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•Curcumin localizes in the lipid droplets of glioblastoma cell.•Susceptibility of glioblastoma cells to curcumin is enhanced by pyrrolidine-2.•Curcumin-induced cell death involves ...caspase-3 activation.
Increased lipid droplet number and fatty acid synthesis allow glioblastoma multiforme, the most common and aggressive type of brain cancer, to withstand accelerated metabolic rates and resist therapeutic treatments. Lipid droplets are postulated to sequester hydrophobic therapeutic agents, thereby reducing drug effectiveness. We hypothesized that the inhibition of lipid droplet accumulation in glioblastoma cells using pyrrolidine-2, a cytoplasmic phospholipase A2 alpha inhibitor, can sensitize cancer cells to the killing effect of curcumin, a promising anticancer agent isolated from the turmeric spice. We observed that curcumin localized in the lipid droplets of human U251N glioblastoma cells. Reduction of lipid droplet number using pyrrolidine-2 drastically enhanced the therapeutic effect of curcumin in both 2D and 3D glioblastoma cell models. The mode of cell death involved was found to be mediated by caspase-3. Comparatively, the current clinical chemotherapeutic standard, temozolomide, was significantly less effective in inducing glioblastoma cell death. Together, our results suggest that the inhibition of lipid droplet accumulation is an effective way to enhance the chemotherapeutic effect of curcumin against glioblastoma multiforme.
Inhibition of carbonic anhydrase IX in glioblastoma multiforme Amiri, Abdolali; Le, Phuong Uyen; Moquin, Alexandre ...
European journal of pharmaceutics and biopharmaceutics,
December 2016, 2016-Dec, 2016-12-00, 20161201, Letnik:
109
Journal Article
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Carbonic anhydrase IX (CAIX) is a transmembrane enzyme upregulated in several types of tumors including glioblastoma multiforme (GBM). GBM is among the most aggressive tumors among ...gliomas. Temozolomide (TMZ) therapy combined with surgical or radiation approaches is the standard treatment but not effective in long term. In this study we tested the treatment with acetazolamide (ATZ), an inhibitor of CAIX, alone or combined with TMZ. The experiments were performed in 2D and 3D cultures (spheroids) using glioblastoma U251N and human brain tumor stem cells (BTSCs). Several proteins implicated in tumor cell death were also investigated. The key results from these studies suggest the following: (1) Cell death of human glioblastoma spheroids and BTSC is significantly increased with combined treatment after 7 days, and (2) the effectiveness of ATZ is significantly enhanced against BTSC and U251N when incorporated into nano-carriers. Collectively, these results point toward the usefulness of nano-delivery of CAIX inhibitors and their combination with chemotherapeutics for glioblastoma treatment.
Background: Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans. Median survival with standard-of-care radiation and chemotherapy with ...temozolomide (TMZ) is 15 months. Median survival without treatment is 4 1/2 months. The treatment of GBMs remains difficult in that no contemporary treatments are curative. In addition, brain tumor stem cells (BTSC), the tumorigenic cells, are postulated to be responsible for recurrence of GBM and may be the main cause of therapeutic failure when targeting GBM with TMZ, which induces apoptosis and necroptosis-based cell death. One way to improve the effectiveness of the current therapies is to use combination of drugs with sensitizers. Tumor cores, including those of GBM, are hypoxic, which is a condition commonly associated with poor responses to chemotherapies. In addition, GBM has a highly glycolytic energy cycle, leading to hyper acidification of the tumour cytoplasm. Recent studies have shown that a carbonic anhydrase (CA) isoform, CA IX, is selectively overexpressed by tumor cells, especially GBM, and shows highly restricted expression in normal tissue. A most exciting recent finding also implicates CA IX in the maintenance of a (breast) cancer stem-cell phenotype. CA IX has a dual role in the growth of hypoxic, CO2 excreting tumors. First, it helps to produce and maintain an internal alkaline pH favorable for tumor growth. Second, it promotes tumor cell invasiveness by stromal acidification. Moreover, the acidification of the extracellular milieu is unfavourable to the obligatory chemical activation of the only current treatment for GBM, TMZ. Hypothesis and main objectives: We hypothesize that inhibition of CA IX by acetazolamide (ATZ, a broad-spectrum CA inhibitor used in clinical treatment of altitude sickness) and an anti-CA IX antibody (provided by an industrial sponsor) will enhance the effectiveness of TMZ in GBM 2D and 3D cell models. Results: CA IX expression was significantly increased by CoCl2 (dose dependent) and the highest cell death was caused by ATZ/TMZ combination after 6 days under hypoxia in U251N monolayers (p<0.01). In spheroids (U251N) CA IX expression was time and size dependent. We demonstrated a presence of CA IX in BTSC in culture. ATZ caused minimal cell death. Combination with TMZ in spheroids caused the most significant cell death after 6 days (P<0.0001) with correlative expression of BAX (p<0.05). Caspase-3 activity was increased most significantly for ATZ/TMZ combination in both 2D and 3D cultures (p<0.0001 and p<0.05 respectively). The encapsulation of ATZ into micelles significantly increased cell death in spheroids at all the time points (1-6 days), alone and in combination with TMZ. All data are representative of at least 2 to 6 independent experiments. Significance: TMZ has a poor in-vitro activity, but it is the only current drug to treat GBM. CA IX inhibition appears to influence cell survival alone and makes cells more sensitive to TMZ. A significant cell death induced in GBM and BTSC by micellar ATZ is an exciting finding which will permit in-vivo evaluations using tumours generated from patient-derived GBM stem cells.
Abstract
The use of functional foods (FFs) for maintaining health and preventing or treating illnesses—in recent years—has been dramatically increased in the literature. There are available valuable ...examples of FFs in ethno medicine from different tribes. Ethnic FFs can be valuable resources for developing FFs science, e.g., introducing memorial FFs as an interdisciplinary ethnopharmacological concept. In this paper, ethnic FFs from Bavi tribe (Kohgiluyeh va Boyerahmad province of Iran) have been studied, and their medical potentials are reported. Data gathering was done by interview with Bavi tribe local healers using a questionnaire. Plant materials were collected and identified, and Bavi FFs were prepared according to local procedures. Information of 21 Bavi tribe FFs was collected which are including 20 different plant species.The results showed that most FFs are used to treat chronic diseases including kidney problems like kidney stones, liver disease, neurological complaints, and GI ulcers and are used as lactogogue, while lesser FFs are used to treat acute diseases and symptoms (43%), including nausea and vomiting, common cold, diarrhea, sore throat, and allergy. Most FFs of Bavi tribe are prepared using aromatic plants (75%) responsible for aroma in the final FF. Probably, aromatic FFs increase patient acceptance, without mimicking unpleasant memory of drug recommendation. Plants that are used in FF are mostly perennial (80%) and wild growing (80%), indicating continuous contact of natives and so having memory with such habitant herbals. Treating diseases by homemade FFs which are prepared by well-known aromatic herbals is a routine procedure among natives like the Bavi tribe. Such easily made FFs with well-known taste and flavors which may change the patient’s mood should be studied in a new approach, “memorial FFs”, as a novel opportunity for healthcare and curing.
We aimed to assess the power of radiomic features based on computed tomography to predict risk of chronic kidney disease in patients undergoing radiation therapy of abdominal cancers.
50 patients ...were evaluated for chronic kidney disease 12 months after completion of abdominal radiation therapy. At the first step, the region of interest was automatically extracted using deep learning models in computed tomography images. Afterward, a combination of radiomic and clinical features was extracted from the region of interest to build a radiomic signature. Finally, six popular classifiers, including Bernoulli Naive Bayes, Decision Tree, Gradient Boosting Decision Trees, K-Nearest Neighbor, Random Forest, and Support Vector Machine, were used to predict chronic kidney disease. Evaluation criteria were as follows: accuracy, sensitivity, specificity, and area under the ROC curve.
Most of the patients (58%) experienced chronic kidney disease. A total of 140 radiomic features were extracted from the segmented area. Among the six classifiers, Random Forest performed best with the accuracy and AUC of 94% and 0.99, respectively.
Based on the quantitative results, we showed that a combination of radiomic and clinical features could predict chronic kidney radiation toxicities. The effect of factors such as renal radiation dose, irradiated renal volume, and urine volume 24-h on CKD was proved in this study.
•Radiomic features based on computed tomography (CT) could predict radiation induced kidney damage.•The random forest algorithm achieved good performance of prediction.•The other modalities of medical imaging and additional clinical data can lead to a better prediction model.
Gas hydrates are solid crystalline compounds formed by water and gas molecules through molecular interactions, typically at low temperatures and high pressures. While gas hydrates are generally known ...as flow assurance challenges for the oil and gas industries (e.g., pipeline blockages), numerous studies have shown the potential application of gas hydrate in carbon capture and storage (CCS).
Due to the more thermodynamic stability of CO2 hydrate compared to other industrial emission gas components like nitrogen, CO2 hydrates have emerged as a viable mechanism for CO2 capture. Moreover, a large volume of CO2 can be stored securely in the stable structure of gas hydrates, providing an additional benefit for CO2 storage in geological formations. Thus, gas hydrates can be suggested as a technology for mitigating CO2 emissions.
Notwithstanding the CO2 hydrate advantages in CCS, they may also present some challenges, particularly in terms of flow assurance. For example, CO2 hydrate formation during CO2 transportation can cause a serious pipeline blockage. Therefore, the fundamental understanding of gas hydrates is crucial for CCS. In the first part of this review, the principle on gas hydrates (especially CO2 hydrates) and CO2 hydrate-based carbon capture are discussed.
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•CO2 gas hydrate-based technology can be used for Carbon Capture and Storage (CCS).•CO2 hydrates offer a sustainable chemistry solution to achieve net zero targets.•Gas hydrates have diverse applications, from energy to CCS, beyond flow assurance.
CO2 hydrate offers some substantial applications for Carbon Capture and Storage (CCS). While CO2 hydrate chemistry and CO2 capture are reviewed in part 1 of this review, CO2 transportation and ...storage are discussed in this part. Basically, CO2 transportation is required between CO2 capture plants and CO2 sequestration sites. It is imperative to acknowledge that most strategies for achieving deep decarbonization are linked to the expansion of the current transport infrastructure. When dealing with substantial distances between CO2 capture plants and CO2 sequestration sites, the expenses associated with CO2 transportation can surpass the capture process itself. Therefore, despite the benefits of CO2 hydrates in CCS, challenges, such as flow assurance issues, may arise. For example, CO2 hydrate formation can lead to pipeline blockages, emphasizing the need for CO2 gas hydrate flow assurance study as discussed in this part.
Additionally, site selection for CO2 storage requires careful consideration. Geological storage, whether in hydrate form or through the injection of CO2 or high-CO2 content mixtures, offers potential advantages, such as long-term storage and self-sealing capabilities. However, there are some challenges like CO2 hydrate processes in porous media, injectivity, flow behaviour in hydrate reservoirs, mechanical behaviour, etc., which are discussed in this review.
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•Concerns about flow assurance arise due to CO2 hydrate formation.•The potential for geological storage lies in CO2 hydrates.•Injecting CO2 or CO2-rich mixtures into gas hydrate reservoirs is explored.•Understanding the mechanical properties of gas hydrates in sediments is crucial.•Field Scale for Hydrate-based Carbon Capture and Storage is explored.
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