Bechbradshaw1626
Since a non-negligible fraction of patients with metastatic melanoma does not experience long-term disease control, even with immunotherapy and targeted therapy, new biomarkers for patient stratification and treatment tailoring are needed in this setting.
We investigated the association of a novel immune-inflammatory blood-based biomarker, the Pan-Immune-Inflammation Value (PIV), with clinical outcomes of patients with metastatic melanoma receiving first-line therapy.
We retrospectively included patients treated at the Fondazione IRCCS Istituto Nazionale dei Tumori of Milan and having an available baseline complete blood cell count (CBC). PIV was calculated as [neutrophil count (10
/mm
) × platelet count (10
/mm
) × monocyte count (10
/mm
)]/lymphocyte count (10
/mm
).
A total of 228 patients were included 119 (52%) had been treated with immunotherapy and 109 (48%) with targeted therapy. PIV was significantly higher in patients with ECOG PS ≥ 1, high disease burden, synchronous metastases, and elevated baseline LDH level. High baseline PIV was independently associated with poor overall survival (adjusted hazard ratio [HR] 2.06; 95% confidence interval [CI] 1.30-3.29; adjusted P=0.002) and progression-free survival (adjusted HR 1.56; 95% CI 1.01-2.41; adjusted P=0.044). High PIV was also associated with primary resistance to both immunotherapy (odds ratio [OR] 3.98; 95% CI 1.45-12.32; P=0.005) and targeted therapy (OR 8.42; 95% CI 2.50-34.5; P < 0.001). PIV showed a promising discrimination ability in terms of AIC and c-index when compared with other CBC-based biomarkers.
PIV may guide the treatment decision process and the development of novel first-line treatment strategies in melanoma, but warrants further study and validation.
PIV may guide the treatment decision process and the development of novel first-line treatment strategies in melanoma, but warrants further study and validation.Gene therapy has been experiencing a breakthrough in recent years, targeting various specific cell groups in numerous therapeutic areas. However, most recent clinical studies maintain the use of traditional viral vector systems, which are challenging to manufacture cost-effectively at a commercial scale. Non-viral vectors have been a fast-paced research topic in gene delivery, such as polymers, lipids, inorganic particles, and combinations of different types. Although non-viral vectors are low in their cytotoxicity, immunogenicity, and mutagenesis, attracting more and more researchers to explore the promising delivery system, they do not carry ideal characteristics and have faced critical challenges, including gene transfer efficiency, specificity, gene expression duration, and safety. This review covers the recent advancement in non-viral vectors research and formulation aspects, the challenges, and future perspectives.Glucocorticoid-induced cataract (GIC)-associated biomarkers were screened by ceRNA network construction. The GIC samples' GSE3040 were obtained from the NCBI-GEO database. selleckchem R's Limma package was used to identify differentially expressed RNAs (DERs) between the normal and GIC samples group (4- and 16-h). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis for the mRNAs in the constructed GIC lncRNA-miRNA-mRNA ceRNA regulation network was implemented. A total of 1665 and 1443 DERs were obtained in the 4- and 16-h group, respectively. At two time points, 256 overlapping DERs were identified, of which 210 (17 lncRNAs and 203 mRNAs) had significant differential expression (4 down- and 206 up-regulated). A total of 534 co-expressed ligation pairs (all up-regulated) were obtained. A ceRNA regulation network was constructed. RPS6KA5, GAB1, CCR7, CCL2, COL4A4, and PPARG were obtained and significantly enriched in the 4 KEGG signaling pathways and were featured as GIC target molecules.
We studied the quality differences between the different hypo-osmotic swelling test (HOST) classes, as measured by criteria of DNA fragmentation, DNA decondensation, and nuclear architecture. The aim was to find particular HOST classes associated with good-quality metrics, which may be potentially used in ICSI (intra-cytoplasmic sperm injection).
Ten patients from the Department of Reproductive Medicine at Tenon Hospital (Paris, France) were included. Their semen samples were collected and divided into two fractions one was incubated in a hypo-osmotic solution as per HOST protocol and sorted by sperm morphology, and a second was incubated without undergoing the HOST protocol to serve as an unsorted baseline. Three parameters were assessed DNA fragmentation (TUNEL assay), DNA decondensation (chromomycin A3 assay), and nuclear architecture (FISH, with telomeric and whole chromosome painting probes). The different HOST classes were evaluated for these three parameters, and statistical analysis was performed for each class versus the unsorted non-HOST-treated sperm. Results with p<0.05 were considered statistically significant.
For each of the parameters evaluated, we found significant differences between HOST-selected spermatozoa and non-selected spermatozoa. Overall, spermatozoa of HOST classes B and B+ exhibited the highest quality based on four metrics (low DNA fragmentation, low DNA decondensation, short inter-telomeric distance, and small chromosome 1 territory area), while spermatozoa of HOST classes A and G exhibited the poorest quality by these metrics.
In addition to their pathophysiological interest, our results open possibilities of sperm selection prior to ICSI, which may allow for optimization of reproductive outcomes in heretofore unstudied patient populations.
In addition to their pathophysiological interest, our results open possibilities of sperm selection prior to ICSI, which may allow for optimization of reproductive outcomes in heretofore unstudied patient populations.
Ra-223 dichloride (
Ra, Xofigo®) is used for treatment of patients suffering from castration-resistant metastatic prostate cancer. The objective of this work was to apply the most recent biokinetic model for radium and its progeny to show their radiopharmacokinetic behaviour. Organ absorbed doses after intravenous injection of
Ra were estimated and compared to clinical data and data of an earlier modelling study.
The most recent systemic biokinetic model of
Ra and its progeny, developed by the International Commission on Radiological Protection (ICRP), as well as the ICRP human alimentary tract model were applied for the radiopharmacokinetic modelling of Xofigo® biodistribution in patients after bolus administration. Independent kinetics were assumed for the progeny of
Ra. The time activity curves for
Ra were modelled and the time integrated activity coefficients, [Formula see text] in the source regions for each progeny were determined. For estimating the organ absorbed doses, the Specific Absorbed Fractions (SAF) and dosimetric framework of ICRP were used together with the aforementioned [Formula see text] values.
