Selective CREB-dependent cyclin expression mediated by the PI3K and MAPK pathways supports glioma cell proliferation.

The cyclic-AMP response element binding (CREB) protein has been shown to have a pivotal role in cell survival and cell proliferation. Transgenic rodent models have revealed a role for CREB in higher-order brain functions, such as memory and drug addiction behaviors. CREB overexpression in transgenic animals imparts oncogenic properties on cells in various tissues, and aberrant CREB expression is associated with tumours. It is the central position of CREB, downstream from key developmental and growth signalling pathways, which gives CREB this ability to influence a spectrum of cellular activities, such as cell survival, growth and differentiation, in both normal and cancer cells. We show that CREB is highly expressed and constitutively activated in patient glioma tissue and that this activation closely correlates with tumour grade. The mechanism by which CREB regulates glioblastoma (GBM) tumour cell proliferation involves activities downstream from both the mitogen-activated protein kinase and phosphoinositide 3-kinase (PI3K) pathways that then modulate the expression of three key cell cycle factors, cyclin B, D and proliferating cell nuclear antigen (PCNA). Cyclin D1 is highly CREB-dependent, whereas cyclin B1 and PCNA are co-regulated by both CREB-dependent and -independent mechanisms. The precise regulatory network involved appears to differ depending on the tumour-suppressor phosphatase and tensin homolog status of the GBM cells, which in turn allows CREB to regulate the activity of the PI3K itself. Given that CREB sits at the hub of key cancer cell signalling pathways, understanding the role of glioma-specific CREB function may lead to improved novel combinatorial anti-tumour therapies, which can complement existing PI3K-specific drugs undergoing early phase clinical trials.

Reduction in tumour cell invasion by pigment epithelium-derived factor is mediated by membrane type-1 matrix metalloproteinase downregulation.

Prostate cancer and breast cancer are major killers among males and females respectively. In this study, pigment epithelium-derived factor (PEDF) was examined for its effect on commonly used human prostate cancer and human breast cancer cell lines. PEDF increased adhesion of cells to collagen-I, with decreased expression of phosphorylated focal adhesion kinase (p-Fak) consistent between the two cell types. Invasion of both tumour cell types through collagen-I was also reduced by PEDF, with decreased expression of membrane type-1 matrix metalloproteinase (MT1-MMP). These results were confirmed with specific antibodies to MT-MMP1. This study provides some vital clues as to which molecular players are perturbed by PEDF treatment of human prostate and breast cancer cells, raising hope that PEDF can in future be trialled against these major cancers in attempts to procure safer yet effective therapies for cancer.

Simultaneous occurrence of synchronous and metachronous tumors with gastrointestinal stromal tumors.

OBJECTIVE: To examine the frequency and clinicopathological features of synchronous and metachronous tumors which occur simultaneously with gastrointestinal stromal tumors (GIST). METHODS: Clinical and pathologic records of 78 patients diagnosed with primary GIST and treated at our institution between 1997 and 2009 were reviewed. RESULTS: GIST occurred simultaneously with other primary GI malignancies in 16.1 % (n = 13) of all patients with GIST. Of the simultaneous secondary tumors, 69.2 % (n = 9) were gastrointestinal tumors, and the remaining were biliary system and breast tumors. GIST most frequently had gastric localization (n = 6, 46.1%). CONCLUSION: Although GIST are uncommon neoplasms, their synchronous and metachronous coexistence with other tumors is rather frequent, mostly as incidental tumors accompanying a gastrointestinal neoplasm. Therefore, during surgery on cases with gastrointestinal neoplasms, the surgeon needs to be careful about a synchronous GIST. At the same time, more detailed studies are needed about the carcinogenesis of dual tumors coexisting with GIST (Tab. 1, Ref. 14).

Significance of nm23 immunoexpression in the prognosis of renal cell carcinoma.

Non-metastatic gene 23 (nm23) is a metastasis suppressor gene that is expressed in all tissues and decreased nm23 expression may be linked to poor prognosis. By immunohistochemical staining of nm23 protein antibodies this study examined the prognostic value of nm23 protein expression in 54 renal cell carcinoma (RCC) patients and analysed its relationship with tumour, node, metastases (TNM) surgical stage, Fuhrman nuclear grade, lymph node involvement and survival. Of the 54 RCC cases studied, 11 (20.4%) showed positive lymph node involvement while 43 (79.6%) were lymph node negative. There was no difference in nm23 protein expression between cases with and without lymph node involvement. In addition, nm23 protein expression was not related to TNM stage, Fuhrman nuclear grade or survival. More extensive studies are required to understand the effect of nm23 protein expression on the biological behaviour of RCC.

Case of solitary eosinophilic granuloma of the sternum.

We report a rare case of eosinophilic granuloma of the sternum in a 13-year-old male patient, who presented with anterior chest pain and a tender mass over the sternum.

An unusual cause of ureteral obstruction in a renal transplant recipient: ureteric aspergilloma.

Mycotic infections in various organ transplant recipients represent severe and often fatal complications. Aspergillosis isolated from the urinary tract occurs quite infrequently in renal transplant recipients. Besides, fungus balls are rare causes of ureteral obstruction. We report a 51-year-old patient with the diagnosis of ureteral obstruction caused by aspergillosis in the early post-renal transplant period, who unfortunately died with the clinical picture of disseminated infection and its complications.

A family with IgA nephropathy and hereditary lymphoedema praecox.

Immunoglobulin A (IgA) nephropathy is the most common primary glomerulonephritis worldwide. The pathogenesis is still unknown and treatment has not yet been established. Rarely it can be associated with other disorders. Its association with hereditary lymphoedema is not reported before. We report four patients, a 60-year-old father, his two sons and his daughter, with hereditary lymphoedema. The family had nine members and in four of them lymphoedema was evident. The other members had neither lymphoedema nor IgA nephropathy. This is the first report of IgA nephropathy in association with hereditary lymphoedema.

High expression of multidrug resistance-1 (MDR-1) and its relationship with multiple prognostic factors in gastric carcinomas in patients in Turkey.

Drug resistance remains a major problem in the treatment of gastric cancer. In Turkey, gastric carcinoma is the second most common cancer and, because the rate of early diagnosis is low, chemotherapy plays an important role in the treatment of the disease. We aimed to investigate expression of the multidrug resistance-1 gene (MDR-1) and its relationship with multiple prognostic factors in gastric cancers. Between 1996 and 1998, a total of 55 patients (37 men and 19 women; median age 55 years) were studied. Sections from specimens of gastric carcinomas were immunohistochemically stained to detect P-glycoprotein (which is associated with MDR-1 expression). We found MDR-1 expression in 48 (87%) of the patients. None of the multiple prognostic factors, including histological type of tumour, correlated with expression of MDR-1. Patients who had low MDR-1 expression had better survival. We conclude that the expression of MDR-1 in gastric cancer is high in Turkey, and this may be related to poor prognosis.