Differences in autophagy-related activity by molecular subtype in triple-negative breast cancer

The aim of this study was to assess the expression of significant components of autophagy including beclin-1, light chain (LC) 3A, LC3B, and p62 in the molecular subtypes of triple-negative breast cancer (TNBC) and to evaluate the implications of the results. Tissues from 119 cases of TNBC were used for a tissue microarray. Expression of cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), claudin 3, claudin 4, claudin7, E-cadherin, androgen receptor (AR), and gamma-glutamyltransferase 1 (GGT-1) was detected by immunohistochemical staining of the tissue microarrays. According to the results, the 119 cases of TNBC were subclassified into basal-like type (CK5/6-positive and/or EGFR-positive group), molecular apocrine type (AR-positive and/or GGT-1-positive group), claudin low type (claudin 3-, claudin 4-, or claudin 7-negative and/or E-cadherin-negative group), mixed type (having the features of more than two types), or null type (none of the above). Immunohistochemical staining for autophagy-related markers including beclin-1, LC3A, LC3B, and p62 was performed to evaluate the difference between clinicopathological parameters. TNBCs were categorized as basal-like type (36 patients, 30.3?%), molecular apocrine type (8 patients, 6.7?%), claudin low type (16 patients, 13.4?%), mixed type (37 patients, 31.1?%), and null type (22 patients, 18.5?%). Expression of nuclear p62 was higher in the molecular apocrine type and claudin low type than in other types of TNBC (p?=?0.008). Expression of beclin-1 was higher in molecular apocrine type than in other TNBC types (p?=?0.039). Expression of LC3A and LC3B showed no difference between the molecular subtypes. Multivariate Cox analysis revealed that the negative expression of p62 was associated with shorter disease-free survival [p?=?0.012; odds ratio, 3.192; 95?% confidence interval (CI), 1.293?C7.882] and shorter overall survival (p?=?0.009; odds ratio, 3.895; 95?% CI, 1.409?C10.771). Among the subtypes of TNBC, molecular apocrine breast cancer showed a higher expression of nuclear p62 and beclin-1 than others, which reflected higher autophagy activity.     

The ‘natural’ body,God and contraceptive use in the southeastern United States

Data collected among African‐American and Caucasian women and men in the southeastern USA indicate that participants' perceptions of nature, God's will and the human body influence reproductive health and decision‐making. Attitudes about the health care system, pharmaceutical companies and government programmes for fertility regulation reinforce these views and may negatively affect willingness to use contraceptive methods consistently and correctly.     

Current status of PET-imaging probes of β-amyloid plaques

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by progressive cognitive decline and memory loss. One of pathological hallmarks of AD is the accumulation and deposition of β-amyloid (Aβ) plaques which is a potential target for the early diagnosis of AD. Positron emission tomography (PET), a sensitive radionuclide imaging technique, has provided opportunities to detect Aβ plaques of AD. PET-imaging probes of Aβ plaques have been extensively developed during the last decade. [¹⁸F]Florbetapir, the ¹⁸F-labeled PET-imaging probe of Aβ plaques, was recently approved by US Food and Drug Administration. A number of follow-on PET-imaging probes are currently being developed in academia and pharmaceutical companies. This article will discuss the recent development of PET-imaging probes from [¹¹C]PIB to [¹⁸F]Florbetapir, which are in clinic trials, and several follow-on probes in preclinical stage.     

Magnetic resonance cholangiography: comparison of two- and three-dimensional sequences for assessment of malignant biliary obstruction

The purpose was to retrospectively compare two-dimensional (2D) magnetic resonance cholangiography (MRC) including breath-hold single-shot rapid acquisition with relaxation enhancement (RARE) and multislice half-Fourier RARE versus navigator-triggered 3D-RARE MRC in the evaluation of biliary malignancy. MRC findings were evaluated in 31 patients with malignant biliary obstruction, including biliary malignancy, gallbladder carcinoma, and ampullary cancer. Two observers independently reviewed the images to assess the overall image quality, artifacts, ductal conspicuity, extent of disease, diagnostic confidence of tumor extent, and origin of tumor. The results were compared with surgical and histopathologic findings. Studies obtained with 3D-MRC were of significantly higher technical quality than those obtained with 2D-MRC. However, the accuracy between two sequences for classification of tumor showed no statistical significance. There was no significant difference between the Az values of 2D- and 3D-MRC for overall tumor extent in bilateral second order branch, intrapancreatic common bile duct (CBD) involvement (Az = 0.889, 0.881 for 2D and Az = 0.903, 0.864 for 3D). Nor was there a significant difference between two sequences in the assessment of the origin of tumor. Although 3D-MRC has superior image quality over 2D-MRC, 3D-MRC showed no statistically significant difference in accuracy compared with 2D-MRC for evaluating the extent of disease in malignant biliary obstructions.     

Ischemia-related changes of glial-derived neurotrophic factor and phosphatidylinositol 3-kinase in the hippocampus: their possible correlation in astrocytes

In the present study, we observed the changes of endogenous expression of glial-cell-line-derived neurotrophic factor (GDNF) and phosphatidylinositol 3-kinase (PI-3 kinase) in the gerbil hippocampus after transient forebrain ischemia and investigated the correlation between GDNF and PI-3 kinase in the ischemic hippocampus. In the sham-operated group, GDNF and PI-3 kinase immunoreactivity was not found in any cells in the hippocampal CA1 region. GDNF, not PI-3 kinase, immunoreactivity was expressed in non-pyramidal cells in the CA1 region at 6 h after ischemic insult. At 12-24 h after ischemia, GDNF and PI-3 kinase immunoreactivity in the CA1 region was similar to that of the sham-operated group. From 2 days after ischemic insult, GDNF- and PI-3-kinase-immunoreactive astrocytes were detected in the CA1 region, and GDNF and PI-3 kinase immunoreactivity in astrocytes was highest in the CA1 region 4 days after ischemic insult. Moreover, at this time point, GDNF and PI-3 kinase were co-localized in some astrocytes. Western blotting showed that ischemia-related changes of GDNF and PI-3 kinase protein levels were similar to the immunohistochemical changes after ischemia. These results suggest that GDNF and PI-3 kinase may be related to delayed neuronal death and that GDNF and PI-3 kinase may be involved in activation of astrocytes.     

Bone marrow edema and associated pain in early stage osteonecrosis of the femoral head: prospective study with serial MR images

PURPOSE: To determine the accuracy of magnetic resonance (MR) cholangiography for demonstration of the biliary tract and detection of biliary complications in patients who have undergone orthotopic liver transplantation. MATERIALS AND METHODS: Breath-hold half-Fourier rapid acquisition with relaxation enhancement MR cholangiography was performed in 25 patients who had undergone orthotopic liver transplantation. MR cholangiograms were prospectively and independently interpreted by two radiologists for depiction of the biliary tract and ductal anastomosis and for complications (eg, biliary dilatation, stricture, stones). MR cholangiographic findings were correlated with findings from direct cholangiography (n = 24) and surgery (n = 1). RESULTS: MR cholangiography completely demonstrated first-order intrahepatic bile ducts in 23 (92%) patients, the donor extrahepatic bile duct in 25 (100%), the recipient extrahepatic bile duct in 17 of 18 (94%), and the anastomosis in 24 (96%). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MR cholangiography for detection of biliary dilatation and stricture were each 100%. Complete interobserver agreement occurred in the detection of biliary dilatation and stricture. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MR cholangiography for detection of stones were 100% for one radiologist and 86%, 100%, 96%, 100%, and 95%, respectively, for the other. Both radiologists agreed on the diagnosis of bile duct stones in six of seven cases (kappa = 0.90). CONCLUSION: MR cholangiography enables accurate depiction of the biliary tract and detection of biliary complications in patients with an orthotopic liver transplant.     

Comparison of four habitual physical activity questionnaires in girls aged 7-15 yr

PURPOSE: Questionnaires provide a practical approach to measuring physical activity in children and adolescents, particularly for large-scale epidemiological studies. The purpose of the present study was to compare four habitual physical activity questionnaires and to assess their long-term reliabilities. METHODS: Subjects were female, aged 7-15 yr (and their parents), who participated in a cohort study in which predictors of the onset of menarche were being investigated. Questionnaires consisted of three single-item and one multi-item habitual physical activity questions and were sent to the 640 participants. Test-retest reliability of the questionnaires was assessed on 100 randomly selected participants 11 months later. RESULTS: The Spearman's correlation coefficient was highest (r = 0.40) between the Godin-Shephard Score and the Perspiration Score and was lowest (r = 0.10) between the Stairs Score and the Specific Activity Score. The correlation coefficients were higher when the questionnaires were reported to have been completed by the parents alone, rather than by parents with the assistance of their daughters. The test-retest reliabilities were r = 0.44 for the Perspiration Score, r = 0.59 for the Stairs Score, r = 0.48 for the Godin-Shephard Score, and r = 0.53 for the Specific Activity Score. The reliabilities were higher when the retest was reported to have been completed by the parents alone. CONCLUSIONS: This study suggests that the Perspiration Score, the Godin-Shephard Score, and the Specific Activity Score may provide simple and practical measures of habitual physical activity for children and adolescents.     

Endoscopic Evaluation of the Quality of the Anastomosis After Esophagectomy with Gastric Tube Reconstruction

BACKGROUND: The morbidity and mortality of anastomotic complications after esophagectomy have gradually decreased in recent years. However, swallowing difficulties and reflux continue to burden patients jeopardizing their quality of life. In the present study we performed endoscopic evaluation of the outcomes of esophagogastrostomy by analyzing the presence of anastomotic stenosis and reflux esophagitis. METHODS: A retrospective analysis was carried out on 74 patients who underwent esophagogastrostomy after esophagectomy by one surgeon between January 1995 and December 2004. Fifty-three patients had an endoscopic examination during follow-up (29 +/- 23.6 months, range = 5-111 months). Reflux esophagitis and stenosis at the anastomostic site were analyzed according to the surgical technique used and the location of the esophagogastrostomy. RESULTS: The mean age at the time of repair was 60.3 +/- 8.87 (range = 39-81) years. Cervical anastomosis was performed in 26 patients and intrathoracic anastomosis in 27 patients. No significant statistical difference in the frequency of anastomotic stenosis was observed between the two groups (p = 0.829); reflux esophagitis was noted in three patients in the cervical anastomosis group and in 14 patients in the intrathoracic anastomosis group (p = 0.041). For all patients, 23 received a hand-sewn esophagogastric anastomosis and 30 a circular stapled one. There was no significant statistical difference in anastomotic stenosis (p = 0.689) and reflux esophagitis (p = 0.879) in comparisons between the two groups. CONCLUSION: Cervical anastomosis resulted in a better outcome for esophagogastrostomy by lowering the risk of reflux esophagitis; this outcome might improve the patient's quality of life.     

A Significant Correlation between Nuclear CXCR4 Expression and Axillary Lymph Node Metastasis in Hormonal Receptor Negative Breast Cancer

Background and objectives In breast cancer, the expression pattern of CXCR4 may be correlated with the degree of axillary lymph node involvement. The aim of this study was to evaluate the contributing factors that contribute to the correlation between CXCR4 expression and axillary lymph node metastasis in breast cancer. Methods Between August 1997 and August 2002, sections of paraffin-embedded tissue were obtained from 107 patients who received optimal treatment for breast cancer. The expression of CXCR4 was evaluated by immunohistochemical staining. Results A significant correlation was found in the expression of nuclear CXCR4 and lymph node metastasis (P = 0.03). We found a significant correlation between a high nuclear expression of CXCR4 and axillary lymphatic metastasis in estrogen and progesterone receptor negative breast cancer (P = 0.01 and P = 0.01). There was a significant correlation between the high expression of nuclear CXCR4 and axillary lymphatic metastasis in comparisons between positive estrogen and/or progesterone receptor expression and negative expression (P = 0.02). Conclusions Our results showed that high expression of nuclear CXCR4 was significantly correlated with lymph node metastasis in breast cancer. The high expression of nuclear CXCR4 in hormone receptor negative breast cancer was associated with a high possibility of lymph node metastasis.     

Laser Punch-Out for Acne Scars

Patients with acne scars want smooth facial skin. However, achieving this is difficult with dermabrasion or chemical peeling. Nor can acne scars be covered with cosmetics, due to their ice-picked or cobblestone appearance. Laser resurfacing is more effective and safer than other conventional methods due to its precision with depth control and variable methods of surface cutting. Even depth resurfacing with a laser shows unsatisfactory results, therefore, for the deep-sited acne scar the cutting methods have to be changed according to the depth and pattern of the scar. For 2 years, starting in January 1996, we treated 71 patients with a high-powered CO₂ laser (Ultrapulse). Different resurfacing methods were applied according to the depth and pattern of the scars. For mild depressed scars, even depth resurfacing was done. For moderate-depth acne scars, the shoulder technique was also used. For the deepest and ice-picked scars, the laser punch-out was combined. Laser resurfacing was carried out at 300–500 mJ, with two to five passes. Laser punch-out was done at 500 mJ, with three to seven continuous passes on the ice-picked scar. From the pathologic findings of acne scars showing that there was thick intradermal scar, we knew that laser punch-out was necessary for improvement of acne scars. Depth-wide, the ice-picked scars improved by over 80% and the sharp demarcated margin of the acne scar faded out. Most of the patients with acne scars were satisfied with laser resurfacing. Only six patients had a second laser treatment, with an interval of 12 months. There were no hypertrophic scars after laser resurfacing, but erythema lasted for 3–12 months. Patients taking oral retinoic acid were not contraindicated for laser resurfacing but required special caution because they had atrophic skin and delayed wound healing. Laser resurfacing is the most versatile method for acne scars, with a high-powered CO₂ laser. The laser punch-out method is better than even depth resurfacing for improving deep acne scars and can be combined with the shoulder technique or even depth resurfacing according to the type of acne scar.