Re-design and evaluation of diclofenac-based carborane-substituted prodrugs and their anti-cancer potential.

In this study, we investigated a novel anti-cancer drug design approach by revisiting diclofenac-based carborane-substituted prodrugs. The redesigned compounds combine the robust carborane scaffold with the oxindole framework, resulting in four carborane-derivatized oxindoles and a unique zwitterionic amidine featuring a nido-cluster. We tested the anti-cancer potential of these prodrugs against murine colon adenocarcinoma (MC38), human colorectal carcinoma (HCT116), and human colorectal adenocarcinoma (HT29).

Cost-effectiveness analysis of radiofrequency renal denervation for uncontrolled hypertension in Canada.

Aims: Catheter-based radiofrequency renal denervation (RF RDN) is an interventional treatment for uncontrolled hypertension. This analysis explored the therapy's lifetime cost-effectiveness in a Canadian healthcare setting.

Materials And Methods: A decision-analytic Markov model was used to project health events, costs, and quality-adjusted life years over a lifetime horizon.

Cost-effectiveness of TAVI in the United Kingdom: a long-term analysis based on 4-year data from the Evolut Low Risk Trial.

Background: The cost-effectiveness of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) has previously been reported across the spectrum of surgical mortality risk. We present an updated analysis specific to the UK based on 4-year data from the Evolut Low Risk Trial, which showed a maintained numerical survival benefit with TAVI.

Catheter-Based Radiofrequency Renal Denervation in the United States: A Cost-Effectiveness Analysis Based on Contemporary Evidence.

Background: Catheter-based radiofrequency renal denervation (RF RDN) has recently been approved as an adjunctive treatment for hypertensive patients without adequate blood pressure control. This study assessed the cost-effectiveness of RF RDN in the United States based on contemporary clinical evidence.

Methods: A decision-analytic Markov model projected costs, quality-adjusted life years (QALY), and clinical events for an active cohort treated with RF RDN and a control cohort treated with standard-of-care (defined as 1, 2, or 3 antihypertensive medications).

Cost-Effectiveness of Radiofrequency Renal Denervation for Uncontrolled Hypertension in Japan.

Radiofrequency renal denervation (RF RDN) is a novel therapy for uncontrolled hypertension. In the recent sham-controlled SPYRAL HTN-ON MED study, office-based systolic blood pressure (oSBP) and nighttime BP were reduced significantly. This study examined the cost-effectiveness of RF RDN in the context of the Japanese healthcare system based on this latest clinical evidence.

Combined PET Radiotracer Approach Reveals Insights into Stromal Cell-Induced Metabolic Changes in Pancreatic Cancer In Vitro and In Vivo.

Pancreatic stellate cells (PSCs) in pancreatic adenocarcinoma (PDAC) are producing extracellular matrix, which promotes the formation of a dense fibrotic microenvironment. This makes PDAC a highly heterogeneous tumor-stroma-driven entity, associated with reduced perfusion, limited oxygen supply, high interstitial fluid pressure, and limited bioavailability of therapeutic agents. In this study, spheroid and tumor xenograft models of human PSCs and PanC-1 cells were characterized radiopharmacologically using a combined positron emission tomography (PET) radiotracer approach.

The heterobivalent (SSTR2/albumin) radioligand [Cu]Cu-NODAGA-cLAB4-TATE enables efficient somatostatin receptor radionuclide theranostics.

Somatostatin type 2 receptor (SSTR2) radionuclide therapy using β particle-emitting radioligands has entered clinical practice for the treatment of neuroendocrine neoplasms (NENs). Despite the initial success of [Lu]Lu‑DOTA-TATE, theranostic SSTR2 radioligands require improved pharmacokinetics and enhanced compatibility with alternative radionuclides. Consequently, this study evaluates the pharmacokinetic effects of the albumin-binding domain cLAB4 on theranostic performance of copper‑67-labeled NODAGA-TATE variants in an SSTR2-positive mouse pheochromocytoma (MPC) model.

Cyclohexanediamine Triazole (CHDT) Functionalization Enables Labeling of Target Molecules with AlF/Ga/In.

The AlF-labeling approach offers a one-step access to radiofluorinated biomolecules by mimicking the labeling process for radiometals. Although these labeling conditions are considered to be mild compared to classic radiofluorinations, improvements of the chelating units have led to the discovery of , which allows AlF-labeling already at ambient temperature. While the suitability of for functionalization and radiofluorination of proteins is well established, its use for small molecules or peptides is less explored.

Programmable Release of Chemotherapeutics from Ferrocene-Based Injectable Hydrogels Slows Melanoma Growth.

Hydrogel-based injectable drug delivery systems provide temporally and spatially controlled drug release with reduced adverse effects on healthy tissues. Therefore, they represent a promising therapeutic option for unresectable solid tumor entities. In this study, a peptide-starPEG/hyaluronic acid-based physical hydrogel is modified with ferrocene to provide a programmable drug release orchestrated by matrix-drug interaction and local reactive oxygen species (ROS).

Carborane Conjugates with Ibuprofen, Fenoprofen and Flurbiprofen: Synthesis, Characterization, COX Inhibition Potential and In Vitro Activity.

The most effective anticancer drugs currently entail substantial and formidable side effects, and resistance of tumors to chemotherapeutic agents is a further challenge. Thus, the search for new anticancer drugs as well as novel therapeutic methods is still extremely important. Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit COX (cyclooxygenase), overexpressed in some tumors.

Cu tumor labeling with hexadentate picolinic acid-based bispidine immunoconjugates.

Discussed are two picolinate appended bispidine ligands (3,7-diazabicyclo[3.3.1]nonane derivatives) in comparison with an earlier described bis-pyridine derivative, which are all known to strongly bind Cu.

Impact of Viscosity on Human Hepatoma Spheroids in Soft Core-Shell Microcapsules.

The extracellular environment regulates the structures and functions of cells, from the molecular to the tissue level. However, the underlying mechanisms influencing the organization and adaptation of cancer in three-dimensional (3D) environments are not yet fully understood. In this study, the influence of the viscosity of the environment is investigated on the mechanical adaptability of human hepatoma cell (HepG2) spheroids in vitro, using 3D microcapsule reactors formed with droplet-based microfluidics.

Cost-effectiveness of catheter-based radiofrequency renal denervation for the treatment of uncontrolled hypertension: an analysis for the UK based on recent clinical evidence.

Aims: Catheter-based radiofrequency renal denervation (RF RDN) has recently been approved for clinical use in the European Society of Hypertension guidelines and by the US Food and Drug Administration. This study evaluated the lifetime cost-effectiveness of RF RDN using contemporary evidence.

Methods And Results: A decision-analytic model based on multivariate risk equations projected clinical events, quality-adjusted life years (QALYs), and costs.

Preclinical evaluation of an F-labeled N-acryloyllysine piperazide for covalent targeting of transglutaminase 2.

Background: Transglutaminase 2 (TGase 2) is a multifunctional protein and has a prominent role in various (patho)physiological processes. In particular, its transamidase activity, which is rather latent under physiological conditions, gains importance in malignant cells. Thus, there is a great need of theranostic probes for targeting tumor-associated TGase 2, and targeted covalent inhibitors appear to be particularly attractive as vector molecules.

Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments.

Radionuclide therapies are an important tool for the management of patients with neuroendocrine neoplasms (NENs). Especially [I]MIBG and [Lu]Lu-DOTA-TATE are routinely used for the treatment of a subset of NENs, including pheochromocytomas, paragangliomas and gastroenteropancreatic tumors. Some patients suffering from other forms of NENs, such as medullary thyroid carcinoma or neuroblastoma, were shown to respond to radionuclide therapy; however, no general recommendations exist.

Radiosynthesis and biological evaluation of [F]AG-120 for PET imaging of the mutant isocitrate dehydrogenase 1 in glioma.

Glioma are clinically challenging tumors due to their location and invasiveness nature, which often hinder complete surgical resection. The evaluation of the isocitrate dehydrogenase mutation status has become crucial for effective patient stratification. Through a transdisciplinary approach, we have developed an F-labeled ligand for non-invasive assessment of the IDH1R132H variant by using positron emission tomography (PET) imaging.

Cost-Effectiveness of Tonic Motor Activation (TOMAC) Therapy for Patients with Restless Legs Syndrome: An Exploratory Analysis.

Introduction: Tonic motor activation (TOMAC) therapy is a novel non-pharmacologic treatment approach for patients suffering from medication-refractory restless legs syndrome (RLS). The objective of this study was to explore the potential cost-effectiveness of TOMAC in the US healthcare system.

Methods: A decision-analytic Markov model was constructed to project strategy-specific treatment costs and benefits over 3 years and lifetime.

Cost associated with diverting ostomy after rectal cancer surgery: a transnational analysis.

Background: Diverting ileostomy and colostomy after total mesorectal excision reduces the risk of complications related to anastomotic leakages but is associated with a reduction in health-related quality of life and long-term economic consequences that are unknown. Our objective was to estimate the lifetime costs of stoma placement after rectal cancer resection in the U.S.

Anti-Cancer Prodrug Cyclophosphamide Exerts Thrombogenic Effects on Human Venous Endothelial Cells Independent of CYP450 Activation-Relevance to Thrombosis.

Cancer patients are at a very high risk of serious thrombotic events, often fatal. The causes discussed include the detachment of thrombogenic particles from tumor cells or the adverse effects of chemotherapeutic agents. Cytostatic agents can either act directly on their targets or, in the case of a prodrug approach, require metabolization for their action.

Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging.

The understanding of the contribution of the tumour microenvironment to cancer progression and metastasis, in particular the interplay between tumour cells, fibroblasts and the extracellular matrix has grown tremendously over the last years. Lysyl oxidases are increasingly recognised as key players in this context, in addition to their function as drivers of fibrotic diseases. These insights have considerably stimulated drug discovery efforts towards lysyl oxidases as targets over the last decade.

Time From Authorization by the US Food and Drug Administration to Medicare Coverage for Novel Technologies.

Importance: A wide variety of novel medical diagnostics and devices are determined safe and effective by the US Food and Drug Administration (FDA) each year, but to our knowledge the literature lacks evidence documenting how long it takes to establish new Medicare coverage for these technologies.

Objective: To measure time from FDA authorization to at least nominal Medicare coverage for technologies requiring a new reimbursement pathway.

Design, Setting, And Participants: In this cross-sectional study, public databases were used to associate each technology to billing codes, determine the effective date of each code and Medicare coverage decisions, and stratify by the maturity of the Medicare coverage.