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Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis
Toshihisa Ishikawa,Hiroshi Nakagawa,Yuichiro Hagiya,Naosuke Nonoguchi,Shin-ichi Miyatake,Toshihiko Kuroiwa
Advances in Pharmacological Sciences , 2010, DOI: 10.1155/2010/587306
Abstract: Accumulating evidence indicates that ATP-binding cassette (ABC) transporter ABCG2 plays a key role in regulating the cellular accumulation of porphyrin derivatives in cancer cells and thereby affects the efficacy of photodynamic therapy and photodynamic diagnosis. The activity of porphyrin efflux can be affected by genetic polymorphisms in the ABCG2 gene. On the other hand, Nrf2, an NF-E2-related transcription factor, has been shown to be involved in oxidative stress-mediated induction of the ABCG2 gene. Since patients have demonstrated individual differences in their response to photodynamic therapy, transcriptional activation and/or genetic polymorphisms of the ABCG2 gene in cancer cells may affect patients' responses to photodynamic therapy. Protein kinase inhibitors, including imatinib mesylate and gefitinib, are suggested to potentially enhance the efficacy of photodynamic therapy by blocking ABCG2-mediated porphyrin efflux from cancer cells. This review article provides an overview on the role of human ABC transporter ABCG2 in photodynamic therapy and photodynamic diagnosis. 1. Introduction Photodynamic therapy (PDT) and photodynamic diagnosis are achieved by a photon-induced physicochemical reaction which is induced by excitation of photosensitizer exposed to light. In the 1960s Lipson and Baldes introduced a hematoporphyrin derivative (HpD), a product derived following by treatment of hematoporphyrin with a mixture of acetic and sulfuric acids and sodium hydroxide [1]. Their development of the hematoporphyrin derivative established the basis of today’s PDT and photodynamic diagnosis [2–6]. PDT utilizes porphyrin derivatives to generate singlet oxygen (1O2) and other reactive oxygen species (ROS) that are potent in killing cancer cell in vivo [7]. The modern era of PDT was founded in the 1970s with the pioneering work of Dougherty and his coworkers who purified HpD later called Photofrin. In 1978, Dougherty et al. had carried out the first human trials of Photofrin on women with advanced breast cancer [8]. Photofrin is still the most widely used photosensitizer in clinical PDT. Recent studies of modern PDT began just two decades ago; therefore there are still unsolved problems. Nevertheless, PDT has many applications in a wide range of fields of both preclinical and clinical sciences. In recent years, remarkable advances were made in photodynamic diagnosis technology that makes it easier to reliably achieve complete excision of malignant gliomas [9–11] and meningiomas [12]. The extent of tumor resection that should be undertaken in patients with
Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors
Toshihisa Ishikawa,Kenkichi Takahashi,Naokado Ikeda,Yoshinaga Kajimoto,Yuichiro Hagiya,Shun-ichiro Ogura,Shin-ichi Miyatake,Toshihiko Kuroiwa
Pharmaceutics , 2011, DOI: 10.3390/pharmaceutics3030615
Abstract: Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma. PDD is achieved by a photon-induced physicochemical reaction which is induced by excitation of protoporphyrin IX (PpIX) exposed to light. Fluorescence-guided gross-total resection has recently been developed in PDD, where 5-aminolevulinic acid (ALA) or its ester is administered as the precursor of PpIX. ALA induces the accumulation of PpIX, a natural photo-sensitizer, in cancer cells. Recent studies provide evidence that adenosine triphosphate (ATP)-binding cassette (ABC) transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of porphyrins in cancer cells and thereby affects the efficacy of PDD. Protein kinase inhibitors are suggested to potentially enhance the PDD efficacy by blocking ABCG2-mediated porphyrin efflux from cancer cells. It is of great interest to develop potent ABCG2-inhibitors that can be applied to PDD for brain tumor therapy. This review article addresses a pivotal role of human ABC transporter ABCG2 in PDD as well as a new?approach of quantitative structure-activity relationship (QSAR) analysis to design potent ABCG2-inhibitors.
Treating Depression with the Mephenesin Analog Skeletal Muscle Relaxant Methocarbamol  [PDF]
Toshihiko Numazawa
Open Journal of Depression (OJD) , 2016, DOI: 10.4236/ojd.2016.54005
Abstract: It is difficult to treat depression because there is no established method for treatment. Many drugs have been developed by Pharmaceutical companies to treat depression. Depression affects many patients. It was necessary to focus on “meprobamate” which was once said to be a magic drug. It was found that “methocarbamol” is more suitable for treating depression than “meprobamate”.
Desalination of Seawater by Liquid Columns and Decompression Boiling (Recovery of Condensation Latent Heat)  [PDF]
Toshihiko Shakouchi
Journal of Water Resource and Protection (JWARP) , 2018, DOI: 10.4236/jwarp.2018.108046
Abstract: In this study, the concept of a new seawater desalination method and equipment using liquid columns of seawater and desalinated fresh water, decompression boiling and evaporation, condensation, and recovery of condensation latent heat are proposed. The equipment consists of seawater and freshwater columns approximately 10 m high with top spaces. The pressure of the top space, the evaporation and condensation area, of the seawater column, for example, is reduced approximately 30 mmHg (abs.) using the seawater column, after which it is heated from the general seawater temperature of 25°C to 30°C to boil and evaporate the seawater. The vapor is cooled by the seawater at approximately 25°C in a heat exchanger, and then, it is condensed and sent to the fresh water column. At this time, the condensation latent heat is recovered to preheat the newly flowing seawater. The evaporation or condensation rate, namely, the production rate of freshwater, by the new desalination equipment is also estimated by the results of the existing quadruplex effect vacuum evaporator used in the salt production industry. This new desalination method and its associated equipment also can be used to purify polluted water and waste water.
Transplantation of human neural stem/progenitor cells overexpressing galectin-1 improves functional recovery from focal brain ischemia in the mongolian gerbil
Junichi Yamane, Satoru Ishibashi, Masanori Sakaguchi, Toshihiko Kuroiwa, Yonehiro Kanemura, Masaya Nakamura, Hiroyuki Miyoshi, Kazunobu Sawamoto, Yoshiaki Toyama, Hidehiro Mizusawa, Hideyuki Okano
Molecular Brain , 2011, DOI: 10.1186/1756-6606-4-35
Abstract: Stem cell-based therapies have been performed in various clinical settings, although many lack scientific evidence of their effectiveness [1]. Among stem cell-based therapies, transplantation of human neural stem/progenitor cells (hNSPCs) is relatively well substantiated by peer-reviewed literatures [2-8]. One reason underlying the relative success of hNSPCs-transplantation is its low occurrence of tumor formation, which is a clear advantage compared with transplantation of embryonic stem cells or their derivatives [9]. Therefore, we have been examining hNSPCs-transplantation in various preclinical animal models and have shown that hNSPCs-transplantation enhances functional recovery following brain ischemia [10] and spinal cord injury (SCI) [11].Brain ischemia, which is caused by occlusion of a cerebral artery, leads to focal tissue loss and death of multiple neuronal cell types within and around the ischemic region. Patients with brain ischemia exhibit persistent motor, sensory or cognitive impairments, which have devastating effects on their quality of life. Apart from acute thrombolysis, which can be used in only a minority of cases, there is still no effective treatment to promote functional recovery after brain ischemia.hNSPCs can generate all principle cell types (i.e., neurons, astrocytes and oligodendrocytes) in the brain and therefore have great therapeutic potential in severe neurological diseases, including brain ischemia [6,12], which induce death of various cell types [13,14]. hNSPCs can be propagated in large quantities for long-term without a notable loss of the ability to proliferate and differentiate [15]. Therefore, cultured hNSPCs are a promising cell source to treat brain diseases.We previously showed that transplantation of cultured hNSPCs reduced infarct volume and improved functional prognosis in a rodent model of brain ischemia [10]. In the damaged brains of the model animals, hNSPCs differentiated into mature neurons within the ischemic regi
Effects of the inhibition of weed communities by winter-flooding  [PDF]
Korehisa Kaneko, Toshihiko Nakamura
Agricultural Sciences (AS) , 2011, DOI: 10.4236/as.2011.24050
Abstract: Winter-flooded paddy field is an agricultural method which putting a water among the winter, it is paid attention as an environmental friendly agriculture. Especially, it is said, winter-flooding is control paddy weeds and there is the farming potential that the annual rice yield is high. However, there is no detailed research about the effects of weed communities by winter-flooding, as the purpose of this study, we investigated the effects of the inhibition of weed communities (life cycle, harmful weed) by winter-flooding at a shore of Inba Lake, Chiba Prefecture, Japan, and compared them to paddy weeds in a dry paddy field. Methods examined the plant height (cm) and the cover degree class of all appearance species in each quadrant frame (1 m2). Quadrant in the two type paddies were 10 frames (D1-D10) at the control, and were 10 frames (W1-W10) at the treatment (Figure 1). In a winter-flooded paddy field, species number and plant volume of winter-annual plants decreased in the third winter after winter-flooding, In particular, the plant volume of Alopecurus aequalis, Cardamine flexuosa decreased significantly. We considered that the cause of this decrease was due to the depth of flooding (more than 10 cm). Eleocharis kuroguwai and Echinochloa oryzoides, which are perennial plants, Sagittaria trifolia, which is an annual plant, increased in a winter-flooded paddy field in the third summer after winter-flooding. We considered that these species grew thicker at places where the seeds germinated, and grew easily, because the conservation situation of the seeds fitted well under the winter-flooding conditions. They started to grow immediately after the drainage of water. The period of drainage coincided with increasing light intensity and temperature. In addition, the annual rice yield of the third year after winter-flooding was higher than that of the habitual practice rice field.
Effect of Ultrasonic Irradiation Conditions on Metal Surface during Multifunction Cavitation  [PDF]
Masataka Ijiri, Toshihiko Yoshimura
Materials Sciences and Applications (MSA) , 2018, DOI: 10.4236/msa.2018.98050
Abstract: Processing using multifunction cavitation (MFC) has recently enabled functional characteristics to be imparted to various materials. It is possible to process a material surface in the same manner as with conventional water jet (WJ) peening; however, the cavitation bubble temperature is different. To further improve this MFC technology, we examine the surface re-forming of low alloy steel (JIS-SCM435) using MFC with various modes of ultrasonic waves. The ultrasonic equipment used for MFC processing includes dual, single, pulse and frequency modulation (FM) ultrasonic modes. Improvement of the residual stress and corrosion resistance was confirmed for all modes. The dual mode showed the maximum values of residual compressive stress and surface potential. The sound pressure at the machining spot was the highest with dual mode, and the temperature in the bubble generated by the WJ nozzle was highest and the amount of dissolved oxygen was lowest. Improvement of the residual stress and corrosion resistance was promoted because the temperature and pressure in the bubble interior during processing was higher than in the other modes.
Brownian motion with multiplicative noises revisited
Takeshi Kuroiwa,Kunimasa Miyazaki
Physics , 2013, DOI: 10.1088/1751-8113/47/1/012001
Abstract: The Langevin equation with multiplicative noise and state-dependent transport coefficient has to be always complemented with the proper interpretation rule of the noise, such as the Ito and Stratonovich conventions. Although the mathematical relationship between the different rules and how to translate from one rule to another are well-established, it still remains controversial what is a more {\it physically} natural rule. In this communication, we derive the overdamped Langevin equation with multiplicative noise for Brownian particles, by systematically eliminating the fast degrees of freedom of the underdamped Langevin equation. The Langevin equations obtained here vary depending on the choice of the noise conventions but they are different representations for an identical phenomenon. The results apply to multi-variable, nonequilibrium, non-stationary systems, and other general settings.
Three-Dimensional X-ray Observation of Atmospheric Biological Samples by Linear-Array Scanning-Electron Generation X-ray Microscope System
Toshihiko Ogura
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021516
Abstract: Recently, we developed a soft X-ray microscope called the scanning-electron generation X-ray microscope (SGXM), which consists of a simple X-ray detection system that detects X-rays emitted from the interaction between a scanning electron beam (EB) and the thin film of the sample mount. We present herein a three-dimensional (3D) X-ray detection system that is based on the SGXM technology and designed for studying atmospheric biological samples. This 3D X-ray detection system contains a linear X-ray photodiode (PD) array. The specimens are placed under a CuZn-coated Si3N4 thin film, which is attached to an atmospheric sample holder. Multiple tilt X-ray images of the samples are detected simultaneously by the linear array of X-ray PDs, and the 3D structure is calculated by a new 3D reconstruction method that uses a simulated-annealing algorithm. The resulting 3D models clearly reveal the inner structure of the bacterium. In addition, the proposed method can easily be used for diverse samples in a broad range of scientific fields.
High-Contrast Observation of Unstained Proteins and Viruses by Scanning Electron Microscopy
Toshihiko Ogura
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046904
Abstract: Scanning electron microscopy (SEM) is an important tool for the nanometre-scale analysis of the various samples. Imaging of biological specimens can be difficult for two reasons: (1) Samples must often be left unstained to observe detail of the biological structures; however, lack of staining significantly decreases image contrast. (2) Samples are prone to serious radiation damage from electron beam. Herein we report a novel method for sample preparation involving placement on a new metal-coated insulator film. This method enables obtaining high-contrast images from unstained proteins and viruses by scanning electron microscopy with minimal electron radiation damage. These images are similar to those obtained by transmission electron microscopy. In addition, the method can be easily used to observe specimens of proteins, viruses and other organic samples by using SEM.
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