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Glycolysis emerges as a new therapeutic target for malignancies. The inhibition of glycolytic activator, PFKFB3, repairs tumor endothelial cell function, and normalizing the tumor microenvironment. We aimed to investigate the significance of PFKFB3 in HCC, and the effects of the PFKFB3 inhibitor, PFK15, in HCC tumor cells and tumor endothelial cells. Double immunofluorescent staining of PFKFB3 and CD31 in HCC tissues revealed that high PFKFB3 expression in both tumor cells and tumor endothelial cells was significantly correlated with poor prognosis. Selleck Veliparib Multivariate analysis identified PFKFB3 expression as an independent prognostic factor. PFK15 suppressed proliferation of HCC cell line and tumor endothelial cells in vitro. In a subcutaneous tumor model of the HCC cell line with tumor endothelial cells, PFK15 suppressed tumor growth and induced apoptosis. Moreover, PFK15 treatment induced tumor vessel normalization, decreasing vessel diameter with pericyte attachment and improving vessel perfusion. High PFKFB3 expression in both tumor cells and tumor endothelial cells was identified as a novel prognostic marker in HCC. Targeting PFKFB3 via PFK15 might be a promising strategy for suppressing tumor growth and inducing tumor vessel normalization.Zinc, ω-3 polyunsaturated fatty acids (PUFAs) and vitamin D are essential nutrients for health, maturation and general wellbeing. Extensive literature searches have revealed the widespread similarity in molecular biological properties of zinc, ω-3 PUFAs and vitamin D, and their similar anti-cancer properties, even though they have different modes of action. These three nutrients are separately essential for good health, especially in the aged. Zinc, ω-3 PUFAs and vitamin D are inexpensive and safe as they are fundamentally natural and have the properties of correcting and inhibiting undesirable actions without disturbing the normal functions of cells or their extracellular environment. This review of the anticancer properties of zinc, ω-3 PUFAs and vitamin D is made in the context of the hallmarks of cancer. The anticancer properties of zinc, ω-3 PUFAs and vitamin D can therefore be used beneficially through combined treatment or supplementation. It is proposed that sufficiency of zinc, ω-3 PUFAs and vitamin D is a necessary requirement during chemotherapy treatment and that clinical trials can have questionable integrity if this sufficiency is not checked and maintained during efficacy trials.The vagus nerve (VN) belongs to the parasympathetic nervous system, which is well known to be involved in the regulation of the functions of organs in the body. The neurotransmitter acetylcholine, released from the cholinergic system including VN, has been known to play an anti-inflammatory role through the efferent pathways in regulating peripheral inflammatory responses profoundly involved in the pathogenesis of diseases. In contrast, anatomically, it connects the central nervous system (CNS) and peripheral organs, including the heart and gastrointestinal (GI) tract. Therefore, it has been recently reported that the VN also plays an important role in the pathogenesis of psychological disorders since it confers varied signals from the GI tract to the CNS, and alteration of microbiota residing in GI definitely influences the condition of neuropsychiatric disorders. Furthermore, the CNS includes microglia, a neuroinflammatory effector in the brain, which is also influenced by the VN to modulate its inflammatory status. Based on significant findings of the VN, the VN stimulation (VNS) has recently drawn attention from many scientific fields. VNS was initially applied to patients with refractory epilepsy, followed by patients with refractory depression. Subsequently, VNS was also attempted to be introduced to other diseases. However, against whichever disease, central or peripheral, detailed underlying mechanisms of VNS involved in neuropsychiatric disorders as well as VNS target molecules in the GI tract and the CNS remains to be studied. In this review, we discuss the mechanisms and predicted responsible factors of VNS in terms of neuropsychiatric disorders.

Cranial radiation therapy (CRT) is a common treatment for pediatric brain tumor patients. However, side effects include significant neurobehavioral dysfunction in survivors. This dysfunction may in part be caused by inflammation, including increased production of tumor necrosis factor alpha (TNFα) and its receptor TNFR1, which can activate the nuclear factor kappa light-chain enhancer of activated B cells (NF-κB). The TNFα blockade abrogates this inflammatory response, although it presents immunologic risks. Thus, modulation of pathway subsets may be preferable. Here, we test whether inhibition of NF-κB activation using an NF-κB essential modulator binding domain (NBD) peptide mitigates CRT-induced neuroinflammation and improves behavioral outcomes.

Male C57BL/6J 28-day old mice were randomized to saline (sham), 5 Gy whole-brain CRT, or CRT + NBD-peptide. Brain tissue was collected after 4 hours or 3 months for Western blot or immunohistochemistry. The cortex, corpus callosum (CC), and dentate gyrus were ter pediatric radiation therapy.

Increasing evidence suggests that patients with a limited number of metastases benefit from SABR to all lesions. However, the optimal dose and fractionation remain unknown. This is particularly true for bone and lymph node metastases. Therefore, a prospective, single-center, dose-escalation trial was initiated.

Dose-Escalation trial of STereotactic ablative body RadiOtherapY for non-spine bone and lymph node metastases (DESTROY) was an open-label phase 1 trial evaluating SABR to nonspine bone and lymph node lesions in patients with up to 3 metastases. Patients with European Cooperative Oncology Group performance status ≤1, an estimated life expectancy of at least 6 months, and histologically confirmed nonhematological malignancy were eligible. Three SABR fractionation regimens, ie, 5 fractions of 7.0 Gy versus 3 fractions of 10.0 Gy versus a single fraction of 20.0 Gy, were applied in 3 consecutive patient cohorts. The rate of ≥grade 3 toxicity, scored according to the Common Toxicity Criteria for Adverse Events v.