Does the immune reaction cause malignant transformation by disrupting cell-to-cell or cell-to-matrix communications?

Tumor progression: In many (perhaps in all) tumor systems, a malignant cancer is preceded by a benign lesion. Most benign lesions do not transform to malignancy and many regress. The final transformative step to malignancy differs from the preceding steps in, among other things, that it often occurs in the absence of the original carcinogenic stimulus. Mechanism of immunostimulation: Relatively low titers of specific immune reactants are known to stimulate, but cell-to-cell or cell-to-matrix interactions appear to be major inhibitors of tumor-growth. Therefore, it seems reasonable to hypothesize that the mechanism of immunostimulation may be an interference with cell-to-cell or cell-to-matrix communication by a sub-lethal immune-reaction. Discussion: While the above hypothesis remains unproven, some evidence suggests that immunity may have a major facilitating effect on tumor growth especially at the time of malignant transformation. There is even some evidence suggesting that transformation in vivo may seldom occur in the absence of immunostimulation of the premalignant lesion. Positive selection by the immune reaction may be the reason that tumors are immunogenic

The Phenotypic Radiation Resistance of CD44+/CD24−or low Breast Cancer Cells Is Mediated through the Enhanced Activation of ATM Signaling

Cancer initiating cells (CIC) are stem-like cells. CIC may contribute not only to the initiation of cancer but also to cancer recurrence because of the resistance of CIC both to chemotherapy and radiation therapy. From the MCF-7 and MDA-MB231 breast cancer cell lines and primary culture of patient breast cancer cells, we isolated by flow cytometry a CIC subset of cells with the CD44+/CD24−or low phenotype. The CD44+/CD24−or low subset showed increased sphere formation and resistance to radiation compared to the non- CD44+/CD24−or low subset. The increased radiation resistance was not dependent on the result of altered non-homologous end joining (NHEJ) DNA repair activity as both NHEJ activity and expression of the various proteins involved in NHEJ were not significantly different between the CD44+/CD24−or low and non- CD44+/CD24−or low subsets. However, activation of ATM signaling was significantly increased in CD44+/CD24−or low cells compared to non- CD44+/CD24−or low cells in both from breast cancer cell lines and primary human breast cancer cells. Application of an ATM inhibitor effectively decreased the radiation resistance of CD44+/CD24−or low subset, suggesting that targeting ATM signaling may provide a new tool to eradicate stem-like CIC and abolish the radiation resistance of breast cancer

Eosinophils in glioblastoma biology

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the eosinophil is a key immunoregulatory cell capable of influencing the activity of both innate and adaptive immune responses. Of central importance to this report is the observation that eosinophil migration to the brain occurs in response to traumatic brain injury and following certain immunotherapeutic treatments for GBM. Although eosinophils have been identified in various central nervous system pathologies, and are known to operate in wound/repair and tumorstatic models, the potential roles of eosinophils in GBM development and the tumor immunological response are only beginning to be recognized and are therefore the subject of the present review

The Ionizing Radiation-Induced Bystander Effect: Evidence, Mechanism, and Significance

It has long been considered that the important biological effects of ionizing radiation are a direct consequence of unrepaired or misrepaired DNA damage occurring in the irradiated cells. It was presumed that no effect would occur in cells in the population that receive no direct radiation exposure. However, in vitro evidence generated over the past two decades has indicated that non-targeted cells in irradiated cell cultures also experience significant biochemical and phenotypic changes that are often similar to those observed in the targeted cells. Further, nontargeted tissues in partial body-irradiated rodents also experienced stressful effects, including oxidative and oncogenic effects. This phenomenon, termed the “bystander response,” has been postulated to impact both the estimation of health risks of exposure to low doses/low fluences of ionizing radiation and the induction of second primary cancers following radiotherapy. Several mechanisms involving secreted soluble factors, oxidative metabolism, gap-junction intercellular communication, and DNA repair, have been proposed to regulate radiation-induced bystander effects. The latter mechanisms are major mediators of the system responses to ionizing radiation exposure, and our knowledge of the biochemical and molecular events involved in these processes is reviewed in this chapter

Alterações cromossômicas causadas pela radiação dos monitores de vídeo de computadores Chromosome abnormalities caused by computer video display monitors' radiation

OBJETIVO: Em decorrência dos questionamentos sobre o efeito deletério das radiações emitidas pelo campo eletromagnético (CEM) dos tipos ELF (extremely low frequency) e VLF (very low frequency) transmitidas pelos monitores de vídeo dos computadores (CRT), foi avaliada a freqüência de anomalias cromossômicas estruturais e a cinética do ciclo celular em indivíduos expostos por seu trabalho à radiação dos CRT. MÉTODOS: A pesquisa de aberrações cromossômicas foi realizada em 2.000 metáfases de primeira divisão celular obtidas de culturas de 48h de linfócitos de sangue venoso periférico de dez indivíduos expostos ao CRT (grupo E) e de dez controles (grupo C). A cinética do ciclo celular foi pesquisada pelos índices mitótico (IM) e de proliferação celular (IPC). RESULTADOS: A análise estatística evidenciou freqüências significativamente maiores de metáfases com anomalias cromossômicas (E=5,9%; C=3,7%) e anomalias/célula (E=0,066±0,026; C=0,040±0,026) nos indivíduos expostos aos CRTs. As alterações citogenéticas mais comuns foram as quebras cromatídicas, com freqüência de 0,034±0,016 no grupo E e de 0,016±0,015 no grupo C. As freqüências de IM e IPC não apresentaram diferenças significantes entre os grupos avaliados. CONCLUSÕES: Os resultados sugerem um efeito genotóxico do CEM emitido pelos CRTs devido à freqüência mais elevada de quebras cromatídicas, enfatizando a necessidade de haver um número maior de estudos com diferentes técnicas que vise a investigar a ação do CEM sobre o material genético.<br>OBJECTIVE: Concerns were raised about the potential damaging effects of electromagnetic field (EMF) radiation emissions of ELF (extremely low frequency) and VLF (very low frequency) computer video display monitors (VDM), it was assessed the frequency of structural chromosome abnormalities and investigated the cell cycle kinetics in individuals occupationally exposed to VDM radiation. METHODS: Chromosome aberrations were investigated in 2,000 first cell cycle metaphases obtained after 48-hour cultures of peripheral blood lymphocytes drawn from 10 individuals occupationally exposed to VDM radiation (group E) and 10 controls (group C). Cell cycle kinetics was studied using the mitotic index (MI) and cellular proliferation index (CPI). RESULTS: Statistical analysis showed significantly higher frequencies of anomalous metaphases (E=5.9%; C=3.7%) and anomaly/cell (E=0.066±0.026; C= 0.040±0.026) in individuals exposed to VDM radiation. The most common cytogenetic alterations seen were chromatid breaks at frequencies of 0.034±0.016 in group E and 0.016±0.015 in group C. There was no significant difference between MI and CPI frequencies in both groups. CONCLUSIONS: The study findings suggest genotoxic effects of EMF emissions revealed by the higher frequency of chromatid breaks in individuals exposed to VDM radiation. However, there is a need of further studies on EMF genetic effects using other investigation methods