Abstract:The current clinical diagnosis and treatment of breast cancer relies on imaging and several prognostic/predictive biomarkers such as estrogen receptor, progesterone receptor, and HER2. Since these biomarkers are mainly derived from primary tumor tissues, they are limited to be applied for monitoring metastases and recurrence, especially after the removal of primary lesion. The discovery of circulating cell-free microRNAs (circulating cf-miRNAs, also called circulating miRNAs) may offer the opportunity to improve the clinical cure patterns of breast cancer. The mechanism of active excretion of cell-free miRNAs via exosomes, microvesicles and other transporters may play an important role in the formation of circulating miRNAs. Cell-free miRNAs, especially circulating miRNAs, not only act as endogenous signaling molecules to influence behaviors of tumor cells and their microenvironment, but also regulate invasion and metastases of breast cancer cells by communication with other signaling pathways to regulate tumor angiogenesis and epithelial-to-mesenchymal phenotypic transition of cancer cells. This article reviews the molecular mechanism of active excretion of circulating miRNAs and the clinical potential of breast cancer-related circulating miRNAs as liquid biopsy biomarkers in diagnosis, prognosis and response evaluation of breast cancer.

Abstract:With the technology development of cold atmospheric plasma (CAP), CAP draws more and more attentions to the biological application due to the low gas temperature and high activity of reactive species produced by CAP. Plasma medicine was also established as an innovative interdisciplinary, combining with the plasma physics, chemistry, life sciences and clinical medicine, etc. Here, we gave a brief introduction about CAP, its generation and composition, the interaction with liquid and tissues, and some of the major applications in biomedical field, such as sterilization, blood coagulation, wound healing, skin disease and dental treatment. In addition, we focused on the application of CAP in cancer treatment. CAP can effectively induce tumor cell death, inhibit cell proliferation and migration, induce differentiation of tumor cells and suppress the potential of stem cells, and can increase the sensitivity to chemotherapy. These beneficial effects shows a promising prospects for CAP application in tumor therapy.

Abstract:Mounting evidence indicates the functional importance of alternative splice variations in cancer pathophysiology. The alternative splicing of caspase-9 plays an important role in non-small cell lung cancer (NSCLC). The splicing of caspase-9 gene generates two isoforms caspase-9a and caspase-9b, the ratio of caspase-9a/9b mRNA is pretty lower in a large proportion of human NSCLC tumors. A low caspase-9a/9b ratio, demanded for the tumorigenecity of NSCLC cells, is correlated with the sensitivity of NSCLC cells to anticancer therapy. Thus, the alternative splicing of caspase-9 suggests a novel and crucial distal mechanism in NSCLC and offers promise of a new target for the development of therapeutics in the defense against cancers. Therefore, this review is to summarize the alternative splicing of caspase-9 and its application in the therapy of NSCLC.

Abstract:Natural polysaccharides such as starch, cyclodextrin and so on are widely used as excipients in pharmacy. These biodegradable, biocompatible, and hydrophilic polysaccharides contain different functional groups (such as hydroxyl, carboxylic acid, amino) that make them ideal for conjugation. In recent years, the utilization of polysaccharides and their derivatives in drug delivery is in the ascendant, these polysaccharides based polymer-drug conjugates are applied to the fields of targeted drug delivery, tissue engineering and bioadhesive technology, and other biomedical applications. This paper presented an overview of the research status of polysaccharide-drug conjugates, including the design and formulation of conjugates, and their applications in drug delivery system. In addition, the functional roles of polysaccharide in conjugate system and the future direction in the developments of polysaccharide-drug conjugates were also been mentioned.

Abstract:The mammalian genome is transcribed in a developmentally regulated manner, generating RNA transcripts ranging from long to short non-coding RNA (ncRNAs). NcRNAs represent up to 98% of the human transcriptome and have an association with organism complexity. MiRNAs are the best-studied class of ncRNAs. MiRNAs are approximately 22 nucleotides long and act as gene negative regulators at a post-transcription level. In humans, the DLK1-DIO3 genomic region, located on human chromosome 14 (14q32), contains one of the largest microRNA clusters with 54 miRNAs in the genome. Many of these miRNAs are differentially expressed by modulating important signaling pathways in several pathologic processes and various cancers. A better understanding of the pathophysiologic importance of the DLK1-DIO3 domain-containing microRNA cluster may contribute to innovative therapeutic strategies in a range of diseases. Here we present an in-depth review of the role the microRNAs of DLK1-DIO3 region may play in controlling tissue homeostasis and in the pathogenesis of mostly cancer. The potential clinical implications of these miRNAs are also discussed.

Abstract:Hepatocellular carcinoma (HCC) is the fifth largest cancer in the world and is the main cause of cancer death. Common treatment for early hepatocellular carcinoma has made some progress, but cancer recurrence, metastasis and drug resistance have not been fundamentally resolved, which can be explained by cancer stem cell theory (cancer stem cell, CSC). In this study, we obtained MHCC-97H sphere cells by suspension enrichment culture method and detected their stem cell characteristics. We deleted the 24 bp of the E1A CR2 region of the adenovirus type 5 and used the Wnt transcription element TCF/TEF to regulate E1A and then inserted the anti-oncogene TSLC1 into the vector to obtain the double targeting oncolytic adenovirus Ad.wnt-E1A(Δ24 bp)- TSLC1. The effect of recombinant adenovirus Ad.wnt-E1A(Δ24 bp)-TSLC1 on the killing effect, cell apoptosis and migration of hepatocarcinoma stem-like cells were detected by MTT, crystal violet, Hoechst staining, cell scratch, Western blot and immunofluorescence, respectively. The results show that MHCC-97H sphere cells have the capability of self-renewal and differentiation, and high expression of hepatocyte stem cell surface marker (such as CD133). After dealt with recombinant virus, it showed obvious killing effect and inhibition of cell migration and EMT (Epithelial-mesenchymal transition). Therefore, ability of targeting inhibition of 97H sphere cells was significantly higher than that of 97H cells (P<0.001). The recombinant virus could induce apoptosis of hepatocellular stem-like cells through caspase pathway. Therefore, the recombinant adenovirus Ad.wnt-E1A (Δ24 bp)- TSLC1 may be a promising therapeutic agent for targeting hepatoma stem cells, which has certain application value to clinical treatment.

Abstract:Protein glycosylation is a common post-translation modification and plays important roles in regulation of protein function. Especially, the abnormal glycosylation plays a critical role in the development and progression of tumor and the metastasis of cancer cells. MiRNAs also play a key role in the development and progression of cancer, but the mechanism how miRNAs affect on the biological functions and induce tumor malignant transformation via glycosylation needs further illustrated. In this study, the expression of glycosyltransferases were analyzed using glycan-related gene chip in miR-10b-overexpressed human normal mammary epithelial cells MCF10A. Then, the alteration of N-glycan and O-glycan was analyzed using the methods established in our laboratory. The expression of glycosyltransferase gene Fut8, MGAT3 and OGT and corresponding glycans were evaluated by qRT-PCR, Western blotting and lectin blotting. Taken together, our results provide the theoretical basis of glycomics on the role of miR-10b in breast cancer.

Abstract:A microscopy based imaging technology was proposed to provide both surface plasmonic resonance (SPR) detection and surface-enhanced Raman scattering (SERS) spectral of attached molecules on a dual-mode biochip. Experimental studies were conducted to reveal that both SPR and SERS signals can be acquired from the same biochip. SPR excitation and low concentration SERS detection are successfully performed on metallic nanogap grating with periodicities of 400 or 600 nm ensuring the SPR excitation under the illumination of 633 or 785 nm irradiation, respectively. The excited SPR propagates on the metallic surface, efficiently excites dipole moment resonance at the nanogap in the grating trough, leading to extremely high local electric field built up at the nanogap and the metallic surface. Therefore, besides SPR detection, SERS evaluation can be conducted to identify the molecules attached on the biochip. The experimental results show that the SPR bulky sensitivity of the dual-mode biochip is S = 68.8°/RIU, and the surface sensitivity is S = 1.5°/(mol·L^-1). The Raman enhancement factor of the dual-mode biochip reaches up to 10⁶ and the minimum detection concentration of 10^-15 mol/L could be achieved. Due to its high-fidelity measurement of the dual-mode chip and the high precision of microscopy imaging technology, multi-channel label-free detection is expected to be widely used in biological detections. Our future work is to achieve the practical application of SPR-SERS dual-mode biological detection.

Abstract:CtIP is one of the key proteins in DNA double strand breaks repair whereby promoting the end resection. It is a known tumor suppressor and interacts with a number of proteins involved in carcinogenesis such as BRCA1, Rb, etc. To better understand the molecular networks of CtIP, CtIP interaction proteins were predicted with online tool PrePPI and PLK1 was found as the novel CtIP interaction protein which plays an essential role in mitosis and also cancer progression. We further validated the novel interaction by immunoprecipitation method. PLK1 showed strong interaction with CtIP. Moreover, Frodock 2.0 tools for docking protein interactions between CtIP and PLK1 was employed. Finally, the immuoprecipitation assay and immunofluorescence staining results showed the interaction between these two proteins are related to DNA damage. Based on these results, we proposed that the CtIP-PLK1 interaction may play important roles in DNA damage response as well as other biological processes.