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Objective: To examine the antitumor activity of zoledronic acid (ZA) combined with androgen deprivation therapy (ADT) for men with treatment-naive prostate cancer and bone metastasis. Methods: We enrolled 227 men with treatment-naive prostate cancer and bone metastasis. Participants were randomly assigned (1:1 ratio) to receive combined androgen blockade alone (CAB group) or ZA with combined androgen blockade (CZ group). Time to treatment failure (TTTF), time to the first skeletal-related event (TTfSRE), and overall survival (OS) rates were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazards model. Median follow-up duration was 41.5 months. Results: Median TTTFs were 12.4 and 9.7 months for the CZ and CAB groups, respectively (HR 0.75; 95 % CI 0.57-1.00; p = 0.051). For men with baseline prostate-specific antigen levels <200 ng/mL, median TTTFs were 23.7 and 9.8 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.35-0.93; p = 0.023). Median TTfSREs were 64.7 and 45.9 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.38-0.88; p = 0.009). OS was similar between the groups. Conclusions: This study failed to demonstrate that combined use of ZA and ADT significantly prolonged TTTF in men with treatment-naive prostate cancer and bone metastasis. However, it generates a new hypothesis that the combined therapy could delay the development of castration resistance in a subgroup of patients with low baseline prostate-specific antigen values <200 ng/mL. The treatment also significantly prolonged TTfSRE but did not affect OS. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome with major components of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. MEN2B is the most aggressive and rarest of the MEN2 variants. Pheochromocytoma in MEN2 is virtually always located in the adrenal medulla, but MEN2-associated extra-adrenal pheochromocytomas (paraganglioma) are rare. A 59-year-old man who has been diagnosed with MEN2B consulted our hospital for surgical treatment of a 10-mm left adrenal mass and a 30-mm retroperitoneal mass. He had paroxysmal elevations in blood pressure and in urinary metanephrine and vanillylmandelic acid values. Laparoscopic excision of the left adrenal gland and retroperitoneal mass was performed. We experienced an extremely rare case of composite paraganglioma-ganglioneuroma concomitant with adrenal metastasis of medullary thyroid carcinoma in a patient with MEN2B. [ABSTRACT FROM AUTHOR]

Laparoendoscopic single-site surgery (LESS) is a step toward the development of minimally invasive surgery. It is initially difficult for surgeons with limited experience to perform the surgery. We describe two cases of left adrenalectomy with a LESS combined with the addition of an accessory port. After a 2.5-cm skin incision was made at the level of the paraumbilicus to insert the primary 12-mm trocar for the laparoscope, a 5-mm nonbladed trocar was placed through the skin incision side-by-side with the primary trocar. A second 3-mm nonbladed trocar was then placed along the anterior axillary line; a multichannel trocar was not used as a single port. Both adrenalectomies were completed successfully. In patients with a minor adrenal tumor, a combined technique using LESS and an additional port is easier than LESS alone and may, therefore, be a bridge between the conventional laparoscopic approach and LESS. [ABSTRACT FROM AUTHOR]

2-Methoxyestradiol (2-ME) has potent antiproliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgen-dependent and independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase--mediated dUTP nick-end labeling assay and measuring microvessel density (MVD) in excised tumors. Animals harboring hormone-dependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, and 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis and a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo and combination therapy resulted in a significant increase in efficacy compared to no treatment controls and trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer. [ABSTRACT FROM AUTHOR]

Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients.Background.The predictor for the result of calcitriol therapy would be useful in the clinical practice of secondary hyperparathyroidism. Fibroblast growth factor-23 (FGF-23) is a newly found circulating phosphaturic factor. Its circulating level is elevated in uremia.Methods.Dialysis patients with plasma intact parathyroid hormone (iPTH) levels greater than 300 pg/mL were included in the study. Calcitriol was intravenously injected three times a week. The patients whose plasma iPTH levels dropped below 300 pg/mL within 24 weeks were defined as those who had been successfully treated. A sandwich enzyme-linked immunosorbent assay (ELISA) system that detects human FGF-23 was applied.Results.Sixty-two patients were analyzed. The pretreatment FGF-23 levels were related to the iPTH levels, calcium× phosphate product levels, and history of active vitamin D therapy. The pretreatment FGF-23, iPTH, and calcium levels were lower in the patients who would be successfully treated with calcitriol. A logistic regression study revealed that the pretreatment iPTH and FGF-23 levels significantly affected the therapy results. Analyses using a receiver-operated curve revealed that FGF-23 was the best screening test for identifying patients with future refractory response to calcitriol therapy. The treatment would be successful in 88.2% of those with FGF-23≤9860 ng/L and iPTH≤591 pg/mL, while it would be successful in only 4.2% of those with FGF-23>9860 ng/L and iPTH>591 pg/mL.Conclusion.Pretreatment serum FGF-23 levels were a good indicator in predicting the response to calcitriol therapy. The measurement of serum FGF-23 levels, especially in combination with iPTH levels, is a promising laboratory examination for the clinical practice of secondary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

AbstractBackground: Prediction of the extent of calcium supplement will facilitate safe and efficient management of hypocalcemia in the early postoperative stage of total parathyroidectomy with autotransplantation (PTXa) in patients with renal osteodystrophy. Methods: The correlation between the extent of calcium deficiency, estimated by the amount of calcium supplement over 48 h after PTXa and using various parameters such as carboxy terminal parathyroid hormone (c-PTH), intact PTH (i-PTH), alkaline phosphatase (ALP), serum calcium, serum phosphorus, duration of hemodialysis, total weight of resected parathyroid glands and degree of subperiosteal resorption of the middle phalanx was examined in 49 patients who underwent PTX with subcutaneous autotransplantation. Bone mineral density (BMD) was also determined before, 3 months and 1 year after PTXa with dual energy X-ray absorptiometry (DEXA) in 13 patients. Results: There was a positive correlation between pre-operative i-PTH level (r = 0.56, P < 0.0005) or ALP level (r = 0.50, P < 0.0005) and the amount of calcium supplement over 48 h after PTXa in these patients. Furthermore, the degree of subperiosteal resorption, determined by Jensen’s classification, was significantly correlated with the amount of calcium supplement after PTX (P < 0.05). Bone mineral density 3 months after (P < 0.0005) and 1 year after PTXa (P < 0.001) significantly increased compared with BMD before PTXa in all patients examined. Conclusion: These findings suggest that the pre-operative determination of i-PTH, ALP levels and degree of subperiosteal resorption allow the management of hypocalcemia safely and efficiently in renal osteodystrophy patients after PTXa. [ABSTRACT FROM AUTHOR]

Lipid organization has been at the center of research on lipid rafts. Dioleoylphosphatidylcholine (DOPC) is a typical unsaturated lipid. Very few studies have reported its thermodynamics in raft-like membranes. Herein, we have developed a highly efficient synthetic method for [C6- 2 H 2 ] oleic acid, and newly synthesized [C6- 2 H 2 ] DOPC. In raft-like oriented bilayers, [C6- 2 H 2 ] DOPC shows clear phase separation and characteristic phase behavior at various temperature. It has been successfully utilized for the comparison of membrane properties between sphingomyelin (SM) and dihydrosphingomyelin (DHSM) membranes. [ABSTRACT FROM AUTHOR]

Abstract: A series of peptide-based transition-state human neutrophil elastase (HNE) inhibitors with N-terminal acidic moieties were synthesized and their inhibitory activity against HNE was evaluated both in vitro and in vivo. Our results show that compounds containing cyclic amide bridged acidic moieties at the N-terminal have not only improved water solubility but also high in vivo potency. Among these compounds, AE-3763 showed remarkable efficacy in hamster models of elastase-induced lung hemorrhage and lipopolysaccharide (LPS)-induced lung injury as well as in a mouse model of LPS/galactosamine-induced acute multiple organ dysfunctions. The water solubility of AE-3763 (>1000mg/ml in H2O) was also far superior to that of any of the other compounds synthesized. Thus, it is believed that AE-3763 would be useful for treatment of HNE-associated respiratory disorders, such as acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and acute exacerbation of chronic obstructive pulmonary disease (COPD). [Copyright &y& Elsevier]