Magnetically Directed Targeting Aggregation of Radiolabelled Ferrite Nanoparticles

Ferrite magnetic nanoparticles (Fe3O4 or iron (II,III) oxide; 15–25 nm of diameter) were developed. These magnetic nanoparticles are a potential vehicle for magnetically induced target aggregation in living animals. In this preliminary study, the radiochemical purity for the radiolabeled magnetic nanoparticles was examined, and the possibility of the magnetically induced targeting of the radio-nanoparticles was evaluated. Our results showed that radiolabeled ferrite nanoparticles can be used as magnetic targeting agents with high labeling efficiency and stability. These particles can be distributed within living animals via intravenous injection, and the biodistribution of the particles can be potentially controlled by external magnetism. These evaluations will be the groundwork for the future development of delivery techniques for radiopharmaceuticals through external magnetic control

Acute Paraparesis Caused by a Giant Cell Tumor of the Thoracic Spine

AbstractGiant cell tumor (GCT) is a benign but locally aggressive skeletal neoplasm of young adults. GCT located in the spine is relatively rare and may need a combination of surgical and adjunctive therapies. Here we present a patient who had intermittent thoracic back pain for two weeks and experienced an acute episode of decreased muscle power of both lower limbs. Magnetic resonance (MR) imaging examinations of the thoracic spine revealed that the patient had severe spinal canal compression caused by pathological fracture due to a tumor within the seventh thoracic vertebra. She underwent an emergent surgical intervention for total removal of the tumor and spinal reconstruction with autologous rib grafts and instruments. Postoperatively, the patient made an uneventful recovery of muscle power of bilateral lower limbs. She subsequently received adjuvant radiotherapy. In a follow-up period of 36 months, the patient had no clinical or radiological evidence of tumor recurrence. Even though spinal location for GCT is a rare event, it should be included in the differential diagnosis in patients with osteolytic lesions or pathological fractures of the vertebra, especially in young female patients sustaining no trauma who had a clinical history of persistent low back pain

Endotoxin and CD14 in the progression of biliary atresia

<p>Abstract</p> <p>Background</p> <p>Biliary atresia (BA) is a typical cholestatic neonatal disease, characterized by obliteration of intra- and/or extra-hepatic bile ducts. However, the mechanisms contributing to the pathogenesis of BA remain uncertain. Because of decreased bile flow, infectious complications and damaging endotoxemia occur frequently in patients with BA. The aim of this study was to investigate endotoxin levels in patients with BA and the relation of these levels with the expression of the endotoxin receptor, CD14.</p> <p>Methods</p> <p>The plasma levels of endotoxin and soluble CD14 were measured with a pyrochrome Limulus amebocyte lysate assay and enzyme-linked immunosorbent assay in patients with early-stage BA when they received the Kasai procedure (KP), in patients who were jaundice-free post-KP and followed-up at the outpatient department, in patients with late-stage BA when they received liver transplantation, and in patients with choledochal cysts. The correlation of CD14 expression with endotoxin levels in rats following common bile duct ligation was investigated.</p> <p>Results</p> <p>The results demonstrated a significantly higher hepatic CD14 mRNA and soluble CD14 plasma levels in patients with early-stage BA relative to those with late-stage BA. However, plasma endotoxin levels were significantly higher in both the early and late stages of BA relative to controls. In rat model, the results demonstrated that both endotoxin and CD14 levels were significantly increased in liver tissues of rats following bile duct ligation.</p> <p>Conclusions</p> <p>The significant increase in plasma endotoxin and soluble CD14 levels during BA implies a possible involvement of endotoxin stimulated CD14 production by hepatocytes in the early stage of BA for removal of endotoxin; whereas, endotoxin signaling likely induced liver injury and impaired soluble CD14 synthesis in the late stages of BA.</p

Impact of ovarian preservation in women with endometrial cancer

AbstractBackgroundBilateral salpingo-oophorectomy (BSO) is standardly performed in the treatment of endometrial cancer. The purpose of this study was to evaluate the impact of ovarian preservation on the outcome of patients with endometrial cancer.MethodsA retrospective cohort study was performed using the 2000–2010 database of endometrial cancer patients who were treated at Taipei Veterans General Hospital. Information regarding patient age, pathologic reports, and follow-up results was abstracted from medical records.ResultsFive hundred and twenty-nine patients were reviewed in this study. Mean age and follow-up duration were 55.7 ± 11.4 years and 37.5 ± 30.1 months, respectively. The median disease-free survival was 31.2 months (range 0.2–126.9 months). There were no significant differences in disease-free survival between stage I patients with ovarian preservation versus those with oophorectomy (p = 0.473). In a multivariate Cox model, ovarian preservation had no effect on disease-free survival [hazard ratio (HR) = 2.72; 95% confidence interval (CI), 0.48–15.59]; however, it was not significantly related to stage and para-aortic lymph node involvement.ConclusionOvarian preservation may be considered in premenopausal women with early-stage low-risk endometrial cancer

Task-Dependent Differences in Operant Behaviors of Rats With Acute Exposure to High Ambient Temperature: A Potential Role of Hippocampal Dopamine Reuptake Transporters

Behavioral or cognitive functions are known to be influenced by thermal stress from the change in ambient temperature (Ta). However, little is known about how increased Ta (i.e., when the weather becomes warm or hot) may affect operant conditioned behavior and the neural substrates involved. The present study thus investigated the effects of high Ta on operant behaviors maintained on a fixed-ratio 1 (FR1) and a differential reinforcement for low-rate responding 10 s (DRL 10-s) schedule of reinforcement. The rats were randomly assigned to three groups receiving acute exposure to Ta of 23°C, 28°C, and 35°C, respectively, for evaluating the effects of high Ta exposure on four behavioral tests. Behavioral responses in an elevated T-maze and locomotor activity were not affected by Ta treatment. Regarding operant tests, while the total responses of FR1 behavior were decreased only under 35°C when compared with the control group of 23°C, those of DRL 10-s behavior were significantly reduced in both groups of 28°C and 35°C. Distinct patterns of inter-response time (IRT) distribution of DRL behavior appeared among the three groups; between-group differences of behavioral changes produced by high Ta exposure were confirmed by quantitative analyses of IRT data. Western blot assays of dopamine (DA) D1 and D2 receptor, DA transporter (DAT) and brain-derived neurotrophic factor (BDNF) were conducted for the sample tissues collected in six brain areas from all the subjects after acute high Ta exposure. Significant Ta-related effects were only revealed in the dorsal hippocampus (dHIP). In which, the DAT levels were increased in a Ta-dependent fashion that was associated with operant behavior changes under high Ta exposure. And, there as an increased level of D1 receptors in the 28°C group. In summary, these data indicate that the performance of operant behavior affected by the present high Ta exposure is task-dependent, and these changes of operant behaviors cannot be attributed to gross motor function or anxiety being affected. The regulation of dHIP DAT may be involved in this operant behavioral change under high Ta exposure

Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/ β

Honokiol, an active compound of Magnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of stemness genes, such as ABCG2, ABCC5, EpCAM, OCT-4, CD133, CD44, and β-catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells. The Wnt signaling transducers such as β-catenin and TCF-4 were decreased in honokiol-treated SP cells, while the β-catenin degradation promoting kinase GSK-3α/β was increased. Consistently, the protein levels of β-catenin downstream targets such as c-Myc and Cyclin D1 were also downregulated. Furthermore, the β-catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT

Down-regulation of PKCζ in renal cell carcinoma and its clinicopathological implications

<p>Abstract</p> <p>Background</p> <p>Metastatic renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy. Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC. Recent studies have shown the atypical PKCζ is an important regulator of tumorigenesis. However, the correlation between PKC<b>ζ </b>expression and the clinical outcome in RCC patients is unclear. We examined the level of PKCζ expression in human RCC.</p> <p>Methods</p> <p>PKCζ mRNA and protein expressions were examined by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) respectively in RCC tissues of 144 patients. Cellular cytotoxicity and proliferation were assessed by MTT.</p> <p>Results</p> <p>PKCζ expression was significantly higher in normal than in cancerous tissues (<it>P </it>< 0.0001) by real-time PCR and IHC. Similarly, PKCζ expression was down-regulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (<it>P </it>= 0.04), but no such association was found in TNM stage (<it>P </it>= 0.13). Tumors with higher PKCζ expression were associated with tumor size (<it>P </it>= 0.048). Expression of higher PKCζ found a poor survival in patients with high tumor grade. Down-regulation of PKCζ showed the significant chemoresistance in RCC cell lines. Inactivation of PKCζ expression enhanced cellular resistance to cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKC<b>ζ </b>siRNA and inhibitor.</p> <p>Conclusions</p> <p>PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.</p