International study into the use of intermittent hormone therapy in the treatment of carcinoma of the prostate : A meta-analysis of 1446 patients

OBJECTIVE: To review pooled phase II data to identify features of different regimens of intermittent hormone therapy (IHT), developed to reduce the morbidity of treating metastatic prostate cancer, and which carries a theoretical advantage of delaying the onset of androgen-independent prostate cancer, (AIPC) that are associated with success, highlighting features which require exploration with prospective trials to establish the best strategies for using this treatment. METHODS: Individual data were collated on 1446 patients with adequate information, from 10 phase II studies with >50 cases, identified through Pubmed. RESULTS: Univariate and multivariate Cox proportional hazard models were developed to predict treatment success with a high degree of statistical success. The prostate-specific antigen (PSA) nadir, the PSA threshold to restart treatment, and medication type and duration, were important predictors of outcome. CONCLUSIONS: The duration of biochemical remission after a period of HT is a durable early indicator of how rapidly AIPC and death will occur, and will make a useful endpoint in future trials to investigate the best ways to use IHT based on the important treatment cycling variables described above. Patients spent a mean of 39% of the time off treatment. The initial PSA level and PSA nadir allow the identification of patients with prostate cancer in whom it might be possible to avoid radical therapy.Peer reviewe

The Lambda-Lambda Interaction and ^{6}_{Lambda Lambda}He

An OBE potential model for the ^{1}S_0 S = -2 interaction is analyzed with emphasis on the role of coupling between the Lambda Lambda, N Xi, and Sigma Sigma channels. Singlet scalar exchange, an approximation to two-pion exchange, is significant in all channels; surprisingly, the one-pion exchange component is almost negligible. The size of the channel coupling as a function of the overall strength of the OBE model potential is examined. Implications of the analysis for the binding energy of ^{6}_{Lambda Lambda}He are considered; the new experimental datum may suggest a consistency between the extracted Lambda Lambda matrix element and the relation implied by SU(3) among OBE baryon-baryon interactions. \\Comment: 4 pages brief report to Physical Review

GLI1 confers profound phenotypic changes upon LNCaP prostate cancer cells that include the acquisition of a hormone independent state

The GLI (GLI1/GLI2) transcription factors have been implicated in the development and progression of prostate cancer although our understanding of how they actually contribute to the biology of these common tumours is limited. We observed that GLI reporter activity was higher in normal (PNT-2) and tumourigenic (DU145 and PC-3) androgen-independent cells compared to androgen-dependent LNCaP prostate cancer cells and, accordingly, GLI mRNA levels were also elevated. Ectopic expression of GLI1 or the constitutively active NGLI2 mutant induced a distinct cobblestone-like morphology in LNCaP cells that, regarding the former, correlated with increased GLI2 as well as expression of the basal/stem-like markers CD44, beta1-integrin, Np63 and BMI1, and decreased expression of the luminal marker AR (androgen receptor). LNCaP-GLI1 cells were viable in the presence of the AR inhibitor bicalutamide and gene expression profiling revealed that the transcriptome of LNCaP-GLI1 cells was significantly closer to DU145 and PC-3 cells than to control LNCaP-pBP (empty vector) cells, as well as identifying LCN2/NGAL as a highly induced transcript which is associated with hormone independence in breast and prostate cancer. Functionally, LNCaP-GLI1 cells displayed greater clonal growth and were more invasive than control cells but they did not form colonies in soft agar or prostaspheres in suspension suggesting that they do not possess inherent stem cell properties. Moreover, targeted suppression of GLI1 or GLI2 with siRNA did not reverse the transformed phenotype of LNCaP-GLI1 cells nor did double GLI1/GLI2 knockdowns activate AR expression in DU145 or PC-3 cells. As such, early targeting of the GLI oncoproteins may hinder progression to a hormone independent state but a more detailed understanding of the mechanisms that maintain this phenotype is required to determine if their inhibition will enhance the efficacy of anti-hormonal therapy through the induction of a luminal phenotype and increased dependency upon AR function

The H-Dibaryon and the Hard Core

The H dibaryon, a single, triply magic bag containing two up, two down and two strange quarks, has long been sought after in a variety of experiments. Its creation has been attempted in $K^-$, proton and most recently in relativistic heavy ion induced reactions. We concentrate on the latter, but our conclusions are more generally applicable. The two baryons coalescing to form the single dibaryon, likely $\Lambda \Lambda$ in the case of heavy ions, must penetrate the short range repulsive barrier which is expected to exist between them. We find that this barrier can profoundly affect the probability of producing the H state, should it actually exist.Comment: 9 pages including 4 figure

Hyperon-hyperon interactions and properties of neutron matter

We present results from Brueckner-Hartree-Fock calculatons for beta stable neutron star matter with nucleonic and hyperonic degress degrees of freedom, employing the most recent parametrizations of the baryon-baryon interaction of the Nijmegen group. It is found that the only strange baryons emergin in beta stable matter up to total barionic densities of 1.2 fm^-3 are $\Sigma^-$ and $\Lambda$. The corresponding equations of state are then used to compute properties of neutron stars such as masses and radii.Comment: 27 pages, LateX, includes 8 PostScript figures, (submitted to PRC

Brueckner Rearrangement Effects in Λ5^5_\LambdaHe and ΛΛ6^6_{\Lambda\Lambda}He

Rearrangement effects in light hypernuclei are investigated in the framework of the Brueckner theory. We can estimate without detailed numerical calculations that the energy of the $\alpha$-core is reduced by more than 2.5 MeV when the $\Lambda$ adheres to $^4$He to form $^5_\Lambda$He. Similar assessment of rearrangement contributions is essential to deduce the strength of $\Lambda\Lambda$ interaction from experimentally observed $\Delta B_{\Lambda\Lambda}$. The recently observed experimental value of $\sim$ 1 MeV for the $\Delta B_{\Lambda\Lambda}$ of \hll suggests that the matrix element of $$ in \hll is around -2 MeV.Comment: 7 pages, to appear in Phys. Rev.

Nuclei, Superheavy Nuclei and Hypermatter in a chiral SU(3)-Modell

A model based on chiral SU(3)-symmetry in nonlinear realisation is used for the investigation of nuclei, superheavy nuclei, hypernuclei and multistrange nuclear objects (so called MEMOs). The model works very well in the case of nuclei and hypernuclei with one Lambda-particle and rules out MEMOs. Basic observables which are known for nuclei and hypernuclei are reproduced satisfactorily. The model predicts Z=120 and N=172, 184 and 198 as the next shell closures in the region of superheavy nuclei. The calculations have been performed in self-consistent relativistic mean field approximation assuming spherical symmetry. The parameters were adapted to known nuclei.Comment: 19 pages, 11 figure

Dihyperon in Chiral Colour Dielectric Model

The mass of dihyperon with spin, parity $J^{\pi}=0^{+}$ and isospin $I = 0$ is calculated in the framework of Chiral colour dielectric model. The wave function of the dihyperon is expressed as a product of two colour-singlet baryon clusters. Thus the quark wave functions within the cluster are antisymmetric. Appropriate operators are then used to antisymmetrize inter-cluster quark wave functions. The radial part of the quark wavefunctions are obtained by solving the the quark and dielectric field equations of motion obtained in the Colour dielectric model. The mass of the dihyperon is computed by including the colour magnetic energy as well as the energy due to meson interaction. The recoil correction to the dihyperon mass is incorporated by Peierls-Yoccoz technique. We find that the mass of the dihyperon is smaller than the $\Lambda-\Lambda$ threshold by over 100 MeV. The implications of our results on the present day relativistic heavy ion experiments is discussed.Comment: LaTeX, 13 page

Measuring vertebrate telomeres: applications and limitations

Telomeres are short tandem repeated sequences of DNA found at the ends of eukaryotic chromosomes that function in stabilizing chromosomal end integrity. In vivo studies of somatic tissue of mammals and birds have shown a correlation between telomere length and organismal age within species, and correlations between telomere shortening rate and lifespan among species. This result presents the tantalizing possibility that telomere length could be used to provide much needed information on age, ageing and survival in natural populations where longitudinal studies are lacking. Here we review methods available for measuring telomere length and discuss the potential uses and limitations of telomeres as age and ageing estimators in the fields of vertebrate ecology, evolution and conservation