H-1 Parvovirus as a Cancer-Killing Agent: Past, Present, and Future

The rat protoparvovirus H-1PV is nonpathogenic in humans, replicates preferentially in cancer cells, and has natural oncolytic and oncosuppressive activities. The virus is able to kill cancer cells by activating several cell death pathways. H-1PV-mediated cancer cell death is often immunogenic and triggers anticancer immune responses. The safety and tolerability of H-1PV treatment has been demonstrated in early clinical studies in glioma and pancreatic carcinoma patients. Virus treatment was associated with surrogate signs of efficacy including immune conversion of tumor microenvironment, effective virus distribution into the tumor bed even after systemic administration, and improved patient overall survival compared with historical control. However, monotherapeutic use of the virus was unable to eradicate tumors. Thus, further studies are needed to improve H-1PV’s anticancer profile. In this review, we describe H-1PV’s anticancer properties and discuss recent efforts to improve the efficacy of H-1PV and, thereby, the clinical outcome of H-1PV-based therapies.

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Extracts of Clove (Syzygium aromaticum) Potentiate FMSP-Nanoparticles Induced Cell Death in MCF-7 Cells

International Journal of Biomaterials ◽

10.1155/2018/8479439 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Firdos Alam Khan ◽

Sultan Akhtar ◽

Dana Almohazey ◽

Munthar Alomari ◽

Sarah Ameen Almofty

Keyword(s):

Cell Death ◽

Cell Viability ◽

Cancer Cells ◽

Cancer Cell ◽

Great Promise ◽

Syzygium Aromaticum ◽

Anticancer Properties ◽

Cancer Cell Death ◽

Combination Approach ◽

Mcf 7

Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer properties, but they do not elicit a significant response on cancer cells when treated alone. In the present study, we have tested fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in combination with crude clove extracts on human breast cancer cells (MCF-7) to examine whether the combination approach enhance the cancer cell death. The MCF-7 cells were treated with different concentrations (1.25 μg/mL, 12.5 μg/mL, 50 μg/mL, 75 μg/mL, and 100 μg/mL) of FMSP-nanoparticles alone and in combination with 50 μg/mL crude clove extracts. The effects of FMSP-nanoparticles alone and combined with clove extracts were observed after 24 hrs and 48 hrs intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4′,6-diamidino-2-phenylindole (DAPI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. We have demonstrated that cancer cell viability was decreased to 55.40% when treated with FMSP-nanoparticles alone, whereas when cancer cells were treated with FMSP-nanoparticles along with crude clove extracts, the cell viability was drastically decreased to 8.50%. Both morphological and quantitative data suggest that the combination of FMSP-nanoparticles plus crude clove extracts are more effective in treating cancer cells and we suggest that the combination treatment of nanoparticles along with clove extracts hold a great promise for the cancer treatments.

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The TAM family as a therapeutic target in combination with radiation therapy

Emerging Topics in Life Sciences ◽

10.1042/etls20170066 ◽

2017 ◽

Vol 1 (5) ◽

pp. 493-500 ◽

Cited By ~ 3

Author(s):

Garth W. Tormoen ◽

Marka R. Crittenden ◽

Michael J. Gough

Keyword(s):

Cell Death ◽

Radiation Therapy ◽

Immune Responses ◽

Cancer Cells ◽

Cancer Cell ◽

Tyrosine Kinases ◽

Cancer Cell Death ◽

Radiation Induced Cancer ◽

Tumor Environment ◽

Radiation Induced

Radiation therapy is primarily a modality to kill cancer cells in the treatment field. It is becoming increasingly clear that radiation therapy can also be used to direct immune responses that have the potential to clear residual local or distant disease outside the treatment field. We believe that cancer cell death is the critical link between these processes. Understanding the handling of dying cancer cells by immune cells in the tumor environment is crucial to facilitate immune responses following radiation therapy. We review the role of the TAM (Tyro3 Axl Mertk) group of receptor tyrosine kinases and their role following radiation-induced cancer cell death in the tumor environment.

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Magneto Mitochondrial Dysfunction Mediated Cancer Cell Death Using Intracellular Magnetic Nano-Transducers

Biomaterials Science ◽

10.1039/d1bm00419k ◽

2021 ◽

Author(s):

Wooram Park ◽

Seok-Jo Kim ◽

Paul Cheresh ◽

Jeanho Yun ◽

Byeongdu Lee ◽

...

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Mitochondrial Dysfunction ◽

Cancer Cells ◽

Cancer Cell ◽

High Sensitivity ◽

Intrinsic Pathway ◽

Cancer Cell Death

Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein,...

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Synergistic Effect Induced by Gold Nanoparticles with Polyphenols Shell during Thermal Therapy: Macrophage Inflammatory Response and Cancer Cell Death Assessment

Cancers ◽

10.3390/cancers13143610 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3610

Author(s):

Valeria De Matteis ◽

Mariafrancesca Cascione ◽

Loris Rizzello ◽

Daniela Erminia Manno ◽

Claudia Di Guglielmo ◽

...

Keyword(s):

Cancer Cells ◽

Cancer Cell ◽

Calcium Release ◽

Chemical Properties ◽

Chemical Route ◽

Au Nps ◽

Anticancer Properties ◽

Cancer Cell Death ◽

Combined Strategy

Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing them for use as heat-synergized tools in the thermal treatment of two types of cancer cells, namely, breast cancer (MCF-7) and neuroblastoma (SH-SY5Y) cells. The cell viability, calcium release, oxidative stress, HSP-70 expression, mitochondrial, and DNA damage, as well as cytoskeleton alteration, were evaluated. Results: Our results clearly demonstrate that the combined strategy markedly exerts anticancer effects against the tested cancer cell, while neither of the single treatments (only heat or only NPs) induced significant changes. Conclusions: Au NP@polyphenols may be powerful agents in cancer treatment.

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Tumor Microenvironment-Triggered In-Situ Cancer Vaccines with Dual Immunogenic Cell Death Inductions for Elevated Antitumor and Antimetastatic Therapy

Nanoscale ◽

10.1039/d1nr02018h ◽

2021 ◽

Author(s):

Jun Lin ◽

Binbin Ding ◽

Pan Zheng ◽

Dong Li ◽

Meifang Wang ◽

...

Keyword(s):

Cell Death ◽

Tumor Microenvironment ◽

Immune Responses ◽

Cancer Immunotherapy ◽

Cancer Vaccines ◽

High Specificity ◽

The Body ◽

Immunogenic Cell Death ◽

Specific Antigens

Cancer vaccine is to make tumor-specific antigens into vaccines, which then are injected back into the body to activate immune responses for cancer immunotherapy. Despite the high specificity and therapeutic...

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Hydrogen Phosphate Selectively Induces MDA-MB-231 Breast Cancer Cell Death in vitro

10.21203/rs.3.rs-956711/v1 ◽

2021 ◽

Author(s):

Aya Shanti ◽

Kenana Al Adem ◽

Cesare Stefanini ◽

Sungmun Lee

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Dihydrogen Phosphate ◽

Human Breast ◽

Hydrogen Phosphate ◽

Cancer Cell Death ◽

Phosphate Ions

Abstract Phosphate ions are the most abundant anions inside the cells, and they are increasingly gaining attention as key modulators of cellular function and gene expression. However, little is known about the effect of inorganic phosphate ions on cancer cells, particularly breast cancer cells. Here, we investigated the toxicity of different phosphate compounds to triple-negative human breast cancer cells (MDA-MB-231) and compared it to that of human monocytes (THP-1). We found that, unlike dihydrogen phosphate (H2PO4−), hydrogen phosphate (HPO42−) at 20 mM or lower concentrations induced breast cancer (MDA-MB-231) cell death more than immune (THP-1) cell death. We correlate this effect to the fact that phosphate in the form of HPO42− raises pH levels to alkaline levels which are not optimum for transport of phosphate into cancer cells. The results in this study highlight the importance of further exploring hydrogen phosphate (HPO42−) as a potential therapeutic for the treatment of breast cancer.

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Macrophage Migration Inhibitory Factor protects cancer cells from immunogenic cell death and impairs anti-tumor immune responses

PLoS ONE ◽

10.1371/journal.pone.0197702 ◽

2018 ◽

Vol 13 (6) ◽

pp. e0197702 ◽

Cited By ~ 20

Author(s):

Kristen N. Balogh ◽

Dennis J. Templeton ◽

Janet V. Cross

Keyword(s):

Cell Death ◽

Immune Responses ◽

Cancer Cells ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Inhibitory Factor ◽

Immunogenic Cell Death ◽

Macrophage Migration

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Immunomodulatory activity of IR700-labelled affibody targeting HER2

Cell Death and Disease ◽

10.1038/s41419-020-03077-6 ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Justyna Mączyńska ◽

Chiara Da Pieve ◽

Thomas A. Burley ◽

Florian Raes ◽

Anant Shah ◽

...

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Light Irradiation ◽

Immunomodulatory Activity ◽

Her2 Positive ◽

Immunological Responses ◽

Cancer Cell Death ◽

Immature Dendritic Cells

Abstract There is an urgent need to develop therapeutic approaches that can increase the response rate to immuno-oncology agents. Photoimmunotherapy has recently been shown to generate anti-tumour immunological responses by releasing tumour-associated antigens from ablated tumour cell residues, thereby enhancing antigenicity and adjuvanticity. Here, we investigate the feasibility of a novel HER2-targeted affibody-based conjugate (ZHER2:2395-IR700) selectively to induce cancer cell death in vitro and in vivo. The studies in vitro confirmed the specificity of ZHER2:2395-IR700 binding to HER2-positive cells and its ability to produce reactive oxygen species upon light irradiation. A conjugate concentration- and light irradiation-dependent decrease in cell viability was also demonstrated. Furthermore, light-activated ZHER2:2395-IR700 triggered all hallmarks of immunogenic cell death, as defined by the translocation of calreticulin to the cell surface, and the secretion of ATP, HSP70/90 and HMGB1 from dying cancer cells into the medium. Irradiating a co-culture of immature dendritic cells (DCs) and cancer cells exposed to light-activated ZHER2:2395-IR700 enhanced DC maturation, as indicated by augmented expression of CD86 and HLA-DR. In SKOV-3 xenografts, the ZHER2:2395-IR700-based phototherapy delayed tumour growth and increased median overall survival. Collectively, our results strongly suggest that ZHER2:2395-IR700 is a promising new therapeutic conjugate that has great potential to be applicable for photoimmunotherapy-based regimens.

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Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

BioMed Research International ◽

10.1155/2015/242437 ◽

2015 ◽

Vol 2015 ◽

pp. 1-14 ◽

Cited By ~ 40

Author(s):

Cory D. Bovenzi ◽

James Hamilton ◽

Patrick Tassone ◽

Jennifer Johnson ◽

David M. Cognetti ◽

...

Keyword(s):

Overall Survival ◽

Tumor Microenvironment ◽

Cancer Cells ◽

Meta Analysis ◽

Critical Role ◽

Disease Free Survival ◽

Free Survival ◽

Cd147 Expression ◽

Cancer Types ◽

Disease Free

Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147.Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses.Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p<0.001for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p<0.0001for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival.Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations.

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