Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and Colorectal Cancer: A Feasibility Study

Background

Cancer stem cells represent a population of immature tumor cells found in most solid tumors. Their peculiar features make them ideal models for studying drug resistance and sensitivity. In this study, we investigated whether cancer stem cells isolation and in vitro sensitivity assay are feasible in a clinical setting.

Methods

Cancer stem cells were isolated from effusions or fresh cancer tissue of 23 patients who progressed after standard therapy failure. Specific culture conditions selected for immature tumor cells that express markers of stemness. These cells were exposed in vitro to chemotherapeutic and targeted agents.

Results

Cancer stem cells were extracted from liver metastases in 6 cases (25%), lung nodules in 2 (8%), lymph node metastases in 3 (12.5%) and pleural/peritoneal/pericardial effusion in 13 (54%). Cancer stem cells were successfully isolated in 15 patients (63%), including 14 with lung cancer (93.3%). A sensitivity assay was successfully performed in 7 patients (30.4%), with a median of 15 drugs/combinations tested (range 5-28) and a median time required for results of 51 days (range 37-95).

Conclusion

The approach used for the STELLA trial allowed isolation of cancer stem cells in a consistent proportion of patients. The low percentage of cases completing the full procedure and the long median time for obtaining results highlights the need for a more efficient procedure.

Trial Registration

ClinalTrials.gov NCT01483001     

From fever to immunity: A new role for IGFBP‐6?

Fever is a fundamental response to infection and a hallmark of inflammatory disease, which has been conserved and shaped through millions of years of natural selection. Although fever is able to stimulate both innate and adaptive immune responses, the very nature of all the molecular thermosensors, the timing and the detailed mechanisms translating a physical trigger into a fundamental biological response are incompletely understood. Here we discuss the consequence of hyperthermic stress in dendritic cells (DCs), and how the sole physical input is sensed as an alert stimulus triggering a complex transition in a very narrow temporal window. Importantly, we review recent findings demonstrating the significant and specific changes discovered in gene expression and in the metabolic phenotype associated with hyperthermia in DCs. Furthermore, we discuss the results that support a model based on a thermally induced autocrine signalling, which rewires and sets a metabolism checkpoint linked to immune activation of dendritic cells. Importantly, in this context, we highlight the novel regulatory functions discovered for IGFBP‐6 protein: induction of chemotaxis; capacity to increase oxidative burst and degranulation of neutrophils, ability to induce metabolic changes in DCs. Finally, we discuss the role of IGFBP‐6 in autoimmune disease and how novel mechanistic insights could lead to exploit thermal stress‐related mechanisms in the context of cancer therapy.     

Situational and dispositional determinants of intentional deceiving

Does opportunity make the thief or are people dispositionally prone to deceive? The interaction between personality and the circumstances surrounding deception is crucial to understand what promotes dishonesty in our society. Due to its inherent spontaneity and sociality, deceptive behaviour may be hardly reproducible in experimental settings. We developed a novel paradigm in the form of an interactive game where participants can choose whether to lie to another person in situations of loss vs. gain, and of no-reputation-risk vs. reputation-risk linked to the disclosure of their deceptive behaviour to others. Thus, our ecological paradigm allowed subjects to spontaneously decide when to lie and face the challenge of deceiving others. In the case of loss, participants lied to reverse the outcome in their favour. Deception was lower in the reputation-risk condition where personality traits concerning social interactions also played an important role.The results suggest that deception is definitely promoted by unfavourable events, and that maintaining one''s own reputation encourages honesty, particularly in socially inclined individuals.     

Please Don't! The Automatic Extrapolation of Dangerous Intentions

Facial emotions and emotional body postures can easily grab attention in social communication. In the context of faces, gaze has been shown as an important cue for orienting attention, but less is known for other important body parts such as hands. In the present study we investigated whether hands may orient attention due to the emotional features they convey. By implying motion in static photographs of hands, we aimed at furnishing observers with information about the intention to act and at testing if this interacted with the hand automatic coding. In this study, we compared neutral and frontal hands to emotionally threatening hands, rotated along their radial-ulnar axes in a Sidedness task (a Simon-like task based on automatic access to body representation). Results showed a Sidedness effect for both the palm and the back views with either neutral and emotional hands. More important, no difference was found between the two views for neutral hands, but it emerged in the case of the emotional hands: faster reaction times were found for the palm than the back view. The difference was ascribed to palm views'' “offensive” pose: a source of threat that might have raised participants'' arousal. This hypothesis was also supported by conscious evaluations of the dimensions of valence (pleasant-unpleasant) and arousal. Results are discussed in light of emotional feature coding.     

Computational modeling of the immune response to tumor antigens

Vaccination protocols designed to elicit anti-cancer immune responses have, many times, failed in producing tumor eradication and in prolonging patient survival. Usually in cancer vaccination, epitopes from one organism are included in the genome or linked with some protein of another in the hope that the immunogenic properties of the latter will boost an immune response to the former. However, recent results have demonstrated that injections of two different vectors encoding the same recombinant antigen generate high levels of specific immunity. Systematic comparison of the efficacy of different vaccination protocols has been hampered by technical limitations, and clear evidence that the use of multiple vectors has advantages over single carrier injections is lacking. We used a computational model to investigate the dynamics of the immune response to different anti-cancer vaccines based on randomly generated antigen/carrier compounds. The computer model was adapted for simulations to this new area in immunology research and carefully validated to the purpose. As a matter of fact, it reproduces a relevant number of experimental observations. The model shows that when priming and boosting with the same construct, competition rather than cooperation develops amongst T cell clones of different specificities. Moreover, from the simulations, it appears that the sequential use of multiple carriers may generate more robust anti-tumor immune responses and may lead to effective tumor eradication in a higher percentage of cases. Our results provide a rational background for the design of novel strategies for the achievement of immune control of cancer.     

Neuropsychopathological comorbidities in learning disorders

Background

Learning Disorders (LD) are complex diseases that affect about 2-10% of the school-age population. We performed neuropsychological and psychopathological evaluation, in order to investigate comorbidity in children with LD.

Methods

Our sample consisted of 448 patients from 7 to 16 years of age with a diagnosis of LD, divided in two subgroups: Specific Learning Disorders (SLD), including reading, writing, mathematics disorders, and Learning Disorders Not Otherwise Specified (LD NOS).

Results

Comorbidity with neuropsychopathologies was found in 62.2% of the total sample. In the LSD subgroup, ADHD was present in 33%, Anxiety Disorder in 28.8%, Developmental Coordination Disorder in 17.8%, Language Disorder in 11% and Mood Disorder in 9.4% of patients. In LD NOS subgroup, Language Disorder was present in 28.6%, Developmental Coordination Disorder in 27.5%, ADHD in 25.4%, Anxiety Disorder in 16.4%, Mood Disorder in 2.1% of patients. A statistically significant presence was respectively found for Language and Developmental Coordination Disorder comorbidity in LD NOS and for ADHD, mood and anxiety disorder comorbidity in SLD subgroup.

Conclusions

The different findings emerging in this study suggested to promote further investigations to better define the difference between SLD and LD NOS, in order to improve specific interventions to reduce the long range consequences.