BACKGROUND Cell‐retained isoforms of vascular endothelial growth factor A (VEGF‐A) have been reported to play an essential role in tumor progression through stromal neovascularization in malignant solid tumors. While more than 95% of nonsmall cell lung carcinoma (NSCLC) expresses cell‐retained VEGF‐A isoform, the clinicopathologic implications of neuropilin (NRP), considered the specific receptor for limited types of VEGF‐A isoform, are not well understood. METHODS The authors examined NRP1 and NRP2 mRNA expression in 68 NSCLCs and 15 extraneoplastic tissues by a densitometry–assisted, semi‐quantitative reverse transcription‐polymerase chain reaction. The authors determined the distinct expression of NRPs using the expression level of NRPs relative by optical density to β2‐microglobulin. The authors also investigated VEGF‐A isoforms, their receptors, and the clinical implications. Vascularity of NSCLC was morphologically estimated on sections immunostained with anti‐CD34 antibody. RESULTS Eleven of 15 extraneoplastic specimens showed NRP1 expression (73.3%) and 8 showed NRP2 expression (53.3%). The expression level of NRP1 or NRP2 of neoplasmic tissue was higher than that of extraneoplastic tissues (P < 0.01, Mann‐Whitney U test). Fifty‐five and 44 NSCLCs expressed NRP1 and NRP2, respectively. Forty patients co‐expressing NRP1 and NRP2 showed significantly poorer prognosis and increased vessel counts as compared to those 28 cases without co‐expression (P < 0.05, log‐rank test; P < 0.05, Mann‐Whitney U test). CONCLUSIONS The co‐expression of NRP1 and NRP2 genes is significantly correlated with tumor progression through neovascularization in NSCLC. These results suggest that both NRP1 and NRP2 are key molecules for stromal vascularization by cell‐retained VEGF in NSCLC. Cancer 2002;95:2196–201. © 2002 American Cancer Society. DOI 10.1002/cncr.10936

No abstract

Acute administration of glucocortiocoids reduces inflammation. Increasing knowledge of the mechanisms of action indicate that pretreatment with glucocorticoids could have organ-protective effects. We investigated whether pretreatment with methylprednisolone (MP) protected the heart against ischemia-reperfusion dysfunction, and we hypothetized that this protection might be due to induction of the cardioprotective heat shock protein 72 (HSP72). Rats were given vehicle or MP-40 mg/kg im as a double injection starting either 24 or 120 h (5 days) before their hearts were excised for Langendorff perfusion (n = 6-11 hearts in each group). MP improved left ventricular function and coronary flow during reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac HSP72 gradually increased in a 24-h time course after MP treatment, and the increase was sustained 5 days afterward (immunoblotting). HSP72 mRNA was either reduced or unchanged, indicating a posttranscriptional regulation. Pretreatment with hydrocortisone or dexamethasone (n = 7-8 hearts of each) similarily increased cardiac HSP72 24 h afterward. This paper demonstrates that glucocorticoids increase cardiac HSP72 and protect organ function against ischemia-reperfusion injury.

Abstract. Vascular endothelial growth factor A (VEGF-A)plays an essential role in tumor progression through stromal neovascularization in malignant solid tumors. Neuropilin (NRP) is considered to be the specific receptor for limited types of VEGF-A isoform, VEGF165. The clinicopathological implications of NRP are not well understood in colon cancer, while almost all colon cancers overexpressed VEGF-A. We examined the expression levels of NRP1 and NRP2 genes in 54 colon cancer cases and paired extraneoplastic tissue with quantitative real-time polymerase chain reaction. The gene expression levels of NRP1 in the tumor (0.431±0.583) were significantly decreased compared to those in the extraneoplastic tissue (0.754±0.799) (paired t-test, p=0.0208). On the other hand, the gene expression levels of NRP2 in the tumor (0.763±0.791) were not decreased compared to those in the extraneoplastic tissue (0.508±0.386) (paired t-test, p=0.0511). Twenty cases, with preserved expression of the NRP1 gene in the tumor, showed a better prognosis as compared to the 34 cases with decreased NRP1 expression (p=0.0258, log-rank test). No significant relationship was noted between NRP2 gene expression and prognosis. The results suggested that preserved NRP1 expression provides colon cancer patients with a better prognosis.

Abstract. The majority of thymomas are histologically characterized by tumor-infiltrating lymphocytes. Mature dendritic cells (DCs) are known to assemble lymphocytes through antigen presentation to T lymphocytes. Fascin, a 55-kDa actin-binding protein and a known marker for mature DCs, regulates filaments necessary for the formation of filopodia in cell migration. Moreover, fascin expression in various epithelial neoplasms has recently been reported to be associated with invasion of tumor cells and clinically aggressive manifestations. In the present study, we investigated fascin expression immunohistochemically in tissues of thymomas and thymic carcinomas surgically resected at our institute. A total of 34 thymomas and 5 thymic carcinomas were included. The amount and immunohistochemical intensity of both fascin + DCs and tumor epithelium were counted and assessed, and the clinicopathological data were also scored. Statistical analyses revealed that the amount of fascin + DCs with the formation of clusters was associated with lymphocyte-rich variants (p=0.002) and cortical differentiation (p=0.037) of thymoma with complication from myasthenia gravis (p=0.002). The quantity of fascin + epithelium was associated with a strong intensity of fascin in infiltrating DCs (p=0.002) with the formation of clusters (p=0.002) and favorable prognosis, as assessed by the Masaoka staging system (p=0.001). The amount of infiltrating DCs (p=0.024) and fascin + epithelium were lower in thymic carcinoma. It was concluded that fascin + epithelium may induce tumor immunity through the surveillance activity of fascin + DCs in thymic neoplasms, thus improving prognosis.

Cardiac myosin-binding protein-C (MyBP-C), also known as C-protein, is one of the major myosin-binding proteins localizing at A-bands. MyBP-C has three isoforms encoded by three distinct genes: fast-skeletal, slow-skeletal, and cardiac type. Herein, we are reporting a novel alternative spliced form of cardiac MyBP-C, MyBP-C(+), which includes an extra 30 nucleotides, encoding 10 amino acids in the carboxyl-terminal connectin/titin binding region. This alternative spliced form of MyBP-C(+) has a markedly decreased binding affinity to myosin filaments and connectin/titin in vitro and does not localize to A-bands in cardiac myocytes. When MyBP-C(+) was expressed in chicken cardiac myocytes, sarcomere structure was markedly disorganized, suggesting it has possible dominant negative effects on sarcomere organization. Expression of MyBP-C(+) is hardly detected in ventricles through cardiac development, but its expression gradually increases in atria and becomes the dominant form after 6 mo of age. The present study demonstrates an age-induced new isoform of cardiac MyBP-C harboring possible dominant negative effects on sarcomere assembly.

No abstract

No abstract