Prognostic factors for survival after first recurrence in breast cancer: a retrospective analysis of 252 recurrent cases at a single institution.

[Introduction]Previous studies have shown that primary breast cancer patients with estrogen receptor (ER)-positive status have better outcomes in terms of both overall survival and disease-free intervals (DFI). However, 25.2 % of our ER-positive patients experienced recurrence. This study aimed to define factors potentially predicting survival after first recurrence in surgically treated patients with stage I–III breast cancer. [Methods]We retrospectively analyzed 252 females with recurrent breast cancer who had undergone surgery and been followed at Kyoto University Hospital in Japan. Age, clinical stage, pathological stage, axillary lymph node involvement, ER status at the time of diagnosis, progesterone receptor status, human epidermal growth factor receptor 2 status, operative method, adjuvant chemotherapy, adjuvant endocrine therapy, use of trastuzumab after recurrence, site of recurrence, DFI, and time of recurrence were examined for possible influences on survival after the first recurrence. [Results]Positive ER status and positive PR status at the time of diagnosis were significantly favorable factors of survival after first recurrence for patients with recurrence, p < 0.001 and p = 0.021, respectively. More than two sites of recurrence (p < 0.001) were associated with shorter survival time after the first recurrence on multivariate analysis. Survival of patients with recurrent breast cancer steadily improved from 1980–1994 to 1995–2008, significantly in ER-negative subgroups. [Conclusions]Positive ER status at the time of diagnosis is a powerful predictor for favorable survival after first recurrence. Survival time after first recurrence of breast cancer has steadily increased in recent decades. Advances in treatments and attitudes about breast cancer have contributed to this improvement in survival after first recurrence

Contribution of hematopoietic stem cells in blood vessel formation

Vascular development consists of vasculogenesis and angiogenesis. The system of TIE2-Angiopoietin (Ang) is involved in angiogenesis. TIE2 regulates adhesion and dissociation between endothelial cells and mural cells, and survival, apoptosis, and chemotaxis of endothelial cells. Ang-2, which is produced by endothelial cells under tissue hypoxia, has been suggested to be a key regulator for the initiation of endothelial cell sprouting from pre-existing vessels. Although Ang-2 binds to TIE2, it does not promote activation of TIE2 on endothelial cells. Ang-2 produced from endothelial cells under hypoxia inhibits the binding of Ang-1 to TIE2. On the other hand, Ang-1 promotes activation of TIE2 and adhesion between endothelial cells and mural cells. Therefore, endothelial cells dissociated from mural cells by Ang-2 are free to move to avascular area where oxygen or nutrient is needed. We recently found that hematopoietic stem cells produce Ang-1 and promote chemotaxis and network formation of TIE2-positive endothelial cells. Moreover, hematopoietic stem cells change their fate into mural cell and stabilize the vessel structure. This novel function may be applied clinically to promote neovascularization by transplanting the hematopoietic stem cells at the desired site.Biomedical Reviews 2003; 14: 1-8

PSF1はマウスの初期発生に必須である

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1614号 , 学位授与年月日 : 平成18年2月1日, 学位授与大学 : 金沢大

Platelet derived growth factor receptor alpha is essential for establishing a microenvironment that supports definitive erythropoiesis

金沢大学大学院自然科学研究科大阪大学微生物病研究所 情報伝達分野The hematopoietic system undergoes a qualitative change during the embryogenesis of most vertebrates. It is designated as the shift of primitive to definitive hematopoiesis and suitable microenvironment must be established to support this shift. While studying the role of platelet derived growth factor receptor α (PDGFR α) in embryonic hematopoiesis, we found that it was expressed in a stromal cell component of liver, a major site of this shift, but not in the yolk sac, the site of primitive hematopoiesis. Thus, we considered that development of PDGFRα positive stromal cells is an essential requirement for this shift. Without PDFGRα positive cell component, erythropoiesis was suppressed in the culture of fetal liver. Moreover, injection of an antagonistic anti-PDGFRα monoclonal antibody during embryogenesis suppressed the production of definitive erythrocytes. These indicated that PDGF exerts its effect on a subset of stromal components to prepare a microenvironment that can support the definitive erythropoiesis. © 2006 The Japanese Biochemical Society

c-Met-Dependent Multipotent Labyrinth Trophoblast Progenitors Establish Placental Exchange Interface

SummaryThe placenta provides the interface for gas and nutrient exchange between the mother and the fetus. Despite its critical function in sustaining pregnancy, the stem/progenitor cell hierarchy and molecular mechanisms responsible for the development of the placental exchange interface are poorly understood. We identified an Epcamhi labyrinth trophoblast progenitor (LaTP) in mouse placenta that at a clonal level generates all labyrinth trophoblast subtypes, syncytiotrophoblasts I and II, and sinusoidal trophoblast giant cells. Moreover, we discovered that hepatocyte growth factor/c-Met signaling is required for sustaining proliferation of LaTP during midgestation. Loss of trophoblast c-Met also disrupted terminal differentiation and polarization of syncytiotrophoblasts, leading to intrauterine fetal growth restriction, fetal liver hypocellularity, and demise. Identification of this c-Met-dependent multipotent LaTP provides a landmark in the poorly defined placental stem/progenitor cell hierarchy and may help us understand pregnancy complications caused by a defective placental exchange

Pillar[6]arene acts as a biosensor for quantitative detection of a vitamin metabolite in crude biological samples

ビタミン代謝物を迅速定量できる超分子バイオセンサーを開発. 京都大学プレスリリース. 2020-12-09.Metabolic syndrome is associated with obesity, hypertension, and dyslipidemia, and increased cardiovascular risk. Therefore, quick and accurate measurements of specific metabolites are critical for diagnosis; however, detection methods are limited. Here we describe the synthesis of pillar[n]arenes to target 1-methylnicotinamide (1-MNA), which is one metabolite of vitamin B3 (nicotinamide) produced by the cancer-associated nicotinamide N-methyltransferase (NNMT). We found that water-soluble pillar[5]arene (P5A) forms host–guest complexes with both 1-MNA and nicotinamide, and water-soluble pillar[6]arene (P6A) selectively binds to 1-MNA at the micromolar level. P6A can be used as a “turn-off sensor” by photoinduced electron transfer (detection limit is 4.38 × 10−6 M). In our cell-free reaction, P6A is used to quantitatively monitor the activity of NNMT. Moreover, studies using NNMT-deficient mice reveal that P6A exclusively binds to 1-MNA in crude urinary samples. Our findings demonstrate that P6A can be used as a biosensor to quantify 1-MNA in crude biological samples

Augmentation of Positive Valence System–Focused Cognitive Behavioral Therapy by Inaudible High-Frequency Sounds for Anhedonia : A Trial Protocol for a Pilot Study

Importance Recent conceptualizations in Research Domain Criteria have indicated that anhedonia, 1 of 2 core symptoms of depression, which can be treatment resistant, is associated with deficits in the positive valence system, and inaudible high-frequency sound therapy has been shown to enhance reward-related brain circuitry. Hence, cognitive behavioral therapy focusing on the positive valence system enhanced with sound therapy could have a synergistic effect on anhedonia.Objective To test the augmentation effect of inaudible high-frequency sounds on the efficacy of positive valence system–focused cognitive behavioral therapy to treat anhedonia.Design, Setting, and Participants In this individual-level allocation, exploratory, single-center randomized superiority pilot trial, patients, therapists, and evaluators will be masked to intervention or placebo assignment. The trial will take place at a national psychiatric referral hospital in Tokyo, Japan, among 44 adult patients with clinically significant anhedonia and moderate to severe depression. Outcomes will be analyzed following the intent-to-treat principle using a repeated-measures mixed model.Intervention The intervention group will participate in 8 weekly sessions of positive valence system–focused cognitive behavioral therapy with in-session exposure to an inaudible high-frequency sound; the comparison group will undergo cognitive behavioral therapy with in-session exposure to a placebo sound.Main Outcomes and Measures The primary outcome is anhedonia assessed using the self-reported Snaith-Hamilton Pleasure Scale. The secondary outcome is anhedonia assessed using the clinician-administered version of the Snaith-Hamilton Pleasure Scale.Discussion Recruitment for this study began in May 2018, and the projected date of final allocation is January 2020. A total of 21 eligible patients were registered for participation as of May 30, 2019. To date, treatments for depression do not guarantee clinically successful outcomes. This pilot trial will provide preliminary evidence of the augmentation effect of high-frequency inaudible sounds on cognitive behavioral therapy for anhedonia. Overall, exposure to an inaudible high-frequency sounds does not require attentional or cognitive effort from either patients or therapists; therefore, results from a future confirmative trial could indicate that cognitive behavioral therapy can be augmented in an effortless manner