Evaluation of a nanocomposite of PEG-curcumin-gold nanoparticles as a near-infrared photothermal agent: an in vitro and animal model investigation

Abstract

Hyperthermia is a promising alternative modality for the conventional cancer treatments. Nanoparticle-mediated photothermal therapy (PTT) has been widely applied for hyperthermia cancer therapy by a near-infrared light irradiation. Some special nanoparticles can convert light energy into heat and destroy the tumor cells. Inspired from the photothermal efficacy of the gold nanoparticles, here we synthesized, characterized, and applied novel photothermal polyethylene glycol-curcumin-gold nanoparticles (PEG-Cur-Au NPs) in cancer PTT. The effect of PEG-Cur-Au NPs upon irradiation by an 808-nm laser on C540 (B16/F10) cell line as well as implanted (bearing) melanoma tumor in inbred C57 mice was investigated. In vitro temperature increment, cell viability evaluation, and histological analyses were performed. The results showed a dose-dependent cytotoxicity of PEG-Cur-Au NPs toward C540 (B16/F10) cell line at concentrations ≥ 25 μg mL⁻¹ with an IC₅₀ value of 42.7 μg mL⁻¹ in dark (and with no toxicity for 10 μg mL⁻¹). On the other hand, 808-nm laser irradiation alone (without using PEG-Cur-Au NPs) for 10 min induced killing effect on the C540 (B16/F10) cell line in a laser power-dependent manner at power density > 0.5 W cm⁻² (no toxicity for 0.5 W cm⁻²). However, PPT using PEG-Cur-Au NPs was tremendously observed after laser illumination. Even under laser irradiation at a power density of 0.5 W cm⁻² of PEG-Cur-Au NPs of concentrations < 10 μg mL⁻¹, PTT of the cells was substantial. Histological analyses and volume measurements of the induced tumors in the mice revealed an appropriate control of the tumors upon PTT by PEG-Cur-Au NPs. Combination of PEG-Cur-Au NP administration and 808-nm diode laser irradiation destroyed the melanoma cancer cells in the animal model.

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Design optimisation of C ion implantation of α-Al2O3 for medical dosimetry

Publication date: 5 September 2018
Source:Materials & Design, Volume 153
Author(s): Mini Agarwal, S.K. Garg, K. Asokan, S. Thulkar, S. Chander, M.K. Dalai, Pratik Kumar
The present work reports the fabrication and characterization of α–Al2O3:C, a highly sensitive low effective atomic number (Zeff = 10.7) OSL material for medical dosimetry, through a new approach of doping via implantation. In this study, a Single Crystalline α–Al2O3 (SCALO) and a Sapphire α–Al2O3 (SALO) are used and implanted with 100 keV of C⁺ at various fluences (mol%) from 2.5 × 10¹⁴ ions cm⁻² (~0.04%) to 6.25 × 10¹⁵ ions cm⁻² (~1%) and are pre-heated up to 220 °C. The structural, optical, morphological and luminescent studies of the Carbon doped α–Al2O3 (α–Al2O3:C) are carried out using X-ray diffraction, Ultraviolet-visible spectroscopy (UV–Vis), Photo-luminescence (PL), Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS), Optically Stimulated Luminescence (OSL), and Thermo-Luminescence (TL). The doping of ~1 mol% of C⁺ is found at an optimized doping level due to its high intensity of luminescence. This phenomenon is studied for heavy charged particle (HCP) dosimetry, which might prove effective for cancer treatment. It is found that α –ALO:C (both the single crystalline and the sapphire alumina) has the capability to measure large radiation doses (~kGy). This is attributed to the generation of stable defects after the incorporation of Carbon that results in a linear response with the dose and in extraordinary efficiency. Thus, this study confirms the development of α–Al2O3 by the novel approach of C⁺ implantation method and the findings result in an efficient medical radiation dosimeter.

Graphical abstract

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The spatial distribution of α phase in laser melting deposition additive manufactured Ti-10V-2Fe-3Al alloy

Publication date: 15 September 2018
Source:Materials & Design, Volume 154
Author(s): Zongge Jiao, Jun Fu, Zhuo Li, Xu Cheng, Haibo Tang, Huaming Wang
Ti-10V-2Fe-3Al alloy specimen has been fabricated by laser melting deposition additive manufacturing technique. Due to the repeated heating and cooling during deposition, complicated and unique phase transformation process take place with forming different microstructures from forging. In this study, a three-dimensional (3D) reconstruction method is used to understand the spatial distribution of α phase in different grains. The results indicated that, in as deposited alloy, α laths has a plate morphology, and they precipitated out from β phase followed a tetrahedral relationship. And the different grain orientation result to the specific different morphology. When the cutting plane parallel to the {100} plane of BCC cell, α laths are perpendicular to each other. If the cutting plane is parallel to the {111} plane, a special morphology with mixture of plate-like and rod-like α phase is founded.

Graphical abstract

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Immuntherapie des Melanoms

Zusammenfassung

Hintergrund

Die Prognose für Patienten mit fernmetastasiertem Melanom war bis zur Zulassung des Anti-CTLA-4-Antikörpers Ipilimumab 2011 mit einem medianen Gesamtüberleben von 6 bis 10 Monaten infaust. Die Zulassung der Immuncheckpointinhibitoren, die für Patienten mit metastasiertem Melanom ein Langzeitüberleben erwirken können, stellt einen Durchbruch dar.

Ziel, Material und Methoden

Die aktuellen zugelassenen Systemtherapien des Melanoms unter Berücksichtigung der Studiendaten, die auf der Jahrestagung 2017 der American Society of Clinical Oncology (ASCO) sowie der European Society for Medical Oncology (ESMO) vorgestellt wurden, werden in dieser Übersichtsarbeit zusammengefasst.

Ergebnisse und Diskussion

Verglichen mit Ipilimumab konnten die beiden zugelassenen Anti-PD-1-Antikörper Pembrolizumab und Nivolumab eine höhere Wirksamkeit bei niedrigerer Toxizität erzielen. Die 2016 zugelassene Immunkombinationstherapie mit Nivolumab und Ipilimumab erzielte eine Ansprechrate von 58 % und eine Dreijahresüberlebensrate von 58 %. Schwere Grad-3/4-Nebenwirkungen traten bei 55 % der Patienten auf. Die frühzeitige Diagnose immunvermittelter Nebenwirkungen unter Immuncheckpointinhibitor-Therapie und ihre adäquate Behandlung ggf. unter Einsatz von systemischen Glukokortikosteroiden und weiteren Immunsuppressiva ist unabdingbare Voraussetzung für den Therapieerfolg. Die Immunkombinationstherapie mit Nivolumab und Ipilimumab erzielte bei Patienten mit metastasiertem Melanom und Hirnmetastasen intrakranielle Ansprechraten von 42–55 %, wobei die Toxizität im Vergleich zu Patienten ohne Hirnmetastasen nicht erhöht war. Aufgrund des erfolgreichen Einsatzes von Immuncheckpointinhibitoren für die Therapie des metastasierten Melanoms werden aktuell mehrere Studien durchgeführt, die insbesondere Anti-PD-1-Antikörper im adjuvanten Setting evaluieren. In aktuellen und zukünftigen Studien werden zunehmend innovative Immunkombinationstherapien, z. B. Anti-PD-1-Antikörper in Kombination mit IDO-Inhibitoren (IDO Indoleamine-pyrrole 2,3-dioxygenase) untersucht. Bisher vorliegende Daten sprechen für eine hohe Wirksamkeit und eine niedrige Toxizität.

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Introduction of a modified double-lumen tube

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Relationship between fresh frozen plasma to packed red blood cell transfusion ratio and mortality in cardiovascular surgery

Abstract

Purpose

The aim of this study was to examine the relationship between FFP (fresh frozen plasma)/pRBC (packed red blood cell) transfusion ratio and outcomes in patients undergoing cardiovascular surgery.

Methods

This is a single center retrospective cohort study performed in a cardiovascular center. Patients undergoing cardiovascular surgery between January 2012 and October 2016 with or without massive transfusion (n = 1453). Patients' outcomes were compared based on FFP/pRBC transfusion ratio (FFP/pRBC > 1 or FFP/pRBC ≤ 1).

Results

In hospital mortality and rate of stroke and myocardial infarction was significantly higher in patients with less than 1 of FFP/pRBC transfusion ratio only in patients with massive transfusion (3.0 vs 8.8%, p = 0.001; 0.7 vs 6.4%, p < 0.001; 1.0 vs 3.2%, p = 0.047, respectively).

Conclusions

Higher FFP/RBC ratio was associated with reduced risk of death, stroke and myocardial infarction only in patients with cardiovascular surgery receiving massive transfusion. Clinicians should be aware that judicious FFP replacement plays a critical role in the successful management of massive transfusion in cardiac surgery.

https://ift.tt/2IBbcOG

PET/RM con 18F-colina en la sospecha de recurrencia del carcinoma de próstata

Publication date: Available online 22 May 2018
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): C. Riola-Parada, J.L. Carreras-Delgado, V. Pérez-Dueñas, M. Garcerant-Tafur, L. García-Cañamaque
ObjetivoEvaluar la utilidad de la PET/RM con ¹⁸F-colina simultánea en la sospecha de recurrencia del carcinoma de próstata y relacionar su tasa de detección de enfermedad con variables analíticas y anatomopatológicas.Material y métodosEstudio retrospectivo de 27 pacientes con carcinoma de próstata que recibieron terapia local como tratamiento primario, a quienes se les realizó una PET/RM con ¹⁸F-colina por sospecha de recurrencia (elevación mantenida de los niveles de PSA). Los hallazgos patológicos de la PET/RM con ¹⁸F-colina fueron validados mediante el análisis anatomopatológico, otras pruebas de imagen o por la respuesta bioquímica al tratamiento oncológico.ResultadosLa PET/RM con ¹⁸F-colina detectó enfermedad en 15 de los 27 pacientes (tasa de detección del 55,56%); 4 (15%) presentaron recurrencia exclusivamente local, 5 (18%) metástasis ganglionares y 7 (26%) metástasis óseas. El PSA medio (PSAmed) a la realización del estudio fue de 2,94ng/mL (rango 0,18-10ng/mL). Los pacientes con PET/RM positiva presentaron un PSAmed de 3,70ng/mL (rango 0,24-10ng/mL), mayor que los pacientes con PET/RM negativa, PSAmed de 1,97ng/mL (rango 0,18-4,38ng/mL), aunque sin diferencias estadísticamente significativas. La puntuación Gleason al diagnóstico de los pacientes con estudio positivo fue de 7,33 (rango 6-9), y la de los pacientes con estudio negativo fue de 7 (rango 6-9), sin diferencias estadísticamente significativas.ConclusiónLa tasa de detección de la PET/RM con ¹⁸F-colina fue considerable pese a los valores relativamente bajos de PSA en nuestra muestra. La influencia de la puntuación Gleason y del nivel de PSA en la tasa de detección de la PET/RM con ¹⁸F-colina no fue estadísticamente significativa.ObjectiveTo evaluate the usefulness of simultaneous ¹⁸F-choline PET/MRI in the suspicion of prostate cancer recurrence and to relate ¹⁸F-choline PET/MRI detection rate with analytical and pathological variables.Material and methods27 patients with prostate cancer who received local therapy as primary treatment underwent a ¹⁸F-choline PET/MRI due to suspicion of recurrence (persistently rising serum PSA level). ¹⁸F-choline PET/MRI findings were validated by anatomopathological analysis, other imaging tests or by biochemical response to oncological treatment.Results¹⁸F-choline PET/MRI detected disease in 15 of 27 patients (detection rate 55.56%). 4 (15%) presented exclusively local recurrence, 5 (18%) lymph node metastases and 7 (26%) bone metastases. Mean PSA (PSAmed) at study time was 2.94ng/mL (range 0.18-10ng/mL). PSAmed in patients with positive PET/MRI was 3.70ng/mL (range 0.24-10ng/mL), higher than in patients with negative PET/MRI, PSAmed 1.97ng/mL (range 0.18-4.38ng/mL), although without statistically significant differences. Gleason score at diagnosis in patients with a positive study was 7.33 (range 6-9) and in patients with a negative study was 7 (range 6-9), without statistically significant differences.Conclusion¹⁸F-choline PET/MRI detection rate was considerable despite the relatively low PSA values in our sample. The influence of Gleason score and PSA level on ¹⁸F-choline PET/MRI detection rate was not statistically significant.



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