Metastasiertes kastrationsresistentes Prostatakarzinom

Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient. Furthermore, predictive markers to facilitate the selection of patients for a specific therapy or sequence of therapies remain an unmet need. However, with the recently discovered androgen receptor splice variant V7, which mediates (cross)resistance to or between abiraterone and enzalutamide, the first such marker has been identified. It is critical to monitor the response to treatments at prespecified intervals in order to optimize treatment sequencing so that the patient does not miss a valuable therapeutic window to receive alternative treatment that may prolong his life along with good symptom control and preservation of quality of life.     

Cholesteryl ester transfer protein in human brain

Summary The evidence that apolipoproteins are found in the cerebrospinal fluid and low-density lipoprotein receptor is found in the brain suggests that the brain may have an active lipid transport system. In plasma, cholesteryl ester transfer protein mediates the exchange and net transfer of cholesteryl ester and triglycerides among lipoproteins. Cholesteryl ester transfer activity was measured in the cerebrospinal fluid and plasma of ten neurologically normal subjects. Cholesteryl ester transfer activity was readily detectable in cerebrospinal fluid (7.4±13% cholesteryl ester was transferred per 20 μl), and this activity was completely abolished with specific antibody against the plasma cholesteryl ester transfer protein. The concentration of cholesteryl ester transfer activity in the cerebrospinal fluid was about 12% of that found in plasma, whereas the concentration of albumin in cerebrospinal fluid was only about 0.6% of that in plasma, suggesting direct synthesis of cholesteryl ester transfer protein within the brain. Cholesteryl ester transfer activity was found in conditioned medium from human neuroblastoma and neuroglioma cells and sheep choroid plexus. The data suggest that cholesteryl ester transfer protein is synthesized and secreted in the brain. This protein could play an important role in the transport and redistribution of lipids within the central nervous system. Deceased January 1991     

Completeness and accuracy of data in spine registries: an independent audit-based study

European Spine Journal - Clinical registries are used for quality management and clinical research. Due to the importance and implications of both aims, completeness and high quality of data are of...     

醋酸环丙孕酮／炔雌醇复方片剂在人体的药代动力学

目的建立人血浆中醋酸环丙孕酮的HPLC—ESI—MS测定方法和丹酰氯衍生化血浆中炔雌醇的HPLC—APCI—MS测定方法,测定女性志愿者口服复方醋酸环丙孕酮片1片后的药代动力学参数,并对受试制剂和参比制剂的生物等效性进行评价。方法血浆样品中的炔雌醇以乙酸乙酯提取后,与丹酰氯发生衍生化反应,进行HPLC—APCI—MS分析,流动相为10mmol·L-1乙酸铵缓冲液（1％甲酸）-甲醇（3：97）。检测离子分别为m／z530．3（炔雌醇的丹酰氯衍生物）、m／z404．3（内标,对羟基联苯的丹酰氯衍生物1。结果在10．43～625．8Pg·ml-1范同内炔雌醇的丹酰氯衍生物与内标的丹酰氯衍生物峰面积比值与浓度呈良好的线性关系,最低定量限为10．43pg·ml-1结论本实验建立的分析方法灵敏、准确、简便,且统计学结果表明两种制剂生物等效。     

Degarelix as an Intermittent Androgen Deprivation Therapy for One or More Treatment Cycles in Patients with Prostate Cancer

Background

Guidelines for prostate cancer treatment suggest that intermittent androgen deprivation (IAD) can be considered for certain patients.

Objective

To evaluate the efficacy and safety of degarelix as IAD for one or more treatment cycle(s) in prostate cancer patients requiring androgen deprivation.

Design, setting, and participants

This open-label uncontrolled multicenter study included patients with prostate-specific antigen (PSA) >4 to 50 ng/ml or PSA doubling time <24 mo. Induction included 7-mo treatment. Off-treatment period started when PSA was ≤4 ng/ml and lasted up to 24 mo based on PSA and testosterone levels. Treatment was reinitiated when PSA was >4 ng/ml.

Intervention

Each induction period included a starting dose of degarelix 240 mg, and thereafter 80 mg once a month for 6 mo, followed by off-treatment periods.

Outcome measurements and statistical analysis

The primary end point was time to PSA >4 ng/ml. Secondary end points were subgroup analysis of the primary end point, time to testosterone >0.5 and >2.2 ng/ml, quality of life (QoL), and sexual function during the first off-treatment period.

Results and limitations

Of 213 patients in the first induction period, 191 entered the first off-treatment period, 35 patients entered the second induction, and 30 entered the second off-treatment period. Only two patients entered the third cycle. Median time to PSA >4 ng/ml and duration of first off-treatment period was 392 d each. Significant differences in time to PSA >4 ng/ml were observed between subgroups stratified by prognostic factors (previous curative treatment, cancer stage, PSA levels, and Gleason scores). Time to testosterone >0.5 and >2.2 ng/ml was 112 and 168 d, respectively. Change in QoL remained nonsignificant, and sexual function gradually improved during the off-treatment period. Adverse events were fewer during the off-treatment period and subsequent treatment cycles.

Conclusions

IAD with degarelix resulted in an improvement in sexual function commensurate with increased testosterone levels while PSA remained suppressed. The treatment for one treatment cycle or more was well tolerated.

Patient summary

Guidelines for prostate cancer treatment suggest that intermittent androgen deprivation (IAD) can be considered for certain patients. IAD with degarelix resulted in improved sexual function commensurate with increased testosterone levels while prostate-specific antigen remained suppressed. The treatment for one treatment cycle or more was well tolerated.

Trial registration

Clinicaltrials.gov identifier NCT00801242.     

Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.     

Lack of correlation between serum lipoproteins and biliary cholesterol saturation in patients with gallstones

It has been suggested that elevated serum lipoprotein cholesterol levels may be a determinant of biliary cholesterol saturation and cholesterol gallstone disease. The aim of this study was to correlate serum lipoprotein cholesterol and apolipoprotein levels with biliary cholesterol saturation in patients with gallstones who participated in the National Cooperative Gallstone Study. Baseline serum lipoprotein and biliary lipid levels were studied in 181 of these patients before they received treatment for dissolution of their gallstones. Neither low-or high-density lipoprotein cholesterol nor apolipoprotein levels correlated with biliary cholesterol saturation. This study, therefore, does not support the concept that serum lipoproteins are a determinant of biliary cholesterol saturation. It is possible, however, that a significant effect of lipoprotein levels is obscured by the greater effects of more important determinants of biliary cholesterol saturation.This project was funded by the National Institute of Arthritis, Metabolism and Digestive Diseases of the Department of Health and Human Services under contract N01-AM-3-2216 and N01-AM-0-2205. The contents of this publication do not necessarily reflect the views or policies of the department nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.