Despite promising preclinical results, average response rates to anti-VEGF therapies, such as bevacizumab, are reduced for most cancers, while incurring in remarkable costs and side effects. Currently, there are no biomarkers available to select patients that can benefit from this therapy. Depending on the individual tumor, anti-VEGF therapies can either block or promote metastasis. In this context, an assay able to predict individual responses prior to treatment, including the impact on metastasis would prove of great value to guide treatment options. Here we show that zebrafish xenografts are able to reveal different responses to bevacizumab in just 4 days, evaluating not only individual tumor responses but also the impact on angiogenesis and micrometastasis. Importantly, we perform proof-of-concept experiments where clinical responses in patients were compared with their matching zebrafish Patient-Derived Xenografts-zAvatars, opening the possibility of using the zebrafish model to screen bevacizumab therapy in a personalized manner.
ObjectiveAlcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking.DesignTwo large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed.ResultsAge and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism.ConclusionsDespite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.
In this case, we believe that EBV triggered both HPS and tubulointerstitial nephritis. Steroid therapy successfully treated the inflammatory syndrome, allowing renal function recovery without compromising EBV infection resolution. .
RESUMOA doença secundária do pénis é uma situação clínica frequentemente associada a doença disseminada e as localizações mais comuns são os órgãos genito-urinários. O prognóstico é mau e as opções de tratamento incluem: penectomia; excisão local; radioterapia; quimioterapia; terapêutica de suporte. Apesar das várias terapêuticas existentes, nenhuma na literatura é apontada como superior às restantes. Os autores documentam o caso de um doente de 66 anos com metástase da glande peniana em contexto de adenocarcinoma do recto, diagnosticada dois anos após o tratamento da doença primária. O doente foi submetido a tratamento paliativo com radio-quimioterapia e permanece assintomático e livre de doença após um ano de seguimento. O follow-up apertado dos doentes com neoplasia do recto é mandatório. A radio-quimioterapia é uma abordagem válida, com bom controlo da doença e melhoria sintomática. Palavras-chave: Metástases; Neoplasias do Pénis/secundária; Neoplasias do Recto; Radioterapia. ABSTRACTSecondary malignancy of the penis is a rare clinical condition, often associated with disseminated genitourinary malignancies. The prognosis is poor and the treatment options include penectomy, local surgical excision, radiation therapy, chemotherapy and supportive therapy. Neither of these therapeutic options lead to superior treatment outcomes in the literature. The authors report the case of a 66 year-old man with a metastasis to the glans penis from a rectal adenocarcinoma, diagnosed two years after radical treatment for primary disease. The patient underwent palliative treatment with radiotherapy and chemotherapy, remaining asymptomatic and disease-free at one year follow-up. Close follow-up of patients with history of rectal adenocarcinoma is very important. Radiochemotherapy is a feasible and effective therapeutic option for penile metastasis, addressing both disease control and symptomatic improvement.
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