We identified nocodazole as a potent antimyeloma drug from a drug screening library provided by the Multiple Myeloma Research Foundation. Nocodazole is a benzimidazole that was originally categorized as a broad-spectrum anthelmintic drug with antineoplastic properties. We found that nocodazole inhibited growth and induced apoptosis of primary and multiresistant multiple myeloma cells cultured alone and in the presence of bone marrow stromal cells. Nocodazole caused cell-cycle prophase and prometaphase arrest accompanied by microtubular network disarray. Signaling studies indicated that increased expression of Bim protein and reduced X-linked inhibitor of apoptosis protein and Mcl-1_L levels were involved in nocodazole-induced apoptosis. Further investigation showed Bcl-2 phosphorylation as a critical mediator of cell death, triggered by the activation of c-jun-NH₂ kinase (JNK) instead of p38 kinase or extracellular signal–regulated kinases. Treatment with JNK inhibitor decreased Bcl-2 phosphorylation and subsequently reduced nocodazole-induced cell death. Nocodazole combined with dexamethasone significantly inhibited myeloma tumor growth and prolonged survival in a human xenograft mouse model. Our studies show that nocodazole has potent antimyeloma activity and that targeting the microtubular network might be a promising new treatment approach for multiple myeloma. Mol Cancer Ther; 10(10); 1886–96. ©2011 AACR.

Lung cancer (LC) is the leading cause of cancer‑related death, with high incidence and mortality rate. Early diagnosis and treatment of LC are imperative to improve the 5‑year survival rate for patients with LC. In recent years, miRNAs as promising biomarkers with high sensitivity and specificity for LC have been studied increasingly. In LC regulatory networks, miRNAs play crucial roles in the occurrence, development and metastasis of non‑small cell lung cancer (NSCLC), such as oncogenic factors, tumor suppressors and regulators. Dysfunctional miRNAs perform tumor‑suppressive or oncogenic functions in the regulation of cell proliferation, invasion, apoptosis, cell cycle disorder and angiogenesis by negatively regulating target genes. In the present review, the biological process of miRNAs was firstly summarized and recent advances in the mechanism of miRNAs involved in tumor formation and development were described. In addition, the present review concentrated on the latest findings on the miRNAs related with circulating free and extracellular vesicles in the early diagnosis of NSCLC. Additionally, the diagnostic performances of circulating free and extracellular vesicles‑associated miRNAs in NSCLC were contrasted. Owing to the increased stability and wide‑ranging practical applicability, miRNA may be one promising biomarker for NSCLC diagnosis.

Background: Accumulating evidence has demonstrated that migration of keratinocytes is critical to wound epithelialization, and defects of this function result in chronic delayed-healing wounds in diabetes mellitus patients, and the migration has been proved to be associated with volume-activated chloride channels. The aim of the study is to investigate the effects of high glucose (HG, 25 mM) on ClC-2 chloride channels and cell migration of keratinocytes. Methods: Newborn Sprague Dawley rats were used to isolate and culture the keratinocyte in this study. Immunofluorescence assay, real-time polymerase chain reaction, and Western blot assay were used to examine the expression of ClC-2 protein or mRNA. Scratch wound assay was used to measure the migratory ability of keratinocytes. Transwell cell migration assay was used to measure the invasion and migration of keratinocytes. Recombinant lentivirus vectors were established and transducted to keratinocytes. Whole-cell patch clamp was used to perform the electrophysiological studies. Results: We found that the expression of ClC-2 was significantly inhibited when keratinocytes were exposed to a HG (25 mM) medium, accompanied by the decline of volume-activated Cl- current (I_Cl,vol), migration potential, and phosphorylated PI3K as compared to control group. When knockdown of ClC-2 by RNAi or pretreatment with wortmannin, similar results were observed, including I_Cl,vol and migration keratinocytes were inhibited. Conclusion: Our study proved that HG inhibited ClC-2 chloride channels and attenuated cell migration of rat keratinocytes via inhibiting PI3K signaling.

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (LC), which is the leading cause of tumor mortality. In recent years, compared with tissue biopsy, which is the diagnostic gold standard for tumor diagnosis, Liquid biopsy (LB) is considered to be a more minimally invasive, sensitive, and safer alternative or auxiliary diagnostic method. However, the current value of LB in early diagnosis of LC is not ideal, so it is particularly important to study the changes in blood composition during the process of tumorigenesis and find more sensitive biomarkers. Purpose: Platelets are a type of abundant blood cells that carry a large amount of RNA. In the LC regulatory network, activated platelets play an important role in the process of tumorigenesis, development, and metastasis. In order to identify predictive liquid biopsy biomarkers for the diagnosis of NSCLC, we summarized the development and function of platelets, the interaction between platelets and tumors, the value of TEP RNA in diagnosis, prognosis, and treatment of NSCLC, and the method for detecting TEP RNA of NSCLC in this article. Conclusion: The application of platelets in the diagnosis and treatment of NSCLC remains at a nascent stage. In addition to the drawbacks of low platelet count and complex experimental processes, the diagnostic accuracy of TEP RNA-seq for cancer in different populations still needs to be improved and validated. At present, a large number of studies have confirmed significant differences in the expression of TEP RNA in platelets between NSCLC patients and healthy individuals. Continuous exploration of the diagnostic value of TEP RNA in NSCLC is of utmost importance. The integration of NSCLC platelet-related markers with other NSCLC markers can improve current tumor diagnosis and prognostic evaluation systems, providing broad prospects in tumor screening, disease monitoring, and prognosis assessment.