ガン チリョウヤク ト フクサヨウ

In Japan, about one-half of population suffers from cancer in their lives, and one-third will die of it. Currently, we have three strategies in the treatment of cancer, i.e., surgical treatment, radiotherapy, and chemotherapy（drug therapy）. Most conventional chemotherapeutic drugs work by impairing cell division, resulting in apototic cell death. However, these drugs have potent side-effects including nausea and vomiting, diarrhea and constipation, anemia, hair loss, hemorrhage, immunosupression and myelosuppression, and secondary neoplasms due to disrupt normal cell growth. Some specific anti-cancer drugs are associated with organ-specific toxicities including cardiovascular disease（e.g., doxorubicin）and lung disease（e.g., bleomycin）. In addition, anti-cancer drugs are applied to patients with maximum tolerated dose（MTD）, side-effects are intolerable to the patients in most cases. In order to improve these unpleasant symptoms, some drugs are approved to cope with the side-effects of chemotherapy（synthetic G-CSF for neutropenia, ５-HT３ inhibitors to block one or more of the signals that cause nausea and vomiting）though, medical staffs should pay attention to these sign of side effects. By the way, recent advances in molecular biology have identified numerous genes and proteins involved in malignant transformation as targets of anticancer therapy. Many moleculartargeted agents are now applied at the bedside. Successful developments of trastuzumab in treating breast cancer, imatinib in chronic myeloid leukemia（CML）and gastrointestinal stromal tumors（ GISTs）, gefitinib and erlotinib in non-small cell lung cancer, sunitinib in GISTs and renal cell carcinoma（RCC）, sorafenib in RCC, and bevacizumab in colorectal cancer, have validated the concept of molecular targeting and raised expectations of patients and oncologists alike. These drugs have high selectivity for tumor cells, provide effective treatment, and produce fewer side effects than are seen with conventional anticancer agents. However, unexpected untoward results may occur during treatment. Special attention will be required

PLAG1 enhances the stemness profiles of acinar cells in normal human salivary glands in a cell type-specific manner

Objectives: Details of the histogenesis of salivary gland tumors are largely unknown. The oncogenic role of PLAG1 in the salivary gland has been demonstrated in vivo. Herein, we demonstrate the roles of PLAG1 in the acinar and ductal cells of normal human salivary glands in an attempt to clarify the early events that occur during the histogenesis of salivary gland tumors. Methods: Normal salivary gland cells with acinar- (NS-SV-AC) and ductal- (NS-SV-DC) phenotypes were transfected with PLAG1 plasmid DNA. Subsequently, the PLAG1 overexpressed and mock cells were examined by cell proliferation, transwell migration, and salisphere formation assays. The expression levels of salivary and pluripotent stem cell markers and differentiation markers were evaluated by quantitative real-time polymerase chain reaction and immunofluorescence. Alterations in transcriptional expressions were investigated via cap analysis of gene expression with gene-enrichment and functional annotation analysis. Results: PLAG1 promoted cell proliferation and transwell migration in the acinar and ductal cells, and markedly enhanced the stemness profiles and luminal cell-like profiles in acinar cells; the stemness profiles were partially increased in the ductal cells. Conclusion: PLAG1 enhanced the stemness profiles in the acinar cells of normal human salivary glands in a cell type-specific manner. Thus, it may be involved in salivary gland tumorigenesis by increasing the stemness character of the normal salivary gland cells

シンコウセイ ドウミャク コウカセイ ビョウヘン ニ タイシ ショウサイナ ビョウリ ソシキガクテキ ケントウ オ オコナイ エタ コウLp（a） ケッショウ ガッペイ 2ガタ トウニョウビョウ ノ 1レイ

We report a case of type 2 diabetes mellitus showing elevated plasma lipoprotein（a）［Lp（a）］levels with various atherosclerotic lesions. A 54-year-old woman diagnosed as having type 2 diabeteswas treated with oral antidiabetic drugs. She had various atherosclerotic lesions, includingcerebral infarction, occlusion of the middle carotid artery and myocardial infarction, along withdiabetes mellitus, hyperlipemia and hypertension and additionally showed a high level of serum Lp（a）. A high plasma level of Lp（a）is considered to be an independent risk factor for atherosclerosis,and it is associated with the development of cerebral infarction, occlusion of the middlecarotid artery and coronary atherosclerosis. Plasma Lp（a）level is predominantly determined bygenetic factors and is not affected by diet or drugs. Aspirin treatment（100 mg/day）lowered theplasma level of Lp（a）by 60%. Pathological findings of the vascular lesions showed that apolipoprotein（a）［apo（a）］, a major apoprotein component of Lp（a）, was deposited in the tunica media ofthe radial artery with rare atherosclerotic lesions and in the inner rim of the fibrous capsular regionwithin the plaque with a large lipid core of the carotid artery. This suggests that Lp（a）stimulatesthe transformation of vascular smooth muscle cells in the tunica media in the early stage of atherosclerosisand that it is associated with fragility of the atherosclerotic lesion in the progressive stage.Hence, plasma Lp（a）levels should be measured for diabetic patients with various atheroscleroticlesions, and aspirin may need to be given to those who have elevated plasma Lp（a）levels in orderto prevent the development of atherosclerotic complications

Characteristic of GAFCHROMIC XR TYPE T dosimetry film

医療の高度化に伴い,近年では長時間のⅩ線透視を行うInterventional Radiology(IVR)手技が頻繁に行われ,副作用としての難治性放射線皮膚障害例の報告が増加している｡確定的影響である放射線皮膚障害はしきい値を超えると発症し,線量に依存して障害の程度が重篤となるため,患者被曝線量の測定が重要である｡しかし,IVRでは照射部位が多彩で,焦点-皮膚間距離が不安定なため,その測定方法は確立されていない｡本研究では,近年IVR等低エネルギー線量測定用フイルムとして開発されたCAFCHROMIC XR TYPE T について性能評価を行い,患者皮膚入射面の被曝線量測定への応用の可能性について検討した｡その結果,線量特性,線質特性,ネット値の安定性に良好な特性を示し,臨床に使用可能であったので報告する｡In recent years, interventional radiology (IVR) using which uses prolomged fluoroscopy has been performed frequently in clinical radiology. Also, reports of radiation skin injuries whose symptoms occur after IVR has been also increasing. These symptoms will become worse if the radiation induced skin injuries are caused by doses which are above the designated threshold, and the grade of injuries are dependent on dose. Therefore, it is important that patient skin dose is measured correctly. But when perfoming IVR, irradiation is complex pricedure, and there is a measurement error with an unfixed source-to-skin distance. So. in this paper, characteristics of GAFCHROMIC XR TYPE T (which are film for low energy X-rays) are performed. Then, they are decided whether the application to the skin surface incidence dose measurement whoud be posible. From these results usefull data can be obtainned; for exanmpe film characteristics, energy factors and stability of sensivility

トクシマシ イシカイ ノ COPD タイサク

In the national project Health Japan 21 （2nd edition） put forward in April 2013, the Ministry of Health, Labour, and Welfare specified chronic obstructive pulmonary disease （COPD） as a targeted lifestyle-related disease, in addition to cancer, heart diseases, and diabetes, and concluded that the establishment of COPD management systems is an important issue to maintain Japanese people’s healthy lives, as the number of deaths from this disease is likely to rapidly increase in the future. In Tokushima Prefecture, the mortality rate associated with COPD has been stably high over the past years ; the nation’ s highest in 2010 and third highest in 2011. In some regions of the western area, particularly mountainous regions, and southern area of the prefecture, the standardized mortality rate among males is double the national mean, highlighting the necessity of rapidly taking countermeasures. Under such circumstances, the Tokushima City Medical Association regarded COPD management as a priority item when developing annual projects this year, and organized the COPD Management and Smoking Cessation Promotion Committee in May. The medical association also presented a tentative plan to conduct association-led individualized COPD assessment at its own expense to the local government of Tokushima, with a view to materializing COPD assessment projects to clarify, evaluate, and analyze the actual situation, including surveys on citizens’ recognition of COPD and those conducted by family doctors to examine the statuses of their patients, involving the local government in the future. During deliberations to examine the feasibility of this plan, the local government proposed a new COPD assessment plan based on the conventional mass pulmonary cancer examination system, in order to deal with those at a high risk of COPD ; following some revisions, the new plan was adopted. The plan consisted of the following steps : > Targeting those meeting the 3 diagnostic criteria specified in the pulmonary cancer interview sheet for COPD assessment : 1） age of 60 or over ; 2） previous smoking habit ; 3） presence of at least one of the subjective COPD symptoms （chronic coughing, sputum, and shortness of breath during activity）. > Providing these patients with a free-consultation coupon to undergo assessment in a registered primary medical examination institution. > Conducting airway obstruction evaluation in primary medical examination institutions using the mass COPD screening interview sheet （COPD-PSTM） and spirometry. > Conducting insurance-covered medical examinations, such as the respiratory function test, chest XP, and CT scans, in secondary medical examination institutions （chest physicians） to establish a definite diagnosis. > Reporting the results of these examinations to family doctors. > If treatment is necessary, developing initial pharmacotherapy plans as part of the standardized treatment of COPD for approximately 3 months, which are implemented by family doctors. In consideration of the rapidly aging Japanese population, the number of potential COPD patients aged 40 and over is expected to reach nearly 7 million soon. In order to deal with such a large number of COPD patients, it is primary care physicians’ duty to provide early diagnosis and treatment, and local medical associations are charged with promoting spirometry through their activities as part of COPD assessment projects, aiming to establish cooperative systems to manage the disease between primary care physicians providing treatment during the stable period and chest physicians providing it during the exacerbation period. As future perspectives, spirometry-promoting seminars to be held in clinical environments are being considered ; participation in these seminars will be a requirement for registered primary COPD examination institutions, and those who have completed such programs will be Tokushima City Medical Association-certified COPD specialists （tentative name）. It is expected that these approaches to carry out the nation’s first COPD assessment projects will improve clinical environments in communities, such as support for smoking cessation, medical professionals’ knowledge of COPD, and the standardization of diagnosis and treatment

Two Novel Mutations in the EYS Gene Are Possible Major Causes of Autosomal Recessive Retinitis Pigmentosa in the Japanese Population

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease including autosomal recessive (ar), autosomal dominant (ad), and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog), which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients. To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study was 18% (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the remaining 9 with only one such mutation). Among these mutations, 2 novel truncating mutations, c.4957_4958insA (p.S1653KfsX2) and c.8868C>A (p.Y2956X), were identified in 16 patients and accounted for 57.1% (20/35 alleles) of the mutated alleles. Although these 2 truncating mutations were not detected in Japanese patients with adRP or Leber's congenital amaurosis, we detected them in Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA mutation was more frequently detected than the c.8868C>A mutation. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population. Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very likely and possible pathogenic mutations, was largely different from the previously reported spectrum in patients from non-Asian populations. Screening for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very effective for the genetic testing and counseling of RP patients in Japan

Efficient and Directive Generation of Two Distinct Endoderm Lineages from Human ESCs and iPSCs by Differentiation Stage-Specific SOX17 Transduction

The establishment of methods for directive differentiation from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is important for regenerative medicine. Although Sry-related HMG box 17 (SOX17) overexpression in ESCs leads to differentiation of either extraembryonic or definitive endoderm cells, respectively, the mechanism of these distinct results remains unknown. Therefore, we utilized a transient adenovirus vector-mediated overexpression system to mimic the SOX17 expression pattern of embryogenesis. The number of alpha-fetoprotein-positive extraembryonic endoderm (ExEn) cells was increased by transient SOX17 transduction in human ESC- and iPSC-derived primitive endoderm cells. In contrast, the number of hematopoietically expressed homeobox (HEX)-positive definitive endoderm (DE) cells, which correspond to the anterior DE in vivo, was increased by transient adenovirus vector-mediated SOX17 expression in human ESC- and iPSC-derived mesendoderm cells. Moreover, hepatocyte-like cells were efficiently generated by sequential transduction of SOX17 and HEX. Our findings show that a stage-specific transduction of SOX17 in the primitive endoderm or mesendoderm promotes directive ExEn or DE differentiation by SOX17 transduction, respectively

Association between social networks and discussions regarding advance care planning among Japanese older adults.

BACKGROUND:Older adults' discussions with family, or with physicians, or with both, about advance care planning (ACP) are increasingly regarded as important for the management of end-of-life care, and yet the factors that induce older adults to engage in ACP discussions are poorly understood. For example, in older adults, is stronger connectedness with family and friends (stronger "networks") associated with ACP discussions? By facilitating, or by impeding ACP discussions? We sought to evaluate the associations between ACP discussions and social networks in Japanese older adults. METHODS:In July 2016 we conducted a cross-sectional survey on 355 community-dwelling patients aged ≥65 years visiting community hospital clinics in Fukushima, Japan. We used the Lubben Social Network Scale (LSNS-6, the shortest available LSNS scale) to assess social networks and recorded two components of social network structure, marital status (dichotomized as "married" vs. "single / other") and living status ("living with others" vs. "living alone"). One item asked if patients had had ACP discussions. We analyzed the LSNS-6 social network and marital and living status data in relation to the occurrence of ACP discussions using multiple logistic regression models with adjustments for possible confounding factors. RESULTS:Respondents' social network was "limited" in 16% of cases; 61% had had ACP discussions. Respondents with a limited social network had a significantly lower tendency to have had ACP discussions than respondents with an "adequate" social network (adjusted odds ratio [AOR]: 0.35; 95% confidence interval [CI]: 0.18-0.66; P < 0.001). Marital status and living status were not significantly associated with ACP discussion. CONCLUSIONS:Among Japanese older adults, weaker social networks may be associated with a lower tendency to discuss ACP. Our findings may help practitioners to quickly screen populations at risk for inadequate ACP discussion by using the LSNS-6