RESUMEN
Aidi injection (ADI), a traditional Chinese biomedical preparation, is a promising adjuvant therapy for gynecologic tumors (GTs), including cervical cancer (CC), endometrial cancer (EC), and ovarian cancer (OC). Although studies have reported positively on ADI therapy, its exact effects and safety in GT patients remain controversial. Therefore, a wide-ranging systematic search of electronic databases was performed for this meta-analysis. Data from 38 trials including 3309 GT patients were analyzed. The results indicated that the combination of conventional treatment and ADI markedly improved the patients' overall response rate (P<0.00001), disease control rate (P<0.00001), and quality of life (P<0.05) compared with conventional treatment alone. Furthermore, patient immunity was enhanced with combined treatment, as indicated by significantly increased percentages of CD3+ (P=0.005) and CD4+ (P<0.00001) and increased CD4+/CD8+ ratio (P=0.001). Most of the adverse events caused by radiochemotherapy such as gastrointestinal issues, leukopenia, thrombocytopenia, and hepatotoxicity, (P<0.05 for all) were significantly alleviated when ADI was used in the GT patients. However, other adverse events such as nephrotoxicity, diarrhea, alopecia, and neurotoxicity did not significantly differ between the two groups. Overall, these results suggest that the combination of conventional and ADI treatment is more effective than conventional treatment alone.
Asunto(s)
Antineoplásicos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Relación CD4-CD8 , Ensayos Clínicos como Asunto , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Neoplasias de los Genitales Femeninos/inmunología , HumanosRESUMEN
There is mounting evidence that the immune system plays an important role in the development and growth of gynecologic malignancies, and preliminary studies show activity of immune checkpoint inhibitors in ovarian, endometrial, and cervix cancer. In this review, we outline the completed trials of immune checkpoint blockade in the treatment of gynecologic malignancies. In addition, we review the ongoing trials in each disease site. The questions of which patients will benefit from immune checkpoint inhibitors and when immune checkpoint inhibitors should be incorporated into the treatment of gynecologic malignancies continue to be largely unanswered. As preclinical and clinical data emerge regarding predictive markers for response and resistance to immune checkpoint inhibitors, rational combination treatment strategies will help to further develop this emerging field in the treatment of gynecologic malignancies.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Femeninos/inmunología , Inmunomodulación/efectos de los fármacos , Terapia Molecular Dirigida , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/farmacología , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/metabolismo , Ensayos Clínicos como Asunto , Terapia Combinada , Evaluación Preclínica de Medicamentos , Femenino , Neoplasias de los Genitales Femeninos/diagnóstico , Neoplasias de los Genitales Femeninos/mortalidad , Humanos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Resultado del TratamientoRESUMEN
Gynaecological malignancies, excluding breast cancer, cause approximately 25,000 deaths yearly among women in the US. Therefore, novel approaches for the prevention or treatment of these diseases are urgently required. In the case of cervical cancer, human papillomavirus (HPV) xenoantigens are readily recognised by the immune system, and their targeting has shown great promise in preclinical models of therapeutic vaccination and in clinical studies of preventative vaccination. A growing body of evidence indicates that ovarian cancer is also immunogenic and can thus be targeted through immunotherapy. This review outlines the principles and problems of immunotherapy for cervical and ovarian cancer, including the authors' personal assessment.
Asunto(s)
Traslado Adoptivo , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/uso terapéutico , Neoplasias de los Genitales Femeninos/terapia , Inmunoterapia , Neoplasias Ováricas/terapia , Papillomaviridae/inmunología , Neoplasias del Cuello Uterino/terapia , Vacunas Virales/uso terapéutico , Animales , Antígenos Heterófilos/inmunología , Ensayos Clínicos como Asunto , Citocinas , Evaluación Preclínica de Medicamentos , Femenino , Neoplasias de los Genitales Femeninos/inmunología , Neoplasias de los Genitales Femeninos/prevención & control , Humanos , Inmunoterapia/métodos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/trasplante , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/prevención & control , Linfocitos T Reguladores , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/prevención & control , Vacunas Atenuadas/uso terapéuticoAsunto(s)
Neoplasias de los Genitales Femeninos/inmunología , Neoplasias de los Genitales Femeninos/psicología , Interleucinas/metabolismo , Espiritualidad , Estrés Fisiológico/etiología , Estrés Fisiológico/inmunología , Factores de Edad , Femenino , Neoplasias de los Genitales Femeninos/metabolismo , Neoplasias de los Genitales Femeninos/terapia , Humanos , Interleucinas/inmunología , Estrés Fisiológico/metabolismo , Tacto TerapéuticoRESUMEN
IMMUNOLOGICAL PARAMETER FOR CANCER PATIENTS: In this paper, we are the first to demonstrate that a disturbed immune system, especially imbalance between monocytes and T cells in peripheral blood mononuclear cells, is closely related to cancer recurrence. We have developed a parameter of immunocompetence in cancer patients, which we designated the monocyte/T cell(M/T) ratio. The M/T ratio was shown to be related to cytotoxic T lymphocyte activity in vitro. Furthermore, the M/T ratio should be useful for earlier detection of recurrence than conventional tumor markers. Early detection of recurrence would permit a timely retreatment decision and contribute to prolonged survival in cancer patients. IMMUNOLOGICAL EFFECTS OF KAMPO MEDICINE: Juzen-taiho-to (TJ-48) is a traditional kampo medicine used in Japan and China. We demonstrated in this paper that CD3+8+ cytotoxic T lymphocytes specific for autologous and HLA shared allogeneic tumor cells were induced from peripheral blood mononuclear cells stimulated by TJ-48 in vitro. Furthermore, we also demonstrated that the M/T ratio is decreased by administration of TJ-48 in patients with gynecologic cancer.
Asunto(s)
Antineoplásicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Neoplasias de los Genitales Femeninos/inmunología , Femenino , Humanos , Técnicas In Vitro , Recurrencia Local de Neoplasia/inmunología , PronósticoAsunto(s)
Terapia Biológica , Terapia Genética , Neoplasias de los Genitales Femeninos/terapia , Inmunoterapia , Terapia Biológica/métodos , Femenino , Genes p53 , Neoplasias de los Genitales Femeninos/inmunología , Humanos , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/terapia , Vacunas contra Papillomavirus , Vacunas/uso terapéuticoAsunto(s)
Neoplasias de los Genitales Femeninos/inmunología , Trastornos Psicofisiológicos/inmunología , Estrés Psicológico/complicaciones , Adaptación Psicológica , Femenino , Neoplasias de los Genitales Femeninos/psicología , Humanos , Sistema Inmunológico/inmunología , Tolerancia Inmunológica/inmunología , Memoria Inmunológica/inmunología , Trastornos Psicofisiológicos/psicología , Factores de Riesgo , Rol del EnfermoAsunto(s)
Condiloma Acuminado/diagnóstico , Neoplasias de los Genitales Femeninos/diagnóstico , Neoplasias de los Genitales Masculinos/diagnóstico , Condiloma Acuminado/tratamiento farmacológico , Condiloma Acuminado/inmunología , Femenino , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Femeninos/inmunología , Neoplasias de los Genitales Masculinos/tratamiento farmacológico , Neoplasias de los Genitales Masculinos/inmunología , Humanos , Immunoblotting , Masculino , Podofilino/efectos adversos , Podofilino/uso terapéuticoAsunto(s)
Terapia por Estimulación Eléctrica/métodos , Endometriosis/terapia , Neoplasias de los Genitales Femeninos/terapia , Adulto , Formación de Anticuerpos , Encéfalo , Enfermedad Crónica , Endometriosis/inmunología , Femenino , Neoplasias de los Genitales Femeninos/inmunología , Humanos , Inmunidad Celular , Trastornos de la Menstruación/inmunología , Trastornos de la Menstruación/terapiaAsunto(s)
Neoplasias del Ano , Condiloma Acuminado , Neoplasias de los Genitales Femeninos , Adolescente , Adulto , Factores de Edad , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/epidemiología , Neoplasias del Ano/terapia , Niño , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/epidemiología , Condiloma Acuminado/inmunología , Condiloma Acuminado/terapia , Criocirugía , Ácido Dicloroacético/administración & dosificación , Electrocirugia , Femenino , Neoplasias de los Genitales Femeninos/diagnóstico , Neoplasias de los Genitales Femeninos/epidemiología , Neoplasias de los Genitales Femeninos/inmunología , Neoplasias de los Genitales Femeninos/terapia , Humanos , Recién Nacido , Masculino , Podofilino/administración & dosificación , Embarazo , Complicaciones Neoplásicas del Embarazo , Recurrencia , Factores Sexuales , Enfermedades de Transmisión Sexual , Ácido Tricloroacético/administración & dosificaciónRESUMEN
The long-term effect of radiotherapy on the immune system were evaluated in 52 patients cured for a gynecologic malignancy from 3 to 15 years. Eighty-seven percent of the patients had no depression in cell-mediated immunity as determined by delayed hypersensitivity reaction to DNCB. The absolute lymphocyte count, as well as the circulating immunoglobulins (IgA, IgG, IgM), were within the normal range. Thus, there were no significant changes in cell-mediated immunity and circulating immunoglobulins several years after radical wide-field radiotherapy.
Asunto(s)
Neoplasias de los Genitales Femeninos/radioterapia , Inmunidad , Adulto , Anciano , Aceite de Crotón/inmunología , Dinitroclorobenceno/inmunología , Femenino , Neoplasias de los Genitales Femeninos/inmunología , Humanos , Inmunidad Celular , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Recuento de Leucocitos , Linfocitos , Persona de Mediana Edad , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/radioterapia , Pruebas Cutáneas , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/radioterapia , Neoplasias Uterinas/inmunología , Neoplasias Uterinas/radioterapiaRESUMEN
To further define and determine the usefulness of CEA, 1100 CEA determinations have been made over the past two years at The Ohio State University Hospitals on patients with a variety of malignant and nonmalignant conditions. Correlation of CEA titers with history and clinical course has yielded interesting results not only in cancers of entodermally derived tissues, for which CEA has become an established adjunct in management, but also in certain other neoplasms and inflammatory states. The current total of 225 preoperative CEA determinations in colorectal carcinomas shows an 81% incidence of elevation, with postoperative titers remaining elevated in patients having only palliative surgery but falling to the negative zone after curative procedures. An excellent correlation exists between CEA levels and grade of tumor (more poorly differentiated tumors showing lower titers). Left-side colon lesions show significantly higher titers than right-side lesions. CEA values have been shown to be elevated in 90% of pancreatic carcinomas studied, in 60% of metastatic breast cancers, and in 35% of other tumors (ovary, head and neck, bladder, kidney, and prostate cancers). CEA levels in 35 ulcerative colitis patients show elevation during exacerbations (51%). During remissions titers fall toward normal, although in 31% still remaining greater than 2.5 ng/ml. In the six colectomies performed, CEA levels all fell into the negative zone postoperatively. Forty percent of adenomatous polyps showed elevated CEA titers (range 2.5-10.0) that dropped following polypectomy to the negative zone. Preoperative and postoperative CEA determinations are important in assessing the effectiveness of surgery. Serial CEA determinations are important in the follow-up period and in evaluation of the other modes of therapy (e.g., chemotherapy). These determinations of tumor antigenicity give the physician added prognostic insight into the behavior of the tumor growth. Rectal examination with guaiac determinations, sigmoidoscopy, cytology, barium enema, and a good clinical evaluation remain the primary tools for detecting colorectal disease. However, in the high-risk patient suspicious of developing cancer, CEA determinations as well as colonoscopy are now being used increasingly and provide additional highly valuable tools in the physician's armamentarium.