RESIRT: A Phase 1 Study of Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres in Patients With Primary Renal Cell Carcinoma

IntroductionSelective internal radiation therapy (SIRT) is a potential treatment of primary renal cell carcinoma (RCC) deemed unsuitable for conventional therapy. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.Patients and MethodsPatients with RCC, unsuitable for, or who declined conventional therapy, were eligible. A single transfemoral micro-catheter administration of yttrium-90 (Y-90) resin microspheres (SIR-Spheres) was delivered super selectively via the renal artery to the tumour at intended radiation doses of 75, 100, 150, 200, 300 Gy and a final cohort with a procedural endpoint of “imminent stasis,” in a dose-escalation design. Post-SIRT follow-up was 12 months. Study endpoints included safety and toxicity 30-days and 12-months post-SIRT and tumour response (RECIST v1.1).ResultsIn total, 21 patients were enrolled, mean (SD) age was 75 (9.3) years, WHO performance status was 0 in 81%, 12 (57%) had stage 3 chronic kidney disease, and 7 (33%) had prior contralateral nephrectomy. Overall, 71% of patients completed 12 months of follow-up. Intended doses were delivered without any dose-limiting toxicity. Seventeen out of 21 (81%) patients experienced an adverse event (AE) from any cause within 30 days post-SIRT; all SIRT-related AEs were grade 1 to 2. Best overall tumour responses were partial response 1/21 (4.8%), stable disease 19/21 (90.5%) and progressive disease 1/21 (4.8%).ConclusionThis study demonstrated good tolerability of SIRT at all dose levels including “imminent stasis” in treating primary tumours in RCC patients otherwise unsuitable for conventional therapy. SIRT with Y-90 resin microspheres may be a feasible treatment option for RCC.     

Acute toxicity of chlorpyrifos to the non-target organism Cnesterodon decemmaculatus

Chlorpyrifos is the most used insecticide in Argentina. Cnesterodon decemmaculatus is a widely distributed, endemic fish from Neotropical America. It attains high densities in the shallow water assemblages of Argentina and Brazil. The aim of this study was to assess the acute toxicity of chlorpyrifos to C. decemmaculatus. The mean 96-h LC₅₀ of three independent determinations was 105.3 (±?3.1) μg/L. Sublethal effects were observed. Swimming behavioral changes at each chlorpyrifos exposure concentration were reported. C. decemmaculatus represents a good model for ecotoxicological risk assessment.     

Flavonoids and stilbenoids as a promising arsenal for the management of chronic arsenic toxicity

Rapid industrial and technological development has impacted ecosystem homeostasis strongly. Arsenic is one of the most detrimental environmental toxins and its management with chelating agents remains a matter of concern due to associated adverse effects. Thus, safer and more effective alternative therapy is required to manage arsenic toxicity. Based on existing evidence, native and indigenous plant-based active biomolecules appear as a promising strategy to mitigate arsenic-induced toxicity with an acceptable safety profile. In this regard, various phytochemicals (flavonoids and stilbenoids) are considered important classes of polyphenolic compounds with antioxidant and chelation effects, which may facilitate the removal of arsenic from the body more effectively and safely with regard to conventional approaches. This review presents an overview of conventional chelating agents and the potential role of flavonoids and stilbenoids in ameliorating arsenic toxicity. This report may provide a roadmap for identifying novel prophylactic/therapeutic strategies for managing arsenic toxicity.     

Effect of Race and Ethnicity on Risk of Radiotherapy Toxicity and Implications for Radiogenomics

AimsPatient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response, molecular pathways and epigenetics. Effects on radiosensitivity and radiotherapy toxicity are not well studied. The aim of the present study was to identify the effects of race and ethnicity on the risk of radiotherapy toxicity.Materials and methodsA systematic review was carried out of PubMed, Ovid Medline and Ovid Embase with no year limit. PRISMA 2020 guidelines were followed. Two independent assessors reviewed papers.ResultsOf 607 papers screened, 46 fulfilled the inclusion criteria. Papers were published between 1996 and 2021 and involved 30–28,354 individuals (median 433). Most involved patients with prostate (33%), breast (26%) and lung (9%) cancer. Both early and late toxicities were studied. Some studies reported a higher risk of toxicity in White men with prostate cancer compared with other races and ethnicities. For breast cancer patients, some reported an increased risk of toxicity in White women compared with other race and ethnic groups. In general, it was difficult to draw conclusions due to insufficient reporting and analysis of race and ethnicity in published literature.ConclusionsReporting of race and ethnicity in radiotherapy studies must be harmonised and improved and frameworks are needed to improve the quality of reporting. Further research is needed to understand how ancestral heritage might affect radiosensitivity and risk of radiotherapy toxicity.     

Review of the environmental prenatal exposome and its relationship to maternal and fetal health

Environmental chemicals comprise a major portion of the human exposome, with some shown to impact the health of susceptible populations, including pregnant women and developing fetuses. The placenta and cord blood serve as important biological windows into the maternal and fetal environments. In this article we review how environmental chemicals (defined here to include man-made chemicals [e.g., flame retardants, pesticides/herbicides, per- and polyfluoroalkyl substances], toxins, metals, and other xenobiotic compounds) contribute to the prenatal exposome and highlight future directions to advance this research field. Our findings from a survey of recent literature indicate the need to better understand the breadth of environmental chemicals that reach the placenta and cord blood, as well as the linkages between prenatal exposures, mechanisms of toxicity, and subsequent health outcomes. Research efforts tailored towards addressing these needs will provide a more comprehensive understanding of how environmental chemicals impact maternal and fetal health.     

The preventive role of wheat germ oil against sertraline‐induced testicular damage in male albino rats

Sertraline is an antidepressant medication used extensively in the therapy of depression. The present investigation was intended to estimate the actual protective role of wheat germ oil on sertraline‐caused testicular injury in albino rats. Sertraline (human therapeutic dose, 15.63 mg/kg) was orally administrated to rats for 28 successive days. Sertraline‐administered rats were concurrently supplemented with wheat germ oil (human therapeutic dose, 68.75 mg/kg) for 28 successive days. Sertraline administration induced an elevation in testicular DNA damage and acute testicular damage illustrated by the histopathological alterations including marked degeneration and necrosis of germ cells lining seminiferous tubules, as well as interstitial oedema, congestion of interstitial blood vessel. Wheat germ oil administration potentially mitigated the histopathological alterations of sertraline‐administered rats. Lipid peroxidation, oxidative stress biomarker, showed a significant elevation in testicular tissue of sertraline‐administered rats. Furthermore, glutathione content and catalase activity were decreased in testicular tissue of sertraline‐administered rats. Serum testosterone level was elevated in sertraline‐administered rats. Wheat germ oil significantly reduced lipid peroxidation of testicular tissue and improved the antioxidant defences. Finally, wheat germ oil has a preventive role against testicular damage induced by sertraline in rats probably via its potential to prevent reactive oxygen species.