Iron is essential to organisms, the liver plays a vital role in its storage. Under pathological conditions, iron uptake by the intestine or hepatocytes increases, allowing excess iron to accumulate in liver cells. When the expression of hepcidin is abnormal, iron homeostasis in humans cannot be regulated, and resulting in iron overload. Hepcidin also regulates the release of iron from siderophores, thereby regulating the concentration of iron in plasma. Important factors related to hepcidin and systemic iron homeostasis include plasma iron concentration, body iron storage, infection, inflammation, and erythropoietin. This review summarizes the mechanism and regulation of iron overload caused by hepcidin, as well as related liver diseases caused by iron overload and treatment.
Background Great progress has been made in understanding the epigenetic regulation of the immune response. However, the influence of RNA N6-methyladenosine (m6A) regulation on the tumor microenvironment (TME) of melanoma is still unknown. Methods We comprehensively evaluated 790 samples of melanoma based on 21 m6A regulator genes and associated these regulators with infiltration characteristics in the TME. We used the m6A score to assess the m6A modification pattern and response to immunotherapy. Results Three distinct m6A modification patterns were identified among 790 melanoma samples, and the patterns correspond to different clinical outcomes. The characteristics of the three modification patterns mainly included three phenotypes: immune inflamed, immune desert and immune excluded. We found that the m6A modification pattern could be applied to assess genetic variations, immune infiltration and prognosis. Based on the m6A score, melanoma patients could be classified into high and low m6A score subgroups. Stromal activation was observed in the high m6A score subgroup, indicating the immune-excluded phenotype. Patients in the low m6A score subgroup had prolonged overall survival and enhanced immune infiltration. Further analysis showed that the low m6A score correlated with a high tumor mutation burden, and better response to anti-PD-1/PD-L1 therapy, which indicated that the low m6A score subgroup might have therapeutic advantages and better clinical effects. Conclusion Our research revealed that m6A modification plays an essential role in shaping TME complexity and diversity of melanoma. Evaluation of m6A modification patterns could provide more information on TME infiltration characteristics and new ideas for immunotherapies.
Objective To describe myeloid sarcoma (MS) that mimic gynecological tumors and provide guidelines for improving the diagnosis and treatment of patients. Methods This case series study retrospectively analyzed the clinicopathological characteristics and oncological outcomes of female patients who were histologically diagnosed with MS after initially presenting with reproductive-system tumors at the Peking Union Medical College Hospital between January 2000 and March 2022. Results There were eight cases in which MS mimicked cervical cancer, ovarian cancer, or hysteromyoma. Six patients had isolated MS, and the other two had acute myeloid leukemia (AML)-M2. The average age was 39.00 ± 14.26. They each sought advice from a gynecological oncologist at the initial visit, complaining of irregular bleeding (3/8), low abdominal pain (3/8), dysmenorrhea (1/8), or an accidentally found mass (1/8). CT/MRI exams revealed that the average tumor size reached 5.65 ± 2.35 cm, with 50% of the tumors being larger than 8 cm. The final diagnoses were confirmed by biopsy (2/8) or postoperative pathology (6/8); the most frequent positive immunohistochemical markers were Ki-67 (60–90%), MPO (100%), LCA (62.5%), CD43 (62.5%), CD117 (62.5%), CD99 (50%), vimentin (37.5%), and lysozyme (25%). MLL/AF9 gene fusions and CEBPA, JAK2, NRAS, and FLT3-TKD mutations were found in the patients. Six (75%) of the patients showed a complete response after upfront treatment using chemotherapy + surgery and experienced no recurrence during follow-up. The overall survival (OS) rate was 72.9%, and the 5-year OS rate was 72.9% (95%CI: 0.4056–1.000). The median OS was 26 months (range: 3–82). Conclusion For patients with isolated MS, treatment by chemotherapy and surgery are radical procedure, and initial treatment using chemotherapy alone should be considered for MS with synchronous intramedullary AML. Poor response to chemotherapy, short interval to leukemia occurrence, and heavy tumor burden (> 10 cm) could indicate a poor prognosis for patients with MS.
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