Gonzalez, Valeria

Inadequate light penetration in tissues restricts photodynamic therapy to treating only superficial tumors. To enable x-ray–excited photodynamic therapy (XPDT) that targets deep-seated tumors, we synthesized a nanoscintillator-photosensitizer complex containing 5% Eu-doped Y 2 O 3 fluorescing at 611 nanometers and decorated with SiO 2 containing the scintillation-coupled photosensitizer methylene blue and a polyethylene glycol coating [PEGylated Y 2 O 3 :Eu@SiO 2 -methylene blue (pYSM)]. When irradiated, pYSMs generate singlet oxygen species in vitro, causing cytotoxicity with hallmarks of immunogenic cell death (calreticulin translocation to the cell membrane). Intravenously administered pYSMs home passively to pancreatic tumor xenografts and, upon 10 gray irradiation, cause significant tumor regression ( P < 0.01). On combining XPDT with anti-PD1 immunotherapy, a distant nonirradiated tumor also regresses via an increase in intratumoral activated CD8 + cytotoxic T cells. Collectively, we advance a systemically delivered XPDT strategy that mediates an antitumor effect in both irradiated and nonirradiated (abscopal) tumors when coupled with immunotherapy, converting an immunologically “cold” tumor to an immunologically “hot” tumor.

This case report describes a conjunctival biopsy of a patient with mpox infection.

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l -glutamic acid and l -lysine within an amphiphilic polymer of poly( l -glutamic acid-co- l -lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate in the periphery and core of tumors without any signs of serum biochemical or hematological alterations, normal organ histopathological abnormalities, or overt deterioration in animal health. Furthermore, P(Glu-co-Lys)-GNRs penetrated the tumor microenvironment to accumulate in the hypoxic cores of tumors to potently radiosensitize heterotopic and orthotopic pancreatic cancers in vivo.

ObjectiveThe uncinate process may play a role in the amount of irrigation penetrance. In this cadaver study, we aimed to investigate if the addition of partial uncinectomy provides better maxillary sinus irrigation penetrance than balloon sinuplasty (BSP) alone.Study DesignCadaveric study.SettingSimulation laboratory at the Mayo Clinic in Florida.MethodsFive fresh‐frozen human cadaveric heads (10 sides) were used to assess maxillary sinus irrigation penetration after 3 interventions performed sequentially: irrigation penetrance with no intervention, irrigation after BSP, and irrigation after BSP and partial removal of the uncinate. Penetrance was recorded with intrasinus endoscopy and scored by 4 blinded observers using a scale from 0 (no irrigation) to 5 (fully irrigated). The diameter of the maxillary ostium was measured before and after BSP. Internal consistency was evaluated with Cronbach’s alpha.ResultsMean ostium size increased from 4.1 to 6.8 mm after BSP (P =. 013). Cronbach’s alpha was 0.93. The median scores of irrigation penetration after no intervention, BSP, and BSP and partial uncinectomy were 2.5, 3, and 4, respectively. We found a significantly higher penetrance following partial uncinectomy plus BSP versus BSP alone (P =. 008). Both interventions had a statistically significant difference in irrigation penetrance as compared with no intervention (P =. 0001).ConclusionMaxillary sinus irrigation penetration increased from baseline after BSP. The addition of a partial uncinectomy to the balloon dilation of the maxillary sinus was associated with a statistically significant increase in irrigation penetrance scores as compared with BSP alone.