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2.
Cancer Immunol Immunother ; 68(12): 1921-1934, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637475

RESUMO

Blockade of the PD-1/PD-L1 pathway with targeted monoclonal antibodies has demonstrated encouraging anti-tumour activity in multiple cancer types. We present the case of a patient with BRAF-negative stage IVC anaplastic thyroid cancer (ATC) treated with the anti-PD-1 monoclonal antibody, pembrolizumab, following radiographic progression on chemoradiation. Blood samples were collected prior to and at four time points during treatment with pembrolizumab. Mass cytometry was used to determine expression of relevant biomarkers by peripheral blood mononuclear cells. Faecal samples were collected at baseline and 4 weeks following treatment initiation; taxonomic profiling using 16S ribosomal RNA (rRNA) gene sequencing was performed. Following treatment, a marked expansion in CD20+ B cell, CD16+ CD56lo NK cell and CD45RO+ CCR7+ central memory CD4+ T-cell populations was observed in the peripheral blood. Proportions of cells expressing the co-receptors TIGIT, OX40 and CD86 also increased during treatment. A high abundance of bacteria of the order Bacteroidales, specifically from the Bacteroidaceae and Rikenellaceae families, was identified in the faecal microbiota. Moreover, the patient's microbiome was enriched in Clostridiales order members Ruminococcaceae, Veillonellaceae and Lachnospiraceae. Alpha diversity of the gut microbiome was significantly higher following initiation of checkpoint therapy as assessed by the Shannon and Simpson index. Our results suggest that treatment with pembrolizumab promotes expansion of T-, B- and NK cell populations in the peripheral blood at the time of tumour regression and have the potential to be implemented as predictive biomarkers in the context of checkpoint blockade therapy. Larger studies to confirm these findings are warranted.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Fezes/microbiologia , Células Matadoras Naturais/imunologia , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Bacteroides , Humanos , Masculino , Microbiota , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , RNA Ribossômico 16S/análise
3.
F1000Res ; 2: 277, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-25075283

RESUMO

Chronic mesenteric ischemia (CMI) is a condition characterized by inadequate blood flow to the bowel resulting from stenosis of one or more of the three mesenteric arteries. Fibromuscular dysplasia is the most common cause in children and young adults; whereas atherosclerosis is the most common cause in the elderly. Treatment is mandatory in symptomatic patients, because it may lead to malnutrition, bowel infarction or even death.Herein, we present the case of a 14-year old male, diagnosed with CMI who underwent percutaneous balloon angioplasty (PTA) followed by stent placement with immediate positive results.

4.
Clin Kidney J ; 5(3): 234-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26069773

RESUMO

Granulomatous interstitial nephritis (GIN) is an uncommon cause of renal failure, which may be caused by drugs. Levetiracetam is an increasingly used anti-epileptic medication that is not known to cause renal toxicity in adults. To our knowledge, levetiracetam has not previously been reported as a cause of GIN. We report the case of a 69-year-old woman who developed haemodialysis-requiring acute renal failure after commencement of treatment with levetiracetam, which was shown to be GIN by renal biopsy. She made a complete recovery with cessation of levetiracetam and treatment with steroids.

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