85 research outputs found
Ambient Synthesis of Tricyclic Naphthalenes via Stepwise Styryl-yne Dearomative Diels{ extendash}Alder Cyclization
A cascade of styrylynols promoted by MnO2 allows the synthesis of fused tricycles with a naphthalene core. The reaction occurs under ambient conditions, offering a practical synthetic tool because of the inexpensive and abundant manganese species. The method affords products through the sequential oxidation of a propargyl alcohol, stepwise Diels-Alder cyclization, and finally rearomatization. According to density functional theory, the usually unfavorable stepwise Diels-Alder mechanism is instead a general tool for eliciting otherwise challenging dearomative annulation
Targeting of RET oncogene by naphthalene diimide-mediated gene promoter G-quadruplex stabilization exerts anti-tumor activity in oncogene-addicted human medullary thyroid cancer
Medullary thyroid cancer (MTC) relies on the aberrant activation of RET proto-oncogene. Though targeted approaches (i.e., tyrosine kinase inhibitors) are available, the absence of complete responses and the onset of resistance mechanisms indicate the need for novel therapeutic interventions. Due to their role in regulation of gene expression, G-quadruplexes (G4) represent attractive targets amenable to be recognized or stabilized by small molecules. Here, we report that exposure of MTC cells to a tri-substituted naphthalene diimide (NDI) resulted in a significant antiproliferative activity paralleled by inhibition of RET expression. Biophysical analysis and gene reporter assays showed that impairment of RET expression was consequent to the NDI-mediated stabilization of the G4 forming within the gene promoter. We also showed for the first time that systemic administration of the NDI in mice xenotransplanted with MTC cells resulted in a remarkable inhibition of tumor growth in vivo. Overall, our findings indicate that NDI-dependent RET G4 stabilization represents a suitable approach to control RET transcription and delineate the rationale for the development of G4 stabilizing-based treatments for MTC as well as for other tumors in which RET may have functional and therapeutic implications
Lower Limb Rehabilitation in Juvenile Idiopathic Arthritis using Serious Games
Patients undergoing physical rehabilitation therapy must perform series of
exercises regularly over a long period of time to improve, or at least not to
worsen, their condition. Rehabilitation can easily become boring because of the
tedious repetition of simple exercises, which can also cause mild pain and
discomfort. As a consequence, patients often fail to follow their
rehabilitation schedule with the required regularity, thus endangering their
recovery. In the last decade, video games have become largely popular and the
availability of advanced input controllers has made them a viable approach to
make physical rehabilitation more entertaining while increasing patients
motivation. In this paper, we present a framework integrating serious games for
the lower-limb rehabilitation of children suffering from Juvenile Idiopathic
Arthritis (JIA). The framework comprises games that implement parts of the
therapeutic protocol followed by the young patients and provides modules to
tune, control, record, and analyze the therapeutic sessions. We present the
result of a preliminary validation we performed with patients at the clinic
under therapists supervision. The feedback we received has been overall very
positive both from patients, who enjoyed performing their usual therapy using
video games, and therapists, who liked how the games could keep the children
engaged and motivated while performing the usual therapeutic routine
Serious Games for Wrist Rehabilitation in Juvenile Idiopathic Arthritis
Rehabilitation is a painful and tiring process involving series of exercises
that patients must repeat over a long period. Unfortunately, patients often
grow bored, frustrated, and lose motivation making rehabilitation less
effective. In the recent years video games have been widely used to implement
rehabilitation protocols so as to make the process more entertaining, engaging
and to keep patients motivated. In this paper, we present an integrated
framework we developed for the wrist rehabilitation of patients affected by
Juvenile Idiopathic Arthritis (JIA) following a therapeutic protocol at the
Clinica Pediatrica G. e D. De Marchi. The framework comprises four video games
and a set modules that let the therapists tune and control the exercises the
games implemented, record all the patients actions, replay and analyze the
sessions. We present the result of a preliminary validation we performed with
four poliarticular JIA patients at the clinic under the supervision of the
therapists. Overall, we received good feedback both from the young patients,
who enjoyed performing known rehabilitation exercises using video games, and
therapists who were satisfied with the framework and its potentials for
engaging and motivating the patients
Histamine receptor expression in the human renal tubules: a comparative pharmacological evaluation
Modulation of survival pathways in ovarian carcinoma cell lines resistant to platinum compounds
Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: A pilot case-control study
Background:Limited therapies are available for large ( 6540 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule 6540 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively (p < 0.001). Subsequently we stratified the HCCs in 3 categories according to the nodule size: 40-50 mm, 51-60 mm, and > 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively (p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC
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