159 research outputs found
Development of a flow process for an easy and fast access to 2-pyrone derivatives
2-Pyrones are compounds widely present in nature and they represent interesting building blocks both in medicinal and synthetic chemistry. Due to their peculiar pharmacological activity and structure, they have attracted much attention during the last decades and several protocols for their synthesis have been developed. In this work we propose the synthesis of bio-sourced 2-pyrones, exploiting continuous-flow conditions for an easy, sustainable and fast access to these important molecules
Antioxidant and UV-Blocking Functionalized Poly(Butylene Succinate) Films
The introduction of a limited number of functional groups on poly(butylene succinate) (PBS) chains by covalent bonding can impart new properties to the polymer without modifying its thermal and mechanical properties. In pursuit of a viable approach to obtain light- and heat-stabilized PBS samples, the nitroxide radical coupling (NRC) reaction between PBS macroradicals and the 3,5-di-tert-butyl-4-hydroxybenzoyl-2,2,6,6-tetramethylpiperidine-1-oxyl radical (BHB-TEMPO), a functionalizing agent bearing a sterically-hindered antioxidant phenol moiety, is here proposed. The reaction was initiated by peroxide and carried out in solution and in a melt. The functionalized materials were characterized by UV-visible spectroscopy (UV-Vis), proton nuclear magnetic resonance (1H-NMR), and size exclusion chromatography (SEC) analysis to gain structural information and by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) to investigate the thermal properties. In addition, films of the samples were subjected to thermal and photo-oxidative aging to assess their resistance to degradative processes. Finally, the PBS film with the highest degree of functionalization showed the ability to protect β-carotene, a molecule found in food and drugs and that is very sensitive to UV light, from degradation. This result suggests the use of this material (either alone or blended with other biopolyesters) for biodegradable and compostable active packaging
Sonication-induced modification of carbon nanotubes: Effect on the rheological and thermo-oxidative behaviour of polymer-based nanocomposites
The aim of this work is the investigation of the effect of ultrasound treatment on the structural characteristics of carbon nanotubes (CNTs) and the consequent influence that the shortening induced by sonication exerts on the morphology, rheological behaviour and thermo-oxidative resistance of ultra-high molecular weight polyethylene (UHMWPE)-based nanocomposites. First, CNTs have been subjected to sonication for different time intervals and the performed spectroscopic and morphological analyses reveal that a dramatic decrease of the CNT's original length occurs with increased sonication time. The reduction of the initial length of CNTs strongly affects the nanocomposite rheological behaviour, which progressively changes from solid-like to liquid-like as the CNT sonication time increases. The study of the thermo-oxidative behaviour of the investigated nanocomposites reveals that the CNT sonication has a detrimental effect on the thermo-oxidative stability of nanocomposites, especially for long exposure times. The worsening of the thermo-oxidative resistance of sonicated CNT-containing nanocomposites could be attributed to the lower thermal conductivity of low-aspect-ratio CNTs, which causes the increase of the local temperature at the polymer/nanofillers interphase, with the consequent acceleration of the degradative phenomena
Inflammation and infiltration: can the radiologist draw a line? MRI versus CT to accurately assess medullary involvement in parosteal osteosarcoma
Cancer causes inflammation as it progresses through healthy tissue. The differentiation of tumoral growth from the surrounding inflammatory change is paramount in planning surgeries seeking to preserve function. This retrospective study aims at illustrating how a careful use of imaging (computed tomography (CT)/magnetic resonance imaging (MRI)) can help to draw the line between infiltration and inflammation. Out of 72 cases of parosteal osteosarcoma in our institution we selected 22 which had pretreatment imaging, and out of those, 14 that had both MRI and CT. Using Fisher’s exact test, we evaluated the performance of each technique on accurately diagnosing medullary tumor infiltration, using histological analysis as a gold standard. All cases (14/14) demonstrated medullary abnormality on MRI, but only 6/14 (42.9%) demonstrated abnormality on CT. The 8/14 cases with MRI abnormality but no CT abnormality (57.1%) showed inflammation with no tumoral cells present on histological analysis. In the cases where the two examinations showed medullary abnormality (6/14) histology demonstrated tumoral infiltration. MRI demonstrated high sensitivity and negative predictive value, but low specificity and low positive predictive value and accuracy (P=1). CT demonstrated high sensitivity, specificity, high positive and negative predictive values and accuracy (P = 0.000333). MRI is highly sensitive for the detection of medullary abnormality but lacks specificity for tumor invasion. Correlation with CT is recommended in all cases of positive MR to add specificity for tumors. The adequate use of the two imaging methods allows to differentiate between inflammatory change and tumoral infiltration in POS, relevant for surgical planning
Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients' bed.
BACKGROUND:
Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects of highly cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark of all malignant tumors. The H\u2009+-rich milieu that anticancer drugs meet once they get inside the tumor leads to their protonation and neutralization, therefore hindering their access into tumor cells. We have previously shown that proton pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading to a consistent chemosensitization of tumors. In this study, we investigated the effects of PPI in chemosensitizing osteosarcoma.
METHOD:
MG-63 and Saos-2 cell lines were used as human osteosarcoma models. Cell proliferation after pretreatment with PPI and subsequent treatment with cisplatin was evaluated by using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre historically controlled trial, was performed to evaluate the activity of a pre-treatment administration of PPIs as chemosensitizers during neoadjuvant chemotherapy based on methotrexate, cisplatin, and adriamycin.
RESULTS:
Preclinical experiments showed that PPI sensitize both human osteosarcoma cell lines and xenografts to cisplatin. A clinical study subsequently showed that pretreatment with PPI drug esomeprazole leads to an increase in the local effect of chemotherapy, as expressed by percentage of tumor necrosis. This was particularly evident in chondroblastic osteosarcoma, an histological subtype that normally shows a poor histological response. Notably, no significant increase in toxicity was recorded in PPI treated patients.
CONCLUSION:
This study provides the first evidence that PPI may be beneficially added to standard regimens in combination to conventional chemotherapy
Comparison of Branched and Linear Perfluoropolyether Chains Functionalization on Hydrophobic, Morphological and Conductive Properties of Multi-Walled Carbon Nanotubes
The functionalization of multi-walled carbon nanotubes (MW-CNTs) was obtained by
generating reactive perfluoropolyether (PFPE) radicals that can covalently bond to MW-CNTs\u2019
surface. Branched and linear PFPE peroxides with equivalent molecular weights of 1275 and
1200 amu, respectively, have been thermally decomposed for the production of PFPE radicals.
The functionalization with PFPE chains has changed the wettability of MW-CNTs, which switched
their behavior from hydrophilic to super-hydrophobic. The low surface energy properties of PFPEs
have been transferred to MW-CNTs surface and branched units with trifluoromethyl groups, CF3,
have conferred higher hydrophobicity than linear units. Porosimetry discriminated the effects of
PFPE functionalization on meso-porosity and macro-porosity. It has been observed that reactive sites
located in MW-CNTs mesopores have been intensively functionalized by branched PFPE peroxide
due to its low average molecular weight. Conductivity measurements at different applied pressures
have showed that the covalent linkage of PFPE chains, branched as well as linear, weakly modified
the electrical conductivity of MW-CNTs. The decomposed portions of PFPE residues, the PFPE
chains bonded on carbon nanotubes, and the PFPE fluids obtained by homo-coupling side-reactions
were evaluated by mass balances. PFPE-modified MW-CNTs have been characterized by X-ray
photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), thermogravimetric analysis
(TGA), static contact angle (SCA), surface area, and porosity measurements
Indications and Limits of Surgery for Spinal Metastases Derived from Lung Cancer: A Single-Center Experience
Lung cancer is the second most frequently diagnosed cancer in the world, and surgery is an integral part of the treatment for spinal metastases. The aims of this retrospective study were to assess the overall survival of surgically treated patients affected by lung cancer spinal metastases and identify any factors related to a better survival rate. We recruited 56 consecutive patients (34 male and 22 female) surgically treated for metastatic lung cancer in the spine from 2009 to 2019. Surgical indications were based on a previously published and validated flow chart following a multidisciplinary evaluation. We assessed the localization of vertebral metastases, the presence of other bone or visceral metastases, neurological status according to the Frankel score, ambulatory autonomy, and general status, measured with the Karnofsky performance scale. The expected prognosis was retrospectively assessed according to the revised Tokuhashi score. The median survival was 8.1 months, with over a third of patients surviving more than 1 year. We observed a global improvement in all clinical parameters after surgical treatment. The Tokuhashi predictive score did not correlate with survival after surgery. The results of this study suggest that the surgical treatment of symptomatic spinal metastases from lung cancer can improve quality of life, even in patients with a shorter life expectancy, by controlling pain and improving autonomy
Dideoxynucleoside HIV reverse transcriptase inhibitors and drug-related hepatotoxicity: a case report
This report regards the case of a 43 year-old HIV-positive woman who developed an episode of serious transaminase elevation during stavudine-including antiretroviral therapy. Diagnostic assessment ruled out hepatitis virus co-infection, alcohol abuse besides other possible causes of liver damage. No signs of lactic acidosis were present. Liver biopsy showed portal inflammatory infiltrate, spotty necrosis, vacuoles of macro- and micro-vesicular steatosis, acidophil and foamy hepatocytes degeneration with organelles clumping, poorly formed Mallory bodies and neutrophil granulocytes attraction (satellitosis). A dramatic improvement in liver function tests occurred when stavudine was discontinued and a new antiretroviral regimen with different nucleoside reverse transcriptase inhibitors was used. The importance of considering hepatotoxicity as an adverse event of HAART including stavudine, even in absence of other signs of mitochondrial toxicity should therefore be underlined. Liver biopsy may provide further important information regarding patients with severe transaminase elevation, for a better understanding of the etiology of liver damage
The sacral chordoma margin
[Objective]: Aim of the manuscript is to discuss how to improve margins in sacral chordoma.
[Background]: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery.
[Methods]: A multidisciplinary meeting of the “Chordoma Global Consensus Group” was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed.
[Results]: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment.
[Conclusion]: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients
N-Hydroxy Derivatives: Key Organocatalysts for the Selective Free Radical Aerobic Oxidation of Organic Compunds
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