<i>mda-7/IL-24</i> Induces Cell Death in Neuroblastoma through a Novel Mechanism Involving AIF and ATM

Bhoopathi, Praveen; Lee, Nathaniel; Pradhan, Anjan K.; Shen, Xue‐Ning; Das, Swadesh K.; Sarkar, Devanand; Emdad, Luni; Fisher, Paul B.

doi:10.1158/0008-5472.can-15-2959

Cited by 32 publications

(34 citation statements)

References 49 publications

(74 reference statements)

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“…A recent study from our group discovered a novel molecular mechanism of MDA‐7/IL‐24‐mediated cell death in neuroblastoma. Specifically, we found that mda‐7/IL‐24 induces ATM‐mediated activation of H2AX and AIF resulting in caspase‐independent apoptosis that appears unique to neuroblastoma cells (Bhoopathi et al, ). Another recent study from our group demonstrates that overexpression of mda‐7/IL‐24 , either via Ad.…”

Section: Mda‐7/il‐24: Novel Multifunctional Cancer Therapeutic Cytokinementioning

confidence: 93%

“…We evaluated the therapeutic efficacy of CTV (Ad.PEG‐E1A‐ mda ‐7) in various cancer models including breast, prostate, pancreatic, renal, melanoma, glioma, and neuroblastoma (Azab et al, ; Bhoopathi et al, ; Greco et al, ; Hamed, Das, et al, ; Hamed, Yacoub, et al, ; Sarkar, Su, Vozhilla, Park, Gupta, et al, ; Sarkar et al, ; Sarkar et al, ). Initial studies were performed using the breast cancer model.…”

Section: It Takes More Than Viral Replication Alone To Treat Cancer mentioning

confidence: 99%

“…Additionally, Ad.5/3 also retains high infectivity in CAR‐expressing tumor cells showing equal efficacy when compared with wild‐type Ad.5, thereby providing an expanded range of utility for Ad.5/3, in both low‐ and high‐CAR‐expressing tumor cells (Dash, Dmitriev, et al, ; Eulitt et al, ). This second‐generation CTV in a tropism‐modified Ad.5/3 virus, Ad.5/3‐ CTV has shown profound primary and ‘ bystander ’ antitumor activity in additional tumor models including prostate cancer, glioblastoma multiforme, pancreatic cancer, renal cancer and neuroblastoma (Azab et al, ; Bhoopathi et al, ; Hamed, Das, et al, ; Hamed, Yacoub, et al, ; Sarkar et al, ).…”

Section: It Takes More Than Viral Replication Alone To Treat Cancer mentioning

confidence: 99%

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Cancer terminator viruses (CTV): A better solution for viral‐based therapy of cancer

Emdad¹,

Das²,

Wang³

et al. 2018

Journal Cellular Physiology

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In principle, viral gene therapy holds significant potential for the therapy of solid cancers. However, this promise has not been fully realized and systemic administration of viruses has not proven as successful as envisioned in the clinical arena. Our research is focused on developing the next generation of efficacious viruses to specifically treat both primary cancers and a major cause of cancer lethality, metastatic tumors (that have spread from a primary site of origin to other areas in the body and are responsible for an estimated 90% of cancer deaths). We have generated a chimeric tropism-modified type 5 and 3 adenovirus that selectively replicates in cancer cells and simultaneously produces a secreted anti-cancer toxic cytokine, melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24), referred to as a Cancer Terminator Virus (CTV) (Ad.5/3-CTV). In preclinical animal models, injection into a primary tumor causes selective cell death and therapeutic activity is also observed in non-injected distant tumors, that is, "bystander anti-tumor activity." To enhance the impact and therapeutic utility of the CTV, we have pioneered an elegant approach in which viruses are encapsulated in microbubbles allowing "stealth delivery" to tumor cells that when treated with focused ultrasound causes viral release killing tumor cells through viral replication, and producing and secreting MDA-7/IL-24, which stimulates the immune system to attack distant cancers, inhibits tumor angiogenesis and directly promotes apoptosis in distant cancer cells. This strategy is called UTMD (ultrasound-targeted microbubble-destruction). This novel CTV and UTMD approach hold significant promise for the effective therapy of primary and disseminated tumors.

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Section: Mda‐7/il‐24: Novel Multifunctional Cancer Therapeutic Cytokinementioning

confidence: 93%

Section: It Takes More Than Viral Replication Alone To Treat Cancer mentioning

confidence: 99%

Section: It Takes More Than Viral Replication Alone To Treat Cancer mentioning

confidence: 99%

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Cancer terminator viruses (CTV): A better solution for viral‐based therapy of cancer

Emdad¹,

Das²,

Wang³

et al. 2018

Journal Cellular Physiology

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“…No significant changes were found between uninfected groups ( Figures 3A1-3A2). A recent study involving a tropism-modified cancer terminator virus (named Ad.5/3-CTV), which selectively replicates in cancer cells producing a robust expression of IL-24 showed induction of apoptosis by modulation of apoptosis-inducing factor (AIF), ATM and g-H2AX (Bhoopathi et al, 2016). A recent study involving a tropism-modified cancer terminator virus (named Ad.5/3-CTV), which selectively replicates in cancer cells producing a robust expression of IL-24 showed induction of apoptosis by modulation of apoptosis-inducing factor (AIF), ATM and g-H2AX (Bhoopathi et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

HIV‐1 infection modulates IL‐24 expression which contributes to cell apoptosis in vitro

Strumillo

Curcio

Carvalho

et al. 2019

Cell Biology International

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Although interleukin-24 (IL-24) has been extensively explored in the immunopathologies of autoimmune diseases, neoplasms, and infections, its role in HIV-1 infection has not been thoroughly elucidated to date. Therefore, the objective of this study was to evaluate the gene and protein expressions of IL-24 at the initial moments of HIV infection in PBMCs. Due to the pro-apoptotic role of IL-24, we evaluated the protein expression of caspase-3, as well as Annexin V/Propidium Iodide flow cytometry and phosphorylation of ERK, which may induce an apoptotic signal block when phosphorylated. The results of this study demonstrated that HIV-1 infection had an impact on the gene and protein expressions of IL-24 and ERK. Annexin V/ Propidium Iodide assay demonstrated decrease in the mechanisms of apoptosis in infected cells after incubation of IL-24 neutralizing antibody. Studies on how HIV-1 regulates IL-24 expression may play a role in characterizing viral persistence mechanisms and designing antiretroviral strategies.

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“…77 IL-24 kaspazdan bağımsız yolla AIF, ATM ve H2AFX regülasyonu üzerinden nöroblastomda hücre ölü-münü indüklemektedir. 78 Bakiye GÖKER BAĞCA ve ark.…”

Section: Hedefe Yöneli̇k Tedavi̇ Yaklaşimi Ve Gelecek Perspekti̇flerunclassified

Neuroblastoma: Genetic, Epigenetic Mechanisms and Targeted Therapy Approaches: Review

Bağca¹,

Avcı²

2017

Turkiye Klinikleri J Neur

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Ö ÖZ ZE ET T Nöroblastom, embriyonik dönemde ortaya çıkan, nöral krest kaynaklı nadir bir kanser tü-rüdür. Santral sinir sistemindeki herhangi bir bölgeden ama sıklıkla böbrek üstü bezlerinden köken almaktadır. Hastalarda genellikle lenf düğümlerine, kemik iliğine ve kemiğe metastaz gerçekleş-mesi sağkalımı olumsuz şekilde etkilemektedir. Nöroblastomun başlangıçta tamamen ailesel bir hastalık olduğu düşünülse de ailesel olanlar tüm hastaların küçük bir bölümünü oluşturmaktadır. Nöroblastom patogenezinde rol aldığı tanımlanmış olan belli başlı mutasyonlar MYCN, ALK, PHOX2B, ATRX ve TERT genlerini içermektedir. Bununla birlikte artık sadece genetik değil epigenetik düzenlenim hatalarının da diğer pek çok hastalıkta olduğu gibi, nöroblastom patogenezinde görev aldığı bilinmektedir. Kromatin yapının regülasyonunu sağlayan histon modifikasyonları, gen ifadesinin kontrolünde görev alan DNA metilasyonu ve ncRNA'lar aracılığıyla gerçekleşen bu düzenlemelerin nöroblastomla ilişkisi araştırılmaktadır. Konvansiyonel tedavi, hastaların prognostik özelliklerine bağlı olarak cerrahi müdahale ile tümörün çıkarılması, kemoterapi, otolog kök hücre nakli ve radyoterapi yaklaşımlarını içermesine rağmen, kemoterapötiklere karşı direnç gelişimi ya da duyarsızlık sorunları sıklıkla ortaya çıkmaktadır. Bu sorunların üste-sinden gelmek, sağkalımı ve yaşam kalitesini artırmak için güncel tedavi yaklaşımları, doğrudan kanser hücresini elimine etmeyi amaçlayan "hedefe yönelik tedavi" yaklaşımlarının geliştirilme-sine odaklanmış durumdadır. Bu çalışmada, nöroblastom genetiği ve epigenetiği hakkında bildiklerimizin ve hedefe yönelik tedavi yaklaşımlarında nerede olduğumuzun güncel literatür verileri ile ortaya konulması amaçlanmıştır.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Nöroblastom; genetik; neoplastik kök hücreler; moleküler hedefe yönelik tedavi A AB BS S T TR RA AC CT T Neuroblastoma is a rare cancer arising in the embryonic stage, originating from the neural crest. It originates from any region of the central nervous system, but often emerges from the adrenal glands. In most cases, metastasis to lymph nodes, bone marrow, and bone affect survival rates adversely. Although neuroblastoma is considered as a completely familial disease at the beginning, familial cases constitute a small part of all cases. The major mutations identified in the pathogenesis of neuroblastoma include MYCN, ALK, PHOX2B, ATRX and TERT genes. Nevertheless, it is now known that not only genetic but also epigenetic aberrations of gene expression are involved in the pathogenesis of neuroblastoma as well as many other diseases. Epigenetic regulations which include histone modifications that regulate the chromatin structure; DNA methylation which is involved in the control of gene expression; and ncRNAs, is being searched in relation to neuroblastoma. Conventional treatment includes surgical removal of tumors, chemotherapy, autologous stem cell transplantation, radiotherapy approaches according to the prognostic features of the patients, however, res...

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mda-7/IL-24 Induces Cell Death in Neuroblastoma through a Novel Mechanism Involving AIF and ATM

Cited by 32 publications

References 49 publications

Cancer terminator viruses (CTV): A better solution for viral‐based therapy of cancer

Cancer terminator viruses (CTV): A better solution for viral‐based therapy of cancer

HIV‐1 infection modulates IL‐24 expression which contributes to cell apoptosis in vitro

Neuroblastoma: Genetic, Epigenetic Mechanisms and Targeted Therapy Approaches: Review

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