Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), among others, play a major role in the pathophysiology of anemia in the cancer patient not only through complex mechanisms of the purely inflammatory situation but also through genetic regulatory aspects of erythropoiesis via GATA-1 and GATA-2, and other factors. In terms of therapy, iron is used more and more; the late side effects of transfusions are not really understood and the recent controversy regarding erythropoietin usage has resulted in regulatory authorities and scientific societies providing several recommendations and guidelines. These various aspects are addressed herein.
Evading apoptosis is a hallmark of B-cell chronic lymphocytic leukemia (CLL) cells and an obstacle to current chemotherapeutic approaches. Inhibiting histone deacetylase (HDAC) has emerged as a promising strategy to induce cell death in malignant cells. We have previously reported that the HDAC inhibitor MGCD0103 induces CLL cell death by activating the intrinsic pathway of apoptosis. Here, we show that MGCD0103 decreases the autophagic flux in primary CLL cells. Activation of the PI3K/AKT/mTOR pathway, together with the activation of caspases, and to a minor extent CAPN1, resulting in cleavage of autophagy components, were involved in MGCD0103-mediated inhibition of autophagy. In addition, MGCD0103 directly modulated the expression of critical autophagy genes at the transcriptional level that may contribute to autophagy impairment. Besides, we demonstrate that autophagy is a pro-survival mechanism in CLL whose disruption potentiates cell death induced by anticancer molecules including HDAC and cyclin-dependent kinase inhibitors. In particular, our data highlight the therapeutic potential of MGCD0103 as not only an inducer of apoptosis but also an autophagy suppressor in both combination regimens with molecules like flavopiridol, known to induce protective autophagy in CLL cells, or as an alternative to circumvent undesired immunomodulatory effects seen in the clinic with conventional autophagy inhibitors.
Primary aortic thrombosis remains a rare entity that can be defined as clotting of the vessel without any obvious atheromatous lesion. Cancer chemotherapy, cocaine intake, essential thrombocythemia, some hypercoagulable states, heparin-induced thrombocytopenia, inflammatory disease of the digestive tract and acute pancreatitis are, beside some cases of rather unknown etiology, the causes of primary aortic thrombosis. Intravenous contrast-enhanced multislice CT, which is widely available, noninvasive and affordable in terms of cost, is the imaging modality of choice for the investigation of primary aortic thrombosis and the assessment of potential complications. Three cases due to chemotherapy, antiphospholipid syndrome and acute pancreatitis are reported.
Most biological anticancer agents are currently developed in the setting of relapsed or refractory disease. Some of them however are under development or are already used in first-line therapy wherein they have improved the prognosis of haematology patients.
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