On the bilinear covariants associated to mass dimension one spinors

In this paper we approach the issue of Clifford algebra basis deformation, allowing for bilinear covariants associated to Elko spinors which satisfy the Fierz-Pauli-Kofink identities. We present a complete analysis of covariance, taking into account the involved dual structure associated to Elko. Moreover, the possible generalizations to the recently presented new dual structure are performed.Comment: 9 pages, 0 figure

Biomarkers for precision immunotherapy in the metastatic setting: Hope or reality?

Precision immunotherapy is a crucial approach to improve the efficacy of anti-cancer treatments, particularly in the metastatic setting. In this respect, accurate patient selection takes advantage of the multidimensional integration of patients' clinical information and tumour-specific biomarkers status. Among these biomarkers, programmed death-ligand 1, tumour-infiltrating lymphocytes, microsatellite instability, mismatch repair and tumour mutational burden have been widely investigated. However, novel tumour-specific biomarkers and testing methods will further improve patients' outcomes. Here, we discuss the currently available strategies for the implementation of a precision immunotherapy approach in the clinical management of metastatic solid tumours and highlight future perspectives

Editorial: metabolic reprogramming in breast cancer

Metabolic reprogramming is an emerging hallmark of breast cancer. A common characteristic of tumor cells is the ability to obtain nutrients from a nutrient-deprived environment and to use them to sustain cancer progression, within crucial metabolic pathways including altered metabolism of glucose, lipids, and amino acids. Also, altered metabolism has been recognized as one of the major mechanisms of resistance to therapies. Important advances have been made to elucidate key mechanisms of metabolic reprogramming which will make possible novel strategies for overcoming breast cancer. However, for metabolic therapy to be effective there is a need to clearly understand the metabolic underpinnings of the different subtypes of breast cancer as well as the role the standard-of-care therapies play in targeting the metabolic phenotype

Decipher the glioblastoma microenvironment: The first milestone for new groundbreaking therapeutic strategies

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. GBM is a polymorphic tumour from both molecular and histological points of view. It consists of different malignant cells and various stromal cells, contributing to tumour initiation, progression, and treatment response. GBM’s microenvironment is multifaceted and is made up of soluble factors, extracellular matrix components, tissue-resident cell types (e.g., neurons, astrocytes, endothelial cells, pericytes, and fibroblasts) together with resident (e.g., microglia) or recruited (e.g., bone marrow-derived macrophages) immune cells. These latter constitute the so-called immune microenvironment, accounting for a substantial GBM’s tumour volume. Despite the abundance of immune cells, an intense state of tumour immunosuppression is promoted and developed; this represents the significant challenge for cancer cells’ immune-mediated destruction. Though literature data suggest that distinct GBM’s subtypes harbour differences in their microenvironment, its role in treatment response remains obscure. However, an in-depth investigation of GBM’s microenvironment may lead to novel therapeutic opportunities to improve patients’ outcomes. This review will elucidate the GBM’s microenvironment composition, highlighting the current state of the art in immunotherapy approaches. We will focus on novel strategies of active and passive immunotherapies, including vaccination, gene therapy, checkpoint blockade, and adoptive T-cell therapies

Some interesting features of new massive gravity

A proof that new massive gravity - the massive 3D gravity model proposed by Bergshoeff, Hohm and Townsend (BHT) - is the only unitary system at the tree level that can be constructed by augmenting planar gravity through the curvature-squared terms, is presented. Two interesting gravitational properties of the BHT model, namely, time dilation and time delay, which have no counterpart in the usual Einstein 3D gravity, are analyzed as well.Comment: Submitted to Classical and Quantum Gravit

Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase

Here, we provide evidence that high ATP production by the mitochondrial ATP-synthase is a new therapeutic target for anticancer therapy, especially for preventing tumor progression. More specifically, we isolated a subpopulation of ATP-high cancer cells which are phenotypically aggressive and demonstrate increases in proliferation, stemness, anchorage-independence, cell migration, invasion and multi-drug resistance, as well as high antioxidant capacity. Clinically, these findings have important implications for understanding treatment failure and cancer cell dormancy. Using bioinformatic analysis of patient samples, we defined a mitochondrial-related gene signature for metastasis, which features the gamma-subunit of the mitochondrial ATP-synthase (ATP5F1C). The relationship between ATP5F1C protein expression and metastasis was indeed confirmed by immunohistochemistry. Next, we used MDA-MB-231 cells as a model system to functionally validate these findings. Importantly, ATP-high MDA-MB-231 cells showed a nearly fivefold increase in metastatic capacity in vivo. Consistent with these observations, ATP-high cells overexpressed (i) components of mitochondrial complexes I-V, including ATP5F1C, and (ii) markers associated with circulating tumor cells (CTCs) and metastasis, such as EpCAM and VCAM1. Knockdown of ATP5F1C expression significantly reduced ATP-production, anchorage-independent growth, and cell migration, as predicted. Similarly, therapeutic administration of the FDA-approved drug, Bedaquiline, downregulated ATP5F1C expression in vitro and prevented spontaneous metastasis in vivo. In contrast, Bedaquiline had no effect on the growth of non-tumorigenic mammary epithelial cells (MCF10A) or primary tumors in vivo. Taken together, our results suggest that mitochondrial ATP depletion is a new therapeutic strategy for metastasis prophylaxis, to avoid treatment failure. In summary, we conclude that mitochondrial ATP5F1C is a promising new biomarker and molecular target for future drug development, for the prevention of metastatic disease progression

Quasi-2D Heisenberg Antiferromagnets [CuX(pyz)2](BF4) with X = Cl and Br

Two Cu2+ coordination polymers [CuCl(pyz)(2)](BF4) 1 and [CuBr(pyz)(2)]-(BF4) 2 (pyz = pyrazine) were synthesized in the family of quasi two-dimensional (2D) [Cu(pyz)(2)](2+) magnetic networks. The layer connectivity by monatomic halide ligands results in significantly shorter interlayer distances. Structures were determined by single crystal X-ray diffraction. Temperature-dependent X-ray diffraction of 1 revealed rigid [Cu(pyz)(2)](2+) layers that do not expand between 5 K and room temperature, whereas the expansion along the c-axis amounts to 2%. The magnetic susceptibility of 1 and 2 shows a broad maximum at similar to 8 K, indicating antiferromagnetic interactions within the [Cu(pyz)(2)](2+) layers. 2D Heisenberg model fits result in J(parallel to) = 9.4(1) K for 1 and 8.9(1) K for 2. The interlayer coupling is much weaker with vertical bar J(perpendicular to)vertical bar = 0.31(6) K for 1 and 0.52(9) K for 2. The electron density, experimentally determined and calculated by density functional theory, confirms the location of the singly occupied orbital (the magnetic orbital) in the tetragonal plane. The analysis of the spin density reveals a mainly sigma-type exchange through pyrazine. Kinks in the magnetic susceptibility indicate the onset of long-range three-dimensional magnetic order below 4 K. The magnetic structures were determined by neutron diffraction. Magnetic Bragg peaks occur below T-N = 3.9(1) K for 1 and 3.8(1) K for 2. The magnetic unit cell is doubled along the c-axis (k = 0, 0, 0.5). The ordered magnetic moments are located in the tetragonal plane and amount to 0.76(8) mu(B)/Cu2+ for 1 and 0.6(1) mu(B)/Cu2+ for 2 at 1.5 K. The moments are coupled antiferromagnetically both in the ab plane and along the c-axis. The Cu2+ g-tensor was determined from electron spin resonance spectra as g(x) = 2.060(1), g(z) = 2.275(1) for 1 and g(x) = 2.057(1), g(z) = 2.272(1) for 2 at room temperature