scholarly journals Treatment Effect of a Vascular-Disrupting Agent Dynamically Monitored by DWI: An Animal Experimental Study

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Danping Huang ◽  
Ruimeng Yang ◽  
Yong Zou ◽  
Hongmei Lin ◽  
Xiangdong Xu ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Diffusion Weighted Imaging ◽  
Tumor Volume ◽  
Control Group ◽  
Vascular Disrupting Agent ◽  
Time Points ◽  
Vx2 Tumor ◽  
Adc Values ◽  
Vascular Disrupting ◽  
Time Point

Objective. To investigate the treatment effect of a vascular-disrupting agent, M410, using diffusion-weighted imaging in a rabbit model of hepatic VX2 tumor. Methods. 28 New Zealand white rabbit models with VX2 liver tumors were established and were randomly divided into M410 (intravenous injection of M410 at a dose of 25 mg/kg every three days) and control (intravenous injection of saline every three days) groups. Conventional and diffusion-weighted imaging (DWI) were acquired on a 3.0 T MR unit at baseline, 4 h, d 1, d 4, d 7, and d 14 posttreatment. B-value with 700 (s/mm2) was chosen during DWI examinations. Tumor volume and apparent diffusion coefficient (ADC) values of the entire tumor and solid component of the tumor at every time point were measured. Two randomly chosen rabbits from each group were sacrificed for H&E staining and CD34 immunohistochemical assessments at each time point. An independent sample t-test was used to assess differences in tumor sizes and ADC values of the entire tumor and solid component of tumors between two groups, with P < 0.05 considered statistically significant. Result. There was no significant difference in tumor volume between the two groups at baseline, 4 h, and d 1. With time, the tumors in the control group grew significantly faster than those in the M410 group, and the average ADC values of the M410 group were lower than those of the control group at d 1 and higher than those of the control group at d 4; as such, there were statistical differences between the two groups at these two time points but not at the other four time points. The following pathological results reflected the underlying morphological changes and vascular alterations. Conclusions. M410 performed well in inhibiting the growth of the hepatic VX2 tumor which could be noninvasively monitored by DWI metrics.

scholarly journals Cytotoxicity assessment of different doses of ozonated water on dental pulp cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ferdiye Küçük ◽  
Sibel Yıldırım ◽  
Serap Çetiner
Keyword(s):  
Cell Viability ◽  
Repeated Measures ◽  
Dental Pulp ◽  
Control Group ◽  
Dental Pulp Cells ◽  
Time Points ◽  
Significant Difference ◽  
Pulp Cells ◽  
Time Point ◽  
Ozonated Water

Abstract Background The purpose of this study was to assess the cytotoxicity of various concentrations of ozonated water (OW) on human primary dental pulp cells. Methods Human primary dental pulp cells were isolated from exfoliated primary canine teeth of an 11-year-old patient with good systemic and oral health. Afterwards, cells were divided into 6 experimental groups; four groups of OW in concentrations of 2 mg/L, 4 mg/L, 8 mg/L, and 16 mg/L, untreated control group, and cell culture without cells. Cytotoxicity was evaluated after exposure for 5-min exposure using Mosmann’s Tetrazolium Toxicity (MTT) assay at 0 h and 48 h time points. Data were analyzed using a repeated measures analysis of variance and Post-hoc tests were performed using Bonferroni correction for multiple comparisons. Results All experimental groups showed proliferation at 0 h time point. However, all groups also experienced a decrease in overtime at 48 h time point (p < 0.05). At both time points 2 mg/L OW showed the highest cell viability as well as proliferation. At 0 h time point, the increase in cell viability for all experimental groups was found statistically significant when compared to positive control group (p < 0.05). At 48 h time point, although 8 mg/L and 16 mg/L OW showed statistically significant reduction in compare to 0 h time point, 2 mg/L and 4 mg/L OW groups didn’t experience any statistically significant difference (p < 0.05). Conclusion Considering our findings, due to ozonated water's induced a higher proliferation rate of dental pulp cells, indicating their biocompatibility and a possible adjuvant on irrigating agent in regenerative endodontic procedures.

scholarly journals The Roles of Skin Fibroblasts at Local Acupoints in Chrono-Acupuncture

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nannan Liu ◽  
Zhengyu Zhao ◽  
Qizhi Zhou ◽  
Xiaohong Zhang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Acupuncture Treatment ◽  
Treatment Time ◽  
Subcutaneous Tissue ◽  
Acupuncture Group ◽  
Control Group ◽  
Model Group ◽  
Time Points ◽  
Group A ◽  
And Control ◽  
Time Point

Objective. The aim of this study was to demonstrate the peripheral mechanisms of chrono-acupuncture by observing acupuncture at different time points affecting relative proteins to regulate the cytoskeleton of fibroblasts differently. Methods. A total of 108 male SD rats (180–220 g) that have basic pain threshold within 3–10 s were selected and randomly divided into group A (n = 72) and control group (n = 36). After the succession of modeling with CFA injection, the rats in group A were randomly divided into model group and acupuncture group, each group containing 36 rats. Then according to the different treatment time, each group was randomly classified into 6 subgroups (ZT0, ZT4, ZT8, ZT12, ZT16, and ZT20), each subgroup containing 6 rats (n = 6). On the second day of successful modeling, the rats in the acupuncture group received acupuncture treatment at the corresponding time point, while the control group and the model group were only tied up at the corresponding time point without any treatments. Methods of operation: use 0.5-inch needles, puncture the rats’ “Zusanli” on the affected limb, with Twirling manipulation for a minute after every five minutes; the treatment lasts thirty minutes in total. After 7 days of treatments, the skin and subcutaneous tissue of rats’ acupoint area of “Zusanli” on the affected limb were taken and then stained by immunofluorescence double staining method to observe the expression of the fibroblast cytoskeleton F-actin and β-tubulin under the LSCM while using western blot to observe the expression of P38MAPK/P-P38MAPK. Results. The expression of the cytoskeleton F-actin and β-tubulin at acupoint area in the acupuncture group was significantly higher than that in the control and model group. The effect of acupuncture on the restructure of the fibroblast cytoskeleton is different at different time points, the most effective time point was at ZT12 while the least at ZT16. Acupuncture can decrease the high expression of P-P38MAPK/P38MAPK in the model group, and the effect has time differences. The expression of P-P38MAPK/P38MAPK increased more significantly at ZT16 than ZT12. Conclusion. The remodeling difference of fibroblast cytoskeleton after receiving acupuncture treatment could be one of the peripheral bases of the chrono-acupuncture.

Efficacy Trial In An Acute Liver Trauma Animal Model Of Novel Infusible Hemostatic Product: Red Blood Cell-Derived Microparticles (RMP)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2342-2342
Author(s):  
Wenche Jy ◽  
Max E Johansen ◽  
Carlos Bidot ◽  
Rifat Pamukcu ◽  
Orlando Gomez-Marin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Loss ◽  
Early Time ◽  
Relative Difference ◽  
Control Group ◽  
Short Term ◽  
Post Injury ◽  
Time Points ◽  
Time Point

Abstract Background Increasing evidence indicates that natural circulating red cell microparticles (RMP) contribute significantly to hemostasis. Accordingly, we produced RMP in vitro by high pressure extrusion of washed RBCs. We previously reported the hemostatic activity of our RMP product in vitro as well as its efficacy in arresting ear bleeding in rabbits, suggesting the potential of RMP as a hemostatic agent (Jy et al Thromb. Haemost., in press). Here we studied its hemostatic efficacy in a rabbit model of acute liver injury, as well as its short-term toxicity. Methods Male New Zealand White rabbits (mean weight 3.8kg) were randomly selected and assigned, one at a time, to an experimental (n = 9) or a control group (n = 10). All animals were sedated with 35mg/kg ketamine, 5mg/kg xylazine, and 0.01mg/kg glycopyrrolate 15 minutes before surgery. They were intubated and anesthetized with 2% isoflurane, and mechanically ventilated at approximately 20 breaths/min. The carotid artery and the jugular vein were canulated, and maintenance saline was administered at 20mL/hr. The abdomen was cleaned and shaved, and an incision was made from lower tip of the sternum to the bladder. A standardized injury of 9 incisions 30mm long by 4mm deep was inflicted to the liver, and two infusions of RMP (1.25x1011/kg) or saline were delivered via jugular catheter, first immediately post-incision, and again 10 minutes post-incision. Blood was collected in gauze pads at 10 min. intervals and weighed to calculate volume lost. Heart rate, blood pressure (BP), and temperature were continually monitored. The blood pressure (BP) of some of the animals fell very low (MAP<15) by 1 hr post-incision and resulted in death. Only those rabbits that survived 2 hr were used in analysis of blood loss and vital signs. Five of the 10 control rabbits survived 2 hr post-surgery (50%) compared to 5 of the 9 RMP-treated rabbits (56%). All surviving rabbits were euthanized with 0.2mL/kg Euthasol after 120 minutes. Results At early time points (30 – 60 min post-injury) when bleeding was most rapid, administration of RMP had no significant effect: mean (± SD) blood loss at 30 min was 46.1 ± 20.6 mL in the control vs. 26.6 ± 9.0 mL (p=0.07) in the RMP group. At 60 min it was 67.2 ± 24.3 mL vs. 53.4 ± 6.9 mL (p=0.23), respectively. Although at these early time points there were not significant differences, a trend of reduced blood loss was observed. At the 90 min time point, blood loss was 78.6 ± 25.9 mL in the control group compared to 55.7 ± 5.6 mL in the RMP group (p<0.05), a relative difference of ≈ 30%. At 120 min, the corresponding values were 89.8 ± 29.3 mL and 57.7 ± 4.4 mL (p < 0.01), a relative difference of ≈ 36% . Vitals were not significantly different between the control and RMP groups at any time point. Drop in BP tended to be greater in controls than in RMP rabbits. The difference in BP was marginally significant at 120 min. post-injury: systolic BP fell by 39.6 ±17.2 mmHg in controls vs. 18.6 ±15.0 mmHg in RMP-treated (p=0.07). In a short-term toxicity test, quadruple dose (5.0x1011/kg of RMP) was administered and effects observed for three hours: no obvious adverse effects on heart rate, BP, or temperature were observed. Conclusion/Discussion We previously reported dose-dependent reduction by RMP infusion in ear bleeding time of thrombocytopenic rabbits. Efficacy of infusions of RMP is evident in this severe hemorrhagic liver injury model after 30 - 60 min of acute injury when rapid bleeding was substantially slowing down. At 90 and 120 min post-injury, significantly less blood loss was observed in the RMP group compared to the controls, with relative differences of 30% and 36%. Studies are in progress to improve the model and to optimize dosages and scheduling of RMP administration for severe bleeding. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Decreased APE-1 by Nitroxoline Enhances Therapeutic Effect in a Temozolomide-resistant Glioblastoma: Correlation with Diffusion Weighted Imaging

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hye Rim Cho ◽  
Nisha Kumari ◽  
Nishant Thakur ◽  
Hien Thi Vu ◽  
Hyeonjin Kim ◽  
...  
Keyword(s):  
Diffusion Weighted Imaging ◽  
Tumor Volume ◽  
Morphological Changes ◽  
Control Group ◽  
Therapeutic Effects ◽  
Adc Value ◽  
Diffusion Weighted ◽  
Resistant Cells

Abstract Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor survival rates. The current standard treatment includes chemotherapy with temozolomide (TMZ), but acquisition of resistance is a persistent clinical problem limiting the successful treatment of GBM. The purpose of our study was to investigate therapeutic effects of nitroxoline (NTX) against TMZ-resistant GBM in vitro and in vivo in TMZ-resistant GBM-bearing mouse model, which was correlated with diffusion-weighted imaging (DWI). For in vitro study, we used TMZ-resistant GBM cell lines and evaluated therapeutic effects of NTX by clonogenic and migration assays. Quantitative RT-PCR was used to investigate the expression level of TMZ-resistant genes after NTX treatment. For in vivo study, we performed 9.4 T MR imaging to obtain T2WI for tumor volume measurement and DWI for assessment of apparent diffusion coefficient (ADC) changes by NTX in TMZ-resistant GBM mice (n = 8). Moreover, we performed regression analysis for the relationship between ADC and histological findings, which reflects the changes in cellularity and apurinic/apyrimidinic endonuclease-1 (APE-1) expression. We observed the recovery of TMZ-induced morphological changes, a reduced number of colonies and a decreased rate of migration capacity in TMZ-resistant cells after NTX treatment. The expression of APE-1 was significantly decreased in TMZ-resistant cells after NTX treatment compared with those without treatment. In an in vivo study, NTX reduced tumor growth in TMZ-resistant GBM mice (P = 0.0122). Moreover, ADC was increased in the NTX-treated TMZ-resistant GBM mice compared to the control group (P = 0.0079), which was prior to a tumor volume decrease. The cellularity and APE-1 expression by histology were negatively correlated with the ADC value, which in turn resulted in longer survival in NTX group. The decreased expression of APE-1 by NTX leads to therapeutic effects and is inversely correlated with ADC in TMZ-resistant GBM. Therefore, NTX is suggested as potential therapeutic candidate against TMZ-resistant GBM.

scholarly journals Multiparametric MRI with diffusion-weighted imaging in predicting response to chemotherapy in cases of osteosarcoma and Ewing’s sarcoma

2020 ◽  
Vol 93 (1115) ◽  
pp. 20200257
Author(s):  
Mahmoud Mohamed Saleh ◽  
Tamer Moustafa Abdelrahman ◽  
Youusef Madney ◽  
Ghada Mohamed ◽  
Ahmed Mohammed Shokry ◽  
...  
Keyword(s):  
Diffusion Weighted Imaging ◽  
Tumor Volume ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Multiparametric Mri ◽  
Dce Mri ◽  
Recist 1.1 ◽  
Progressive Group ◽  
Adc Values ◽  
Modified Recist

Objective: To evaluate the multiparametric MRI in predicting chemotherapy response in pathologically proven cases of osteosarcoma and Ewing’s sarcoma. Correlation between the tumor size changes and internal breakdown using RECIST 1.1, modified RECIST, quantitative apparent diffusion coefficient (ADC) and tumor volume as well as dynamic contrast-enhanced MRI (DCE-MRI). Methods: The study included 104 patients pathologically proved osteosarcoma (53) and Ewing`s sarcoma (51) underwent MRI examinations; before and after chemotherapy. All patients were assessed using the RECIST 1.1 criteria, m-RECIST, quantitative ADC, and tumor volume evaluation. 21 patients underwent DCE-MRI curve type with quantitative parameters. Correlation between the different evaluations was carried out. Results were correlated with the post-operative pathology in 42 patients who underwent surgery and for statistical evaluation, Those patients were classified into responders (≥90% necrosis) and non-responders (<90% necrosis). Results: The initial mean ADC of 104 patients of osteosarcoma and Ewing’s sarcoma (0.90 ± 0.29) and (0.71 ± 0.16) respectively, differed significantly from that after treatment (1.62 ± 0.46) and (1.6 ± 0.39) respectively with (p<0.001). ADC variations (ADC%) in the non-progressive group were higher than those of the progressive group (128.3 ± 63.49 vs 36.34 ± 78.7) % with (p<0.001). ADC values and ADC variations were inversely correlated with morphologic changes, regardless of the effectiveness of chemotherapy expressed as changes in tumor size based on (RECIST 1.1, RECIST, and 3D volume). Linear regression analysis revealed a Pearson correlation coefficient of r=-0.427, -0.498 and -0.408, respectively with (p<0.001). An increase in the ADC value was not always associated with a reduction in tumor volume. The disease control rate (defined as the percentage of CR+PR+SD patients) was 89.4% and 93.9% according to RECIST 1.1 and m-RECIST respectively. 42 out of the 104 patients had postsurgical histological evaluation as regards the chemotherapeutic response divided into two groups. ADC values showed a statistically significant difference between Group A and Group B being more evident with minimum ADC% (p<0.001). Conclusion: Quantitative diffusion-weighted imaging with ADC mapping and ADC % after chemotherapy allows a detailed analysis of the treatment response in osteosarcoma and Ewing’s sarcoma. The therapeutic response can be underestimated using RECIST 1.1, so the modified RECIST should be also considered. Advances in knowledge: Quantitative ADC especially ADC% provided an accurate non-invasive tool in the assessment of post-therapeutic cases of osteosarcoma and Ewing's sarcoma

scholarly journals Feasibility and possible value of quantitative semi-automated diffusion weighted imaging volumetry of neuroblastic tumors

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sebastian Gassenmaier ◽  
Ilias Tsiflikas ◽  
Jörg Fuchs ◽  
Robert Grimm ◽  
Cristian Urla ◽  
...  
Keyword(s):  
Diffusion Weighted Imaging ◽  
Tumor Volume ◽  
Integrated Analysis ◽  
Volume Comparison ◽  
Total Tumor Volume ◽  
Diffusion Weighted ◽  
Parametric Data ◽  
Significant Difference ◽  
Neuroblastic Tumors ◽  
Adc Values

Abstract Background To assess the feasibility and possible value of semi-automated diffusion weighted imaging (DWI) volumetry of whole neuroblastic tumors with apparent diffusion coefficient (ADC) map evaluation after neoadjuvant chemotherapy. Methods Pediatric patients who underwent surgical resection of neuroblastic tumors at our institution from 2013 to 2019 and who received a preoperative MRI scan with DWI after chemotherapy were included. Tumor volume was assessed with a semi-automated approach in DWI using a dedicated software prototype. Quantitative ADC values were calculated automatically of the total tumor volume after manual exclusion of necrosis. Manual segmentation in T1 weighted and T2 weighted sequences was used as reference standard for tumor volume comparison. The Student’s t test was used for parametric data while the Wilcoxon rank sum test and the Kruskal-Wallis test were applied for non-parametric data. Results Twenty seven patients with 28 lesions (neuroblastoma (NB): n = 19, ganglioneuroblastoma (GNB): n = 7, ganglioneuroma (GN): n = 2) could be evaluated. Mean patient age was 4.5 ± 3.2 years. Median volume of standard volumetry (T1w or T2w) was 50.2 ml (interquartile range (IQR): 91.9 ml) vs. 45.1 ml (IQR: 98.4 ml) of DWI (p = 0.145). Mean ADC values (× 10− 6 mm2/s) of the total tumor volume (without necrosis) were 1187 ± 301 in NB vs. 1552 ± 114 in GNB/GN (p = 0.037). The 5th percentile of ADC values of NB (614 ± 275) and GNB/GN (1053 ± 362) provided the most significant difference (p = 0.007) with an area under the curve of 0.848 (p < 0.001). Conclusions Quantitative semi-automated DWI volumetry is feasible in neuroblastic tumors with integrated analysis of tissue characteristics by providing automatically calculated ADC values of the whole tumor as well as an ADC heatmap. The 5th percentile of the ADC values of the whole tumor volume proved to be the most significant parameter for differentiation of the histopathological subtypes in our patient cohort and further investigation seems to be worthwhile.

scholarly journals Effects of Gargling with an Aroma Solution on Xerostomia, Halitosis, and Salivary pH in Hemodialysis Patients – A Randomized Controlled Trial

2019 ◽  
Vol 13 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Min Young Oh ◽  
Mi-Kyoung Cho
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Hemodialysis Patients ◽  
Control Group ◽  
Fluid Restriction ◽  
Time Points ◽  
Randomized Controlled ◽  
Salivary Ph ◽  
Experimental Group ◽  
Time Point

Background: Despite developments in renal replacement therapy, therapeutic fluid restriction reportedly induces xerostomia in 28.2~85.5% of hemodialysis patients, which causes serious inconveniences in their daily living and is detrimental to their quality of life. Objective: The purpose of this study was to identify the effects of gargling with an aroma solution (A-Solution) on xerostomia, halitosis, and salivary pH in hemodialysis patients. Methods: This study design was a randomized controlled trial. The participants of this study were 56 hemodialysis patients of E General Hospital in Seoul, Korea. They were divided into an experimental group (n=28) treated by gargling with 20 ml of A-Solution for 15 seconds and a control group (n=28) where pateints did not gargle with A-Solution, and data were collected from October 1 to November 15, 2013. The outcome variables were measured in the pretest and at 5, 30, 60, and 120 minutes in the two groups. The collected data were analyzed using SPSS (version 18.0 for Windows). Results: Xerostomia was lower in the experimental group than in the control group at each time point apart from the pretest and differed significantly in the interaction between groups and time points. Salivary pH and halitosis differed significantly between the experimental and control groups, across time points, and in the interaction between group and time point. Conclusion: The findings of this study suggest that aroma gargling is a useful oral-care intervention for solving oral problems experienced by hemodialysis patients such as xerostomia and halitosis.

Alterations of the Bone Marrow Stromal Microenvironment in Adult Patients with Leukemia before and after the Treatment

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2668-2668
Author(s):  
Tamara Sorokina ◽  
Irina Shipounova ◽  
Alexey Bigildeev ◽  
Nina I. Drize ◽  
Larisa A. Kuzmina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Control Group ◽  
Time Points ◽  
Before And After ◽  
Blast Cells ◽  
Blast Count ◽  
Time Point

Abstract Background Bone marrow (BM) microenvironment is involved in the initiation and propagation of normal hematopoiesis as well as hematological diseases. Leukemia and high dose chemotherapy affect both hematopoietic and stromal precursor cells. Multipotent mesenchymal stromal cells (MMSCs) are the essential element of both healthy and leukemic hematopoietic microenvironment. Aims To investigate two types of stromal precursor cells, MMSCs and their more differentiated progeny CFU-Fs, derived from the BM of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) patients before and after therapy. Methods 74 newly diagnosed cases (33 AML, 21 ALL, 20 CML) were involved in the study after informed consent. BM was aspirated prior to any treatment (time-point 0) and at days 37, 100 and 180 since the beginning of treatment of acute leukemia (AL) and +3, +6 and +12 months for CML (time-points 1-3). MMSCs were cultured in aMEM with 10% fetal calf serum. Time to P0 and cumulative MMSC production after 3 passages were evaluated. CFU-F concentration was analyzed in standard conditions. Results At the time of the diagnosis the percentage of blast cells in the bone marrow of patients with AML was 22-86,6% (median 64%). After the induction therapy complete remission (CR) was achieved in 58% of patients. Patients who didn't achieve CR were switched to the alternative chemotherapy regimens. The percentage of blast cells in the bone marrow of patients with ALL at the diagnosis was 68-97% (median 88%). After the induction therapy complete remission (CR) was achieved in 90% of patients. Time needed to reach P0 reflects the quantity of MMSC in the BM sample. The time to P0 in control group was 13.7 ± 0.3 days. The elongation of time to P0 in AL MMSC cultures at the time of the diagnosis (Table 1) suggested the reduction of MMSC number or their decreased proliferative potential due to leukemic expansion. After the induction therapy time to P0 reached the normal level, but subsequently lengthened during the consolidation therapy and before the maintenance therapy, that can be explained by the chemotherapy influence. In CML MMSC cultures time to P0 was also significantly longer during the whole observation period due to the continuous therapy and maintaining disease. Cumulative MMSC production in control group was 7.1 ± 1 x 106 cells. In patients with AML it was 1/3 of the donor's at the time of the diagnosis with no difference at time-points 1, 2 and 3, indicating the impaired proliferative abilities of MMSC at the AML manifestation due to the disease aggressiveness or the patient's elder age. Cumulative MMSC production in patients with ALL and CML didn't differ from donor's. BM blast count did not correlate with MMSC production. Among patients with AL, who didn't achieve CR, the time to P0 and total MMSC production did not differ significantly from that of the patients in remission. CFU-F concentration in the BM of AL patients was significantly lower (almost halved) than in donors (25.4 ± 3.1 per 106 BM cells) at the time-point 0 with no difference at time-points 1, 2 and 3. CFU-F concentration in the BM of CML patients was also nearly 40% lower than in control group at the time-point 0 with its following restoration at time-point 1 and subsequent drop at next time-points (up to 5 fold lower) at time-point 3) (Table 1), reflecting the long-lasting lesion of these group of precursors during the course of the disease. There were no correlations between BM blast count and CFU-F concentration in all nosologies studied. Conclusion The study supports the major influence of leukemic cells and chemotherapy on the BM microenvironment. The two types of studied precursors are affected differently. Future studies are needed to evaluate the role of MMSCs in leukemia pathogenesis. Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals MRI-Based Characterization of Vascular Disruption by 5,6-Dimethylxanthenone-Acetic Acid in Gliomas

2009 ◽  
Vol 29 (8) ◽  
pp. 1373-1382 ◽  
Author(s):  
Mukund Seshadri ◽  
Michael J Ciesielski
Keyword(s):  
Acetic Acid ◽  
Relaxation Rate ◽  
Vascular Disrupting Agent ◽  
Vascular Disruption ◽  
Kaplan Meier ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Magnetic Resonance Imaging Mri ◽  
Vascular Disrupting

The well-vascularized nature of gliomas has generated a lot of interest in antiangiogenic therapies. However, the potential of vascular disrupting agents (VDAs) against gliomas has not been investigated extensively. In this study, we examined the in vivo efficacy of the tumor-VDA 5,6-dimethylxanthenone-4-acetic acid (DMXAA) against gliomas. Contrast-enhanced magnetic resonance imaging (MRI) and diffusion-weighted MRI were used to characterize the vascular and cellular responses of GL261 and U87 gliomas to DMXAA treatment. Therapeutic efficacy was assessed by Kaplan-Meier survival analysis. Before VDA treatment, minimal enhancement was detected within the tumor in both models. Longitudinal relaxation rate ( R1 = 1/ T1) maps acquired 24 h after treatment showed marked extravasation and accumulation of the contrast agent in the tumor indicative of treatment-induced vascular disruption. Normalized change in relaxation rate (ΔR1) values of the tumor showed a significant increase ( P<0.01 GL261; P<0.05 U87) after therapy compared with baseline estimates. Mean apparent diffusion coefficient (ADC) values were significantly increased ( P = 0.015) 72 h after therapy in GL261 but not in U87 gliomas. Vascular disrupting agent therapy resulted in a significant ( P<0.01) increase in median survival in both models evaluated. The results highlight the potential of VDAs against gliomas and the utility of MRI in the assessment of glioma response to VDA therapy.

Effects of a vascular disrupting agent for cancer treatment on normal tissue evaluated by PIXE analysis using quantum dots

2014 ◽  
Vol 24 (01n02) ◽  
pp. 59-65
Author(s):  
A. Terakawa ◽  
K. Ishii ◽  
S. Matsuyama ◽  
Y. Kikuchi ◽  
K. Kusano ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Blood Flow ◽  
Normal Tissue ◽  
Kidney Tissue ◽  
Treated Group ◽  
Control Group ◽  
Vascular Disrupting Agent ◽  
Tissue Samples ◽  
Pixe Analysis ◽  
Vascular Disrupting

The effects of the vascular disrupting agent AVE8062 on tumor and normal tissue samples were investigated by particle-induced X-ray emission (PIXE) analysis using quantum dots (QDs). We investigated fibrosarcoma tumors in mice, and used kidney tissue as a control. Non-targeted QDs were used to characterize the tissue regions where blood flow is interrupted by AVE8062. We found that the concentration of the QDs in the tumors and kidneys exposed to AVE8062 was lower than that of the control group. Sub-millimeter PIXE analysis (with a beam size of 0.5 [Formula: see text] 0.5 mm2) was used to investigate the spatial distribution of QDs in the tissue samples. We found that the QDs were accumulated in localized regions of the kidney section of the AVE8062-treated group whereas the QDs were uniformly distributed in the control kidney. This suggests that AVE8062 caused blood flow interruption not only in the tumor samples but also in the normal blood vessels in the kidneys.

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