Small cell lung cancer cells express EGFR and tyrosine phosphorylation of EGFR is inhibited by gefitinib ("Iressa", ZD1839)

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ("Iressa", ZD1839) has demonstrated anti-tumor activity in non-small cell lung cancer (NSCLC) and has been approved in over 20 countries. NSCLC has been reported to express high levels of EGFR. However, gefitinib appears to be more effective against adenocarcinoma than squamous cell carcinoma, the latter expressing more EGFR. In the present study, we evaluated the effect of gefitinib against the small cell lung cancer (SCLC) cell lines NCI-H82, NCI-H209, NCI-H510, NCI-H526 and NCI-H660. SCLC has been reported to express a low to undetectable level of EGFR. We compared the effects of gefitinib between cell lines with detectable and undetectable EGFR expression. First, we evaluated expression levels of EGFR and HER2/neu by Western blotting and immunoprecipitation respectively; EGFR protein was detected in two of the five SCLC cell lines, whereas HER2/neu was not detected in any. Next, we analyzed expression levels of phosphorylated ERK1/2 and compared these results with EGFR (HER-1/ErbB1) and HER2/neu (ErbB2) expression levels, as EGFR conducts signals through Ras-Raf-MAPK pathway; gefitinib inhibited phosphorylation of ERK1/2 by EGF addition in cell lines with detectable and undetectable EGFR expression. These data suggest that gefitinib is potentially effective against cancers with low EGFR expression such as SCLC.     

Perioperative Prostaglandin E1 Treatment for the Prevention of Postoperative Complications After Esophagectomy: A Randomized Clinical Trial

Purpose We conducted a prospective randomized clinical study to examine whether perioperative prostaglandin E1 (PGE1) could help in the prevention of postoperative complications after esophagectomy for esophageal cancer.Methods Forty patients with esophageal cancer eligible for radical esophagectomy were randomly assigned to an experimental group (n = 20), given perioperative PGE1, or to a control group (n = 20), given standard postoperative treatment. The main clinical endpoints examined were the incidence of postoperative complications, hospitalization, duration of systemic inflammatory response syndrome (SIRS), portal vein blood flow, and serum bilirubin levels.Results Severe postoperative complications developed in five patients in the control group and two in the PGE1 group. There was one surgery-related death in the control group. The duration of SIRS was significantly shorter in the PGE1 group than in the control group (5.74 days vs 7.50 days; P = 0.047). Portal vein flow was also significantly lower on postoperative day (POD) 1 in the control group than in the PGE1 group (P = 0.042). Maximum postoperative serum bilirubin levels were significantly lower in patients treated with PGE1, at 2.91 vs 4.38mg/dl in the control group (P = 0.040).Conclusions The perioperative administration of PGE1 helps maintain adequate portal blood flow, improves hyperbilirubinemia, and attenuates the duration of SIRS, thereby reducing the risk of postoperative complications after esophagectomy and lymphadenectomy for esophageal cancer.     

Laminin gamma2-chain fragment circulating level increases in patients with metastatic pancreatic ductal cell adenocarcinomas

Laminin-5 (LN5) is expressed solely by epithelial cells and considered to enhance cell migration after being cleaved by proteases, leading to the shedding of the N-terminal fragment of the LN5 gamma2-chain (G2F). We estimated circulating G2F level in 181 patients with various digestive diseases and 15 healthy subjects. The G2F level in pancreatic ductal cell adenocarcinoma patients with liver metastases was markedly elevated, but that in patients without liver metastases was not significantly elevated. The G2F levels in patients with benign pancreatic tumours (pancreatic cysts and intraductal papillary mucinous tumours) were similar to that in healthy volunteers. On the other hand, the level of the gamma1-chain is a common constituent of several laminin heterotrimers. The N-terminal fragment of gamma1-chain (G1F) in the circulation of these patients was also determined, and a slight increase in G1F levels was observed only in hepatocellular carcinoma patients. Interestingly, a significant increase in circulating G2F/G1F ratio was observed in patients with bile duct and gallbladder carcinoma, as well as in those with metastatic pancreatic ductal cell adenocarcinoma. The increase in the circulating G2F level, particularly compared with circulating G1F level, should correlated with LN5 overexpression in invasive carcinomas, independently of basement membrane metabolism in the entire body.     

Cross-ethnic differences in perception of emotion in schizophrenia

BACKGROUND: The purpose of this study was to examine cross-ethnic differences in Perception of Emotion (POE) in schizophrenia. POE is an emerging construct in schizophrenia and involves the recognition and accurate identification of emotion in the facial and vocal expression of others. It has been implicated as relevant to instrumental functioning in schizophrenia, as well as a potential core deficit or marker for the disorder. Studies have shown the role of culture in shaping the expression and perception of emotion in non-clinical samples. It was hypothesized that ethnic minorities would have lower POE scores than Caucasians, and that the differences on POE would remain significant after controlling for neurocognition. METHOD: Individuals, 131, diagnosed with schizophrenia or schizoaffective disorder participated in the study. There were 59 Euro-American Caucasian, 56 were African-American, and 16 were Latino. Neurocognition was measured as a standardized sum of five neuropsychological measures. Perception of Emotion was measured with facial and voice recognition tasks. RESULTS: Both Latinos and African-Americans scored lower on POE than Caucasians. The cross-ethnic differences on POE remained significant after controlling for neurocognition and overall symptom level. Post hoc analyses showed some support for the predictive validity of the POE measure across cultural contexts. CONCLUSIONS: These results suggest that POE in schizophrenia is influenced by ethnicity, and that the ethno-cultural mechanisms influencing POE transcend the shared variation of POE and neurocognition. These results have implications for theories of cross-cultural emotion recognition, measurement bias in POE research, and for the place of culture in the study of POE in schizophrenia.     

Attention-deficit and hyperactive neurobehavioural characteristics induced by perinatal hypothyroidism in rats

Thyroid hormone is essential for the proper development of the mammalian central nervous system (CNS). In the present study, we examined behavioural alterations caused by transient perinatal hypothyroidism induced by an anti-thyroid drug, propylthiouracil (PTU). This drug produces perinatal disruption of the thyroid system and subsequent behavioural changes, which we investigated using a series of behavioural tests and focusing particularly on attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In the open field test, both male and female rats that had experienced perinatal hypothyroidism (HT rats) showed an increased percent of locomotion behaviour and reduced grooming behaviour, suggesting that HT rats may be hyperactive and show fewer anxiety characteristics. Neither male nor female HT rats showed retention in the passive avoidance test. Male HT rats showed a significantly lower rate of correct avoidance responses than control rats in earlier sessions in the active avoidance test. In addition, we observed significant increases in the number of times that rats crossed the partition during inter-trial intervals and the percent of failure of avoidance during 5 s electrical stimuli in HT rats, suggesting that HT rats are restless, have a shortened attention span and panic easily. In measuring spontaneous motor activity during a period of darkness, male HT rats appeared to plunge into active phase with short, quick steps, while male control rats showed only long active phases during a stress-free period of darkness. These abnormal behavioural characteristics in HT rats might coincide with those found in some cases of ADHD.     

Immunohistochemical localization of gastrin-releasing peptide receptor in the mouse brain

Gastrin-releasing peptide (GRP) is a mammalian bombesin (BN)-like peptide that binds with high affinity to the GRP receptor (GRP-R). Previous behavioral studies using mice and rats showed that the GRP/GRP-R system mediates learning and memory by modulating neurotransmitter release in the local GABAergic network of the amygdala and the nucleus tractus solitarius (NTS). To date, the precise distribution of GRP-R in the brain has not been elucidated. We used a synthetic peptide derived from mouse GRP-R to generate affinity-purified antibodies to GRP-R and used immunohistochemistry to determine the distribution of GRP-R in the mouse brain. The specificity of anti-GRP-R antibody was confirmed in vitro using COS-7 cells transiently expressing GRP-R and in vivo using GRP-R-deficient and wild-type mouse brain sections. GRP-R immunoreactivity was widely distributed in the isocortex, hippocampal formation, piriform cortex, amygdala, hypothalamus, and brain stem. In particular, GRP-R immunoreactivity was observed in the lateral (LA), central, and basolateral amygdaloid (BLA) nuclei and NTS, which are important regions for memory performance. Double-labeling immunohistochemistry demonstrated that subpopulations of GRP-R are present in GABAergic neurons in the amygdala. Consequently, GRP-R immunoreactivity was observed in the GABAergic neurons of the limbic region. These anatomical results provide support for the idea that the GRP/GRP-R system mediates memory performance by modulating neurotransmitter release in the local GABAergic network.     

Time course and sequence of pathological changes in the cerebellum of microsphere-embolized rats

Ischemia is a major cause of damage to the central nervous system as a consequence of stroke or trauma. Here, we analyzed with high temporal resolution the time course of pathological changes in the neurons (granule and Purkinje cells) and glia (Bergmann and astroglia cells) in the cerebellar cortex and white matter. The period studied ranged from 30 min to 7 days after a microsphere-induced embolism used as a model of stroke and multi-infarct dementia. Some pathological changes in the neurons in the cerebellar cortex were identified early, that is, beginning at 3 h after the microsphere-induced embolism, and glial pathology appeared only later. The pathological changes in the white matter also appeared slightly later, that is, 6 h after embolism and were less pronounced than those in the cerebellar cortex. This suggests that neuronal pathology is induced more rapidly and/or more easily than the glial pathology. In addition, BrdU staining shows that cell proliferation is limited to a 1-day period beginning about 1 day after the embolism. These data demonstrate that changes after an ischemic lesion of the cerebellum proceeds from upper cerebellar cortex to deeper cerebellar cortex or white matter and also that microsphere-induced changes proceed from neuronal to glial pathology.