scholarly journals Proton minibeam radiation therapy: a promising therapeutic approach for radioresistant tumors

2021 ◽  
Vol 344 (4) ◽  
pp. 409-420
Author(s):  
Yolanda Prezado
Author(s):  
Sima Kazemi ◽  
Rasoul Mirzaei ◽  
Mohammad Sholeh ◽  
Sajad Karampoor ◽  
Fariba Keramat ◽  
...  

2020 ◽  
Vol 21 (3) ◽  
pp. 777 ◽  
Author(s):  
Lewis E. Fry ◽  
Caroline F. Peddle ◽  
Alun R. Barnard ◽  
Michelle E. McClements ◽  
Robert E. MacLaren

RNA editing aims to treat genetic disease through altering gene expression at the transcript level. Pairing site-directed RNA-targeting mechanisms with engineered deaminase enzymes allows for the programmable correction of G>A and T>C mutations in RNA. This offers a promising therapeutic approach for a range of genetic diseases. For inherited retinal degenerations caused by point mutations in large genes not amenable to single-adeno-associated viral (AAV) gene therapy such as USH2A and ABCA4, correcting RNA offers an alternative to gene replacement. Genome editing of RNA rather than DNA may offer an improved safety profile, due to the transient and potentially reversible nature of edits made to RNA. This review considers the current site-directing RNA editing systems, and the potential to translate these to the clinic for the treatment of inherited retinal degeneration.


2017 ◽  
Vol 26 (144) ◽  
pp. 170044 ◽  
Author(s):  
Sabine Geiger ◽  
Daniela Hirsch ◽  
Felix G. Hermann

Besides cancer and cardiovascular diseases, lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions no effective and curative treatment options are available. Cell therapies offer a novel therapeutic approach due to their inherent anti-inflammatory and anti-fibrotic properties. Mesenchymal stem/stromal cells (MSC) are the most studied cell product. Numerous preclinical studies demonstrate an improvement of disease-associated parameters after MSC administration in several lung disorders, including chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis. Furthermore, results from clinical studies using MSCs for the treatment of various lung diseases indicate that MSC treatment in these patients is safe. In this review we summarise the results of preclinical and clinical studies that indicate that MSCs are a promising therapeutic approach for the treatment of lung diseases. Nevertheless, further investigations are required.


Author(s):  
Maryam Hosseini ◽  
Mostafa Haji-Fatahaliha ◽  
Farhad Jadidi-Niaragh ◽  
Jafar Majidi ◽  
Mehdi Yousefi

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi24-vi24
Author(s):  
Anthony Sloan ◽  
Harry Hoffman ◽  
Peggy Harris ◽  
Christine Lee-Poturalski ◽  
Theresa Elder ◽  
...  

Abstract The effect of platelets on oncogenesis has been studied extensively in cancer metastasis, but not in glioblastoma (GBM), where metastasis is rare. Here we identify the unique crosstalk between glioma stem cells (GSCs) and platelets within GBM solid tumors that enhance disease progression. Targeting GSCs is considered a promising therapeutic approach; however, no clear method has been identified. High platelet counts have been associated with poor clinical outcome in many cancers including ovarian and endometrial cancer. While platelets are known to affect progression of other tumors, mechanisms by which platelets influence GBM oncogenesis are unknown. Immunofluorescence, qPCR, and western blot were used to evaluate the presence of GSCs and platelets and their colocalization in GBM patient tissue at University Hospitals-Seidman Cancer Center. Functional assays followed by RNA sequencing were conducted to determine the functional effect of healthy and GBM platelets on growth of patient derived, autologous GSCs. Our clinical studies suggest elevated platelet counts positively correlate with GSC proliferation and negatively correlate with overall survival in patients with GBM. Patients with high platelet counts ( >350k/µl) had a median survival time of 9 months compared to 16 months median survival for patients with normal platelet count (150-350/µl) (p<0.05). We demonstrate platelet and GSC co-localization in GBM solid tissue and platelet exposure to patient derived GSCs cell lines results in a ≥ 3-fold increase in GSC proliferation compared to GSCs not exposed to platelets (p<0.0005). Similarly we found that platelets increased the self-renewing capacity by enhancing the average sphere size (p < 0.005), and increasing the GSC “Stem-like” transcriptional pattern (P< 0.05). Conversely, pharmacologic inhibition of platelet activation reversed the effect of platelets on GSC proliferation (p ranging from 0.05-0.005). These studies suggests the platelet-GSC interactions appear to stimulate GBM oncogenesis, identifying a potential therapeutic target for the treatment of GBM.


2021 ◽  
Vol 8 ◽  
Author(s):  
Tingting Cao ◽  
Bing Xie ◽  
Siyuan Yang ◽  
Jiaqi Wang ◽  
Xiao Yang ◽  
...  

Acute urinary retention (AUR) is a troublesome urological disease, which causes various lower urinary tract symptoms. However, only few studies explored and evaluated the effective treatments to improve AUR. We aimed to find an effective approach to cure AUR through comparing the efficacy of existing classical low-frequency transcutaneous electrical nerve stimulation (TENS) and novel intravesical electrical stimulation (IVES). A total of 24 AUR female rats were divided into 3 groups as follows: control, TENS, and IVES groups. Rats in the control group had no fake stimulation. Rats in the TENS and IVES groups underwent transcutaneous or intravesical stimulation of a symmetrical biphasic rectangular current pulse with a frequency of 35 Hz, 30 min per day, for seven consecutive days. IVES significantly reduced the actin expression in the submucosal layer but increased its expression in the detrusor layer (p= 0.035,p= 0.001). The neovascularization in the submucosal layer in the IVES group was significantly increased than in the other 2 groups (p= 0.006). Low-frequency IVES performed better than TENS in terms of simultaneously relieving bladder hyperactivity, accelerating epithelial recovery, and strengthening detrusor muscle. IVES may be a promising therapeutic approach for bladder dysfunction, specifically for AUR and overactive bladder in clinical practice.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Analaura Santiago-Perez ◽  
Yaritza Inostroza-Nieves ◽  
Daniel Gil de la Madrid ◽  
Isamar Alicea ◽  
Christopher Vega ◽  
...  

Protein disulfide isomerase (PDI) is an oxidoreductase that mediates thiol/disulfide interchange reactions and has been reported to play a critical role in thrombus formation following vascular injury. PDI has also been shown to regulate leukocyte adherence to the endothelium and nitric oxide delivery. We recently reported that PDI is present at high levels and regulates erythrocyte homeostasis and Gardos Channel activity in humans with Sickle Cell Disease (SCD). Thus, PDI inhibition has been proposed as a promising therapeutic approach to ameliorate both the vascular and hematological complications of SCD. Syzygium jambos (S. jambos) is purported to have anti-inflammatory and antioxidant properties. However, the regulation of PDI activity by S. jambos has not been studied. We studied in vitro PDI activity in the presence of the S. jambos aqueous leaf extract using a PDI insulin turbidity assay. We observed significant reductions in PDI activity at 25 μg/mL (66.0 ± 9.7%, p<0.01, n=3), 50 μg/mL (83.3 ± 6.0%, p<0.01, n=3), and 100 μg/mL (91.6 ± 11.5%, p<0.01, n=3). S. jambos extract showed a dose-dependent anti-PDI activity with an IC50 of 14.40 μg/mL. We then tested the effects of S. jambos on endothelin-1 (ET-1)-stimulated PDI activity in human endothelial cells. Using a fluorescence based PDI activity assay, we observed that ET-1 increased PDI activity (1.7 ± 0.7 folds, n=3) that was dose-dependently blocked by S. jambos extract. In addition, we observed that ET-1 stimulated ex vivo human polymorphic nucleated (PMN) leukocyte migration toward the endothelial cells that was likewise dose-dependently blocked by S. jambos extract. (p<0.01, n=3). We also quantified the levels of reactive oxygen species (ROS) production in ET-1 treated endothelial cells. ET-1 stimulation significantly increased ROS levels [3 fold] when compared to vehicle treatment (p<0.05, n=3). S. jambos extract reduced ET-1 stimulated ROS to baseline levels (p<0.05, n=3). Our results suggest that S. Jambos may represent a novel pharmacological approach to treat complications of SCD.


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