In a double blind randomized study, the bisphosphonate drug Pamidronate (Aredia) significantly protected Durie-Salmon stage III multiple myeloma patients from osteolytic bone disease. In the patient sub-group on salvage chemotherapy. Pamidronate treatment was also significantly associated with prolonged survival. To test if this drug could induce direct antitumor effects, we exposed myeloma cells to increasing concentrations of Pamidronate or a more potent bisphosphonate, Zoledronate. A concentration-and time-dependent cytotoxic effect was detected on four of five myeloma cell lines as well as three specimens obtained directly from myeloma patients. Zoledronate-induced cytotoxicity was significantly greater than that of Pamidronate. Cytotoxicity could not be explained by bisphosphonate-induced chelation of extracellular calcium or secondary decrease in production of the myeloma growth factor interleukin-6. Morphological examination, DNA electrophoresis and cell cycle analysis indicated that the bisphosphonate-induced cytotoxic effect consisted of a combination of cytostasis and apoptotic myeloma cell death. Enforced expression of BCL-2 protected against the apoptotic death but not against cytostasis. Most cytotoxic effects were seen between 10 and 100 M of drug. The results suggest a possible direct anti-tumor effect in myeloma patients treated with bisphosphonates which may participate in their significantly increased survival. This hypothesis should now be further tested in clinical trials.

Autoimmune diseases (such as rheumatoid arthritis, asthma, autoimmune bowel disease) are a complex disease. Improper activation of the immune system or imbalance of immune cells can cause the immune system to transform into a proinflammatory state, leading to autoimmune pathological damage. Recent studies have shown that autoimmune diseases are closely related to CD4+ T helper cells (Th). The original CD4 T cells will differentiate into different T helper (Th) subgroups after activation. According to their cytokines, the types of Th cells are different to produce lineage-specific cytokines, which play a role in autoimmune homeostasis. When Th differentiation and its cytokines are not regulated, it will induce autoimmune inflammation. Autoimmune bowel disease (IBD) is an autoimmune disease of unknown cause. Current research shows that its pathogenesis is closely related to Th17 cells. This article reviews the role and plasticity of the upstream and downstream cytokines and signaling pathways of Th17 cells in the occurrence and development of autoimmune bowel disease and summarizes the new progress of IBD immunotherapy.

Colorectal cancer (CRC) is one of the most common types of malignancy worldwide. Distant metastasis is a key cause of CRC-associated mortality. MEIS2 has been identified to be dysregulated in several types of human cancer. However, the mechanisms underlying the regulatory role of MEIS2 in CRC metastasis remain largely unknown. For the first time, the present study demonstrated that MEIS2 serves a role as a promoter of metastasis in CRC. In vivo and in vitro experiments revealed that knockdown of MEIS2 significantly suppressed CRC migration, invasion and the epithelial-mesenchymal transition. Furthermore, microarray and bioinformatics analyses were performed to investigate the underlying mechanisms of MEIS2 in the regulation of CRC metastasis. Additionally, it was identified that a high expression of MEIS2 was significantly associated with a shorter overall survival time for patients with CRC. The present study demonstrated that MEIS2 may serve as a novel biomarker for CRC.

Sorafenib a multi-target tyrosine kinase inhibitor, is the first-line drug for treating advanced hepatocellular carcinoma (HCC). Mechanistically, it suppresses tumor angiogenesis, cell proliferation and promotes apoptosis. Although sorafenib effectively prolongs median survival rates of patients with advanced HCC, its efficacy is limited by drug resistance in some patients. In HCC, this resistance is attributed to multiple complex mechanisms. Previous clinical data has shown that HIFs expression is a predictor of poor prognosis, with further evidence demonstrating that a combination of sorafenib and HIFs-targeted therapy or HIFs inhibitors can overcome HCC sorafenib resistance. Here, we describe the molecular mechanism underlying sorafenib resistance in HCC patients, and highlight the impact of hypoxia microenvironment on sorafenib resistance.

MicroRNAs (miRNAs/miRs), non-coding single-stranded RNAs of length 18-24 nucleotides, can modulate gene expression through post-transcriptional control. As such, they can influence tumor proliferation, apoptosis, invasion, metastasis as well as chemotherapy resistance by regulating certain downstream genes. In this context, miR-200b-3p, one particular member of the miR-200 family, possesses the ability to suppress tumor progression. However, many studies have suggested that, in certain cases, this miRNA may also promote the development of some tumors due to differences in the microenvironments and molecular backgrounds of different cancers. This review summarizes previous studies on the involvement of miR-200b-3p in tumors, including the underlying mechanism. Contents 1. Introduction 2. Mechanism of action of miR-200b-3p in cancer 3. miR-200b-3p function is dependent on cancer type 4. Mechanism of miR-200b-3p regulation 5. Conclusion

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Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and is a highly heterogeneous and fatal disease. At present, the main method of treatment of AML is chemotherapy, but patients who relapse often develop resistance and are not sensitive to chemotherapy. Chinese medicine network pharmacology can provide new ideas about improving AML resistance.Methods: The gene expression data of relapsed drug-resistant AML and primary AML are from Gene Expression Omnibus (GEO) database. Based on the network pharmacology of traditional Chinese medicine, the effective components and target genes of Jiedu Huayu Decoction were analyzed. we performed Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) analyses, Protein-protein interaction (PPI) network and construction on overlapping genes. We will perform prognostic analysis and gene correlation analysis of overlapping genes in GEPIA. The binding energy between the differential gene and the active ingredient of the drug was studied by molecular docking.Results: We found that quercetin, the active ingredient in Jiedu Huayu Decoction, can target CXCL10, thereby improving AML resistance.Conclusions: In this study, we found that quercetin improves drug resistance in acute myeloid leukemia by targeting CXCL10 based on the GEO database and the network pharmacology study of Chinese medicine.

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