Colon carcinoma is the second most common cause of death from cancer. The isolation and characterization of tumorigenic colon cancer cells may help to devise novel diagnostic and therapeutic ...procedures. Although there is increasing evidence that a rare population of undifferentiated cells is responsible for tumour formation and maintenance, this has not been explored for colorectal cancer. Here, we show that tumorigenic cells in colon cancer are included in the high-density CD133+ population, which accounts for about 2.5% of the tumour cells. Subcutaneous injection of colon cancer CD133+ cells readily reproduced the original tumour in immunodeficient mice, whereas CD133- cells did not form tumours. Such tumours were serially transplanted for several generations, in each of which we observed progressively faster tumour growth without significant phenotypic alterations. Unlike CD133- cells, CD133+ colon cancer cells grew exponentially for more than one year in vitro as undifferentiated tumour spheres in serum-free medium, maintaining the ability to engraft and reproduce the same morphological and antigenic pattern of the original tumour. We conclude that colorectal cancer is created and propagated by a small number of undifferentiated tumorigenic CD133+ cells, which should therefore be the target of future therapies.
Besides action vitality forms, facial expressions represent another fundamental social cue which enables to infer the affective state of others. In the present study, we proposed the iCub robot as an ...interactive and controllable agent to investigate whether and how different facial expressions, associated to different action vitality forms, could modulate the motor behaviour of participants. To this purpose, we carried out a kinematic experiment in which 18 healthy participants observed video-clips of the iCub robot performing a rude or gentle request with a happy or angry facial expression. After this request, they were asked to grasp an object and pass it towards the iCub robot. Results showed that the iCub facial expressions significantly modulated participants motor response. Particularly, the observation of a happy facial expression, associated to a rude action, decreased specific kinematic parameters such as velocity, acceleration and maximum height of movement. In contrast, the observation of an angry facial expression, associated to a gentle action, increased the same kinematic parameters. Moreover, a behavioural study corroborated these findings, showing that the perception of the same action vitality form was modified when associated to a positive or negative facial expression.
Actions with identical goals can be executed in different ways (gentle, rude, vigorous, etc.), which D. N. Stern called vitality forms D. N. Stern,
(2010). Vitality forms express the agent's ...attitudes toward others. In a series of fMRI studies, we found that the dorso-central insula (DCI) is the region that is selectively active during both vitality form observation and execution. In one previous experiment, however, the middle cingulate gyrus also exhibited activation. In the present study, in order to assess the role of the cingulate cortex in vitality form processing, we adopted a classical vitality form paradigm, but making the control condition devoid of vitality forms using jerky movements. Participants performed two different tasks: Observation of actions performed gently or rudely and execution of the same actions. The results showed that in addition to the insula, the middle cingulate cortex (MCC) was strongly activated during both action observation and execution. Using a voxel-based analysis, voxels showing a similar trend of the blood-oxygen-level-dependent (BOLD) signal in both action observation and execution were found in the DCI and in the MCC. Finally, using a multifiber tractography analysis, we showed that the active sites in MCC and DCI are reciprocally connected.
Regulatory T cell (Treg) therapy using recipient‐derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ ...transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor‐MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA‐A2‐specific CARs were engineered: one comprising a CD28‐CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA‐A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA‐A2‐expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune‐mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation.
Human HLA class I–allospecific regulatory T cells generated using chimeric antigen receptor technology exhibit an enhanced suppressive capacity in the presence of their target antigen, and inhibit undesired alloimmune‐mediated damage of human skin grafts more effectively than polyclonal regulatory T cells. See page 854 for Brouard and Mooney's editorial.
Abstract
MicroRNAs (miRs) are small non-coding RNA molecules, which are involved in the development of various malignancies, including prostate cancer (PCa). miR-17-5p is considered the most ...prominent member of the miR-17-92 cluster, with an essential regulatory function of fundamental cellular processes. In many malignancies, up-regulation of miR-17-5p is associated with worse outcome. In PCa, miR-17-5p has been reported to increase cell proliferation and the risk of metastasis. In this study, prostatectomy specimens from 535 patients were collected. Tissue microarrays were constructed and in situ hybridization was performed, followed by scoring of miR-17-5p expression on different tumor compartments. High expression of miR-17-5p in tumor epithelium was associated with biochemical failure (BF,
p
< 0.001) and clinical failure (CF,
p
= 0.019). In multivariate analyses, high miR-17-5p expression in tumor epithelial cells was an independent negative prognostic factor for BF (HR 1.87, 95% CI 1.32–2.67,
p
< 0.001). In vitro analyses confirmed association between overexpression of miR-17-5p and proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145). In conclusion, our study suggests that a high cancer cell expression of miR-17-5p was an independent negative prognostic factor in PCa.
Recent studies on the comparison between the Multi Aperture Scintillation Sensor (MASS) and Generalized Scintillation Detection and Ranging (G-SCIDAR) profiler techniques have suggested significant ...discrepancies between the results delivered by the two instruments. MASS has been largely used in the recent site testing campaigns for the future next generation giant telescopes i.e. the European Extremely Large Telescope, the Thirty Meter Telescope (TMT) and the Giant Magellan Telescope (GMT) and is still used to monitor the conditions of world-class astronomical sites, as well as to deliver free atmosphere turbulence profiles to feed Adaptive Optics performance simulations. In this paper, we explore a different approach in the comparison between MASS and Generalized SCIDAR techniques with respect to previous studies, in order to provide a method for the use of the MASS data bases accumulated at European Southern Obseratory Paranal Observatory in Adaptive Optics simulations.
Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, ...sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia.
431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires.
Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer's disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson's disease dementia.
A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.
PDF
