VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects

Despite setbacks, the clinical development of antiangiogenic agents has accelerated remarkably over the past 3-4 years. Consequently, there are currently three direct inhibitors of the VEGF pathway approved for use in cancer therapy. Other agents that block the VEGF pathway are in advanced stages of clinical development and have shown promising results. With these exciting developments come crucial questions regarding the use of these new molecular-targeted agents, alone or in combination with standard cytotoxic or targeted agents. Importantly, the mechanisms of action of anti-VEGF therapy remain unknown. Here, we discuss several potential mechanisms of action such as tumor vascular normalization, bone marrow-derived cell recruitment blockade and cytostatic effects of anti-VEGF therapy. We review the current progress, the major stumbling blocks and the future directions for anti-cancer therapy using anti-VEGF agents, emphasizing clarification of the underlying molecular mechanisms of action and biomarker identification and validation.     

Anti-angiogenic gene therapy of cancer: current status and future prospects

The discovery of endogenous inhibitors of angiogenesis has made it possible to test the hypothesis that blocking the angiogenic switch may keep tumor growth in check, and has added a new investigational arm to the field of cancer gene therapy. Angiogenesis inhibitors are heterogeneous in origin and potency, and their growing list includes proteolysis products of larger molecules with a different function, such as angiostatin, endostatin and vasostatin, modulators of vascular endothelial growth factor activity, such as sFLT-1, and some cytokines/chemokines with marked anti-endothelial activity, such as IL-12, IFN-alpha, and CXCL10. Pre-clinical studies have clearly indicated that these factors are essentially cytostatic and that they need long-term administration in order to obtain prolonged anti-tumor effects, representing a rational basis for their delivery by a gene therapy approach. The experimental approaches attempted to date, reviewed herein, indicate overall that anti-angiogenic gene therapy has efficacy mainly as an early intervention strategy and that a better understanding of the biological mechanisms underlying resistance to angiogenesis inhibition, as well as appropriate combined treatments, are required to generate a conceptual advancement which could drive the field towards successful management of established tumors.     

Carriers and channels: current progress and future prospects

Recent advances in the understanding of biological transport and in the design of artificial transport systems have resulted from the structural elucidation of the K⁺ ion channel and from synthesis of artificial receptors for cations and anions, as well as neutral and zwitterionic organic molecules. Sensors, gated carriers, and self-assembling capsules and nanotubes are all important offsprings of current efforts to mimic natural transport across biomembranes.     

Targeted induction of apoptosis for cancer therapy: current progress and prospects

Important breakthroughs in cancer therapy include clinical application of antibodies, such as Rituximab, and small inhibitory molecules, such as Iressa and Velcade. In addition, recent reports have indicated the therapeutic potential of physiological pro-apoptotic proteins such as TRAIL and galectin-1. Although unrelated at first glance, each strategy relies on the deliberate and selective induction of apoptosis in malignant cells. Importantly, therapy-resistance in cancer is frequently associated with de-regulation in the mechanisms that control apoptosis. However, cancer cells are often reliant on these molecular aberrations for survival. Therefore, selective induction of apoptosis in cancer cells but not normal cells seems feasible. Here, we review recent progress and prospects of selected novel anti-cancer approaches that specifically target and sensitize cancer cells to apoptosis.     

Energy crops: current status and future prospects

Energy crops currently contribute a relatively small proportion to the total energy produced from biomass each year, but the proportion is set to grow over the next few decades. This paper reviews the current status of energy crops and their conversion technologies, assesses their potential to contribute to global energy demand and climate mitigation over the next few decades, and examines the future prospects. Previous estimates have suggested a technical potential for energy crops of～400 EJ yr^?1 by 2050. In a new analysis based on energy crop areas for each of the IPCC SRES scenarios in 2025 (as projected by the IMAGE 2.2 integrated assessment model), more conservative dry matter and energy yield estimates and an assessment of the impact on non‐CO₂ greenhouse gases were used to estimate the realistically achievable potential for energy crops by 2025 to be between 2 and 22 EJ yr^?1, which will offset～100–2070 Mt CO₂‐eq. yr^?1. These results suggest that additional production of energy crops alone is not sufficient to reduce emissions to meet a 550 μmol mol^?1 atmospheric CO₂ stabilization trajectory, but is sufficient to form an important component in a portfolio of climate mitigation measures, as well as to provide a significant sustainable energy resource to displace fossil fuel resources. Realizing the potential of energy crops will necessitate optimizing the dry matter and energy yield of these crops per area of land through the latest biotechnological routes, with or without the need for genetic modification. In future, the co‐benefits of bioenergy production will need to be optimized and methods will need to be developed to extract and refine high‐value products from the feedstock before it is used for energy production.     

Cacao biotechnology: current status and future prospects

Theobroma cacao—The Food of the Gods, provides the raw material for the multibillion dollar chocolate industry and is also the main source of income for about 6 million smallholders around the world. Additionally, cocoa beans have a number of other nonfood uses in the pharmaceutical and cosmetic industries. Specifically, the potential health benefits of cocoa have received increasing attention as it is rich in polyphenols, particularly flavonoids. At present, the demand for cocoa and cocoa‐based products in Asia is growing particularly rapidly and chocolate manufacturers are increasing investment in this region. However, in many Asian countries, cocoa production is hampered due to many reasons including technological, political and socio‐economic issues. This review provides an overview of the present status of global cocoa production and recent advances in biotechnological applications for cacao improvement, with special emphasis on genetics/genomics, in vitro embryogenesis and genetic transformation. In addition, in order to obtain an insight into the latest innovations in the commercial sector, a survey was conducted on granted patents relating to T. cacao biotechnology.     

Cell therapy in critical limb ischemia: current developments and future progress

Critical limb ischemia (CLI) is a syndrome manifested by ischemic rest pain, non-healing ulcers and tissue loss. CLI patients are at very high risk of amputation and experience poor physical function, leading to severe morbidity and mortality. The fundamental goal for CLI treatment is to relieve ischemic rest pain, heal ulcers, prevent limb loss and improve the quality of life, thereby extending the survival of the patient. Surgical or endovascular revascularization aimed at increasing blood flow is currently available for limb salvage in CLI. However, up to 30% of CLI patients are not suitable for such interventions because of high operative risk or unfavorable vascular anatomy. Therefore exploring new and more effective strategies for revascularization of ischemic limbs is imperative for the establishment of a viable therapeutic alternative. With the emergence of new approaches, this review describes up-to-date progress and developments in cell-based therapy as a novel and promising alternative for CLI treatment. Preliminary clinical data have established the safety, feasibility and efficacy of stem cells, and numerous studies are underway to consolidate this evidence further. However, significant hurdles remain to be addressed before this research can be responsibly translated to the bedside. In particular, we need better understanding of the behavior of cells post-transplantation and to learn how to control their survival and migration proliferation/differentiation in the hostile pathologic environment. Future research should focus on methods of isolation, optimal dosage, appropriate cell type, route of administration, role of tissue-derived factors and supportive endogenous stimulation.     

The nitrile-degrading enzymes: current status and future prospects

Nitrile-converting enzymes are becoming commonplace in the synthesis of pharmaceuticals and commodity chemicals. These versatile biocatalysts have potential applications in different fields including synthetic biocatalysis and bioremediation. This review attempts to describe in detail the three major classes of nitrile-converting enzymes, namely nitrilases, nitrile hydratases and amidases. Various aspects of these enzymes including their occurrence, mechanism of action, characteristics and applicability in different sectors have been elaborately elucidated. Cloning of genes related to nitrile-converting enzymes is also discussed.     

Vitamin K series: current status and future prospects

The Vitamin K series, particularly menaquinone, have been attracting research attention, due to the potential in reducing both osteoporosis and cardiovascular diseases. This review provides an overview of the types of vitamin K and their health benefits. This is followed by a critical review of the various biotechnological approaches used in the production of menaquinone, including solid and liquid state fermentations, extraction and recovery. The currently available market information is summarized and future growth prospects are discussed. Recommendations are also given for areas of future research in order to improve the production process for menaquinone and reduce costs.     

Chemotherapy of human African trypanosomiasis: current and future prospects

Three of the four currently approved drugs for the treatment of African trypanosomiasis (sleeping sickness) were developed over 50 years ago. All of the current therapies are unsatisfactory for various reasons, including unacceptable toxicity, poor efficacy, undesirable route of administration, and drug resistance. The possible modes of action of these drugs are briefly reviewed, as are the possible mechanisms of resistance. The intermediate and long-term prospects for the development of safer, effective drugs are discussed.     

Genetic engineering of millets: current status and future prospects

This review summarizes progress on the genetic transformation of millets and discusses the future prospects for the development of improved varieties. Only a limited number of studies have been carried out on genetic improvement of millets despite their nutritional importance in supplying minerals, calories and protein. Most genetic transformation studies of millets have been restricted to pearl millet and bahiagrass and most studies have been limited to the assessment of reporter and marker gene expression. Biolistic-mediated gene delivery has been frequently used for the transformation of millets but Agrobacterium-mediated transformation is still lagging. Improved transformation of millets, allied to relevant gene targets which may offer, for example, improved nutritional quality, resistance to abiotic and biotic stresses, and resistance to fungal infection will play important roles in millet improvement.     

Molecular basis of obesity: current status and future prospects

Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of "deep phenotyping" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.     

Genetic transformation of wheat: current status and future prospects

Genetic transformation is a reverse genetics tool for validation of target genes and crop improvement. However, due to its low efficiency and genotype dependency, wheat is considered a recalcitrant plant for genetic transformation. During the last 20 years, various in vitro and in planta transformation methods have been reported in wheat. Until now, biolistic particle and Agrobacterium-mediated wheat transformation methods using immature embryos as explants have been the two major transformation approaches. In addition to immature embryos, other explant types, such as mature embryos, anther-derived calli, inflorescences, apical meristems, and other floral organs, have been employed; however, they need further optimization. In addition to the common marker genes, such as bar, hpt and gus, other effective markers, ALS, AtMYB12 and pmi, have been successfully used for selection of positive transgenic plants. Numerous agronomic trait genes such as biotic stress resistance or tolerance genes have been transferred into wheat plants. Future prospects, such as recipient wheat cultivars and explants, marker free issues, and transgene silencing, are discussed. The objective of this review is to summarize current successful techniques for wheat transformation and stimulate further research into long-term wheat improvement by genetic engineering approaches.     

Management of COVID-19: current status and future prospects

COVID-19, a highly transmissible pandemic disease, is affecting millions of lives around the world. Severely infected patients show acute respiratory distress symptoms. Sustainable management strategies are required to save lives of the infected people and further preventing spread of the virus. Diagnosis, treatment, and vaccination development initiatives are already exhibited from the scientific community to fight against this virus. In this review, we primarily discuss the management strategies including prevention of spread, prophylaxis, vaccinations, and treatment for COVID-19. Further, analysis of vaccine development status and performance are also briefly discussed. Global socioeconomic impact of COVID-19 is also analyzed as part of this review.     

Genomics of brown algae: current advances and future prospects

The analysis of the complete genome sequence of the filamentous brown alga Ectocarpus provided many new insights into brown algal biology and has improved our understanding of how this organism has adapted to its seashore environment. Since the publication of the genome sequence in 2010, numerous studies have continued the analysis of the constituent genes or have combined genome data with experimental work, allowing progress in several key areas, including metabolism and reproductive biology. Ectocarpus will continue to be exploited as a model organism in future years, but genomic approaches should also be extended to additional brown algal species in order to fully exploit the diversity of this phylogenetic group and to facilitate the application of new knowledge to economically important seaweeds such as kelps.     

Mechanistic simulations of inflammation: current state and future prospects

Inflammation is a normal, robust physiological process. It can also be viewed as a complex system that senses and attempts to resolve homeostatic perturbations initiated from within the body (for example, in autoimmune disease) or from the outside (for example, in infections). Virtually all acute and chronic diseases are either driven or modulated by inflammation. The complex interplay between beneficial and harmful arms of the inflammatory response may underlie the lack of fully effective therapies for many diseases. Mathematical modeling is emerging as a frontline tool for understanding the complexity of the inflammatory response. A series of articles in this issue highlights various modeling approaches to inflammation in the larger context of health and disease, from intracellular signaling to whole-animal physiology. Here we discuss the state of this emerging field. We note several common features of inflammation models, as well as challenges and prospects for future studies.     

Human astrovirus diagnosis and typing: current and future prospects

Human astroviruses (HAstV) are important human pathogens causing gastroenteritis worldwide. The increased recognition of astroviruses as the cause of sporadic outbreaks of disease is due to the recent availability of improved diagnostic methods. During the last decade, most epidemiological surveys have chosen astrovirus-specific RT-PCR as screening methods. In addition to serotyping by molecular techniques, new typing methods are being developed that may also identify other viral properties related to virulence. The information provided by different typing assays is required for a better understanding of both the antigenic diversity and the molecular mechanisms of pathogenicity.