Identification of the nuclear export signal in the helix–loop–helix inhibitor Id1

AbstractId proteins play important roles in cellular differentiation and proliferation by negatively regulating basic helix–loop–helix transcription factors. Although their intracellular localization may change depending on the biological situation, little is known about the molecular determinants underlying such changes. Here we report the identification of a nuclear export signal (NES) in Id1. The identified NES was different from that of Id2, but had the ability to confine heterologous green fluorescent protein to the cytoplasm. Thus, our results indicate that the intracellular localization of Id1 is regulated differently from that of Id2

Long-Term Outcome of Proton Therapy and Carbon-Ion Therapy for Large (T2a–T2bN0M0) Non–Small-Cell Lung Cancer

IntroductionAlthough many reports have shown the safety and efficacy of stereotactic body radiotherapy (SBRT) for T1N0M0 non–small-cell lung cancer (NSCLC), it is rather difficult to treat T2N0M0 NSCLC, especially T2b (>5 cm) tumor, with SBRT. Our hypothesis was that particle therapy might be superior to SBRT in T2 patients. We evaluated the clinical outcome of particle therapy for T2a/bN0M0 NSCLC staged according to the 7th edition of the International Union Against Cancer (UICC) tumor, node, metastasis classification.MethodsFrom April 2003 to December 2009, 70 histologically confirmed patients were treated with proton (n = 43) or carbon-ion (n = 27) therapy according to institutional protocols. Forty-seven patients had a T2a tumor and 23 had a T2b tumor. The total dose and fraction (fr) number were 60 (Gray equivalent) GyE/10 fr in 20 patients, 52.8 GyE/4 fr in 16, 66 GyE/10 fr in 16, 80 GyE/20 fr in 14, and other in four patients, respectively. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, Version 4.0.ResultsThe median follow-up period for living patients was 51 months (range, 24–103). For all 70 patients, the 4-year overall survival, local control, and progression-free survival rates were 58% (T2a, 53%; T2b, 67%), 75% (T2a, 70%; T2b, 84%), and 46% (T2a, 43%; T2b, 52%), respectively, with no significant differences between the two groups. The 4-year regional recurrence rate was 17%. Grade 3 pulmonary toxicity was observed in only two patients.ConclusionParticle therapy is well tolerated and effective for T2a/bN0M0 NSCLC. To further improve treatment outcome, adjuvant chemotherapy seems a reasonable option, whenever possible

A new experimental system for irradiating tumors in mice using a linear accelerator under specific pathogen-free conditions.

We developed a reliable system for the irradiation of xenografted tumors in mice which allows for accurate local irradiation under specific pathogen-free conditions. The system presented here consists of acrylic supports for mice and an acrylic box connected to a pump through 0.22 microns pore-sized filters. Mice with xenotransplanted tumors growing on their right hind legs were set on the supports and put into the box in a laminar flow hood. The tumors of 7 mice were irradiated simultaneously with X-rays of 6 and 10 MV generated by a linear accelerator at a dose rate of 3.1-4.7 Gy/min. The air was ventilated through filters during irradiation in the closed box. Microorganism tests confirmed that no bacteria entered or left the box. One of the significant characteristics of this setup is that it allows for irradiation under conditions of acute hypoxia, which is obtained using an integrated tourniquet. The dose variation among 7 tumors was less than 1%. The rest of the mouse's body was shielded effectively by a half-field technique and a lead block. As a result, the whole body dose for the mice was 0-4% of the total dose absorbed by the tumor. Due to the high dose rate and the ability to irradiate 7 mice simultaneously under specific pathogen-free conditions, this new system can be considered a time-saving and valuable tool for radiation oncology research.</p

Candidiasis attributable to gastric ulcer

Candida症は真菌の一種のカンジダ属,特にCandida albicansによって起される疾病であり,本来は正常な皮膚,粘膜,糞便,喀痰,尿などに常在して人体に害を及ぼさない.近年各種の抗生物質,ステロイド製剤の開発に伴って,適応疾患に此等が容易に投与されており,此等薬剤の使用による副作用として色々な現象が現われて来ているが,そのうちの重要なる疾患の一つにCandida症が挙げられる.此のCandida症は上記薬剤の投与に依るのみならず,他疾患に基づく抵抗性の低下した患者においても認められることは周知の如くであり,例えば,白血病,再生不良性貧血,糖尿病等の患者,化学療法を受けた悪性腫瘍患者にも好発し易い.此等の場合多くは食道Candida症として見られることが多いが,今回我々の遭遇した患者は上記薬剤の投与もなく,心窩部痛を主訴として来院したものであり,食道,胃等の上部消化管X線検査によって,胃体中部小彎側に潰瘍像が認められ,潰瘍周辺部の粘膜像も不整を示しており一応悪性化が考えられた症例である.症例.患者は47才,主婦.主訴:約2週間前よりの心窩部痛.家族歴:特記すべきものなし.既往歴:生来健康であり薬剤常用等の経験はない.現病歴約2週間前より心窩部痛を来たし,その疼痛は心窩部をつまみ挙げる様であり特に空腹時に強く感じられ,時には夜中にも疼痛を来たすことがあった. 臨床検査 RBC,508×10(4),WBC,9200.分画像に異常なし.Hgb.16.0g/dl,MCV 98.0,GOT 26u,GPT 16u.尿一般検査では特に著変を認めない. 上部消化管X線検査 食道造影検査にては造影剤の通過は正常で狭窄等の異常所見なく,又粘膜レリーフ像にも著変は認められなかった.(Fig 1. A,B)胃造影検査では充満像では胃角部の短縮及び胃角上部小彎の不整が認められた.(Fig 2. C)圧迫撮影では小彎側中央部よりや,上方に潰瘍ニッシエがあり(Fig 2. D)潰瘍周辺は不整にして,通常みられる良性胃潰瘍よりもwallの巾が広く,又粘膜像においても潰瘍周辺部の顆粒状隆起,レリーフの不整が見られ,良性潰瘍像と少し異ったレ線像を呈しているので潰瘍癌の疑を持ち胃生検を行なうことにした. 胃内視鏡所見 胃体中部小彎側に大きな潰瘍による陥凹部を認め,その辺縁は平滑であったが,潰瘍部の周辺は隆起し潰瘍表面は不整で出血を認めた.そこで潰瘍部のうち3ヶ所をえらんで組織生検を行った. 生検組織所見 岡山大学医学部病理学教室に依頼した病理診断所見によれば,「Gastric ulcer with candidiasis and repairing mucosa, no malignancy｣ であり,間質にはround cell infiltrationがある. bleedingを伴っており,ulcer floorにはfungusが増殖している.再生上皮,異型性は余りない. (Fig.4, E.F.G.H) 以上の結果によりCandidaが増殖している場合には,組織学的に悪性度は認め難い場合でもcancerを完全に否定し得ないこともあり手術に踏切った. 摘出標本組織診断 「Gastric ulcer (Ul-Ⅳ) and chronic active gastritis, no malignancy.」ulcer floorはnecrotic massとgranulationが著明で此のgranulation changeはadipose tissueに及んでいる(Ul-Ⅳ).mucosaは比較的異型性は軽度でmalignancyの所見は認められず,間質はround cellのnodular infiltrationが著明に見られた.以上の如く生検並に手術摘出標本の組織所見によって胃レ線所見において悪性像の如く考えられたのは胃潰瘍に併存したCandidiasisの為によって,斯くの如きレ線像を呈したものと思われる.術后経過における種々の臨床検査成績に著変なく患者は順調である.Candidiasis induced by antibiotics or steroid substances has often been reported. However, we found candidiasis in woman of 47 years which followed gastric ulcer without administration of such substances. This is extremely rare in Japan