Three-dimensional visualization of thoracodorsal artery perforators using photoacoustic imaging

Introduction: Diagnostic imaging modalities to evaluate the three-dimensional distribution of thoracodorsal artery perforators (TDAPs) are lacking. In this study, TDAPs were visualized and characterized using photoacoustic imaging. Material and methods: In this study, 34 sites in the lateral chest wall of 18 individuals were analyzed. The region extending 5 cm ventral and 5 cm dorsal to the lateral edge of the latissimus dorsi (LD) and 5–15 cm from the posterior axillary fold was scanned using photoacoustic imaging. The largest perforator closest to the edge of the LD was characterized. The location of the stem portion and the orientation of the longest cutaneous branch of the perforator were described. The relationship between the maximal depth of delineation on photoacoustic images and the depth of the deep fascia was assessed. Results: On average, 2.6 perforators (range, 1–5 perforators) were visualized in the region of interest. The distribution of the TDAP stem portion was similar to that in previous studies. Cutaneous branches were preferentially oriented in a medial-caudal direction. The length of delineated cutaneous branches varied (range, 7–78 mm) depending on the thickness of the subcutaneous layer. Vessels under the LD were observed when the subcutaneous layer was thin. Conclusion: Photoacoustic imaging can successfully visualize TDAPs in three dimensions. Visualization of TDAPs varied by the thickness of the subcutaneous layer. A thin deep fascia of the LD might be a cause of deep laser penetration

ATM suppresses c-Myc overexpression in the mammary epithelium in response to estrogen

ATM遺伝子変異による乳癌発症機構を解明 --HBOC症候群の乳腺特異的発癌機構の解明に貢献--. 京都大学プレスリリース. 2023-02-09.ATM gene mutation carriers are predisposed to estrogen-receptor-positive breast cancer (BC). ATM prevents BC oncogenesis by activating p53 in every cell; however, much remains unknown about tissue-specific oncogenesis after ATM loss. Here, we report that ATM controls the early transcriptional response to estrogens. This response depends on topoisomerase II (TOP2), which generates TOP2-DNA double-strand break (DSB) complexes and rejoins the breaks. When TOP2-mediated ligation fails, ATM facilitates DSB repair. After estrogen exposure, TOP2-dependent DSBs arise at the c-MYC enhancer in human BC cells, and their defective repair changes the activation profile of enhancers and induces the overexpression of many genes, including the c-MYC oncogene. CRISPR/Cas9 cleavage at the enhancer also causes c-MYC overexpression, indicating that this DSB causes c-MYC overexpression. Estrogen treatment induced c-Myc protein overexpression in mammary epithelial cells of ATM-deficient mice. In conclusion, ATM suppresses the c-Myc-driven proliferative effects of estrogens, possibly explaining such tissue-specific oncogenesis

Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2‐mutation carriers

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients

Non-clinical studies for oncology drug development

Non-clinical studies are necessary at each stage of the development of oncology drugs. Many experimental cancer models have been developed to investigate carcinogenesis, cancer progression, metastasis, and other aspects in cancer biology and these models turned out to be useful in the efficacy evaluation and the safety prediction of oncology drugs. While the diversity and the degree of engagement in genetic changes in the initiation of cancer cell growth and progression are widely accepted, it has become increasingly clear that the roles of host cells, tissue microenvironment, and the immune system also play important roles in cancer. Therefore, the methods used to develop oncology drugs should continuously be revised based on the advances in our understanding of cancer. In this review, we extensively summarize the effective use of those models, their advantages and disadvantages, ranges to be evaluated and limitations of the models currently used for the development and for the evaluation of oncology drugs

Real-time 3D Photoacoustic Visualization System with a Wide Field of View for Imaging Human Limbs [version 2; referees: 2 approved]

Background: A breast-specific photoacoustic imaging (PAI) system prototype equipped with a hemispherical detector array (HDA) has been reported as a promising system configuration for providing high morphological reproducibility for vascular structures in living bodies. Methods: To image the vasculature of human limbs, a newly designed PAI system prototype (PAI-05) with an HDA with a higher density sensor arrangement was developed. The basic device configuration mimicked that of a previously reported breast-specific PAI system. A new imaging table and a holding tray for imaging a subject's limb were adopted. Results: The device’s performance was verified using a phantom. Contrast of 8.5 was obtained at a depth of 2 cm, and the viewing angle reached up to 70 degrees, showing sufficient performance for limb imaging. An arbitrary wavelength was set, and a reasonable PA signal intensity dependent on the wavelength was obtained. To prove the concept of imaging human limbs, various parts of the subject were scanned. High-quality still images of a living human with a wider size than that previously reported were obtained by scanning within the horizontal plane and averaging the images. The maximum field of view (FOV) was 270 mm × 180 mm. Even in movie mode, one-shot 3D volumetric data were obtained in an FOV range of 20 mm in diameter, which is larger than values in previous reports. By continuously acquiring these images, we were able to produce motion pictures. Conclusion: We developed a PAI prototype system equipped with an HDA suitable for imaging limbs. As a result, the subject could be scanned over a wide range while in a more comfortable position, and high-quality still images and motion pictures could be obtained

Efficacy of laser capture microdissection plus RT-PCR technique in analyzing gene expression levels in human gastric cancer and colon cancer

<p>Abstract</p> <p>Background</p> <p>Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase gene expressions are reported to be valid predictive markers for 5-fluorouracil sensitivity to gastrointestinal cancer. For more reliable predictability, their expressions in cancer cells and stromal cells in the cancerous tissue (cancerous stroma) have been separately investigated using laser capture microdissection.</p> <p>Methods</p> <p>Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase mRNA in cancer cells and cancerous stroma from samples of 47 gastric and 43 colon cancers were separately quantified by reverse transcription polymerase chain reaction after laser capture microdissection.</p> <p>Results</p> <p>In both gastric and colon cancers, thymidylate synthase and orotate phosphoribosyltransferase mRNA expressions were higher (p < 0.0001, p <0.0001 respectively in gastric cancer and P = 0.0002, p < 0.0001 respectively in colon cancer) and dihydropyrimidine dehydrogenase mRNA expressions were lower in cancer cells than in cancerous stroma (P = 0.0136 in gastric cancer and p < 0.0001 in colon cancer). In contrast, thymidine phosphorylase mRNA was higher in cancer cells than in cancerous stroma in gastric cancer (p < 0.0001) and lower in cancer cells than in cancerous stroma in colon cancer (P = 0.0055).</p> <p>Conclusion</p> <p>By using this method, we could estimate gene expressions separately in cancer cells and stromal cells from colon and gastric cancers, in spite of the amount of stromal tissue. Our method is thought to be useful for accurately evaluating intratumoral gene expressions.</p

破裂脳動脈瘤の発症12日目に別の未破裂脳動脈瘤が破裂した1例

　67歳女性．以前より左中大脳動脈・脳底動脈本幹・左海綿静脈洞部内頚動脈に未破裂脳動脈瘤を指摘されていた．突然に激しい頭痛・嘔気が出現し，その5日後に他院でsubarachnoid hemorrhage（SAH）を指摘されたため，当院紹介となった．CT で左シルビウス裂・左大脳半球脳溝を中心にSAH を認めるも，脳幹周囲には認めなかった．緊急DSA では，左中大脳動脈瘤は4.9mm でbleb を伴っていたが，脳底動脈瘤は6.5mm，左内頚動脈瘤は2.9mm で，いずれもblebはなかった．左中大脳動脈瘤の破裂と考え，緊急で同部位にコイル塞栓術を施行し，ほぼ完全閉塞された．しかし，第12病日に突然昏睡状態となり，CT で橋腹側を中心に新たなSAH を認めた．脳底動脈瘤の破裂と診断し，緊急コイル塞栓術を行った．術後意識状態は改善し，NPH に対しVP シャントを追加し，mRS1で自宅退院となった．短期間で2個の動脈瘤が破裂した比較的稀な症例と考えられ，報告する．　We report a rare case of recurrent bleeding caused by another cerebral aneurysm during the subacute phase of aneurymal subarachnoid hemorrhage (SAH). A 67-yearold woman developed severe headache and visited our hospital on the 5th day from the onset. Her computed tomography (CT) confirmed SAH, and her angiography revealed three intracranial aneurysms: a 4.9-mm left middle cerebral artery aneurysm (MCA An) with bleb formation, a 6.5-mm basilar trunk aneurysm (BA trunk An) without bleb, and a 2.9-mm internal carotid cavernous sinus aneurysm without bleb. As the SAH was present mostly in the left cerebral hemisphere and left Sylvian fissure without the involvement of the basal cistern. MCA An was thought to bleed. Subsequently, she underwent coil embolization and recovered well. However, she suddenly became comatose on the 12th day from the onset. Her CT showed diffuse SAH localized around the prepontine cistern. Second angiography demonstrated the expanded BA trunk An. Coil embolization was then successfully performed. VP shunt insertion was added for hydrocephalus secondary to SAH, and left our hospital with favorable outcome

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

ジュギョウ ヲ コエタ PBL ノ テンカイ コロナカ ニ オケル ジュウガイ プロジェクト ニ カンスル ジッセン ホウコク

近年、野生動物によって引き起こされる獣害が日本各地で大きな社会問題となっている。筆者らは、2019年度に大阪大学で開講されたProject-Based Learning(PBL)1)型授業「フィールド・プロジェクト2)」で、獣害が深刻な滋賀県高島市のX地区周辺で課題解決に取り組んだ。授業は解決策の提案をもって終了したが、提案の改善を重ねて実装に繋げるという過程で実践力を身につけたいという思いから、授業担当教員および地域住民（課題提供者）の協力を得て、PBL形式での学びを継続することにした。新型コロナウイルス感染症拡大によって計画の変更を余儀なくされることもあったが、状況に適応して実現可能なことに着手し、活動を展開した。本活動はPBLを授業だけに留めず、授業終了後も学習目標を掲げ、課題解決に向けて実装に取り組もうとした点で、PBLの継続性に示唆を与え得る事例である。In recent years, agricultural damage caused by wild animals has become a major social problem in various parts of Japan. The authors have tackled the beast damage problem around a district of Takashima City, Shiga Prefecture. This activity started in a project-based-learning (PBL) class coursework called "Field Project" at Osaka University in 2019. The authors made some proposals by the end of the class, but had a desire to acquire practical skills in the process of improving and implementing the pr oposals. So, we decided to continue PBL-style learning in cooperation with a professor and the community residents. However, the pandemic of COVID-19 made us change our plan and there was some limitation to what the authors could do. This activity was beyo nd a class coursework, but we set learning goals and tried to implement our ideas. Therefore, this can give some suggestions to the continuity of PBL