Mixed Nanosized Polymeric Micelles as Promoter of Doxorubicin and miRNA-34a Co-Delivery Triggered by Dual Stimuli in Tumor Tissue.

Dual stimuli-sensitive mixed polymeric micelles (MM) are developed for co-delivery of the endogenous tumor suppressor miRNA-34a and the chemotherapeutic agent doxorubicin (Dox) into cancer cells. The novelty of the system resides in two stimuli-sensitive prodrugs, a matrix metalloproteinase 2 (MMP2)-sensitive Dox conjugate and a reducing agent (glutathione, GSH)-sensitive miRNA-34a conjugate, self-assembled in a single particle decorated with a polyethylene glycol corona for longevity, and a cell-penetrating peptide (TATp) for enhanced intracellular delivery. The MMP2-sensitivity of the system results in threefold higher cytotoxicity in MMP2-overexpressing HT1080 cells compared to low MMP2-expressing MCF7 cells.

Management of hyperthyroidism in children.

Treatment of hyperthyroidism in children differs according to its etiology; in particular, the optimal therapy of Graves' disease (GD) remains a matter of debate and there is currently no evidence-based therapeutic strategy that is universally adopted in all the countries. Areas covered: The most recent treatment strategies in the different pediatric conditions which may be associated with hyperthyroidism. We searched PubMed and Cochrane (1990 to 2016) in order to identify articles to include in this review using the following terms: Hyperthyroidism, Childhood, Antithyroid drug therapy, Thyroidectomy, Radioactive iodine.

Transferrin-Targeted Nanoparticles Containing Zoledronic Acid as a Potential Tool to Inhibit Glioblastoma Growth.

The treatment of glioblastoma (GBM) is a challenge for the biomedical research since cures remain elusive. Its current therapy, consisted on surgery, radiotherapy, and concomitant chemotherapy with temozolomide (TMZ), is often uneffective. Here, we proposed the use of zoledronic acid (ZOL) as a potential agent for the treatment of GBM.

Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid.

Cancer-specific drug delivery represents an attractive approach to prevent undesirable side-effects and increase the accumulation of the drug in the tumor. Surface modification of nanoparticles such as liposomes with targeting moieties specific to the up-regulated receptors on the surface of tumor cells thus represents an effective strategy. Furthermore, since this receptor expression can be heterogeneous, using a dual-combination of targeting moieties may prove advantageous.

Lipid-based siRNA Delivery Systems: Challenges, Promises and Solutions Along the Long Journey.

RNA interference (RNAi) is an evolutionary conserved highly specific gene-silencing mechanism initiated by small interfering RNA (siRNA) molecules. Fast-paced preclinical and clinical studies helped the siRNA technology become an efficient tool for undruggable targets in different diseases including genetic diseases, viral diseases and cancer. Despite great feature of siRNAs that can down-regulate any protein in the cells, the full potential and the success of the preclinical studies could not be translated into largely successful clinical outcomes.

CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis.

The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active.

Zoledronic acid-encapsulating self-assembling nanoparticles and doxorubicin: a combinatorial approach to overcome simultaneously chemoresistance and immunoresistance in breast tumors.

The resistance to chemotherapy and the tumor escape from host immunosurveillance are the main causes of the failure of anthracycline-based regimens in breast cancer, where an effective chemo-immunosensitizing strategy is lacking.The clinically used aminobisphosphonate zoledronic acid (ZA) reverses chemoresistance and immunoresistance in vitro. Previously we developed a nanoparticle-based zoledronic acid-containing formulation (NZ) that allowed a higher intratumor delivery of the drug compared with free ZA in vivo.

Use of the SMAS flap for reconstruction of the parotid lodge.

The purpose of our study was to evaluate the benefits of the SMAS flap in patients with benign tumours of the parotid gland treated by superficial parotidectomy. We carried out a retrospective chart review on 123 patients suffering from benign tumours of the parotid gland admitted to our Institution between March 1997 and March 2010. A superficial parotidectomy was performed in all the cases reported.

Bilateral hypertrophy of masseteric and temporalis muscles, our fifteen patients and review of literature.

Objective: The association of bilateral hypertrophy of temporalis and masseteric muscles is a rare clinical entity. The origin of the condition is unclear, causing cosmetic problems, pain, and functional impairment.

Patients And Methods: In this paper we analyzed 15 patients treated at the Department of Maxillo-Facial Surgery of the University of Naples Federico II, from 2000 to 2013, for temporalis and/or masseteric muscle hypertrophy, and in particular, a rare case of a patient with a marked bilateral swelling of the temporalis and masseteric region, in conjunction with a review of the literature.

Lipid Nanovectors to Deliver RNA Oligonucleotides in Cancer.

The growing knowledge on the mechanisms of gene silencing and gene regulation by non-coding RNAs (ncRNA), mainly small interfering RNA (siRNA) and microRNA (miRNA), is providing a significant boost to the development of new therapeutic strategies for the treatment of cancer. However, the design of RNA-based therapeutics is hampered by biopharmaceutical issues, thus requiring the use of suitable delivery strategies. In this regards, lipid nanovectors have been successfully investigated to deliver RNA in different forms of cancer.

Recent advances in siRNA delivery.

In the 1990s an unexpected gene-silencing phenomena in plants, the later called RNA interference (RNAi), perplexed scientists. Following the proof of activity in mammalian cells, small interfering RNAs (siRNAs) have quickly crept into biomedical research as a new powerful tool for the potential treatment of different human diseases based on altered gene expression. In the past decades, several promising data from ongoing clinical trials have been reported.

siRNA Delivery by Stimuli-Sensitive Nanocarriers.

Since its discovery in the late 1990, small interfering RNA (siRNA) have quickly crept into the biopharmaceutical research as a new and powerful tool for the treatment of different human diseases based on altered gene-expression. Despite promising data from many pre-clinical studies, concrete hurdles still need to be overcome to bring therapeutic siRNAs in clinic. The design of stimuli-sensitive nanopreparations for gene therapy is a lively area of the current research.

The non-octarepeat copper binding site of the prion protein is a key regulator of prion conversion.

The conversion of the prion protein (PrP(C)) into prions plays a key role in transmissible spongiform encephalopathies. Despite the importance for pathogenesis, the mechanism of prion formation has escaped detailed characterization due to the insoluble nature of prions. PrP(C) interacts with copper through octarepeat and non-octarepeat binding sites.

Self-assembling nanoparticles encapsulating zoledronic acid revert multidrug resistance in cancer cells.

The overexpression of ATP binding cassette (ABC) transporters makes tumor cells simultaneously resistant to several cytotoxic drugs. Impairing the energy metabolism of multidrug resistant (MDR) cells is a promising chemosensitizing strategy, but many metabolic modifiers are too toxic in vivo. We previously observed that the aminobisphosphonate zoledronic acid inhibits the activity of hypoxia inducible factor-1a (HIF-1a), a master regulator of cancer cell metabolism.

Intracellular Delivery of Nanoparticles with Cell Penetrating Peptides.

The functionalization of nanoparticles (NPs) with cell penetrating peptides (CPPs) constitutes a breakthrough for the intracellular delivery of therapeutic and diagnostic payloads. In late 1998, a significant cellular uptake of a small protein from the HIV-1 virus, namely TAT peptide (TATp), was observed. Thereafter, research began on design of similarly acting peptides, and the coupling of NPs with these novel CPPs.

Early Discrimination between Transient and Permanent Congenital Hypothyroidism in Children with Eutopic Gland.

Aim: To analyze the factors that might allow an early discrimination between permanent (P) and transient (T) congenital hypothyroidism (CH).

Methods: Clinical, biochemical and imaging data of 64 children with eutopic gland, who were positively screened and treated for CH during the period 1998-2011, were retrospectively analyzed.

Results: During a 3-year treatment period, the mean doses of L-thyroxine (L-T4) per kilogram of body weight at various times were significantly lower in the 46 children with T CH than in the remaining 18 with P CH.

Facial osteomas: fourteen cases and a review of literature.

Objective: Osteomas are benign tumors that frequently affect the cranio-facial region, especially the temporal bones, jaw and sinus. This lesion very rarely involves the maxillary bones. The aim of our study is to describe our surgical case series and to evaluate the diagnosis and management of peripheral craniofacial osteomas with a review of the literature.

Assessment of the genetic polymorphism and physiological characterization of indigenous Oenococcus oeni strains isolated from Aglianico del Vulture red wine.

The aim of this study was a reliable intra-species discrimination and strain biodiversity in Oenococcus oeni populations of two different Aglianico wineries by molecular, biochemical, and physiological characterization. Pulsed field gel electrophoresis (PFGE) analysis revealed a high polymorphism related to the origin (winery) of strains, while differential display PCR (DD-PCR) allowed a further discrimination of strains from the same winery. Moreover, the heterogeneity of these natural populations was investigated by capillary electrophoresis and enzymatic assays.

Mucoepidermoid carcinoma of the base of tongue.

Mucoepidermoid carcinoma (MEC) is the most common malignant, locally-invasive tumour of the salivary glands, and accounts for approximately 35% of all malignancies of the major and minor salivary gland. Minor salivary glands are scattered in different areas of the oral cavity such as palate, retromolar area, floor of the mouth, buccal mucosa, lips and tongue. MECs of tongue base are not common.

Peculiarities of autoimmune thyroid diseases in children with Turner or Down syndrome: an overview.

Unlabelled: Aim of this commentary is to summarize the salient literature news on the relationships between autoimmune thyroid diseases (ATDs) and either Down syndrome (DS) or Turner syndrome (TS).According to literature reports both Hashimoto's thyroiditis (HT) and Graves' disease (GD) are more frequent in children with DS or TS than in those without these chromosomopathies.An up-regulation of proinflammatory cytokines might be responsible for the enhanced susceptibility of TS children to ATDs, whereas a dysregulation of immune system may favor the development of ATDs in DS.

Comparative study between partial inferior turbinotomy and microdebrider-assisted inferior turbinoplasty.

Purpose: The purpose of our study was to compare the inferior turbinotomy and the microdebrider-assisted inferior turbinoplasty in patients with hypertrophy of the inferior turbinate.

Material And Methods: We carried out a retrospective review of 205 patients, 96 women and 109 men, with a mean age of 48 years, operated on for hypertrophy of the inferior turbinate between May 2005 and May 2012. Forty-seven patients were excluded from our study because in these patients, nasal obstruction was caused by a specific pathologic condition (allergy, tumors or polyps, recurrent rhinosinusitis, etc).

Warthin's tumour: Aetiopathogenesis dilemma, ten years of our experience.

Despite the volume of studies written after the initial report by Hildebrand (1895) on Warthin's tumour (WT), its aetiopathogenesis continues to be an unresolved and controversial question. Many different genetic and/or environmental aetiological factors seem to act on heterotopic ductal inclusions and may give rise to WT following an unknown tumorigenic event. Recent studies discussed the importance of immunological reactions during the formation of the tumour.

Multifunctional Polymeric Micelles Co-loaded with Anti-Survivin siRNA and Paclitaxel Overcome Drug Resistance in an Animal Model of Ovarian Cancer.

Ovarian cancer is a dreadful disease estimated to be the second most common gynecologic malignancy worldwide. Its current therapy, based on cytoreductive surgery followed by the combination of platinum and taxanes, is frequently complicated by the onset of multidrug resistance (MDR). The discovery that survivin, a small antiapoptotic protein, is involved in chemoresistance provided a new prospect to overcome MDR in cancer, because siRNA could be used to inhibit the expression of survivin in cancer cells.

Survey on etiological diagnosis of diabetes in 1244 Italian diabetic children and adolescents: impact of access to genetic testing.

Type 2 and monogenic diabetes are emerging causes of diabetes in youths. Among 1244 Italian patients <18 years of age, 91.9% had type 1, 0.

Head and neck myxofibrosarcoma: a case report and review of the literature.

Introduction: Myxofibrosarcoma is the most common soft tissue sarcoma that occurs in late adult life, peaking in the seventh decade, and it is mainly encountered in the lower extremities. Myxofibrosarcoma of the head and neck are extremely rare. To the best of our knowledge, only 19 cases have been described in the head and neck so far.