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The Advantages and Versatility of Carrier-Free Nanodrug and Nanoparticle Systems for Cancer Therapy
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
In addition, these NPs can be employed as carriers but with a therapeutic role for different drug molecules, paving the way for combinational therapies, such as PDT and PTT, and further enhancing their antitumor efficacy with laser and/or NIR irradiation. Furthermore, carrier-free nanodrugs can be constructed with immunotherapeutic agents that inhibit the tumor recurrence and strengthen chemotherapy. For instance, as shown in Figure 1.34, the aforementioned PTX–IDM nano-assemblies [511] showed almost twofold higher tumor inhibition compared to the free PTX- and the IDM–PTX mixture-treated group (a, b). The treatment with PTX–IDM nano-assemblies increased the apoptosis of the tumor cell (TUNEL) resulting in effective inhibition on proliferation (c). It is also demonstrated that the amount of PTX in the tumor site was much higher (d). This efficacy was then demonstrated with analysis of macrophage phenotype in tumor microenvironment (e) by analyzing CD68, CD206 (a biomarker of anti-inflammatory macrophage), and CD86 (a biomarker of pro-inflammatory macrophage). It was shown that the concentration of TNF-α, which has a cytotoxic effect on cancer cells, was higher in the groups treated with PTX–IDM mixture and PTX–IDM nano-assemblies. Attractively, the concentration of IL-10, which can promote angiogenesis and proliferation of cancer cells, was dramatically decreased only in the PTX–IDM nano-assembly-treated group, whereas all the control groups represent high concentrations (f).
Role of iPSCs in Disease Modeling: Gaucher Disease and Related Disorders
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Daniel K. Borger, Elma Aflaki, Ellen Sidransky
In addition to dopaminergic neurons, Panicker et al. (9) and Tiscornia et al. (10) also differentiated GD iPSCs into macrophages, by way of monocytes. Both studies used CD14 and CD163 as markers of macrophage differentiation, with Panicker et al. (9) including CD68 and Tiscornia et al. (10) including CD11b and CD33. In all cases, control and GD iPSC lines produced macrophages at similar efficiencies. To further confirm that reduced GCase activity does not impact the iPSC differentiation process, Tiscornia et al. (10) used a lentiviral vector to transduce their type 2 GD iPSC line with wild-type GBA1, which restored GCase activity to control levels. They then compared the differentiation efficiency of both transduced and nontransduced lines and found that both produced cells with similar marker patterns upon differentiation to macrophages (10). Taken together, these results suggest that the metabolic defect in GD has little to no effect on either the reprogramming or the differentiation processes.
Reduction and Fixation of Sacroiliac joint Dislocation by the Combined Use of S1 Pedicle Screws and an Iliac Rod
Published in Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White, Advances in Spinal Fusion, 2003
Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White
Fresenius, Bad Homburg, Germany) in a cylinder and allowed to rest for 30 min at 37°C to permit the sedimentation of erythrocytes. The resulting supernatant was centrifuged at 400 g for 7.5 min, and the pellet was washed and suspended in PBS. This cell suspension was loaded carefully onto three volumes of Ficoll-sodium metrizoate (Lymphoprep; Nyegaerd, Oslo, Norway; density = 1.077 g/mL) and centrifuged at 400 g for 30 min. The layer of mononuclear cells was washed and suspended in Hanks’ balanced salt solution, supplemented with 0.5% human serum albumin (HBSS + 0.5% HAS), and used as a monocyte source. Monocytic cells were allowed to adhere to the surface of the plastic tissue culture vessel during incubation at 37°C for 16 h and were separated from non-adherent lymphocytic cells by being washed with prewarmed PBS/1% (v/v) FCS. Growth medium was added to the adherent cell cultures, which were then incubated at 37°C in a humidified atmosphere with 6% (v/v) C02 until ready for use. Cells were examined at 3 days postplating, at which time they had differentiated into monocyte-derived macrophages, regardless of their incubation temperature. More than 95% of the adherent cells were macrophages, defined by the recently identified KP-1 (CD68) (DAKO) mature macrophage marker [12]. Finally, color development was established by treating macrophages with AEC (DAKO) at room temperature for 5 min. Alamar Blue Assay
Diagnosis and management of implant debris-associated inflammation
Published in Expert Review of Medical Devices, 2020
Stuart B. Goodman, Jiri Gallo, Emmanuel Gibon, Michiaki Takagi
Excess production of ‘Moderate’- and ‘Small’-sized particles induces a foreign body type cellular response and chronic inflammation (Figure 3). This occurs both in the interfacial tissue between bone and implants and the regenerated capsular tissue around artificial joints [44]. CD68+ monocytes and macrophages are the responsible cell types for handling these wear debris by the process of phagocytosis. Macrophages have been subcategorized as naïve M0, proinflammatory M1, and anti-inflammatory M2. M1 macrophages are dominant in the foreign body granuloma [45]. Another consequence of a foreign body and chronic inflammatory reaction is the fusion of macrophages into foreign body giant cells. Fibroblasts can encapsulate the particles to the collagenous fibrous bed. Fibroblasts and vascular endothelial cells frame the granuloma. Neutrophil infiltration is scarce. If neutrophils are found to a greater degree, then indolent infection is suspected [46]. Lymphocyte infiltration is occasionally observed in the macrophage dominant foreign body granuloma, but limited [16]. Mast cells are also recognized, but the precise role is still unclear [47,48].