Intrinsic Oncolytic Activity of Hoshino Mumps Virus Vaccine Strain Against Human Fibrosarcoma and Cervical Cancer Cell Lines


avatar Behnam Alirezaie ORCID 1 , 2 , avatar Ashraf Mohammadi ORCID 2 , * , avatar Arash Ghalyanchi Langeroudi 1 , avatar Roozbeh Fallahi ORCID 3 , avatar Ali Reza Khosravi ORCID 1 , **

Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Department of Human Viral Vaccines, Razi Vaccine and Serum Research Institute (RVSRI), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
Department of Research, Production and Breeding of Laboratory Animals, Razi Vaccine and Serum Research Institute (RVSRI), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
Corresponding Authors:

how to cite: Alirezaie B, Mohammadi A, Ghalyanchi Langeroudi A, Fallahi R, Khosravi A R. Intrinsic Oncolytic Activity of Hoshino Mumps Virus Vaccine Strain Against Human Fibrosarcoma and Cervical Cancer Cell Lines. Int J Cancer Manag. 2020;13(9):e103111. doi: 10.5812/ijcm.103111.



The use of oncolytic viruses as therapeutic agents is a promising treatment for various human cancers. Several viruses have been extensively examined to achieve tumor cell death.


This study aimed at evaluating the natural oncolytic activity of mumps Hoshino vaccine strain against two human cancer cell lines, that is, HT1080 fibrosarcoma and HeLa cervical adenocarcinoma cell lines.


The cytolytic activity of the virus was evaluated using an MTT assay. Apoptosis was detected by Annexin-V/propidium iodide (PI) staining and analyzed via flow cytometry. To indicate viral replication in vivo, nude mice with HeLa heterografts were treated with the Hoshino strain of mumps virus.


It was found that human fibrosarcoma and cervical cells were more sensitive to the mumps Hoshino strain, even at a very low multiplicity of infection (MOI) compared to normal human diploid cells. The results also showed that the Hoshino strain induced apoptosis in both cancer cells. A preliminary in vivo study revealed the significant suppression of tumor growth in the group treated with the mumps Hoshino strain compared to the control group.


The Hoshino vaccine strain of mumps virus showed promising oncolytic activities against human fibrosarcoma and cervical adenocarcinoma cells.

1. Background

Currently, human cancers are the leading cause of disease-related mortality and continue to be major health problems. Although current therapeutic strategies in oncology, including the use of chemical anti-cancer drugs, radiation, surgical methods, or combinations of these modalities, are valuable tools for the treatment of some human tumors, other approaches appear to be ineffective. In recent years, many efforts have been made to find novel methods for the treatment of different human tumors. Viral therapy with oncolytic viruses (OVs) is one of the most important areas of cancer therapy. Evidence shows that various viruses, such as some members of the Paramyxoviridae family exhibit oncolytic activity (1-4).

The wild-type Urabe strain of mumps virus (MuV) was reported to exhibit significant oncolytic activities against different human cancers in the mid-1970’s (5). The MuV belongs to the order Mononegavirales, the family Paramyxoviridae, the subfamily Rubulavirinae, and the genus Orthorubulavirus. Mumps, as one of several childhood infectious diseases, is a vaccine-preventable disease. However, the extensive use of attenuated vaccine strains has reduced the prevalence of this disease around the world (6). Although MuV has long been used as an anti-tumor agent in preclinical (7) and uncontrolled clinical trials (8-10). Limited studies have been recently conducted in this area. More recently, however, some natural and chimeric MuV strains have been studied as potential anti-cancer agents (11-16).

The attenuated Hoshino vaccine strain is one of the several commercial mumps vaccine strains, which is derived from a genotype-B wild-type MuV isolate and used as a vaccine in Japan, Korea, and Iran. This temperature-sensitive vaccine strain was developed by culturing on specific pathogen-free (SPF) chicken embryo cells at 32ºC, using the plaque cloning technique (17). Experimental studies on infections in monkeys, as well as clinical trials (18), have shown that this vaccine strain is both safe and effective. It is also extensively used in Iran.

2. Objectives

To the best of our knowledge, no study has been yet published on the oncolytic activity of the Hoshino vaccine strain of MuV. Therefore, this study aimed at elucidating the natural oncolytic activity of this commercially available vaccine strain against two human cancer cell lines, that is, HT1080 fibrosarcoma and HeLa cervical adenocarcinoma cell lines.

3. Methods

3.1. Cells and Virus

The HT1080 cell line was obtained from the Iranian Biological Resource Center (IBRC, Tehran, Iran). Normal human diploid (MRC-5) and HeLa cells were also obtained from the Human Viral Vaccine Department of Razi Vaccine and Serum Research Institute (RVSRI, Karaj, Iran). The cells were grown and passaged, using the Dulbecco’s modified eagle medium (DMEM; Sigma-Aldrich, St. Louis, MO, USA), containing 10% (v/v) fetal bovine serum (FBS; Gibco, Waltham, MA, USA) at 37ºC. The virus stock (Hoshino strain) was propagated in a primary SPF chicken embryo fibroblast (CEF) cell. The harvested virus was then extracted from the cell debris, using a 0.2-µm syringe filter (Sartorius, Goettingen, Germany). The infectivity titer (50% cell culture infective dose [CCID50]) was measured in the HeLa cell line, using a standard method, and virus titers were calculated according to the Spearman-Kärber method.

3.2. In Vitro Cell Viability Analysis

HeLa, HT1080, and MRC-5 cells (5,000 cells/well) were cultured in 100 µL of DMEM medium (Sigma-Aldrich, St. Louis, MO, USA), supplemented with 5% (v/v) FBS (Gibco, Waltham, MA, USA) and incubated for 24 hours at 37ºC in a 5% CO2 atmosphere in the air. To investigate the effects of viruses, the cells were infected with the Hoshino strain at a series of multiplicity of infection (MOI), including 0, 0.002, 0.02, 0.2, and 2 in 96-well plates (Orange Scientific, Braine-l’Alleud, Belgium). After 96 hours, the medium was replaced with a fresh one, containing 1 mg/mL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; Sigma Life Science, St. Louis, MO, USA).

The plates were incubated for four hours at 37ºC in a 5% CO2 atmosphere in the air. The supernatants were then removed and 100 µL of dimethyl sulfoxide (DMSO; BDH Chemicals Ltd., Poole, England) was added to each well. Cell viability was measured at 570 and 630 nm, using an enzyme-linked immunosorbent assay (ELISA) plate reader (Dynex MRX II, Chantilly, VA, USA). Virus infection was induced in triplicate. The results of cell viability are presented as the survival percentage of infected cells versus uninfected control cells, which were considered to have 100% viability. Data are presented as mean ± standard deviation (SD) of three measurements.

3.3. Apoptosis Measurements

Annexin-V/propidium iodide (PI) staining was performed for apoptosis analysis. The apoptotic cells were detected on day 4 post-infection, using the fluorescein isothiocyanate (FITC)-Annexin V apoptosis detection kit with PI (Biolegend, San Diego, CA, USA), according to the manufacturer’s instructions. All flow cytometric measurements were performed at the Iranian Biological Resource Center (IBRC, Tehran, Iran). Data were analyzed, using the Flowing software V. 2.5.1. Differences in the median fluorescence intensity were compared, using paired t-test, and statistical significance was defined as P < 0.05.

3.4. In Vivo Analysis (Subcutaneous Tumor Heterograft Model)

In this preliminary experimental study, six-week-old male athymic B6 nude mice were obtained from Pasteur Institute of Iran (North Research Center). The mice were kept in separate ventilated cages and fed autoclaved standard laboratory chow and tap water ad libitum. The experiments and procedures were approved by the Ethics Committee of Razi Institute (approval number: RVSRI.REC.98.001). The HeLa cells (106), resuspended in 100 µL of phosphate-buffered saline (PBS), were subcutaneously implanted in the right flanks of mice, using an insulin syringe. Afterward, the animals were placed back into their cages and examined twice a week for tumor growth. The length and width of the tumors were measured with a Vernier caliper. The tumor volume (mm3) was calculated as follows (19):

Tumor volume = Length × Width2 × 0.5

When the tumors reached a diameter of 5 - 10 mm, the heterograft mice were divided into two groups as follows: (i) intratumoral administration of MuV Hoshino strain; and (ii) intratumoral administration of clarified cell lysates (mock). The treatment group received four doses of the virus at 2.5 × 105 CCID50/dose twice a week for two weeks (total dose= 1 × 106 CCID50). The mice were euthanized as soon as they lost more than 20% of body weight, or neurological deficits emerged, or the tumor diameter exceeded 2.5 cm.

3.5. Statistical Analysis

Both in vitro and in vivo data are presented as mean ± standard deviation (SD). Datasets were compared by independent t-test in SPSS version 15. Statistical significance was set at P < 0.05.

4. Results

4.1. In Vitro Analysis

To determine the impact of viral dose (MOI) on viral cytotoxicity, MTT assays were performed on the HeLa, HT1080, and MRC-5 cell lines at different viral MOIs (Figure 1). Based on the results, the two cancer cell lines (HeLa and HT1080) showed almost the same sensitivity to this vaccine strain. Human fibrosarcoma and cervical cells were more sensitive to the MuV Hoshino strain, even at MOI of 0.02, compared to normal human diploid cells (MRC-5). Also, the overall mean effect of the virus at MOI of 2 was significant against non-cancerous cells (P < 0.00001).

The oncolytic effects of MuV Hoshino strain on human tumor cell lines versus non-cancerous control cells in vitro. A, Viability of the HT1080 cell line and human diploid MRC-5 cells, infected with the MuV Hoshino strain at different MOIs after 96 hours. B, Viability of HeLa cell line and human diploid MRC-5 cells infected with MuV at different MOIs after 96 hours. Asterisks indicate statistical significance (P &lt; 0.05) against non-cancerous human diploid MRC-5 cells at the corresponding time point. Error bars indicate standard errors of the means.

4.2. Apoptosis Measurements

The effect of MuV Hoshino strain on the induction of apoptosis was assessed, using Annexin-V/PI staining. The flow cytometry results revealed that apoptosis occurred when cancer cells were treated with the MuV Hoshino strain (Figure 2). The left bottom quadrant of the cytograms indicates the total number of viable cells, while the left top quadrant represents non-viable (necrotic) cells with PI uptake. Also, the right quadrants represent the number of apoptotic cells. The apoptotic cell count was significantly higher in HeLa and HT1080 cells, infected with the MuV Hoshino strain (P < 0.05).

Apoptosis induction by the MuV Hoshino strain on HT1080 and HeLa cells (one of the three experiments is shown here). Bar graphs illustrate the percentage of apoptotic cells in the three experiments. Data are presented as mean ± SD. Asterisks indicate statistical significance versus the control (P &lt; 0.05).

4.3. In Vivo Analysis

The HeLa cells were injected into the subcutaneous flank of male nude mice to determine the in vivo replication and oncolytic activity of Hoshino strain. For this purpose, MuV was administrated following tumor formation. Tumor nodules became visible within the first 10 days after implantation in 100% of inoculated mice. The groups of heterograft mice showed similar tumor volumes before treatment (P = 0.1290). All animals exhibited tumor growth for 30 days after receiving the first dose. On average, the MuV-treated animals showed a slower rate of tumor growth, compared to the control animals (Figure 3). The pairwise comparison of tumor volume revealed a significant delay in the tumor growth of the attenuated MuV-treated group, compared to the control group (P = 0.01769). This finding indicated that the attenuated MuV Hoshino strain exhibited effective oncolytic activity in vivo.

Therapeutic effects of the attenuated MuV Hoshino strain in the HeLa heterograft model. Asterisks indicate statistical significance versus the control group (P &lt; 0.05) at the corresponding time point.

5. Discussion

Oncolytic virotherapy is a novel immunotherapeutic approach for the treatment of different cancers (20). To date, some oncolytic viruses have been approved for cancer treatment and some are being currently tested in different preclinical models and clinical trial phases (21). The use of paramyxovirus oncolytic viruses, such as MuV, for the treatment of human malignancies, is a promising approach to integrate current therapeutic strategies (1-3). The known receptor of MuV, sialic acid sugar, is overexpressed on the surface of different tumor cells (22). This feature makes MuV a desirable candidate for the treatment of various cancers. Accordingly, different strains of MuV, derived from different isolates, have been examined as OVs (5, 7-16).

The first clinical trials of Urabe MuV strain showed its oncolytic and immunotherapeutic potentials (5, 8-10). The results of preclinical studies have also shown that some natural and engineered MuV strains exhibit oncolytic activities against tumor cell lines in vitro and in vivo (7, 11-16). The present study supports previous studies, where the oncolytic properties of other natural MuV vaccine strains were demonstrated against different human cancer cell lines, including melanoma (12), ovarian cancer (13), different solid malignancies (14), fibrosarcoma, adenocarcinoma (15), leukemia, and lymphoma (16).

The most important advantage of using attenuated vaccine strains, such as Hoshino strain, in oncolytic therapy is that it is both well-characterized and safe (commercially licensed for application). In the current study, an accepted and standard MTT assay was performed to evaluate the effects of MuV Hoshino strain on the viability of cells. Based on the Figure 1, the MuV Hoshino strain, even at very low MOIs, exhibited significant oncolytic activity against fibrosarcoma and cervical cancer cell lines. However, at an MOI of 2, the results were significantly different from non-cancerous cells (P < 0.00001). This suggests that the MuV Hoshino vaccine strain has greater oncolytic activities against fibrosarcoma and cervical cancer cell lines, compared to non-cancerous fibroblast-like MRC-5 cells. In other words, the results revealed the selectivity of MuV Hoshino strain for the lysis of these cancer cells.

Annexin-V/PI staining is one of the most widely used techniques for evaluating apoptosis quantitatively (23). This assay was used in the present study to analyze the effect of MuV Hoshino strain on apoptosis induction in the infected cells. The results revealed that the apoptotic and necrotic cell population significantly increased in both treated cancerous cells. Similar results have been observed regarding other MuV strains (14-16, 24). According to previous studies, MuV induces cellular apoptosis by upregulation of interleukin-1 beta (IL-1β) (24), or Fas/Fas ligand (FasL), or both (16).

Although previous studies have indicated that MuV SH and V proteins can have anti-apoptotic functions (25-28), apoptosis may be the predominant mechanism in the oncolytic activity of the MuV Hoshino strain, possibly due to the altered expression of some apoptotic receptors (29, 30), besides changes in apoptotic signaling pathways in these cancer cells. Moreover, HeLa is one of the cancer cell lines, which contains wild-type Kirsten rat sarcoma viral oncogene homolog K-RAS (31). A previous study showed that K-RAS mutations resulted in resistance to apoptosis (32). Therefore, the higher level of apoptosis in the HeLa cell line may be related to the increased apoptosis by K-RAS expression in response to viral replication.

Moreover, the treatment of heterograft mice with the MuV Hoshino strain at typical doses for vaccination revealed significant oncolytic activities following intratumoral therapy. The MuV virotherapy is a suitable candidate for cervical and fibrosarcoma cancers, because the tumors are solid. This method allows for direct intratumoral injection into the tumor site and minimizes virus inactivation by specific anti-virus neutralizing antibodies in the circulation system (33). Also, direct injection into solid tumors increases its spread in cancerous cells and decreases normal tissue damage (34). One of the possible accelerators of cell sensitivity to MuV is viral attachment (with high affinity) due to the high expression of MuV receptors (sialic acid residues) on the cell membrane.

5.1. Conclusion

Although the oncolytic activity of the MuV Hoshino strain needs to be confirmed in future preclinical studies, the primary findings of this study indicated that this commercially available attenuated MuV vaccine strain might be potentially used as an oncolytic therapeutic agent to treat fibrosarcoma and cervical cancers. Further research is necessary to explain the potential oncolytic activity of this strain against other cancer cell lines.



  • 1.

    Lech PJ, Russell SJ. Use of attenuated paramyxoviruses for cancer therapy. Expert Rev Vaccines. 2010;9(11):1275-302. doi: 10.1586/erv.10.124. [PubMed: 21087107].

  • 2.

    Matveeva OV, Guo ZS, Senin VM, Senina AV, Shabalina SA, Chumakov PM. Oncolysis by paramyxoviruses: preclinical and clinical studies. Mol Ther Oncolytics. 2015;2. doi: 10.1038/mto.2015.17. [PubMed: 26640815]. [PubMed Central: PMC4667943].

  • 3.

    Matveeva OV, Kochneva GV, Zainutdinov SS, Ilyinskaya GV, Chumakov PM. [Oncolytic Paramyxoviruses: Mechanism of Action, Preclinical and Clinical Studies]. Mol Biol (Mosk). 2018;52(3):360-79. Russian. doi: 10.7868/S0026898418030023. [PubMed: 29989571].

  • 4.

    Ahmad U, Ahmed I, Keong YY, Abd Manan N, Othman F. Inhibitory and apoptosis-inducing effects of Newcastle disease virus strain AF2240 on mammary carcinoma cell line. Biomed Res Int. 2015;2015:127828. doi: 10.1155/2015/127828. [PubMed: 25821783]. [PubMed Central: PMC4363544].

  • 5.

    Asada T. Treatment of human cancer with mumps virus. Cancer. 1974;34(6):1907-28. doi: 10.1002/1097-0142(197412)34:6<1907::aid-cncr2820340609>;2-4. [PubMed: 4611607].

  • 6.

    Minor PD. Live attenuated vaccines: Historical successes and current challenges. Virology. 2015;479-480:379-92. doi: 10.1016/j.virol.2015.03.032. [PubMed: 25864107].

  • 7.

    Oka N. Experimental Studies of Antineoplastic Therapy Using Mumps Virus for Malignant Brain Tumor. J Kansai Med Univ. 1988;40(1):19-43. doi: 10.5361/jkmu1956.40.1_19.

  • 8.

    Okuno Y, Asada T, Yamanishi K, Otsuka T, Takahashi M, Tanioka T, et al. Studies on the use of mumps virus for treatment of human cancer. Biken J. 1978;21(2):37-49. [PubMed: 749908].

  • 9.

    Sato M, Urade M, Sakuda M, Shirasuna K, Yoshida H, Maeda N, et al. Attenuated mumps virus therapy of carcinoma of the maxillary sinus. Int J Oral Surg. 1979;8(3):205-11. doi: 10.1016/s0300-9785(79)80020-4. [PubMed: 118126].

  • 10.

    Shimizu Y, Hasumi K, Okudaira Y, Yamanishi K, Takahashi M. Immunotherapy of advanced gynecologic cancer patients utilizing mumps virus. Cancer Detect Prev. 1988;12(1-6):487-95. [PubMed: 2972361].

  • 11.

    Ammayappan A, Russell SJ, Federspiel MJ. Recombinant mumps virus as a cancer therapeutic agent. Mol Ther Oncolytics. 2016;3:16019. doi: 10.1038/mto.2016.19. [PubMed: 27556105]. [PubMed Central: PMC4980112].

  • 12.

    Ammour YI, Ryabaya OO, Milovanova AV, Sidorov AV, Shohin IE, Zverev VV, et al. [Oncolytic Properties of a Mumps Virus Vaccine Strain in Human Melanoma Cell Lines]. Mol Biol (Mosk). 2018;52(4):659-66. doi: 10.1134/S002689841804002X. [PubMed: 30113031].

  • 13.

    Myers R, Greiner S, Harvey M, Soeffker D, Frenzke M, Abraham K, et al. Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer. Cancer Gene Ther. 2005;12(7):593-9. doi: 10.1038/sj.cgt.7700823. [PubMed: 15746945].

  • 14.

    Son HA, Zhang L, Cuong BK, Van Tong H, Cuong LD, Hang NT, et al. Combination of Vaccine-Strain Measles and Mumps Viruses Enhances Oncolytic Activity against Human Solid Malignancies. Cancer Invest. 2018;36(2):106-17. doi: 10.1080/07357907.2018.1434539. [PubMed: 29485292].

  • 15.

    Yan YF, Chen X, Zhu Y, Wu JG, Dong CY. Selective cytolysis of tumor cells by mumps virus S79. Intervirology. 2005;48(5):292-6. doi: 10.1159/000085097. [PubMed: 15956796].

  • 16.

    Zhang LF, Tan DQ, Jeyasekharan AD, Hsieh WS, Ho AS, Ichiyama K, et al. Combination of vaccine-strain measles and mumps virus synergistically kills a wide range of human hematological cancer cells: Special focus on acute myeloid leukemia. Cancer Lett. 2014;354(2):272-80. doi: 10.1016/j.canlet.2014.08.034. [PubMed: 25193462].

  • 17.

    Sasaki K, Higashihara M, Inoue K, Igarashi Y, Makino S. Studies on the development of a live attenuated mumps virus vaccine. I. Attenuation of the Hoshino "wild" strain of mumps virus. Kitasato Arch Exp Med. 1976;49(1-2):43-52. [PubMed: 828947].

  • 18.

    Makino S, Yamane Y, Sasaki K, Nagashima T, Higashihara M. Studies on the development of a live attenuated mumps virus vaccine. II. Development and evaluation of the live "Hoshino" mumps vaccine. Kitasato Arch Exp Med. 1976;49(1-2):53-62. [PubMed: 1025341].

  • 19.

    Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol. 1989;24(3):148-54. doi: 10.1007/BF00300234. [PubMed: 2544306].

  • 20.

    Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2016;15(9):660. doi: 10.1038/nrd.2016.178. [PubMed: 30907381].

  • 21.

    Li L, Liu S, Han D, Tang B, Ma J. Delivery and Biosafety of Oncolytic Virotherapy. Front Oncol. 2020;10:475. doi: 10.3389/fonc.2020.00475. [PubMed: 32373515]. [PubMed Central: PMC7176816].

  • 22.

    Bull C, Stoel MA, den Brok MH, Adema GJ. Sialic acids sweeten a tumor's life. Cancer Res. 2014;74(12):3199-204. doi: 10.1158/0008-5472.CAN-14-0728. [PubMed: 24830719].

  • 23.

    Wlodkowic D, Skommer J, Darzynkiewicz Z. Flow cytometry-based apoptosis detection. Methods Mol Biol. 2009;559:19-32. doi: 10.1007/978-1-60327-017-5_2. [PubMed: 19609746]. [PubMed Central: PMC3863590].

  • 24.

    Takikita S, Takano T, Narita T, Takikita M, Ohno M, Shimada M. Neuronal apoptosis mediated by IL-1 beta expression in viral encephalitis caused by a neuroadapted strain of the mumps virus (Kilham Strain) in hamsters. Exp Neurol. 2001;172(1):47-59. doi: 10.1006/exnr.2001.7773. [PubMed: 11681839].

  • 25.

    Woznik M, Rodner C, Lemon K, Rima B, Mankertz A, Finsterbusch T. Mumps virus small hydrophobic protein targets ataxin-1 ubiquitin-like interacting protein (ubiquilin 4). J Gen Virol. 2010;91(Pt 11):2773-81. doi: 10.1099/vir.0.024638-0. [PubMed: 20702650].

  • 26.

    Wilson RL, Fuentes SM, Wang P, Taddeo EC, Klatt A, Henderson AJ, et al. Function of small hydrophobic proteins of paramyxovirus. J Virol. 2006;80(4):1700-9. doi: 10.1128/JVI.80.4.1700-1709.2006. [PubMed: 16439527]. [PubMed Central: PMC1367141].

  • 27.

    Franz S, Rennert P, Woznik M, Grutzke J, Ludde A, Arriero Pais EM, et al. Mumps Virus SH Protein Inhibits NF-kappaB Activation by Interacting with Tumor Necrosis Factor Receptor 1, Interleukin-1 Receptor 1, and Toll-Like Receptor 3 Complexes. J Virol. 2017;91(18). doi: 10.1128/JVI.01037-17. [PubMed: 28659487]. [PubMed Central: PMC5571265].

  • 28.

    Rosas-Murrieta NH, Santos-Lopez G, Reyes-Leyva J, Jurado FS, Herrera-Camacho I. Modulation of apoptosis by V protein mumps virus. Virol J. 2011;8:224. doi: 10.1186/1743-422X-8-224. [PubMed: 21569530]. [PubMed Central: PMC3113304].

  • 29.

    Screaton GR, Mongkolsapaya J, Xu XN, Cowper AE, McMichael AJ, Bell JI. TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL. Curr Biol. 1997;7(9):693-6. doi: 10.1016/s0960-9822(06)00297-1. [PubMed: 9285725].

  • 30.

    Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM. An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science. 1997;277(5327):815-8. doi: 10.1126/science.277.5327.815. [PubMed: 9242610].

  • 31.

    Romano D, Maccario H, Doherty C, Quinn NP, Kolch W, Matallanas D. The differential effects of wild-type and mutated K-Ras on MST2 signaling are determined by K-Ras activation kinetics. Mol Cell Biol. 2013;33(9):1859-68. doi: 10.1128/MCB.01414-12. [PubMed: 23459937]. [PubMed Central: PMC3624182].

  • 32.

    Moon DO, Kim BY, Jang JH, Kim MO, Jayasooriya RG, Kang CH, et al. K-RAS transformation in prostate epithelial cell overcomes H2O2-induced apoptosis via upregulation of gamma-glutamyltransferase-2. Toxicol In Vitro. 2012;26(3):429-34. doi: 10.1016/j.tiv.2012.01.013. [PubMed: 22269385].

  • 33.

    Russell L, Peng KW, Russell SJ, Diaz RM. Oncolytic Viruses: Priming Time for Cancer Immunotherapy. BioDrugs. 2019;33(5):485-501. doi: 10.1007/s40259-019-00367-0. [PubMed: 31321623]. [PubMed Central: PMC6790338].

  • 34.

    Raja J, Ludwig JM, Gettinger SN, Schalper KA, Kim HS. Oncolytic virus immunotherapy: future prospects for oncology. J Immunother Cancer. 2018;6(1):140. doi: 10.1186/s40425-018-0458-z. [PubMed: 30514385]. [PubMed Central: PMC6280382].

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