DEK::AFF2 Fusion Sinonasal and Skull Base Nonkeratinizing Squamous Cell Carcinoma: A Clinical Outcome Study Compared With Conventional Sinonasal Squamous Cell Carcinoma.

DEK::AFF2 fusion nonkeratinizing squamous cell carcinoma (NKSCC) is an emerging entity in the sinonasal tract, temporal bone, and skull base. However, the clinical behavior of these tumors has not been well studied. Here, we report the largest cohort of DEK::AFF2 carcinomas to determine if morphology, mitotic rate, and/or Ki-67 IHC are associated with patient outcomes, including a comparison with high-risk human papillomavirus (HPV)-associated and independent patients.

A Cone Beam CT Bronchoscopy Study of the Ultrathin Cryoprobe for Biopsy of Peripheral Lung Lesions.

Background: Compared with the standard cryoprobe, the novel ultrathin 1.1 mm cryoprobe (UTCP) has improved ergonomics, shape memory, and flexibility. The performance of UTCP has demonstrated promising results in several small trials.

Association of Meier-Gorlin and microcephalic osteodysplastic primordial dwarfism type II clinical features in an individual with CDK5RAP2 primary microcephaly.

Autosomal recessive primary microcephaly type 3 (MCPH3) caused by pathogenic variations in CDK5RAP2, is characterized by sensorineural hearing loss, abnormality of skin pigmentation, ocular defects and severe microcephaly associated with neurodevelopmental delay. In this study, we expand the phenotype of MCPH3 as we describe a 10-year-old girl with a biallelic exonic frameshift variant in CDK5RAP2 displaying previously unreported features usually associated with Meier-Gorlin and microcephalic osteodysplastic primordial dwarfism type II (MOPDII). We further describe the clinical phenotype of this form of centrosomal-based primary microcephaly and emphasize the importance of skeletal defect screening in affected individuals.

Smart PEG-Block-PLA/PLA Nanosystems: Impact of the Characteristics of the Polymer Blend on the Redox Responsiveness.

Nanocarriers (NCs) were designed from three polymer blends (B1, B2 and B3) and investigated as smart drug delivery systems (SDDS). The blends are composed of a "smart" copolymer, where methoxy poly(ethylene glycol) and poly(lactic acid) are connected via a redox-responsive disulfide bond (mPEG-SS-PLA), and of a "conventional" polymer, poly(lactic acid) (PLA). They differ by mPEG-SS-PLA/PLA ratio and PLA molecular weight.

Formulation of Lipid-Based Nanoparticles for Simultaneous Delivery of Lapatinib and Anti-Survivin siRNA for HER2+ Breast Cancer Treatment.

In this work, lipid-based nanoparticles (LBNP) were designed to combine tyrosine kinase inhibitor (TKI) Lapatinib (LAPA) with siRNA directed against apoptosis inhibitor protein Survivin (siSurvivin) in an injectable form. This nanosystem is based on lipid nanocapsules (LNCs) coated with a cationic polymeric shell composed of chitosan grafted through a transacylation reaction. The hydrophobic LAPA is solubilized in the inner oily core, while hydrophilic siRNA is associated electrostatically onto the nanocarrier’s surface.

Combination of Nanovectorized siRNA Directed against Survivin with Doxorubicin for Efficient Anti-Cancer Activity in HER2+ Breast Cancer Cells.

According to Globocan 2020, breast cancer is considered one of the most common cancers affecting women and is one of the leading causes of death in over 100 countries. The available classical treatment options do not always give satisfactory outcomes, and some patients develop resistance to these treatments. This study aims to investigate the combination of nanovectorized siRNA directed against anti-apoptotic protein Survivin (siSurvivin) by targeted stealth magnetic siRNA nanovectors (TS-MSN), designed in our lab, with Doxorubicin (DOX), as an option for HER2+ breast cancer treatment.

synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model.

Apoptosis is an important process that directly affects the response of cancer cells to anticancer drugs. Among different factors involved in this process, the BcL-xL protein plays a critical role in inhibiting apoptosis induced by chemotherapy agents. Henceforth, its downregulation may have a synergistic activity that lowers the necessary dose of anticancer agents.

WITHDRAWN: In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model.

This article was withdrawn from International Journal of Pharmaceutics in order to be published in International Journal of Pharmaceutics: X. The Publisher apologizes for any inconvenience this may cause.

Nanoparticles design considerations to co-deliver nucleic acids and anti-cancer drugs for chemoresistance reversal.

Chemoresistance and hence the consequent treatment failure is considerably challenging in clinical cancer therapeutics. The understanding of the genetic variations in chemoresistance acquisition encouraged the use of gene modulatory approaches to restore anti-cancer drug efficacy. Many smart nanoparticles are designed and optimized to mediate combinational therapy between nucleic acid and anti-cancer drugs.

Two-step formulation of magnetic nanoprobes for microRNA capture.

MicroRNAs (miRs) belong to a family of short non-coding endogenous RNAs. Their over-expression correlates with various pathologies: for instance, miRNA-155 (miR-155) is over-expressed upon the development of breast cancers. However, the detection of miRs as disease biomarkers suffers from insufficient sensitivity.

Targeted nanomedicine with anti-EGFR scFv for siRNA delivery into triple negative breast cancer cells.

A targeted nanomedicine with humanized anti-EGFR scFv (NM-scFv) was developed for siRNA delivery into triple negative breast cancer (TNBC) cells. NM-scFv consisted of i) targeted nanovector (NV-scFv): nano-cargo with targeting properties; ii) siRNA: pharmacological agent and iii) cationic polymers (chitosan, poly-L-arginine): for siRNA complexation and endosomal escape. NV-scFv was based on superparamagnetic nanoparticle (SPION) labeled with Dylight™680, a PEG layer and a humanized anti-EGFR scFv.

Homogeneous distribution of fatty ester-based active cosmetic ingredients in hydrophilic thin films by means of nanodispersion.

Objective: Cosmetic films and patches are interesting forms to promote skin penetration of active ingredients as they ensure their long stay on the treated zone of the skin. Nevertheless, currently developed films and patches are most of all hydrophilic and are not adapted to the hydrophobic molecules. The aim of this study was to establish whether nanodispersion of fatty acid-based active cosmetic ingredients (ACI) could be a manner to introduce high concentrations of those ACI in hydrophilic films.

Model Affitin and PEG modifications onto siRNA lipid nanocapsules: cell uptake and biodistribution improvements.

Malignant melanoma is an aggressive tumor, associated with the presence of local and/or distant metastases. The development of gene therapy by the use of small interfering RNA (siRNA) represents a promising new treatment. However, the protection of this biomolecule is necessary in order for it to be intravenously administrated, for example its incorporation into nanomedicines.

gH625 Cell-Penetrating Peptide Promotes the Endosomal Escape of Nanovectorized siRNA in a Triple-Negative Breast Cancer Cell Line.

The use of small interfering RNA (siRNA) to regulate oncogenes appears as a promising strategy in the context of cancer therapy, especially if they are vectorized by a smart delivery system. In this study, we investigated the cellular trafficking of a siRNA nanovector (called CS-MSN) functionalized with the cell-penetrating peptide gH625 in a triple-negative breast cancer model. With complementary techniques, we showed that siRNA nanovectors were internalized by both clathrin- and caveolae-mediated endocytosis.

Formulation and in vitro evaluation of a siRNA delivery nanosystem decorated with gH625 peptide for triple negative breast cancer theranosis.

The development of an efficient small interfering RNA (siRNA) delivery system has held scientists interest since the discovery of the RNA interference mechanism (RNAi). This strategy gives hope for the treatment of many severe diseases. Herein, we developed hybrid nanovectors able to deliver siRNA to triple negative breast cancer cells.

Subsequent breast and high grade serous carcinomas after risk-reducing salpingo-oophorectomy in BRCA mutation carriers and patients with history of breast cancer.

Risk-reducing salpingo-oophorectomy (RRSO) is a procedure to reduce the risk of adnexal cancer in BRCA mutation carriers and for hormonal manipulation in women with breast cancer (BC). The goal of the study is to report the frequency of subsequent BC and high-grade serous carcinoma (HGSC) following RRSO in BRCA1 and BRCA2 mutation carriers and in patients with personal history of BC with or without BRCA mutation. A series of 147 consecutive patients who received a RRSO were reviewed.

MAGI2 is an independent predictor of biochemical recurrence in prostate cancer.

Background: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer.

Correlation between invasive mammary carcinoma grade and size in ultrasound-guided core needle biopsy and subsequent surgical excision.

The purpose of this study was to correlate the histologic grade, mitotic rate and size of invasive mammary carcinomas (IMC) on ultrasound (US) core needle biopsy (CNB) and the follow-up excision (FUE). The underestimation and overestimation of the grades by CNB were 11% and 8%. CNBs were more specific for grade 3 tumors.

siRNA delivery system based on magnetic nanovectors: Characterization and stability evaluation.

Gene therapy and particularly small interfering RNA (siRNA) is a promising therapeutic method for treatment of various human diseases, especially cancer. However the lack of an ideal delivery system limits its clinical applications. Effective anticancer drug development represents the key for translation of research advances into medicines.

Identification of partial SLC20A2 deletions in primary brain calcification using whole-exome sequencing.

Primary brain calcification (PBC) is a dominantly inherited calcifying disorder of the brain. SLC20A2 loss-of-function variants account for the majority of families. Only one genomic deletion encompassing SLC20A2 and six other genes has been reported.

Incidental placenta increta at the time of prophylactic hysterectomy for Lynch syndrome: Insights into individualized decision-making and surgical timing.

•Increta in a prophylactic hysterectomy specimen for Lynch syndrome is rare.•Individualizing risk-reducing procedures after childbearing is important.•Shared decision making should include the timing of prophylactic surgery.

Testing spatial measures of alcohol outlet density with self-rated health in the Australian context: Implications for policy and practice.

Introduction And Aims: Reducing access to alcohol is an important and cost-effective strategy for decreasing alcohol consumption and associated harm. Yet this is a less common approach to alcohol control in Australia. The aim of this research was to ascertain which alcohol outlet density spatial measures were related to long-term health outcomes, and the extent to which this differs for those living in more or less disadvantaged neighbourhoods.

Modelling the response surface to predict the hydrodynamic diameters of theranostic magnetic siRNA nanovectors.

Short interfering RNAs (siRNAs) appear to be a promising tool to treat various human diseases, such as cancer via the RNA interference (RNAi) mechanism. Since the systemic administration of siRNAs is limited by their capacity to attain the site of action, novel delivery systems are needed. Previously, we reported the formulation of magnetic siRNA nanovectors (MSN) using electrostatic assembly of the following components: (1) functionalized superparamagnetic iron oxide nanoparticles (SPIONs) able to act as agents for magnetic resonance imaging (MRI) and/or thermal therapy, (2) siRNAs as active molecules and (3) chitosan to protect siRNAs and to enhance their transfection efficacy.

Use of experimental design methodology for the development of new magnetic siRNA nanovectors (MSN).

Short interfering RNAs (siRNAs) can downregulate the synthesis of proteins and thus be used to treat certain diseases where the protein synthesis is upregulated, such as cancer. The challenge is to deliver siRNAs in the target cell as they are rapidly degraded by nucleases and have difficulties to cross the cellular membranes. Superparamagnetic iron oxide nanoparticles (SPIONs) are widely studied as platforms for smart biocompatible nanosystems which can be used for magnetic drug targeting and magnetic resonance imaging.