Preclinical Pharmacokinetics in Tumors and Normal Tissues of the Antigene PNA Oligonucleotide MYCN-Inhibitor BGA002.

Although has been considered an undruggable target, alterations confer poor prognosis in many pediatric and adult cancers. The novel -specific inhibitor BGA002 is an antigene peptide nucleic acid oligonucleotide covalently bound to a nuclear localization signal peptide. In the present study, we characterized the pharmacokinetics (PK) of BGA002 after single and repeated administration to mice using a novel specific enzyme-linked immunosorbent assay.

The role of laboratory medicine in a value-based healthcare system: the example of heart failure patient management in the Italian context.

Objective: As of today, healthcare systems worldwide face severe challenges that undermine their sustainability. The value-based healthcare (VBHC) approach has been proposed as a strategic and methodological framework to ensure the delivery of the best patient outcomes with economic efficiency. Through the illustrative example of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) for heart failure (HF) patient management in the context of the Italian National Healthcare system, this article explores the role that in vitro diagnostics (IVDs) can play in enabling value-based care models.

Effect of Brewing Methods on Acrylamide Content and Antioxidant Activity: Studying Eight Different Filter Coffee Preparations.

The aim of this study was to investigate the parameters affecting the extraction of positive molecules such as chlorogenic acids and antioxidants, as well as potentially carcinogenic substances such as acrylamide, in different coffee brewing methods. Three coffee varieties, each assigned a different roasting degree, were used to prepare coffee brews following eight different preparation methods. Acrylamide was quantified using the HPLC-MS/MS instrument, while chlorogenic acids and caffeine were quantified using the HPLC-DAD system.

Antigene Silencing by BGA002 Inhibits SCLC Progression Blocking mTOR Pathway and Overcomes Multidrug Resistance.

Small-cell lung cancer (SCLC) is the most aggressive lung cancer type, and is associated with smoking, low survival rate due to high vascularization, metastasis and drug resistance. Alterations in family members are biomarkers of poor prognosis for a large number of SCLC. In particular, alterations define SCLC cases with immunotherapy failure.

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.

Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features.

Precision Anti-Cancer Medicines by Oligonucleotide Therapeutics in Clinical Research Targeting Undruggable Proteins and Non-Coding RNAs.

Cancer incidence and mortality continue to increase, while the conventional chemotherapeutic drugs confer limited efficacy and relevant toxic side effects. Novel strategies are urgently needed for more effective and safe therapeutics in oncology. However, a large number of proteins are considered undruggable by conventional drugs, such as the small molecules.

The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma.

Background: Neuroblastoma is a deadly childhood cancer, and MYCN-amplified neuroblastoma (MNA-NB) patients have the worst prognoses and are therapy-resistant. While retinoic acid (RA) is beneficial for some neuroblastoma patients, the cause of RA resistance is unknown. Thus, there remains a need for new therapies to treat neuroblastoma.

Spiral wire localization of lung nodules: procedure effectiveness and oncological usefulness.

Background: In the last years, a large number of techniques and devices for localizing small pulmonary nodules prior to resection have been developed with the aim of facilitating minimally invasive surgery (VATS). However, each device presents pros and cons and there is no unanimous consensus. We report our experience with an uncommon wire system with spiral shape for percutaneous marking.

A Novel MYCN-Specific Antigene Oligonucleotide Deregulates Mitochondria and Inhibits Tumor Growth in MYCN-Amplified Neuroblastoma.

Approximately half of high-risk neuroblastoma is characterized by MYCN amplification. N-Myc promotes tumor progression by inducing cell growth and inhibiting differentiation. MYCN has also been shown to play an active role in mitochondrial metabolism, but this relationship is not well understood.

Single-row vs. double-row arthroscopic rotator cuff repair: clinical and 3 Tesla MR arthrography results.

Background: Arthroscopic rotator cuff repair has become popular in the last few years because it avoids large skin incisions and deltoid detachment and dysfunction. Earlier arthroscopic single-row (SR) repair methods achieved only partial restoration of the original footprint of the tendons of the rotator cuff, while double-row (DR) repair methods presented many biomechanical advantages and higher rates of tendon-to-bone healing. However, DR repair failed to demonstrate better clinical results than SR repair in clinical trials.

Percutaneous decompression of lumbar spinal stenosis with a new interspinous device.

Objective: This study was designed to evaluate the feasibility of the implantation of a new interspinous device (Falena) in patients with lumbar spinal stenosis. The clinical outcomes and imaging results were assessed by orthostatic MR during an up to 6-month follow-up period.

Methods: Between October 2008 and February 2010, the Falena was implanted at a single level in 26 patients (17 men; mean age, 69 (range, 54-82) years) who were affected by degenerative lumbar spinal stenosis.

Percutaneous ablative treatment of metastatic bone tumours: visual analogue scale scores in a short-term series.

Introduction: The aim of this study was to examine the role of palliative percutaneous secondary lesions bone treatment by comparing the visual analogue scale (VAS) scores of cryoablation plus vertebroplasty versus radiofrequency (RF) plus vertebroplasty so as to determine their feasibility, reliability and efficacy in a short-term series.

Methods: Combined RF thermal ablation plus osteoplasty or cryoablation plus osteoplasty was performed in osteolytic secondary bone localisations in 30 consecutive patients who were suffering from pain refractory to conservative therapies. We evaluated pain with the VAS during the preoperative period and at four hours, 24 hours, one week, one month, three months and six months post procedure.

Future directions in percutaneous vertebroplasty.

The first percutaneous vertebroplasty, used to treat a painful cervical haemangioma, was performed by a French team in 1984 and reported in the literature in 1987. This technique has rapidly become the standard of care for treatment of medically refractory painful vertebral compression fractures. Vertebral fractures usually become evident because of pain of varying intensity that reduces the patient's quality of life, producing functional limitations, depression, disability, height loss, spinal instability and kyphotic deformity associated with impaired lung capacity.

Percutaneous cryoablation and vertebroplasty: a case report.

A 70-year-old man with a painful vertebral metastasis was treated with combined percutaneous cryoablation and vertebroplasty therapy (CVT) in one session. The patient was suffering from diffuse visceral metastasized cholangiocarcinoma. After several weeks of back pain, magnetic resonance imaging documented a single L2 bone metastasis.

Malignant renal neoplasms: correlation between ADC values and cellularity in diffusion weighted magnetic resonance imaging at 3 T.

Purpose: This study aimed at exploring the feasibility of high-field diffusion-weighted magnetic resonance imaging (DW-MRI) (3 T) and to correlate apparent diffusion coefficient (ADC) values with tumour cellularity in renal malignancies.

Materials And Methods: Thirty-seven patients (ten healthy volunteers and 27 patients with suspected renal malignancy) underwent T1-, T2-weighted and T1-weighted contrast-enhanced magnetic resonance imaging (MRI). Diffusion-weighted images were obtained with a single-shot spin-echo echo-planar imaging (SE-EPI) sequence with a b value of 500 s/mm(2).

Percutaneous combined therapy for painful sternal metastases: a radiofrequency thermal ablation (RFTA) and cementoplasty protocol.

Background: Radiofrequency thermal ablation (RFTA) has recently been introduced for the treatment of painful bone metastases. We report the outcome of one combined protocol session of percutaneous RFTA and cementoplasty on a painful sternal breast cancer metastasis of a 66-year-old patient.

Patients And Methods: A sternal lesion was identified at a repeated CT scan during the oncological follow-up.