Abstract Purpose: Radium-223 dichloride (radium-223, Xofigo), a targeted alpha therapy, is currently used for the treatment of patients with castration-resistant prostate cancer (CRPC) bone metastases. This study examines mode-of-action and antitumor efficacy radium-223 in two xenograft models. Experimental Design: Mice bearing intratibial LNCaP or LuCaP 58 tumors were randomized into groups (n = 12–17) based on lesion grade and/or serum PSA level administered (300 kBq/kg) vehicle, twice at...

Prebiotics, probiotics and synbiotics are dietary ingredients with the potential to influence health mucosal systemic immune function by altering composition of gut microbiota. In present study, a candidate prebiotic (xylo-oligosaccharide, XOS, 8 g/d), probiotic ( Bifidobacterium animalis subsp. lactis Bi-07, 10 9 colony-forming units (CFU)/d) or synbiotic (8 g XOS+10 CFU Bi-07/d) was given healthy adults (25–65 years) for 21 d. The aim identify effect supplements on bowel habits,...

BackgroundBone metastases are associated with increased morbidity and poor prognosis in breast cancer patients. Radium-223 dichloride is a calcium mimetic that localizes to bone, providing targeted therapy for skeletal metastasis.

Obesity and dyslipidemia are hallmarks of metabolic cardiovascular diseases. Polydextrose (PDX), a soluble fiber has lipid lowering effects. We hypothesize that PDX reduces triglycerides cholesterol by influencing gut microbiota, which in turn modulate intestinal gene expression. C57BL/6 male mice were fed Western diet (WD) ±75 mg twice daily oral gavage for 14 days. Body weight food intake monitored daily. Fasting plasma lipids, caecal microbiota expression intestine liver measured after...

Dietary fibers are associated with enhanced satiety. However, the mechanism of different dietary contributing to satiety-related gastrointestinal (GI) peptide release, especially in an obese population, is still poorly understood. Polydextrose (PDX), a water-soluble glucose polymer, has demonstrated its ability reduce energy intake at subsequent meal, but action requires further research. Also, there limited evidence on capacity regulate subjective feelings appetite. This study examines...

Elderly adults have alterations in their gut microbiota and immune functions that are associated with higher susceptibility to infections metabolic disorders. Probiotics prebiotics, synbiotic combinations food supplements been shown improve both function. The objective of this randomised, double-blind, placebo-controlled, cross-over human clinical trial was study function the healthy elderly adults. Volunteers (n 37) consumed prebiotic galacto-oligosaccharides (GOS; 8 g/d), probiotic...

Abstract Purpose: Preclinical tumor growth experiments often result in heterogeneous datasets that include growing, regressing, or stable profiles the treatment and control groups. Such confounding intertumor variability may mask true effects especially when less aggressive alternatives are being evaluated. Experimental design: We developed a statistical modeling approach which growing poorly categories were automatically detected by means of an expectation-maximization algorithm coupled...

Three independent trials were conducted to evaluate postprandial triglyceride (TG) responses in subjects with different lipid metabolism. The effect of polydextrose (PDX), a soluble non-digestible carbohydrate, on response was also studied using practically relevant, high fat meal interventions.A total 19 normolipidemic (average BMI 24.1 kg/m(2)), 21 overweight/hyperlipidemic 29.6 kg/m(2)) and 18 obese/non-diabetic 33.6 included the study. On two separate occasions all ate high-fat meals...

To assess the effect of Lactobacillus acidophilus (American Type Culture Collection (ATCC) 700396) on enterotoxigenic Escherichia coli (ETEC) infection, in present study, a parallel, double-blind, placebo-controlled 4-week intervention was performed healthy males. The subjects largely consumed their habitual diet, but had to abstain from consuming dairy foods generally high Ca. were randomised into L. (dose 10 9 colony-forming units twice daily; n 20) or placebo ( 19) group. After an...

Polydextrose (PDX) reduces subsequent energy intake (EI) when administered at midmorning in single-blind trials of primarily normal-weight men. However, it is unclear if this effect also occurs PDX given breakfast time. Furthermore, for ecological validity, desirable to study a female population, including those risk obesity. We studied the effects PDX, served as part or preload, on EI and other appetite-related parameters healthy overweight females. Per earlier studies, primary outcome was...

Radium-223 dichloride and enzalutamide are indicated for metastatic castration-resistant prostate cancer their combination is currently being investigated in a large phase 3 clinical trial. Here, we evaluated the antitumor efficacy of radium-223, enzalutamide, intratibial LNCaP model mimicking metastasized to bone. In vitro experiments revealed that radium-223 inhibited cell proliferation showed synergistic efficacy. The also demonstrated enhanced vivo efficacy, as determined by measuring...

Abstract Radium-223 dichloride (radium-223) is a targeted alpha therapy that binds to newly formed abnormal bone in metastases and induces DNA double-strand breaks (DSBs) cancer cells, osteoblasts osteoclasts. used for the treatment of patients with metastatic castration-resistant prostate (mCRPC). Darolutamide an androgen receptor inhibitor indicated hormone-sensitive or non-metastatic CRPC. We studied antitumor effects radium-223 combination darolutamide using LNCaP human cells vitro...

Osteolytic bone disease is a hallmark of multiple myeloma (MM) mediated by MM cell proliferation, increased osteoclast activity, and suppressed osteoblast function. The proteasome inhibitor bortezomib targets cells improves health in patients. Radium-223 dichloride (radium-223), the first targeted alpha therapy approved, specifically metastases, where it disrupts activity both tumor tumor-supporting mouse models breast prostate cancer metastasis. We hypothesized that radium-223 combination...

Despite treatment, prostate cancer commonly progresses into castration-resistant (CRPC), which remains largely incurable, requiring the development of new interventions. Darolutamide is an orally administered second-generation androgen receptor inhibitor indicated for patients with non-metastatic CRPC or metastatic hormone-sensitive cancer. Here, we evaluated effect (AR) inhibition by darolutamide in combination DNA double-strand-break-inducing targeted radium-223 alpha therapy vitro and...

Abstract Multiple myeloma (MM) is the second most common blood cancer after non Hodgkin lymphoma. It a monoclonal B-cell neoplasia with clinical hallmarks of multiple osteolytic lesions causing bone pain, fractures and hypercalcemia. Chemo- or radiotherapy may induce remissions, but MM generally thought to be incurable. Our aim was observe effects cathepsin inhibitor VBY-825 on tumor burden in syngeneic 5TGM1 mouse model using immunocompetent C57BL/KaLwRij mice. potent cathepsins K, L, B, V,...

Abstract Radium-223, a bone-specific alpha particle therapy, increased survival of patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases (Parker et al., NEJM 2013) 177Lu-PSMA-617 is small molecule radioligand that delivers beta-particle radiation to cells expressing prostate-specific membrane antigen (PSMA). Despite improving overall heavily pretreated mCRPC (Sator 2021), responses are often not durable many develop progressive disease presumably due...

An increased risk of non-pathological fractures in patients with prostate cancer and bone metastases has been associated combination treatment radium-223, abiraterone, prednisone/prednisolone the absence bone-protecting agents. Here, we investigated possible mechanisms leading to this outcome using an intratibial LNCaP model mimicking metastases. Male NOD.scid mice were inoculated intratibially cells treated vehicle, prednisone, zoledronic acid, or their combinations for 28 days. Serum TRACP...

Federated learning (FL), a distributed machine paradigm, enables multiple clients to train models locally on their data while only sharing model updates with the central server. However, this process can be computationally intensive and resource-consuming, leading communication overheads scalability issues. In study, we investigate robustness reliability of Regularized Weight Aggregation (RegAgg) compare its performance an additional regularization layer aggregating weights for federated...

Abstract Radium-223 dichloride (radium-223, Xofigo®), a targeted alpha-therapy, improves overall survival in prostate cancer patients with bone metastases. It inhibits disease progression by reducing tumor growth and tumor-induced pathological reaction breast mouse models. is actively incorporated into the matrix osteoblasts. Multiple myeloma (MM) characterized increased osteoclast reduced or no osteoblast activity. Bortezomib (Velcade®), treatment for MM, restores impaired activity MM....

Abstract Radium-223 dichloride (Ra-223) is a targeted alpha therapy that binds to newly formed bone matrix in metastases and induces double-stranded DNA breaks cancer cells, osteoblasts, osteoclasts. Ra-223 showed survival benefit patients with bone-metastatic castration-resistant prostate pivotal phase 3 trial. Recently, trial of combination abiraterone acetate (AA) prednisone/prednisolone (P), an increased risk fractures was observed, which could be largely diminished by concurrent...