1, is a potent oncolytic agent. The interaction of oncolytic herpes viruses with the tumor microenvironment has not been well characterized. We injected HF10 into tumors of patients with recurrent breast carcinoma, and sought to determine its effects on the tumor microenvironment. Six patients with recurrent breast cancer were recruited to the study. Tumors were divided into two groups: saline-injected (control) and HF10-injected (treatment). We investigated several parameters including neovascularization (CD31) and tumor lymphocyte infiltration (CD8, CD4), determined by immunohistochemistry, and apoptosis, determined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Median apoptotic cell count was lower in the treatment group (P ¼ 0.016). Angiogenesis was significantly higher in treatment group (P ¼ 0.032). Count of CD8-positive lymphocytes infiltrating the tumors was higher in the treatment group (P ¼ 0.008). We were unable to determine CD4-positive lymphocyte infiltration. An effective oncolytic viral agent must replicate efficiently in tumor cells, leading to higher viral counts, in order to aid viral penetration. HF10 seems to meet this criterion; furthermore, it induces potent antitumor immunity. The increase in angiogenesis may be due to either viral replication or the inflammatory response.

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“…Thus, it is suggested that by enhancing tumor oxygenation it is possible to make CSCs more susceptible to current treatments. For example, hyperthermia is used to promote tumor reoxygenation [220–223], radiosensitization [224] and heat shock [225, 226] in cancer cells. However, current clinical implementations of hyperthermia have been limited due to the nonspecific heating to the normal tissues and organs and consequent treatment-limiting side effects [227, 228].…”

Section: Nanomedicine-based Therapies Against Cscsmentioning

confidence: 99%

Can nanomedicines kill cancer stem cells?

Zhao

Alakhova

Kabanov

2013

Advanced Drug Delivery Reviews

119

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Most tumors are heterogeneous and many cancers contain small population of highly tumorigenic and intrinsically drug resistant cancer stem cells (CSCs). Like normal stem cell, CSCs have ability to self-renew and differentiate to other tumor cell types. They are believed to be a source for drug resistance, tumor recurrence and metastasis. CSCs often overexpress drug efflux transporters, spend most of their time in non-dividing G0 cell cycle state, and therefore, can escape the conventional chemotherapies. Thus, targeting CSCs is essential for developing novel therapies to prevent cancer relapse and emerging of drug resistance. Nanocarrier-based therapeutic agents (nanomedicines) have been used to achieve longer circulation times, better stability and bioavailability over current therapeutics. Recently, some groups have successfully applied nanomedicines to target CSCs to eliminate the tumor and prevent its recurrence. These approaches include 1) delivery of therapeutic agents (small molecules, siRNA, antibodies) that affect embryonic signaling pathways implicated in self-renewal and differentiation in CSCs, 2) inhibiting drug efflux transporters in an attempt to sensitize CSCs to therapy, 3) targeting metabolism in CSCs through nanoformulated chemicals and field-responsive magnetic nanoparticles and carbon nanotubes, and 4) disruption of multiple pathways in drug resistant cells using combination of chemotherapeutic drugs with amphiphilic Pluronic block copolymers. Despite clear progress of these studies the challenges of targeting CSCs by nanomedicines still exist and leave plenty of room for improvement and development. This review summarizes biological processes that are related to CSCs, overviews the current state of anti-CSCs therapies, and discusses state-of-the-art nanomedicine approaches developed to kill CSCs.

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Hyperthermia potentiates oncolytic herpes viral killing of pancreatic cancer through a heat shock protein pathway

Cited by 23 publications

References 58 publications

Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma

Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

Can nanomedicines kill cancer stem cells?

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