Nasopharyngeal carcinoma: molecular biomarker discovery and progress

Nasopharyngeal carcinoma (NPC) is a rare malignancy in most part of the world and it is one of the most confusing, commonly misdiagnosed and poorly understood diseases. The cancer is an Epstein-Barr virus-associated malignancy with a remarkable racial and geographical distribution. It is highly prevalent in southern Asia where the disease occurs at a prevalence about a 100-fold higher compared with other populations not at risk. The etiology of NPC is thought to be associated with a complex interaction of genetic, viral, environmental and dietary factors. Thanks to the advancements in genomics, proteomics and bioinformatics in recent decades, more understanding of the disease etiology, carcinogenesis and progression has been gained. Research into these components may unravel the pathways in NPC development and potentially decipher the molecular characteristics of the malignancy. In the era of molecular medicine, specific treatment to the potential target using technologies such as immunotherapy and RNAi becomes formulating from bench to bedside application and thus makes molecular biomarker discovery more meaningful for NPC management. In this article, the latest molecular biomarker discovery and progress in NPC is reviewed with respect to the diagnosis, monitoring, treatment and prognostication of the disease

Rhynchophylline Protects Cultured Rat Neurons against Methamphetamine Cytotoxicity

Rhynchophylline (Rhy) is an active component isolated from species of the genus Uncaria which has been used for the treatment of ailments to the central nervous system in traditional Chinese medicine. Besides acting as a calcium channel blocker, Rhy was also reported to be able to protect against glutamate-induced neuronal death. We thus hypothesize that Rhy may have neuroprotective activity against methamphetamine (MA). The primary neurons were cultured directly from the cerebral cortex of neonatal rats, acting as in vitro model in the present study. The neurotoxicity of MA and the protective effect of Rhy were evaluated by MTT assay. The effects of MA, Rhy or their combination on intracellular free calcium concentration ([Ca2+]i) were determined in individual neocortical neurons by the Fluo-3/AM tracing method. The MTT assay demonstrated that MA has a dose-dependent neurotoxicity in neuronal cultures. The addition of Rhy prior to the exposure to MA prevented neuronal death. Time course studies with the Fluo-3/AM probe showed that Rhy significantly decreased neuronal [Ca2+]i which was elevated by the exposure to MA. Our results suggested that Rhy can protect the neuronal cultures against MA exposure and promptly attenuate intracellular calcium overload triggered by MA challenge. This is the first report demonstrating an inhibitory effect of Rhy against MA impairment in cultured neurons in vitro

CD44 Suppression Improved the Chemosensitivity of HT-29 Colorectal Cancer Cells to 5-Fluorouracil and Inhibited Cell Migration

Purpose: CD44 plays a pivotal role through tumorigenesis by regulating cancer cell metastasis, stemness, and chemosensitivity and is considered a promising therapeutic target for human cancers, including colorectal cancer (CRC). Therefore, the present research aimed to examine the simultaneous therapeutic effect of CD44 silencing and 5-fluorouracil (5-FU) on in vitro tumorigenesis of CRC cells. Methods: CD44 expression was initially evaluated in TCGA datasets and CRC tissues. Furthermore, functional analysis was performed on HT-29 CRC cells overexpressing CD44. The cells were transfected with CD44 siRNA and then treated with 5-FU. Consequently, to explore the combination therapy effect on cell viability, migration, apoptosis, and chromatin fragmentation, we performed MTT assay, scratch assay, Annexin V/PI staining and DAPI staining assays, respectively. The spheroid and colony formation assays were further employed to investigate stemness features. The gene expression at protein and mRNA levels were explored using western blotting and qPCR. Results: Our findings illustrated that CD44 was significantly overexpressed in CRC tissues compared to normal samples. The suppression of CD44 considerably promoted the chemosensitivity of HT-29 cells to 5-FU by apoptosis induction. Also, the combination therapy led to overexpression of apoptotic genes, including P53, caspase-3, and caspase-9, as well as downregulation of AKT1 expression. Furthermore, CD44 suppression, separately or combined with 5-FU, hindered stemness properties in HT-29 cells via downregulation of Sox2 and Nanog expression. Besides, the combination therapy remarkably downregulated MMPs and suppressed CRC cell migration. Conclusion: Considering its involvement in chemosensitivity to 5-FU, CD44 could be suggested as a potential target for improving the efficiency of CRC chemotherapy

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Application of Proteomics in Chinese Medicine Research

Abstract: Proteomics technologies can be applied to simultaneously study the function, organization, diversity, and dynamic variety of a cell or a whole tissue. The integrative approach of proteomics is in line with the holistic concept and practices of traditional Chinese medicine (TCM). In this review, the technologies of proteomics, their adoption leverages the depth and breadth of TCM research are introduced. This article presents some examples to illustrate the use of proteomics technologies in the study of pharmacological effects and their action mechanisms relevant to TCM. Proteomics technologies could be used to screen the target molecules of the TCM actions, identify new bioactive components, and elucidate the underlying mechanisms of their effects. With proteomics approaches, it was found that the Siwu decoction could regulate the protein expression of the bone marrow of blood (Xue) deficient mice, including some proteins and enzymes involved in the hemopoiesis system. Ganoderma lucidum spores might promote the survival and axon regeneration of injured spinal motor neurons in rats by regulating the expression levels of proteins involved in the energy and tissue regeneration system. Polygonatum zanlanscianense Pamp exhibited cytotoxicity towards human myeloblast leukemia HL-60 cells through multiple apoptosisincluding pathways. Panax ginseng might be beneficial to patients suffering from diabetes mellitus and its complications by alleviating inflammation. Taken together with a discussion on the challenges and perspectives, this paper provides an overview of the recent developments of proteomics technologies in TCM research, and contends that proteomics will play an important role in the modernization and internationalization of TCM

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MET-Targeting Anticancer Drugs—De Novo Design and Identification by Drug Repurposing

The Met protein is a cell surface receptor tyrosine kinase predominantly expressed in epithelial cells. Aberrant regulation of MET is manifested by numerous mechanisms including amplification, mutations, deletion, fusion of the MET proto-oncogene, and protein overexpression. They represent the common causes of drug resistance to conventional and targeted chemotherapy in numerous cancer types. There is also accumulating evidence that MET/HGF signaling drives an immunosuppressive tumor microenvironment and dampens the efficacy of cancer immunotherapy. Substantial research effort has been invested in designing Met-targeting drugs with different mechanisms of action. In this review, we summarized the current preclinical and clinical research about the development of Met-targeting drugs for cancer therapeutics. Early attempts to evaluate Met-targeted therapies in clinical trials without selecting the appropriate patient population did not produce satisfactory outcomes. In the era of personalized medicine, cancer patients harboring MET exon 14 alterations or MET amplification have been found to respond well to Met-inhibitor therapy. The application of Met inhibitors to overcome drug resistance in cancer patients is discussed in this paper. Given that kinases play critical roles in cancer development, numerous kinase-mediated signaling pathways are attractive targets for cancer therapy. Existing kinase inhibitors have also been repurposed to new kinase targets or new indications in cancer. On the other hand, non-oncology drugs have also been repurposed for treating cancer through kinase inhibition as one of their reported anticancer mechanisms

DNA Expression Profi les of Non-Small Cell Lung Cancer

DNA expression profi ling using microarray technology has been applied to studies on the molecular classifi cation of lung cancers, pathogenetic alterations in gene expressions and cellular pathways,prediction of prognosis and metastasis, customized therapies, and drug development. Due to the wide variation in technical factors, different cohorts of patients and biological heterogeneity, the major hurdle to successful clinical application is lack of robustness, reliability and reproducibility of data. With betterstandardization and better analytic approaches to cut down the noises from the high dimensionality of data,microarray technologies may be ready to make its way to the doctor's offi ce with contribution to personalized treatment of lung cancer in the future