ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis.

Grade IV astrocytoma or glioblastoma multiforme (GBM) is one of the most aggressive and lethal tumors affecting humans. ADAR2-mediated A-to-I RNA editing, an essential post-transcriptional modification event in brain, is impaired in GBMs and astrocytoma cell lines. However, the role of ADAR2 editing in astrocytomas remains to be defined. Here, we show that ADAR2 editing rescue in astrocytomas prevents tumor growth in vivo and modulates an important cell cycle pathway involving the Skp2/p21/p27 proteins, often altered in glioblastoma. We demonstrate that ADAR2 deaminase activity is essential to inhibit tumor growth. Indeed, we identify the phosphatase CDC14B, which acts upstream of the Skp2/p21/p27 pathway, as a novel and critical ADAR2 target gene involved in glioblastoma growth. Specifically, ADAR2-mediated editing on CDC14B pre-mRNA increases its expression with a consequent reduction of the Skp2 target protein, as shown both in vitro and in vivo. We found that, compared to normal brain, both CDC14B editing and expression are progressively impaired in astrocytomas from grade I to IV, being very low in GBMs. These findings (1) demonstrate that post-transcriptional A-to-I RNA editing might be crucial for glioblastoma pathogenesis, (2) identify ADAR2-editing enzyme as a novel candidate tumor suppressor gene and (3) provide proof of principle that ADAR2 or its substrates may represent a suitable target(s) for possible novel, more effective and less toxic approaches to the treatment of GBMs.

[The perceived quality of routine daily communication in dialogues between health care workers]. / Qualità percepita della comunicazione nella daily routine: il dialogo tra le figure sanitarie.

In our day-to-day professional experience as doctors and chemists, we have often noted the poor quality of communication between us and other healthcare workers. We have observed how this in turn can adversely affect communication with the patient, which not only results in poor service to patients themselves, but also impairs the quality of our own work. Moreover, we are convinced that certain such behaviours are ubiquitous. We have therefore sought to evaluate this aspect of our professional life, using literature available on-line. The results reveal the existence of a large number of publications dedicated to relationships between different professions, and representing every possible position: from those frankly critical of other healthcare workers, to those seeking simply to understand these phenomena, to those planning strategies to overcome long-lasting animosities. Even the Italian Health Ministry, in its treatment of themes related to clinical risk, has devoted considerable attention to the quality of communication between healthcare workers. The conclusion we have reached is that there are two areas which are crucial to the improvement of inter-professional relations, namely: sufficient training in these matters in University courses, and a shift in conflicting ethical positions, which often reflect individual professional experience.

[Informed consent. Doctor and patient: comparison of view points]. / Consenso informato. Medico e paziente: punti di vista a confronto.

Starting with an examination of the ethical and legal need for informed consent, the authors set out to assess the perception of the issue by physicians and patients, with particular reference to the Italian context, but also in comparison with international experience, which emerges from an analysis of the heterogeneous material on the Internet. Regardless of local laws, there seems to be a substantial overlap between the way in which the Italian community of doctors and patients and the international community experience informed consent, which often is not the assurance of an effective therapeutic relationship that we would like it to be.

[From empowerment to customer satisfaction: experience of a medical oncology unit]. / Dall'empowerment alla customer satisfaction: l'esperienza diuna struttura di oncologia medica.

AIM: The purpose of the study was the objective assessment of the outpatients satisfaction of the Medical Oncology Unit in Colleferro (USL Roma G), Italy. MATERIALS AND METHODS: A retrospective survey conducted on 584 patients using a closed questionnaire focusing on nine items assess the degree of satisfaction expressed by patients relating to the different aspects of the service. The main aspects object of analysis were the accommodation, the relationship with the staff, the comfort of the structure and the health assistance received. RESULTS: The survey showed a high percentage of overall satisfaction for each of the nine parameters evaluated. There were no significant differences appreciated on a personal variables. CONCLUSIONS: The evaluation of customer satisfaction is a useful tool to measure patients approval and to meet their needs.

[Bioethics and pharmacoeconomics: a difficult balance]. / Bioetica e farmacoeconomia: un difficile equilibrio.

While economic resources continue to decrease, there is a growing demand for health treatment. This faces health workers with an ethical dilemma. They are caught between, on the one hand, their responsibility to the individual patient and, on the other hand, the obvious need to make new treatments available to the largest number of patients. This clearly highlights the need for a regulated system of allocation of resources, whose rules must be agreed to by all operators in the field.

A light, nontoxic interleukin 12 protocol inhibits HER-2/neu mammary carcinogenesis in BALB/c transgenic mice with established hyperplasia.

With a slight asynchronous but consistent progression, all of the mammary glands of female BALB/c mice transgenic for the transforming rat HER-2/neu oncogene progress to atypical hyperplasia and to invasive carcinoma. Previous studies have shown that chronic administration of interleukin (IL) 12 started at the 2nd week of age hampers this progression because of its ability to inhibit tumor angiogenesis and activate a nonspecific immune response. Here we show that a similar inhibition is achieved when 7-week-old mice with fully blown atypical hyperplasia receive a weekly injection of 100 ng IL-12 for 16 times. This lower-dose and later IL-12 administration induces high and sustained levels of serum IFN-gamma equivalent to those elicited by more frequent administrations. A lower-dose and less toxic treatment may thus be envisaged as a possible option in the management of preneoplastic mammary lesions.

Interleukin 12-activated lymphocytes influence tumor genetic programs.

T-lymphocytes (LYs) from normal and IFN-gamma knockout mice were activated by anti-CD3 and anti-CD28 antibodies and cultured in inserts in the presence of interleukin (IL)-12 (IL-12-activated LYs) or not (activated LYs). Their ability to modulate the genetic programs of two tumor lines growing at the bottom of transwells was evaluated. cDNA gene expression array, reverse transcription-PCR, and protein expression showed that LPS, transcription termination factor 1, transforming growth factor, and fibroblast growth factor genes were up-modulated by factors other than IFN-gamma released by activated LYS: The high levels of IFN-gamma released by normal IL-12-activated LYs up-modulated the expression of STAT1, IRF-1, LMP2, LMP7, monokine induced by IFN-gamma, monocyte chemoattractant protein 1, and angiopoietin 2 genes but down-modulated the expression of vascular endothelial growth factor. PA28, IFN-inducible protein 10, inducible NO synthetase, and macrophage-inhibitory protein 2 genes were up-modulated by factors released only by IL-12-activated LYs apart from IFN-gamma. The opposite modulations of vascular endothelial growth factor expression and of angiopoietin 2, monokine induced by IFN-gamma, IFN-inducible protein 10, and inducible NO synthetase by IL-12-activated LYs fit in well with the inhibition of angiogenesis that characterizes the antitumor activity of IL-12. T-LYs thus modify a tumor's behavior so that it becomes a party to its own inhibition.

[Clinical evaluation of the efficacy of the combined determination of serum markers CEA, CA 19.9, CA 72.4 as indexes of gastro-intestinal tract neoplasms]. / Valutazione clinica dell'efficacia dell'associazione dei markers sierici CEA, CA 19.9, CA 72.4 come indici di neoplasia del tratto gastro-intestinale.

The aim of our study was to evaluate the usefulness of the tumor markers CA 72.4, CEA and CA 19.9 in the monitoring of gastrointestinal carcinomas. Our experience demonstrated the usefulness of the determination of CA 72.4 in the follow up of patients with gastrointestinal neoplasms.

HTLV-I and HIV-1 infection in patients with lymphadenopathy syndrome detected during routine breast screening at a tumor prevention center.

Lymphadenopathy with no apparent cause had been reported in a group of women participating in a mammary tumor prevention program. A screening for retrovirus infection was organized to detect the virus as possible etiological agents. Data show a high percentage of positivity for HIV-1 among these lymphadenopathy patients, and surprisingly for HTLV-I, while no such positivity for either virus was found in matched controls or in patients where a different causal agent for lymphadenopathy was found. Of 26 seropositives, 23 deny any risk factor for HIV-1 and do not come from a HTLV-I known endemic area, but while it is impossible to exclude their knowledge of risk factors, it is worth noting that none of them presented a HTLV-I/HIV-1 double infection, which is very frequent in intravenous drug abusers, the major risk group in Italy. On the basis of these data spread of HTLV-I and HIV-1 appears to be more important in Italy than previously thought, and not confined to well-defined groups or, at least, among those who believe they do not belong to a risk group and therefore can represent a major vehicle for virus diffusion. Institution of screening for HTLV-I in blood donors should be taken immediately, and retrovirus infection risk criteria must be revised.