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1.
Int J Mol Sci ; 21(18)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32962135

RESUMO

B cell-depleting therapies have recently proven to be clinically highly successful in the treatment of multiple sclerosis (MS). This study aimed to determine the effects of the novel type II anti-human CD20 (huCD20) monoclonal antibody (mAb) obinutuzumab (OBZ) on spinal cord degeneration in a B cell-dependent mouse model of MS. Double transgenic huCD20xHIGR3 (CD20dbtg) mice, which express human CD20, were immunised with the myelin fusion protein MP4 to induce experimental autoimmune encephalomyelitis (EAE). Both light and electron microscopy were used to assess myelination and axonal pathology in mice treated with OBZ during chronic EAE. Furthermore, the effects of the already established murine anti-CD20 antibody 18B12 were assessed in C57BL/6 wild-type (wt) mice. In both models (18B12/wt and OBZ/CD20dbtg) anti-CD20 treatment significantly diminished the extent of spinal cord pathology. While 18B12 treatment mainly reduced the extent of axonal pathology, a significant decrease in demyelination and increase in remyelination were additionally observed in OBZ-treated mice. Hence, the data suggest that OBZ could have neuroprotective effects on the CNS, setting the drug apart from the currently available type I anti-CD20 antibodies.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antígenos CD20/imunologia , Antineoplásicos Imunológicos/administração & dosagem , Linfócitos B/imunologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Animais , Anticorpos Monoclonais/administração & dosagem , Antígenos CD20/metabolismo , Axônios/efeitos dos fármacos , Axônios/imunologia , Axônios/patologia , Linfócitos B/patologia , Doença Crônica/tratamento farmacológico , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Eletrônica , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Esclerose Múltipla Crônica Progressiva/imunologia , Esclerose Múltipla Crônica Progressiva/patologia , Proteína Básica da Mielina/imunologia , Proteína Proteolipídica de Mielina/imunologia , Proteínas de Neurofilamentos/sangue , Proteínas Recombinantes de Fusão/imunologia , Medula Espinal/imunologia , Medula Espinal/patologia , Medula Espinal/ultraestrutura
2.
J Clin Med ; 13(10)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38792526

RESUMO

Skin cancer is a global and increasingly prevalent issue, causing significant individual and economic damage. UV filters in sunscreens play a major role in mitigating the risks that solar ultraviolet ra-diation poses to the human organism. While empirically effective, multiple adverse effects of these compounds are discussed in the media and in scientific research. UV filters are blamed for the dis-ruption of endocrine processes and vitamin D synthesis, damaging effects on the environment, induction of acne and neurotoxic and carcinogenic effects. Some of these allegations are based on scientific facts while others are simply arbitrary. This is especially dangerous considering the risks of exposing unprotected skin to the sun. In summary, UV filters approved by the respective governing bodies are safe for human use and their proven skin cancer-preventing properties make them in-dispensable for sensible sun protection habits. Nonetheless, compounds like octocrylene and ben-zophenone-3 that are linked to the harming of marine ecosystems could be omitted from skin care regimens in favor of the myriad of non-toxic UV filters.

3.
Curr Oncol ; 29(5): 2909-2919, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35621627

RESUMO

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive Non-Hodgkin lymphoma (NHL) characterised by the presence of neoplastic lymphoid cells within small- and medium-sized blood vessels. According to the clinical presentation, the current WHO classification distinguishes the 'classic' (formerly 'Western') from a hemophagocytic syndrome-associated (formerly 'Asian') variant. A third 'cutaneous' variant has been proposed, characterised by a good prognosis and unique clinical features. While laboratory findings can hint at diagnosis, symptoms are rather nonspecific, and deep skin biopsy supported by further measures such as bone marrow aspiration and positron emission tomography-computed tomography scanning is needed to make a definite diagnosis. Treatment is comprised of anthracycline-based chemotherapy supplemented with rituximab and central nervous system prophylaxis. While there are various prognostic models for NHL, only one is specific to IVLBCL, which does not sufficiently represent some patient groups, especially regarding the lack of differentiation within the patient collective with skin involvement. This underlines the necessity for the establishment of further prognostic models in particular for IVLBCL patients with cutaneous manifestations.


Assuntos
Linfoma Difuso de Grandes Células B , Neoplasias Cutâneas , Biópsia , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prognóstico , Rituximab/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-33578996

RESUMO

Early detection of melanoma is critical to reduce the mortality and morbidity rates of this tumor. Total body photography (TBP) may aid in the early detection of melanoma. To summarize the current evidence on TBP for the early detection of melanoma, we performed a systematic literature search in Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for eligible records up to 6th August 2020. Outcomes of interest included melanoma incidence, incisional and excisional biopsy rates, as well as the Breslow's index of detected tumors. Results from individual studies were described qualitatively. The risks of bias and applicability of the included studies was assessed using the QUADAS-2 checklist. In total, 14 studies published between 1997 and 2020 with an overall sample size of n = 12082 (range 100-4692) were included in the qualitative analysis. Individuals undergoing TBP showed a trend towards a lower Breslow's thickness and a higher proportion of in situ melanomas compared to those without TBP. The number needed to excise one melanoma varied from 3:1 to 14.3:1 and was better for lesions that arose de novo than for tracked ones. The included studies were judged to be of unclear methodological concern with specific deficiencies in the domains "flow and timing" and "reference standard". The use of TBP can improve the early detection of melanoma in high-risk populations. Future studies are warranted to reduce the heterogeneity of phenotypic risk factor definition and the technical implementation of TBP. Artificial intelligence-assisted analysis of images derived from 3-D TBP systems and digital dermoscopy may further improve the early detection of melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Inteligência Artificial , Dermoscopia , Humanos , Melanoma/diagnóstico , Fotografação , Sensibilidade e Especificidade , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia
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