Search results for "phosphonate"

Lamivudine/Adefovir Treatment Increases the Rate of Spontaneous Mutation of Hepatitis B Virus in Patients.

2016

The high levels of genetic diversity shown by hepatitis B virus (HBV) are commonly attributed to the low fidelity of its polymerase. However, the rate of spontaneous mutation of human HBV in vivo is currently unknown. Here, based on the evolutionary principle that the population frequency of lethal mutations equals the rate at which they are produced, we have estimated the mutation rate of HBV in vivo by scoring premature stop codons in 621 publicly available, full-length, molecular clone sequences derived from patients. This yielded an estimate of 8.7 × 10-5 spontaneous mutations per nucleotide per cell infection in untreated patients, which should be taken as an upper limit estimate becau…

How do skeletal morbidity rate and special toxicities affect 12-week versus 4-week schedule zoledronic acid efficacy? A systematic review and a meta-…

2019

Abstract Background Zoledronic Acid is a bisphosphonate used in a 4-week schedule for the treatment of bone metastases. Some randomized trials supported its role also when administered every 12 weeks. Methods we performed a systematic review and a meta-analysis in order to evaluate the two different schedules in terms of skeletal morbidity rate (SMR), skeletal related events (SRE) and adverse events (AEs). Results our results showed a clinical difference favouring the 12-week schedule in terms of AEs (RR 1.17, 95% CI 1.06–1.29). No signifcant differences were found for SMR (RR 0.97, 95% CI 0.84–1.13) and SRE (RR 1.02, 95% CI 0.89–1.16). Conclusions Our findings support in clinical practice …

Identification of the Privileged Position in the Imidazo[1,2-a]pyridine Ring of Phosphonocarboxylates for Development of Rab Geranylgeranyl Transfera…

2017

Members of the Rab GTPase family are master regulators of vesicle trafficking. When disregulated, they are associated with a number of pathological states. The inhibition of RGGT, an enzyme responsible for post-translational geranylgeranylation of Rab GTPases represents one way to control the activity of these proteins. Because the number of molecules modulating RGGT is limited, we combined molecular modeling with biological assays to ascertain how modifications of phosphonocarboxylates, the first reported RGGT inhibitors, rationally improve understanding of their structure-activity relationship. We have identified the privileged position in the core scaffold of the imidazo[1,2-a]pyridine r…

Mesenchymal Transition of High-Grade Breast Carcinomas Depends on Extracellular Matrix Control of Myeloid Suppressor Cell Activity

2016

SummaryThe extracellular matrix (ECM) contributes to the biological and clinical heterogeneity of breast cancer, and different prognostic groups can be identified according to specific ECM signatures. In high-grade, but not low-grade, tumors, an ECM signature characterized by high SPARC expression (ECM3) identifies tumors with increased epithelial-to-mesenchymal transition (EMT), reduced treatment response, and poor prognosis. To better understand how this ECM3 signature is contributing to tumorigenesis, we expressed SPARC in isogenic cell lines and found that SPARC overexpression in tumor cells reduces their growth rate and induces EMT. SPARC expression also results in the formation of a h…

Non-Radiation Based Early Pain Relief Treatment Options for Patients With Non-Small Cell Lung Cancer and Cancer Induced Bone Pain: A Systematic Review

2020

Introduction: Cancer induced bone pain (CIBP) is frequent in patients with non-small cell lung cancer (NSCLC). Radiation therapy continues to be the gold standard for treatment of painful bone metastases, however only a limited number of metastases can be irradiated. We evaluated non-radiation based early CIBP relief options in NSCLC through a systematic review. Methods: Systematic review including all prospective articles published between 01-1994 and 06-2020 on Pubmed, Cochrane Library and ClinicalTrials.gov database. Inclusion: nonradiation based trials evaluating CIBP early pain relief options (initially defined as pain score evaluated within two weeks, because of no randomized trials, …

Drugs and diseases: Summary and consensus statements of group 1. The 5th EAO Consensus Conference 2018

2018

OBJECTIVES: The task of this working group was to update the knowledge about the use of drugs and biologicals affecting healing of soft tissue and bone during implant treatment or procedures associated with it. Moreover, the impact of titanium particles and biocorrosion on complications and implant survival has been analysed. MATERIALS AND METHODS: The literature in the areas of interest (platelet concentrates, antiresorptive drugs as well as implant-host interaction) was screened using systematic reviews for the former two areas, whereas a narrative critical review was performed for the latter topic. Two manuscripts on platelet concentrates, one manuscript on antiresorptive drugs and one m…

Evaluation of Safety and Dosimetry of 177Lu-DOTA-ZOL for Therapy of Bone Metastases

2021

Palliative treatment of bone metastasis using radiolabeled bisphosphonates is a well-known concept proven to be safe and effective. A new therapeutic radiopharmaceutical for bone metastasis is 177Lu-DOTA-zoledronic acid (177Lu-DOTA-ZOL). In this study, the safety and dosimetry of a single therapeutic dose of 177Lu-DOTA-ZOL were evaluated on the basis of a series of SPECT/CT images and blood samples. Methods: Nine patients with exclusive bone metastases from metastatic castration-resistant prostate cancer (mCRPC) (70.8 ± 8.4 y) and progression under conventional therapies participated in this prospective study. After receiving 5,780 ± 329 MBq 177Lu-DOTA-ZOL, patients underwent 3-dimensional …

Treatments for post-menopausal osteoporotic women, what's new? How can we manage long-term treatment?

2016

Since the mid-1980s, postmenopausal osteoporosis (PMO) has been considered a serious public health concern because of the associated fractures. Pharmacological therapies that effectively reduce the number of fractures by improving bone mass have been and are being developed continuously. Most current agents inhibit bone loss by reducing bone resorption, but emerging therapies may increase bone mass by stimulating bone formation. Furthermore, nowadays, the most representative pharmaceuticals have been prescribed long enough to include the reporting of some adverse effects. This review discusses osteoporotic drugs that are approved or are under investigation for the treatment of post-menopaus…

Cost-effectiveness of buffered soluble alendronate 70 mg effervescent tablet for the treatment of postmenopausal women with osteoporosis in Italy

2021

Summary The use of buffered soluble alendronate 70 mg effervescent tablet, a convenient dosing regimen for bisphosphonate therapy, seems a cost-effective strategy compared with relevant alternative treatments for postmenopausal women with osteoporosis aged 60 years and over in Italy. Introduction To assess the cost-effectiveness of buffered soluble alendronate (ALN) 70 mg effervescent tablet compared with relevant alternative treatments for postmenopausal osteoporotic women in Italy. Methods A previously validated Markov microsimulation model was adjusted to the Italian healthcare setting to estimate the lifetime costs (expressed in €2019) per quality-adjusted life-years (QALY) of buffered …

2021

Background: Immunomodulatory properties of bisphosphonates (BP) are suggested to contribute to the development of medication-associated osteonecrosis of the jaw (MRONJ). Furthermore, bisphosphonate-derived immune modulation might contribute to the anti-metastatic effect observed in breast cancer patients. Macrophages are potential candidates for the mediation of immunomodulatory effects of bisphosphonates. The study aimed to investigate the influence of bisphosphonates alone and in combination with surgical trauma on systemic macrophage polarization (M1 vs. M2) using an in vivo rat model. Methods: A total of 120 animals were divided into four groups. Groups 2 and 4 were treated with 8 × 40 …