ABSTRACT
The cluster of differentiation 34 (CD34) family, which includes CD34, podocalyxin-like protein 1 (PODXL), and PODXL2, are type-I transmembrane sialomucins and markers of hematopoietic stem cells (HSCs) and vascular-associated tissues. CD34 family proteins are expressed by endothelial cells and hematopoietic precursors. PODXL is well known to be associated with invadopodia formation and to promote the epithelial-mesenchymal transition, tumor migration and invasion. PODXL expression was correlated with poor survival of cancer patients. However, the role of PODXL2 in cancer has been less fully explored. To reveal the novel role of PODXL2 in breast cancer, the present study evaluated PODXL2 levels in relation to clinical outcomes of cancer patients by performing a bioinformatics analysis using the Oncomine database, Kaplan-Meier plots, and the CCLE database. Empirical validation of bioinformatics predictions was conducted utilizing the short hairpin (sh)-RNA silencing method for PODXL2 in the BT474 invasive ductal breast carcinoma cell line. The bioinformatics analysis revealed that PODXL2 overexpression was correlated with poor survival of breast cancer patients, suggesting an oncogenic role of PODXL2 in breast carcinoma. In a validation experiment, knockdown of PODXL2 in BT474 cells slightly influenced cell proliferation, suppressed migration, and inhibited expressions of downstream molecules, including Ras-related C3 botulinum toxin substrate 1 (Rac1), phosphorylated (p)-Akt (S473), and p-paxillin (Y31) proteins. In addition, knockdown of PODXL2 reduced expression levels of cancer stem cell (CSC) markers, including Oct-4 and Nanog, and the breast CSC marker aldehyde dehydrogenase 1 (ALDH1). Collectively, our present study demonstrated that PODXL2 plays a crucial role in cancer development and could serve as a potential prognostic biomarker in breast cancer patients.
Subject(s)
Breast Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Proto-Oncogene Proteins c-akt/metabolism , Sialoglycoproteins/metabolism , Breast Neoplasms/genetics , Cell Cycle/genetics , Cell Cycle/physiology , Cell Line, Tumor , Computational Biology , Epithelial-Mesenchymal Transition/genetics , Epithelial-Mesenchymal Transition/physiology , Female , Humans , Proto-Oncogene Proteins c-akt/genetics , Sialoglycoproteins/geneticsABSTRACT
The treatment of pain with complementary and alternative medicine has gradually attracted international attention. Traditional Chinese medicine(TCM) with clear composition and mechanism will become a new starting point for new drug research and development. Siegesbeckiae Herba is a commonly used TCM herb in the treatment of rheumatic arthralgia. With a clear chemical composition, Siegesbeckiae Herba has a long history of clinical application and a certain modern research basis in the treatment of chronic pain. It has good research and development prospects in the treatment of analgesia. Based on the occurrence principle of pain and the known mechanism of action of Siegesbeckiae Herba, we discussed the advance of studies on Siegesbeckiae Herba in three aspects, namely inflammatory pain, neuropathic pain and cancer pain, so as to provide reference for further basic research and development and application of new TCM.
Subject(s)
Asteraceae , Chronic Pain , Drugs, Chinese Herbal , Humans , Medicine, Chinese TraditionalABSTRACT
Objectives: To review the evidence of acupuncture for acute and preventive treatment of migraine for further awareness of the effect of acupuncture for migraine. Design: An overview of systematic reviews and meta-analyses (SR/MAs) for randomized controlled trials. Material and Methods: We searched PubMed, Embase, the Cochrane Library, China Knowledge Resource Integrated Database, VIP Chinese Journal Full Text Database, WANFANG Data, and China Biology Medicine disc from their establishment to May 27, 2018. SR/MAs of randomized controlled trials comparing the effect of the acupuncture intervention with another treatment control in migraine patients were included. Results: 428 SRs were identified, and 15 of them were included. Only 4 SR/MAs were assessed by GRADE, which showed certainty of most evidence being low or very low. Assessed by AMSTAR-2, fourteen was critically low rating overall confidence in the results, and 1 was low rating overall confidence in the results. Evidence suggested that acupuncture has a significant advantage of pain improvement, efficacy, and safety relative to blank control, sham acupuncture, or drug treatment, but some of these results are contradictory. Conclusions: We found that acupuncture on treating migraine has the advantage for pain improvement and safety, but the quality of SR/MAs of acupuncture for migraine remains to be improved.