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Evodiamine (EVO) is an active medicinal compound derived from the traditional herbal medicine Evodia rutaecarpa. It has been reported that evodiamine has several beneficial biological properties, including anticancer and anti-inflammatory activities. However, the in vitro and in vivo anticancer activities of EVO against the growth of glioblastoma cells remain undefined. EVO induced significant decreases in the viability of U87 and C6 glioma cells, but not of primary astrocytes, according with the occurrence of apoptotic characteristics including DNA ladders, caspase-3 and poly(ADP ribose) polymerase (PARP) protein cleavage, and hypodiploid cells. The disruption of the mitochondrial membrane potential (MMP) was detected, and it was found that the peptidyl caspase-9 inhibitor, Z-LEHD-FMK, significantly prevented glioma cells from EVO-induced apoptosis. Increased c-Jun N-terminal kinase (JNK) protein phosphorylation by EVO was observed, and the addition of JNK inhibitors, SP600125 and JNKI inhibited the EVO-induced apoptosis was inhibited. Additionally, EVO treatment induced G2/M arrest with increased polymerized tubulin protein expression in U87 and C6 cells. Elevated expressions of the cyclin B1, p53, and phosphorylated (p)-p53 proteins were detected in EVO-treated glioma cells, and these were inhibited by JNK inhibitors. An in vivo study showed that EVO significantly reduced the growth of gliomas elicited by the subcutaneous injection of U87 cells with increases in cyclin B1, p53, and p-p53 protein expressions in tumors. An analysis of eight EVO-related chemicals showed that alkyl groups at position 14 in EVO are important for its anti-glioma effects which involve both apoptosis and G2/M arrest. Evidence is provided that supports EVO induction of apoptosis and G2/M arrest via the activation of JNK-mediated gene expression and disruption of MMP in glioblastoma cells. EVO was shown to penetrate the blood–brain barrier; EVO is therefore predicted to be a promising compound for the chemotherapy of glioblastomas and deserves further investigations.

Glioblastoma is the most common primary malignant tumor of the central nervous system, with an annual incidence of 5.26 per 100000 people. The clinical outcome of standard therapy and the survival rate remain poor; therefore, there is an unmet need for a new strategy to treat this lethal disease. Although amentoflavone was known to have anticancer potential in various types of cancers, its antiglioblastoma ability and mechanism remain unrecognized. We demonstrated that amentoflavone may suppress glioblastoma invasion and migration by transwell assay. Moreover, we established NF-$\kappa$B reporter gene system and used that for verifying NF-$\kappa$B inhibition efficacy of amentoflavone on in vitro and in vivo studies. Here, we indicated that amentoflavone not only diminished NF-$\kappa$B activation, but also reduced NF-$\kappa$B-mediated downstream oncogenes expression, such as MMP-2, MMP-9, XIAP, cyclinD1 and VEGF, which was elucidated by Western blot and immunohistochemistry (IHC). Tumor growth inhibition and NF-$\kappa$B reduction was found in the amentoflavone treatment group, which was revealed by the glioblastoma-bearing animal model. In this study, we also used ERK inhibitor and NF-$\kappa$B inhibitor (QNZ) to confirm whether the beneficial result of amentoflavone on glioblastoma was mainly regulated by blockage of ERK/NF-$\kappa$B signaling. In summary, ERK/NF-$\kappa$B signaling pathway has a role in the inhibition of tumor growth by amentoflavone in glioblastoma.

Gliomas are the mostly observed form of primary brain tumor, and glioblastoma multiforme (GBM) shows the highest incidence. The survival rate of GBM is fairly poor; thus, discovery of effective treatment options is required. Among several suggested targets for therapy, the Axl/IL-6/STAT3 signaling pathway has gained recent interest because of its important role within cancer microenvironment. Quercetin, a plant flavonoid, is well known for its anticancer action. However, the effect of quercetin on Axl has never been reported. Quercetin treatment significantly reduced cell viability in two GBM cell lines of U87MG and U373MG while keeping 85% of normal astrocytes alive. Further western blot assays suggested that quercetin induces apoptosis but does not affect Akt or mitogen-activated protein kinases, factors related to cell proliferation. Quercetin also decreased IL-6 release and phosphorylation of STAT3 in GBM cells. In addition, gene expression, protein expression, and half-life of synthesized Axl protein were all suppressed by quercetin. By applying shRNA for knockdown of Axl, we could confirm that the role of Axl was crucial in the apoptotic effect of quercetin on GBM cells. In conclusion, we suggest quercetin as a potential anticancer agent, which may improve cancer microenvironment of GBM via the Axl/IL-6/STAT3 pathway.

Carpal tunnel syndrome is a common condition with many aetiologies. We present a case report of a glioblastoma which presented as carpal tunnel syndrome, and highlights that the most proximal site for pathology is not the spinal cord.

China’s 2018 Future Science Prize winners announced.

China tops world in alcohol-related deaths.

Nanotech to inhibit wheat sprouting.

New antibacterial hydrogel for wound healing.

Genetically modified Zika virus vaccine to treat brain tumour.

Semi-elastic nanoparticles to deliver drugs.

Chinese stent for heart disease reported safe in European patients.

First China-developed drug for colorectal cancer approved in China.

More medicines added to the national list of essential medicines.

Recent revisions in Chinese regulations open new doors for contract research organisations.

The following topics are under this section:

• ASIA-PACIFIC — Predisposition of age-related muscle loss among elderly with Type 2 Diabetes.
• ASIA-PACIFIC — Unravelling the Mystery of Ankylosing Spondylitis
• ASIA-PACIFIC — Improving Mental Health through Mindfulness Training
• ASIA-PACIFIC — Strengthening international collaboration to combat the next global health threat
• ASIA-PACIFIC — DNA repair in human cells by Class 1 CRISPR gene editing system
• ASIA-PACIFIC — Visualization of Dengue in Vietnam
• ASIA-PACIFIC — Elucidation of Thermal Bleaching of Coral Reefs by Internal Waves
• ASIA-PACIFIC — Understanding the genetic effects of disease manifestation by RNA editing
• ASIA-PACIFIC — Contributory effects of each brain cell type in development of Alzheimer’s Disease
• ASIA-PACIFIC — Mobile Health Programme for better Type 2 Diabetes patient outcomes
• REST OF THE WORLD — Successful delivery of Glioblastoma drug across Blood-Brain Barrier in mice models
• REST OF THE WORLD — Prescription drugs for children with chronic kidney disease may be toxic to kidneys
• REST OF THE WORLD — Recommendation for preventive drug-of-choice for post-menopausal women
• REST OF THE WORLD — Study shows students who are able to manage emotions perform better in school

The following topics are under this section:

• ASIA-PACIFIC — Shedding Light on COVID-19 Vaccine Development
• ASIA-PACIFIC — Community-led Interventions for Improving Blood Pressure Control
• ASIA-PACIFIC — Importance of Redox Homeostasis in Potential Treatment of Disease
• ASIA-PACIFIC — Novel Processor Architecture to Solve Complex Mathematical Problems
• ASIA-PACIFIC — Uncovering Mechanisms of the Human Biological Clock
• ASIA-PACIFIC — Discovery of Healthy Stomach Stem Cells Reveals Cancer Origins
• ASIA-PACIFIC — Cataloguing Cancer “fingerprints” to Map Cancer Genomes
• ASIA-PACIFIC — Creating a Circular Economy using Greenhouse Gases
• REST OF THE WORLD — Guide for Liquid Biopsy in Individual Glioblastoma Patients
• REST OF THE WORLD — Multi-purpose use of Breast and Kidney Cancer Drugs
• REST OF THE WORLD — The Two Faces of Immune Cells
• REST OF THE WORLD — Fine Particle Air Pollution Linked to Development of Kidney Disease

For the month of August 2021, APBN looks at some of the progress made in cancer research. In Features, we have Yie Hou Lee and Michael Birnbaum from the Singapore-MIT Alliance for Research and Technology Critical Analytics for Manufacturing Personalized-Medicine (SMART-CAMP) to share about the future of CAR T cell manufacturing. Next, a team of researchers from the National Neuroscience Institute, National University of Singapore, and the Duke-NUS Medical School enlightens us on the difficulty of treating glioblastoma brain tumours and how they plan to address its critical issues. Then we have Dr. Chi-Jui Liu and Hsiao Yun Lu to talk about hereditary cancers and how we may improve our odds in this game of roulette. In Columns, we have an analysis by Dr. Ping-Chung Leung on the integrative use of Traditional Chinese Medicine in managing treatment outcomes of COVID-19 patients and a reflection by Dr. Chris Nave on the lessons we can take away from the development of COVID-19 vaccines. Finally, in Spotlights, we share highlights from the Vaccines World Summit 2021 and an interview with Mr. Abel Ang, Group Chief Executive of Advanced MedTech on how their new venture AbAsia Biolabs can help meet Singapore’s need for increased COVID-19 test kits as we enter a new normal.

In this paper, we analyze a new Ito stochastic differential equation model for untreated human glioblastomas. The model was the best fit of the average growth and variance of 94 pairs of a data set. We show the existence and uniqueness of solutions in the positive spatial domain. When the model is restricted in the finite domain $(0,b)$, we show that the boundary point 0 is unattainable while the point $b$ is reflecting attainable. We prove there is a unique ergodic stationary distribution for any non-zero noise intensity, and obtain the explicit probability density function for the stationary distribution. By using Brownian bridge, we give a representation of the probability density function of the first passage time when the diffusion process defined by a solution passes the point $b$ firstly. We carry out numerical studies to illustrate our analysis. Our mathematical and numerical analysis confirms the soundness of our randomization of the deterministic model in that the stochastic model will set down to the deterministic model when the noise intensity approaches zero. We also give physical interpretation of our stochastic model and analysis.

Glioblastoma are the most common and malignant primary brain tumor, and actual treatments consist of surgery (when possible), radiotherapy and chemotherapy. Recent discoveries in biology revealed the important role of radioresistant cancer stem cell in the tumor proliferation and also showed that differentiated tumor cells can revert to a stem-like state because of radiation. These discoveries can be used to create mathematical models to study and plan new optimized radiotherapy schedules. In literature, some models have already been developed on murine population. The aim of this study was to reproduce these models, to perform a sensitivity analysis to find the most sensitive parameters and to adapt them to standard schedules used with human patients. We found that the most sensitive parameters are those involving tumor cell proliferation, radio-sensibility and quiescence times of both stem and tumor cells.

Heterogeneous high-throughput biological data become readily available for various diseases. The amount of data points generated by such experiments does not allow manual integration of the information to design the most optimal therapy for a disease. We describe a novel computational workflow for designing therapy using Ariadne Genomics Pathway Studio software. We use publically available microarray experiments for glioblastoma and automatically constructed ResNet and ChemEffect databases to exemplify how to find potentially effective chemicals for glioblastoma — the disease yet without effective treatment. Our first approach involved construction of signaling pathway affected in glioblastoma using scientific literature and data available in ResNet database. Compounds known to affect multiple proteins in this pathway were found in ChemEffect database. Another approach involved analysis of differential expression in glioblastoma patients using Sub-Network Enrichment Analysis (SNEA). SNEA identified angiogenesis-related protein Cyr61 as the major positive regulator upstream of genes differentially expressed in glioblastoma. Using our findings, we then identified breast cancer drug Fulvestrant as a major inhibitor of glioblastoma pathway as well as Cyr61. This suggested Fulvestrant as a potential treatment against glioblastoma. We further show how to increase efficacy of glioblastoma treatment by finding optimal combinations of Fulvestrant with other drugs.

Glioblastoma multiforme (GBM) is an aggressive and fatal brain tumor that tends to occur in older adults and has several subtypes. The fact that the mechanisms of initiation and progression of glioblastoma are not yet known is an obstacle to the treatment of the disease. For this reason, studies have been carried out in recent years to develop new therapeutic approaches. Photodynamic therapy (PDT) is a procedure that has been approved and is considered safe in most clinical trials. With the help of a photosensitizer (PS), tumor growth regression is promoted, aiming to prolong the survival of patients with glioma progression. It is extremely important to conduct studies focused on the development, application, and biodistribution of possible candidates for these photosensitizing drugs. Phthalocyanines (Pcs) are good photosensitizers for this purpose. Here, we describe an approach to the application of photodynamic therapy with metal-phthalocyanines [zinc-phthalocyanine (ZnPc) and cobalt-phthalocyanine (CoPc)] and their carboxylic acid derivatives in U87-MG cell lines. For the phototoxicity study, percent viability values were calculated using the MTT test. The results showed that cell death was effectively induced in U87-MG cells. In our study, the phthalocyanines applied in the in vitro treatment of glioblastoma cell lines with PDT have shown high toxicity and the treatment has been successful. Our findings highlight the potential of ZnPc-COOH and CoPc-COOH with their carboxylic acid derivatives as biological material for biomedical applications in the treatment of glioblastoma cells.

Glioblastoma (GBM) is a deadly disease with a poor prognosis, there is therefore a crucial need for novel therapeutic targets. Current preclinical models of GBM fail to predict clinical outcomes, thus, new translationally relevant models are urgently needed for reliable therapeutic target validation. 3D spheroid culture of cancer cells has been shown to better reflect tumour biology than 2D monolayer culture, as has culturing cells in flow-based microfluidic devices, which mimic key aspects of the tumour microenvironment. Gene knockdown by siRNA is a key preclinical target validation tool, however, siRNA-mediated knockdown of cancer spheroids in microfluidic culture has not yet been demonstrated. Here we describe a simple and robust microfluidic device that can maintain GBM spheroids (U87 cells) for at least 7 days. Via RNA sequencing analysis, we demonstrate that spheroids grown in microfluidic culture are more proliferative than spheroids grown in static plate culture and downregulate genes associated with cell adhesion, potentially offering insights into the metastatic process. Comparison of target gene (PRMT2 and RAB21) knockdown using siRNA between 2D monolayer cultured cells, static spheroid culture and spheroids maintained in the microfluidic device showed that gene expression (as measured by quantitative-PCR) was significantly reduced in all culture systems. Knockdown was most efficient in cells grown in 2D monolayer culture followed by static spheroid culture, but we also demonstrate $\sim 40\%$ knockdown efficiency using the microfluidic device. In summary, this study describes an easy-to-use microfluidic culture platform and provides evidence that pre-clinical siRNA-mediated target validation studies will be possible in flow systems that mimic tumour physiology.