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PeerJ 2023Zirconia, a crystalline oxide of zirconium, holds good mechanical, optical, and biological properties. The metal-free restorations, mostly consisting of... (Review)
Review
Zirconia, a crystalline oxide of zirconium, holds good mechanical, optical, and biological properties. The metal-free restorations, mostly consisting of all-ceramic/zirconia restorations, are becoming popular restorative materials in restorative and prosthetic dentistry choices for aesthetic and biological reasons. Dental zirconia has increased over the past years producing wide varieties of zirconia for prosthetic restorations in dentistry. At present, literature is lacking on the recent zirconia biomaterials in dentistry. Currently, no article has the latest information on the various zirconia biomaterials in dentistry. Hence, the aim of this article is to present an overview of recent dental zirconia biomaterials and tends to classify the recent zirconia biomaterials in dentistry. This article is useful for dentists, dental technicians, prosthodontists, academicians, and researchers in the field of dental zirconia.
Topics: Zirconium; Biocompatible Materials; Ceramics; Dentistry
PubMed: 37465158
DOI: 10.7717/peerj.15669 -
Clinical Cancer Research : An Official... Sep 2023We report updated clinical outcomes from a phase II study of pembrolizumab, trastuzumab, and chemotherapy (PTC) in metastatic esophagogastric cancer in conjunction with...
PURPOSE
We report updated clinical outcomes from a phase II study of pembrolizumab, trastuzumab, and chemotherapy (PTC) in metastatic esophagogastric cancer in conjunction with outcomes from an independent Memorial Sloan Kettering (MSK) cohort.
PATIENTS AND METHODS
The significance of pretreatment 89Zr-trastuzumab PET, plasma circulating tumor DNA (ctDNA) dynamics, and tumor HER2 expression and whole exome sequencing was evaluated to identify prognostic biomarkers and mechanisms of resistance in patients treated on-protocol with PTC. Additional prognostic features were evaluated using a multivariable Cox regression model of trastuzumab-treated MSK patients (n = 226). Single-cell RNA sequencing (scRNA-seq) data from MSK and Samsung were evaluated for mechanisms of therapy resistance.
RESULTS
89Zr-trastuzumab PET, scRNA-seq, and serial ctDNA with CT imaging identified how pre-treatment intrapatient genomic heterogeneity contributes to inferior progression-free survival (PFS). We demonstrated that the presence of intensely avid lesions by 89Zr-trastuzumab PET declines in tumor-matched ctDNA by 3 weeks, and clearance of tumor-matched ctDNA by 9 weeks were minimally invasive biomarkers of durable PFS. Paired pre- and on-treatment scRNA-seq identified rapid clearance of HER2-expressing tumor clones with expansion of clones expressing a transcriptional resistance program, which was associated with MT1H, MT1E, MT2A, and MSMB expression. Among trastuzumab-treated patients at MSK, ERBB2 amplification was associated with improved PFS, while alterations in MYC and CDKN2A/B were associated with inferior PFS.
CONCLUSIONS
These findings highlight the clinical relevance of identifying baseline intrapatient heterogeneity and serial ctDNA monitoring of HER2-positive esophagogastric cancer patients to identify early evidence of treatment resistance, which could guide proactive therapy escalation or deescalation.
Topics: Humans; Female; Receptor, ErbB-2; Programmed Cell Death 1 Receptor; Radioisotopes; Zirconium; Biomarkers, Tumor; Esophageal Neoplasms; Stomach Neoplasms; Trastuzumab; Breast Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37406106
DOI: 10.1158/1078-0432.CCR-22-3769 -
Cureus Jan 2024Hyperkalemia has been defined as a condition where a serum potassium level is >5.5 mmol/l. It is associated with fatal dysrhythmias and muscular dysfunction. Certain... (Review)
Review
Hyperkalemia has been defined as a condition where a serum potassium level is >5.5 mmol/l. It is associated with fatal dysrhythmias and muscular dysfunction. Certain medical conditions, such as chronic kidney disease (CKD), diabetes mellitus, and others, can lead to hyperkalemia. Many of the signs of hyperkalemia are nonspecific. A history and physical examination can be beneficial in the diagnosis of the condition. In this regard, certain characteristic electrocardiogram findings are associated with hyperkalemia along with laboratory potassium levels. In acute and potentially lethal conditions, hyperkalemia treatments include glucose and insulin, bicarbonate, calcium gluconate, beta-2 agonists, hyperventilation, and dialysis. There are several drugs, both old and new, that can additionally aid in the reduction of serum potassium levels. The present investigation evaluated some of these different drugs, including sodium polystyrene sulfonate (SPS), sodium zirconium cyclosilicate (SZC), and patiromer. These drugs each have increased selectivity for potassium and work primarily in the gastrointestinal (GI) tract. Each of these medications has unique benefits and contraindications. Clinicians must be aware of these medications when managing patients with hyperkalemia.
PubMed: 38406030
DOI: 10.7759/cureus.52994 -
Frontiers in Medicine 2023Hyperkalemia (HK) is a life-threatening condition that often occurs in patients with chronic kidney disease (CKD). High serum potassium (sKsK) is responsible for a... (Review)
Review
Hyperkalemia (HK) is a life-threatening condition that often occurs in patients with chronic kidney disease (CKD). High serum potassium (sKsK) is responsible for a higher risk of end-stage renal disease, arrhythmias and mortality. This risk increases in patients that discontinue cardio-nephroprotective renin-angiotensin-aldosterone system inhibitor (RAASi) therapy after developing HK. Hence, the management of HK deserves the attention of the clinician in order to optimize the therapeutic strategies of chronic treatment of HK in the CKD patient. The adoption in clinical practice of the new hypokalaemic agents patiromer and sodium zirconium cyclosilicate (SZC) for the prevention and chronic treatment of HK could allow patients, suffering from heart failure and chronic renal failure, to continue to benefit from RAASi therapy. We have updated a narrative review of the clear variables, correct definition, epidemiology, pathogenesis, etiology and classifications for HK among non-dialysis CKD (ND CKD) patients. Furthermore, by describing the prognostic impact on mortality and on the progression of renal damage, we want to outline the strategies currently available for the control of potassium (K+) plasma levels.
PubMed: 37583425
DOI: 10.3389/fmed.2023.1178140 -
Materials (Basel, Switzerland) Nov 2023The increased demand for implants that do not pose a threat to patients diagnosed using high-resolution magnetic resonance imaging and concerns arising from titanium...
The increased demand for implants that do not pose a threat to patients diagnosed using high-resolution magnetic resonance imaging and concerns arising from titanium allergies require the development of alternative implant materials. One promising concept is a use of zirconium as corrosion-resistant, nontoxic material that is lower in magnetic susceptibility. To achieve this, safe and efficient surface treatment methods of zirconium metal have to be developed. In this study, zirconium samples were treated with fluoride-free and fluoride-containing etching mixtures to determine their effect on the surface of Zr. SEM images were taken to investigate the preliminary effects of the etchants. Then, a second set of experiments was carried out using mixtures of HF-HSO and ammonium persulfate-fluoride salts, as they gave the most promising results in the first trial. SEM images were taken and measurements on roughness, wettability, and atomic composition were made. The results showed an even zirconium surface in APS-fluoride salts, along with the formation of pits (1-3 μm) similar to those found in commercially available implants. There was no significant increase in the roughness of the treated samples. The addition of NO ions in the form of KNO speeded up etching and promoted pit formation. The HF-HSO mixture was found to give unsatisfying results, as the surface was too rough and the formed pits were too large. It was concluded that etching zirconium in ammonium persulfate and fluoride salts is a promising area of research for the preparation of zirconium implants; however, further research has to be carried out on sandblasted samples.
PubMed: 38068148
DOI: 10.3390/ma16237404 -
Materials (Basel, Switzerland) Aug 2023The review focuses on the surface modification of Zr and its alloys, which is necessary to expand the applications of these kinds of materials. Data on the properties of... (Review)
Review
The review focuses on the surface modification of Zr and its alloys, which is necessary to expand the applications of these kinds of materials. Data on the properties of pure zirconium and its alloys are presented. Since surface engineering and the operation of the above materials are in most cases associated with the formation of oxide coatings, information on the characteristics of ZrO is given. In addition, attention is paid to phasing in the zirconium-oxygen system. It is noted that the most effective method of surface engineering of Zr and its alloys is plasma electrolytic modification (PEM) technology. Specific examples and modes of modification are described, and the reached results are analyzed. The relevance, novelty and originality of the review are determined by the insufficient knowledge about a number of practical features concerning the formation of functional oxide coatings on Zr and some of its alloys by the technology of PEM. In particular, the information on the phase composition and possibilities of stabilization of the tetragonal and cubic modifications of ZrO, the effects of the component composition of electrolyte solutions and electrolyte suspensions, and the specifics of the treatment of additive shaping and deformed materials are rather contradictory. This review aims to collect recent advances and provide insights into the trends in the modification of Zr and its alloys, promote the formulation of practical recommendations and assess the development prospects.
PubMed: 37629834
DOI: 10.3390/ma16165543 -
Molecular Pharmaceutics Jun 2023Galectin-3 binding protein (Gal-3BP) is a glycoprotein that is overexpressed and secreted by several cancers and has been implicated as a marker of both tumor...
Galectin-3 binding protein (Gal-3BP) is a glycoprotein that is overexpressed and secreted by several cancers and has been implicated as a marker of both tumor progression and poor prognosis in melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, and breast cancer. The expression of Gal-3BP by a variety of neoplasms makes it an enticing target for both diagnostics and therapeutics, including immuno-positron emission tomography (immunoPET) probes and antibody-drug conjugates (ADCs). Herein, we report the development, characterization, and evaluation of a pair of Gal-3BP-targeting radioimmunoconjugates for Zr-immunoPET. A humanized anti-Gal-3BP antibody, 1959, and its corresponding ADC, 1959-sss/DM4 (DM4 = ravtansine), were modified with desferrioxamine (DFO) to yield DFO-1959 and DFO-1959-sss/DM4 immunoconjugates bearing 1-2 DFO/monoclonal antibody. Both DFO-modified immunoconjugates retained their affinity for Gal-3BP in enzyme-linked immunosorbent assay experiments. The chelator-bearing antibodies were radiolabeled with zirconium-89 ( ≈ 3.3 d) to produce radioimmunoconjugates ─ [Zr]Zr-DFO-1959 and [Zr]Zr-DFO-1959-sss/DM4 ─ with high specific activity (>444 MBq/mg, >12 mCi/mg) and stability (>80% intact after 168 h in human serum at 37 °C). In mice bearing subcutaneous Gal-3BP-secreting A375-MA1 xenografts, [Zr]Zr-DFO-1959 clearly delineated tumor tissue, reaching a maximum tumoral activity concentration (54.8 ± 15.8%ID/g) and tumor-to-background contrast (tumor-to-blood = 8.0 ± 4.6) at 120 h post-injection. The administration of [Zr]Zr-DFO-1959 to mice bearing subcutaneous Gal-3BP-expressing melanoma patient-derived xenografts produced similarly promising results. [Zr]Zr-DFO-1959 and [Zr]Zr-DFO-1959-sss/DM4 exhibited nearly identical pharmacokinetic profiles in the mice bearing A375-MA1 tumors, though the latter produced higher uptake in the spleen and kidneys. Both [Zr]Zr-DFO-1959 and [Zr]Zr-DFO-1959-sss/DM4 effectively visualized Gal-3BP-secreting tumors in murine models of melanoma. These results suggest that both probes could play a role in the clinical imaging of Gal-3BP-expressing malignancies, particularly as companion theranostics for the identification of patients likely to respond to Gal-3BP-targeted therapeutics such as 1959-sss/DM4.
Topics: Animals; Humans; Mice; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Deferoxamine; Galectin 3; Immunoconjugates; Lung Neoplasms; Melanoma; Positron-Emission Tomography; Zirconium
PubMed: 37191353
DOI: 10.1021/acs.molpharmaceut.3c00241 -
Journal of Nuclear Medicine : Official... Jul 2023Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC)...
Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC) accounts for 80% of primary liver cancer cases. Glypican-3 (GPC3) is a heparan sulfate proteoglycan that histopathologically defines HCC and represents an attractive tumor-selective marker for radiopharmaceutical imaging and therapy for this disease. Single-domain antibodies are a promising scaffold for imaging because of their favorable pharmacokinetic properties, good tumor penetration, and renal clearance. Although conventional lysine-directed bioconjugation can be used to yield conjugates for radiolabeling full-length antibodies, this stochastic approach risks negatively affecting target binding of the smaller single-domain antibodies. To address this challenge, site-specific approaches have been explored. Here, we used conventional and sortase-based site-specific conjugation methods to engineer GPC3-specific human single-domain antibody (HN3) PET probes. Bifunctional deferoxamine (DFO) isothiocyanate was used to synthesize native HN3 (nHN3)-DFO. Site-specifically modified HN3 (ssHN3)-DFO was engineered using sortase-mediated conjugation of triglycine-DFO chelator and HN3 containing an LPETG C-terminal tag. Both conjugates were radiolabeled with Zr, and their binding affinity in vitro and target engagement of GPC3-positive (GPC3) tumors in vivo were determined. Both Zr-ssHN3 and Zr-nHN3 displayed nanomolar affinity for GPC3 in vitro. Biodistribution and PET/CT image analysis in mice bearing isogenic A431 and A431-GPC3 xenografts, as well as in HepG2 liver cancer xenografts, showed that both conjugates specifically identify GPC3 tumors. Zr-ssHN3 exhibited more favorable biodistribution and pharmacokinetic properties, including higher tumor uptake and lower liver accumulation. Comparative PET/CT studies on mice imaged with both F-FDG and Zr-ssHN3 showed more consistent tumor accumulation for the single-domain antibody conjugate, further establishing its potential for PET imaging. Zr-ssHN3 showed clear advantages in tumor uptake and tumor-to-liver signal ratio over the conventionally modified Zr-nHN3 in xenograft models. Our results establish the potential of HN3-based single-domain antibody probes for GPC3-directed PET imaging of liver cancers.
Topics: Humans; Animals; Mice; Liver Neoplasms; Carcinoma, Hepatocellular; Single-Domain Antibodies; Radioisotopes; Glypicans; Positron Emission Tomography Computed Tomography; Antibodies, Monoclonal; Tissue Distribution; Cell Line, Tumor; Positron-Emission Tomography; Zirconium
PubMed: 36997331
DOI: 10.2967/jnumed.122.265171 -
Clinical Kidney Journal Feb 2024Sodium zirconium cyclosilicate (SZC), a novel drug used for treating hyperkalaemia, is effective in reducing serum potassium levels. The effects of potassium adsorbents...
Mortality and hyperkalaemia-associated hospitalisation in patients with chronic kidney disease: comparison of sodium zirconium cyclosilicate and sodium/calcium polystyrene sulfonate.
BACKGROUND
Sodium zirconium cyclosilicate (SZC), a novel drug used for treating hyperkalaemia, is effective in reducing serum potassium levels. The effects of potassium adsorbents on the mortality and hyperkalaemia-associated hospitalisation rates remain unclear. We aimed to examine how mortality and hyperkalaemia-associated hospitalisation rates vary with usage of various potassium adsorbents.
METHODS
This retrospective study used patients' data between April 2008 and August 2021 obtained from a large-scale Japanese medical claims database. Consecutive patients with chronic kidney disease (CKD) prescribed potassium adsorbents were enrolled and divided into three groups according to the adsorbent type [SZC, calcium polystyrene sulfonate (CPS), and sodium polystyrene sulfonate (SPS)] and were observed for 1 year. The primary outcome was a composite of mortality and hyperkalaemia-associated hospitalisation.
RESULTS
In total, 234, 54 183, and 18 692 patients were prescribed SZC, CPS, and SPS, respectively. The SZC group showed a higher event-free survival rate than the other two groups. The hazard ratio for the primary outcome in the CPS and SPS groups was similar in the analyses of the subgroups of patients who did not receive renal replacement therapy and those who received haemodialysis. The SZC group had a higher renin-angiotensin-aldosterone system inhibitors (RAASi) continuation rate compared to CPS and SPS groups, the difference being especially significant for SPS.
CONCLUSIONS
This real-world study demonstrated the therapeutic effect of SZC in reducing mortality and hyperkalaemia-associated hospitalisations. The high RAASi continuation rate in the SZC group might be a contributing factor for improvement of the primary outcome.
PubMed: 38404365
DOI: 10.1093/ckj/sfae021