Oncolytic activity of reovirus in HPV positive and negative head and neck squamous cell carcinoma.
Oncolytic activity of reovirus in HPV positive and negative head and neck squamous cell carcinoma.
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DOI：
10.1186/s40463-015-0062-x
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发表时间：
2015-02-24
期刊：
影响因子：
--
通讯作者：
Seikaly H
中科院分区：
文献类型：
--
作者：
Cooper T;Biron VL;Fast D;Tam R;Carey T;Shmulevitz M;Seikaly H
晚期头颈癌患者的管理需要多学科和多模式的治疗方法，包括手术，放疗和化疗的组合。这些毒性治疗方案显著改善了人乳头瘤病毒（HPV）相关口咽癌的不同人群的生存结局。HPV阴性的头颈部鳞状细胞癌（HNSCC）仍然是治疗的挑战，因为目前的治疗方案仅在生存方面有适度的改善，需要创新和新的治疗方法。溶瘤病毒作为低毒性辅助癌症治疗是HNSCC的新型、潜在有效的治疗方法。一种这样的溶瘤病毒是呼吸道孤儿肠道病毒或呼肠孤病毒。HNSCC细胞对呼肠孤病毒感染和呼肠孤病毒诱导的细胞死亡的易感性先前已被证明，但尚未在HPV阳性和阴性HNSCC细胞系中进行比较。比较呼肠孤病毒对HPV阳性和阴性HNSCC细胞系的感染性和溶瘤活性。用连续稀释的呼肠孤病毒感染七种HNSCC细胞系。UM-SCC-47和UM-SCC-104两株细胞系均为16型HPV阳性。感染后18小时使用基于细胞的ELISA测定法测量感染性。在感染后96小时，使用亚甲蓝活力测定法测定溶瘤活性。使用非线性回归模型计算感染和导致50%给定细胞系中细胞死亡所需的病毒量（EC 50）。比较EC 50值。与HPV阳性细胞系相比，HPV阴性细胞对病毒感染和溶瘤更敏感。18 h时感染性的EC 50范围为感染复数（MOI）值（PFU/细胞）18.6（SCC-9）至3133（UM-SCC 104）。96 h时细胞死亡的EC 50范围为MOI（PFU/细胞）1.02×102（UM-SCC-14 A）至3.19×108（UM-SCC-47）。最不敏感细胞系（UM-SCC-47）和最敏感细胞系（UM-SCC 14 A）在96 h时的细胞死亡EC 50之间存在3×106倍差异。与HPV阳性HNSCC相比，HPV阴性HNSCC细胞系似乎表现出更大的呼肠孤病毒感染性和病毒介导的溶瘤作用。呼肠孤病毒显示出作为HNSCC的新型疗法的前景，并且可能在HPV阴性患者中特别有益。
The management of patients with advanced stages of head and neck cancer requires a multidisciplinary and multimodality treatment approach which includes a combination of surgery, radiation, and chemotherapy. These toxic treatment protocols have significantly improved survival outcomes in a distinct population of human papillomavirus (HPV) associated oropharyngeal cancer. HPV negative head and neck squamous cell carcinoma (HNSCC) remains a challenge to treat because there is only a modest improvement in survival with the present treatment regimens, requiring innovative and new treatment approaches. Oncolytic viruses used as low toxicity adjunct cancer therapies are novel, potentially effective treatments for HNSCC. One such oncolytic virus is Respiratory Orphan Enteric virus or reovirus. Susceptibility of HNSCC cells towards reovirus infection and reovirus-induced cell death has been previously demonstrated but has not been compared in HPV positive and negative HNSCC cell lines. To compare the infectivity and oncolytic activity of reovirus in HPV positive and negative HNSCC cell lines. Seven HNSCC cell lines were infected with serial dilutions of reovirus. Two cell lines (UM-SCC-47 and UM-SCC-104) were positive for type 16 HPV. Infectivity was measured using a cell-based ELISA assay 18 h after infection. Oncolytic activity was determined using an alamar blue viability assay 96 h after infection. Non-linear regression models were used to calculate the amounts of virus required to infect and to cause cell death in 50% of a given cell line (EC50). EC50 values were compared. HPV negative cells were more susceptible to viral infection and oncolysis compared to HPV positive cell lines. EC50 for infectivity at 18 h ranged from multiplicity of infection (MOI) values (PFU/cell) of 18.6 (SCC-9) to 3133 (UM-SCC 104). EC50 for cell death at 96 h ranged from a MOI (PFU/cell) of 1.02×102 (UM-SCC-14A) to 3.19×108 (UM-SCC-47). There was a 3×106 fold difference between the least susceptible cell line (UM-SCC-47) and the most susceptible line (UM-SCC 14A) EC50 for cell death at 96 h. HPV negative HNSCC cell lines appear to demonstrate greater reovirus infectivity and virus-mediated oncolysis compared to HPV positive HNSCC. Reovirus shows promise as a novel therapy in HNSCC, and may be of particular benefit in HPV negative patients.
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影响因子：
3.1
作者：
Mendez, II;Hermann, LL;Coombs, KM
通讯作者：
Coombs, KM
影响因子：
2.7
作者：
HASHIRO, G;LOH, PC;YAU, JT
通讯作者：
YAU, JT
影响因子：
50.5
作者：
Bossi, P.;Orlandi, E.;Licitra, L.
通讯作者：
Licitra, L.
DOI：
10.1002/hed.21439
发表时间：
2011-02-01
影响因子：
2.9
作者：
Lau, Harold Y.;Brar, Sony;Magliocco, Anthony M.
通讯作者：
Magliocco, Anthony M.
影响因子：
5.6
作者：
El-Mofty, SK;Lu, DW
通讯作者：
Lu, DW