ABSTRACT
Schwannoma (neurilemmoma) is a peripheral nerve sheath tumor and commonly occurs singularly on the head, neck, and trunk. Giant schwannoma is rarely located on the retroperitoneum and pelvic cavity. The majority of symptoms caused by the tumor are due to the effect of its mass. Surgical resection is enough to treat the tumor. Schwannoma is reported usually as benign, and despite incomplete resection of the tumor, the risk of recurrence and metastasis is low. A schwannoma on the retroperitoneum that was preoperatively misdiagnosed as a malignant adnexal mass in a 60-year-old menopausal woman is presented, with a brief review of the literature.
Subject(s)
Neurilemmoma/pathology , Retroperitoneal Neoplasms/pathology , Retroperitoneal Space/pathology , Female , Humans , Middle Aged , Neurilemmoma/surgery , Retroperitoneal Neoplasms/surgery , Retroperitoneal Space/surgeryABSTRACT
OBJECTIVE: Human papillomavirus (HPV) infection play a significant role in cervical carcinogenesis, and HPV oncoprotein E7 has important functions in the formation and maintenance of cervical cancers. Interleukin-12 (IL-12) has been reported to induce cellular immune responses, and has also been demonstrated to suppress the growth of tumors and the expression of E7. Here, we investigate the utility of adenovirus E7 (AdE7) and adenovirus IL-12 (AdIL-12) for protection against TC-1 tumor using an animal model. METHODS: The antitumor effects induced by AdIL-12 and/or E7 were assessed by measurements of tumor size. E7-specific antibody and INF-gamma production in sera were measured, as were T-helper cell proliferative responses. Cytotoxic T-lymphocytes (CTL) and T cell subset depletion studies were also performed. RESULTS: Infection of tumor sites with a combination of AdIL-12 and AdE7 resulted in an antitumor effect which was significantly more profound than that which resulted from singular infections with either AdIL-12 or AdE7. Combined infection resulted in regression of 9-mm-sized tumors in approximately 80% of our experimental animals as compared to the PBS group. Serum levels of E7-specific antibody and INF-gamma production, as well as T-helper cell proliferative responses, were found to be significantly higher in coinfected with AdIL-12 and AdE7 group than in single infection with either AdIL-12 or AdE7 group. CTL responses only exhibited by the AdIL-12 and AdE7 coinjected group suggested that these tumor suppression effects were mediated primarily by CD8+ and, to a lesser degree, by CD4+ T cells. CONCLUSION: Combined injection with adenovirus carrying IL-12 and E7 induced significant antitumor immunity against TC-1 tumors. They may prove useful in clinical applications for the treatment of HPV-associated tumors.
Subject(s)
Interleukin-12/immunology , Lung Neoplasms/therapy , Oncogene Proteins, Viral/immunology , Uterine Cervical Neoplasms/immunology , Uterine Cervical Neoplasms/therapy , Adenoviridae/genetics , Animals , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Female , Humans , Immunoglobulin G/biosynthesis , Immunoglobulin G/immunology , Interleukin-12/biosynthesis , Interleukin-12/genetics , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Mice , Mice, Inbred C57BL , Oncogene Proteins, Viral/biosynthesis , Oncogene Proteins, Viral/genetics , Papillomavirus E7 Proteins , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/immunology , T-Lymphocytes, Cytotoxic/immunology , Transfection , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/virologyABSTRACT
PURPOSE: Human papillomavirus (HPV) infection has a significant role in cervical carcinogenesis, and HPV oncoprotein E7 plays an important part in the formation and maintenance of cervical cancer. Interleukin-12 (IL-12) has been reported to induce a cellular immune response, and to suppress the tumor growth and the E7 production. Here we describe the use of adenoviral delivery of the HPV 16 E7 subunit (AdE7) along with adenoviral delivery of IL-12 (AdIL-12) in mice with HPV-associated tumors. MATERIALS AND METHODS: Mice were injected with TC-1 cells to establish TC-1 tumor, and then they were immunized with AdIL-12 and/or AdE7 intratumorally. The anti tumor effects induced by AdIL-12 and/or E7 were evaluated by measuring the size of the tumor. E7-specific antibody and INF-gamma production in sera, and the T-helper cell proliferative responses were then measured. Cytotoxic T-lymphocyte (CTL) and T cell subset depletion studies were also performed. RESULTS: Combined AdIL-12 and AdE7 infection at the tumor sites significantly enhanced the antitumor effects more than that of AdIL-12 or AdE7 single infection. This combined infection resulted in regression of the 9 mm sized tumors in 80% of animals as compare to the PBS group. E7-specific antibody and INF-gamma production in the sera, and the T-helper cell proliferative responses were significantly higher with coinfection of AdIL-12 and AdE7 than with AdIL-12 or AdE7 alone. CTL response induced by AdIL-12 and AdE7 in the coinjected group suggested that tumor suppression was mediated by mostly CD8+ and only a little by the CD4+ T cells. CONCLUSION: IL-12 and E7 application using adenovirus vector showed antitumor immunity effects against TC-1 tumor, and this system could be use in clinical applications for HPV-associated cancer.
