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Chemoconvulsants
Published in Steven L. Peterson, Timothy E. Albertson, Neuropharmacology Methods in Epilepsy Research, 2019
For the quantification studies, the dose of the test substance is varied until a minimum of three dose levels has been tested, with at least two points lying between the limits of 0% and 100% protection. The medium effective dose (ED50) and 95% confidence interval are then calculated by probit analysis.11 Although the above description applies to mice, identical studies can be undertaken with rats (n = 8 to 10 rats per group), provided that the appropriate CD97 of PTZ (e.g., 70 to 90 mg/kg) has been employed. The CD97 is estimated by injecting various doses of PTZ into groups of eight mice. Individual mice are observed for the presence or absence of a minimal clonic seizure; the number of mice in each group displaying a seizure is recorded. The CD97 and 95% confidence interval can be calculated by probit analysis. As discussed below, choosing a different seizure endpoint is not without consequences when attempting to interpret the results obtained from the s.c. PTZ test. For example, the pharmacological profile associated with PTZ-induced “minimal” clonic seizures is more discriminatory for drugs active against generalized absence and myoclonic seizures, whereas the profile associated with PTZ-induced tonic extension is nondiscriminatory with respect to clinical classes of AEDs (see discussion below).
Nuclear Imaging of Adoptive Cell Therapies
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Bennink et al. (19) evaluated a noninvasive scintigraphic technique able to assess 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO)–labeled neutrophil trafficking in a mouse model of dextran sulfate sodium (DSS)–induced colitis. SPECT of the abdomen was performed one hour after reinjection of 1.35 mCi of labeled neutrophils. Colonic uptake of 99mTc-HMPAO neutrophils was determined with dedicated animal pinhole SPECT in mice with DSS-induced colitis and correlated well with histological findings, wet colon weight, and clinical weight loss. The neutrophil uptake ratio was reduced significantly by blocking of neutrophil migration capacity with the CD97 antibody.
Platelet count correlates with stage and predicts survival in melanoma
Published in Platelets, 2019
Saleh Rachidi, Maneet Kaur, Tim Lautenschlaeger, Zihai Li
When cancer cells leave the primary tumor and enter blood stream, they activate surrounding platelets via molecules such as HMB1 [6] and ADP [7], inducing microthrombus formation. This in turn shields cancer cells from the immune attack by natural killer cells [7]. Mice with defective platelet function are protected from melanoma dissemination to their lungs; however, this protection is mitigated by depletion of natural killer cells [8]. Platelets also propagate tumor cell metastasis independent of natural killer cells [9]. CD97 on cancer cells activates platelets to release lysophosphatidic acid (LPA), thus facilitating trans-endothelial migration [10]. We have also shown that platelets activate TGFβ and suppress antitumor T lymphocytes, thus aiding in melanoma progression [11]. Platelet-derived TGFβ also acts directly on cancer cells inducing epithelial-mesenchymal transition, thus increasing their metastatic potential [12]. Moreover, platelets secrete CXCL5 and CXCL7 which recruit granulocytes to cancer cells, leading to the formation of early metastatic niches [13].
Examining the role of nickel and NiTi nanoparticles promoting inflammation and angiogenesis
Published in Journal of Immunotoxicology, 2022
Anup K. Srivastava, Dustin M. Snapper, Jiwen Zheng, Banu S. Yildrim, Sandeep Srivastava, Steven C. Wood
To build on these findings and to better characterize the angiogenic potential of NiTi NP, the current study employed the DIVAA system. Here, this system concentrated angiogenesis within silicone tubes filled with a mixture of NiTi NP and Matrigel. The DIVVA system has been critical in demonstrating that the CD97 protein is required for adhesion and inflammatory cell migration as well as tumor progression and neoangiogenesis (Guedez et al. 2003; Wang et al. 2005). The system has also been used to assess effects of anti-angiogenic agents (reviewed in Napoli et al. 2011). What is novel in the present work is use of the DIVAA system in the context of metallic wear particles rather than its historic use to evaluate effects of drugs or biologics.
Investigating Mechanisms of Response or Resistance to Immune Checkpoint Inhibitors by Analyzing Cell-Cell Communications in Tumors Before and After Programmed Cell Death-1 (PD-1) Targeted Therapy: An Integrative Analysis Using Single-cell RNA and Bulk-RNA Sequencing Data
Published in OncoImmunology, 2021
Yi-Quan Jiang, Zi-Xian Wang, Ming Zhong, Lu-Jun Shen, Xue Han, Xuxiazi Zou, Xin-Yi Liu, Yi-Nan Deng, Yang Yang, Gui-Hua Chen, Wuguo Deng, Jin-Hua Huang
Notably, several ligand-receptor pairs identified in the current study not only have a positive effect on antitumor immunity but also show direct suppression of tumor cells. It was reported that targeting WNT5A could suppress the metastasis of melanoma.29 On the other hand, WNT5A secreted by melanoma cells can drive DC tolerance, and inhibition of WNT5A can reverse DC tolerance and enhance anti-PD-1 efficacy.30,31 In our study, the WNT5A-PTPRK interactions between CAFs and CAFs/endothelial cells/myofibroblasts/tumor cells were decreased. Therefore, WNT5A-related interactions seem to play a negative role in immune surveillance and anti-PD-1 therapy. However, the specific mechanisms by which these WNT5A-related interactions between CAFs and other cells affect antitumor immunity require further clarification. CD74 was shown to promote tumor cell survival by interacting with macrophage migration inhibitory factor (MIF).12 On the other hand, blockade of CD74-MIF signaling in macrophages and DCs could restore the antitumor immune response of macrophages and DCs and subsequently improve the antitumor ability of cytotoxic T cells.32 Consistent with this, in our study, the CD74-MIF interactions between DCs/macrophages/B cells and all types of cells were significantly different between responders (downregulated) and nonresponders (upregulated). In addition, the CD74-COPA and CD74-APP interactions showed the same patterns as the CD74-MIF interaction. However, no previous study has uncovered the antitumor-related functions of these interactions, and further research is needed. CD55 and CD97 (ADGRE5), two membrane-bound complement regulatory proteins (mCRPs), play a role in regulating the complement system. On the one hand, it was reported that CD97 could promote tumor aggressiveness in hepatocellular carcinoma.33 On the other hand, a previous study indicated that the binding of CD97 to CD55 could induce the differentiation of naïve T cells into cells that behave like Tregs, and some data have suggested that the presence of CD55 and CD97 negatively regulates the response to checkpoint inhibitor therapy.34 Consistent with this idea, in our study, CD97-CD55 interactions between B cells/CD8 T cells/NK cells and B cells/CAFs/CD4 T cells/CD8 T cells/DCs/macrophages/myofibroblasts/NK cells/Tregs were relatively weaker in responders than in nonresponders.