The method used was an indirect radioimmune precipitation test followed by polyacrylamide gel electrophoretic analysis of immune precipitates. MRI findings were typical; four patients had bilateral anterior temporal lesions and three had unilateral-temporal lesions. Oncolytic HSV-1 vectors expressing “suicide” genes (thymidine kinase, cytosine deaminase, rat cytochrome P450) or immunostimulatory genes (IL-12, GM-CSF, etc.) have been constructed to maximize tumor destruction through multimodal therapeutic mechanisms. Rejection or significant growth inhibition of challenged tumor cells was observed. Translation of HSV-Tk in the Ad-infected cells was measured by Western blot analysis. They generated mammospheres, which had cancer stem cell properties. In summary, all the preclinical and clinical data have suggested that HSV-based oncolytic virotherapies could likely be developed as a new generation of cancer vaccines for the treatment of solid tumors.
At MOIs of 0.01 to 1, EGFP expression is seen by flow cytometry in 100% of OCUM cells within 5 days after infection. Here, we examined the efficacy of an oncolytic herpes simplex virus type 2 (oHSV2) in killing colon cancer cells and colon cancer stem-like cells (CSLCs). RESULTS: In the in vivo study, tumor growth was suppressed and long-term survival rates were prolonged. After Ad-INSM1p-HSV-tk infection, the levels of HSV-tk protein expression were consistent with INSM1 promoter activities. This can be clinically important not just for improving efficacy but also for permitting lower and less toxic chemotherapeutic doses. We reasoned that both fusogenic strategies, incorporated into a single oncolytic HSV, might significantly improve virotherapy for ovarian cancer. These results provide additional rationale for the application of HSV 1 vector gene therapy for colorectal cancer.
For example, in our Ad.HSVtk/GCV intrapleural mesothelioma trial,6 complete tumor regression, associated with long-term (>4.5 years) survival was observed in two patients (unpublished data). M6c tumors but did extend the survival of intracerebral tumor bearing mice. Modifications include deleting nonessential regulatory proteins, proteins involved with nucleic acid metabolism, and host immunomodulating proteins. Although the use of HSV-1(Gbeta) was associated with systemic toxicity, HSV-G47Delta appears to possess a selective oncolytic activity. They generated mammospheres, which had cancer stem cell properties. Because GJIC appears to be a mediator of the bystander effect both in vitro and in vivo, here we review possible molecular strategies for enhancing the extent of tumor cell death by increasing the intratumoral GJIC capacity. The results showed enhanced levels of luciferase activities in the tumour region but not in the normal brain parenchyma.
Infection with oHSV G47Delta (ICP6(-), gamma34.5(-), alpha47(-)) not only killed GBM-SCs but also inhibited their self-renewal as evidenced by the inability of viable cells to form secondary tumor spheres. Note: In calculating the moving wall, the current year is not counted. This makes G47Δ more effective than G207 in killing tumor cells. We also showed that G47∆ was able to induce the regression of tumor xenografts in BALB/c nude mice and demonstrated the ability of G47∆ to synergize with paclitaxel by killing both NCSCs and CSCs, suggesting that oHSV may be an effective treatment modality for patients with breast cancer. We further showed that miR-143 and miR-145 inhibited the expression of the ICP4 gene at the translational level by targeting the corresponding 3′-UTR in a dose-dependent manner. Several independent studies suggest that HSV-2 infections correlate with a higher than normal incidence of cervical cancer. NV1020 resulted in a higher production of viral progeny compared to G207.
Among 21 non-small cell lung cancer cases in which CTC values were consecutively monitored, 81% showed treatment-related decreases, which was also found after treatments in the other solid tumors. Because effective therapy is available with the early use of antiviral agents, it is important to be aware of the potential for viral infection and to recognize the signs and symptoms that are evident early in its course. For oral cancer, a prime candidate virus is herpes simplex virus type-1 (HSV-1) which has several relevant features. Abstract New therapies are needed for metastatic breast cancer patients. Meningeal metastasis is a fatal complication of breast cancer that affects 5-8% of patients. Cancer Gene Therapy (2011) 18, 123–134; doi:10.1038/cgt.2010.62; published online 8 October 2010 Top of pageIntroduction The hypoxia-inducible factor (HIF) pathway is activated in many human primary tumors, metastases and cancer stem cells.1, 2, 3, 4 This is associated with increased patient mortality and resistance to chemo- and radio-therapies.5, 6 In contrast, the HIF pathway is inhibited in normal, healthy tissues. We report an exaggerated dermatological inflammatory condition in an immunocompromised patient.
Discovery of new cancer biomarkers and advances in targeted gene delivery mechanisms have made gene-directed enzyme prodrug therapy (GDEPT) an attractive method for treating cancer. Oncolytic virotherapy is an attractive approach that uses live viruses to selectively kill cancer cells. BACKGROUND: Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer.