RESUMEN
Malignant melanoma is a neuroendocrine tumor that contains somatostatin receptors (SSTRs). Adjuvant therapy for melanoma is limited. Because melanomas arise from neural crest cells, we sought to evaluate the distribution of SSTR subtypes found in these tumors and their functional significance by imaging with 111In-pentetreotide scintigraphy (OctreoScan). Octreotide binds with greatest affinity to SSTR2 and SSTR5. Studying the expression of SSTRs in melanoma may demonstrate a potential role for octreotide in the treatment of melanoma. A series of 23 melanomas from 17 patients who underwent resection of regional or distant metastases were evaluated for the presence of SSTRs by the reverse transcriptase-polymerase chain reaction (RT-PCR) using primers specific for SSTR1 through SSTR5. Identity of RT-PCR products was confirmed by Southern blot analysis. Sixteen patients underwent preoperative OctreoScan. SSTR1 was expressed in 96% of tumors, SSTR2 in 83%, SSTR3 in 61%, SSTR4 in 57%, and SSTR5 in 9%. OctreoScan imaged 63% of tumors. There was no correlation between SSTR subtype expression and OctreoScan result. Most of the melanomas expressed mRNA for SSTR1 and SSTR2, with approximately half expressing SSTR3 and SSTR4. The SSTR mRNA for SSTR2 appears to be transcribed into functional protein that binds 111In-pentetreotide in more than half of these patients. Although OctreoScan has limited sensitivity for localizing melanomas, tumors that can be imaged by OctreoScan may be amenable to adjuvant therapy with octreotide or targeted therapy with high-energy radioisotope-labeled octreotide. These studies clearly define melanoma as a neuroendocrine tumor, which may open new avenues for tumor control.
Asunto(s)
Melanoma/metabolismo , Tumores Neuroendocrinos/metabolismo , Receptores de Somatostatina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Femenino , Humanos , Radioisótopos de Indio , Masculino , Melanoma/diagnóstico por imagen , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico por imagen , Octreótido/uso terapéutico , Cintigrafía , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Tamoxifen is considered an antiestrogen against breast cancer, yet it has known estrogenic side effects. We hypothesized that long-term administration of tamoxifen may significantly increase circulating estrogen levels in women with breast cancer. METHODS: Serum dehydroepiandrosterone (DHEA), estrone (E1), and estradiol (E2) levels were prospectively measured in 47 breast cancer patients before and during tamoxifen therapy for 2 years. Differences in baseline and peak hormone levels during treatment were compared, and significance was determined by paired Student's t test. RESULTS: Mean DHEA levels increased by 133% from 61 mg/L to 142 mg/L (P <0.001) and mean E2 levels increased by 239% from 28 pg/mL to 95 pg/mL (P <0.05). Mean E1 levels increased by 264% from 42 pg/mL to 153 pg/mL (P = 0.06). CONCLUSIONS: Long-term tamoxifen therapy can be associated with increased serum levels of DHEA, E1, and E2. Elevated serum estrogens may explain tamoxifen's estrogenic effects and may represent a mechanism for the development of drug resistance.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Estrógenos/sangre , Tamoxifeno/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/sangre , Deshidroepiandrosterona/sangre , Estradiol/sangre , Estrona/sangre , Femenino , Humanos , Menopausia/sangre , Persona de Mediana Edad , Estudios Prospectivos , Tamoxifeno/sangreRESUMEN
On the basis that melanomas are of neural crest origin and might contain somatostatin receptors, the authors utilized 111In Pentetreotide (OctreoScan) to image 16 melanoma patients with known sites of disease. Twelve of 16 patients were positive with 38 percent imaging all sites. No lesion less than 1.5 cm imaged nor did one ocular and one amelanotic melanoma. Of the five described somatostatin receptors, OctreoScan binds only 2 and 5 suggesting that not all melanomas contain those receptors. It is concluded that melanomas contain somatostatin receptors and that this property might be used for imaging, tumor suppression with Octreotide, and/or as a target for Octreotide labelled with therapeutic agents such as immune complexes, chemotherapeutic agents or high energy radioisotopes.