RESUMO
Immature teratomas (IT) are rare and recurrences uncommon. A 12-year-old female with grade 3 (high-grade) ovarian IT underwent surgical resection but experienced early recurrences; the first was treated with surgery but the second was metastatic and managed with chemotherapy, resulting in growing-teratoma-syndrome and need for further surgery. She now remains well in uneventful clinical follow-up. We believe chemotherapy could be reserved for very carefully selected recurrent IT cases, which may alter the natural history of disease.
Assuntos
Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia , Quimioterapia Adjuvante , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/terapia , Tratamentos com Preservação do Órgão/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Teratoma/diagnóstico por imagem , Teratoma/terapia , alfa-Fetoproteínas/análiseRESUMO
PURPOSE: Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (HPV) types. It is frequently multifocal and recurrence after conventional treatment is high. Boosting HPV-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. We have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (TA-HPV) in women with anogenital intraepithelial neoplasia. EXPERIMENTAL DESIGN: Twelve women, aged 42-54 years with high-grade HPV-positive vulval or vaginal intraepithelial neoplasia of up to 15 years duration, completed a Phase II study of TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18. RESULTS: The vaccine was well tolerated. Five of 12 (42%) patients showed at least a 50% reduction in total lesion diameter over 24 weeks with 1 patient showing complete regression of her lesion. Overall, 83% of women showed some improvement with an average decrease in lesion size of 40%. All cases showed an increased IgG titer and T-cell response to the vaccinia virus. An IFN-gamma enzyme-linked immunospot assay using pooled 22-mer peptides spanning HPV-16 E6 and E7 showed an increased specific T-cell response after vaccination in 6 of the 10 cases available for testing. There was no increase in specific cytotoxic response to selected individual HLA class I-restricted HPV-16 E6/7 peptides. CONCLUSIONS: The results suggest that the vaccine may have an effect on HPV-positive vulval intraepithelial neoplasia/vaginal intraepithelial neoplasia and that additional studies are warranted to develop an effective therapeutic vaccine.
Assuntos
Vacinas Anticâncer/uso terapêutico , Carcinoma in Situ/terapia , Proteínas de Ligação a DNA , Papillomaviridae/genética , Infecções por Papillomavirus/terapia , Proteínas Repressoras , Vaccinia virus/genética , Neoplasias Vaginais/terapia , Neoplasias Vulvares/terapia , Adolescente , Adulto , Vacinas Anticâncer/efeitos adversos , Carcinoma in Situ/imunologia , Carcinoma in Situ/virologia , Feminino , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Papillomaviridae/imunologia , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Segurança , Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia , Neoplasias Vaginais/imunologia , Neoplasias Vaginais/virologia , Neoplasias Vulvares/imunologia , Neoplasias Vulvares/virologiaRESUMO
Endometrial cancer is the most common gynecologic malignancy, frequently arising in association with obesity and diabetes mellitus. To identify gene pathways contributing to endometrial cancer development, we studied the transcriptome of 20 endometrial cancers and 11 benign endometrial tissues using cDNA microarrays. Among the transcript changes identified in endometrial cancer were up-regulation of the nuclear hormone receptors peroxisome proliferator-activated receptors (PPAR) alpha and gamma, whereas retinoid X receptor beta was down-regulated. To clarify the contribution of PPARalpha to endometrial carcinogenesis, we did experiments on cultured endometrial carcinoma cells expressing this transcript. Treatment with fenofibrate, an activating ligand for PPARalpha, significantly reduced proliferation and increased cell death, suggesting that altered expression of nuclear hormone receptors involved with fatty acid metabolism leads to deregulated cellular proliferation and apoptosis. These results support further investigation of members of the PPAR/retinoid X receptor pathway as novel therapeutic targets in endometrial cancer.
Assuntos
Neoplasias do Endométrio/patologia , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Morte Celular , Linhagem Celular , Linhagem Celular Tumoral , Citoplasma/metabolismo , DNA Complementar/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/terapia , Feminino , Genes Reporter , Humanos , Imuno-Histoquímica , Ligantes , Hibridização de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/patologia , PPAR alfa/metabolismo , PPAR gama/metabolismo , RNA/química , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Endometrial carcinoma is the commonest type of female genital tract malignancy in the developed countries. Endometrial carcinoma is usually confined to the uterus at the time of diagnosis and as such usually carries an excellent prognosis with high curability. Our understanding and management of endometrial cancer have continuously developed. Current controversies focus on screening and early detection, the extent of nodal surgery, and the changing roles of radiation therapy and chemotherapy and will be discussed in this paper.