Gene Carriers and Transfection Systems Used in the Recombination of Dendritic Cells for Effective Cancer Immunotherapy

Dendritic cells (DCs) are the most potent antigen-presenting cells. They play a vital role in the initiation of immune response by presenting antigens to T cells and followed by induction of T-cell response. Reported research in animal studies indicated that vaccine immunity could be a promising alternative therapy for cancer patients. However, broad clinical utility has not been achieved yet, owing to the low transfection efficiency of DCs. Therefore, it is essential to improve the transfection efficiency of DC-based vaccination in immunotherapy. In several studies, DCs were genetically engineered by tumor-associated antigens or by immune molecules such as costimulatory molecules, cytokines, and chemokines. Encouraging results have been achieved in cancer treatment using various animal models. This paper describes the recent progress in gene delivery systems including viral vectors and nonviral carriers for DC-based genetically engineered vaccines. The reverse and three-dimensional transfection systems developed in DCs are also discussed

Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence

NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from concentrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa

Local recurrence after rectal endoscopic submucosal dissection: a case of tumor cell implantation

We report a case of local recurrence of cancer after rectal endoscopic submucosal dissection (ESD). A 52-year-old male underwent a curative resection with ESD for rectal intramucosal cancer. Seventy-four months after ESD, surveillance colonoscopy showed an elevated lesion on the ESD scar, suspicious of a recurrence. The patient subsequently underwent a low anterior resection (intersphincteric) with lymph node dissection. Pathology revealed a well-differentiated adenocarcinoma, similar to the ESD specimen. We suspected that the local recurrence was caused by implantation of tumor cells during the ESD, due to surgical manipulation performed with the tumor in an exposed setting for a long period of time

Immune Cell Recruitment and Cell-Based System for Cancer Therapy

Immune cells, such as cytotoxic T lymphocytes, natural killer cells, B cells, and dendritic cells, have a central role in cancer immunotherapy. Conventional studies of cancer immunotherapy have focused mainly on the search for an efficient means to prime/activate tumor-associated antigen-specific immunity. A systematic understanding of the molecular basis of the trafficking and biodistribution of immune cells, however, is important for the development of more efficacious cancer immunotherapies. It is well established that the basis and premise of immunotherapy is the accumulation of effective immune cells in tumor tissues. Therefore, it is crucial to control the distribution of immune cells to optimize cancer immunotherapy. Recent characterization of various chemokines and chemokine receptors in the immune system has increased our knowledge of the regulatory mechanisms of the immune response and tolerance based on immune cell localization. Here, we review the immune cell recruitment and cell-based systems that can potentially control the systemic pharmacokinetics of immune cells and, in particular, focus on cell migrating molecules, i.e., chemokines, and their receptors, and their use in cancer immunotherapy

Optimization of Protein Therapies by Polymer-Conjugation as an Effective DDS

Due to recent advances in disease proteomics, many disease-related proteins have been found. It is expected that there will be therapeutically useful proteins among them. However, it is clinically difficult to use most proteins as effective and safe drugs because of their very low stability and pleiotropic actions in vivo. To promote disease proteomic based drug development for protein therapies, we have attempted to develop an optimal polymer-conjugation system for improving the therapeutic potency of proteins. In this review, we introduce this innovative protein-drug system

Production of Chimeric Mice by Exchanging Nuclei from Blastomeres of the Two-Cell Embryo

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Decreased iron stores in patients with Helicobacter pylori infection is improved by eradication without corresponding changes in the intake of iron and vitamin C

Background: The relationship between Helicobacter pylori infection and iron metabolism has not been well studied in Japan. We examined the association of H. pylori infection and its eradication to iron metabolism. Methods: A total of 654 adults who completed a health survey in 2012 were enrolled. H. pylori stool antigen was tested and serum antibody titer and serum iron, ferritin and pepsinogen levels were estimated. Subjects reported on their daily intake of the diets to calculate daily intake of iron and vitamin C. Among the H. pylori-infected patients surveyed in 2012, 177 patients completed the same health survey in 2014. For these patients, the change of daily intake of iron and vitamin C and serum iron and ferritin levels were examined. Results: In 2012, 244 subjects (37.3%) were considered as infected with H. pylori. In male subjects aged 35–64 years, serum level of ferritin was 77.5 (SD 53.1) ng/mL in infected patients and 130.6 (114.3) ng/mL in non-infected subjects (p < 0.05). In female subjects who received successful eradication therapy, serum level of ferritin increased from 47.9 (35.2) to 61.0 (35.4) ng/mL (p < 0.05). The daily intake of iron and vitamin C was not significantly different between H. pylori-infected and non-infected subjects. Successful eradication did not change daily intake of iron and vitamin C. Conclusions: Lower serum levels of ferritin were observed in Japanese patients with H. pylori infection. Eradication of H. pylori increased the serum level of ferritin without corresponding changes in the intake of iron and vitamin C