Peptide-Platinum(IV) Conjugation Minimizes the Negative Impact of Current Anticancer Chemotherapy on Nonmalignant Cells.

The relative success of platinum (Pt)-based chemotherapy comes at the cost of severe adverse side effects and is associated with a high risk of pro-oncogenic activation in the tumor microenvironment. Here, we report the synthesis of C-POC, a novel Pt(IV) cell-penetrating peptide conjugate showing a reduced impact against nonmalignant cells. In vitro and in vivo evaluation using patient-derived tumor organoids and laser ablation inductively coupled plasma mass spectrometry indicates that C-POC maintains robust anticancer efficacy while displaying diminished accumulation in healthy organs and reduced adverse toxicity compared to the standard Pt-based therapy. Likewise, C-POC uptake is significantly lowered in the noncancerous cells populating the tumor microenvironment. This results in the downregulation of versican, a biomarker of metastatic spreading and chemoresistance that we found upregulated in patients treated with standard Pt-based therapy. Altogether, our findings underscore the importance of considering the off-target impact of anticancer treatment on normal cells to improve drug development and patient care.

Long-term platinum-based drug accumulation in cancer-associated fibroblasts promotes colorectal cancer progression and resistance to therapy.

A substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence of drug resistance. Here, we apply elemental imaging to the mapping of CT biodistribution after therapy in residual colorectal cancer and achieve a comprehensive analysis of the genetic program induced by oxaliplatin-based CT in the tumor microenvironment. We show that oxaliplatin is largely retained by cancer-associated fibroblasts (CAFs) long time after the treatment ceased. We determine that CT accumulation in CAFs intensifies TGF-beta activity, leading to the production of multiple factors enhancing cancer aggressiveness. We establish periostin as a stromal marker of chemotherapeutic activity intrinsically upregulated in consensus molecular subtype 4 (CMS4) tumors and highly expressed before and/or after treatment in patients unresponsive to therapy. Collectively, our study underscores the ability of CT-retaining CAFs to support cancer progression and resistance to treatment.

Comparison of Mg/Ca concentration series from Patella depressa limpet shells using CF-LIBS and LA-ICP-MS.

The elemental composition of marine mollusk shells can offer valuable information about environmental conditions experienced by a mollusk during its lifespan. Previous studies have shown significant correlations between Mg/Ca concentration ratios measured on biogenic carbonate of mollusk shells and sea surface temperature (SST). Here we propose the use of Laser-Induced Breakdown Spectroscopy (LIBS) and the validation of the Calibration-Free LIBS (CF-LIBS) approach for the rapid measurement and estimation of Mg/Ca molar concentration profiles within Patella depressa Pennant, 1777 limpet shells. To achieve these objectives, results derived from CF-LIBS methodology are compared with those obtained from an established analytical technique for this purpose, such as Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Concentration series obtained with both methodologies show defined temporal patterns and reflect the season-of-capture in each specimen. The results evidence a significant correlation (R2 = 0.63-0.81) between CF-LIBS and LA-ICP-MS Mg/Ca molar concentration profiles within four live-collected P. depressa shells. Averaged error for the molar concentration estimated with CF-LIBS was lower than 10% in every specimen. The comparison between the results obtained from two techniques used in this study has allowed us to demonstrate for the first time that Mg/Ca molar concentration measured in biogenic carbonates were accurately inferred using CF-LIBS technique. The CF-LIBS approach validation represents great potential for the rapid and large-scale paleoenvironmental and archaeological analysis of this mollusk species, which is frequently found in archaeological sites.

Migration and brackish environment use of Prochilodus lineatus (Characiformes: Prochilodontidae) inferred by Sr:Ca ratio transects of otolith

The streaked prochilod, Prochilodus lineatus, represents the most important fishery in the La Plata Basin (South America). Our objective was to analyze brackish environment use by the streaked prochilod captured from Paraná and Uruguay rivers. To accomplish this, lapillus otolith sections were analyzed for Sr:Ca with laser ablation-inductively coupled plasma-mass spectrometry (LA ICP-MS) to infer habitat use of fish. To the interpretation of transects, a threshold that represents the transition between freshwater and brackish environments was calculated using the Sr:Ca ratio of the otolith edge of specimens captured in the first section of the La Plata Estuary (salinity ≥ 0.5 PSU). The percentage of fish using the estuary was higher in the Paraná (37%) than the Uruguay River (5%). Change-point analysis showed that fish entered the estuary between 1 and 3 times throughout life at a wide range of ages (0-15 years). These incursions had no obvious periodicity. This information should be integrated into future management actions, which should also be specific to each area since migration patterns differ between the major rivers of the basin.(AU)

El sábalo, Prochilodus lineatus, representa la pesquería más importante en la Cuenca del Río de la Plata (Sudamérica). Nuestro objetivo fue analizar el uso del hábitat estuarino del sábalo proveniente de los ríos Uruguay y Paraná. Para esto, se analizó la relación Sr:Ca en secciones de otolitos lapilli por ablación láser acoplada a espectrometría de masas con fuente de plasma de acoplamiento inductivo (LA ICP-MS) para inferir el uso de hábitat. Para interpretar las transectas, un umbral que representa la transición entre los ambientes de agua dulce y estuarino, fue calculado usando la relación Sr:Ca del borde del otolito de especímenes capturados en la primera sección del estuario del Plata (salinidad ≥0.5 UPS). El porcentaje de peces que usaron el estuario fue más elevado para el Paraná (37%) en relación al Uruguay (5%). El análisis de cambio puntual mostro que los individuos ingresan al estuario entre 1 a 3 veces a lo largo de la vida en un amplio rango de edades (0-15 años). Las incursiones no mostraron una periodicidad notoria. Esta información debería integrarse a futuras acciones de manejo que deberían ser específicas para cada área considerando los patrones de migración que difieren entre los grandes ríos de la Cuenca.(AU)

Depth profiling with modified dc-Grimm and rf-Grimm-type glow discharges operated with high gas flow rates and coupled to a high-resolution mass spectrometer.

The improved analytical capability of direct-current (dc) and radiofrequency (rf) "fast flow" glow discharges coupled to a sector field mass spectrometer (GD-SFMS) are presented. In particular, the effect of GD chamber design has been studied to obtain suitable crater shapes for depth-profile analysis of solid samples while maintaining the high sensitivity and stability of this source. In this study it was observed that the distance between the sample surface and the end of the flow tube is critical and so careful optimisation is needed. Under optimum conditions plane crater profiles, with high ion-signal sensitivity and sufficient stability, were obtained. The capability to determine qualitative and semi-quantitative depth profiles is presented here using, as model, a coated sample of certified thickness. Finally, the depth resolution achieved for qualitative depth profiles obtained by rf-GD-(SF)MS is compared with that for the well-established rf-GD optical emission spectroscopy (OES) technique.