A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer.

Unlabelled: Although localized prostate cancer is relatively indolent, advanced prostate cancer manifests with aggressive and often lethal variants, including neuroendocrine prostate cancer (NEPC). To identify drivers of aggressive prostate cancer, we leveraged transposon mutagenesis in a mouse model based on prostate-specific loss-of-function of and . Compared with control mice, mice developed more aggressive prostate tumors, with increased incidence of metastasis.

Goos-Hänchen shift for coupled vibrational modes in a semiconductor structure.

We present a theoretical investigation of the Goös-Hanchen shift (GHS) experienced by acoustic and optical vibrational modes reflected and transmitted from the surfaces of a semiconductor thin film sandwiched between two semi-infinite media. Our study focuses on the impact of the incident angle on the GHS, considering the coupling between longitudinal and transverse modes. For acoustic vibrations, our findings reveal that the GHS can reach magnitudes up to seven times larger than the thickness of the thin film and up to 20 times larger than the incident wavelength.

In vivo genome-wide CRISPR screening identifies CITED2 as a driver of prostate cancer bone metastasis.

Most cancer deaths are due to metastatic dissemination to distant organs. Bone is the most frequently affected organ in metastatic prostate cancer and a major cause of prostate cancer deaths. Yet, our partial understanding of the molecular factors that drive bone metastasis has been a limiting factor for developing preventative and therapeutic strategies to improve patient survival and well-being.

Belowground insect herbivory induces systemic volatile emissions that strengthen neighbouring plant resistance aboveground.

Plants transmit ecologically relevant messages to neighbouring plants through chemical cues. For instance, insect herbivory triggers the production of herbivore-induced plant volatiles (HIPVs), which can enhance neighbouring plant defences. HIPVs are emitted from directly damaged plant tissues and from systemic, nondamaged tissues.

OncoLoop: A Network-Based Precision Cancer Medicine Framework.

Unlabelled: Prioritizing treatments for individual patients with cancer remains challenging, and performing coclinical studies using patient-derived models in real time is often unfeasible. To circumvent these challenges, we introduce OncoLoop, a precision medicine framework that predicts drug sensitivity in human tumors and their preexisting high-fidelity (cognate) model(s) by leveraging drug perturbation profiles. As a proof of concept, we applied OncoLoop to prostate cancer using genetically engineered mouse models (GEMM) that recapitulate a broad spectrum of disease states, including castration-resistant, metastatic, and neuroendocrine prostate cancer.

Tuning the decay of sound in a viscous metamaterial.

Using analytical results for viscous dissipation in phononic crystals, we calculate the decay coefficient of a sound wave propagating at low frequencies through a two-dimensional phononic crystal with a viscous fluid background. It is demonstrated that the effective acoustic viscosity of the phononic crystal may exceed by two to four orders of magnitude the natural hydrodynamic viscosity of the background fluid. Moreover, the decay coefficient exhibits dependence on the direction of propagation; that is, a homogenized phononic crystal behaves like an anisotropic viscous fluid.

A MYC and RAS co-activation signature in localized prostate cancer drives bone metastasis and castration resistance.

Understanding the intricacies of lethal prostate cancer poses specific challenges due to difficulties in accurate modeling of metastasis in vivo. Here we show that mice (for -) develop prostate cancer with a high penetrance of metastasis to bone, thereby enabling detection and tracking of bone metastasis in vivo and ex vivo. Transcriptomic and whole-exome analyses of bone metastasis from these mice revealed distinct molecular profiles conserved between human and mouse and specific patterns of subclonal branching from the primary tumor.

Longitudinal Immune Profiling Reveals Unique Myeloid and T-cell Phenotypes Associated with Spontaneous Immunoediting in a Prostate Tumor Model.

The theory of cancer immunoediting, which describes the dynamic interactions between tumors and host immune cells that shape the character of each compartment, is foundational for understanding cancer immunotherapy. Few models exist that facilitate in-depth study of each of the three canonical phases of immunoediting: elimination, equilibrium, and escape. Here, we utilized NPK-C1, a transplantable prostate tumor model that we found recapitulated the three phases of immunoediting spontaneously in immunocompetent animals.

NSD2 is a conserved driver of metastatic prostate cancer progression.

Deciphering cell-intrinsic mechanisms of metastasis progression in vivo is essential to identify novel therapeutic approaches. Here we elucidate cell-intrinsic drivers of metastatic prostate cancer progression through analyses of genetically engineered mouse models (GEMM) and correlative studies of human prostate cancer. Expression profiling of lineage-marked cells from mouse primary tumors and metastases defines a signature of de novo metastatic progression.

Nonreciprocal Linear Transmission of Sound in a Viscous Environment with Broken P Symmetry.

Reciprocity is a fundamental property of the wave equation in a linear medium that originates from time-reversal symmetry, or T symmetry. For electromagnetic waves, reciprocity can be violated by an external magnetic field. It is much harder to realize nonreciprocity for acoustic waves.

Genetically Engineered Mouse Models of Prostate Cancer in the Postgenomic Era.

Recent genomic sequencing analyses have unveiled the spectrum of genomic alterations that occur in primary and advanced prostate cancer, raising the question of whether the corresponding genes are functionally relevant for prostate tumorigenesis, and whether such functions are associated with particular disease stages. In this review, we describe genetically engineered mouse models (GEMMs) of prostate cancer, focusing on those that model genomic alterations known to occur in human prostate cancer. We consider whether the phenotypes of GEMMs based on gain or loss of function of the relevant genes provide reliable counterparts to study the predicted consequences of the corresponding genomic alterations as occur in human prostate cancer, and we discuss exceptions in which the GEMMs do not fully emulate the expected phenotypes.

Strategies for overcoming tropical disease by ruthenium complexes with purine analog: Application against Leishmania spp. and Trypanosoma cruzi.

Tropical diseases currently constitute a major health problem and thus a challenge in the field of drug discovery. The current treatments show serious disadvantages due to cost, toxicity, long therapy duration and resistance, and the use of metal complexes as chemotherapeutic agents against these ailments appears to be a very attractive alternative. Herein, we describe three newly synthesized ruthenium complexes with a bioactive molecule, the purine analogue 5,6,7-trimethyl-1,2,4-triazolo[1,5-a]pyrimidine (tmtp): cis,fac-[RuCl(dmso)(tmtp)] (1), mer-[RuCl(dmso)(HO)(tmtp)]·2HO (2) and fac,cis-[RuCl(HO)(tmtp)] (3).

Metallothionein 1G promotes the differentiation of HT-29 human colorectal cancer cells.

Metallothioneins (MTs) are a family of low-molecular-weight, cysteine-rich proteins involved in zinc and redox metabolism, that are epigenetically downregulated during colorectal cancer (CRC) progression, but may be re-induced with a variety of agents. Since loss of MT expression is associated with a worse prognosis, in the present study we investigated the effects of overexpression of the most significantly downregulated isoform in CRC, namely MT1G, on the HT-29 cell line. Overexpression of MT1G resulted in xenograft tumors with an aberrant morphology, characterized by an evident increase in mucin-containing cells that were identified as goblet cells under electron microscopy.

Goos-Hänchen effect for optical vibrational modes in a semiconductor structure.

We study the tunneling of optical vibrational modes with transverse horizontal polarization that impinge, at a given angle, on a semiconductor heterostructure. We find a large influence of the Goos-Hänchen shift on tunneling times. In particular, a Goos-Hänchen shift larger than the barrier thickness is reported for the first time.

Chirped dual periodic structures for photonic Bloch oscillations and Zener tunneling.

Experimental evidence of photon Wannier-stark ladders (WSLs) and Zener tunneling (ZT) in one dimensional dual-periodical (DP) optical superlattices based on Porous Silicon (PSi), is presented. An introduction of linear gradient in physical thickness of the layers, composed of five stacks of two different periodic substructures, resulted in the appearance of four WSLs resonances and resonant Zener tunneling of nearest resonances of two consecutive WSLs. Theoretical analysis of time-resolved reflection spectra as a function of gradient reveals the presence of photonic Bloch oscillations (BOs) and an eventual tunneling at a specific value of linear gradient (20%), has been demonstrated through scattering maps.

Tunneling times of acoustic phonon packets through a distributed Bragg reflector.

The longwave phenomenological model is used to make simple and precise calculations of various physical quantities such as the vibrational energy density, the vibrational energy, the relative mechanical displacement, and the one-dimensional stress tensor of a porous silicon distributed Bragg reflector. From general principles such as invariance under time reversal, invariance under space reflection, and conservation of energy density flux, the equivalence of the tunneling times for both transmission and reflection is demonstrated. Here, we study the tunneling times of acoustic phonon packets through a distributed Bragg reflector in porous silicon multilayer structures, and we report the possibility that a phenomenon called Hartman effect appears in these structures.

Localization of acoustic modes in periodic porous silicon structures.

The propagation of longitudinal acoustic waves in multilayer structures based on porous silicon and the experimental measurement of acoustic transmission for the structures in the gigahertz range are reported and studied theoretically. The considered structures exhibit band gaps in the transmission spectrum and these are localized modes inside the band gap, coming from defect layers introduced in periodic systems. The frequency at which the acoustic resonances appear can be tuned by changing the porosity and/or thickness of the defect layer.

Metallothionein 1G and zinc sensitize human colorectal cancer cells to chemotherapy.

Metallothioneins (MT) are a family of low molecular weight proteins that are silenced during colorectal cancer progression, mainly through epigenetic mechanisms, and this loss is associated with poor survival. In this article, we show that overexpression of the MT1G isoform sensitizes colorectal cell lines to the chemotherapeutic agents oxaliplatin (OXA) and 5-fluorouracil (5-FU), in part through enhancing p53 and repressing NF-κB activity. Despite being silenced, MTs can be reinduced by histone deacetylase inhibitors such as trichostatin A and sodium butyrate.

Development of a novel methodology for cryopreservation of melanoma cells applied to CSF470 therapeutic vaccine.

CSF470 vaccine is a mixture of four lethally irradiated melanoma cell lines, administered with BCG and GM-CSF, which is currently being tested in a Phase II/III Clinical trial in stage II/III melanoma patients. To prepare vaccine doses, irradiated melanoma cell lines are frozen using dimethyl sulfoxide (Me(2)SO) and stored in liquid nitrogen (liqN(2)). Prior to inoculation, doses must be thawed, washed to remove Me(2)SO and suspended for clinical administration.

IL-2- or IL-15-activated NK cells enhance Cetuximab-mediated activity against triple-negative breast cancer in xenografts and in breast cancer patients.

Triple-negative breast cancer (TNBC) patients do not benefit from target-specific treatments and is associated with a high relapse rate. Epidermal growth factor receptor is frequently expressed in TNBC and is a candidate for new therapies. In this work, we studied Cetuximab-mediated immune activity by NK cells.

Protein expression changes during human triple negative breast cancer cell line progression to lymph node metastasis in a xenografted model in nude mice.

Triple negative breast cancers (TNBC) lacking hormone receptors and HER-2 amplification are very aggressive tumors. Since relevant differences between primary tumors and metastases could arise during tumor progression as evidenced by phenotypic discordances reported for hormonal receptors or HER-2 expression, in this analysis we studied changes that occurred in our TNBC model IIB-BR-G throughout the development of IIB-BR-G-MTS6 metastasis to the lymph nodes (LN) in nude mice, using an antibody-based protein array to characterize their expression profile. We also analyzed their growth kinetics, migration, invasiveness and cytoskeleton structure in vitro and in vivo.

Demonstration of photon Bloch oscillations and Wannier-Stark ladders in dual-periodical multilayer structures based on porous silicon.

: Theoretical demonstration and experimental evidence of photon Bloch oscillations and Wannier-Stark ladders (WSLs) in dual-periodical (DP) multilayers, based on porous silicon, are presented. An introduction of the linear gradient in refractive indices in DP structure, which is composed by stacking two different periodic substructures N times, resulted in the appearance of WSLs. Theoretical time-resolved reflection spectrum shows the photon Bloch oscillations with a period of 130 fs.

Tunable resonance transmission modes in hybrid heterostructures based on porous silicon.

: In this work, we report the experimental results and theoretical analysis of strong localization of resonance transmission modes generated by hybrid periodic/quasiperiodic heterostructures (HHs) based on porous silicon. The HHs are formed by stacking a quasiperiodic Fibonacci (FN) substructure between two distributed Bragg reflectors (DBRs). FN substructure defines the number of strong localized modes that can be tunable at any given wavelength and be unfolded when a partial periodicity condition is imposed.