Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A role for iron in carcinogenesis is supported by evidence that iron metabolism proteins are modulated in cancer progression. To date, however, the expression of iron regulatory protein-2 (IRP2), which is known to regulate several iron metabolism proteins, has not been assessed in colorectal cancer. Expression of IRP2 was assessed by quantitative RT-PCR and immunohistochemistry in human colorectal cancer tissue. By interrogating The Cancer Genome Atlas (TCGA) database, expression of IRP2 and transferrin receptor-1 (TfR1) was assessed relative to common mutations that are known to occur in cancer. The impact of suppressing IRP2 on cellular iron metabolism was also determined by using siRNA and by using the MEK inhibitor trametinib. IRP2 was overexpressed in colorectal cancer compared to normal colonic mucosa and its expression was positively correlated with TfR1 expression. In addition, IRP2 expression was associated with mutations in BRAF. The MEK inhibitor trametinib suppressed IRP2 and this was associated with a suppression in TfR1 and the labile iron pool (LIP). Moreover, epidermal growth factor stimulation resulted in decreased ferritin expression and an increase in the LIP which were independent of IRP2. Results presented here suggest that ablating IRP2 provides a therapeutic platform for intervening in colorectal tumorigenesis.
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PMID:BRAF mutations are associated with increased iron regulatory protein-2 expression in colorectal tumorigenesis. 2828 25

Hemophagocytic lymphohistiocytosis (HLH) has been only rarely reported in patients with BRAF-mutated advanced melanoma treated with targeted therapies and never with first-line dabrafenib/trametinib combination thus far. Two patients treated with first-line dabrafenib and trametinib combination therapy for metastatic melanoma presented with sudden occurrence of fever, cytopenia, rhabdomyolysis, hepatic cytolysis, hypertriglyceridemia and very high ferritin levels after few weeks of treatment, associated with concomitant epstein-barr virus (EBV) reactivation in one patient. In both cases, drug-induced HLH was primarily considered owing to a high H-score and the absence of other etiology. Patients rapidly improved after treatment discontinuation associated with oral steroids in one patient and did not relapse after subsequent treatment resumption with a concurrent anti-BRAF/anti-MEK combination. In metastatic melanoma HLH may occur either spontaneously in the absence of any treatment as a paraneoplastic condition, related to an intercurrent infection or drug-induced mainly with various immunotherapy or with dabrafenib and trametinib following immunotherapy. However, such observations are scarce and these are the first cases of HLH occurring during first-line treatment with dabrafenib and trametinib in advanced melanoma to our knowledge. Pathomechanisms remain to be elucidated since triggering factors may encompass the treatment itself but also other significant actors including viral reactivation along with the underlying disease. The liability of treatment should be considered in cases of HLH occurring in patients with advanced melanoma successfully treated with a combined targeted therapy. A rechallenge with a concurrent anti-BRAF/anti-MEK can be proposed in this setting.
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PMID:Hemophagocytic lymphohistiocytosis in advanced melanoma treated with dabrafenib and trametinib combination: two cases. 3278 32

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening condition. HLH in infants and young children is usually inherited, which is then classified as primary HLH. Secondary HLH, in contrast, is caused by many different conditions such as infections, cancer or medication and affects mostly adults. HLH is a hyperinflammatory condition, which may mimic an acute septic shock. We report on a 68-year-old patient with malignant melanoma with lymph node metastases. Due to the lymphogenic progression, treatment was switched from nivolumab to dabrafenib and trametinib. Twenty-one days after initiation of BRAF/MEK inhibitor therapy, the patient presented to our emergency department with clinical signs of infection such as fever and fatigue. Laboratory tests showed excessive inflammation levels without identifying an underlying pathogen. Two days later, the patient developed an increasing pancytopenia. After extending the diagnosis, we found very high ferritin levels, hypertriglyceridemia, hypofibrinogenemia and a soluble CD25 receptor. Based on the laboratory results, prolonged fever and splenomegaly, we were able to diagnose HLH as the underlying condition. We immediately initiated treatment with intravenous prednisone, which remarkably improved the clinical symptoms. After full recovery, we reinitiated anti-tumor treatment with vemurafenib and cobimetinib, which was tolerated without side effects. Due to the relatively nonspecific nature of the clinical signs and symptoms and the significant overlap with other diseases such as sepsis, the diagnosis of HLH is often delayed. This explains, in part, the high morbidity and mortality rate. Our case shows that early treatment with steroids is effective. However, much work remains in order to raise awareness and improve the understanding of the pathophysiology of this condition.
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PMID:Hemophagocytic lymphohistiocytosis of a melanoma patient under BRAF/MEK-inhibitor therapy following anti-PD1 inhibitor treatment: a case report and review to the literature. 3323 45