- Paclitaxel with or without trametinib or pazopanib in advanced wild-type BRAF Melanoma (PACMEL): a multicentre, open-label, randomised, controlled phase II trial. [Journal Article]
- AOAnn Oncol 2018 Nov 14
- CONCLUSIONS: In this phase II trial, adding trametinib to paclitaxel chemotherapy for BRAF-wt melanoma improved PFS and substantially increased ORR but did not impact OS. This study was registered with the EU Clinical Trials Register, number EudraCT 2011-002545-35, and with the ISRCTN registry, number 43327231.
- Protein denaturation caused by heat inactivation detrimentally affects biomolecular corona formation and cellular uptake. [Journal Article]
- NNanoscale 2018 Nov 14
- Adsorption of blood proteins to the surface of nanocarriers is known to be the critical factor influencing cellular interactions and eventually determining the successful application of nanocarriers ...
Adsorption of blood proteins to the surface of nanocarriers is known to be the critical factor influencing cellular interactions and eventually determining the successful application of nanocarriers as drug carriers in vivo. There is an increasing number of reports summarizing large data sets of all identified corona proteins. However, to date our knowledge about the multiple mechanisms mediating interactions between proteins and nanocarriers is still limited. In this study, we investigate the influence of protein structure on the adsorption process and focus on the effect of heat inactivation of serum and plasma, which is a common cell culture procedure used to inactivate the complement system. As in general routine lab procedure, heat inactivation was performed at 56 °C for 30 min in order to denature heat labile proteins. When nanocarriers were exposed to native versus heat inactivated serum, we saw that the cellular uptake by macrophages was significantly affected. These results were then correlated with an altered corona composition that depended on the treatment of the protein source. In summary, we were able to prove that the protein structure is one of the key parameters determining protein corona formation.
- Vemurafenib-induced histiocytoid neutrophilic panniculitis simulating myeloid leukaemia cutis. [Journal Article]
- CBCancer Biol Ther 2018 Nov 14; :1-3
- Neutrophilic panniculitis is an infrequent but characteristic adverse event under therapy with BRAF inhibitors (BRAFi). Since the approval of vemurafenib for treatment of metastatic melanoma in 2011,...
Neutrophilic panniculitis is an infrequent but characteristic adverse event under therapy with BRAF inhibitors (BRAFi). Since the approval of vemurafenib for treatment of metastatic melanoma in 2011, only two cases of neutrophilic panniculitis in malignancies other than melanoma have been published. Histiocytoid infiltrates of immature neutrophils resembling histiocytes or myelocytes have been reported in Sweet's syndrome and rarely in other neutrophilic dermatoses. We describe a novel variant of neutrophilic panniculitis with histiocytoid myeloid cells in an early lesion from a patient treated with vemurafenib in combination with an anti-EGFR (epidermal growth factor receptor) agent for metastatic colon carcinoma, three weeks after initiation of therapy. Recognizing this variant of panniculitis associated to BRAFi can avoid misinterpretation of the atypical subcutaneous infiltrate as myeloid leukaemia cutis.
- Socioeconomic Status and the Prevalence of Skin and Atopic Diseases in Five European Countries. [Journal Article]
- ADActa Derm Venereol 2018 Nov 14
- The aim of this study was to investigate the association between socioeconomic status and the prevalence of self-reported skin and atopic diseases in the general population of 5 European countries. A...
The aim of this study was to investigate the association between socioeconomic status and the prevalence of self-reported skin and atopic diseases in the general population of 5 European countries. A random sample was drawn from the general population aged 18-74 years, based on electoral precincts. Socioeconomic status was estimated by combining net household income with the highest education of respondents. A total of 7,904 subjects were included in this analysis. The lifetime prevalence of "contact dermatitis" ranged from 13.1% (95% confidence interval (95% CI 11.8-14.4%) in subjects with low socioeconomic status, to 19.1% (95% CI 17.5-20.8%) in those with high socio-economic status. In younger subjects skin cancer was more prevalent in the middle or high socioeconomic status groups compared with the low socioeconomic status group (odds ratio 2.4; 95% CI 1.4-4.3); however, this effect was not found in elderly subjects. The lifetime prevalence for at least 1 atopic disease was 61.2% (95% CI 59.4-63.0%) in the low and 82.8% (95% CI 81.1-84.3%) in the high socioeconomic status group. Individuals with middle or high socioeconomic status reported an overall higher prevalence of skin and atopic diseases compared with those with low socioeconomic status. These findings may reflect differences in reporting, which are likely to result in an underdiagnoses, especially for skin cancer in the younger age groups with low socioeconomic status.
- Topical Application of a Vitamin A Derivative and Its Combination With Non-ablative Fractional Laser Potentiates Cutaneous Influenza Vaccination. [Journal Article]
- FMFront Microbiol 2018; 9:2570
- Skin contains a large number of antigen presenting cells, making intradermal (ID) injection one of the most effective ways for vaccine administration. However, although current adjuvants may cause se...
Skin contains a large number of antigen presenting cells, making intradermal (ID) injection one of the most effective ways for vaccine administration. However, although current adjuvants may cause severe local reactions and inflammations in the skin, no adjuvant has been approved for ID vaccination so far. Here, we report that topical application of all-trans retinoic acid (ATRA), a vitamin A derivative produced in the human body, augmented cutaneous influenza vaccination. The adjuvant effects were evaluated in a murine vaccination/challenge model by using A/California/07/2009 pandemic vaccine (09V) or a seasonal influenza vaccine (SIV). ATRA drove a Th2-biased immune response, as demonstrated by profoundly elevated IgG1 titer rather than IgG2 titer. Combining ATRA with a non-ablative fractional laser (NAFL), which represents a new category of vaccine adjuvant utilizing physical stimuli to induce self-immune stimulators, further enhanced the efficacy of influenza vaccines with a more balanced Th1/Th2 immune response. The dual adjuvant strengthened cross-reactive immune responses against both homogenous and heterogeneous influenza viral strains. Analysis of gene expression profile showed that ATRA/NAFL stimulated upregulation of cytosolic nucleic acid sensors and their downstream factors, leading to a synergistic elevation of type I interferon expression. Consistent with this finding, knocking out IRF3 or IRF7, two key downstream regulatory factors in most nucleic acid sensing pathways, resulted in a significant decrease in the adjuvant effect of ATRA/NAFL. Thus, our study demonstrates that the self molecule ATRA could boost cutaneous influenza vaccination either alone or ideally in combination with NAFL.
- Stathmin is a potential therapeutic target but not a prognostic marker in melanoma: an immunohistochemical study of 323 melanocytic lesions. [Journal Article]
- MRMelanoma Res 2018 Nov 12
- In several solid tumors, an increased stathmin expression is associated with both poor prognosis and resistance to certain chemotherapy types. However, the data regarding melanocytic lesions are very...
In several solid tumors, an increased stathmin expression is associated with both poor prognosis and resistance to certain chemotherapy types. However, the data regarding melanocytic lesions are very limited. The goals of our study are as follows: the assessment of stathmin expression in benign and malignant melanocytic lesions, and the significance of its expression for the differential diagnostics between benign and malignant lesions; the analysis of the prognostic significance of stathmin expression in melanoma; and the evaluation of stathmin expression in melanoma and melanoma metastases with respect to possible therapeutic targeting. Immunohistochemical analysis of stathmin expression was done in 323 melanocytic lesions, including 205 primary cutaneous melanomas, 60 melanoma metastases, and 58 melanocytic nevi. Stathmin expression was found in all analyzed groups of melanocytic lesions. Using the H-scoring system, the observed intensity of expression was as follows: melanocytic nevi: 146.1 (mean) and 150 (median); melanomas: 116.7 (mean) and 110 (median); and melanoma metastases: 136.8 (mean) and 140 (median). The stathmin expression was significantly lower in the cohort of primary melanomas when compared with metastases and nevi (P=0.001). The stathmin expression showed no prognostic significance. The high stathmin expression in melanoma suggests that stathmin might be a promising marker for therapeutic targeting in ongoing clinical trials. Compared with several other solid tumors, stathmin expression in melanoma showed no prognostic significance. The potential use of stathmin expression in differential diagnostics is limited by its common expression, and despite the statistically significant differences between nevi and melanoma, it may not be used in this setting.
- Tattoos among elite football players during the 2018 FIFA World Cup Russia. [Journal Article]
- JEJ Eur Acad Dermatol Venereol 2018 Nov 13
- Currently 10 to 30% of the general population has tattoos. Professional athletes harbor visible tattoos during sports events and advertisement. Motivations for tattoos may include body embellishment,...
Currently 10 to 30% of the general population has tattoos. Professional athletes harbor visible tattoos during sports events and advertisement. Motivations for tattoos may include body embellishment, expression of personal values or group affiliation. Tattoos may bolster ego, be the expression of physical strength and of traits of aggression and rebelliousness. We wondered whether being tattooed reflects players' performance and discipline. We investigated this hypothesis among elite football players during the 2018 FIFA World Cup. This article is protected by copyright. All rights reserved.
- Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial. [Journal Article]
- JOJAMA Oncol 2018 Oct 25
- CONCLUSIONS: Nivolumab led to improved 3-year overall survival vs dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma.
- Association of APOA5 and APOC3 Genetic Polymorphisms With Severity of Hypertriglyceridemia in Patients With Cutaneous T-Cell Lymphoma Treated With Bexarotene. [Journal Article]
- JDJAMA Dermatol 2018 Oct 24
- CONCLUSIONS: These results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.
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- Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. [Journal Article]
- NMedNat Med 2018 Nov 12
- The recent successes of immunotherapy have shifted the paradigm in cancer treatment, but because only a percentage of patients are responsive to immunotherapy, it is imperative to identify factors im...
The recent successes of immunotherapy have shifted the paradigm in cancer treatment, but because only a percentage of patients are responsive to immunotherapy, it is imperative to identify factors impacting outcome. Obesity is reaching pandemic proportions and is a major risk factor for certain malignancies, but the impact of obesity on immune responses, in general and in cancer immunotherapy, is poorly understood. Here, we demonstrate, across multiple species and tumor models, that obesity results in increased immune aging, tumor progression and PD-1-mediated T cell dysfunction which is driven, at least in part, by leptin. However, obesity is also associated with increased efficacy of PD-1/PD-L1 blockade in both tumor-bearing mice and clinical cancer patients. These findings advance our understanding of obesity-induced immune dysfunction and its consequences in cancer and highlight obesity as a biomarker for some cancer immunotherapies. These data indicate a paradoxical impact of obesity on cancer. There is heightened immune dysfunction and tumor progression but also greater anti-tumor efficacy and survival after checkpoint blockade which directly targets some of the pathways activated in obesity.