Search

Abnormal biosyntheses of steroid hormones and dysregulation of steroid hormone receptors contribute to breast cancer metastasis but the mechanisms of that are poorly understand. Here we report a stress hormone producing enzyme, Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11β1) promotes breast cancer metastasis. HSD11β1 was ectopically expressed in seventy-one percent of triple-negative breast tumors and correlated with shorter overall survival. HSD11β1 significantly promoted breast cancer metastasis through induction of epithelial-to-mesenchymal transition (EMT); conversely, pharmacologic and genetic inhibition of HSD11β1 suppressed metastatic progression of breast cancer cells. Moreover, 11-hydroxyprogesterone (11-OHP) whom HSD11β1 produced in breast cancer cells, conferred metastatic properties on non-metastatic breast cancer cells through induction of EMT. We identified Peroxisome Proliferator-activated Receptor Alpha (PPAR-α) as essential for both HSD11β1 and 11OHP-driven EMT. Knockdown of PPAR-α induced MET on HSD11β1-expressing breast cancer cells. Taken together, HSD11β1 promotes breast cancer metastasis and would be a novel target for suppressing breast cancer metastasis.

Adding taxane to an anthracycline-based regimen improves survival in node-positive breast cancer patients, as shown by clinical trials and meta-analyses. However, no studies have analyzed the number of metastatic lymph nodes in patients with estrogen receptor (ER)-positive cancer. This study investigated whether adding a taxane to an anthracycline-based regimen improved prognosis in node-positive, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients in a real-world setting. Using Japanese Breast Cancer Society registry data, we compared disease-free survival (DFS) of patients with ER-positive, HER2-negative breast cancer, excluding those receiving neoadjuvant chemotherapy, between those who received an anthracycline-based regimen followed by a taxane-based regimen (A + T) and those who received only an anthracycline-based regimen (A w/o T), stratified by lymph node status. A Cox proportional hazards model was used to evaluate DFS in both groups. There were 4566 eligible patients with ER-positive, HER2-negative breast cancer. During the median follow-up period of 60 months, there were 481 recurrences and 149 deaths. There was no significant difference in DFS between the A + T and A w/o T groups among patients with 1–3 positive nodes, while there was a significant difference among patients with ≥ 4 positive nodes. In patients with ER-positive, HER2-negative breast cancer, adding taxane to an anthracycline regimen did not improve DFS in patients with metastasis in 1–3 lymph nodes. We considered that the group without the addition of taxane might be present in patients with ER-positive, HER2-negative lymph node metastases.

A triplex-forming oligonucleotide (TFO) can recognize the homopurine-homopyrimidine sequence in DNA duplexes and inhibit the transcription of targeted mRNAs. Recently, we reported that N-acetyl-2,7-diamino-1,8-naphthyridine (DANac), incorporated into a TFO, has high binding ability and base recognition selectivity for the pyrimidine bases in the purine-rich chain of the DNA duplex at pH 7.4. However, it was found in this study that the difference in the Tm values between the pyrimidine bases and purine bases decreased by more than 4 °C at pH 6.0–7.0. To improve the low base recognition selectivity of the TFO, we designed a new artificial base, DAQac, with a quinoline skeleton. The Tm values of the triplexes containing DAQac:T-A or DAQac:C-G were more than 13 °C higher than those of the triplexes containing DAQac:A-T or DAQac:G-C at pH 7.4. We also observed that under more acidic conditions (pH 6.0–7.0), the base recognition selectivity of DAQac in a triplex was higher than that of DANac, although the binding ability of DAQac in a triplex was similar to that of DANac. Additionally, we found that DAQac, incorporated into the TFO, could accurately recognize the MeC-G base pair in the hairpin DNA, similar to the C-G base pair.

Image recognition using artificial intelligence with deep learning through convolutional neural networks (CNNs) has dramatically improved and been increasingly applied to medical fields for diagnostic imaging. We developed a CNN that can automatically detect gastric cancer in endoscopic images. A CNN-based diagnostic system was constructed based on Single Shot MultiBox Detector architecture and trained using 13,584 endoscopic images of gastric cancer. To evaluate the diagnostic accuracy, an independent test set of 2296 stomach images collected from 69 consecutive patients with 77 gastric cancer lesions was applied to the constructed CNN. The CNN required 47 s to analyze 2296 test images. The CNN correctly diagnosed 71 of 77 gastric cancer lesions with an overall sensitivity of 92.2%, and 161 non-cancerous lesions were detected as gastric cancer, resulting in a positive predictive value of 30.6%. Seventy of the 71 lesions (98.6%) with a diameter of 6 mm or more as well as all invasive cancers were correctly detected. All missed lesions were superficially depressed and differentiated-type intramucosal cancers that were difficult to distinguish from gastritis even for experienced endoscopists. Nearly half of the false-positive lesions were gastritis with changes in color tone or an irregular mucosal surface. The constructed CNN system for detecting gastric cancer could process numerous stored endoscopic images in a very short time with a clinically relevant diagnostic ability. It may be well applicable to daily clinical practice to reduce the burden of endoscopists.

The SCRIT (Self-Confining RI Ion Target) facility has been constructed at RIKEN to make the electron-RI scattering experiment possible for the first time in the world. At SCRIT, the angular momentum distribution of scattered electrons is measured by WiSES (Window-frame Spectrometer for Electron Scattering) which consists of a dipole magnet and front/rear drift chambers, covering a solid angle of $\sim$80 mSr with an intrinsic momentum resolution of $\Delta p/p\sim10^{-3}$. Also the luminosity of the electron-RI scattering is estimated from bremsstrahlung photons measured by LMon (Luminosity Monitor) to obtain the absolute cross-section of the scattering. The LMon consists of a CsI calorimeter to measure the photon energy, and plastic fiber scintillators to measure the 2D hit distribution of the bremsstrahlung photons. In 2015-2016 the first physics experiment has been performed using $^{132}\rm Xe$ target, then the luminosity and angular distributions were successfully measured at the electron beam energy of 150-300 MeV, achieving a luminosity above $10^{27}cm^{-2}$s$^{-1}$. In this article, we present the performances of the WiSES and LMon detectors obtained by using the $^{132}\rm Xe$ experiment data.

The aim of this study was to evaluate functional differences between the left and right sides of the ventricular septum in children with right ventricular overload.Radial, longitudinal, and circumferential strain on both sides of the ventricular septum were compared using speckle-tracking echocardiography in patients with preoperative atrial septal defects (n = 22), postoperative tetralogy of Fallot (n = 23) and age-matched normal controls (n = 44). The duration between peak strain of the left and right ventricular septum (TLt-Rt) was also evaluated.Radial and circumferential strain in the control group were significantly higher on the left than the right ventricular septum (41.3 ± 12.8% vs 22.6 ± 6.8% and -28.0 ± 5.4% vs -22.5 ± 4.8%, respectively; P.0001 for both), whereas longitudinal strain did not significantly differ (-22.0 ± 4.9% and -20.7 ± 5.2%, respectively). TLt-Rt was 52.9 ± 35.6, 33.4 ± 29.0, and 38.7 ± 31.0 msec for radial, longitudinal, and circumferential strain, respectively. Longitudinal and circumferential strain on both sides were significantly increased in patients with atrial septal defects compared with controls (P.05), although radial strain was similar on both sides. Radial strain on the right side was significantly increased in patients with tetralogy of Fallot compared with controls (P.05), whereas that on the left side was significantly reduced (P.001). Longitudinal strain on both sides was significantly decreased (P.01 and P.001 for the left and right sides, respectively). In addition, TLt-Rt in patients with tetralogy of Fallot was significantly increased with radial and circumferential deformation (P.05 for both).Deformation of both sides of the ventricular septum functionally differed. Bilayer analysis of the ventricular septum can help in the evaluation of right ventricular performance under volume and pressure overload.

The chance to use the Internet as a communications tool has been increasing, and the consultation businesses for customers at remote places are diversifying in their communication media and forms. In the remote consultation, the lack of non-verbal information is reported as one of the reasons for inefficiency and customer's dissatisfaction compared with the face-to-face consultation. The technique for supplementing non-verbal information with a TV telephone is proposed, and helps to confirm understanding degree or the utterance timing by watching the movement of the face. But the displayed face of the partner causes strong feeling of strain between strangers and the participants also care about background scene displayed on the monitor producing risks in the consultation tasks. In this paper, we propose a remote consultation method that uses avatar technology in the virtual space in order to provide non-verbal information and also avoiding the problem of TV telephone at the same time. The effectiveness of the proposed remote consultation method is confirmed by experiments.

Diabetic mastopathy is an uncommon tumor-like proliferation of fibrous tissue of the breast that usually occurs in a patient who has suffered from type I diabetes mellitus of long duration. Here we report a rare case of diabetic mastopathy that occurred in type II non-insulin dependent diabetes mellitus. This patient was a 63-year-old postmenopausal woman. Mammography, ultrasonography and MR imaging could not distinguish it from breast cancer. Although the core needle biopsy specimen showed fibrosis without evidence of malignancy, excisional biopsy was performed. Histological findings demonstrated typical diabetic mastopathy with keloid-like fibrosis, perivascular lymphocytic infiltration, and lymphocytic lobulitis without evidence of malignancy. These lymphocytes were composed predominantly of B-cells. Five months after surgical biopsy, a nodular formation approximately 4 cm in diameter recurred adjacent to the resected end of the biopsy.

Background Liver metastasis is an important factor determining prognosis in colorectal cancer. The objective of this study was to assess whether colorectal cancer cells in the drainage veins can be detected by measuring telomerase activity and its detection is correlated with liver metastasis. Methods Telomeric repeat amplification protocol assay in combination with an immunomagnetic sorting was used for measuring telomerase activity of epithelial cells in blood samples collected from mesenteric (tumor-drainage) vein and peripheral vessels of 41 colorectal cancer patients. Telomerase activity was calculated as relative telomerase activity (RTA) against a control template and analyzed in terms of liver metastasis. Results RTA of mesenteric blood samples was significantly higher in patients with liver metastasis (60.8%; n = 7) than in those without metastasis (19.7%; n = 34; P = .019). The RTA of peripheral blood sample was also higher in patients with liver metastasis (26.8%) than in those without metastasis (11.1%; p = .17). Moreover, 57% of cases with liver metastasis exhibited a positive telomerase activity in mesenteric blood sample, whereas it was 18% in cases without metastasis. Conclusions Our assay was proven to be a feasible method for detecting cancer cells in tumor-drainage veins. High telomerase activity of mesenteric blood samples reflected the existence of liver metastasis of colorectal cancer.

Pulmonary artery sling is frequently combined with tracheal stenosis, and occasionally combined with congenital heart defects. However, there are few reports of successfully treated cases that were combined with single ventricle. In this article, we report a successfully treated case of pulmonary artery sling combined with tracheal stenosis, single ventricle, pulmonary atresia, vascular ring, and bilateral superior vena cava. A male infant was referred to our hospital for central cyanosis, and was diagnosed with single ventricle (tricuspid stenosis, multiple ventricular septal defect, and hypoplastic right ventricle)with pulmonary atresia by echocardiogram. Tracheal stenosis was shown at cardiac catheterization. Pulmonary artery sling and tracheal diverticulum were diagnosed by computed tomography (CT) and magnetic resonance imaging(MRI)examination. Furthermore, the patient was complicated by vascular ring, which consisted of right aortic arch, an aberrant left subclavian artery, and patent ductus arteriosus, and this ductus arteriosus was connected to the left subclavian artery and pulmonary arterial trunk. After 6 months of medical treatment, including continuous infusion of prostaglandin, re-evaluation was performed by cardiac catheterization. We considered that bidirectional cavo-pulmonary shunt was appropriate for the patient since his pulmonary vasculature had matured well. An operation was performed under the use of cardio-pulmonary bypass. Release of vascular ring by division of the ductus, bilateral bidirectional cavo-pulmonary shunt, and a slide tracheoplasty for tracheal stenosis were performed simultaneously. His recovery was uneventful, and he is currently waiting to receive a Fontan-type operation.

The current study assessed relationships between the ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity (tricuspid E/e') and right ventricular (RV) function in children after tetralogy of Fallot (TOF) repair. The RV function of 25 asymptomatic children with surgically repaired TOF (age 3.3 ± 2.0 years) was assessed by echocardiography and cardiac catheterization. Right ventricular end-diastolic pressure and volume (RVEDP and RVEDV), systolic pressure, and ejection fraction, as well as mean pulmonary arterial pressure, mean right atrial pressure (RAP), and the severity of both pulmonary regurgitation (PR) and tricuspid regurgitation (TR) were assessed in terms of the contribution to tricuspid E/e'. Univariate analysis discovered a relationship between tricuspid E/e' and RVEDV (R(2) = 0172), pressure half-time of PR (PR-PHT) (R(2) = 0.173), and TR grade (R(2) = 0.145) (p < 0.01 for each). After multivariate adjustment, PR-PHT was significantly associated with tricuspid E/e' (β = 0.210; p < 0.001). Tricuspid E/e' was not significantly associated with RVEDP or RAP. In conclusion, tricuspid E/e' does not indicate RV diastolic function but reflects the severity of PR in asymptomatic children after TOF repair.

We describe the role and regulation of intermediate-conductance Ca2+-activated K+ (IKca) channels in cardiovascular pathophysiologies such as hypertension and restenosis. Blood vessels in vivo are continuously exposed to hemodynamic forces. These include shear stresses on the luminal surface generated by blood flow, cyclic distension due to the vascular wave caused by the pulsatility of the blood flow, and endocrine and local factors including angiotensin II (Ang II) and endothelin-1. Cell membrane stretch activates IKca channels. The activation is associated with extracellular Ca2+ influx through stretch-activated nonselective cation channels, and is also modulated by the F-actin cytoskeleton and the activation of PKC. Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels. Mechanical stress and Ang II regulate the migration and proliferation of vascular smooth muscle cells. The modulation of IKca channels in artery smooth muscle cells has an important role in cell migration and proliferation. In this review, we will discuss the physiological and pathophysiological role of IKca channel in cells closely associated with vascular biology and the initiation and progression of vascular disease.

Background: A lots of articles published regarding the usefulness of multidetector-row computed tomography (MDCT) in children with congenital heart disease (CHD) mostly describe that it can be an alternative to the invasive catheterization and angiography. The unique diagnostic features of this imaging modality have been largely ignored or disregarded. We described the pathological conditions that cannot be diagnosed by conventional angiography with cardiac catheterization but can be accurately diagnosed by MDCT. Methods: We retrospectively reviewed non-ECG-gated MDCT images acquired from 452 children and young adults with CHD between 2005 and 2010 in our institute. In this article, we focused on the diagnostic advantages of MDCT, and indicated five pathological conditions. (1) When Blalock-Taussig shunt total occlusion prevents catheter insertion into the artificial vessel and angiography is ruled out, the peripheral pulmonary artery during the peripheral pulmonary artery can be imaged and diagnosed using MDCT based on blood flow supplied from many small collateral vessels originating from the aorta. (2) The location and protrusion of the device in the vessel after coil embolization to treat patent ductus arteriosus can be accurately visualized by virtual endoscopy using MDCT. (3) Calcification of patches, synthetic blood vessels, and other prostheses that is indistinct on conventional angiograms is clear on MDCT. (4) Simultaneous MDCT observations of the anatomical relationships between arterial and venous systems on the same image can clarify the detail diagnosis for surgical treatment. (5) Compression of the airways by the great vessels and pulmonary segmental emphysematous change can be diagnosed by MDCT. Results and Conclusions: Among patients with CHD, MDCT is useful not only as a non-invasive alternative to conventional angiography, but also as a tool for specific morphological diagnoses. In the future, it will be necessary to accumulate experience in the recognition of cardiovascular conditions under which MDCT is necessary and to perform as the appropriate examination. Cardiol Res. 2011;2(4):150-159 doi: https://doi.org/10.4021/cr61w

Background: Serum heart-type fatty acid-binding protein (H-FABP) is widely applied as a marker of cardiac myocyte injury. Recently, it has been reported that levels of H-FABP are elevated in adult patients with chronic heart failure and thus provide useful prognostic information. The aim of the present study was to examine the relationships between serum H-FABP levels and pathophysiological characteristics in children and adolescents with congenital heart disease (CHD). Methods and Results: Serum H-FABP levels were preoperatively and postoperatively measured in 238 consecutive patients with CHD aged 1-31 years. The relationships between H-FABP levels and severity of heart failure, circulatory status and laboratory data were cross-sectionally analyzed. Multivariate regression analysis indicated that serum H-FABP levels are independently affected by age, New York Heart Association functional class, creatine kinase MB, creatinine and arterial oxygen saturation (standard regression coefficients, -0.378, 0.237, 0.422, 0.615, and -0.210, respectively). Neither left ventricular ejection fraction nor B-type natriuretic peptide correlated with H-FABP levels. Conclusions: H-FABP could serve as a new monitoring tool to provide information that will guide the optimal therapy and management of CHD patients. (Circ J 2011; 75: 1992-1997)

Background The present study aimed to evaluate the prevalence and the location of segmental emphysematous change in congenital heart disease (CHD) patients with increased pulmonary blood flow using multidetector-row computed tomography (MDCT). Methods A total of 129 consecutive patients (mean age, 5.8±5.4 years; range, 1 month to 24 years) underwent MDCT angiography of the thorax. The frequency of emphysematous change was evaluated in patients with ventricular septal defect (VSD, n =61), atrial septal defect (ASD, n =27), patent ductus arteriosus (PDA, n =36) and complete atriventriclar septal defect (CAVSD, n =5). In 59 patients who underwent cardiac catheterisation, the relationships between the emphysematous change and both pulmonary to systemic blood flow ratio (Qp/Qs) and mean pulmonary arterial pressure (mPAP) were evaluated. Results The emphysematous change was detected in 57 patients (44.2%) out of 129 patients. The frequency of segmental emphysematous change in left side was higher than in right side (14.8% vs. 6.5%). Both Qp/Qs and mPAP affected the presence of emphysema. Conclusion MDCT can provide accurate detection of segmental emphysema in patients with CHD. Emphysematous change is not uncommon pathological lesion in children and adolescents with CHD.

Telomerase is expressed in human germ tissues and in the majority of primary human tumors. The catalytic subunit of telomerase, hTERT is one of the most important components of telomerase. In this study we attempted to show by means of immunohistochemistry the association between hTERT expression and recurrence in 128 colorectal cancer patients surgically treated in the University of Tokyo Hospital.Immunostaining was performed in a conventional manner using a commercial monoclonal antibody.In our results, negative TERT immunoreactivity in the primary lesion was significantly associated with advanced tumor stage (p=0.0007), the presence of lymph node metastasis (p=0.00018) and recurrence (p0.0001). Recurrence-free survival rate was significantly lower in patients with negative TERT immunoreactivity (p=0.0002). In the same way, if limited in patients without metastatic lymph nodes at surgery or in patients with T3 or T4 tumor, the recurrence-free survival rate was significantly lower in those with negative TERT immunoreactivity (p=0.019, p=0.016).Negative TERT immunoreactivity may be a novel indicator for poor prognosis of colorectal cancer patients and additional studies with a larger number of patients may lead to identifying patients at high risk for recurrence more accurately.