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Background: Tumor cell migration is a prerequisite for metastasis formation. The role of the actin-modulating protein, gelsolin, in metastasis is controversial, as previous studies have reported associations with both worse and better prognosis., Materials and Methods: We analysed the association of gelsolin mRNA levels with metastasis-free survival in three cohorts (n=766) of patients with node-negative breast cancer. To determine its effect on migration, gelsolin expression was down-regulated as well as overexpressed in breast cancer cell lines., Results: Higher gelsolin expression correlated with lower tumor stage and grade, and slower cell proliferation, and was associated with longer metastasis-free survival (hazard ratio (HR)=0.60, p<0.001) in patients with estrogen receptor-positive (ER(+)) erb-b2 receptor tyrosine kinase 2-negative (HER2(-)) tumors. Conversely, the opposite association was observed in those with ER(-)HER(-) tumors (HR=1.95, p=0.014). Down-regulation of gelsolin using siRNA in MCF-7 and MDA-MB-468 cells increased cell migration, whereas overexpression had the opposite effect., Conclusion: High gelsolin levels are associated with better prognosis in ER(+)HER2(-) breast cancer and a reduction in tumor cell migration., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The emergence of blood-borne epithelial-derived tumour cells in breast cancer patients is generally supposed to be an indicator of cancer cell spread but only a very small percentage of these cells ultimately initiate metastases. In this study, we investigated the presence of the cell cycle marker Ki-67 in mammary tumour cells isolated from patients' blood and SKBR3 breast carcinoma cells by confocal laser scanning microscopy. We also compared the immunostaining patterns for Ki-67 of blood-borne tumour cells from the patients with actively migrating cells within a collagen matrix. Both circulating tumour cells and migrating SKBR3 cells were found to be in G1- or S-phase. These findings will have impact on adjuvant chemotherapy as circulating tumour cells that are within the active part of the cell cycle are highly susceptible to chemotherapeutic agents and therefore can be killed while they migrate to distant organs to build a metastasis.

In a non-randomized pilot study, 10 patients with histological proof of metastatic colorectal adenocarcinoma were treated by hyperthermia/chemotherapy protocol (41,8 degrees C and 1000 mg 5-FU). Plasma levels of 5-FU were determined after single dose at normothermia and hyperthermia. Plasma concentration time course was consistent with a two-compartment pharmacokinetic open model, with first order kinetic and was significantly altered by hyperthermic treatment. Cytotoxicity of 5-FU was substantially enhanced at hyperthermia (41.8 degrees C) as judged from the clonogenic surviving fractions from established human colon cancer cell lines. Our in vitro and in vivo results suggest that whole body hyperthermia combined with 5-FU is an active combination to develop further in the treatment of colorectal carcinomas.

Brain tumours were induced in inbred Fischer rats (F344) by methylnitrosourea. A pleomorphic glioma (78-219) was established in vitro and propagated as 78FR-G-219 permanent cell line. These cells were modified either by dimethylsulfate or by trinitrobenzene sulfonic acid. Antisera were raised against both native an chemically latered cells in syngeneic rats. The cytotoxicity of these sera was tested against the native glioma cell line as target, by means of the 14C-nicotinamide release. The methylated cells induced a complement--dependent humoral cytotoxicity in the range of that produced by native cells (20%); trinitrophenylation, however, resulted in a two-fold increased cytotoxic humoral immune response. Effects of chaotropic salts on methylated cell surface structure suggested a mode of action different from that of trinitrophenylation, which could be further substantiated by scanning electron microscopy. Furthermore, a new tool for the evaluation of cell surface structure, secondary ion mass spectrometry, was applied on our cell system. Significantly different ionized fragments were obtained from normal brain cells and glioma cells, respectively.

Evidence that experimental neural tumors contain glia specific and glioma-associated antigens is reviewed. The fact that glioma cells share antigens with normal glia cells is of crucial importance for the histogenetic immunodiagnosis of intracranial neoplasms. Moreover, the increasing use of in vitro techniques in neuro-oncology has accentuated the necessity for employment of cell-type characteristic antigens. This allows for objective identification of the various types of brain tumor cells, and also for ascertaining the neurological nature of long-term cultured cells. Humoral and cell-mediated immune reactions to gliomas could be demonstrated in autochthonous and syngeneic hosts. Since glioma-associated antigens are rather weak and glioma cells are low immunogens, various approaches for enhancing glioma-cell immunogenicity have been described, such as treatment with membrane-modifying enzymes, or haptenization with various chemicals. Recently, nitrophenylation of glioma cells has become available for artificially increasing the immunogenicity of these cells. Furthermore, methods have recently been worked out by which monoclonal antibodies of predefined specificity can be produced in order to analyze the nature of glioma-associated antigens. Such methods may have a significant impact on clinical immunodiagnostics, and perhaps on the development of new immunotherapeutic approaches.