Reversal of cycloheximide-induced amnesia by adrenergic receptor stimulation

Amnesia for a multiple trial appetitive spatial dicrimination habit induced by the protein synthesis inhibitor cycloheximide (CXM) was reversed by peripheral injections of both alpha (clonidine) and beta (isoproterenol) norepinephrine receptor stimulators. Stimulation of dopamine receptors with piribedil and acetylcholine receptors with pilocarpine was ineffective in reversing amnesia. The clonidine-induced recovery was blocked by phentolamine and the isoproterenol recovery by propranolol. Examination of the temporal parameters of clonidine-induced recovery indicated that the amnesia was prevented if the agonist was injected either before training and CXM treatment, up to 1 hr after training and up to 3 hr prior to testing. Clonidine also alleviated amnesia induced by another protein synthesis inhibitor anisomycin, for a shock motivated brightness discrimination habit. These data suggest that the transient amnesia induced by CXM may be a consequence of disruption of adrenergic mechanisms and more specifically that norepinephrine may play an important role in memory retrieval.     

Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy resistance in the majority of solid tumors

BACKGROUND: Glucocorticoids have been used widely in conjunction with cancer therapy due to their ability to induce apoptosis in hematological cells and to prevent nausea and emesis. However, recent data including ours, suggest induction of therapy-resistance by glucocorticoids in solid tumors, although it is unclear whether this happens only in few carcinomas or is a more common cell type specific phenomenon. MATERIAL AND METHODS: We performed an overall statistical analysis of our new and recent data with 157 tumor probes evaluated in vitro, ex vivo and in vivo. The effect of glucocorticoids on apoptosis, viability and cell cycle progression under diverse clinically important questions was examined. RESULTS: New in vivo results demonstrate glucocorticoid-induced chemotherapy resistance in xenografted prostate cancer. In an overall statistical analysis we found glucocorticoid-induced resistance in 89% of 157 analysed tumor samples. Resistance is common for several cytotoxic treatments and for several glucocorticoid-derivatives and due to an inhibition of apoptosis, promotion of viability and cell cycle progression. Resistance occurred at clinically achievable peak plasma levels of patients under anti-emetic glucocorticoid therapy and below, lasted for a long time, after one single dose, but was reversible upon removal of glucocorticoids. Two nonsteroidal alternative anti-emetic agents did not counteract anticancer treatment and may be sufficient to replace glucocorticoids in cotreatment of carcinoma patients. CONCLUSION: These data demonstrate the need for prospective clinical studies as well as for detailed mechanistic studies of GC-induced cell-type specific pro- and anti-apoptotic signalling.     

Solitäre Irismetastase bei Mammakarzinom

BACKGROUND: The prevalence of intraocular metastases from breast cancer is approximately 4-5%. Solitary metastases of the iris are rare. We report on successful treatment of a solitary iris metastasis using electron beam irradiation. CASE REPORT: A 30-year-old patient presented with an amelanotic tumor of the iris and the anterior chamber angle of her right amblyopic eye. The patient had undergone left-sided breast-conserving surgery and lymph node dissection 3 years before followed by chemotherapy and radiotherapy. The iris tumor was considered a metastasis. Fractionated electron beam irradiation was performed applying a total dose of 50 Gy in fractions of 5 x 2 Gy/week, electrons (9 MeV). The iris metastasis was completely resolved 13 months after radiotherapy. Until now no signs of cataract have been detected and visual acuity has remained stable. CONCLUSION: Electron beam irradiation of this iris metastasis was an effective treatment for preserving visual acuity and ocular function with tolerable acute toxicity and so far no adverse side effects.     

Retinopathy secondary to radiation therapy for squamous cell carcinoma

This report discusses a case of radiotherapy-induced retinopathy following treatment of squamous cell carcinoma. Treatment of the carcinoma with external beam radiotherapy to the supraorbital region and base of the skull was followed by the onset of retinopathy. The sensory retina, as well as other central nervous system tissues, is highly resistant to radiation damage; however, the retinal vasculature is extremely sensitive to radiation damage, producing a retinopathy that is characteristic of other vascular occlusive diseases. Management is discussed.     

Therapeutic angiogenesis: a new treatment approach for ischemic heart disease--part I

Angiogenesis is the biologic process of forming new blood vessels and is being investigated as an innovative therapeutic approach to help manage ischemic heart disease and peripheral vascular disease. Research studies have identified various angiogenic growth factors and progenitor cells that can enhance new blood vessel formation. Preclinical investigations in animal models have explored the potential use of growth factors with and without progenitor cells to treat myocardial ischemia. The results of clinical trials with growth factor infusions and gene therapy techniques to enhance growth factor production have shown some promise, but therapeutic angiogenesis remains at an early stage of development.     

Tumoural CXCL16 expression is a novel prognostic marker of longer survival times in renal cell cancer patients

The aim of our study was to analyse the expression of CXCL16, ADAM10 and CXCR6 in renal cell carcinoma (RCC) tissue and to correlate the expression pattern with clinicopathologic data, including patient survival. Furthermore, we investigated CXCL16, ADAM10 and CXCR6 expressions by FACS, immunofluorescence and ELISA analysis in renal carcinoma cell lines. Our immunohistochemical analysis on tissue microarray of renal cancer samples of 104 patients revealed that ADAM10 correlated significantly with tumour stage, pathological nodal status, M status and lymphangiosis carcinomatosa. CXCL16, CXCR6 and ADAM10 were significantly increased in papillary carcinomas. Importantly, high levels of CXCL16 expression in renal cancer tissue correlated with better survival of patients, and CXCL16 correlated inversely to the tumour stage. In addition, inhibition of CXCL16 induced the migration of renal cancer cells assuming an anti-migratory function of transmembrane CXCL16. Taken together, our data demonstrate that downregulation of CXCL16 plays an important role in renal cancer development and progression, and that CXCL16 in RCC is an independent prognostic marker for better patient survival.     

CD24 is a marker of exosomes secreted into urine and amniotic fluid

Exosomes are small membrane vesicles that are secreted from a variety of cell types into various body fluids including the blood and urine. These vesicles are thought to play a role in cell-cell interactions. CD24 is a small but extensively glycosylated protein linked to the cell surface by means of a glycosyl-phosphatidylinositol anchor. In this study we found that CD24 is present in membrane vesicles characterized as exosomes that were isolated from the urine of normal individuals. CD24 was expressed by both tubule cells and podocytes and treatment of the latter with a cholesterol-extracting agent, but not with a calcium ionophore, caused the release of CD24-containing exosomes. Using CD24 as a marker, we found exosomes in the urine of newborn infants and in the amniotic fluid of pregnant women with similar findings made in mice. Interestingly, studies with CD24 knockout mice showed that the exosomes are released from the fetus but not from the mother; however, exosome release was similar from both the knockout and the wild-type mice. This indicates that CD24 is not essential for exosome formation or release but may be a convenient exosome marker. Our studies suggest that exosomal secretion from the embryonic kidney could play a biological role at the fetal-maternal interphase.