Therapies In Japan Research Articles

PMS83 - Patterns of Disease Remission Among Patients With Rheumatoid Arthritis Treated With Biologic Therapies In Japan

PMS83 - Patterns of Disease Remission Among Patients With Rheumatoid Arthritis Treated With Biologic Therapies In Japan

Comments by Zhichao Zhang, on Monetary Policy and Structural Decline: Lessons from Japan for the European Crisis

Zhichao Zhang: Schnabl’s paper on Japanese lessons for the European crisis is informative and insightful. The paper carefully examines the origins of the crises, crisis triggers, and consequences of crisis therapies in both Japan and Europe. It then draws lessons from the Japanese experience in the spirit of Hayek (1929, 1944). The paper maintains that the Japanese case shows that, in the face of crisis, the Keynesian stimulus would lead to the malfunctioning of the market mechanism. This is evidenced in the hysteresis of the lowinterest rate and high government debt environment, the erosion of the allocation and signalling of the interest rate, the gradual quasi-nationalization of financial institutions, and gradual real income losses. Given that Europe has taken a similar path in its policy response to the crisis, the paper indicates that Europe may suffer similar consequences that Japan has experienced in recent decades.

The Impact of Chronic Social Stress on Emotional Behavior in Mice and the Therapeutic Effect of Peripheral Mild-Heat Stimulation

In today’s stressful society, mental diseases such as adjustment disorder, affective disorders including anxiety and depression, and chronic fatigue syndrome could be attributed to social stress and are considered as serious social problems. It has been long known in the acupuncture and moxibustion therapies in Japan and China that stimulation at Zhongwan and Taichong points have effects on stress-related anxiety and depression. In the present study, we therefore tested the effect of peripheral mild-heat stimulation at Zhongwan and Taichong on anxiety and brain biochemistry using a mouse model of chronic social stress. Male ddY mice (4 weeks old) were stressed by isolated rearing for 6 weeks. They received mild-heat stimulation (43℃ for 5 min) at Zhongwan and Taichong under isoflurane anesthesia after 4 weeks of the social isolation 3 times a week for 2 weeks, using the “Stress Free Apparatus” (Ryoken Co., Ltd). Control mice received only isoflurane anesthesia. Group-reared mice also underwent the same stimulus/anesthesia sessions. Two days after the last peripheral heat stimulation, anxiety was determined by the light/dark box test as the time spent in the light compartment and the number of transfer between the light and dark compartments. Before and after the last stimulation, blood was collected from an artery at the back of the eye, and serum corticosterone, immunoglobulin E (IgE) which was an index of the inflammatory immune system, and interleukin 6 (IL-6) were measured using ELISA Kit. The frontal cortex was collected after the behavioral test, and the dopamine and serotonin contents were measured also by ELISA Kit. A significant decrease of the time spent in the light compartment was observed after the isolated rearing (p < 0.01). Mild-heat stimulation significantly increased the time spent in the light compartment, indicating an anti-anxiety effect. Serum corticosterone, IgE and IL-6 were increased after stress, and the amount of serotonin in the frontal cortex was found decreased. The increased corticosterone, IgE and IL-6 were cancelled by mild-heat stimulation. These results suggest that chronic social isolation has negative biological and emotional impacts in mice and that peripheral mild-heat stimulation alleviates at least part of these stress effects.

Regulatory Frameworks for Gene and Cell Therapies in Japan.

The regulations for the human use of advanced therapy medical products such as gene and cell therapy products have evolved in accordance with advance of clinical experience, scientific knowledge, and social acceptance to these technologies. In Japan, two laws, the Pharmaceuticals and Medical Devices (PMD) Act and the Act on the Safety of Regenerative Medicine (ASRM), were enacted in November 2014. The PMD Act defines regenerative medical products for the first time and introduces a system for the conditional and time-limited marketing authorization of regenerative medical products. Under ASRM, the responsibilities of medical institutions to ensure the safety and provide transparency of such medical technologies are described. Amendments to accompanying guidelines for these two Acts are currently in preparation. It is expected that the new legislative frameworks will promote the timely development of new products and technologies, to bring safe and effective regenerative medicines to Japanese patients.

New Governmental Regulatory System for Stem Cell-Based Therapies in Japan.

Regenerative medicine using stem cells is expected to provide tools for the replacement or repair of damaged tissues, opening up the possibility of treating many diseases that cannot otherwise be effectively treated. To promote the development of and access to regenerative medicine, it is important to take a balance of expedited provision of innovative therapies and appropriate steps to ensure safety and efficacy. While most developed countries have various regulatory frameworks for clinical trials and medical treatments involving stem cells, the Act on the Safety of Regenerative Medicine and the Revised Pharmaceutical Affairs Law have recently been simultaneously passed by the Japanese Diet. According to the former act, these medical technologies are categorized into 3 classes depending on their anticipated potential risk to human health, and the specific procedures falling into each class are determined. In addition, the act enables medical institutions to commission cell processing by business facilities outside the institution (even foreign facilities) that fulfill the requirements set out by the Ministry of Health, Labour and Welfare, with the aim to promote collaboration between academia and industry from an early stage. According to the latter law, a therapeutic product for regenerative medicine is defined as a product distinct from pharmaceuticals and medical devices, enabling regenerative medical products to be given a conditional, time-limited marketing authorization much earlier than that under the previous system. The new legal framework of regenerative medicine is expected to achieve the aim to develop and promote regenerative medicine, aiming at timely provision of safe and effective therapies and products.

Clinical significance of KRAS gene mutation and epidermal growth factor receptor expression in Japanese patients with squamous cell carcinoma of the larynx, oropharynx and hypopharynx

The significance of epidermal growth factor receptor (EGFR) signaling has been recognized in various cancers and anti-EGFR therapies in Japan are currently under consideration in squamous cell carcinoma of the head and neck (SCCHN) similar to colorectal cancer. However, there was no established survey regarding heterogeneous EGFR protein expression in Japanese SCCHN patients. The purpose of this study is to examine the relationship between EGFR expression or KRAS mutation (related to the alteration of EGFR pathway) and the clinicopathological characteristics of SCCHN. We retrospectively examined the expression of EGFR protein by immunohistochemistry and KRAS gene mutation at codons 12 and 13 by using paraffin-embedded and formalin-fixed primary tumor tissues from 205 patients with SCCHN who underwent surgery at National Cancer Center Hospital East. In 200 of the 205 patients (97.6 %), EGFR protein was expressed despite intratumoral heterogeneity. No patients had KRAS mutation at codons 12 or 13, and all 183 tumors showed wild-type KRAS. Positive rate of EGFR protein expression was significantly associated with better disease free survival (DFS) (P = 0.0471) and the intensity of EGFR protein expression showed a tendency for better DFS (P = 0.1034). Both higher EGFR positive rate and more intense EGFR expression were significantly associated with well differentiated subtype of squamous cell carcinoma (P = 0.0003 and P = 0.0007, respectively). Most SCCHN patients may be good candidates for the anti-EGFR therapies.

Genetic variation in the natriuretic peptide system and heart failure

Heart failure (HF) is a modern epidemic and is one of the few cardiovascular diseases which is increasing in prevalence. The growing importance of the Natriuretic Peptide (NP) system in HF is well recognized. Laboratory tests for B-type Natriuretic Peptide (BNP) have proven value as diagnostic and prognostic tools in HF and are now part of routine clinical care. Furthermore, recombinant atrial natriuretic peptide (ANP) (carperitide) and BNP (nesiritide) and are approved HF therapies in Japan and the US, respectively and additional natriuretic peptides (e.g., CNP, urodilatin, and designer NPs) are under investigation for use in HF. Common genetic sequence variants are increasingly being recognized as determinants of disease risk or drug response and may help explain a portion of the inter-individual variation in the human NP system. This review describes current knowledge of NP system genetic variation as it pertains to HF as well as ongoing studies and where the field is expected to progress in the near future. To briefly summarize, NP system genetic variants have been associated with alterations in gene expression, NP levels, and cardiovascular disease. The next step forward will include specific investigations into how this genetic variation can advance 'Personalized Medicine', such as whether they impact the utility of diagnostic BNP testing or effectiveness of therapeutic NP infusion. This is already in progress, with pharmacogenetic studies of nesiritide currently underway. We expect that within 5 years there should be a reasonable idea of whether NP system genetic variation will have important clinical implications.

Effects of Anma therapy (traditional Japanese massage) on body and mind

Anma therapy is a traditional style of Japanese massage, one of touch and manual therapies, and one of the most popular CAM therapies in Japan. It was brought from China in the 6th century and, while based on the theory of Chinese medicine, it developed in Japan according to Japanese preference and has recently come to include theories of Western medicine. The purpose of this study was to clarify the physical and psychological effects of Anma therapy. Fifteen healthy female volunteers in their fifth decade, with chronic muscle stiffness in the neck and shoulder, received two interventions: 40-min Anma therapy and 40-min rest intervention. The design was cross-over design. Participants were randomly divided into two groups. Group A was started on Anma therapy from the first day followed by the rest intervention after a 3-day interval. The order of the Anma therapy and the rest intervention reversed for Group B. Visual Analogue Scale (VAS) score for muscle stiffness in the neck and shoulder, state anxiety score, and salivary cortisol concentration levels and secretory immunoglobulin A (s-IgA) were measured pre- and post-interventions. Anma therapy significantly reduced VAS scores and state anxiety scores. S-IgA concentration levels increased significantly across both groups. Anma therapy reduced muscle stiffness in the neck and shoulder and anxiety levels in this pilot study of 50-year-old females.

Recent trends in patient characteristics and therapeutic choices for interstitial cystitis: Analysis of 282 Japanese patients

We investigated the characteristics of recent male and female patients diagnosed with interstitial cystitis (IC), then investigated which therapy was chosen by the attending urologist. Materials were 282 IC patients diagnosed and treated during the past 3 years (sampling from Japanese IC database). Gender, age, medical history and predominant symptoms were investigated. In addition, we investigated the interval before a diagnosis was established. In laboratory findings, we investigated voided volume, urinalysis findings and cystoscopic findings. Regarding therapy, we investigated which therapy was chosen as the first line. The gender ratio was about 1.0:5.6 (male : female). Regarding age distribution, patients in their 60s were the most frequent (65 cases, 31.3%). The interval before diagnosis of IC was 36.5 months on average (1-360 months). Regarding medical history, intrapelvic surgery was the most common and repeated urinary tract infection was next. The most frequent symptom was urinary frequency (295 cases, 98.3%). Urinary urgency was noted in 186 cases (62%) and supra-pubic pain was noted in 125 cases (41.6%). The once voided volume was 104.3 mL on average (50-200 mL). The most common cystoscopic finding was glomerulation (158 cases). Ulcer was present in only 19 cases. The most widely carried out therapy was hydrodistension (208 cases, 67.9%). Oral suplatast tosilate (197 cases, 65.6%), antihistamine (77 cases, 25.6%) and intravesical dimethylsulfoxide (69 cases, 23%) followed. Regarding characteristics, the age distribution was older than other countries. The most frequent symptom was urinary frequency. Oral suplatast tosilate was one of the popular therapies in Japan.

Accelerator for Medical Applications and Electron Acceleration by Laser Plasma

In this article, the current status of radiation therapies in Japan and updated medical accelerators are reviewed. For medical use, there is a strong demand of a compact and flexible accelerator. At present, however, we have only two choices of the S-band linac with one or two rotation axis combined with the multi leaf collimator, or the X-band linac with a rather flexible robotic arm. In addition, the laser plasma cathode that is the second generation of the laser wake-field accelerator (LWFA) is studied as a high-quality electron source for medical use though it is still at the stage of the basic research. The potential of LWFA as medical accelerator near future is discussed based on updated results of laser plasma cathode experiment in Univ. of Tokyo.

Analysis of the efficacy of standard anticancer therapies in Japan.

Eighty patients with prostatic carcinoma were treated by antiandrogen therapy with chlormadinone acetate and diethylstilbestrol diphosphate. Numerous papers have shown that the survival rates of patients with low-grade prostatic carcinomas are higher than those of patients in advanced stages; however, in this study, no statistically significant difference in the ten-year survival rates of these groups was demonstrated. Residual cancer cells in the primary lesions were observed in 90% of the patients who underwent autopsy following death. The results of this study suggest that antiandrogen therapy is not sufficiently effective for the treatment of patients with prostatic carcinoma.

Abstracts of Obstetrical and Gynecological Hormone Therapies in Japan

Abstracts of Obstetrical and Gynecological Hormone Therapies in Japan