1,721,146 research outputs found

    Hepatitis C virus infection and mixed cryoglobulinemia

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    Hepatitis C virus (HCV) chronic infection is recognized as the major cause of mixed cryoglobulinemia (MC). Its persistence represents a continuous stimulus for host immune system with production of circulating immune complexes (ICs), one-third of them with cryoprecipitate property. Several factors contribute to the biological activities of ICs, many of which are not completely known. Among them, complement factors play a crucial role in the cold-insoluble ICs-mediated vasculitis, involving primarily small blood vessels in different tissues including skin, kidney, peripheral, and central nervous system. Liver represents the major target of HCV infection with inflammatory infiltrates, resembling secondary lymphoid follicles. Cytokine like CXCL13 contribute to B-cell homing in intraportal lymphoid aggregates, in which B-cell clonal selection may arise. B-cell clonal expansion starts as an antigen-driven event and expands towards indolent and malignant B-cell proliferation. Occurrence of intrahepatic Bcell clonalities correlates with extrahepatic clinical manifestations of HCV infection. In this context, cryoglobulinemic patients should be considered a peculiar HCV-infected population that needs a clinical multidisciplinary approach and more articulated therapeutic measures

    Precancerous colorectal lesions (Review).

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    Colorectal cancer (CRC) is a common and often lethal tumor. Over the last 25 years, remarkable progress has been made in understanding its biological and molecular features and in elucidating the steps involved in colon carcinogenesis. This, in turn, has led to a more rational and effective clinical approach to the treatment of CRC. While colorectal adenoma is the most frequent precancerous lesion, other potentially premalignant conditions, including chronic inflammatory bowel diseases and hereditary syndromes, such as familial adenomatous polyposis, Peutz-Jeghers syndrome and juvenile polyposis, involve different sites of the gastrointestinal tract with an overall incidence of less than 5%. In all such cases, disease recognition at an early stage is essential to devise suitable preventive cancer strategies. These topics are addressed in this review, along with the most important epidemiological, pathogenetic and clinical features that lead to malignant transformation. Novel biomarkers for early cancer prediction, detection, prognostic evolution, and the response to treatment are critically assessed as well. Continued improvements in our knowledge of the molecular basis of CRC and the transfer of this information into daily clinical practice will reduce the burden of this disease

    Anogenital lichen sclerosus et atrophicus lesions in a case series of cancer patients on immunotherapy

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    Lichenoid reactions are one of the most frequently observed toxicities with anticancer agents and, recently, a rapid emergence of immunotherapies in oncology has hastened the need to better characterize their unique toxicity profiles, particularly for less common skin toxicities, including anogenital lichen sclerosus et atrophicus (LSA). This case series describes four patients with advanced cancer (one melanoma, two lung cancers, and one kidney tumor) developing LSA lesions while receiving an immunotherapy. Medical records from 2017 to 2020 were retrospectively reviewed. Two patients received pembrolizumab, anti-programmed cell death-1 (PD-1), one nivolumab, anti-programmed cell death-1 (PD-1), and one ipilimumab, an immune checkpoint inhibitor. LSA emerged after a median of 3 months (range, 2–4 months) from starting immunotherapy. All LSA cases were grade 2. Three cases occurred on the penis and one case on the anus. All patients improved after a specific treatment for LSA, and no LSA-related antineoplastic treatment interruption/life-threatening condition were reported. To date, this is the first case series of LSA lesions associated with immunotherapy. Early LSA recognition and management is helpful in cancer patients on immunotherapy allowing a long survival and treatment response

    Targeted radioactive therapy for prostate cancer

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    Michael Hofman and colleagues report more frequent prostate-specific antigen response and prolonged progression-free survival with lutetium-177 [177Lu]Lu-PSMA-617, compared with cabazitaxel, in patients with metastatic castrationresistant prostate cancer with high prostate-specific membrane antigen (PSMA) expression

    Neuroendocrine differentiation in prostate cancer: Current and emerging therapy strategies

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    Neuroendocrine differentiation (NED) secondary to androgen deprivation therapy (ADT) may be frequent in various stages of prostate cancer (PC), particularly in castration-resistant PC (CRPC). NED generally involves more aggressive PC clinical behavior and an unfavorable prognosis. The identification of neuropeptides secreted by NE cells and of different proliferative and anti-apoptotic pathways has led to attention being focused on probable diagnostic targets and therapeutic options for a subtype of PC. Emerging evidence suggests that the acquisition of epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) phenotype are associated with the development of NED in PC, responsible for a complex interaction between ADT, the onset of CRPC and NED, in which EMT and CSC could play a central role, providing potential therapeutic targets. In this article, we review the pathogenetic, prognostic and predictive significance of NED in human PC, providing an insight into innovative agents capable of treating and perhaps preventing NED occurrence. © 2014 Elsevier Ireland Ltd

    New prognostic biomarkers in metastatic castration-resistant prostate cancer

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    Prostate cancer is one of the most frequent cancers in men and is a common cause of cancer-related death. Despite significant progress in the diagnosis and treatment of this tumor, patients who relapse after radical treatments inevitably develop metastatic disease. Patient stratification is therefore key in this type of cancer, and there is an urgent need for prognostic biomarkers that can define patients’ risk of cancer-related death. In the last 10 years, multiple prognostic factors have been identified and studied. Here, we review the literature available and discuss the most common aberrant genomic pathways in metastatic castration-resistant prostate cancer shown to have a prognostic relevance in this setting
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