Oncolytic herpes simplex virus vectors are a promising strategy for cancer therapy, as direct cytotoxic agents, inducers of antitumor immune responses, and as expressers of anticancer genes. Progress is dependent upon representative preclinical models to evaluate therapy. In this study, two families of oncolytic herpes simplex virus vectors (G207 and NV1020 series) that have been in clinical trials were examined for the treatment of breast cancer, using the C3(1)/T-Ag transgenic mouse model. Female mice spontaneously develop mammary carcinomas, and the C3(1)/T-Ag-derived tumor cell line M6c forms implantable tumors. Both in vitro and in vivo, G47D, derived from G207 by deletion of ICP47 and the US11 promoter, was more efficacious than G207. Whereas NV1023, derived from NV1020 by deletion of ICP47 and insertion of LacZ, was as cytotoxic to M6c cells in vitro as G47D, it did not inhibit the growth of s.c. M6c tumors but did extend the survival of intracerebral tumor bearing mice. In contrast, NV1042, NV1023 expressing interleukin 12, inhibited s.c. M6c tumor growth to a similar extent as G47D, but was less effective than NV1023 in intracerebral tumors. In the spontaneously arising mammary tumor model, when only the first arising tumor per mouse was treated, G47D inhibited the growth of a subset of tumors, and when all tumors were treated, G47D significantly delayed tumor progression. When the first mammary tumor was treated and the remaining mammary glands removed, NV1042 was more efficacious than G47D at inhibiting the growth and progression of injected tumors. (Cancer Res 2005; 65(4): 1532-40)
Oncolytic viruses are an innovative therapeutic strategy for cancer, wherein viral replication and cytotoxicity are selective for tumor cells. Here we show the efficacy of systemically administered oncolytic viruses for the treatment of spontaneously arising tumors, specifically the use of oncolytic herpes simplex viruses (HSV) administered i.v. to treat spontaneously developing primary and metastatic prostate cancer in the transgenic TRAMP mouse, which recapitulates human prostate cancer progression. Four administrations of systemically delivered NV1023 virus, an HSV-1/HSV-2 oncolytic recombinant, to TRAMP mice at 12 or 18 weeks of age (presence of prostate adenocarcinoma or metastatic disease, respectively) inhibited primary tumor growth and metastases to lymph nodes. Expression of interleukin 12 (IL-12) from NV1042 virus, a derivative of NV1023, was additionally effective, significantly reducing the frequency of development of prostate cancer and lung metastases, even when the mice were treated after the onset of metastasis at 18 weeks of age. NV1042-infected cells, as detected by 5-bromo-4-chloro-3-indolyl-B-D-galactopyranoside staining for Lac Z expressed by the virus, were present in prostate tumors 1 week after the final virus injection and viral DNA was detected at 2 weeks after final virus injection by real-time PCR in primary and metastatic tumors but not in liver or blood. No toxicity was observed in any of the treated mice. The efficacy of the IL-12-expressing NV1042 virus in this aggressive prostate cancer model using a clinically relevant treatment paradigm merits its consideration for clinical studies.
Energy based devices (EBD) have been developed, implemented and increasingly applied in thyroid surgery because they can provide a combined dissection and haemostatic effect. In particular, advantages of EBD have been described in terms of efficacious haemostasis, reduction of procedureassociated time, reduced incision length, less operative blood loss and transfusion need, decreased postoperative drain, pain and hospital stay. In addition, EBD are essential for endoscopic procedures. On the contrary, a potential drawback is the increased health care costs. This paper reviews relevant medical literature published on the safety of new devices for achieving hemostasis and dissection around the recurrent laryngeal nerve (RLN).
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