The glutamatergic system outside the CNS and in cancer biology

Glutamate is a major excitatory neurotransmitter in the CNS. The signalling machinery consists of: glutamate receptors, which are responsible for signal input; plasma glutamate transporters, which are responsible for signal termination; and vesicular glutamate transporters for signal output through exocytic release. Recently, data have suggested that the glutamatergic system plays an important role in non-neuronal tissues. In addition, the expression of glutamatergic system has been implicated in tumour biology. This review outlines the evidence, which suggests that the glutamatergic system may have an important role in cancer biology. © 2005 Ashley Publications

Molecular diagnosis of the viral component in cardiomyopathies: Pathopgysiological, clinical and therapeutic implications

Background: Myocarditis is defined as the inflammation of myocardium associated with cardiac dysfunction. Despite this clear-cut definition, diagnosis and etiologic treatment continue to create considerable debate. Viral infections are frequent causes of myocarditis and there is evidence that persistent viral infection is associated with poor prognosis in different subtypes of cardiomyopathy. Objective: To review methods for diagnosis of viral myocarditis and present the use of polymerase chain reaction (PCR)-based protocols for evaluating viral infection in myocarditis/cardiomyopathies. Methods: A review of published literature. Results/conclusion: There is increasing evidence that PCR-based protocols can provide reliable molecular evidence for the presence of viral infection in myocardium. Thus application of molecular techniques will allow collection and analysis of more information on the epidemiology of viral cardiomyopathies, patient risk stratification and appropriate medical treatment. © 2008 Informa UK Ltd

Molecular detection of tyrosinase transcripts in peripheral blood from patients with malignant melanoma: Correlation of PCR sensitivity threshold with clinical and pathologic disease characteristics

Background: Positive molecular detection of tyrosinase transcripts (TYR mRNA) in RNA extracts of peripheral blood (PB) samples from patients with malignant melanoma provides evidence of disease dissemination. Methods: Total RNA extracted from PB was quantified and subjected to RT-PCR under ultra-sensitive and reduced-sensitivity PCR conditions using SSRT-II. Positive TYR mRNA detection in 78 melanoma patients and 40 healthy volunteers was correlated with clinical stage, Breslow's evaluation of tumor thickness, Clark's assessment of tumor invasion, the location of the primary tumor site, and tumor histology. The assay sensitivity was evaluated by spiking PB with the melanoma cell line SK-MEL-28. Results: Using ultra-sensitive PCR conditions, eight out of 40 RNA (20%) samples from healthy volunteers and 50 out of 78 RNA (64.1%) samples from melanoma patients tested positive. Using reduced-sensitivity PCR conditions, we found only two positives in 40 RNA samples from healthy subjects and 20 positives in 78 RNA samples (25.6%) from melanoma patients. Only positive PCR samples for the reduced-sensitivity PCR assay correlated significantly with stage IV (metastatic) disease (p=0.0395). There was no significant correlation between positive TYR mRNA samples for either PCR condition (ultra-sensitive and reduced-sensitivity) with Breslow's classification of tumor thickness, Clark's assessment of tumor invasion, location of the primary tumor site, and type of tumor histology. Conclusions: We conclude that reduced-sensitivity rather than ultra-sensitive PCR conditions correlate with clinical stage in melanoma patients. © 2006 by Walter de Gruyter

Detection of the circulating tumor cells in cancer patients

As the presence of tumor cells circulating in the blood is associated with systemic disease and shortened survival, the establishment of a method to detect circulating tumor cells (CTCs) is of critical importance for a more concise staging and follow-up of cancer patients. Recently, the most robust strategies for the determination of CTCs are the PCR-based methods and the CellSearch ® system that exploits the immunofluorescent characterization and isolation of cancer cells. Herein, we analyzed the experimental strategies used for determining CTCs with respect to accuracy, sensitivity and reproducibility in cancers of the breast, colon, prostate and melanoma. © 2010 Future Medicine Ltd

Adriamycin in combination with dexamethasone and octreotide lacks activity on the treatment of a 4T1 metastatic breast cancer model

The aim of this study was to evaluate whether the palliative treatment for metastatic disease with dexamethasone (DEX) plus octreotide (OCT) can improve the anticancer effects of the standard treatment with adriamycin (ADR) on a 4T1 metastatic breast cancer (MBC) model. 4T1 cells were first characterized for the expression of the somatostatin receptors 1-5 and were then inoculated onto the femur of BALB/C mice. Investigation protocols used 4T1 cell proliferation and invasion assays, analysis of radiographic images of the bone metastatic lesions, and overall survival of the diseased animals. The triple combination treatment regime (ADR+OCT+DEX) was ineffective for growth inhibition and showed an antagonistic effect on ADR activity in the 4T1 cell line in both proliferation and invasion assays. ADR treatment following the administration of the DEX+OCT regimen decreased the anticancer activity of ADR both on the grading of the bone metastatic lesions and on the overall survival of diseased animals. Moreover, the palliation treatment with OCT+DEX and in combination with ADR rather caused disease progression of the metastatic disease and bone lesions in a 4T1 MBC model in vivo. These results suggest that the administration of the DEX+OCT regimen, although may preserve palliative effects, neutralizes or reverses the anticancer effects of ADR on a 4T1 MBC model in vitro and in vivo. The simultaneous use of these drugs should be considered carefully in clinical practice. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved