Overview on topical 5-ALA photodynamic therapy use for non melanoma skin cancers

Ultraviolet radiation (UV) contributes to a variety of skin diseases including inflammation, degenerative aging, and cancer. Historically, humans have been exposed to UV radiation mainly through occupational exposure; recreational UV exposure, however, has increased dramatically in recent years, because of outdoor leisure activities and to purposely tan for cosmetic purposes. Both UVB and UVA radiation have been shown to cause DNA damage and immunosuppression, the important forms of biological damage that lead to NMSC. Nonmelanoma skin cancer (NMSC) is the most common malignancy, whose public health significance is often unrecognized which continues to grow at an alarming rate, becoming an occupational disease. Available treatments alternative to surgery include photodynamic therapy, electrochemotherapy, cryotherapy, ablative lasers, 5-fluorouracil, imiquimod, ingenol mebutate, and diclofenac. Among these, photodynamic therapy is a noninvasive technique with excellent cosmetic outcome and good curative results, when used in initial stages of skin cancers for superficial lesions. It is administered under numerous and significantly varied regimens and there are a wide range of cure rates reported, permitting treatment of large and multiple lesions with excellent cosmetic results. This is an overview of photodynamic applications especially for the treatment of NMSC, with a short focus on daylight modality. © 2014 Carmen Cantisani et al

High-MgO lavas associated to CFB as indicators of plume-related thermochemical effects: the case of ultra-titaniferous picrite-basalt from the Northern Ethiopian-Yemeni plateau

A comprehensive petrological and geochemical dataset is reported in order to define the thermo-compositional characteristics of Ti (Fe)-enriched picrite-basalt lavas (HT2, TiO2 3-7 wt%), erupted close to the axial zone of the inferred Afar mantle plume, at the centre of the originally continuous Ethiopian-Yemeni CFB plateau (ca. 30Ma) which is zonally arranged with progressively lower Ti basalts (HT1, TiO2 2-4 wt%; LT, TiO2 1-3 wt%) toward the periphery. Integrated petrogenetic modelling based on major and trace element analyses of bulk rocks, minerals and melt inclusions in olivines, as well as Sr-Nd-Pb-He-O isotope compositional variations enables us to make several conclusions. 1) The phase equilibria constraints indicate that HT2 primary picrites were generated at ca. 1570°C mantle potential temperatures (Tp) in the pressure range 4-5 GPa whereas the HT1 and LT primary melts formed at shallower level (< 2 to 3 GPa, Tp 1530 °C for HT1 and 1430°C for LT). Thus the Afar plume head was a thermally and compositionally zoned melting region with maximum excess temperatures of 300-350°C with respect to the ambient mantle. 2) The HT2 primary melts upwelled nearly adiabatically to the base of the continental crust (ca. 1 GPa) where fractionation of olivine, followed by clinopyroxene, led to variably differentiated picritic and basaltic magmas. 3) Trace element modelling requires that the primary HT2 melts were generated - either by fractional or batch melting (F 9-10%) - from a mixed garnet peridotite source (85%) with 15% eclogite (derived from transitional MORB protoliths included in Panafrican terranes) that has to be considered a specific Ti-Fe and incompatible element enriched component entrained by the Afar plume. 4) The LT, HT1 and HT2 lavas have 143Nd/144Nd = 0.5131-0.5128, whereas Sr-Pb isotopes are positively correlated with TiO2, varying from 87 Sr/86Sr 0.7032 and 206Pb/204Pb 18.2 in LT basalts to 87Sr/86Sr 0.7044 and 206Pb/204Pb 19.4 in HT2 picrite-basalts. High 3He/4He (15-20 RA) ratios are exclusively observed in HT2 lavas, confirming earlier evidence that these magmas require a component of deep mantle in addition to eclogite, while the LT basalts may more effectively reflect the signature of the pre-existing mantle domains. The comparison between high-MgO (13-22%) lavas from several Phanerozoic CFB provinces (Karoo, Paranà-Etendeka, Emeishan, Siberia, Deccan, North Atlantic Province) shows that they share extremely high mantle potential temperatures (Tp 1550-1700°C) supporting the view that hot mantle plumes are favoured candidates for triggering many LIPs. However, the high incompatible element and isotopic variability of these high-MgO lavas (and associated CFB) suggest that plume thermal anomalies are not necessarily accompanied by significant and specific chemical effects, which depend on the nature of mantle materials recycled during the plume rise, as well as by the extent of related mantle enrichments (if any) on the pre-existing lithospheric section

The IARC Perspective on Colorectal Cancer Screening

Colorectal cancer, which is the third most common cancer in men and the second most common in women, represents almost 10% of the annual global cancer incidence. Incidence rates of colorectal cancer show a strong positive gradient with an increasing level of economic development. Even so, the net 5-year rate of survival decreases with lower levels of income, with rates reaching 60% in high-income countries but falling to 30% or less in low-income countries. Established risk factors for colorectal cancer include consumption of processed meats, consumption of alcoholic beverages, tobacco smoking, and excess body fat, whereas consumption of dietary fiber and dairy products and increased levels of physical activity decrease the risk. In addition, certain subgroups of the population are at increased risk owing to genetic predisposition (e.g., the Lynch syndrome), a family or personal history of colorectal neoplasia, or medical conditions (e.g., inflammatory bowel disease) that have been associated with colorectal cancer

Corrigendum to "Overview on Topical 5-ALA Photodynamic Therapy Use for Non Melanoma Skin Cancers"

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Nintedanib-Containing Dual Conjugates Targeting αVβ6 Integrin and Tyrosine Kinase Receptors as Potential Antifibrotic Agents

αVβ6 Integrin plays a fundamental role in the activation of transforming growth factor-β (TGF-β), the major profibrotic mediator; for this reason, αVβ6 ligands have recently been forwarded to clinical phases for the therapy of fibrotic diseases. Herein, we report the synthesis and in vitro biological evaluation as antifibrotic agents of three new covalent conjugates, constituted by c(AmpLRGDL), an αVβ6 integrin-recognizing small cyclopeptide, and nintedanib, a tyrosine kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF) treatment. One of these conjugates recapitulates optimal in vitro antifibrotic properties of the two active units. The integrin ligand portion within the conjugate plays a role in inhibiting profibrotic stimuli, potentiating the nintedanib effect and favoring the selective uptake of the conjugate in cells overexpressing αVβ6 integrin. These results may open a new perspective on the development of dual conjugates in the targeted therapy of IPF

Body fatness and cancer - viewpoint of the IARC working group

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Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential

Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential