A Radial Sclerosing Lesion Mimicking Breast Cancer on Mammography in a Young Woman

A spiculated mass on a mammogram is highly suggestive of malignancy. We report the case of a 32-year-old woman with a radial sclerosing lesion that mimicked breast cancer on mammography. She visited her physician after palpating a lump in her left breast. Mammography showed architectural distortion in the upper inner quadrant of the left breast. Ultrasonography showed a low echoic area with an ambiguous boundary. Core needle biopsy was performed because of the suspicion of malignancy. Histological examination did not reveal any malignant cells. After 6 months, the breast lump became larger and the patient was referred to our hospital. Mammography performed in our hospital showed a spiculated mass, and therefore mammotome biopsy was performed. Histological examination revealed dense fibroelastic stroma with a wide variety of mastopathic changes, leading to a diagnosis of a radial sclerosing lesion. One year after the biopsy, the lump on her left breast had disappeared and mammography showed no spiculated mass

The AAA-ATPase VPS4 Regulates Extracellular Secretion and Lysosomal Targeting of α-Synuclein

Many neurodegenerative diseases share a common pathological feature: the deposition of amyloid-like fibrils composed of misfolded proteins. Emerging evidence suggests that these proteins may spread from cell-to-cell and encourage the propagation of neurodegeneration in a prion-like manner. Here, we demonstrated that α-synuclein (αSYN), a principal culprit for Lewy pathology in Parkinson's disease (PD), was present in endosomal compartments and detectably secreted into the extracellular milieu. Unlike prion protein, extracellular αSYN was mainly recovered in the supernatant fraction rather than in exosome-containing pellets from the neuronal culture medium and cerebrospinal fluid. Surprisingly, impaired biogenesis of multivesicular body (MVB), an organelle from which exosomes are derived, by dominant-negative mutant vacuolar protein sorting 4 (VPS4) not only interfered with lysosomal targeting of αSYN but facilitated αSYN secretion. The hypersecretion of αSYN in VPS4-defective cells was efficiently restored by the functional disruption of recycling endosome regulator Rab11a. Furthermore, both brainstem and cortical Lewy bodies in PD were found to be immunoreactive for VPS4. Thus, VPS4, a master regulator of MVB sorting, may serve as a determinant of lysosomal targeting or extracellular secretion of αSYN and thereby contribute to the intercellular propagation of Lewy pathology in PD

Prognostic significance of overexpression of c-Met oncoprotein in cholangiocarcinoma

http://dx.doi.org/10.1038/bjc.2011.199Background:Cholangiocarcinoma (CC) is a highly malignant carcinoma. We attempted to clarify the prognostic significance of c-Met overexpression and its association with clinicopathological factors in patients with CC. Patients and methods:One hundred and eleven patients with intrahepatic CC (IHCC) and 136 patients with extrahepatic CC (EHCC) who had undergone curative surgery were divided immunohistologically into c-Methigh and c-Metlow groups. Clinicopathological factors and outcomes were compared between the groups. C-Met and epidermal growth factor receptor (EGFR) expression was also examined in 10 CC cell lines. Results:The positivity of c-Met was 45.0% in IHCC and 68.4% in EHCC; c-Methigh expression was demonstrated in 11.7% of IHCC and 16.2% of EHCC. C-Methigh expression was significantly correlated with the 5-year survival rate for CC overall (P=0.0046) and for IHCC (P=0.0013), histopathological classification in EHCC, and for EGFR overexpression in both IHCC and EHCC. Coexpression and coactivation of c-Met and EGFR were also observed in CC cell lines. Multivariate analysis revealed that c-Methigh expression was an independent predictor of poor overall and disease-free survival in patients with IHCC. Conclusions:c-Met overexpression is associated with EGFR expression and is a poor prognostic factor in CC

Behavioral change stage might moderate the impact of multifaceted interventions on non‐attendance from medical care among patients with type 2 diabetes: The Japan Diabetes Outcome Intervention Trial‐2 Large‐Scale Trial 007 (J‐DOIT2‐LT007)

Abstract Aims/Introduction Non‐attendance from regular medical care is a major problem in diabetes patients. This study aimed to examine the impact of a multifaceted lifestyle intervention by face‐to‐face approach (FFA) on non‐attendance from regular medical care in comparison with that by telephone from the technical support center (TSC). Materials and Methods This was secondary analysis from a 1‐year, prospective, cluster randomized, intervention study. Patients with type 2 diabetes, who were regularly visiting primary care physicians cluster‐randomized into the control or intervention (TSC or FFA according to resource availability of the district medical associations) groups, were consecutively recruited. The primary end‐point was non‐attendance from regular medical care. The interaction between the type of intervention (TSC vs FFA) and behavioral change stage (pre‐ vs post‐action stage) in diet and exercise for the dropout rate was assessed. Results Among the 1,915 participants (mean age 56 ± 6 years; 36% women) enrolled, 828, 564 and 264 patients belonged to the control, TSC and FFA groups, respectively. We found evidence suggestive of an interaction between the intervention type and behavioral change stage in diet (P = 0.042) and exercise (P = 0.038) after adjusting for covariates. The hazard ratios (95% confidence interval) of FFA to TSC were 0.21 (0.05–0.93) and 7.69 (0.50–117.78) in the pre‐action and post‐action stages for diet, respectively, whereas they were 0.20 (0.05–0.92) and 4.75 (0.29–73.70) in the pre‐action and post‐action stages for exercise. Conclusions Among diabetes patients, the impact of multifaceted intervention on non‐attendance from medical care might differ by the behavioral change stage

Successful Fluorescence-Guided Surgery on Human Colon Cancer Patient-Derived Orthotopic Xenograft Mouse Models Using a Fluorophore-Conjugated Anti-CEA Antibody and a Portable Imaging System

Background: Fluorescence-guided surgery (FGS) can enable successful cancer surgery where bright-light surgery often cannot. There are three important issues for FGS going forward toward the clinic: (a) proper tumor labeling, (b) a simple portable imaging system for the operating room, and (c) patient-like mouse models in which to develop the technology. The present report addresses all three. Materials and Methods: Patient colon tumors were initially established subcutaneously in nonobese diabetic (NOD)/severe combined immune deficiency (SCID) mice immediately after surgery. The tumors were then harvested from NOD/SCID mice and passed orthotopically in nude mice to make patient-derived orthotopic xenograft (PDOX) models. Eight weeks after orthotopic implantation, a monoclonal anti-carcinoembryonic antigen (CEA) antibody conjugated with AlexaFluor(®) 488 (Molecular Probes Inc., Eugene, OR) was delivered to the PDOX models as a single intravenous dose 24 hours before laparotomy. A hand-held portable fluorescence imaging device was used. Results: The primary tumor was clearly visible at laparotomy with the portable fluorescence imaging system. Frozen section microscopy of the resected specimen demonstrated that the anti-CEA antibody selectively labeled cancer cells in the colon cancer PDOX. The tumor was completely resected under fluorescence navigation. Histologic evaluation of the resected specimen demonstrated that cancer cells were not present in the margins, indicating successful tumor resection. The FGS animals remained tumor free for over 6 months. Conclusions: The results of the present report indicate that FGS using a fluorophore-conjugated anti-CEA antibody and portable imaging system improves efficacy of resection for CEA-positive colorectal cancer. These data provide the basis for clinical trials

Integration of Porous Coordination Polymers and Gold Nanorods into Core–Shell Mesoscopic Composites toward Light-Induced Molecular Release

Besides conventional approaches for regulating in-coming molecules for gas storage, separation, or molecular sensing, the control of molecular release from the pores is a prerequisite for extending the range of their application, such as drug delivery. Herein, we report the fabrication of a new porous coordination polymer (PCP)-based composite consisting of a gold nanorod (GNR) used as an optical switch and PCP crystals for controlled molecular release using light irradiation as an external trigger. The delicate core–shell structures of this new platform, composed of an individual GNR core and an aluminum-based PCP shell, were achieved by the selective deposition of an aluminum precursor onto the surface of GNR followed by the replication of the precursor into aluminum-based PCPs. The mesoscopic structure was characterized by electron microscopy, energy dispersive X-ray elemental mapping, and sorption experiments. Combination at the nanoscale of the high storage capacity of PCPs with the photothermal properties of GNRs resulted in the implementation of unique motion-induced molecular release, triggered by the highly efficient conversion of optical energy into heat that occurs when the GNRs are irradiated into their plasmon band. Temporal control of the molecular release was demonstrated with anthracene as a guest molecule and fluorescent probe by means of fluorescence spectroscopy