RESUMEN
Androgen deprivation therapy is the mainstay of treatment for prostate cancer. Given its frequent failure, new therapy that reduces prostate cancer progression would be a breakthrough in treating this disease. Bisphosphonates are well-established agents for treating skeletal-related events (SREs) in prostate cancer patients with bone metastases. Exposure to bisphosphonates may not only reduce the incidence of SREs, but also have anticancer effects by modulating a patient's immunity. The purpose of this study was to examine the effect of zoledronate (ZOL) on gamma delta T cells, serum prostate-specific antigen (PSA) levels, and velocities. The effect of ZOL, with and without IL-2, on gamma delta T cell activation was examined in vitro. Furthermore, the activated state and the number of gamma delta T cells and changes in serum PSA levels were examined for patients who received ZOL infusion for the prevention of SREs. We found that ZOL activated gamma delta T cells, and the number of gamma delta T cell was increased when IL-2 was administered with ZOL in vitro. Comparisons before and after the first ZOL infusion revealed that gamma delta T cells in peripheral blood were activated by ZOL. Moreover, after the first ZOL treatment, reduction in serum PSA was observed in 3 of 11 patients, and reduction in PSA velocity was observed in 5 of 10 patients. Our findings indicate that ZOL stimulates gamma delta T cells in vivo and in vitro. This study provides further insight into the ability of gamma delta T cells to induce an antitumor immune response.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Imidazoles/farmacología , Activación de Linfocitos/efectos de los fármacos , Neoplasias de la Próstata/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Linfocitos T/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunoterapia , Interleucina-2/farmacología , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/terapia , Linfocitos T/inmunología , Ácido ZoledrónicoRESUMEN
5-Fluorouracil (5-FU) and its prodrugs are used to treat various cancers. Response to 5-FU-based chemotherapy and expression of 5-FU-related enzymes differ among cancers. The objective of the present study was to investigate the relationship between the expression of 5-FU-related enzymes and clinicopathologic factors in bladder cancer. Formalin-fixed, paraffin-embedded sections of 44 bladder cancers and 27 normal bladders were included in this study. After laser capture microdissection, "Danenberg tumor profile," was performed for the measurement of 5-FU-related enzymes. There was no significant difference between dihydropyrimidine hydrogenase (DPD) mRNA expression in bladder cancer and in normal bladder. On the contrary, mRNA expressions of orotate phosphoribosyltransferase (OPRT), thymidylate synthase (TS), and thymidine phosphorylase (TP) in bladder cancer were higher than those in normal bladder. Compared with previously reported DPD mRNA expressions in other types of cancer, DPD mRNA expression in bladder cancer was relatively low. The 5-FU-related enzymatic condition of bladder cancer is favorable for 5-FU.
Asunto(s)
Dihidrouracilo Deshidrogenasa (NADP)/genética , Fluorouracilo/metabolismo , Regulación Enzimológica de la Expresión Génica/fisiología , Orotato Fosforribosiltransferasa/genética , Timidina Fosforilasa/genética , Timidilato Sintasa/genética , Neoplasias de la Vejiga Urinaria/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Western Blotting , Dihidrouracilo Deshidrogenasa (NADP)/metabolismo , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Orotato Fosforribosiltransferasa/metabolismo , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Timidina Fosforilasa/metabolismo , Timidilato Sintasa/metabolismo , Vejiga Urinaria/enzimología , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/enzimología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Sperm cryopreservation before chemotherapy in young males is recommended because of chemotherapy's gonadotoxic effects. However, many patients miss sperm banking, and consequently are often sterile. Two azoospermic patients presented to us after chemotherapy, and we obtained sperm from them by testicular sperm extraction (TESE). One patient was 32 years old and had been treated with six cycles of cisplatin, etoposide and bleomycin (BEP) chemotherapy and one cycle of high-dose chemotherapy for stage III non-seminoma. Histopathology of the testicular specimen showed germinal aplasia with focal islands of full spermatogenesis. Although two intracytoplasmic sperm injection (ICSI) cycles were performed, pregnancy was not achieved. The other patient was 33 years old who was treated with four cycles of BEP chemotherapy for stage II seminoma. Histopathology of the testicular specimen showed Sertoli-cell-only syndrome. Ongoing pregnancy was achieved after one ICSI cycle. TESE should be considered in patients with persistent azoospermia after chemotherapy if frozen sperm samples are not available.
Asunto(s)
Azoospermia/etiología , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Espermatozoides , Neoplasias Testiculares/tratamiento farmacológico , Recolección de Tejidos y Órganos , Adulto , Humanos , MasculinoRESUMEN
A giant cystic formation was found behind the prostate of a 69-year-old man who presented with urinary retention. Ultrasonography, computed tomography scans and magnetic resonance imaging revealed a large cystic intrapelvic mass and biopsy of the cyst wall diagnosed papillary cyst adenocarcinoma. Immunohistochemically, the tumor originated from the prostate.