Novel Macrocyclic NLRP3 Inhibitors.

Aberrant activation of NLRP3 due to persistent tissue damage, misfolded proteins or crystal deposits has been linked to multiple chronic inflammatory disorders such as cryopyrin-associated periodic syndrome (CAPS), neurodegenerative diseases, gouty arthritis, and numerous others. Hence, there has been an increasing interest in NLRP3 inhibitors as therapeutics. A first generation of NLRP3 inhibitors bearing a sulfonylurea core such as MCC950 (developed by Pfizer) were discovered by phenotypic screening, however their mode of action was only elucidated later.

High-Throughput Screening Using iPSC-Derived Neuronal Progenitors to Identify Compounds Counteracting Epigenetic Gene Silencing in Fragile X Syndrome.

Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused in most of cases by epigenetic silencing of the Fmr1 gene. Today, no specific therapy exists for FXS, and current treatments are only directed to improve behavioral symptoms. Neuronal progenitors derived from FXS patient induced pluripotent stem cells (iPSCs) represent a unique model to study the disease and develop assays for large-scale drug discovery screens since they conserve the Fmr1 gene silenced within the disease context.

Clinical added-value of 18FDG PET in neuroendocrine-merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer with neuroendocrine differentiation. We studied the potential value of 18FDG PET in the management of MCC. Eleven patients with MCC were examined by 18FDG PET and PET-CT for staging purpose (n=4) or for detection of recurrence (n=7).

18F-FDG PET in children with lymphomas.

Purpose: The aim of this study was to retrospectively evaluate the performance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in children with lymphomas, at various stages of their disease.

Methods: Twenty-eight children (mean age 12.5 years, 14 girls, 14 boys) with Hodgkin's disease (HD, n=17) or non-Hodgkin's lymphoma (NHL, n=11) were evaluated.

Fluorinated tracers for imaging cancer with positron emission tomography.

2-[18F]fluoro-2-deoxy-D-glucose (FDG) is currently the only fluorinated tracer used in routine clinical positron emission tomography (PET). Fluorine-18 is considered the ideal radioisotope for PET imaging owing to the low positron energy (0.64 MeV), which not only limits the dose rate to the patient but also results in a relatively short range of emission in tissue, thereby providing high-resolution images.

In vivo imaging of chemotherapy-induced apoptosis in human cancers.

Rationale: Induction of apoptosis in sensitive tumor cells is the main mechanism of action of chemotherapy agents in human cancers. Also, the assessment of drug-induced apoptosis soon after chemotherapy may be an early predictor of treatment efficacy.

Patients And Methods: A phase I/II study was prospectively conducted in 15 patients presenting with proven lung cancers (n = 10), breast cancers (n = 2), and lymphomas (n = 3) to assess the value of the (99m)Tc-radiolabeled recombinant human (rh) Annexin V for imaging apoptosis immediately after completion of the first course of chemotherapy.

Staging of primary cervical cancers: the role of nuclear medicine.

In nuclear medicine, [18F]-fluorodeoxyglucose positron emission tomography (18FDG PET) and lymphatic mapping and sentinel lymphadenectomy (LM/SL) may significantly improve the staging of primary cervical cancers. Indeed, the disease progresses in a 'level by level' fashion to regional nodes through the lymphatic channels, and also to extra-nodal sites via the hematogenous stream. Additionally, the sub-optimal efficacy of routine radiological protocols, while new combined therapies are proving to be more efficient, stresses the need for alternative staging procedures.

Contribution of whole-body 18FDG PET imaging in the management of cervical cancer.

Objective: The objective of this study was to assess the contribution of [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG PET) imaging in the management of cervical cancer.

Methods: Fully corrected whole-body PET was performed in 60 patients (pts) with proven cervical cancer. In pretreatment staging, 22 pts underwent PET in addition to routine protocol including International Federation of Obstetrics and Gynecology (FIGO) staging and pelvic magnetic resonance imaging (MRI).

Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis.

Purpose: Many anticancer therapies exert their therapeutic effect by inducing apoptosis in target tumors. We evaluated in a Phase I study the safety and the feasibility of (99m)Tc-Annexin V for imaging chemotherapy-induced apoptosis in human cancers immediately after the first course of chemotherapy.

Experimental Design: Fifteen patients presenting with lung cancer (n = 10), lymphoma (n = 3), or breast cancer (n = 2) underwent (99m)Tc-Annexin V scintigraphy before and within 3 days after their first course of chemotherapy.

Staging of regional nodes in AJCC stage I and II melanoma: 18FDG PET imaging versus sentinel node detection.

Primary Purpose: The staging of regional nodes by means of sentinel node detection has been shown to accurately detect subclinical nodal metastases from cutaneous melanoma. On the other hand, the oncological applications of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG PET) are, nowadays, firmly established. However, the sensitivity of such metabolic imaging for staging the regional nodes in primary melanoma remains debatable.