Probiotics for coral aquaculture: challenges and considerations

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Global networks for invasion science: benefits,challenges and guidelines

Much has been done to address the challenges of biological invasions, but fundamental questions (e.g., which species invade? Which habitats are invaded? How can invasions be effectively managed?) still need to be answered before the spread and impact of alien taxa can be effectively managed. Questions on the role of biogeography (e.g., how does biogeography influence ecosystem susceptibility, resistance and resilience against invasion?) have the greatest potential to address this goal by increasing our capacity to understand and accurately predict invasions at local, continental and global scales. This paper proposes a framework for the development of ‘Global Networks for Invasion Science’ to help generate approaches to address these critical and fundamentally biogeographic questions. We define global networks on the basis of their focus on research questions at the global scale, collection of primary data, use of standardized protocols and metrics, and commitment to long-term global data. Global networks are critical for the future of invasion science because of their potential to extend beyond the capacity of individual partners to identify global priorities for research agendas and coordinate data collection over space and time, assess risks and emerging trends, understand the complex influences of biogeography on mechanisms of invasion, predict the future of invasion dynamics, and use these new insights to improve the efficiency and effectiveness of evidence-based management techniques. While the pace and scale of global change continues to escalate, strategic and collaborative global networks offer a powerful approach to inform responses to the threats posed by biological invasions.     

CAR-T therapy: Prospects in targeting cancer stem cells

Cancer stem cells (CSCs), a group of tumour cells with stem cell characteristics, have the ability of self-renewal, multi-lineage differentiation and tumour formation. Since CSCs are resistant to conventional radiotherapy and chemotherapy, their existence may be one of the root causes of cancer treatment failure and tumour progression. The elimination of CSCs may be effective for eventual tumour eradication. Because of the good therapeutic effects without major histocompatibility complex (MHC) restriction and the unique characteristics of CSCs, chimeric antigen receptor T-cell (CAR-T) therapy is expected to be an important method to eliminate CSCs. In this review, we have discussed the feasibility of CSCs-targeted CAR-T therapy for cancer treatment, summarized current research and clinical trials of targeting CSCs with CAR-T cells and forecasted the challenges and future direction from the perspectives of toxicity, persistence and potency, trafficking, infiltration, immunosuppressive tumour microenvironment, and tumour heterogeneity.     

Radiation protection: the NCRP guidelines and some considerations for the future.

The National Council on Radiation Protection and Measurements (NCRP) in the USA and the International Commission on Radiological Protection (ICRP), worldwide, were formed about 1928 and have since made recommendations on appropriate levels of protection from ionizing radiation for workers and for the public. These recommendations and much of the guidance provided by these organizations have usually been adopted by regulatory bodies around the world. In the case of the NCRP, the levels have fallen from 0.1 roentgen per day in 1934 to the current 5 rem per year (a factor of about 5). The present levels recommended by both the ICRP and the NCRP correspond to reasonable levels of risk where the risks of harm from ionizing radiation are compared with the hazards of other, commonly regarded, as safe, industries. Some considerations for the future in radiation protection include trends in exposure levels (generally downward for the average exposure to workers) and improvements in risk estimation; questions of lifetime limits, de minimis levels, and partial body exposures; plus problems of high LET radiations, acceptability of risk, synergisms, and risk systems for protection.     

CAR-T cells and solid tumors: tuning T cells to challenge an inveterate foe

Recent reports on the impressive efficacy of adoptively transferred T cells to challenge cancer in early phase clinical trials have significantly raised the profile of T cell therapy. Concomitantly, general expectations are also raised by these reports, with the natural aspiration to deliver this therapy over a wide range of tumor indications. Chimeric antigen receptors (CARs) endow T cell populations with defined antigen specificities that function independently of the natural T cell receptor and permit targeting of T cells towards virtually any tumor. Here, we review the current clinical application of CAR-T cells and relate clinical efficacy and safety of CAR-T cell trials to parameters considered critical for CAR engineering, classified as the three T's of CAR-T cell manipulation.     

Clinical trials of CAR-T cells in China

Novel immunotherapeutic agents targeting tumor-site microenvironment are revolutionizing cancer therapy. Chimeric antigen receptor (CAR)-engineered T cells are widely studied for cancer immunotherapy. CD19-specific CAR-T cells, tisagenlecleucel, have been recently approved for clinical application. Ongoing clinical trials are testing CAR designs directed at novel targets involved in hematological and solid malignancies. In addition to trials of single-target CAR-T cells, simultaneous and sequential CAR-T cells are being studied for clinical applications. Multi-target CAR-engineered T cells are also entering clinical trials. T cell receptor-engineered CAR-T and universal CAR-T cells represent new frontiers in CAR-T cell development. In this study, we analyzed the characteristics of CAR constructs and registered clinical trials of CAR-T cells in China and provided a quick glimpse of the landscape of CAR-T studies in China.     

Establishing a master's degree programme in bioinformatics: challenges and opportunities

The development of the Bioinformatics MS degree program at the University of Illinois, the challenges and opportunities associated with such a process, and the current structure of the program is described. This program has departed from earlier University practice in significant ways. Despite the existence of several interdisciplinary programs at the University, a few of which grant degrees, this is the first interdisciplinary program that grants degrees and formally recognises departmental specialisation areas. The program, which is not owned by any particular department but by the Graduate College itself, is operated in a franchise-like fashion via several departmental concentrations. With four different colleges and many more departments involved in establishing and operating the program, the logistics of the operation are of considerable complexity but result in significant interactions across the entire campus.     

CD166-specific CAR-T cells potently target colorectal cancer cells

Chimeric antigen receptor (CAR) T-cell therapy is emerging as an effective cancer treatment, such as for hematological malignancies, however its effectiveness as an approach to treat solid tumors, such as in colorectal cancer (CRC), remains to be better developed. One area of intense development has been in the identification and characterization of novel cancer-related ligand receptors for CAR design and evaluation. It is known that the CD6 receptors CD166 and CD318 are highly expressed in CRC, and several CAR-Ts have also been explored in preclinical and clinical studies for the treatment of CRC, with promising safety and efficacy findings. Here, we constructed a CAR based on the extracellular domain of CD6 and demonstrate its cytotoxic effect in target positive human CRC cell lines. Unexpectedly, we found that CD6-CAR-T cells targeted CD166 instead of CD318. Furthermore, CD6-CAR-T cells show robust cytotoxicity to CD166-positive cell lines in a dose-dependent manner with cytokine IFN-γ significantly released. Particularly, CD6-CAR-T cells show potent cytotoxicity targeting CRC cancer stem cells (CSCs), highlighting that CD6-CAR-T is a promising approach for the therapy of CRC.     

Design considerations and challenges for mechanical stretch bioreactors in tissue engineering

With the increase in average life expectancy and growing aging population, lack of functional grafts for replacement surgeries has become a severe problem. Engineered tissues are a promising alternative to this problem because they can mimic the physiological function of the native tissues and be cultured on demand. Cyclic stretch is important for developing many engineered tissues such as hearts, heart valves, muscles, and bones. Thus a variety of stretch bioreactors and corresponding scaffolds have been designed and tested to study the underlying mechanism of tissue formation and to optimize the mechanical conditions applied to the engineered tissues. In this review, we look at various designs of stretch bioreactors and common scaffolds and offer insights for future improvements in tissue engineering applications. First, we summarize the requirements and common configuration of stretch bioreactors. Next, we present the features of different actuating and motion transforming systems and their applications. Since most bioreactors must measure detailed distributions of loads and deformations on engineered tissues, techniques with high accuracy, precision, and frequency have been developed. We also cover the key points in designing culture chambers, nutrition exchanging systems, and regimens used for specific tissues. Since scaffolds are essential for providing biophysical microenvironments for residing cells, we discuss materials and technologies used in fabricating scaffolds to mimic anisotropic native tissues, including decellularized tissues, hydrogels, biocompatible polymers, electrospinning, and 3D bioprinting techniques. Finally, we present the potential future directions for improving stretch bioreactors and scaffolds. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:543–553, 2016     

Remote controlling of CAR-T cells and toxicity management: Molecular switches and next generation CARs

Cell-based immunotherapies have been selected for the front-line cancer treatment approaches. Among them, CAR-T cells have shown extraordinary effects in hematologic diseases including chemotherapy-resistant acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL). In this approach, autologous T cells isolated from the patient''s body genetically engineered to express a tumor specific synthetic receptor against a tumor antigen, then these cells expanded ex vivo and re-infusion back to the patient body. Recently, significant clinical response and high rates of complete remission of CAR T cell therapy in B-cell malignancies led to the approval of Kymriah and Yescarta (CD19-directed CAR-T cells) were by FDA for treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Despite promising therapeutic outcomes, CAR T cells also can elicit the immune-pathologic effects, such as Cytokine Release Syndrome (CRS), Tumor Lysis Syndrome (TLS), and on-target off-tumor toxicity, that hampered its application. Ineffective control of these highly potent synthetic cells causes discussed potentially life-threatening toxicities, so researchers have developed several mechanisms to remote control CAR T cells. In this paper, we briefly review the introduced toxicities of CAR-T cells, then describe currently existing control approaches and review their procedure, pros, and cons.     

Anti-BCMA CAR-T cells for treatment of plasma cell dyscrasia: case report on POEMS syndrome and multiple myeloma

Background

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome still has no standard treatment. On the basis that both POEMS syndrome and myeloma have an underlying plasma cell dyscrasia, anti-myeloma therapy can be expected to be useful for POEMS syndrome. Chimeric antigen receptor T (CAR-T) cells targeting B cell maturation antigen (BCMA) has been used in the treatment of relapsed and refractory multiple myeloma (RRMM). No POEMS syndrome cases treated with anti-BCMA CAR-T cells have been reported.

Case presentation

Here, we, for the first time, report a POEMS syndrome case treated with anti-BCMA CAR-T cells. A 49-year-old female with incapacitating POEMS syndrome that progressed on lenalidomide treatment was enrolled in a phase I study involving anti-BCMA CAR-T cells (ChiCTR-OPC-16009113). Another patient with RRMM who had undergone six prior lines treatments was also enrolled in the study. They received infusions of anti-BCMA CAR-T cells. Both patients achieved a stringent complete response. Complete remission persisted in the patient with POEMS syndrome and lasted for 7.6 months before a relapse in RRMM patient. Both patients had toxicity consistent with the grade 1 cytokine release syndrome.

Conclusions

This is the first report of treatment by anti-BCMA CAR-T cells in POEMS syndrome. Our findings demonstrate the anti-BCMA CAR-T cell treatment may be a feasible therapeutic option for patients with POEMS syndrome and RRMM who do not respond well to traditional therapies.

Trial registration

ChiCTR-OPC, ChiCTR-OPC-16009113. Registered 29 August 2016.

     

Trop-2 targeted CAR-T cells inflict enhanced killing of ovarian cancer cells

T cell modified by chimeric antigen receptor (CAR) is considered one of the most promising tumor therapies for its almost magic effect in the treatment of hematologic malignancies. Encouraged by breakthroughs in this area, we produced Trop-2-redirected chimeric antigen receptor-modified T (Trop-2 CAR-T) cells and tested their function on ovarian cancer cells in vitro molecular cloning. Gene recombination technology was introduced to construct the Trop-2 CAR vector. The expression of Trop-2 CAR on 293T cells was tested by western blot. The effect of Trop-2 CAR-T cells on the proliferation of ovarian cancer cells was evaluated by CCK-8 assay. We found that Trop-2 CAR-T cells prominently inhibited the growth of ovarian cancer cells with Trop-2 antigen expression (P<0.05), moreover, high levels of IFN-γ and IL-2 were detected in supernatant by ELISA (P<0.01). These results suggest that Trop-2 CAR-T cells have the potential to be a clinical treatment for patients with Trop-2 positive ovarian cancer.     

Pluripotent Stem Cells Models for Huntington＇s Disease： Prospects and Challenges

Pluripotent cellular models have shown great promise in the study of a number of neurological disorders.Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types,providing a system for researchers to monitor disease progression during neurogenesis,along with serving as a platform for drug discovery.A number of stem cell derived models have been employed to establish in vitro research models of Huntington’s disease that can be used to investigate cellular pathology and screen for drug and cell-based therapies.Although some progress has been made,there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved.In this article we review current stem cell models that have been reported,as well as discuss the issues that impair these studies.We also highlight the prospective application of Huntington’s disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine.     

Endothelial progenitor cells: diagnostic and therapeutic considerations

Endothelial progenitor cells (EPCs) may be defined as adherent cells derived from peripheral blood- or bone marrow-derived mononuclear cells demonstrating acLDL uptake and isolectin-binding capacity. The number of circulating EPCs inversely correlates with the number of cardiovascular risk factors and is reduced in cardiovascular disease. This measurement may therefore serves as a surrogate marker for cardiovascular disease risk. EPC numbers can be modified by various means. However, the effectiveness of risk-factor modification on EPC number and function is currently unknown. Furthermore, EPCs may be used as a potential therapy for a variety of vascular disease states including ischaemia, restenosis and pulmonary hypertension. This review provides an update on multiple factors that affect EPC number as well as highlighting the potential use of EPCs as a novel marker of vascular dysfunction. Furthermore, potential gene- and/or EPC-based approaches to a number of vascular disease states are explored.     

iPSCs from cancer cells: challenges and opportunities

Reprogramming and oncogenic transformation are stepwise processes that share many similarities, and induced pluripotent stem cells (iPSCs) generated from cancer cells could illuminate molecular mechanisms underlying the pathogenesis of human cancer. Deciphering the barriers underlying the reprogramming process of primary cancer cells could reveal information on the links between pluripotency and oncogenic transformation that would be instrumental for therapy development.