DNA-nanorobot-guided thrombin-inducing tumor infarction: raising new potential clinical concerns.

DNA-nanorobot-guided thrombin-inducing tumor infarction (DNA NanorobotTh-ITI) is emerging as a powerful therapeutic strategy for treatment of solid cancers. The technology represents a major advance in the application of DNA nanotechnology for anticancer therapy. More importantly, the technology is being translated from preclinical studies to the clinic owing to its promising anticancer effects with fewer toxicities demonstrated in preclinical settings.

Elusive Neurotoxicity in T Cell-Boosting Anticancer Therapies.

Several T cell-boosting anticancer therapies (including anti-CD19 CAR-T cells and bi-specific T cell engagers, BiTEs) have been approved by the FDA for specific clinical indications. Their potency has been demonstrated in various clinical trials, but some life-threatening complications such as neurotoxicity remain poorly understood. Thus, by conducting multifaceted investigations, a better understanding of T cell immunotherapy-associated neurotoxicity to bridge the gap between basic research and clinical practice is urgently needed.

Approved CAR T cell therapies: ice bucket challenges on glaring safety risks and long-term impacts.

Two autologous chimeric antigen receptor (CAR) T cell therapies (Kymriah™ and Yescarta™) were recently approved by the FDA. Kymriah™ is for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute lymphoblastic leukemia and Yescarta™ is for the treatment of adult patients with R/R large B cell lymphoma. In common, both are CD19-specific CAR T cell therapies lysing CD19-positive targets.

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research-practice gaps, challenges, and insights.

To date, five cancer treatment modalities have been defined. The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known.

Activation of CECR1 in M2-like TAMs promotes paracrine stimulation-mediated glial tumor progression.

Background: The majority of glioma-associated microglia/macrophages have been identified as M2-type macrophages with immune suppressive and tumor supportive action. Recently, the extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) was shown to regulate macrophage maturation. In this study, we investigate the role of CECR1 in the regulation of the glioma-associated macrophage response.

Expression site of P2RY12 in residential microglial cells in astrocytomas correlates with M1 and M2 marker expression and tumor grade.

The role of resident microglial cells in the pathogenesis and progression of glial tumors is still obscure mainly due to a lack of specific markers. Recently P2RY12, a P2 purinergic receptor, was introduced as a specific marker for microglial cells under normal and pathologic conditions. Here we analyzed the expression of P2RY12 in astrocytomas of various malignancy grades in relation to markers for M1 and M2 macrophage activation profiles by using two web-based glioma datasets and confocal immunohistochemistry to 28 astrocytoma samples grades II-IV.

Pregnancy Zone Protein is Increased in the Alzheimer's Disease Brain and Associates with Senile Plaques.

Increased levels of pregnancy zone protein (PZP) were found in the serum of persons who later developed Alzheimer's disease (AD) in comparison to controls who remained dementia free. We suggested that this increase is due to brain derived PZP entering the blood stream during the early phase of the disease. Here we investigate the possible involvement of PZP in human AD pathogenesis.

Circulating glioma biomarkers.

Validated biomarkers for patients suffering from gliomas are urgently needed for standardizing measurements of the effects of treatment in daily clinical practice and trials. Circulating body fluids offer easily accessible sources for such markers. This review highlights various categories of tumor-associated circulating biomarkers identified in blood and cerebrospinal fluid of glioma patients, including circulating tumor cells, exosomes, nucleic acids, proteins, and oncometabolites.

Fast tracking of co-localization of multiple markers by using the nanozoomer slide scanner and NDPViewer.

The detection of co-localization of immunohistochemical markers in tissues or cells requires the application of the confocal laser scanning microscope (CLSM) to multiple immunofluorescence (MIF) stainings. CLSM is operationally sophisticated but requires time-consuming procedures of imaging and reconstruction, and a professional operator is required for manipulation of the microscopic system. Therefore, this technique is less suitable for the examination of many samples in a short time.

Intratumoral, not circulating, endothelial progenitor cells share genetic aberrations with glial tumor cells.

Literature data indicate that glioma stem cells may give rise to both tumor cells and endothelial progenitor cells (EPCs). Malignant glioma patients usually have increased levels of circulating (EPCs) and these cells are known to contribute to the glioma neovasculature. In this study we compared the intratumoral and circulating EPCs of glioma patients for a set of common glioma genotypical aberrations (amplification of EGFR; deletion of PTEN and aneusomy of chromosomes 7 and 10).

Isocitrate dehydrogenase 1R132H mutation in microglia/macrophages in gliomas: indication of a significant role of microglia/macrophages in glial tumorigenesis.

Somatic mutation of Isocitrate dehydrogenase 1 (IDH1) at the locus of R132 (IDH1 (R132H)) occurs in > 70% of WHO grade II-III gliomas and secondary glioblastomas. To date it remains unknown whether the mutation is restricted to glial tumor cells. Microglial cells are the resident macrophages in the central nervous system.

HeNe laser (633 nm)-coupled confocal microscope allows simulating magnetic resonance imaging/computed tomography scan of the brain and eye: a noninvasive optical approach applicable to small laboratory animals.

Magnetic resonance imaging (MRI) and computed tomography (CT) are noninvasive medical imaging techniques used for the detailed visualization of internal organs of the human body. Because CT uses X-rays for imaging, there is a risk of radiation exposure. In contrast, MRI uses radiowaves and magnetic fields for imaging; thus, there are no reported biological hazards.

Glut1/SLC2A1 is crucial for the development of the blood-brain barrier in vivo.

Objective: The overall permeability of the blood-brain barrier (BBB) is regulated by specialized cerebral endothelial cells and their junctional complexes, consisting of adherens junctions (AJs) and tight junctions (TJs). Among the members of the glucose transporters (Glut), Glut1 is a unique molecule expressed in the cerebral endothelial cells. Glut1 and the junctional proteins are concomitantly downregulated in situations in which breakdown of the BBB has taken place.

Haemoglobin staining for in vivo portraying of functional vasculature in experimental zebrafish embryos.

Characterization of functional vessels is required either for monitoring hemodynamics or patterning of functional vasculature in experimental models. Haemoglobin (Hb) staining is a traditionally used approach for determining the differentiation of erythroid cells. In this investigation, we tested if HB staining can be used for portraying of functional vasculature in experimental zebrafish embryos.

Expression sites of colligin 2 in glioma blood vessels.

In a previous study using state-of-the-art proteomic techniques, we identified colligin 2 (HSP47) as a glioma blood vessel-specific protein. In the present study we precisely localized the expression of colligin 2 in the blood vessels of diffusely infiltrating gliomas and relate the expression to the distinct cellular components of the vessels by using multiple immunolabeling and confocal microscopy. We grouped the glioma blood vessels into morphological categories ranging from normal looking capillaries to vessels with hypertrophic and sclerotic changes.

Caldesmon is essential for cardiac morphogenesis and function: in vivo study using a zebrafish model.

The zebrafish homologue of caldesmon is similar to the mammalian low molecular weight caldesmon (l-CaD). In this study, we explored the effects of caldesmon knockdown on vertebrate heart development in vivo. In a zebrafish model caldesmon was knocked down resulting in defective cardiac morphogenesis, muscularization and function.

A crucial role of caldesmon in vascular development in vivo.

Aims: We explored the in vivo effects of knockdown of caldesmon on vascular development in zebrafish.

Methods And Results: We investigated the effects of caldesmon knockdown on the vascular development in a zebrafish model with special attention for the trunk and head vessels including the aortic arches. We examined the developing fishes at various time points.