The lack of effective therapies for advanced prostate cancer mandates continued development of alternative treatment strategies. Insights into the regulation of immune responses and the malignant process have facilitated the emergence of new immune-based strategies, currently under investigation in clinical trials. Like other forms of targeted therapy, cancer vaccines hold the promise of achieving cancer control without inducing overt toxicity. Many prostate cancer vaccines at different phases of development have been tested in clinical trials. Vaccination strategies under consideration include: immunization with defined antigenic preparations such as synthetic peptides, proteins or plasmid DNA; antigen-loaded dendritic cells; manipulated tumor cells; or with viral vectors engineered to express immunogenic genes. Although the underlying mechanisms of immunization may vary, all strategies share the common goal of eliciting immune responses against prostate tumor-associated antigens or of enhancing an otherwise weak antitumor response in the cancer patient. Unlocking the therapeutic potential of cancer vaccines will require a thorough understanding of cellular and molecular mechanisms that modulate the immune response. In this review, we provide an overview of vaccine-based strategies for prostate cancer therapy, discuss their mechanisms of action, and provide relevant clinical trial data. 相似文献
Background: Hypotension due to vasodilation during subarachnoid block (SAB) for elective cesarean delivery may be harmful. Heart rate variability (HRV), reflecting autonomic control, may identify patients at risk of hypotension.
Methods: Retrospectively, HRV was analyzed in 41 patients who were classified into one of three groups depending on the decrease in systolic blood pressure (SBP): mild (SBP > 100 mmHg), moderate (100 > SBP > 80 mmHg), or severe (SBP < 80 mmHg). Prospectively, HRV and hemodynamic data of 19 patients were studied. Relative low frequency (LF), relative high frequency (HF), and LF/HF ratio were analyzed.
Results: Retrospective analysis of HRV showed a significantly higher sympathetic and lower parasympathetic drive in the groups with moderate and severe compared with mild hypotension before SAB (median, 25th/75th percentiles): LF/HF: mild: 1.2 (0.9/1.8), moderate: 2.8 (1.8/4.6), P < 0.05 versus mild; severe: 2.7 (2.0/3.5), P < 0.05 versus mild. Results were confirmed by findings of LF and HF. Prospectively, patients were grouped according to LF/HF before SAB: low-LF/HF: 1.5 (1.1/2.0) versus high-LF/HF: 4.0 (2.8/4.7), P < 0.05; low-LF: 58 +/- 9% versus high-LF: 75 +/- 10%, P < 0.05; low-HF: 41 +/- 10% versus high-HF: 25 +/- 10%, P < 0.05. High-risk patients had a significantly lower SBP after SAB (76 +/- 21 vs. 111 +/- 12 mmHg; P < 0.05). 相似文献
Background Hemorrhage from pancreatic-enteric anastomosis after pancreaticoduodenectomy (PD) is a critical condition due to its difficult
accessibility and delicate condition, and therefore remains a major challenge for the surgeon in charge.
Objective This study analyzed presentation and management of pancreatogastrostomy hemorrhage (PGH) after PD to determine the respective
roles of endoscopy and surgery.
Patients and methods Patients who underwent PD with pancreatogastrostomy between 1989 and January 2008 were identified from a pancreatic resection
database and analyzed with regards to PGH, treatment strategy and outcome, and incidence of postoperative complications.
Results Out of 265 consecutive patients with PD, 10 patients (3.7%) experienced an episode of PGH, detected on average on postoperative
day 5. No patient with PGH died during hospital stay as opposed to a mortality rate of 2.7% in patients without PGH. Morbidity
rates were 50% versus 48% and length of hospital stay was 23 versus 21 days for patients with and without PGH, respectively,
with no statistical differences between the groups. Endoscopic approach to control PGH was successful in nine patients. Pancreatogastrostomies
were not compromised regarding procedure or air insufflations and no concomitant development of pancreatic fistula was observed.
Open surgery was inevitable in one patient with recurrent PGH in order to achieve hemostasis, but resulted in pancreatic fistula
and protracted hospital stay.
Conclusions The present study demonstrates a feasible endoscopic approach for the management of PGH with high success rate and no concomitant
procedure-related morbidity.
Medical illustrations: Lothar Knorn, Bonn. 相似文献
The purpose of this study was to analyse the outcome and its influencing factors in patients whose therapy was converted from calcineurin inhibitors (CNI) to sirolimus (SRL) due to chronic allograft nephropathy (CAN).
Materials and methods
Therapies of 78 patients (44 men) with CAN from three European transplant centres were converted from CNI therapy to SRL and followed 24 months. Slopes for creatinine clearance before and after conversion were calculated. Influencing factors were analysed by a multivariance analysis.
Results
The slope of the creatinine clearance improved significantly (?0.90 vs. ?0.34 ml min?1 month?1; p?<?0.01). In patients whose therapy was converted from cyclosporine A (CyA) to SRL, the slope improved significantly, whereas conversion from Tacrolimus (Tac) to SRL did not affect the slope. The benefit was more pronounced in (1) patients with low or moderate baseline creatinine clearance, (2) patients receiving SRL after conversion without additional mycophenolate mofetil and (3) patients with low or moderate proteinuria.
Conclusion
Conversion from CyA to SRL but not from Tac to CRL is associated with a reduced loss of renal allograft function in patients with CAN. 相似文献
The aim of this study was to test the validity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (QLQ‐C30) and Head and Neck Module (QLQ‐H&N35) for patients who have undergone surgery due to laryngeal cancer.
Methods.
A total of 323 patients from 6 different centers in Germany who had been operated on completed the QLQ‐C30 and the QLQ‐H&N35 in addition to being surveyed in a personal interview.
Results.
Multitrait scaling analysis confirmed the proposed scale structure of both questionnaires. Cronbach's alpha of the QLQ‐C30 scales ranged from 0.64 (Cognitive Functioning) to 0.94 (Global Health Status); the alpha of the QLQ‐H&N35 ranged from 0.55 (Speech) to 0.90 (Sexuality). Known‐groups comparisons showed multiple differences in sociodemographic and clinical variables.
Purpose: To investigate the possible relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin (OPN) levels measured in mouse serum.Material and methods: Experiments were performed in CDF1 mice that were either non-tumour bearing or with different sized tumours implanted in the right rear foot. Osteopontin levels in extracted mouse blood serum and tissue from the transplanted tumours were measured using an ELISA assay. The tumour oxygenation status was estimated using the Eppendorf Histograph and the fraction of oxygen partial pressure (pO2) values ≤5 mm Hg (HF5) was calculated. Necrosis was measured in haematoxylin and eosin-stained sections. Tumour hypoxia was increased by placing animals in a low-oxygen (10%) environment. Single radiation doses (240 kV x-rays) were given locally to tumours under ambient or clamped conditions and response assessed using a tumour control assay.Results: Serum OPN levels increased linearly with increasing tumour volume and this increase correlated with tumour OPN. HF5 and necrosis also increased with increasing tumour volume, but this increase was non-linear. Converting the HF5 results into equivalent tumour volume gave results that were directly correlated to OPN serum levels. Placing mice in a 10% oxygen environment for 12 hours significantly increased HF5. However, serum OPN only increased if reoxygenation occurred before measurement. Radiobiological hypoxic fraction in this tumour model did not change with increasing tumour size, but the total number of hypoxic cells did increase.Conclusions: These findings suggest that serum OPN measurement may predict the proportion of hypoxic cells in this tumour model, although increased serum OPN levels simply resulting from an increased tumour burden can not be ruled out. 相似文献
Open surgical reconstruction of the lateral ulnar collateral ligament is the standard treatment for symptomatic posterolateral rotatory instability of the elbow. It involves dissection and retraction of the lateral elbow muscles, which have been shown to be secondary stabilizers of the lateral elbow. We introduce a new muscle-protecting technique for single-strand lateral ulnar collateral ligament reconstruction and report on the isometry and primary stability when compared with a conventional muscle-splitting procedure. It was hypothesized that percutaneous lateral ulnar collateral ligament reconstruction provided isometry over the range of motion and that stability was comparable with a conventional open procedure.
Methods
In sixteen human cadaver arms, the intact and the lateral collateral ligament complex-deficient situation was tested. Open lateral ulnar collateral ligament reconstruction was performed using a single-strand palmaris graft with humeral and ulnar tenodesis screw fixation. Posterolateral rotational stability was compared with a new reconstruction method, which percutaneously places a single-strand palmaris graft with humeral and ulnar tenodesis screw fixation.
Results
Both open and percutaneous lateral ulnar collateral ligament reconstruction provided isometry over the range of motion and restored posterolateral stability to that of the intact situation. No significant differences between open and percutaneous reconstruction were found.
Conclusions
Percutaneous lateral ulnar collateral ligament reconstruction aims to preserve the lateral elbow muscles and to minimize soft tissue dissection. It has been shown that in an in vitro setup, this new procedure provides isometry over the range of motion and sufficiently restores posterolateral rotatory stability. 相似文献