Neoadjuvant sipuleucel-T induces both Th1 activation and immune regulation in localized prostate cancer.

Sipuleucel-T is the only FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. The mechanism by which this treatment improves survival is not fully understood. We have previously shown that this treatment can induce the recruitment of CD4 and CD8 T cells to the tumor microenvironment. In this study, we examined the functional state of these T cells through gene expression profiling. We found that the magnitude of T cell signatures correlated with the frequency of T cells as measured by immunohistochemistry. Sipuleucel-T treatment was associated with increased expression of Th1-associated genes, but not Th2-, Th17 - or Treg-associated genes. Post-treatment tumor tissues with high CD8+T cell infiltration was associated with high levels of CXCL10 expression. On in situ hybridization, CXCL10+ cells colocalized with CD8+T cells in post-treatment prostatectomy tumor tissue. Neoadjuvant sipuleucel-T was also associated with upregulation of immune inhibitory checkpoints, including CTLA4 and TIGIT, and downregulation of the immune activation marker, dipeptidylpeptidase, DPP4. Treatment-associated declines in serum PSA were correlated with induction of Th1 response. In contrast, rises in serum PSA while on treatment were associated with the induction of multiple immune checkpoints, including CTLA4, CEACAM6 and TIGIT. This could represent adaptive immune resistance mechanisms induced by treatment. Taken together, neoadjuvant sipuleucel-T can induce both a Th1 response and negative immune regulation in the prostate cancer microenvironment

Demonstrating anyonic fractional statistics with a six-qubit quantum simulator

Anyons are exotic quasiparticles living in two dimensions that do not fit into the usual categories of fermions and bosons, but obey a new form of fractional statistics. Following a recent proposal [Phys. Rev. Lett. 98, 150404 (2007)], we present an experimental demonstration of the fractional statistics of anyons in the Kitaev spin lattice model using a photonic quantum simulator. We dynamically create the ground state and excited states (which are six-qubit graph states) of the Kitaev model Hamiltonian, and implement the anyonic braiding and fusion operations by single-qubit rotations. A phase shift of $\pi$ related to the anyon braiding is observed, confirming the prediction of the fractional statistics of Abelian 1/2-anyons.Comment: revised version 3, revTex, 4.3 pages, 4 figures, notes and reference adde

Possible JPC=0+−J^{PC} = 0^{+-} Exotic State

We study the possible exotic states with $J^{PC} = 0^{+-}$ using the tetraquark interpolating currents with the QCD sum rule approach. The extracted masses are around 4.85 GeV for the charmonium-like states and 11.25 GeV for the bottomomium-like states. There is no working region for the light tetraquark currents, which implies the light $0^{+-}$ state may not exist below 2 GeV.Comment: 13 pages, 11 figures, 2 table

A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer.

Lessons learnedThe combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored.BackgroundAndrogen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer. Preclinical data have shown that the two pathways compensate for each other when one is inhibited, and combined inhibition of AR and PI3K signaling may be a viable strategy to prevent or overcome castration resistance.MethodsThis phase I study evaluated the safety and tolerability of abiraterone acetate and prednisone combined with BEZ235, a dual PI3K and mTORC1/2 inhibitor, in men with progressive metastatic castration resistant prostate cancer (mCRPC) who have not received prior chemotherapy.ResultsSix patients (n = 6) were treated at the starting dose level of abiraterone acetate 1,000 mg with prednisone 5 mg twice daily and BEZ235 200 mg twice daily in a 3 + 3 dose escalation design. The study was terminated early because three of the six patients (50%) experienced dose-limiting toxicities: grade 3 mucositis, grade 3 hypotension, and grade 4 dyspnea and pneumonitis. All six patients had previously progressed on abiraterone/prednisone. The median treatment duration was 27 days (range: 3-130 days). No prostate-specific antigen (PSA) decline or objective response were observed.ConclusionThe combination of standard-dose abiraterone/prednisone with BEZ235 200 mg twice daily was poorly tolerated in patients with mCRPC. The on-target and off-target effects of dual PI3K and mTORC inhibition likely contributed to the unacceptable toxicity profile. The Oncologist 2017;22:503-e43

Право територіальної громади села щодо розпорядження землею: юридична природа та порядок здійснення

В статье исследуются вопросы правовой природы и механизм реализации территориальной общиной села права коммунальной собственности на землю, соотношения прав территориальной общины села и представительского органа местного самоуправления - сельского совета, относительно осуществления прав на распоряжение землей. Анализируется правосубъектность территориальной общины села относительно распоряжения землей коммунальной собственности. Ключевые слова: коммунальная собственность на землю, право территориальной общины села на землю, распоряжение землями в пределах населенных пунктов, разграничение земель, прекращения права коммунальной собственности на землю.In the article are explored the questions of legal nature and mechanism of realization territorial society communal ownership rights on land, correlations of rights for territorial society of village and representative organ of local self-government - village soviet, in relation to realization of rights to disposing of land. Rights of territorial society is analysed sat down in relation to disposing of land of community property. Key words: community property on the land, right of village territorial society on the land, disposing of land in settlements, differentiating of land, stopping right of community property on the land