Comparison of Conventional 2D CC (Cranio-Caudal) + MLO (Medio-Lateral Oblique) Bi-Directional Photography and 2D-MLO + DBT-MLO (Digital Breast Tomosynthesis) in Mammography Examination

Introduction: Mammography (MMG) is an excellent examination for breast cancer detection and is widely used in both screening and clinical practice. However, the breast thickness and background the concentration of the mammary gland is large among individuals, and the mammary gland and cancer may overlap and it may not be possible to point out a lesion. In recent years, digital breast tomosynthesis (hereinafter referred to as DBT) has been introduced to solve these problems, and its usefulness has been reported in clinical practice. Therefore, in anticipation of a higher cancer detection rate etc., we compared the conventional 2D CC + MLO 2-way MMG examination with 2DMLO + DBTMLO 2-way MMG examination.Materials and Methods: The combination of 2D CC + MLO and 2DMLO + DBTMLO was read for 95 cases of breast cancer taking 2D CC and MLO and DBT MLO from May 2016 to October 2017. It was judged that the category 3 or more required detailed examination, cancer detection, and cancer detection rates were compared. Subjects were 28 to 87 years of age (median: 55 years), breast composition: high concentration 15.8% (15 cases), heterogeneous high concentration 47.4% (45 cases), mammary gland 28.4% (27 cases), Fatty was 8.4% (8 cases).Results: The cancer detection rate was 87% for the 2D CC + MLO combination and 94% for the 2DMLO + DBTMLO combination in 95 cases of breast cancer. The interpretation time was 95 minutes for the 2D CC + MLO combination and 110 minutes for the 2DMLO + DBTMLO combination.The breast cancer detected only by the combination of 2D CC + MLO was scattered in 1 case and was classified as Category 3 by FAD. Breast cancer detected only by the combination of 2DMLO + DBTMLO: 8 cases with uneven distribution of breast composition, 3 cases with scattered mammary gland, 3 cases with 5 cases with disordered construction, Category 4 with 3 cases with FAD was.Conclusion: Both 2D CC + MLO combination and 2DMLO + DBTMLO combination are considered useful for screening MMG examination. In particular, we would like to consider the introduction to medical examinations for the addition of MMG in DBT, but the issue of the amount of image information, the problem of exposure to radiation, the direction of imaging, the establishment of interpretation methods etc. are future issues

Live-Cell Chromosome Dynamics and Outcome of X Chromosome Pairing Events during ES Cell Differentiation

SummaryRandom X inactivation represents a paradigm for monoallelic gene regulation during early ES cell differentiation. In mice, the choice of X chromosome to inactivate in XX cells is ensured by monoallelic regulation of Xist RNA via its antisense transcription unit Tsix/Xite. Homologous pairing events have been proposed to underlie asymmetric Tsix expression, but direct evidence has been lacking owing to their dynamic and transient nature. Here we investigate the live-cell dynamics and outcome of Tsix pairing in differentiating mouse ES cells. We find an overall increase in genome dynamics including the Xics during early differentiation. During pairing, however, Xic loci show markedly reduced movements. Upon separation, Tsix expression becomes transiently monoallelic, providing a window of opportunity for monoallelic Xist upregulation. Our findings reveal the spatiotemporal choreography of the X chromosomes during early differentiation and indicate a direct role for pairing in facilitating symmetry-breaking and monoallelic regulation of Xist during random X inactivation

Variant PRC1 competes with retinoic acid-related signals to repress Meis2 in the mouse distal forelimb bud

10 p.-3 fig.-1 tab.Suppression of Meis genes in the distal limb bud is required for proximal-distal (PD) specification of the forelimb. Polycomb group (PcG) factors play a role in downregulation of retinoic acid (RA)-related signals in the distal forelimb bud, causing Meis repression. It is, however, not known whether downregulation of RA-related signals and PcG-mediated proximal gene repression are functionally linked. Here, we reveal that PcG factors and RA-related signals antagonize each other to polarize Meis2 expression along the PD axis in mouse. Supported by mathematical modeling and simulation, we propose that PcG factors are required to adjust the threshold for RA-related signaling to regulate Meis2 expression. Finally, we show that a variant Polycomb repressive complex 1 (PRC1), incorporating PCGF3 and PCGF5, represses Meis2 expression in the distal limb bud. Taken together, we reveal a previously unknown link between PcG proteins and downregulation of RA-related signals to mediate the phase transition of Meis2 transcriptional status during forelimb patterning.This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) (23249015 to H.K.), the Japan Agency for Medical Research and Development (AMED) (JP18gm0510016 to H.K. and T.K.), the Special Postdoctoral Researcher Program of RIKEN (to N.Y.-K.), the Regional Innovation Program from MEXT (to T.K.) and the Cross-ministerial Strategic Innovation Promotion Program (SIP) from Cabinet Office, Government of Japan (to T.K. and H.K.).Peer reviewe

Challenge and Outcome for the Prostate Squamous Cell Carcinoma Which Developed 8 Years after Low-Dose-Rate Brachytherapy Approached by a Combined Multimodal Treatment with High-Dose-Rate Interstitial Brachytherapy, External Beam Radiation Therapy, and Chemotherapy

Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT

Pancreatic RECK inactivation promotes cancer formation, epithelial-mesenchymal transition, and metastasis

膵癌悪性化の分子機構解明 --RECK発現の低下が膵癌の浸潤・転移を引き起こす--. 京都大学プレスリリース. 2023-09-19.RECK is downregulated in various human cancers; however, how RECK inactivation affects carcinogenesis remains unclear. We addressed this issue in a pancreatic ductal adenocarcinoma (PDAC) mouse model and found that pancreatic Reck deletion dramatically augmented the spontaneous development of PDAC with a mesenchymal phenotype, which was accompanied by increased liver metastases and decreased survival. Lineage tracing revealed that pancreatic Reck deletion induced epithelial-mesenchymal transition (EMT) in PDAC cells, giving rise to inflammatory cancer-associated fibroblast–like cells in mice. Splenic transplantation of Reck-null PDAC cells resulted in numerous liver metastases with a mesenchymal phenotype, whereas reexpression of RECK markedly reduced metastases and changed the PDAC tumor phenotype into an epithelial one. Consistently, low RECK expression correlated with low E-cadherin expression, poor differentiation, metastasis, and poor prognosis in human PDAC. RECK reexpression in the PDAC cells was found to downregulate MMP2 and MMP3, with a concomitant increase in E-cadherin and decrease in EMT-promoting transcription factors. An MMP inhibitor recapitulated the effects of RECK on the expression of E-cadherin and EMT-promoting transcription factors and invasive activity. These results establish the authenticity of RECK as a pancreatic tumor suppressor, provide insights into its underlying mechanisms, and support the idea that RECK could be an important therapeutic effector against human PDAC

Transcriptional Signature and Memory Retention of Human-Induced Pluripotent Stem Cells

Genetic reprogramming of somatic cells to a pluripotent state (induced pluripotent stem cells or iPSCs) by over-expression of specific genes has been accomplished using mouse and human cells. However, it is still unclear how similar human iPSCs are to human Embryonic Stem Cells (hESCs). Here, we describe the transcriptional profile of human iPSCs generated without viral vectors or genomic insertions, revealing that these cells are in general similar to hESCs but with significant differences. For the generation of human iPSCs without viral vectors or genomic insertions, pluripotent factors Oct4 and Nanog were cloned in episomal vectors and transfected into human fetal neural progenitor cells. The transient expression of these two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described here revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference. Moreover, the episomal reprogramming strategy represents a safe way to generate human iPSCs for clinical purposes and basic research