FHOD1 is upregulated in gastric cancer and promotes the proliferation and invasion of gastric cancer cells

Gastric cancer (GC) is one of the main causes of cancer-associated morbidity and mortality worldwide. The present study aimed to investigate the role of the gene encoding formin homology 2 domain containing 1 (FHOD1) protein in GC development. Data from The Cancer Genome Atlas were firstly analyzed, and immunohistochemistry was conducted on GC tissues. The results demonstrated that FHOD1 expression in GC tissues was significantly increased compared with adjacent non-tumor tissues. Furthermore, the expression level of FHOD1 was negatively associated with the overall survival of patients with GC. For the functional studies, lentivirus-mediated short hairpin RNA against FHOD1 and FHOD1-overexpression vectors were constructed to knockdown and overexpress the expression level of FHOD1 in human GC cell lines, respectively. The results indicated that FHOD1 knockdown inhibited the proliferation, colony formation and migratory and invasive abilities of GC cells. Conversely, overexpression of FHOD1 in GC cells promoted soft-agar colony formation and migratory and invasive abilities. In addition, it was demonstrated that genes of which expression levels were correlated with FHOD1 were enriched in the Gene Ontology term of ‘extracellular matrix (ECM) structural constituent’, suggesting that FHOD1 may serve an important role in the regulation of ECM. In conclusion, the present study demonstrated that FHOD1 may exert an oncogenic role in cultured GC cells and be inversely associated with the overall survival of patients with GC.     

EGFR, HER2, and HER3 Expression in Laryngeal Primary Tumors and Corresponding Metastases

Background There are several substances available to target members of the epidermal growth factor receptor (EGFR) family, both for imaging in nuclear medicine and for various forms of therapy. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as a target in systemic tumor therapy. To date, the expression of EGFR family members has only been determined in primary laryngeal carcinomas, and we have not found published data regarding the receptor status in corresponding metastatic lesions. Methods Expression of EGFR, HER2, and HER3 was investigated immunohistochemically in both lymph node metastases and corresponding primary laryngeal squamous carcinomas (n = 40). Results EGFR overexpression (2+ or 3+) was found in 87.5% (35/40) of the laryngeal primary tumors and 82.5% (33/40) of the corresponding lymph node metastases. There was a good agreement between the primary tumors and the paired metastases regarding EGFR expression. HER2 overexpression was found in only four cases (10.5%) of the studied primary tumors and in all cases the HER2 expression was retained in the paired metastases. Another two metastases gained HER2 status when compared to the corresponding primary tumors. Strong HER3 staining was found in 26.7% of both the primary tumors and the corresponding metastases. Conclusions The high frequency and stability in EGFR expression is encouraging for efforts to use EGFR targeting agents (e.g. Iressa, Tarceva, Erbitux or radiolabeled antibodies) for therapy of laryngeal carcinoma. For a few laryngeal carcinoma patients with HER2 overexpression, anti-HER2 agents could possibly be used.     

Tiam 1基因在喉癌中的表达和意义

目的研究T淋巴瘤侵袭转移基因Tiam 1(T lymphoma invasion/metastasis 1)表达与喉癌浸润转移的关系.方法应用逆转录聚合酶链反应(RT-PCR)检测30例喉癌组织、12例喉癌转移的颈部淋巴结和10例正常喉部组织Tiam 1 mRNA的表达.结果有颈淋巴结转移和无颈淋巴结转移的喉癌原发灶Tiam 1 mRNA高表达率分别为75%(6/8)和18.2%(4/22),P=0.0072;有癌转移和无癌转移的淋巴结Tiam 1 mRNA高表达率分别为100%(8/8)和25%(1/4),P=0.0182.30例喉癌有10例Tiam 1 mRNA高表达,高表达率为33.3%.结论 Tiam 1 mRNA表达与喉癌浸润转移呈相关关系.     

Prohibitin: a potential biomarker for tissue-based detection of gastric cancer

BACKGROUND: Prohibitin (PHB) was found to be overexpressed in breast cancer and thus is suggested as a biomarker in that disease. A few studies have investigated the PHB expression pattern in gastric cancer by two-dimensional gel electrophoresis. Uncertainties still existed on whether PHB expression could indicate the differentiation and apoptosis degree of gastric cancer and whether PHB protein as well as anti-PHB antibody could be a biomarker in the serum of the gastric cancer patient. In this study, the expression levels of PHB protein and mRNA of the tissues as well as PHB antigen and anti-PHB antibody in serum of patients with gastric cancer were systemically examined. METHODS: Immunohistochemistry and real-time PCR were used to detect expression levels of PHB protein and mRNA in gastric cancer tissues. Recombinant PHB antigen was identified by Western blotting. The expression of PHB antigen and anti-PHB antibody was investigated by ELISA and TRFIA. Bcl-2 expression was examined by immunohistochemistry. RESULTS: By immunohistochemistry and real-time PCR analyses, PHB protein and mRNA were both overexpressed in gastric cancer tissues compared to adjacent normal gastric tissues (P < 0.01). Moreover, an elevated PHB expression pattern paralleled the differentiation degree and Bcl-2 protein expression in gastric cancer. However, no significant differences of PHB protein and anti-PHB antibody expression were detected in serum of gastric cancer patients and that of healthy volunteers. CONCLUSIONS: These results indicated that PHB could be a potential diagnostic and differentiation biomarker of gastric cancer for tissue-based detection by immunohistochemistry and real-time PCR, but not for serum-based detection.     

Effect of Qi-protecting powder （Huqi San） on expression of c-jun,c-fos and c-myc in diethylnitrosamine-mediated hepatocarcinogenesis

To study the inhibitory effect of Huqi San （Qi- protecting powder） on rat prehepatocarcinoma induced by diethylinitrosamine （DEN） by analyzing the mutational activation of c-fos proto-oncogene and over-expression of c-jun and c-myc oncogenes. METHODS： A Solt-Farber two-step test model of prehepatocarcinoma was induced in rats by DEN and 2-acetylaminofluorene （AAF） to investigate the modifying effects of Huqi San on the expression of c-jun, c-fos and c-myc in DEN-mediated hepatocarcinogenesis. Huqi San was made of eight medicinal herbs containing glycoprival granules, in which each milliliter contains 0.38 g crude drugs. T-glutamy-transpeptidase-isoenzyme （T-GTase） was determined with histochemical methods. Level of 8-hydroxydeoxyguanosine （OHdG） formed in liver and c-jun, c-fos and c-myc proto-oncogenes were detected by immunohistochemical methods. RESULTS： The level of 8-OHdG, a mark of oxidative DNA damage, was significantly decreased in the liver of rats with prehepatocarcinoma induced by DEN who received 8 g/kg body weight or 4 g/kg body weight Huqi San before （1 wk） and after DEN exposure （4 wk）. Huqi San- treated rats showed a significant decrease in number of T-GT positive foci （P 〈 0.001, prevention group： 4.96-0.72 vs 29.46-2.17; large dose therapeutic group： 7.53-0.88 vs 29.46-2.17）. On the other hand, significant changes in expression of c-jun, c-fos and c-myc were found in Huqi San-treated rats. CONCLUSION： Activation of c-jun, c-fos and c-myc plays a crucial role in the pathogenesis of liver cancer.Huqi San can inhibit the over-expression of c-jun, c-fos and c-myc oncogenes and liver preneolastic lesions induced by DEN.     

Angiotensin II subtype 1 (AT1) receptors contribute to ischemic contracture and regulate chemomechanical energy transduction in isolated transgenic rat (alphaMHC-hAT1)594-17 hearts

BACKGROUND: The role of AT1 receptors in myocardial ischemia/reperfusion injury is unclear. We, therefore, investigated the effects of the AT1 receptor antagonist irbesartan (Irb) in isolated hearts of selective myocardial AT1 overexpressing transgenic [transgenic(alphaMHC-hAT1)594-17] and Sprague-Dawley rats (SD) subjected to ischemia/reperfusion injury. METHODS AND RESULTS: Hearts of 4-week-old male SD or transgenic rats were isolated and perfused with Krebs-Henseleit buffer with or without 10 microM Irb in Langendorff mode. After 15 min of stabilization, pressure-volume curves were obtained and the hearts subjected to 20 min ischemia followed by 30 min reperfusion. A second set of pressure-volume curves was obtained thereafter. Left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), total coronary flow (CF) and oxygen consumption (MVO2) were recorded continuously. Myocardial efficiency was derived from the slope of relations of MVO2 to pressure/volume area. After 20 min ischemia, LVEDP was significantly higher in transgenic than in SD (35.7+/-1.8 vs. 29.2+/-1.0 mmHg, P<0.05) or Irb treated transgenic hearts (24.3+/-1.6 mmHg, P<0.05). Myocardial efficiency was increased by Irb before ischemia. Ischemia increased efficiency in SD but not in transgenic rats, Irb increased efficiency in transgenic hearts post-ischemia. CONCLUSION: Transgenic hearts developed ischemic contracture more rapidly than SD hearts as indicated by higher LVEDP during ischemia. This response was antagonized by Irb, indicating a role of AT1 receptors in ischemic contracture, AT1-receptors also appear to be involved in the control of myocardial efficiency.     

Islet amyloid polypeptide in the islets of Langerhans: friend or foe?

Islet amyloid polypeptide (IAPP), or amylin, was originally discovered as the constituent peptide in amyloid occurring in human insulinomas and in pancreatic islets in human subjects with Type II (non-insulin-dependent) diabetes mellitus. Its normal expression in beta cells and its co-secretion with insulin in response to nutrient stimuli, suggest a metabolic function for the peptide. Specifically, IAPP has most frequently been shown to inhibit insulin secretion, implying that IAPP has a role in the regulation of islet hormone homeostasis. The physiological significance of IAPP in islets has been difficult to assess; very high IAPP concentrations are required to alter insulin secretion. Moreover, until recently, IAPP receptors have not been characterised at the molecular level, thus leaving the actual target cells for IAPP unidentified. Furthermore, in experimental diabetes in rodents, the ratio of IAPP expression to that of insulin invariably is increased. In view of the pleiotropic effects attributed to IAPP, such regulation could be both adverse and beneficial in diabetes. Metabolic characterisation of mice carrying a null mutation in the IAPP gene or which overexpress IAPP in beta cells have recently confirmed that IAPP is a physiological inhibitor of insulin secretion. Based on experiments in which IAPP-deficient mice develop a more severe form of alloxan-induced diabetes, we argue that the action of IAPP in the islets normally is beneficial for beta-cell function and survival; thus, the established up regulation of IAPP expression compared with that of insulin in experimental rodent diabetes could serve to protect islets under metabolically challenging circumstances. [Diabetologia (2000) 43: 687–695]     

Fecundity and life span in transgenic Drosophila melanogaster overexpressing hsp70

In the present study, we investigated the effect of hsp70 over expression on some life history components in transgenic fruit flies. We measured life span in mated flies and fecundity in flies subjected or not subjected to a heat shock inducing hsp70. Heat shock increased life span of the parental line, but not of the transgenic lines. Genetic manipulation of the flies altered their fecundity, but the heat shock had no effect on fecundity. To conclude, we have observed some costs of genetic manipulation by itself on life span and fecundity. However, the over expression of thehsp70 extra copies by the exposure to heat did not alter the studied variables. This revised version was published online in July 2006 with corrections to the Cover Date.