Older adults: Are they ready to adopt health-related ICT?

BackgroundThe proportion of older adults in the population is steadily increasing, causing healthcare costs to rise dramatically. This situation calls for the implementation of health-related information and communication technologies (ICT) to assist in providing more cost-effective healthcare to the elderly. In order for such a measure to succeed, older adults must be prepared to adopt these technologies. Prior research shows, however, that this population lags behind in ICT adoption, although some believe that this is a temporary phenomenon that will soon change.ObjectivesTo assess use by older adults of technology in general and ICT in particular, in order to evaluate their readiness to adopt health-related ICT.MethodWe employed the questionnaire used by Selwyn et al. in 2000 in the UK, as well as a survey instrument used by Morris and Venkatesh, to examine the validity of the theory of planned behavior (TPB) in the context of computer use by older employees. 123 respondents answered the questions via face-to-face interviews, 63 from the US and 60 from Israel. SPSS 17.0 was used for the data analysis.ResultsThe results show that although there has been some increase in adoption of modern technologies, including ICT, most of the barriers found by Selwyn et al. are still valid. ICT use was determined by accessibility of computers and support and by age, marital status, education, and health. Health, however, was found to moderate the effect of age, healthier older people being far more likely to use computers than their unhealthy coevals. The TPB was only partially supported, since only perceived behavioral control (PBC) emerged as significantly affecting intention to use a computer, while age, contrary to the findings of Morris and Venkatesh, interacted differently for Americans and Israelis. The main reason for non-use was ‘no interest’ or ‘no need’, similar to findings from data collected in 2000.ConclusionsAdoption of technology by older adults is still limited, though it has increased as compared with results of the previous study. Modern technologies have been adopted (albeit selectively) by older users, who were presumably strongly motivated by perceived usefulness. Particularly worrying are the effects of health, PBC, and the fact that many older adults do not share the perception that ICT can significantly improve their quality of life. We therefore maintain that older adults are not yet ready to adopt health-related ICT. Health-related ICT for the elderly should be kept simple and demonstrate substantial benefits, and special attention should be paid to training and support and to specific personal and cultural characteristics. These are mandatory conditions for adoption by potential unhealthy and older consumers.     

Cystatin C takes part in melanoma-microglia cross-talk: possible implications for brain metastasis

The development of melanoma brain metastasis is largely dependent on mutual interactions between the melanoma cells and cells in the brain microenvironment. Here, we report that the extracellular cysteine protease inhibitor cystatin C (CysC) is involved in these interactions. Microglia-derived factors upregulated CysC secretion by melanoma. Similarly, melanoma-derived factors upregulated CysC secretion by microglia. Whereas CysC enhanced melanoma cell migration through a layer of brain endothelial cells, it inhibited the migration of microglia cells toward melanoma cells. CysC was also found to promote the formation of melanoma three-dimensional structures in matrigel. IHC analysis revealed increased expression levels of CysC in the brain of immune-deficient mice bearing xenografted human melanoma brain metastasis compared to the brain of control mice. Based on these in vitro and in vivo experiments we hypothesize that CysC promotes melanoma brain metastasis. Increased expression levels of CysC were detected in the regenerating brain of mice after stroke. Post-stroke brain with melanoma brain metastasis showed an even stronger expression of CysC. The in vitro induction of stroke-like conditions in brain microenvironmental cells increased the levels of CysC in the secretome of microglia cells, but not in the secretome of brain endothelial cells. The similarities between melanoma brain metastasis and stroke with respect to CysC expression by and secretion from microglia cells suggest that CysC may be involved in shared pathways between brain metastasis and post-stroke regeneration. This manifests the tendency of tumor cells to highjack physiological molecular pathways in their progression.     

Astrocytes facilitate melanoma brain metastasis via secretion of IL‐23

Melanoma is the leading cause of skin cancer mortality. The major cause of melanoma mortality is metastasis to distant organs, frequently to the brain. The microenvironment plays a critical role in tumourigenesis and metastasis. In order to treat or prevent metastasis, the interactions of disseminated tumour cells with the microenvironment at the metastatic organ have to be elucidated. However, the role of brain stromal cells in facilitating metastatic growth is poorly understood. Astrocytes are glial cells that function in repair and scarring of the brain following injury, in part via mediating neuroinflammation, but the role of astrocytes in melanoma brain metastasis is largely unresolved. Here we show that astrocytes can be reprogrammed by human brain‐metastasizing melanoma cells to express pro‐inflammatory factors, including the cytokine IL‐23, which was highly expressed by metastases‐associated astrocytes in vivo. Moreover, we show that the interactions between astrocytes and melanoma cells are reciprocal: paracrine signalling from astrocytes up‐regulates the secretion of the matrix metalloproteinase MMP2 and enhances the invasiveness of brain‐metastasizing melanoma cells. IL‐23 was sufficient to increase melanoma cell invasion, and neutralizing antibodies to IL‐23 could block this enhanced migration, implying a functional role for astrocyte‐derived IL‐23 in facilitating the progression of melanoma brain metastasis. Knocking down the expression of MMP2 in melanoma cells resulted in inhibition of IL‐23‐induced invasiveness. Thus, our study demonstrates that bidirectional signalling between melanoma cells and astrocytes results in the formation of a pro‐inflammatory milieu in the brain, and in functional enhancement of the metastatic potential of disseminated melanoma cells. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The angiogenic factors CXCL8 and VEGF in breast cancer: regulation by an array of pro-malignancy factors

The regulation of secretion of the angiogenic factors CXCL8 and Vascular Endothelial Growth Factors (VEGF) was determined in breast tumor cells and in monocytic cells (as host cells that contribute to breast cancer). CXCL8 secretion, and partly the secretion of VEGF, were up-regulated in monocytic cells, but not in breast tumor cells, by the CC chemokines CCL5 and CCL2. EGF potently up-regulated CXCL8 secretion by breast tumor cells, and its effect was promoted by a consecutive treatment of the cells by estrogen and progesterone. These findings provide evidence for a complex set of pro-malignancy factors that may control the expression of angiogenic mediators at breast tumor sites.     

Perioperative biobehavioral interventions to prevent cancer recurrence through combined inhibition of β-adrenergic and cyclooxygenase 2 signaling

Evidence suggests that excess perioperative activation of the sympathetic nervous system and the consequent release of catecholamines (ie, epinephrine and norepinephrine) in the context of cancer surgery and inflammation may significantly facilitate prometastatic processes. This review first presents biomedical processes that make the perioperative timeframe pivotal in determining long-term cancer outcomes nonproportionally to its short duration (days to weeks). Then, it analyzes the various mechanisms via which the excess release of catecholamines can facilitate the progression of cancer metastases in this context by directly affecting the malignant tissues and by regulating, via indirect pathways, immunological and other mechanisms that affect metastatic progression in the tumor microenvironment and systemically. In addition, this review addresses the need to supplement β-adrenoreceptor blockade with cyclooxygenase 2 inhibition, especially during surgery and shortly thereafter, because similar mechanisms are simultaneously activated by surgery-induced inflammatory responses. Importantly, this review presents translational and clinical evidence showing that perioperative β-adrenoreceptor blockade and cyclooxygenase 2 inhibition can reduce the prometastatic process and cancer recurrence, and the clinical feasibility and safety of this approach are demonstrated as well. Lastly, alternative psychophysiological approaches to the use of β-adrenergic blockers are presented because a substantial portion of patients have medical contraindications to this pharmacological treatment. The adaptation of existing psychophysiological interventions to the perioperative period and principles for constructing new approaches are discussed and exemplified. Overall, pharmacobehavioral interventions, separately or in combination, could transform the perioperative timeframe from being a prominent facilitator of metastatic progression to an opportunity for arresting or eliminating residual disease, potentially improving long-term survival rates in cancer patients.     

The melanoma brain metastatic microenvironment: aldolase C partakes in shaping the malignant phenotype of melanoma cells – a case of inter‐tumor heterogeneity

Previous studies indicated that microglia cells upregulate the expression of aldolase C (ALDOC) in melanoma cells. The present study using brain‐metastasizing variants from three human melanomas explores the functional role of ALDOC in the formation and maintenance of melanoma brain metastasis (MBM). ALDOC overexpression impacted differentially the malignant phenotype of these three variants. In the first variant, ALDOC overexpression promoted cell viability, adhesion to and transmigration through a layer of brain endothelial cells, and amplified brain micrometastasis formation. The cross‐talk between this MBM variant and microglia cells promoted the proliferation and migration of the latter cells. In sharp contrast, ALDOC overexpression in the second brain‐metastasizing melanoma variant reduced or did not affect the same malignancy features. In the third melanoma variant, ALDOC overexpression augmented certain characteristics of malignancy and reduced others. The analysis of biological functions and disease pathways in the ALDOC overexpressing variants clearly indicated that ALDOC induced the expression of tumor progression promoting genes in the first variant and antitumor progression properties in the second variant. Overall, these results accentuate the complex microenvironment interactions between microglia cells and MBM, and the functional impact of intertumor heterogeneity. Since intertumor heterogeneity imposes a challenge in the planning of cancer treatment, we propose to employ the functional response of tumors with an identical histology, to a particular drug or the molecular signature of this response, as a predictive indicator of response/nonresponse to this drug.

Abbreviations

ALDOC

aldolase C

BBB

blood–brain barrier

BEC

brain endothelial cells

CM

conditioned medium

CNS

central nervous system

ECM

extracellular matrix

MBM

melanoma brain metastasis

MCM

melanoma‐conditioned medium

MGCM

microglia‐conditioned medium

MMP‐2

matrix metalloproteinase‐2

RS9

ribosomal protein S9

TEM

transendothelial migration

β2m

β2 microglobulin