RESUMO
BACKGROUND: Retinoic acid (RA) has antiproliferative as well as redifferentiating effects in thyroid cancers. Similar effects have been seen with phenylacetate (PA) therapy. These observations prompted us to evaluate the potential antiproliferative effects of the combination of RA and PA in follicular thyroid cancer. METHODS: Three follicular cell lines were treated in vitro with varying concentrations of all-trans RA or PA alone or in combination. Growth was measured by dimethyl-thiazol-diphenyltetrazolium bromide assays. RESULTS: RA (1-2.5 micromol/L) and PA (1-10 mmol/L) alone inhibited cell growth in a time- and dose-dependent manner, with maximum effect at 5 days. The combination of RA and PA had synergistic antiproliferative effects. In the FTC-133 cell line, RA alone (2.5 micromol/L) inhibited growth 16% and PA alone (10 mmol/L) inhibited growth 35% versus controls, whereas the combination of the 2 inhibited growth by 60% at 5 days (P < .005). Similar results were seen with FTC-236 and FTC-238 cell lines. CONCLUSIONS: Our results support that RA and PA have antiproliferative effects in follicular thyroid cancer and are synergistic. The combination of RA and PA may be beneficial in the treatment of advanced thyroid cancers for which conventional therapy fails or as an adjuvant to radioactive iodine therapy in aggressive tumors.
Assuntos
Antineoplásicos/farmacologia , Fenilacetatos/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tretinoína/farmacologia , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Humanos , Neoplasias da Glândula Tireoide/patologia , Células Tumorais CultivadasRESUMO
The only definitive therapy for patients with pheochromocytoma is surgical resection [1,2**]. Advances in preoperative medical management of hypertension/hypovolemia and improved intraoperative anesthetic care have reduced the operative mortality rate for pheochromocytoma to less than 5% in most series. In addition, accurate preoperative localization studies have eliminated the need for extensive exploratory laparotomy. Focused approach and laparoscopic resection have become the new "gold standard," with a reduced morbidity [4**]. Large or locally invasive pheochromocytomas may still require open resection.
Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , 3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/terapia , Medula Suprarrenal/metabolismo , Adrenalectomia/métodos , Antagonistas Adrenérgicos alfa/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Catecolaminas/metabolismo , Catecolaminas/urina , Diagnóstico por Imagem , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Laparoscopia , Metanefrina/urina , Síndromes Neoplásicas Hereditárias , Cuidados Paliativos , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Feocromocitoma/metabolismo , Feocromocitoma/terapia , Taquicardia/tratamento farmacológico , Taquicardia/etiologiaRESUMO
BACKGROUND: Without angiogenesis, tumor growth is limited to a few millimeters, the limit of diffusion. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen and a major regulator of angiogenesis. METHODS: To investigate the relationship between VEGF and thyroid tumor angiogenesis, we xenografted human dermal matrix inoculated with FTC-133 cells into nude mice or directly injected FTC-133 cells subcutaneously. To block the function of VEGF, the neutralizing anti-VEGF monoclonal antibody A.4.6.1 (mAb A.4.6.1) was injected intraperitoneally twice weekly. As control, an antibody of the same isotype (Ab 5B6) or phosphate buffer saline solution (PBS) was used. To evaluate the dermal matrix as a model for angiogenesis studies, recombinant human VEGF was inoculated into the dermal matrix pocket and xenografted into mice. RESULTS: In the dermal matrix angiogenesis model, the number of blood vessels paralleled the concentration of recombinant human VEGF and was highest at 100 ng/mL. Mice that were treated with the mAb A4.6.1 developed fewer blood vessels (mean, 6.6 per HPF) than control mice (18 per HPF in Ab 5B6 and 22 per HPF in PBS; P <.01). Tumors from mice that were treated with mAb A.4.6.1 were much smaller (mean +/- SD, 0.09 +/- 0.02 gm) at 5 weeks, compared with the tumors treated with Ab 5B6 (5.38 +/- 1.15 gm) or PBS (4.0 +/- 0.72 gm; P <.001). CONCLUSIONS: VEGF is produced by the follicular thyroid cancer cell line and stimulates angiogenesis and growth of thyroid cancer. This stimulation can be blocked by mAb A.4.6.1.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Fatores de Crescimento Endotelial/antagonistas & inibidores , Linfocinas/antagonistas & inibidores , Neoplasias da Glândula Tireoide/terapia , Animais , Fatores de Crescimento Endotelial/fisiologia , Feminino , Humanos , Linfocinas/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neovascularização Patológica/prevenção & controle , Neoplasias da Glândula Tireoide/patologia , Transplante Heterólogo , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Primary hyperparathyroidism, once thought to be a rare disease entity, is now a common problem. It can be diagnosed with nearly 100% accuracy. Surgical therapy is the only definitive cure for this disease, and normocalcemia is achieved in 95% of patients at initial operation when performed by an experienced surgeon. Even when the operation is initially unsuccessful, most of the patients with persistent disease can subsequently be cured. Although some clinicians have proposed that asymptomatic patients can be medically managed, the cost of such treatment, problems with patient compliance with long-term follow-up, the increased risk of premature death associated with primary hyperparathyroidism, and the low morbidity of operation support a liberal policy for exploration in most patients. The authors believe that nonoperative therapy should be limited to older patients with multiple comorbid conditions and minimal hypercalcemia and clinical manifestations.