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Critical Reviews in Oncology/hematology Jun 2024Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and... (Review)
Review
CONTEXT
Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities.
OBJECTIVE
To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors.
EVIDENCE ACQUISITION
A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included dermatologic/cutaneous adverse events, risk factors, and pathophysiology in conjunction with the following classes of therapies; immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib, and androgen receptor antagonists (ARAs).
EVIDENCE SYNTHESIS
Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender.
CONCLUSIONS
Dermatologic AEs may impact patients' quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.
PubMed: 38906514
DOI: 10.1016/j.critrevonc.2024.104420 -
Molecular Biology Reports Jun 2024Senecavirus A (SV-A) is an RNA virus that belongs to the genus Senecavirus within the family Picornaviridae. This study aimed to analyze factors that can influence the...
BACKGROUND
Senecavirus A (SV-A) is an RNA virus that belongs to the genus Senecavirus within the family Picornaviridae. This study aimed to analyze factors that can influence the molecular diagnosis of Senecavirus A, such as oligonucleotides, RNA extraction methods, and RT-qPCR kits.
METHODS
Samples from suspected cases of vesicular disease in Brazilian pigs were analyzed for foot-and-mouth disease, swine vesicular disease, and vesicular stomatitis. All tested negative for these diseases but positive for SV-A. RT-qPCR tests were used, comparing different reagent kits and RNA extraction methods. Sensitivity and repeatability were evaluated, demonstrating efficacy in detecting SV-A in clinical samples.
RESULTS
In RNA extraction, significant reduction in Cq values was observed with initial dilutions, particularly with larger supernatant volumes. Trizol and Maxwell showed greater sensitivity in automated equipment protocols, though results varied in tissue tests. RT-qPCR kit comparison revealed differences in amplification using viral RNA but minimal differences with plasmid DNA. Sensitivity among methods was comparable, with slight variations in non-amplified samples. Repeatability tests showed consistent results among RT-qPCRs, demonstrating similarity between methods despite minor discrepancies in Cq values.
CONCLUSIONS
Trizol, silica columns, and semi-automated extraction were compared, as well as different RT-qPCR kits. The study found significant variations that could impact the final diagnosis.
Topics: Animals; Picornaviridae; Swine; Picornaviridae Infections; RNA, Viral; Swine Diseases; Sensitivity and Specificity; Real-Time Polymerase Chain Reaction; Swine Vesicular Disease; Foot-and-Mouth Disease; Brazil; Reproducibility of Results
PubMed: 38904698
DOI: 10.1007/s11033-024-09692-2 -
Cureus Jun 2024Heat-activated polymethyl methacrylate (PMMA) is the most common and widely accepted denture base material. Two important drawbacks are the development of denture...
Comparative Evaluation of the Flexural Strength of Heat-Activated Polymethyl Methacrylate Denture Base Resin With and Without 0.2% by the Weight of Silver Nanoparticles Cured by Conventional and Autoclave Methods: An In Vitro Study.
PURPOSE
Heat-activated polymethyl methacrylate (PMMA) is the most common and widely accepted denture base material. Two important drawbacks are the development of denture stomatitis and the high incidence of fracture of denture bases. The present study investigated the effect of adding 0.2% by weight of silver nanoparticles (AgNps) and using the autoclave method of terminal boiling on the flexural strength of heat-activated PMMA denture base resin.
METHODS
A total of 40 samples of heat-activated PMMA blocks were divided into four groups, with 10 samples (n = 10) in each group. Group 1 consisted of unmodified heat-activated PMMA resin (PMMA-1) polymerized by the conventional method of terminal boiling (conventional curing); Group 2 consisted of 0.2% by weight AgNPs added to heat-activated PMMA resin (PMMA-2) polymerized by conventional curing; Group 3 consisted of PMMA-1 polymerized by the autoclave method of terminal boiling (autoclave curing); and Group 4 consisted of PMMA-2 polymerized by autoclave curing. The flexural strength was tested using a universal testing machine. Descriptive statistics were expressed as mean ± SD and median flexural strength. Kruskal-Wallis ANOVA with Mann-Whitney U post hoc test was applied to test for statistical significance between the groups. The level of significance was set at p<0.05.
RESULTS
The results showed a statistically significant reduction in flexural strength in Group 2 compared to Group 1. The samples from Group 4 showed a statistically significant increase in flexural strength compared to Group 2. The Group 4 denture base had the highest flexural strength (115.72 ± 7.27 MPa) among the four groups, followed by Group 3 (104.16 ± 4.85 MPa). The Group 1 samples gave a flexural strength of 101.45 ± 3.13 MPa, and Group 2 gave the lowest flexural strength (85.98 ± 3.49 MPa) among the four groups tested.
CONCLUSION
The reduction in flexural strength of the heat-activated PMMA denture base after adding 0.2% by weight of AgNP as an antifungal agent was a major concern among manufacturers of commercially available denture base materials. It was proved in the present study that employing the autoclave curing method of terminal boiling for the polymerization of 0.2% by weight of AgNp-added heat-activated PMMA denture base resulted in a significantly higher flexural strength compared to the conventional curing method of terminal boiling for polymerization. Unmodified heat-activated PMMA gave higher flexural strength values when polymerized by autoclave curing compared to the conventional curing method of terminal boiling.
PubMed: 38903978
DOI: 10.7759/cureus.62675 -
Ugeskrift For Laeger Jun 2024
PubMed: 38903041
DOI: 10.61409/V71198 -
Archives of Virology Jun 2024Bovine papular stomatitis virus (BPSV) is a parapoxvirus that infects cattle, causing skin lesions on the udder and mouth. There have been few studies on the prevalence...
Bovine papular stomatitis virus (BPSV) is a parapoxvirus that infects cattle, causing skin lesions on the udder and mouth. There have been few studies on the prevalence and molecular characteristics of BPSV in Iraq. Here, we describe the prevalence, phylogenetic analysis, and clinico-epidemiological features of BPSV in cattle in Al-Qadisiyah, Iraq. A total of 264 animals were examined for teat and oral lesions, and BPSV was detected by PCR in 79.9% (211/264) of cattle and calves with skin lesions. The lesions included ulcers, papules, and scabby proliferative areas. The BPSV strains from Iraq clustered phylogenetically with BPSV strains detected in the USA. Further studies are needed to explore the evolution and epidemiology of this virus in the region.
Topics: Animals; Cattle; Iraq; Cattle Diseases; Parapoxvirus; Phylogeny; Poxviridae Infections; Prevalence; Female
PubMed: 38902518
DOI: 10.1007/s00705-024-06061-z -
Dental Materials : Official Publication... Jun 2024The permeability of triamcinolone acetonide (TA), from bilayer mucoadhesive buccal films, through a biomimetic membrane, Permeapad™, was investigated employing Franz...
OBJECTIVES
The permeability of triamcinolone acetonide (TA), from bilayer mucoadhesive buccal films, through a biomimetic membrane, Permeapad™, was investigated employing Franz diffusion cell. The delivery systems composition and ethyl cellulose (EC) backing layer, on drug permeability, were assessed.
METHODS
Three TA-loaded films were tested; hydroxypropyl methylcellulose (HPMC K4M; bilayer [F1] and monolayer), HPMC K4M/Polyvinylpyrrolidone (PVP): 90/10 [F2], and HPMC K15M film [F3]. All films contained propylene glycol (PG-plasticiser). TA solution alone was used as a control. TA permeability via a Permeapad™ barrier, simulating buccal mucosa, was assessed over 8 h using a Franz diffusion cell. TA permeated into the receptor compartment, released in the donor compartment, and located on/within the Permeapad™ barrier were analysed using UV-spectrophotometer.
RESULTS
45.7 % drug retention within the Permeapad™ barrier was delivered from F1 (highest). F1, F2, and F3 significantly improved the TA's permeability through Permeapad™, compared to TA solution alone (e.g., 8.5 % TA-solution, 21.5 %-F1), attributed to the synergy effect of HPMC and propylene glycol acting as penetration enhancers. F1 displayed a significant increase in drug permeability (receptor compartment; 21.5 %) compared to F3 (17.0 %). PVP significantly enhanced drug permeability (27.5 %). Impermeable EC backing layer controlled unidirectional drug release and reduced drug loss into the donor compartment (e.g., ∼28 % for monolayer film to ∼10 % for bilayer film, F1).
SIGNIFICANCE
The mucoadhesive films demonstrated improved TA permeability via Permeapad™. The findings suggest that these bilayer mucoadhesive films, particularly F1, hold promise for the effective topical treatment of oral mucosa disorders, such as recurrent aphthous stomatitis and oral lichen planus.
PubMed: 38902145
DOI: 10.1016/j.dental.2024.06.016 -
Journal of Virology Jun 2024Animal models of authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require operation in biosafety level 3 (BSL-3) containment. In the...
Animal models of authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require operation in biosafety level 3 (BSL-3) containment. In the present study, we established a mouse model employing a single-cycle infectious virus replicon particle (VRP) system of SARS-CoV-2 that can be safely handled in BSL-2 laboratories. The VRP [ΔS-VRP(G)-Luc] contains a SARS-CoV-2 genome in which the spike gene was replaced by a firefly luciferase (Fluc) reporter gene (Rep-Luci), and incorporates the vesicular stomatitis virus glycoprotein on the surface. Intranasal inoculation of ΔS-VRP(G)-Luc can successfully transduce the Rep-Luci genome into mouse lungs, initiating self-replication of Rep-Luci and, accordingly, inducing acute lung injury mimicking the authentic SARS-CoV-2 pathology. In addition, the reporter Fluc expression can be monitored using a bioluminescence imaging approach, allowing a rapid and convenient determination of viral replication in ΔS-VRP(G)-Luc-infected mouse lungs. Upon treatment with an approved anti-SARS-CoV-2 drug, VV116, the viral replication in infected mouse lungs was significantly reduced, suggesting that the animal model is feasible for antiviral evaluation. In summary, we have developed a BSL-2-compliant mouse model of SARS-CoV-2 infection, providing an advanced approach to study aspects of the viral pathogenesis, viral-host interactions, as well as the efficacy of antiviral therapeutics in the future.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and pathogenic in humans; thus, research on authentic SARS-CoV-2 has been restricted to biosafety level 3 (BSL-3) laboratories. However, due to the scarcity of BSL-3 facilities and trained personnel, the participation of a broad scientific community in SARS-CoV-2 research had been greatly limited, hindering the advancement of our understanding on the basic virology as well as the urgently necessitated drug development. Previously, our colleagues Jin et al. had generated a SARS-CoV-2 replicon by replacing the essential spike gene in the viral genome with a Fluc reporter (Rep-Luci), which can be safely operated under BSL-2 conditions. By incorporating the Rep-Luci into viral replicon particles carrying vesicular stomatitis virus glycoprotein on their surface, and via intranasal inoculation, we successfully transduced the Rep-Luci into mouse lungs, developing a mouse model mimicking SARS-CoV-2 infection. Our model can serve as a useful platform for SARS-CoV-2 pathological studies and antiviral evaluation under BSL2 containment.
PubMed: 38899934
DOI: 10.1128/jvi.00504-24 -
Head and Neck Pathology Jun 2024Uremic stomatitis is often unfamiliar to healthcare professionals. This study presents five cases of uremic stomatitis, providing a comprehensive analysis of their... (Review)
Review
BACKGROUND
Uremic stomatitis is often unfamiliar to healthcare professionals. This study presents five cases of uremic stomatitis, providing a comprehensive analysis of their demographic distribution, clinicopathological features, and management strategies based on existing literature.
METHODS
Data were collected from centers across Brazil, Argentina, Venezuela, and Mexico. Electronic searches were conducted in five databases supplemented by manual scrutiny and gray literature.
RESULTS
The series consisted of three men and two women with a mean age of 40.2 years. Lesions mostly appeared as white plaques, particularly on the tongue (100%). The median blood urea level was 129 mg/dL. Histopathological analysis revealed epithelial changes, including acanthosis and parakeratosis, with ballooned keratinocytes in the suprabasal region. Oral lesions resolved subsequent to hemodialysis in three cases (75%). Thirty-seven studies comprising 52 cases of uremic stomatitis have been described hitherto. Most patients were male (65.4%) with a mean age of 43.6 years. Clinically, grayish-white plaques (37.3%) and ulcers/ulcerations (28.9%) were common, particularly on the tongue (30.9%). Hemodialysis was performed on 27 individuals. The resolution rate of oral lesions was 53.3%.
CONCLUSION
Earlier recognition of uremic stomatitis, possibly associated with long-term uremia, holds the potential to improve outcomes for patients with undiagnosed chronic kidney disease.
Topics: Humans; Male; Female; Adult; Uremia; Stomatitis; Middle Aged; Latin America; Renal Dialysis
PubMed: 38896178
DOI: 10.1007/s12105-024-01652-3 -
Advanced Healthcare Materials Jun 2024Noninflammatory apoptosis is transformed into inflammatory pyroptosis by activating caspase-3 to lyse gasdermin E (GSDME), and this process can be used as an effective...
Noninflammatory apoptosis is transformed into inflammatory pyroptosis by activating caspase-3 to lyse gasdermin E (GSDME), and this process can be used as an effective therapeutic strategy. Thus, a selective and powerful inducer of activated caspase-3 plays a vital role in pyroptosis-based cancer therapy. Herein, a human cell membrane vesicle-based nanoplatform (HCNP) is designed for photodynamic therapy (PDT). HCNP is modified with vesicular stomatitis virus G-protein (VSVG) to anchor nano-photosensitizers on the tumor cell membrane. Photosensitizers are bonded to HCNP by clicking chemical reaction as pyroptosis inducers. The results show that HCNP effectively disrupts the mitochondrial function of cells by generating reactive oxygen species (ROS) upon laser irradiation; concomitantly, GSDME is cleaved by activated caspase-3 and promotes pyroptosis of lung cancer cells. Here an effective intervention strategy is proposed to induce pyroptosis based on light-activated PDT.
PubMed: 38895987
DOI: 10.1002/adhm.202401616 -
Cancers May 2024This was an observational study prospectively evaluating the effectiveness and safety of aflibercept/FOLFIRI administered in second-line mCRC per the reimbursement...
BACKGROUND
This was an observational study prospectively evaluating the effectiveness and safety of aflibercept/FOLFIRI administered in second-line mCRC per the reimbursement criteria in Poland.
METHODS
Consecutive mCRC patients who progressed with first-line oxaliplatin-based chemotherapy received aflibercept (4 mg/kg IV) followed by FOLFIRI every 2 weeks until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); overall survival (OS) and safety were the secondary endpoints.
RESULTS
A total of 93 patients were treated at 17 Polish sites. A median of 10 cycles was administered. Over a median treatment duration of 5.3 months, median PFS and median OS were 8.4 months [95% CI, 6.9-9.9] and 27.0 months [95% CI, 23.9-30.1], respectively. There was no significant impact of primary tumor location, metastatic site, or KRAS status on PFS and OS. Main grade ≥ 3 adverse events were neutropenia (16%), hypertension (8%), diarrhea (4%), and stomatitis (4%).
CONCLUSIONS
The benefits/risks of Aflibercept plus FOLFIRI administered per the Polish reimbursement criteria in second-line treatment of mCRC after failure of a prior oxaliplatin-based regimen is confirmed.
PubMed: 38893113
DOI: 10.3390/cancers16111992