A simple and efficient method for the synthesis of pyrimido[1,2- a ]benzimidazoles and pyrimido[1,2- b ]indazoles by a three-component [3 + 2 + 1] annulation catalyzed by FeCl ₃ has been established.

Background: Tumor-associated calcium signal transducer 2 (TROP2) is over expressed in various kinds of human cancers and plays important roles in the proliferation, invasion and metastasis of tumor cells. However, the expression and molecular mechanism of TROP2 in thyroid papillary carcinoma (PTC) are unclear.

Previous studies reported the early diagnostic values of plasma Epstein-Barr virus (EBV)-DNA. The present study aimed to assess the relationship between the concentration of plasma EBV-DNA and the number of CD8⁺PD-1⁺(programmed cell death-1,PD-1) and regulatory T (Treg) cells in patients with nasopharyngeal carcinoma (NPC) who were treated with intensity-modulated radiotherapy (IMRT). This study included 37 patients treated with IMRT. Peripheral blood samples were collected two times for each patient, before radiation therapy and 1 week after the treatment. Further, the numbers of CD4⁺, Treg, CD8⁺, and CD8⁺PD1⁺ cells were determined by flow cytometry. The changes after IMRT were determined by comparing the numbers of neutrophils, lymphocytes, CD4⁺, Treg, CD8⁺, CD8⁺PD1⁺ cells, and the concentration of plasma EBV-DNA between pretreatment and post-treatment groups. IMRT could reduce the expression level of PD-1 and the number of Treg cells. The concentration of plasma EBV-DNA and the expression level of CD8⁺PD-1⁺ were closely associated with the occurrence and development of NPC. Thus, EBV-DNA can be used as an important marker for early diagnosis, and IMRT can strongly reduce the copies of EBV-DNA. This study showed that IMRT could reverse T-cell exhaustion and reduce the copies of EBV-DNA. In clinical practice, plasma EBV-DNA is a sensitive biomarker for diagnosis, prognosis, and evaluation of clinical efficacy.

Outcomes of icotinib combined with concurrent chemoradiotherapy in locally advanced cervical cancer

Objectives: Dual specificity phosphatase 1 (DUSP1) is high-expressed in various cancers and plays an important role in the cellular response to agents that damage DNA. We aimed to investigate the expressions and mechanisms of DUSP1 signaling pathway regulating cytarabine (Ara-C) resistance in acute myeloid leukemia (AML). Methods: Immunohistochemistry was performed on bone marrow biopsy specimens from AML and controls to explore the expression of DUSP1. Western blot and Q-PCR were used to detect the protein and mRNA expression levels. MTT assay was used to detect the proliferation of cells. Cell apoptosis was detected by flow cytometry. The immune protein-protein interaction (PPI) network of DUSP1 was analyzed in the platform of Pathway Commons, and immune infiltration analysis was used to study the immune microenvironment of AML. Results: We found that the expression levels of DUSP1 in AML patients exceeded that in controls. Survival analysis in public datasets showed that AML patients with higher levels of DUSP1 had poor clinical outcomes. Further public data analysis indicated that DUSP1 was overexpressed in NRAS mutated AML. DUSP1 knockdown by siRNA could sensitize AML cells to Ara-C treatments. The phosphorylation level of mitogen-activated protein kinase (MAPK) pathway was significantly elevated in DUSP1 down-regulated NRAS G13D mutated AML cells. The PPI analysis showed DUSP1 correlated with immune gene CREB1 and CXCL8 in NRAS mutated AML. We also revealed a correlation between tumor-infiltrating immune cells in RAS mutated AML microenvironment. Conclusion: Our findings suggest that DUSP1 signaling pathways may regulate Ara-C sensitivity in AML.