Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients.

BackgroundKetoconazole is a well-known CYP17-targeted systemic treatment for castration-resistant prostate cancer (CRPC). However, most of the published data has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy setting has not been as widely described. Chemotherapy-naïve patients treated with attenuated doses of ketoconazole (200-300 mg three times daily) had PSA response rate (>50% decline) of 21-62%. We hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerability in the CRPC post-chemotherapy state.MethodsMen with CRPC and performance status 0-3, adequate organ function and who had received prior docetaxel were treated with low-dose ketoconazole (200 mg orally three times daily) and hydrocortisone (20 mg PO qAM and 10 mg PO qPM) until disease progression. Primary endpoint was PSA response rate (>50% reduction from baseline) where a rate of 25% was to be considered promising for further study (versus a null rate of <5%); 25 patients were required. Secondary endpoints included PSA response >30% from baseline, progression-free survival (PFS), duration of stable disease and evaluation of adverse events (AEs).ResultsThirty patients were accrued with median age of 72 years (range 55-86) and median pre-treatment PSA of 73 ng ml(-1) (range 7-11,420). Twenty-nine patients were evaluable for response and toxicity. PSA response (>50% reduction) was seen in 48% of patients; PSA response (>30% reduction) was seen in 59%. Median PFS was 138 days; median duration of stable disease was 123 days. Twelve patients experienced grade 3 or 4 AEs. Of the 17 grade 3 AEs, only 3 were attributed to treatment. None of the two grade 4 AEs were considered related to treatment.ConclusionsIn docetaxel pre-treated CRPC patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. A prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy

Desalination effluents and the establishment of the non-indigenous skeleton shrimp Paracaprella pusilla Mayer, 1890 in the south-eastern Mediterranean

A decade long monitoring programme has revealed a flourishing population of the non-indigenous skeleton shrimp Paracaprella pusilla in the vicinity of outfalls of desalination plants off the Mediterranean coast of Israel. The first specimens were collected in 2010, thus predating all previously published records of this species in the Mediterranean Sea. A decade-long disturbance regime related to the construction and operation of the plants may have had a critical role in driving the population growth

p38α (MAPK14) critically regulates the immunological response and the production of specific cytokines and chemokines in astrocytes.

In CNS lesions, "reactive astrocytes" form a prominent cellular response. However, the nature of this astrocyte immune activity is not well understood. In order to study astrocytic immune responses to inflammation and injury, we generated mice with conditional deletion of p38α (MAPK14) in GFAP+ astrocytes. We studied the role of p38α signaling in astrocyte immune activation both in vitro and in vivo, and simultaneously examined the effects of astrocyte activation in CNS inflammation. Our results showed that specific subsets of cytokines (TNFα, IL-6) and chemokines (CCL2, CCL4, CXCL1, CXCL2, CXCL10) are critically regulated by p38α signaling in astrocytes. In an in vivo CNS inflammation model of intracerebral injection of LPS, we observed markedly attenuated astrogliosis in conditional GFAPcre p38α(-/-) mice. However, GFAPcre p38α(-/-) mice showed marked upregulation of CCL2, CCL3, CCL4, CXCL2, CXCL10, TNFα, and IL-1β compared to p38αfl/fl cohorts, suggesting that in vivo responses to LPS after GFAPcre p38α deletion are complex and involve interactions between multiple cell types. This finding was supported by a prominent increase in macrophage/microglia and neutrophil recruitment in GFAPcre p38α(-/-) mice compared to p38αfl/fl controls. Together, these studies provide important insights into the critical role of p38α signaling in astrocyte immune activation

Magnetic field controlled reversal of ferroelectric polarization in conical spin ordered multiferroics : Monte Carlo simulation

Author name used in this publication: 姚晓燕Author name used in this publication: 羅永祥Author name used in this publication: 刘俊明2009-2010 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Monte Carlo simulation on ferroelectric response to magnetic field in an elastic lsing spin chain

Author name used in this publication: 姚晓燕Author name used in this publication: Veng Cheong Lo, 羅永祥Author name used in this publication: 刘俊明2009-2010 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Magnetoelectric coupling induced by exchange striction in frustrated Ising spin chain : Monte Carlo simulation

Author name used in this publication: Veng Cheong Lo2008-2009 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

The influence of magnetic anisotropy on magnetoelectric behavior in conical spin ordered multiferroic state

2009-2010 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Research fund for the control of infectious diseases: commissioned studies

Research Fund for the Control of Infectious Diseases: Research Dissemination Reportspublished_or_final_versio

The clinicopathological features and importance of p53, Rb, and mdm2 expression in phaeochromocytomas and paragangliomas

Aims - Phaeochromocytomas and paragangliomas are uncommon. The aims of this study were to analyse the characteristics and the possible roles of p53, Rb, and mdm2 alterations in these tumours. Methods - The clinicopathological features of 65 patients (31 men, 34 women) with phaeochromocytomas or paragangliomas were analysed. The tumours were studied for the expression of p53, Rb, and mdm2 by immunohistochemical methods. Results - Thirty nine of the patients had phaeochromocytomas and 26 had paragangliomas. Bilateral tumours were noted in eight of the patients and malignant tumours were seen in 13. Paragangliomas were often small, non-functional, and presented incidentally, whereas phaeochromocytomas were usually large, functional, and symptomatic, p53 overexpression, loss of Rb expression, and mdm2 overexpression were seen in four, 43, and 37 of the patients, respectively. Three of the four patients with p53 overexpression had bilateral tumours. Loss of Rb expression was often found in phaeochromocytomas, whereas mdm2 overexpression was more frequently seen in paragangliomas. The 10 year survival rate of patients with malignant tumours was 45%. Two patients died of tumour metastases more than 10 years after resection of the primary tumours. Conclusions - Phaeochromocytomas and paragangliomas had distinctive clinical features and genetic alterations. The prognosis of patients with these tumours was related to the malignant potential, p53 overexpression, more common in bilateral phaeochromocytomas and paragangliomas, could be a marker for this tumour subgroup.published_or_final_versio

Draft genome sequence of an actinobacterium, Brachybacterium muris strain UCD-AY4

© 2013 Lo et al. Here we present the draft genome of an actinobacterium, Brachybacterium muris UCD-AY4. The assembly contains 3,257,338 bp and has a GC content of 70%. This strain was isolated from a residential bath towel and has a 16S rRNA gene 99.7% identical to that of the original B. muris strain, C3H-21