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Oncolytic virus therapy is currently regarded as a promising approach in cancer immunotherapy. It has greater therapeutic advantages for colorectal cancer that is prone to distant metastasis. However, the therapeutic efficacy and clinical application of viral agents alone for colorectal cancer remain suboptimal. In this study, an engineered oncolytic vaccinia virus (OVV-Luc) that expresses the firefly luciferase gene is developed and loaded Chlorin e6 (Ce6) onto the virus surface through covalent coupling, resulting in OVV-Luc@Ce6 (OV@C). The OV@C infiltrates tumor tissue and induces endogenous luminescence through substrate catalysis, resulting in the production of reactive oxygen species. This unique system eliminates the need for an external light source, making it suitable for photodynamic therapy (PDT) in deep tissues. Moreover, this synergistic effect between PDT and viral immunotherapy enhances dendritic cell maturation, macrophage polarization, and reversal of the immunosuppressive microenvironment. This synergistic effect has the potential to convert a "cold" into a "hot" tumor, it offers valuable insights for clinical translation and application., (© 2024 Wiley‐VCH GmbH.)

The quantum yield of reactive oxygen species is of central importance for the development of organic photosensitizers and photodynamic therapy (PDT). A common molecular design approach for optimizing organic photosensitizers involves the incorporation of heavy atoms into their backbones. However, this raises concerns regarding heightened dark cytotoxicity and a shortened triplet-state lifetime. Herein, we demonstrate a heavy-atom-free (HAF) photosensitizer design strategy founded on the singlet fission (SF) mechanism for cancer PDT. Through the "single-atom surgery" approach to deleting oxygen atoms in pyrazino[2,3- g ]quinoxaline skeleton photosensitizers, photosensitizers PhPQ and TriPhPQ are produced with Huckel's aromaticity and Baird's aromaticity in the ground state and triplet state, respectively, enabling the generation of two triplet excitons through SF. The SF process endows photosensitizer PhPQ with an ultrahigh triplet-state quantum yield (186%) and an outstanding 1 O 2 quantum yield (177%). Notably, HAF photosensitizers PhPQ and TriPhPQ enhanced PDT efficacy and potentiated αPD-L1 immune check blockade therapy in vivo , which show their promise for translational oncology treatment.

Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. STATEMENT OF SIGNIFICANCE: Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, hypoxia effect, and administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of intercellular messengers by facilitating the transport of proteins, lipids, nucleic acids, and therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, and engineerable characteristics have additionally led to their application as drug delivery vehicles. The therapeutic efficacy of exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, and peptides. Given their potential as targeted delivery vehicles to enhance the efficiency of treatment while minimizing adverse effects, exosomes exhibit considerable promise. Stem cells are considered advantageous sources of exosomes due to their distinctive characteristics, including regenerative and self-renewal capabilities, which make them well-suited for transplantation into injured tissues, hence promoting tissue regeneration. However, there are notable obstacles that need to be addressed, including immune rejection and ethical problems. Exosomes produced from stem cells have been thoroughly studied as a cell-free strategy that avoids many of the difficulties involved with cell-based therapy for tissue regeneration and cancer treatment. This review provides an in-depth summary and analysis of the existing knowledge regarding exosomes, including their engineering and cardiovascular disease (CVD) treatment applications., Competing Interests: Authors Z-WL and J-YC were employed by Zhejiang Healthfuture Biomedicine Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pang, Shao, Xu, Lin, Chen, Chen, Mou and Hu.)

Chemoimmunotherapy is an effective cancer treatment method. Drugs are always combined and used in treating cancer. However, the characteristic of drugs varies, making it challenging to control their release kinetics utilizing delivery devices with a single microstructure. In this study, we attempted to uniformly size drugs of varying molecular weights and confine them in a compartment where immune cells may be recruited and moved freely. Dextran microgels were created as modular drug libraries to address the cryogel burst release of small molecule drugs. Then, modular drug libraries and granulocyte-macrophage colony-stimulating factor (GM-CSF) were integrated into cryogels for a combined treatment. Herein, alginate was zwitterion modified to avoid the immune reaction generated by the material. Because of its macroporous structure, the cryogel could be injected into the body, eliminating invasive surgical procedures. Results demonstrated that multiscale delivery platforms could improve the synergistic effect of various medications on tumor treatment.

Lymph node metastasis is a frequent occurrence in a variety of tumour forms and poses an enormous challenge to cancer treatment. This process is critical to the development of the disease and is frequently linked to a poor prognosis. Over 90% of cancerous cells move through lymph nodes, making them important entry routes for the spread of cancer cells. The prognosis of cancer patients is significantly impacted by lymph node metastases, which also affects treatment choices. Targeting lymph node metastases presents numerous difficulties for conventional medication delivery techniques. It is still very difficult to selectively target cancer cells in lymph nodes without risking injury to healthy organs and unforeseen consequences. Additionally, systemic delivery of drugs is hampered by the slow flow rate of lymphatic vessels. Chemotherapeutic medicines' poor solubility and stability further reduce their effectiveness when taken orally. Additionally, the extracellular matrix that surrounds lymph node tumours is extensive, which makes it difficult for conventional pharmaceutical delivery systems to reach cancer cells. The development of nanocarriers for precise drug delivery to LNs has attracted a lot of interest to overcome these obstacles. Most solid tumours first spread through the lymphatic system, hence effective drug administration to these tissues is essential for better therapeutic results. Nanocarriers have several benefits, including the capacity to pass through barriers like blood-brain barriers and membranes to reach the lymphatic system. High medication dosages can be enclosed thanks to the physicochemical characteristics of nanocarriers, such as their higher surface-to-volume ratio. Additionally, ligands, antibodies, polymers, or biological molecules can be attached to nanocarrier surfaces to change their properties, allowing for the targeted delivery of lymph node epithelial cells. This use of nanocarriers for drug delivery maximizes on-target effects and related adverse effects while improving the effectiveness of medication delivery to target locations. More research and development in this field is needed to optimize nanocarrier design, increase targeting capabilities, and expand clinical applications for better cancer care., (© 2023. The Author(s).)

Objective: MED subunits have been reported to be associated with various types of tumors, however, the potential role of MED7 in hepatocellular carcinoma (HCC) was still unclear. The aim of the study was to explore the role of MED7 in HCC., Methods: In this study, MED7 mRNA expression levels between HCC and adjacent normal tissues were first analyzed by several public datasets. Then we utilized a tissue microarray (TMA) to investigate the clinical role of MED7 in HCC by immunohistochemistry (IHC). Meanwhile, the potential mechanisms of MED7 based on gene-gene correlation analyses were also explored., Results: High mRNA level of MED7 correlated with advanced stage and worse grade of differentiation. IHC results showed that MED7 protein level was upregulated in HCC and associated with Edmondson grade and Microvascular invasion in 330 cases of HCC. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that MED7 co-expressed genes participate primarily in ribonucleoprotein complex biogenesis, protein targeting, mRNA processing and nucleoside triphosphate metabolic process et cetera. Further analysis also revealed that MED7 mRNA level has significant correlation with immune cells infiltration levels., Conclusion: MED7 was upregulated in HCC and correlated with progression of HCC. Meanwhile, MED7 may promote HCC through participating in multiple gene networks to influence tumorigenesis as well as immune response in HCC microenvironment.

Oncolytic viruses have found a good place in the treatment of cancer. Administering oncolytic viruses directly or by applying genetic changes can be effective in cancer treatment through the lysis of tumor cells and, in some cases, by inducing immune system responses. Moreover, oncolytic viruses induce antitumor immune responses via releasing tumor antigens in the tumor microenvironment (TME) and affect tumor cell growth and metabolism. Despite the success of virotherapy in cancer therapies, there are several challenges and limitations, such as immunosuppressive TME, lack of effective penetration into tumor tissue, low efficiency in hypoxia, antiviral immune responses, and off-targeting. Evidence suggests that oncolytic viruses combined with cancer immunotherapy-based methods such as immune checkpoint inhibitors and adoptive cell therapies can effectively overcome these challenges. This review summarizes the latest data on the use of oncolytic viruses for the treatment of cancer and the challenges of this method. Additionally, the effectiveness of mono, dual, and triple therapies using oncolytic viruses and other anticancer agents has been discussed based on the latest findings., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Global Challenges published by Wiley‐VCH GmbH.)

Introduction: Benign airway stenosis is a severe disease that can result in death with improper treatment. Clinicians must know about airway stents to choose the best one in their daily practice., Areas Covered: PubMed, Embase, and other electronic databases and websites were searched to identify relevant randomized controlled trials and meta-analyses. This review summarizes different types of airway stents and analyzes their advantages and disadvantages., Expert Opinion: Increasing attention has been given to the indications and prognosis of benign airway stenosis treated with different airway stents. With more investigations and data, better alternatives to silicone stents could be developed in the future.

Introduction: Many nanocarriers have been developed to react physicochemically to exterior stimuli like ultrasonic, light, heat, and magnetic fields, along with various internal stimuli including pH, hypoxia, enzyme, and redox potential. Nanocarriers are capable to respond various stimuli within the cancer cells to enable on-demand drug delivery, activation of bioactive compounds, controlled drug release, and targeting ligands, as well as size, charge, and conformation conversion, enabling sensing and signaling, overcoming multidrug resistance, accurate diagnosis, and precision therapy., Areas Covered: Carbohydrates are ubiquitous biomolecules with a high proclivity for supramolecular network formation. Numerous carbohydrate-based nanomaterials have been used in biological solicitations and stimuli-based responses. Particular emphasis has been placed on the utilization of carbohydrate-based NPs and nanogels in various fields including imaging, drug administration, and tissue engineering. Because the assembly process is irreversible, carbohydrate-based systems are excellent ingredients for the development of stimulus-responsive nanocarriers for cancer-targeted chemotherapy. This review aims to summarise current research on carbohydrate-based nanomaterials, with an emphasis on stimuli-sensitive nanocarriers for cancer-targeted chemotherapy., Expert Opinion: Carbohydrates-based stimulus-responsive nanomaterials have been proved highly efficient for targeted delivery of anticancer drugs, thus leading to effective chemotherapy with minimum off-target effects.

Estuaries are one of the most crucial areas for the transformation and burial of terrestrial organic carbon (TerrOC), playing an important role in the global carbon cycle. While the transformation and degradation of TerrOC are mainly driven by microorganisms, the specific taxa and degradation processes involved remain largely unknown in estuaries. We collected surface sediments from 14 stations along the longitudinal section of the Pearl River Estuary (PRE), P. R. China. By combining analytical chemistry, metagenomics, and bioinformatics methods, we analyzed composition, source and degradation pathways of lignin/lignin-derived aromatic fragments and their potential decomposers in these samples. A diversity of bacterial and archaeal taxa, mostly those from Proteobacteria (Deltaproteobacteria, Gammaproteobacteria etc.), including some lineages (e.g., Nitrospria, Polyangia, Tectomicrobia_uc) not previously implicated in lignin degradation, were identified as potential polymeric lignin or its aromatic fragments degraders. The abundance of lignin degradation pathways genes exhibited distinct spatial distribution patterns with the area adjacent to the outlet of Modaomen as a potential degradation hot zone and the Syringyl lignin fragments, 3,4-PDOG, and 4,5-PDOG pathways as the primary potential lignin aromatic fragments degradation processes. Notably, the abundance of ferulic acid metabolic pathway genes exhibited significant correlations with degree of lignin oxidation and demethylation/demethoxylization and vegetation source. Additionally, the abundance of 2,3-PDOG degradation pathways genes also showed a positive significant correlation with degree of lignin oxidation. Our study provides a meaningful insight into the microbial ecology of TerrOC degradation in the estuary., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death globally. Although the mortality rate in some parts of the world, such as East Asia, is still high, new treatments and lifestyle changes have effectively reduced deaths from this type of cancer. One of the main challenges of this type of cancer is its late diagnosis and poor prognosis. GC patients are usually diagnosed in the advanced stages of the disease, which is often associated with peritoneal metastasis (PM) and significantly reduces survival. This type of metastasis in patients with GC poses a serious challenge due to limitations in common therapies such as surgery and tumor resection, as well as failure to respond to systemic chemotherapy. To solve this problem, researchers have used virotherapy such as reovirus-based anticancer therapy in patients with GC along with PM who are resistant to current chemotherapies because this therapeutic approach is able to overcome immune suppression by activating dendritic cells (DCs) and eventually lead to the intrinsic activity of antitumor effector T cells. This review summarizes the immunopathogenesis of peritoneal metastasis of gastric cancer (PMGC) and the details for using virotherapy as an effective anticancer treatment approach, as well as its challenges and opportunities., Competing Interests: KL, Y-LZ, and P-YH were employed by Guangdong Techpool Bio-pharma Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shao, Yang, Zhang, Wang, Li, Zhao, Mou and Hu.)

Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre-clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient-derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre-clinical evaluation of onco-immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

As an important trace element, iron plays an essential role in many biology processes like cell proliferation, metabolism, and mitochondrial function. However, the disruption of iron homeostasis tends to cells death and human diseases due to it servers as mediator to promote the production of reactive oxygen species (ROS). In this review, first we introduced the mechanism of complex iron-mediated ROS involved in apoptosis, necroptosis, ferroptosis and pyroptosis. Next, we discussed the controversial role of excess iron and iron deficiency in tumor. Finally, we discussed the anti-cancer effects of iron on both sides, and novel iron-related strategies. This review outlined the mechanisms and regulation of iron homeostasis and iron-mediated ROS in tumors, and discussed the iron-related treatments., Competing Interests: None., (AJCR Copyright © 2021.)

The applications of hydrogels in biomedical field has been since multiple decades. Discoveries in biology and chemistry render this platform endowed with much engineering potentials and growing continuously. Novel approaches in constructing these materials have led to the production of complex hybrid hydrogels systems that can incorporate both natural and synthetic polymers and other functional moieties for mediated cell response, tunable release kinetic profiles, thus they are used and research for diverse biomedical applications. Recent advancement in this field has established promising techniques for the development of biorelevant materials for construction of hybrid hydrogels with potential applications in the delivery of cancer therapeutics, drug discovery, and re-generative medicines. In this review, recent trends in advanced hybrid hydrogels systems incorporating nano/microstructures, their synthesis, and their potential applications in tissue engineering and anticancer drug delivery has been discussed. Examples of some new approaches including click reactions implementation, 3D printing, and photopatterning for the development of these materials has been briefly discussed. In addition, the application of biomolecules and motifs for desired outcomes, and tailoring of their transport and kinetic behavior for achieving desired outcomes in hybrid nanogels has also been reviewed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cai, Chen, Fu, Du, Yang, Mou and Hu.)

Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed.

Aims: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase implicated to have a role in tumor suppression. However, the relationship between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to detect the expression of KAT6B in HCC tissues and analyze its connection with the clinicopathological features of HCC., Methods: First, we performed immunohistochemical staining on 250 HCC tissues and 222 non-tumor liver tissues to examine the expression of KAT6B.Then the relation between KAT6B expression and clinicopathological parameters was analyzed by chi-square test, and the overall survival analysis was conducted by Kaplan-Meier survival method. In addition, based on the Oncomine expression array online and the UALCAN database, we compared KAT6B expression differences between normal liver tissues and HCC tissues more broadly., Results: Compared with normal tissues, KAT6B expression was significantly lower in HCC tissues. Low KAT6B expression was found to be related to gender, AFP level, and tumor size. According to the online database, KAT6B expression was found to be decreased in HCC tissues and high in normal tissues., Conclusions: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B may be a potential tumor suppressor in liver cancer.

Oncolytic virus (OV) immunotherapy is characterized by viruses which specifically target cancer cells and cause their cytolysis. They provide a unique and promising new tool for the eradication of cancer as they interact with and affect the tumor microenvironment (TME), vasculature, and immune system. Advancements of genetic engineering have allowed for these viruses to be armed in such a way to have enhanced targeting, strong immunomodulation properties, and an ability to modify the TME. However, there are still major limitations in their use, mostly due to difficulties in delivering the viral particles to the tumors and in ensuring that the immunomodulatory properties are able to stimulate the host immune response to mount a complete response. Using novel delivery systems and using OVs as a complementary therapy in a combinatorial treatment have shown some significant successes. In this review, we discuss the major issues and difficulties in using OVs as anti-tumor agents and some of the strategies put in place so far to overcome these limitations. KEY POINTS: • Oncolytic viruses (OVs) infect cancer cells and cause their cytolysis. • The major limitations in using OVs as anti-tumor therapy were discussed. • The potential strategies to overcome these limitations were summarized.

Wounds present serious medical complications and their healing requires strategies that promote angiogenesis, deposition of collagen as well as re-epithelialization of wounds. Currently used conventional wound healing strategies have become less effective due to various issues associated with them. Thus, novel strategies are needed to be developed for early and effective healing of wounds. Metal-organic frameworks (MOFs), formed by linking of metal ions through organic bridging ligands, are highly tunable hybrid materials and have attracted more considerable scientific attention due to their charming and prominent properties, such as abundant pore structures and multiple functionalities. Surface engineering of MOFs with unique ligands can overcome issues associated with conventional wound healing methods, thus resulting in early and effective wound healing. This review has been undertaken to elaborate wound healing, and the use of surface engineered MOFs for effective and rapid wound healing. The process of wound healing will be discussed followed by a detailed review of recent literature for summarizing applications of surface engineered MOFs for wound healing. MOFs wound healing will be discussed in terms of their use as antibacterial agents, therapeutic delivery vehicles, and dressing systems in wound healing., (Copyright © 2020 Fu, Chen, Cai, Tao, Fan and Mou.)

Beta-glucosidase (GBA), also known as acid β-glucosidase, exhibits an activity of glucosylceramidase (EC 3.2.1.45). Three main isoforms of β-glucosidases have been identified in mammals: GBA1, GBA2, and GBA3. The deficiency of these enzymes leads to glucosylceramide accumulation, resulting in Gaucher's disease. The present study is focused on the cytosolic β-glucosidase, GBA3, and its relationship with hepatocellular carcinoma (HCC). The expression of GBA3 mRNA in HCC was evaluated first using the TCGA database, and then by immunohistochemistry using tissue microarrays of 328 clinically characterized HCC samples and 151 non-tumor liver controls. Moreover, the presence of a correlation between GBA3 expression and clinicopathological characteristics of patients was examined. The obtained results indicated that the expression of GBA3 mRNA was significantly lower in HCC than in the adjacent non-tumor liver tissues. The expression of GBA3 was inversely related to the number of tumors (p=0.041), tumor size (p<0.001), Edmondson grade (p=0.007), microvascular invasion (p=0.049), patient status (p<0.001), and α-fetoprotein level (p<0.001). Patients exhibiting low GBA3 expression had a shorter survival time than those with high expression (p<0.001). In conclusion, the decreased GBA3 expression is strongly associated with a poor prognosis in HCC patients, and GBA3 may be a potential therapeutic target for HCC.

Tumor associated macrophages (TAMs) are the most frequent immune cells within tumor microenvironment (TME). There is growing evidence that TAMs are involved in tumor progression via multiple mechanisms. TAMs create an immunosuppressive TME by producing growth factors, chemokines, and cytokines which modulate recruitment of immune cells and inhibit anti-tumor responses. They also serve as angiogenesis promoting cells by production of pro-angiogenic factors and matrix metalloproteinases (MMPs) and vascular constructing which guarantee supplying oxygen and nutrients to solid tumor cells. Furthermore, TAMs play important functions in tumor metastasis through contributing to invasion, extravasation, survival, intravasation, and colonization of tumor cells. In this review, we summarized macrophage classification, TAMs polarization, and mechanisms underlying TAM-promoting angiogenesis and metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Oncolytic virotherapy is a promising antitumor strategy which utilizes the lytic nature of viral replication to kill cancer cells. Oncolytic viruses (OVs) can induce cancer cell death and trigger immune responses to metastatic cancer in vivo. Reverse genetic systems have aided the insertion of anticancer genes into various OVs to augment their oncolytic capacity. Furthermore, OVs target and destroy the population of tumor-initiating cancer stem cells. These cancer stem cells are associated with metastasis and development of resistance to conventional anticancer approaches. Targeting cancer stem cells is essential since killing only differentiated tumor cells may lead to enrichment of cancer stem cells and thus indicate a poor prognosis. In this review, we summarize the oncolytic activity of various classes of OVs towards different types of cancer stem cells and also discuss the synergistic activity achieved by the combination of OVs with traditional therapies on chemo- and radiotherapy-resistant cancer stem cells.

Within the past decade, immune-checkpoint inhibitors (ICPIs), including anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, are undoubtfully the most remarkable advances in cancer therapy. The immune responses are modulated by these ICPIs via blocking the inhibitory PD-1/PD-L1 path and result in immune activation in the suppressive microenvironment of the tumor. While ICPIs result in benefits for numerous patients with malignancy and lead to disease control and survival, toxicity and safety problems have emerged as well. Although immune mediated adverse effects due to ICPIs could involve any organ system, skin, endocrine glands, and gastrointestinal tract, are one of the most commonly affected. Fortunately, in most of the cases, these immune‑mediated adverse effects (imAEs) are manageable, while in some cases these toxicities are fulminant and fatal and lead to the withdrawal of treatment. Numerous attempts have been started and are continuing to reduce the incidence rate of imAEs. Further studies are required for a better understanding of these imAEs, decrease the occurrence, and lighten the severity. In this work, we overview the imAEs and also, highlight the most important aspects of the imAEs management., (Copyright © 2020 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

The role of forkhead box O3 (FOXO3) as a tumor suppressor gene and its association with the human lifespan is well documented. However, several studies have indicated that high expression of FOXO3 is also significantly associated with tumorigenesis. The aim of the present study was to determine the clinical significance of FOXO3 in the development and prognosis of hepatocellular carcinoma (HCC). mRNA expression data of FOXO3 from The Cancer Genome Atlas database was analyzed through the UALCAN online tool to compare the expression of FOXO3 between HCC and normal liver tissues. Subsequently, the expression of FOXO3 at the protein level was investigated via immunohistochemical staining of 314 HCC and 150 non-cancerous liver tissue samples. The association between protein expression and clinicopathological parameters was analyzed using the χ 2 test, and the effect of FOXO3 expression on survival was assessed via Kaplan-Meier analysis. The expression of FOXO3 mRNA was significantly higher in HCC in comparison with healthy tissues. High FOXO3 protein expression was revealed in 43/150 non-cancerous liver tissues, and in 238/314 HCC samples. A significant association was demonstrated between FOXO3 expression and metastasis, Tumor-Node-Metastasis stage, Edmondson grade, α-fetoprotein level and overall survival. In conclusion, the high expression of FOXO3 predicts a poor prognosis in patients with HCC, indicating this protein as a potential therapeutic target in HCC., (Copyright: © Song et al.)

Background: Citron kinase (CIT) is a protein related to cytokinesis and is an important abscission regulator. However, the relationship between CIT and hepatocellular carcinoma (HCC) is unclear. The aim of this study was to investigate the expression CIT in HCC tissues, and explore the connection between this expression and clinicopathological characteristics of HCC., Methods: Immunohistochemistry staining on 235 HCC tissues and 96 non-tumorous liver tissues controls was performed to examine the CIT protein expression. We then analyzed the correlation between protein expression and clinicopathological parameters via χ 2 tests, and we performed overall survival analyses via the Kaplan-Meier survival approach. Based on the online Oncomine Expression Array and UALCAN databases, we more broadly compared CIT mRNA expression between normal and HCC tissues. Finally, we compared CIT mRNA expression in these databases to protein expression in our study and explored potential sources for any observe differences., Results: Compared to normal tissues, CIT expression was significantly lower in HCC tissues. Low CIT expression was found to be related to gender, tumor size, Edmondson Grade, Microvascular invasion, serum AFP levels and poor overall survival. Based on the online databases, CIT mRNA expression was found to be high in HCC tissues and decreased in normal tissues. We hypothesize that this unexpected result is due to a negative feedback loop whereby low protein CIT levels mediate increased CIT mRNA levels., Conclusions: Lower CIT protein levels are associated with a poorer prognosis in HCC patients, and lower CIT protein levels may mediate a negative feedback loop leading to increased CIT mRNA levels., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2020.03.58). All authors reports grants from Zhejiang Province Bureau of Health, during the conduct of the study., (2020 Translational Cancer Research. All rights reserved.)

Microcarriers are 100- to 300-micron support matrices that permit the growth of adherent cells in bioreactor systems. They have a larger surface area to volume ratio in comparison to single cell monolayers, enabling cost-effective cell production and expansion. Microcarriers are composed of a solid matrix that must be separated from expanded cells during downstream processing stages. The detachment method is chosen on the basis of several factors like cell type, microcarrier surface chemistry, cell confluency and degree of aggregation. The development of microcarriers with a range of physiochemical properties permit controlled cell and protein associations that hold utility for novel therapeutics. In this review, we provide an overview of the recent advances in microcarrier cell culture technology. We also discuss its significance as an ex vivo research tool and the therapeutic potential of newly designed microcarrier systems in vivo.

Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin-related protein (DC-SIGNR) is a transmembrane receptor primarily involved in pathogen recognition by the innate immune system, with particular importance for viral recognition. DC-SIGNR may also be associated with tumorigenesis. The aim of the present study was to investigate the association between DC-SIGNR expression, development of hepatocellular carcinoma (HCC), and clinicopathological features. Immunohistochemistry was used to assess DC-SIGNR protein expression in HCC and paired non-cancerous tissue samples. DC-SIGNR expression was lower in HCC tissues compared with adjacent non-tumor tissue samples. The expression of DC-SIGNR was associated with small tumor size, low Edmondson grade and high patient long term survival rates. Bioinformatics analyses were performed on several datasets to assess the potential function of DC-SIGNR and related genes; the data revealed that DC-SIGNR mRNA expression was lower in HCC tissues compared with non-cancerous controls, and analyses of ten-year survival rates indicated patients with low DC-SIGNR expression exhibited shorter average survival times. In conclusion, decreased DC-SIGNR expression in HCC tissues may be a relevant predictive biomarker of clinical prognosis, in addition to being a viable therapeutic target for HCC treatment., (Copyright: © Xia et al.)

The process of metastasis is characterized by the shedding of tumor cells into the bloodstream, where they are transported to other parts of the body to seed new tumors. These cells, known as circulating tumor cells (CTCs), have the potential to reveal much about an individual cancer case, and theoretically can aid in the prediction of outcomes and design of precision treatments. Recent advances in technology now allow for the robust and reproducible characterization of CTCs from a simple blood draw. Both the number of circulating cells and important molecular characteristics correlated with clinical phenotypes such as drug resistance can be obtained and used for real-time prognostic analysis. Molecular characterization can provide a snapshot of the activity of the main tumor (serving as a "liquid biopsy") and early warnings concerning changes such as the development of resistance, and aid in predicting the efficacy of different therapeutic approaches for treatment optimization. Herein, the authors review the current clinical use of CTCs as prognostic biomarkers for several different cancers. The quantification of CTCs can lead to more accurate staging and decision making regarding options such as adjuvant chemotherapy., (© 2019 American Cancer Society.)

Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. In vitro experiments show that loaded drugs exhibit acidic pH (pH ∼ 5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable in vivo complete healing of MRSA biofilm infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.

Administration of oncolytic viruses (OVs) is an emerging anticancer strategy that exploits the lytic nature of viral replication to enhance the killing of malignant cells. OVs can be used as tools to directly induce cancer cell death and to trigger local and/or systemic immune responses to metastatic cancer in vivo. The effectiveness of OV therapy was initially highlighted by the clinical use of the genetically modified herpes virus, talimogene laherparepvec, for melanoma therapy. A number of OVs are now being evaluated as potential treatments for cancer in clinical trials. In spite of being engineered to specifically target tumor cells, the safety and off-target effects of OV therapy are a concern. The potential safety concerns of OVs are highlighted by current clinical trial criteria, which exclude individuals harbouring other viral infections and people who are immunocompromised. Despite the potential for adverse effects, clinical trials to date revealed relatively minimal adverse immune-related effects, such as fever. With advances in our understanding of virus replication cycles, several novel OVs have emerged. Reverse genetic systems have facilitated the insertion of anticancer genes into a range of OVs to further enhance their tumor-killing capacity. In this review, we highlight the recent advances in OV therapy for a range of human cancers in in vitro and in in vivo animal studies. We further discuss the future of OVs as a therapeutic strategy for a range of life-threatening cancers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To investigate the prognostic significance of miR-199a-3p and its role in invasion and metastasis in gastric cancer., Methods: miR-199a-3p expression in 436 formalin-fixed and 39 frozen gastric cancer tissues was investigated by in situ hybridization and RT-PCR, respectively. The role of miR-199a-3p in the migration and invasion of gastric cancer cells was determined in overexpression and inhibitor studies using transwell assays and the SGC-7901, BGC-823 and MGC-803 gastric cancer cells lines. The effect of miR-199a-3p expression on ethanolamine kinase 1 (ETNK1) levels was determined by western botting., Results: miR-199a-3p was significantly up-regulated in AGS, SGC-7901, BGC-823 and MGC-803 gastric cancer cells, when compared with GES-1 non-malignant gastric epithelial cells. In situ hybridization studies revealed that human non-tumor gastric mucosa samples were negative for miR-199a-3p expression, while 162 of 436 (37.16%) cases of gastric cancer demonstrated positive expression. miR-199a-3p overexpression was associated with tumor size, Lauren classification, depth of invasion, lymph node and distant metastasis, TNM stage and prognosis. In patients with I, II and III stage tumors, high miR-199a-3p expression was associated with a significantly lower 5-year survival rate. miR-199a-3p overexpression was associated with increased cell migration and invasion. ETNK1 expression was inhibited following miR-199a-3p overexpression in BGC-823 and SGC-7901 cells, and elevated following miR-199a-3p suppression in MGC-803 cells., Conclusion: miR-199a-3p is highly expressed in gastric cancer, and correlates with invasion, metastasis and prognosis. miR-199a-3p regulates the invasion and migration of gastric cancer cells by targeting ETNK1. Consequently, miR-199a-3p may serve as a prognostic indicator in gastric cancer., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Bacterial infections pose mounting public health concerns and cause an enormous medical and financial burden today. Rapid and sensitive detection of pathogenic bacteria at the point of care (POC) remains a paramount challenge. Here, we report a novel concept of bacteria-instructed click chemistry and employ it for POC microbial sensing. In this concept of bacteria-instructed click chemistry, we demonstrate for the first time that pathogenic bacteria can capture and reduce exogenous Cu 2+ to Cu + by leveraging their unique metabolic processes. The produced Cu + subsequently acts as a catalyst to trigger the click reaction between gold nanoparticles (AuNPs) modified with azide and alkyne functional molecules, resulting in the aggregation of nanoparticles with a color change of the solution from red to blue. In this process, signal amplification from click chemistry is complied with the aggregation of functionalized AuNPs, thus presenting a robust colorimetric strategy for sensitive POC sensing of pathogenic bacteria. Notably, this colorimetric strategy is easily integrated in a smartphone app as a portable platform to achieve one-click detection in a mobile way. Moreover, with the help of the magnetic preseparation process, this smartphone app-assisted platform enables rapid (within 1 h) detection of Escherichia coli with high sensitivity (40 colony-forming units/mL) in the complex artificial sepsis blood samples, showing great potential for clinical early diagnosis of bacterial infections.

Cancer is a complex multifactorial disease for which many promising therapeutic strategies such as immunotherapy are emerging. Malignant cells frequently express aberrant cell surface carbohydrates, which differentiate them from normal "healthy" cells. This characteristic presents a window for the development of synthetic carbohydrate antigen-based cancer vaccines which can be recognized by the immune system and can bring about T cell-dependent immune responses. Antibodies generated against the carbohydrate antigens partake in the inactivation of carbohydrate-decorated cancer cells, by slowing down tumor cell growth and inducing cancer cell apoptosis. Novel synthetic strategies for carbohydrate antigens have led to several synthetic cancer vaccine candidates. In the present review, we describe the latest progress in carbohydrate-based cancer vaccines and their clinical evaluation in various cancers.

Atherosclerosis (AS) is a chronic inflammatory disease characterized by accumulating deposition of lipids in the arterial intima. Notably, macrophages participate centrally in the pathogenesis of this deadly disease. In this study, we established AS mouse models in order to investigate the effect of microRNA-133b (miR-133b) on vulnerable plaque formation and vascular remodeling in AS and explore the potential functional mechanisms. The expression of miR-133b was altered or the Notch-signaling pathway was blocked in the AS mouse models in order to evaluate the proliferation, migration, and apoptosis of macrophages. It was observed that miR-133b was upregulated in AS, which might target MAML1 to regulate the Notch-signaling pathway. AS mice with downregulated miR-133b or inhibited Notch-signaling pathway presented with a reduced AS plaque area, a decreased positive rate of macrophages, and an increased positive rate of vascular smooth muscle cells. Moreover, Notch-signaling pathway blockade or miR-133b downregulation inhibited the macrophage viability and migration and accelerated the apoptosis. This study provides evidence that downregulated miR-133b expression may inhibit the immune responses of macrophages and attenuate the vulnerable plaque formation and vascular remodeling in AS mice through the MAML1-mediated Notch-signaling pathway, highlighting miR-133b as a novel therapeutic target for AS., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite substantial efforts to develop novel therapeutic strategies for treating hepatocellular carcinoma (HCC), the effectiveness and specificity of available drugs still require further improvement. Previous work has shown that exogenous ceramide can play a key role in inducing the apoptotic death of cancer cells, however, the poor water-solubility of this compound has hampered its use for cancer treatment. In the present study, we used polyethylene glycol (PEG) and polyethylenimine (PEI) co-conjugated ultra-small nano-GO (NGO-PEG-PEI) loaded with C6-ceramide (NGO-PEG-PEI/Cer) as a strategy for HCC treatment. We assessed the biological role of NGO-PEG-PEI/Cer, and we assessed its antitumor efficacy against HCC both in vitro and in vivo in combination with the chemotherapeutic drug sorafenib. We found that NGO-PEG-PEI significantly enhanced the cellular uptake of C6-ceramide. By investigating the mechanism of cellular delivery, we determined that the internalization of NGO-PEG-PEI/Cer progressed primarily via a clathrin-mediated mechanism. The combination of NGO-PEG-PEI/Cer and sorafenib exhibited synergy between these two drugs. Further work revealed that NGO-PEG-PEI/Cer may play a role in subverting multidrug resistance (MDR) in HCC cells by inactivating MDR and Akt signaling. NGO-PEG-PEI/Cer also significantly inhibited tumor growth and improved survival times in vivo , and the synergetic effect of NGO-PEG-PEI/Cer combined with sorafenib was also observed in drug-resistant HCC xenografts. In conclusion, our NGO-PEG-PEI nanocomposite is an effective nano-platform for loading C6-ceramide for therapeutic use in treating HCC, exhibiting high cancer cell killing potency in this tumor model. The NGO-PEG-PEI/Cer/sorafenib combination additionally represents a promising potential therapeutic strategy for the treatment of drug-resistant HCC.

Bacterioplankton are the major driving force for biogeochemical cycles in estuarine ecosystems, but the communities that mediate these processes are largely unexplored. We sampled in the Pearl River Estuary (PRE) to examine potential differences in the taxonomic composition of resident (DNA-based) and active (RNA-based) bacterioplankton communities in free-living and particle-associated fractions. MiSeq sequencing data showed that the overall bacterial diversity in particle-associated fractions was higher than in free-living communities. Further in-depth analyses of the sequences revealed a positive correlation between resident and active bacterioplankton communities for the particle-associated fraction but not in the free-living fraction. However, a large overlapping of OTUs between free-living and particle-associated communities in PRE suggested that the two fractions may be actively exchanged. We also observed that the positive correlation between resident and active communities is more prominent among the abundant OTUs (relative abundance > 0.2%). Further, the results from the present study indicated that low-abundance bacterioplankton make an important contribution towards the metabolic activity in PRE.

Corticotropin releasing hormone binding protein (CRHBP) mediates the reaction between corticotropin releasing hormone (CRH) and corticotropin releasing hormone receptors (CRHRs). It is expressed in a number of organs, and the expression of CRHBP is associated with tumorigenesis and cancer progression. The aim of the present study was to investigate CRHBP expression levels in hepatocellular carcinoma (HCC) and its association with patient clinicopathological characteristics as well as prognosis. The expression of CRHBP was examined by immunohistochemistry in 169 HCC tissues and 151 adjacent non-tumorous tissues. The results were validated by western blotting using patient tissues and liver cancer cell lines. The association of CRHBP expression with clinicopathological patient characteristics and survival rate was analyzed statistically. Expression of CRHBP was detected in 142/151 (94.0%) non-tumorous liver tissues, and 84/169 (49.7%) HCC tissues (P<0.001). The expression of CRHBP was negatively associated with tumor size (P=0.013), Edmondson Grade (P=0.002), hepatitis B virus antigen (P=0.020), and α-fetoprotein levels (P=0.014). Patients exhibiting low CRHBP expression were associated with shorter survival time compared with those exhibiting high CRHBP expression (P=0.012). The results of western blotting analysis suggest that reduced CRHBP expression is frequently observable in patients with HCC. Low CRHBP expression in HCC tissues may be a predictor of clinical prognosis and a potential therapeutic target for HCC.

To investigate the expression and clinical significance of long noncoding RNA (lncRNA) in gastric cancer, we applied microarray analysis to obtain expression profiles of protein-coding genes and lncRNAs in tumor and paired adjacent nontumor tissues. We found that 41 lncRNAs were up-regulated and 31 lncRNAs were down-regulated more than 2-fold in gastric cancer versus noncancerous tissues (ratio >2.0, P < .01). We established a coexpression network of the differentially expressed lncRNAs and targeted coding genes that included 17 lncRNAs and 16 coding genes. Because the results of microarray analysis showed that lncRNA M26317 was up-regulated in gastric cancer tissues, we examined the expression level of M26317 in 103 gastric cancer tissues by reverse-transcription polymerase chain reaction and 436 gastric cancer tissues by in situ hybridization. Our data confirmed that M26317 was up-regulated in gastric cancer tissues. Moreover, expression of M26317 correlated with patient age, size of tumor, Lauren's classification, depth of invasion, lymph node and distant metastasis, TNM stage, and poor prognosis (P < .05), but was not associated with sex, location of tumor, and differentiation (P > .05). M26317 may have an important role in malignant transformation and metastasis of gastric cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Aim: Hypercalcemia is a potentially fatal and not rare complication of hepatocellular carcinoma (HCC), and its underlying mechanism remains unclear. Parathyroid hormone (PTH) is the most important regulator of the concentrations of calcium and phosphate in blood; parathyroid hormone-related protein (PTHrP) was the most frequent cause of humoral hypercalcemia of malignancy; parathyroid hormone 1 receptor (PTH1R) is the common receptor for PTH and PTHrP. The aim of this study is to investigate the expression of PTH, PTHrP, and PTH1R in HCC tissues, and their relationship with clinical pathological characters in HCC., Methods: First, a meta-analysis based on online Oncomine Expression Array database was conducted to compare the different mRNA expression of PTH1R, PTH and PTHrP between hepatocellular carcinoma and normal tissues. Then, the protein expression level of differentially expressed gene was examined by immunohistochemistry staining in 223 HCC tissues and 102 non-tumorous liver tissues controls. The relationship between the protein expression and clinicopathological parameters was analyzed by χ2 test, and overall survival analysis was performed using Kaplan-Meier survival analysis., Results: PTH1R mRNA expression was significantly lower in HCC tissues compared with normal tissues, while the expression of PTH and PTHrP showed no significant difference between HCC tissues and normal tissues. High PTH1R protein expression was found in 90/102 cases of adjacent non-tumorous liver tissues, and in 91 of 223 cases of HCC tissues. PTH1R expression was significantly related to tumor size, Edmondson Grade, AFP, and overall survival., Conclusions: PTH1R may be the major cause of hypercalcemia in HCC, and the decreased PTH1R expression was a poor prognosis in HCC.

The combination of oncolytic adenoviruses and specific chemotherapy agents is fast emerging as a novel therapeutic approach for resistan the patocellular carcinoma (HCC) cells. A detailed analysis of the network between adenovirus and chemotherapeutic agents can help design an effective strategy to combat HCC. We sought to investigate whether a combined treatment of ZD55-TRAIL and quercetin can have an enhanced cell-killing effect on HCC cells. In-vitro experiments showed that quercetin can enhance ZD55-TRAIL mediated growth inhibition and apoptosis in HCC cells. In addition, we showed that quercetin reduced ZD55-TRAIL mediated NF-κB activation and down-regulated its downstream targets, which in turn promoted the pro-apoptotic action of ZD55-TRAIL. Furthermore, in-vivo experiments in mice injected with HuH-7 cells resulted in significantly greater reduction in tumour growth and volume following combined ZD55-TRAIL and quercetin treatment. In conclusion, we demonstrated that quercetin could sensitize human HCC cells to apoptosis via ZD55-TRAIL in-vitro and in-vivo and presented ZD55-TRAIL and quercetin combination as a suitable anti-HCC therapy.

Chronic myeloid leukemia (CML) is a myeloproliferative pathology, originating from the hematopoietic cancer stem cells (hCSCs) due to the Bcl-Abl Philadelphia chromosome transformation. However, targeting these hCSCs as an effective anti-CML strategy is relatively less explored. Ovatodiolide (Ova) is a natural diterpenoid isolate of Anisomeles indica with broad anticancer activity. In this study, we investigated the anti-hCSCs potential of Ova against CD34 + /CD38 - , CD34 + /CD38 + , and unsorted K562 cell lines using flow cytometry, western blot, RT-PCR, genomic mapping, and tumorsphere formation assays. We demonstrated that compared to unsorted K562 and CD34 + /CD38 + , CD34 + /CD38 - cells were significantly enriched with Oct4, Sox2, CD133, Bcr-Abl, p-CrkL and p-Stat5 protein and/or mRNA. Furthermore, we showed that Ova alone or by enhancing the therapeutic potential of Imatinib, reduced the viability of CML cell lines, dose-dependently, irrespective of the cancer stemness, as well as markedly inhibit the Bcr-Abl, p-CrkL, Stat5, and MDR protein expression levels in CD34 + cells. Mechanistic investigations revealed a significant up-regulation of hsa-miR-155, which resulted in the reduction of dysregulating the PIK3CA expression in Ova-treated K562 CD34 + /CD38 - cells. Additionally, Ova alone or in combination with Imatinib suppressed the hCSC traits of the CD34 + /CD38 - cells, resulting in loss of their ability to form tumorspheres, enhanced apoptosis, increase in the Bax/Bcl-2 ratio, and dysregulation of the PI3K/AKT/mTOR signaling pathway. Together, these results demonstrate the PI3K/AKT/mTOR signaling-mediated anti-hCSC effect of Ova in CML, as well as suggest a likely role for Ova as a small molecule PI3K/mTOR dual inhibitor, thus, extending its potential benefit to other mTOR-mediated pathologies.

The homeobox protein homeobox (HOXA9) is a transcriptional factor that regulates patterning during embryogenesis and controls cell differentiation. HOXA9 dysfunction has been implicated in certain cancers. However, the role of HOXA9 in gastric cancer is poorly understood. The present study investigated HOXA9 and its cofactor PBX homeobox 3 (PBX3) expression in patients with gastric cancer. Paired tissue samples from 24 patients and paraffin embedded tissues of gastric cancer patients (104 males and 24 females) were included. HOXA9 and PBX3 expression levels were determined by reverse transcription quantitative polymerase chain reaction in fresh tissues, and by immunohistochemical staining in paraffin embedded tissues. The association between HOXA9/PBX3 expression and clinicopathological features was established. The results demonstrated that HOXA9 and PBX3 mRNA levels were significantly upregulated (P=0.032 for HOXA9 and P=0.031 for PBX3) in gastric cancer tissue. Immunohistochemical staining revealed that HOXA9 expression was associated with differentiation, lymph node metastasis and tumor-node-metastasis (TNM) stage, and PBX3 expression was associated with lymph node metastasis and TNM stage. Correlation analysis revealed a high coincidental expression of HOXA9 and PBX3 levels in gastric cancer (r=0.391; P<0.001). Survival analysis showed that high expression of HOXA9 or PBX3 was associated with poor survival of gastric cancer, and multivariate analysis using Cox's regression model showed that PBX3 expression was an independent prognostic factor in gastric cancer. There was elevated expression of HOXA9 and PBX3 in gastric cancer patients, and high-level expression of those proteins was associated with poor prognosis of gastric cancer. The present study underlines the significance of HOXA9/PBX3 in the development of gastric cancer.

Background and Aim: ZW10 interacting kinetochore protein 1 (Zwint-1), one of the major kinetochore proteins, is essential for kinetochore function, such as spindle assembly checkpoint function and kinetochore-microtubule attachment. Recently, it has been found over-expressed in some human cancers, including ovarian cancer, bladder cancer, and pulmonary adenocarcinoma. However, few studies of the expression of Zwint-1 in hepatocellular carcinoma (HCC) have been reported. This study is aimed to investigate the expression of Zwint-1 and its relationship with clinical pathological characters in HCC., Methods: The expression of Zwint-1 protein was analyzed by immunohistochemistry staining on tissue microarrays containing 171 HCC tissues and 187 control non-tumorous liver tissues. The relationships between the Zwint-1 expression and the clinicopathological parameters, and survival analysis were investigated using SPSS software 13.0., Results: Zwint-1 was found uniformly expressed in adjacent non-tumorous liver tissues (184/187, 98.40%), while was significantly decreased in HCC tissues, or even absent (150 of 171, 61.82%, P <0.001). The expression of Zwint-1 was negatively associated with age, tumor size, and Edmondson Grade. Besides, HCC patients with low Zwint-1 expression were also correlated with poor overall survival of the patients., Conclusions: Decreased expression of Zwint-1 was associated with poor prognosis in HCC., Competing Interests: None., (IJCEP Copyright © 2017.)

Although advancements in medical technology supporting cancer diagnosis and treatment have improved survival, these technologies still have limitations. Recently, the application of noninvasive imaging for cancer diagnosis and therapy has become an indispensable component in clinical practice. However, current imaging contrasts and tracers, which are in widespread clinical use, have their intrinsic limitations and disadvantages. Nanotechnologies, which have improved in vivo detection and enhanced targeting efficiency for cancer, may overcome some of the limitations of cancer diagnosis and therapy. Theranostic nanoparticles have great potential as a therapeutic model, which possesses the ability of their nanoplatforms to load targeted molecule for both imaging and therapeutic functions. The resulting nanosystem will likely be critical with the growth of personalized medicine because of their diagnostic potential, effectiveness as a drug delivery vehicle, and ability to oversee patient response to therapy. In this review, we discuss the achievements of modern nanoparticles with the goal of accurate tumor imaging and effective treatment and discuss the future prospects.

Osteoporosis is a disease characterized by structural deterioration of bone tissue, leading to skeletal fragility with increased fracture risk. Calcium phosphates (CaPs) are widely used in bone tissue engineering strategies as they have similarities to bone apatite except for the absence of trace elements (TEs) in the CaPs. Bioactive glasses (BGs) have also been used successfully in clinic for craniomaxillofacial and dental applications during the last two decades due to their excellent potential for bonding with bone and inducing osteoblastic differentiation. In this study, we evaluated the osteogenic effects of the ionic dissolution products of the quaternary Si-Sr-Zn-Mg-codoped CaP (TEs-CaP) or 45S5 Bioglass® (45S5 BG), both as mixtures and separately, on rat bone marrow-derived mesenchymal stem cells (rOMSCs & rMSCs) from osteoporotic and normal animals, using an MTT test and Alizarin Red S staining. The materials enhanced cell proliferation and osteogenic differentiation, especially the combination of the BG and TEs-CaP. Analysis by quantitative PCR and ELISA indicated that the expression of osteogenic-specific genes and proteins were elevated. These investigations suggest that the TEs-CaP and 45S5 BG operate synergistically to create an extracellular environment that promotes proliferation and terminal osteogenic differentiation of both osteoporotic and normal rMSCs.

Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics. Secretable trimeric TRAIL (stTRAIL) contains the receptor-binding domain of TRAIL, a death ligand that induces apoptosis in tumor cells. To overexpress stTRAIL, MenSCs were infected with efficient adenoviral serotype 35 vectors that had no influence on its broad multipotency and low immunophenotype. The modified MenSCs served as an excellent local drug delivery system for tumor site-specific targeted delivery and demonstrated therapeutic efficacy in an animal xenografts tumor model of U-87 MG cells. The MenSC-stTRAIL cells induced antitumor effects in vitro by significantly increasing apoptosis ( P < 0.05). It also significantly reduced tumor burden in vivo ( P < 0.05). The results showed that the proliferation of tumor cells was significantly reduced ( P < 0.05). The MenSC, as a cellular delivery vehicle has a wide potential therapeutic role, which includes the treatment of tumors., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 μL·L -1 ) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC Δ and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCΔ-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine., (Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Introduction: Ceramide is a bioactive lipid which functions as a tumor suppressor, regulating processes such as cell proliferation, differentiation, senescence and apoptosis. However, several challenges need to be overcome in order to realize the therapeutic potential of such a bioactive lipid combination regimen, including the hydrophobic and hemolytic nature of the lipids., Areas Covered: In this review, we briefly describe the biological function of ceramide, then the delivery systems that have been developed to improve the pharmacology of ceramide have been summarized. In addition, combination therapies based on these delivery systems to reveal the interactions between therapeutic drugs and ceramide were also highlighted. Furthermore, future perspective before the extension of ceramide's applications in cancer treatment will also be discussed., Expert Opinion: Although ceramide has attracted tremendous attention in targeted cancer treatment, its levels are usually suppressed by over-expression of ceramide-metabolizing enzymes or down-regulation of ceramide-generating enzymes. Thus, finding ways to increase ceramide by exogenous treatment in cancer cells is desired. Therefore, translating these bioactive lipids into clinical usage requires a variety of methods, and appropriately designed delivery systems may play the direct and important role in this process.

The coxsackie and adenovirus receptor (CAR) is considered a tumor suppressor and critical factor for the efficacy of therapeutic strategies that employ the adenovirus. However, data on CAR expression levels in colorectal cancer are conflicting and its clinical relevance remains to be elucidated. Immunohistochemistry was performed on tissue microarrays containing 251 pairs of colon cancer and adjacent normal tissue samples from Chinese Han patients to assess the expression levels of CAR. Compared with healthy mucosa, decreased CAR expression (40.6% vs. 95.6%; P<0.001) was observed in colorectal cancer samples. The CAR immunopositivity in tumor tissues was not significantly associated with gender, age, tumor size, differentiation, TNM stage, lymph node metastasis or distant metastasis in patients with colon cancer. However, expression of CAR is present in 83.3% of the tumor tissues from patient with colorectal liver metastasis, which was significantly higher than those without liver metastasis (39.6%; P=0.042). At the plasma membrane, CAR was observed in 29.5% normal mucosa samples, which was significantly higher than in colorectal cancer samples (4.0%; P<0.001). In addition, the survival analysis demonstrated that the expression level of CAR has no association with the prognosis of colorectal cancer. CAR expression was observed to be downregulated in colorectal cancer, and it exerts complex effects during colorectal carcinogenesis, potentially depending on the stage of the cancer development and progression. High CAR expression may promote liver metastasis. With regard to oncolytic therapy, CAR expression analysis should be performed prior to adenoviral oncolytic treatment to stratify Chinese Han patients for treatment.