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991.
Alessandro Del Conte Elisa De Carlo Elisa Bertoli Brigida Stanzione Alberto Revelant Manuela Bertola Michele Spina Alessandra Bearz 《International journal of molecular sciences》2022,23(12)
Patients with non-small cell lung cancer (NSCLC) develop bone metastasis (BoM) in more than 50% of cases during the course of the disease. This metastatic site can lead to the development of skeletal related events (SREs), such as severe pain, pathological fractures, spinal compression, and hypercalcemia, which reduce the patient’s quality of life. Recently, the treatment of advanced NSCLC has radically changed due to the advent of immunotherapy. Immune checkpoint inhibitors (ICI) alone or in combination with chemotherapy have become the main therapeutic strategy for advanced or metastatic NSCLC without driver gene mutations. Since survival has increased, it has become even more important to treat bone metastasis to prevent SRE. We know that the presence of bone metastasis is a negative prognostic factor. The lower efficacy of immunotherapy treatments in BoM+ patients could be induced by the presence of a particular immunosuppressive tumor and bone microenvironment. This article reviews the most important pre-clinical and clinical scientific evidence on the reasons for this lower sensitivity to immunotherapy and the need to combine bone target therapies (BTT) with immunotherapy to improve patient outcome. 相似文献
992.
Elisa De Carlo Elisa Bertoli Alessandro Del Conte Brigida Stanzione Eleonora Berto Alberto Revelant Michele Spina Alessandra Bearz 《International journal of molecular sciences》2022,23(12)
The therapeutic landscape in patients with advanced non-small-cell lung cancer harboring oncogenic biomarkers has radically changed with the development of targeted therapies. Although lung cancers are known to frequently metastasize to the brain, oncogene-driven non-small-cell lung cancer patients show a higher incidence of both brain metastases at baseline and a further risk of central nervous system progression/relapse. Recently, a new generation of targeted agents, highly active in the central nervous system, has improved the control of intracranial disease. The intracranial activity of these drugs poses a crucial issue in determining the optimal management sequence in oncogene-addicted non-small-cell lung cancer patients with brain metastases, with a potential change of paradigm from primary brain irradiation to central nervous system penetrating targeted inhibitors. 相似文献
993.
Gabriele A. Trombetti Alessandra Mezzelani Alessandro Orro 《International journal of molecular sciences》2022,23(12)
Chronic pain is a widespread disorder affecting millions of people and is insufficiently addressed by current classes of analgesics due to significant long-term or high dosage side effects. A promising approach that was recently proposed involves the systemic inhibition of the voltage-gated sodium channel Nav1.7, capable of cancelling pain perception completely. Notwithstanding numerous attempts, currently no drugs have been approved for the inhibition of Nav1.7. The task is complicated by the difficulty of creating a selective drug for Nav1.7, and avoiding binding to the many human paralogs performing fundamental physiological functions. In our work, we obtained a promising set of ligands with up to 5–40-fold selectivity and reaching 5.2 nanomolar binding affinity by employing a proper treatment of the problem and an innovative differential in silico screening procedure to discriminate for affinity and selectivity against the Nav paralogs. The absorption, distribution, metabolism, and excretion (ADME) properties of our top-scoring ligands were also evaluated, with good to excellent results. Additionally, our study revealed that the top-scoring ligand is a stereoisomer of an already-approved drug. These facts could reduce the time required to bring a new effective and selective Nav1.7 inhibitor to the market. 相似文献
994.
Maurizio Benaglia Giuseppe Celentano Mauro Cinquini Alessandra Puglisi Franco Cozzi 《Advanced Synthesis \u0026amp; Catalysis》2002,344(2):149-152
A tyrosine‐derived imidazolidin‐4‐one was immobilized on a modified poly(ethylene glycol) and converted in situ into a soluble polymer‐supported catalyst for the enantioselective Diels–Alder cycloaddition of acrolein to 1,3‐cyclohexadiene (up to 92% ee) and 2,3‐dimethyl‐1,3‐butadiene (73% ee). Catalyst recycling (up to four cycles) was accompanied by some loss of the chemical efficiency and marginal erosion of the enantioselectivity. 相似文献
995.
Maurizio Benaglia Mauro Cinquini Franco Cozzi Alessandra Puglisi Giuseppe Celentano 《Advanced Synthesis \u0026amp; Catalysis》2002,344(5):533-542
(2S,4R)‐4‐Hydroxyproline has been anchored to the monomethyl ether of poly(ethylene glycol), MW 5000, by means of a succinate spacer to afford a soluble, polymer‐supported catalyst (PEG‐Pro) for enantioselective aldol and iminoaldol condensation reactions. This organic catalyst can be considered as a minimalistic version of a type I aldolase enzyme, with the polymer chain replacing the enzyme's peptide backbone, and the proline residue acting as the enzyme's active site. In the presence of PEG‐Pro (0.25–0.35 mol equiv.), acetone reacted with enolizable and non‐enolizable aldehydes and imines to afford β‐ketols and β‐aminoketones in good yield and high enantiomeric excess (ee), comparable to those obtained using non‐supported proline derivatives as the catalysts. Extension of the PEG‐Pro‐promoted condensation to hydroxyacetone as the aldol donor opened an access to synthetically relevant anti‐α,β‐dihydroxyketones and syn‐α‐hydroxy‐β‐aminoketones, that were obtained in moderate to good yields, and good to high diastereo‐ and enantioselectivity. Exploiting its solubility properties, the PEG‐Pro catalyst was easily recovered and recycled to promote all of the above‐mentioned reactions, that occurred in slowly diminishing yields but virtually unchanged ee's. 相似文献
996.
997.
998.
The first example of an asymmetric β‐peroxidation of nitroalkenes is disclosed. The reaction is promoted by catalytic loadings of a commercially available diaryl‐2‐pyrrolidinemethanol derivative and tert‐butyl hydroperoxide as the oxidant. A synthetically useful class of peroxides is obtained in good yield and enantioselectivity (up to 84% ee). 相似文献
999.
Alessandra Colombini Paola De Luca Davide Cangelosi Carlotta Perucca Orfei Enrico Ragni Marco Vigan Michela Malacarne Mauro Castagnetta Marco Brayda-Bruno Domenico Coviello Laura de Girolamo 《International journal of molecular sciences》2021,22(17)
Vitamin D showed a protective effect on intervertebral disc degeneration (IDD) although conflicting evidence is reported. An explanation could be due to the presence of the FokI functional variant in the vitamin D receptor (VDR), observed as associated with spine pathologies. The present study was aimed at investigating—through high-throughput gene and protein analysis—the response of human disc cells to vitamin D, depending on the VDR FokI variants. The presence of FokI VDR polymorphism was determined in disc cells from patients with discopathy. 1,25(OH)2D3 was administered to the cells with or without interleukin 1 beta (IL-1β). Microarray, protein arrays, and multiplex protein analysis were performed. In both FokI genotypes (FF and Ff), vitamin D upregulated metabolic genes of collagen. In FF cells, the hormone promoted the matrix proteins synthesis and a downregulation of enzymes involved in matrix catabolism, whereas Ff cells behaved oppositely. In FF cells, inflammation seems to hamper the synthetic activity mediated by vitamin D. Angiogenic markers were upregulated in FF cells, along with hypertrophic markers, some of them upregulated also in Ff cells after vitamin D treatment. Higher inflammatory protein modulation after vitamin D treatment was observed in inflammatory condition. These findings would help to clarify the clinical potential of vitamin D supplementation in patients affected by IDD. 相似文献
1000.
Costantino Balestra Kate Lambrechts Simona Mrakic-Sposta Alessandra Vezzoli Morgan Levenez Peter Germonpr Fabio Virgili Gerardo Bosco Pierre Lafre 《International journal of molecular sciences》2021,22(17)
Inflammation is an adaptive response to both external and internal stimuli including infection, trauma, surgery, ischemia-reperfusion, or malignancy. A number of studies indicate that physical activity is an effective means of reducing acute systemic and low-level inflammation occurring in different pathological conditions and in the recovery phase after disease. As a proof-of-principle, we hypothesized that low-intensity workout performed under modified oxygen supply would elicit a “metabolic exercise” inducing a hormetic response, increasing the metabolic load and oxidative stress with the same overall effect expected after a higher intensity or charge exercise. Herein, we report the effect of a 5-week low-intensity, non-training, exercise program in a group of young healthy subjects in combination with the exposure to hyperoxia (30% and 100% pO2, respectively) or light hypoxia (15% pO2) during workout sessions on several inflammation and oxidative stress parameters, namely hemoglobin (Hb), redox state, nitric oxide metabolite (NOx), inducible nitric oxide synthase (iNOS), inflammatory cytokine expression (TNF-α, interleukin (IL)-6, IL-10), and renal functional biomarkers (creatinine, neopterin, and urates). We confirmed our previous reports demonstrating that intermittent hyperoxia induces the normobaric oxygen paradox (NOP), a response overlapping the exposure to hypoxia. Our data also suggest that the administration of modified air composition is an expedient complement to a light physical exercise program to achieve a significant modulation of inflammatory and immune parameters, including cytokines expression, iNOS activity, and oxidative stress parameters. This strategy can be of pivotal interest in all those conditions characterized by the inability to achieve a sufficient workload intensity, such as severe cardiovascular alterations and articular injuries failing to effectively gain a significant improvement of physical capacity. 相似文献