Cancer Immunotherapy: Harnessing the Immune System to Fight Cancer

Not availabl

Cancer immunotherapy: Current and future perspectives on a therapeutic revolution

N/

Cu-catalyzed Si-NWS grown on “carbon paper” as anodes for Li-ion cells

The very high theoretical capacity of the silicon (4200mAh/g more than 10 times larger than graphite), environmental-friendly, abundant and low-cost, makes it a potential candidate to replace graphite in high energy density Li-ion batteries. As a drawback, silicon suffers from huge volume changes (300%) on alloying and dealloying with Li, leading a structural deformation that induces disruption. The use of nanostructured silicon materials has been shown to be an effective way to avoid this mechanical degradation of the active material. In this paper the synthesis of silicon nanowires, grown on a highly porous 3D-like carbon paper substrate by CVD using Cu as the catalyst, is presented. The use of carbon paper allows to achieve remarkable loadings of active material (2-5 mg/cm2) and, consequently, high capacity densities. The silicon electrode was investigated both morphologically and electrochemically. To improve the electrochemical performance various strategies have been carried out. It was observed that a very slow first cycle (C/40), which helps the formation of a stable solid electrolyte interphase on the silicon surface, improves the performance of the cells; nevertheless, their cycle life has been found not fully satisfactory. Morphological analysis of the Si-NWs electrodes before and after cycling showed the presence of a dense silicon layer below the nanowires which could reduce the electrical contact between the active material and the substrate

Pathologic Complete Response in Urothelial Carcinoma Patients Receiving Neoadjuvant Immune Checkpoint Inhibitors: A Meta-Analysis

Background. Immune checkpoint inhibitors (ICIs) have been evaluated as neoadjuvant treatment in urothelial carcinoma (UC) patients, with these agents reporting encouraging pathologic complete response (pCR) rates. Herein, we performed a systematic review and meta-analysis aimed at evaluating the incidence of pCR in UC patients treated with neoadjuvant ICI. Moreover, we investigated the impact of PD-L1 expression in this patient population, exploring the possible role of PD-L1 status as predictive biomarker. Materials and Methods. We retrieved all the relevant trials through PubMed/Medline, Cochrane Library and EMBASE; moreover, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible trials assessed pre-operative ICI in UC patients. Results. Our meta-analysis has highlighted a pooled pCR rate of 36.6% in the overall population; interestingly, pCR was higher in PD-L1 positive compared with PD-L1 negative UCs (49.5% versus 35.1%, respectively). Conclusions. Positive signals emanating from neoadjuvant immunotherapy should encourage the scientific community to persist in the long road toward finding more effective treatments for UC patients

Detergents and chaotropes for protein solubilization before two-dimensional electrophoresis

Because of the outstanding ability of two-dimensional electrophoresis to separate complex mixtures of intact proteins, it would be advantageous to apply it to all types of proteins, including hydrophobic and membrane proteins. Unfortunately, poor solubility hampers the analysis of these molecules. As these problems arise mainly in the extraction and isoelectric focusing steps, the solution is to improve protein solubility under the conditions prevailing during isoelectric focusing. This chapter describes the use of chaotropes and novel detergents to enhance protein solubility during sample extraction and isoelectric focussing, and discusses the contribution of these compounds to improving proteomic analysis of membrane proteins

Correlation between mechanical properties and processing conditions in rubber-toughened wood polymer composites

The use of wood fibers is a deeply investigated topic in current scientific research and one of their most common applications is as filler for thermoplastic polymers. The resulting material is a biocomposite, known as a Wood Polymer Composite (WPC). For increasing the sustainability and reducing the cost, it is convenient to increase the wood fiber content as much as possible, so that the polymeric fraction within the composite is thereby reduced. On the other hand, this is often thwarted by a sharp decrease in toughness and processability-a disadvantage that could be overcome by compounding the material with a toughening agent. This work deals with the mechanical properties in tension and impact of polypropylene filled with 50 wt.% wood flour, toughened with different amounts (0%, 10%, and 20%) of a polypropylene-based thermoplastic vulcanizate (TPV). Such properties are also investigated as a function of extrusion processing variables, such as the feeding mode (i.e., starve vs. flood feeding) and screw speed. It is found that the mechanical properties do depend on the processing conditions: the best properties are obtained either in starve feeding conditions, or in flood feeding conditions, but at a low screw speed. The toughening effect of TPV is significant when its content reaches 20 wt.%. For this percentage, the processing conditions are less relevant in governing the final properties of the composites in terms of the stiffness and strength

Evidence of a kallikrein inhibitor in human kidney. A new ring of the kallikrein-renin-angiotensin-aldosterone chain

By means of immunohistochemical reactions, the authors proved the inhibitor II-related immunoreactivity in distal convoluted tubules of human kidney. A sharp inhibitor II-related immunoreactivity was also present in the blood vessels' wall. On the contrary, in the wall of proximal tubules and glomeruli only low reactivity was found. The demonstration of an inhibitor II-related immunoreactivity in the distal convoluted tubules and vessels of human kidney represents a strong evidence that an inhibitor of kallikrein exists and acts also in humans as an important key in the kallikrein-renin-angiotensin aldosterone chain and hitherto confirms the experimental data of the literature. The proved inhibitor in the human kidney may intervene in the modulation of the kallikrein-kinin system and thus represents a key role in the intrarenal mechanisms related to the blood flow and arterial pressure regulation

Innate immune activating ligand SUMOylation affects tumor cell recognition by NK cells

Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma. Concurrently, we found that PVR is preferentially located in intracellular compartments in human multiple myeloma cell lines and malignant plasma cells and that inhibition of the SUMO pathway promotes its translocation to the cell surface, increasing tumor cell susceptibility to NK cell-mediated cytolysis. Our findings provide the first evidence of an innate immune activating ligand regulated by SUMOylation, and confer to this modification a novel role in impairing recognition and killing of tumor cells.Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma. Concurrently, we found that PVR is preferentially located in intracellular compartments in human multiple myeloma cell lines and malignant plasma cells and that inhibition of the SUMO pathway promotes its translocation to the cell surface, increasing tumor cell susceptibility to NK cell-mediated cytolysis. Our findings provide the first evidence of an innate immune activating ligand regulated by SUMOylation, and confer to this modification a novel role in impairing recognition and killing of tumor cells

Mitochondrial proteomics: analysis of a whole mitochondrial extract with two-dimensional electrophoresis

Mitochondria are complex organelles, and their proteomics analysis requires a combination of techniques. The emphasis in this chapter is made first on mitochondria preparation from cultured mammalian cells, then on the separation of the mitochondrial proteins with two-dimensional electrophoresis (2DE), showing some adjustment over the classical techniques to improve resolution of the mitochondrial proteins. This covers both the protein solubilization, the electrophoretic part per se, and the protein detection on the gels, which makes the interface with the protein identification part relying on mass spectrometry

Molecular mechanisms related to hormone inhibition resistance in prostate cancer

Management of metastatic or advanced prostate cancer has acquired several therapeutic approaches that have drastically changed the course of the disease. In particular due to the high sensitivity of prostate cancer cells to hormone depletion, several agents able to inhibit hormone production or binding to nuclear receptor have been evaluated and adopted in clinical practice. However, despite several hormonal treatments being available nowadays for the management of advanced or metastatic prostate cancer, the natural history of the disease leads inexorably to the development of resistance to hormone inhibition. Findings regarding the mechanisms that drive this process are of particular and increasing interest as these are potentially related to the identification of new targetable pathways and to the development of new drugs able to improve our patients’ clinical outcomes