Collapsin Response Mediator Protein 4 Expression is Associated with Liver Metastasis and Poor Survival in Pancreatic Cancer

Background

Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer.

Methods

Expression of crmp genes in 11 pairs of pancreatic cancer and corresponding noncancerous pancreas tissues were examined by real-time RT-PCR. Knockdown of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. Furthermore, CRMP4 protein levels in primary tumors of pancreatic cancer (n = 53) were examined by immunohistochemistry and compared with the clinicopathological features of the tumors.

Results

Of all the CRMPs, only CRMP4 was differentially expressed in pancreatic cancer tissues (p = 0.008). CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. The expression of CRMP4 was detected immunohistochemically in 34 (64.2 %) of the 53 pancreatic cancer samples, and CRMP4 expression was correlated with severe venous invasion (p = 0.044), stage (p = 0.019), and liver metastasis (p = 0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival.

Conclusions

Our results suggested that CRMP4 is significantly associated with poor prognosis by promoting liver metastasis and can serve as a novel therapeutic target for pancreatic cancer.

     

Acupuncture stimulation to the sacral segment affects state of vigilance in rats

The effects of acupuncture stimulation to the sacral segment on electroencephalograms (EEGs) and activity of locus coeruleus (LC) neurons were examined in urethane-anesthetized rats. In 71 of 112 trials, when EEGs displayed small amplitude and high frequency, stimulation to the sacral segment-induced large amplitude and slow EEGs with a latency of <450s and duration ranged from 32s to >42 min. Stimulus-induced EEGs comprised significant increases in delta power and significant decreases in theta and beta powers. After intraperitoneal administration of bicuculline, stimulation to the sacral segment failed to induce changes in EEG pattern. Firing rate of noradrenergic LC neurons decreased significantly from 2.9+/-1.5 to 1.1+/-0.8 Hz (n=11, p<0.001). Decreased neuronal activity exhibited close relationships with increased EEG amplitude. These results suggest that acupuncture stimulation to the sacral segment changes the state of animals from light anesthesia to deep anesthesia, and that this change is mediated by GABAergic systems suppressing the activity of noradrenergic LC neurons.     

Screening and management for ischemic heart disease in patients undergoing emergency surgery for a type A acute aortic dissection

Purpose

We assessed the incidence of coronary artery disease (CAD) during hospitalization after emergency surgery for a type A acute aortic dissection.

Methods

A total of 123 patients underwent multi-slice computed tomography (MSCT) scans during an early stage after surgery. The patients were divided into two groups: group I consisted of 14 patients (11.4 %) who had coronary artery stenosis of more than 75 % on MSCT, and group II consisted of 109 patients (88.6 %) who had no coronary lesions.

Results

The prevalence of diabetes, dyslipidemia and a smoking history was significantly higher in group I. Although the serum low-density lipoprotein cholesterol levels were similar, the high-density lipoprotein cholesterol (HDL) level was significantly lower in group I (36.4 ± 7.9 mg/dl) than in group II (49.6 ± 13.5 mg/dl, P = 0.0005). The maximum carotid intima-media thickness (IMT) was significantly thicker in group I (1.17 ± 0.37 mm) compared to group II (0.96 ± 0.33 mm, P = 0.0297). The logistic regression analysis detected that a carotid IMT over 1.1 mm (odds ratio 4.35, P = 0.0371) and HDL less than 40 mg/dl (odds ratio 3.90, P = 0.0482) were predictors for CAD.

Conclusions

CAD screening should be recommended for patients with aortic dissection who have several atherosclerosis risk factors, even after emergency surgery.     

Comparing the Efficacy of a Microperforated Titanium Membrane for Guided Bone Regeneration with an Existing Mesh Retainer in Dog Mandibles

Acute-type lateral ridge defects (25 mm × 6 mm × 5 mm) were bilaterally created in the mandibles of four dogs (two defects per animal). The defects were reconstructed with particulate autologous bone and covered with a microperforated titanium membrane (Ti-honeycomb membrane, TiHM) or an existing conventional titanium mesh as control. The samples were dissected after 16 weeks postoperatively and processed for radiographic, histologic, and histomorphometric analyses. Regenerated tissue and bone volume were significantly larger in the TiHM group than in the control group (p = 0.05; p = 0.049). In contrast, bone mineral density was similar between the two groups. Histomorphometric analysis revealed that the regenerated bone area and calcific osseous area were larger in the TiHM group than in the control group; however, the differences were not significant. The efficacy of TiHM was generally satisfactory with the potential to become a standard tool for the GBR procedure; however, early membrane exposure will be a major problem to overcome.     

Membrane Apheresis Technology: Historical Perspective and New Trends toward Bioincompatible Systems

Abstract: During the past 25 years, membrane apheresis technology has been well developed through the use of biocompatible devices and immunomodulation. Now, however, we must move into a new era reconsidering the concepts of apheresis technology and considering the urgent need to develop a bioincompatible apheresis system. In the past, our aim in this field was to develop the best blood compatible system possible. With these systems, best efforts were made to reduce procedurally induced immunomodulation effects. However, it is these authors' opinion that procedurally induced immunomodulation effects should be augmented rather than reduced by incorporating such a bioincompatible apheresis system. Augmented immunoactivation and immunosuppression introduced by such systems should add therapeutic effects to the apheresis procedures. Therefore, we anticipate that the current marginally effective diseases may benefit from this strategic change in apheresis procedures.     

Pneumothorax after diagnostic laparoscopy

Here we want to call laparoscopist's attention to pneumothorax after diagnostic laparoscopy. Diagnostic laparoscopy has less complications, compared with laparoscopic surgery. In our experience, only one case (0.04%) developed pneumothorax during routine diagnostic laparoscopic procedure. This complication is presented in a 50-year-old female. She complained of dyspnea just after the decrease of intraabdominal pressure and deflation of intraperitoneal gas. The chest roentgenogram showed a right pneumothorax, and a right chest tube was inserted with immediate relief of tension. Pneumothorax during diagnostic laparoscopy is relatively rare but a major complication; Medline literature research showed six reported cases of pneumothorax after diagnostic laparoscopy from 1983 to 1998 including our case. The etiology was idiopathy in 5 and diaphragmatic injury in 1. Hypotension, elevation of inspiratory pressure, dyspnea, a decrease in systemic oxygen saturation, and loss of breath sounds suggest tension pneumothorax. The clinical condition of the patients improved rapidly because of the easy diffusion of the gas used in laparoscopy. Diagnostic laparoscopists should be aware of this complication and treat ventilatory problems.     

Osteodystrophy in patients with chronic hepatitis and liver cirrhosis

Bone mineral density (BMD) of the lumber vertebrae and factors related to bone metabolism were determined in patients with chronic viral hepatitis and patients with liver cirrhosis to clarify correlations between hepatic dysfunction, considered to be one of the causes of hepatic osteodystrophy, and decrease in bone mass. BMD of the second to fourth lumbar vertebrae was determined with a Lunar (Madison, WI, USA) DPX, a dual-energy X-ray absorptiometry diagnostic system. BMD was significantly lowest in patients with liver cirrhosis, followed by patients with chronic hepatitis, and healthy subjects, in this order. There was a significantly positive but weak correlation between albumin and BMD. Levels of 25(OH)D and 1,25(OH)₂D were significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. BMD and vitamin D were decreased in all patients whose cholinesterase (ChE) was below 0.3ΔpH. Urinary pyridinoline(Upyr) was significantly higher in the patients with liver cirrhosis, in whom bone mass was decreased, than in the patients with chronic hepatitis, whereas serum osteocalcin levels were distributed in the upper normal range in patients with chronic hepatitis and those with liver cirrhosis. There was a positive correlation between 25(OH)D and serum osteocalcin levels in patients with liver cirrhosis. These results indicate that osteogenesis is decreased and suggest that the decrease in BMD which occurs in viral liver cirrhosis, probably related to decreased, bone formation and slight promotion of bone resorption, reflects deranged hepatic function. This is the first report of Upyr and urinary deoxypyridinoline (UDpyr) determination in patients with liver cirrhosis and patients with chronic hepatitis. The negative correlation of Upyr and UDpyr with ChE is a novel finding.     

Detectability of Neural Tracts and Nuclei in the Brainstem Utilizing 3DAC‐PROPELLER

Despite clinical importance of identifying exact anatomical location of neural tracts and nuclei in the brainstem, no neuroimaging studies have validated the detectability of these structures. The aim of this study was to assess the detectability of the structures using three‐dimensional anisotropy contrast‐periodically rotated overlapping parallel lines with enhanced reconstruction (3DAC‐PROPELLER) imaging. Forty healthy volunteers (21 males, 19 females; 19‐53 years, average 23.4 years) participated in this study. 3DAC‐PROPELLER axial images were obtained with a 3T‐MR system at four levels of the brainstem: the lower midbrain, upper and lower pons, and medulla oblongata. Three experts independently judged whether five tracts (corticospinal tract, medial lemniscus, medial longitudinal fasciculus, central tegmental and spinothalamic tracts) and 10 nuclei (oculomotor and trochlear nuclei, spinal trigeminal, abducens, facial, vestibular, hypoglossal, prepositus, and solitary nuclei, locus ceruleus, superior and inferior olives) on each side could be identified. In total, 240 assessments were made. The five tracts and eight nuclei were identified in all the corresponding assessments, whereas the locus ceruleus and superior olive could not be identified in 3 (1.3%) and 16 (6.7%) assessments, respectively. 3DAC‐PROPELLER seems extremely valuable imaging method for mapping out surgical strategies for brainstem lesions.     

Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition

Cell competition is a biological process by which unfit cells are eliminated from “cell society.” We previously showed that cultured mammalian epithelial Madin‐Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by “normal” MDCK cells. However, the molecular mechanism underlying the elimination of active YAP‐expressing cells was unknown. Here, we used high‐throughput chemical compound screening to identify cyclooxygenase‐2 (COX‐2) as a key molecule triggering cell competition. Our work shows that COX‐2‐mediated PGE₂ secretion engages its receptor EP2 on abnormal and nearby normal cells. This engagement of EP2 triggers downstream signaling via an adenylyl cyclase‐cyclic AMP‐PKA pathway that, in the presence of active YAP, induces E‐cadherin internalization leading to apical extrusion. Thus, COX‐2‐induced PGE₂ appears a warning signal to both abnormal and surrounding normal cells to drive cell competition.