Traitement de glioblastomes par livraison convection-augmentée de médicaments platinés et leurs formulations liposomales combinée à la radiothérapie

Abstract : Glioblastoma is the most common and aggressive brain cancer in adults. The current standard-of-care treatment includes surgical resection, radiation therapy with concomitant and adjuvant temozolomide (TMZ) chemotherapy. However, the addition of TMZ to radiation therapy only increased the median survival time (MeST) by 2.5 months. This limited improvement is partially attributable to the low accumulation of chemotherapeutic drugs in the brain tumor due to the blood-brain barrier (BBB). Thus, new delivery methods such as intra-arterial, BBB disruption and convection-enhanced delivery (CED) have been proposed to overcome this limitation. Besides, timing tumor irradiation to coincide with the maximal concentration of platinum-DNA adducts could result in improved tumor control. In this study, CED of cisplatin and oxaliplatin, their respective liposomal formulations Lipoplatin™, Lipoxal™, and carboplatin with or without 15 Gy of radiation therapy has been carried out in F98 glioma bearing Fischer rats to assess their toxicity and MeST. The amount of platinum-DNA adducts in the tumor at 4 h and 24 h after CED was measured and irradiation was administered at these two different time periods to test the concomitant effect. In addition, four liposomal carboplatin formulations with different chemo-physical properties were prepared and their toxicity and MeST were also evaluated in this animal model. Among the tested platinum drugs, carboplatin and Lipoxal™ demonstrated a highest maximum-tolerated dose of 25 µg and 30 µg respectively. CED of carboplatin showed the longest MeST of 38.5 days, and increased to 54.0 days with the addition of 15 Gy radiation therapy. However, radiation at 4 h after CED of either oxaliplatin or carboplatin did not show any survival improvement when compared to radiation at 24 h, although the quantity of platinum-DNA adducts at 4 h was higher than at 24 h after CED. In the four liposomal carboplatin formulations, anionic pegylated liposomal carboplatin showed the longest MeST of 49.5 days, due to its longer tumoral retention time and probably larger distribution volume in the brain.Résumé : Le glioblastome est le cancer primaire du cerveau le plus courant et agressif chez l’adulte. Le traitement standard comprend la résection chirurgicale, la radiothérapie et la chimiothérapie concomitante et adjuvante avec le témozolomide(TMZ). L'addition de TMZ combinée la radiothérapie a augmenté la survie médiane (MeST) de 2,5 mois. Cette faible amélioration est partiellement due à l'accumulation limitée de médicaments chimiothérapeutiques dans la tumeur cérébrale à cause de la barrière hémato-encéphalique (BBB). Ainsi, de nouvelles méthodes comme l’injection intraartérielle, la rupture osmotique de la barrière hémato-encéphalique, la livraison augmentée par convection (CED) ont été suggérées pour surmonter ce problème. En plus, l’optimisation de l’irradiation de la tumeur lorsque le maximum d’adduits platine-ADN est atteint pourrait aboutir à un meilleur contrôle de la tumeur. Dans cette étude, nous avons injecté par CED le cisplatine, l’oxaliplatine, avec leur formulation liposomale Lipoplatin™, Lipoxal™ ainsi que le carboplatine avec ou sans radiation de 15 Gy. La toxicité et le temps de MeST ont été mesurés chez des rats Fischer porteurs du gliome. La quantité d'adduits platine-ADN dans la tumeur a été mesurée 4 h et 24 h après CED. L’irradiation de la tumeur a été effectuée à ces deux temps pour tester l'effet concomitant. En plus, quatre formulations liposomales de carboplatine avec différentes propriétés chimiophysiques ont été préparées et leur toxicité et MeST combiné à la radiation ont également été évalués. Parmi les drogues de platine testées, le carboplatine et Lipoxal™ ont démontré respectivement la dose maximale tolérée la plus élevée, soit 25 µg et 30 µg. La MeST du carboplatine était la plus longue avec 38,5 jours qui a augmenté à 54,0 jours avec l’addition de 15 Gy de radiothérapie. Toutefois, l’irradiation à 4 h après CED effectuée avec l'oxaliplatine et le carboplatine n'a pas amélioré la MeST comparé à l’irradiation à 24 h, bien que la quantité d'adduits platine-ADN à 4 h était supérieure à celle mesurée à 24 h après CED. Pour les quatre formulations liposomales de carboplatine, celle pégylée négatif a démontré la plus longue MeST, soit 49,5 jours

The use of deep learning methods in low-dose computed tomography image reconstruction : a systematic review

Conventional reconstruction techniques, such as filtered back projection (FBP) and iterative reconstruction (IR), which have been utilised widely in the image reconstruction process of computed tomography (CT) are not suitable in the case of low-dose CT applications, because of the unsatisfying quality of the reconstructed image and inefficient reconstruction time. Therefore, as the demand for CT radiation dose reduction continues to increase, the use of artificial intelligence (AI) in image reconstruction has become a trend that attracts more and more attention. This systematic review examined various deep learning methods to determine their characteristics, availability, intended use and expected outputs concerning low-dose CT image reconstruction. Utilising the methodology of Kitchenham and Charter, we performed a systematic search of the literature from 2016 to 2021 in Springer, Science Direct, arXiv, PubMed, ACM, IEEE, and Scopus. This review showed that algorithms using deep learning technology are superior to traditional IR methods in noise suppression, artifact reduction and structure preservation, in terms of improving the image quality of low-dose reconstructed images. In conclusion, we provided an overview of the use of deep learning approaches in low-dose CT image reconstruction together with their benefits, limitations, and opportunities for improvement

High-resolution crop yield and water productivity dataset generated using random forest and remote sensing

Accurate and high-resolution crop yield and crop water productivity (CWP) datasets are required to understand and predict spatiotemporal variation in agricultural production capacity; however, datasets for maize and wheat, two key staple dryland crops in China, are currently lacking. In this study, we generated and evaluated a long-term data series, at 1-km resolution of crop yield and CWP for maize and wheat across China, based on the multiple remotely sensed indicators and random forest algorithm. Results showed that MOD16 products are an accurate alternative to eddy covariance flux tower data to describe crop evapotranspiration (maize and wheat RMSE: 4.42 and 3.81 mm/8d, respectively) and the proposed yield estimation model showed accuracy at local (maize and wheat rRMSE: 26.81 and 21.80%, respectively) and regional (maize and wheat rRMSE: 15.36 and 17.17%, respectively) scales. Our analyses, which showed spatiotemporal patterns of maize and wheat yields and CWP across China, can be used to optimize agricultural production strategies in the context of maintaining food security

Evaluation of Rock Burst Propensity and Rock Burst Mechanism in Deep Phosphate Mines: A Case Study of Sujiapo Phosphate Mine, Hubei Province, China

Rockburst is one of the major problems in rock underground engineering and mechanics. To make a risk assessment of rockburst and improve the mine safety index, some evaluation systems for rockburst propensity have been proposed and applied, and progress has been made in the study of high-value mines and single evaluation systems, but these evaluation systems are still immature for deep low and medium grade phosphate mines with more complex influencing factors. Therefore, to solve this problem, this study takes the phosphate mining area of the Sujiapo phosphate mine as the main research object, and combines the characteristics of the deep rockburst of the phosphate mine and its physical and mechanical properties; the evaluation system combines fuzzy mathematical method and multiple evaluation methods to determine the propensity of rockburst of deep mining of Sujiapo phosphate mine. The JSM-500LV SEM and acoustic emission results are used to analyze the microscopic mechanism of rockburst from the morphology and composition of the rocks, and the rationality of the evaluation system is further demonstrated. The study shows that dolomite and phosphorite in the study area are moderate rockburst, and shale has a weak rockburst tendency; because the roof dolomite and phosphorite crystallization degree are higher, the elastic modulus is large. Under the action of external load, the roof dolomite stored more elastic strain energy. Deformation damage consumes less energy. The energy released to the outside world after the damage is large, more likely to occur brittle damage, and the rockburst tendency is high. Therefore, the evaluation system combining multiple evaluation methods can comprehensively determine rockburst in phosphate mines

Concomitant Chemoradiation Therapy with Gold Nanoparticles and Platinum Drugs Co-Encapsulated in Liposomes

A liposomal formulation of gold nanoparticles (GNPs) and carboplatin, named LipoGold, was produced with the staggered herringbone microfluidic method. The radiosensitizing potential of LipoGold and similar concentrations of non-liposomal GNPs, carboplatin and oxaliplatin was evaluated in vitro with the human colorectal cancer cell line HCT116 in a clonogenic assay. Progression of HCT116 tumor implanted subcutaneously in NU/NU mice was monitored after an irradiation of 10 Gy combined with either LipoGold, GNPs or carboplatin injected directly into the tumor by convection-enhanced delivery. Radiosensitization by GNPs alone or carboplatin alone was observed only at high concentrations of these compounds. Furthermore, low doses of carboplatin alone or a combination of carboplatin and GNPs did not engender radiosensitization. However, the same low doses of carboplatin and GNPs administered simultaneously by encapsulation in liposomal nanocarriers (LipoGold) led to radiosensitization and efficient control of cell proliferation. Our study shows that the radiosensitizing effect of a combination of carboplatin and GNPs is remarkably more efficient when both compounds are simultaneously delivered to the tumor cells using a liposomal carrier