Evaluation of LY2606368 Therapy in Combination With Cyclophosphamide or Gemcitabine for Children and Adolescents With Refractory or Recurrent Group 3/Group 4 or SHH Medulloblastoma Brain Tumors

Author(s):  
Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.


Author(s):  
E.J. Prendiville ◽  
S. Laliberté Verdon ◽  
K. E. Gould ◽  
K. Ramberg ◽  
R. J. Connolly ◽  
...  

Endothelial cell (EC) seeding is postulated as a mechanism of improving patency in small caliber vascular grafts. However the majority of seeded EC are lost within 24 hours of restoration of blood flow in previous canine studies . We postulate that the cells have insufficient time to fully develop their attachment to the graft surface prior to exposure to hemodynamic stress. We allowed EC to incubate on fibronectin-coated ePTFE grafts for four different time periods after seeding and measured EC retention after perfusion in a canine ex vivo shunt circuit.Autologous canine EC, were enzymatically harvested, grown to confluence, and labeled with 30 μCi 111 Indium-oxine/80 cm 2 flask. Four groups of 5 cm x 4 mm ID ePTFE vascular prostheses were coated with 1.5 μg/cm.2 human fibronectin, and seeded with 1.5 x 105 EC/ cm.2. After seeding grafts in Group 1 were incubated in complete growth medium for 90 minutes, Group 2 were incubated for 24 hours, Group 3 for 72 hours and Group 4 for 6 days. Grafts were then placed in the canine ex vivo circuit, constructed between femoral artery and vein, and subjected to blood flow of 75 ml per minute for 6 hours. Continuous counting of γ-activity was made possible by placing the seeded graft inside the γ-counter detection crystal for the duration of perfusion. EC retention data after 30 minutes, 2 hours and 6 hours of flow are shown in the table.


VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


Author(s):  
Hawraa M. Murad ◽  
Tamadhur Hani Hussein ◽  
Audai Sulaiman Khudhair ◽  
Manal Muhi Murad ◽  
Jawad Kadhim Faris

This study was conducted to find out hepatoprotective activity of hesperidin (HES) 100mg/kg body weight (b.w.) against ciprofloxacin (CPX) 100 mg/kg induced hepatotoxicity in local breed rabbits .CPX is a broad spectrum antibiotic used for treatment of many bacterial infections. Twenty four male rabbits were divided into four groups ,group1: control, (1 ml/kg Saline orally) group 2: CPX (100 mg/kg orally) for (14) consecutive days , group 3: HES (100 mg//kg) orally for (14) consecutive days group 4: CPX (100 mg/kg orally) plus HES (100 mg//kg orally ) for (14) consecutive days. All the rabbits were killed on the (15) day of the experiment, and then the blood, and livers samples were taken. CPX induced hepatotoxicity was proved by a significant (p less than 0.01) reduction in the body weight ,and a significant (p less than 0.01) increased serum aspartate transaminase (AST), alanine transaminase (ALT) , Malonaldehyde enzyme (MAD) and histopathological changes. Protective hepatic toxicity effect and oxidative damage caused by CPX significantly (p less than 0.01) increasing in body weight and significantly (p less than 0.01) decreasing AST , ALT, MAD and improving tissue morphology in HES (100 mg//kg) . These results assure that HES (100 mg//kg) antioxidant effects can protect CPX-induced hepatotoxicity in rabbits.


2019 ◽  
Vol 17 (4) ◽  
pp. 354-364
Author(s):  
Hassan Al-Thani ◽  
Moamena El-Matbouly ◽  
Maryam Al-Sulaiti ◽  
Noora Al-Thani ◽  
Mohammad Asim ◽  
...  

Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA). Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively. Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control. Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.


2020 ◽  
Vol 06 ◽  
Author(s):  
Ngan Nguyen Hoang ◽  
Thang Duong Minh ◽  
Tuan Anh Hoang ◽  
Son Le Ngoc Bich ◽  
Duong Nguyen Huu ◽  
...  

Objectives: Evaluate the effects of "XGTQ" in the treatment of cirrhosis induced by Carbon tetrachloride (CCL4) in combination with alcohol and high-fat diet on Wistar rats. Materials and methods: Cirrhosis on white rats was induced by subcutaneously injecting CC14 at an initial dose of 5,0ml/kg, followed by 1,2ml/kg once a week in 10 weeks. Then, fed with synthetic food, added 20% fat, and 0.05% cholesterol and iron oxalate. Rats were administered every day with plain water and 1 day with water mixed with 30% ethanol. The rats were randomly divided into 5 groups and given distilled water (group 1 and 2 or control group), silymarin (group 3 or reference group) or the "XGTQ" drug extract (group 4, 5) for 4 weeks. Collected blood for biochemical test and liver were dissected to evaluate weight, morphology and quantified 4-hydroxyproline to evaluate fibrosis and collagen accumulation. Results: In cirrhotic wistar rats, "XGTQ" drug at 19.6 g/kg/24h and 58.8 g/kg/24h showed the ability of reducing the activity of enzymes AST, ALT in the blood (p<0.01), increasing plasma albumin and decreasing prothrobin time (p<.05); improving physical condition, macroscopic and microscopic images of H&E-stained liver; decreasing the concentration of hydroxyproline in the liver and reducing the level of cirrhosis on the masson-stained templates. The effects of "XGTQ" increased with the dose, and was equivalent to silymarin at the dose of 70 mg/kg/24h. Conclusion: The extract of "XGTQ" drug is effective in treating cirrhosis in Wistar rats.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 936.2-937
Author(s):  
F. Milatz ◽  
J. Klotsche ◽  
M. Niewerth ◽  
J. Hörstermann ◽  
D. Windschall ◽  
...  

Background:In patients with JIA, growth impairment and variance in body composition are well-known long-term complications that may be associated with prolonged drug therapy (e.g. glucocorticoids) as well as impaired physical and psychosocial well-being. An increased accumulation of body fat represents a significant risk factor for metabolic abnormalities and a modifiable variable for a number of comorbidities. Recently, evidence has emerged in favour of the potential negative influence of overweight on the course of the disease and treatment response [1].Objectives:The study aimed a) to estimate the prevalence of underweight, overweight and obesity in children and adolescents with JIA compared to the general population, and b) to investigate correlates of patients’ weight status.Methods:A cross-sectional analysis of physicians’ recorded body weights and heights of patients with JIA enrolled in the NPRD in the year 2019 was performed. Underweight (BMI <10th), overweight (BMI >90th) and obesity (BMI >97th) were defined according to age- and sex-specific percentiles used in the German reference system. For comparison with data from the general population [2], sex- and age-matched pairs of 3-17-year-old patients and controls were generated. A multinomial logistic regression analysis was performed to examine the association between weight status and patients’ clinical and self-reported outcomes.Results:In total, data from 6.515 children and adolescents with JIA (age 11.2 ± 4.1 years, disease duration 4.9 ± 3.8 years, 67% girls, 40% persistent oligoarthritis) were included. Of these, 3.334 (age 5.9 ± 2.1 years, 52.5% girls) could be considered for matched-pair analysis. Compared with the general population, patients underweight, overweight and obesity rates were 10.6% (vs. 8.1%), 8.8% (vs. 8.5%) and 6.1% (vs. 5.7%), respectively. No significant sex differences were found in either group. Largest difference in prevalence was registered for underweight, specifically in the age group 3-6 years (12.9% patients vs. 5.9% controls). Similar to the general population, higher rates of overweight were observed in adolescent patients than in affected children (19.1% age group 11-13 vs. 8.4% age group 3-6). While the highest underweight prevalence was registered in patients with RF+ polyarthritis (16%), patients with Enthesitis-related arthritis (22%), psoriatic arthritis (21%) and systemic JIA (20%) showed the highest overweight rates (including obesity). Younger age (OR = 0.51, 95% CI = 0.31-0.83), more frequent physical activity (OR = 0.92, 95% CI = 0.85-0.99) and high parental vocational education (OR = 0.39, 95% CI = 0.18-0.80) were independently associated with a lower likelihood of being overweight/obese.Conclusion:The overall prevalence of underweight, overweight and obesity in children and adolescents with JIA is comparable to that found in the general population. Behavioural health promotion, including regular physical activity, as part of the treatment strategy in JIA should preventively already begin at preschool age and necessarily be made accessible to patients of all educational levels.References:[1]Giani T et al. The influence of overweight and obesity on treatment response in juvenile idiopathic arthritis. Front Pharmacol 2019;10:637.[2]Schienkiewitz A et al. BMI among children and adolescents: prevalences and distribution considering underweight and extreme obesity. Bundesgesundheitsbl 2019;62:1225–1234.Acknowledgements:The National Paediatric Rheumatological Database has been funded by AbbVie, Chugai, Novartis and GSK.Disclosure of Interests:Florian Milatz: None declared, Jens Klotsche: None declared, Martina Niewerth: None declared, Jana Hörstermann: None declared, Daniel Windschall: None declared, Frank Weller-Heinemann Speakers bureau: Pfizer, AbbVie, SOBI, Roche and Novartis., Frank Dressler: None declared, Rainer Berendes: None declared, Johannes-Peter Haas: None declared, Gerd Horneff: None declared, Kirsten Minden Speakers bureau: Pfizer, AbbVie, Consultant of: Novartis


2021 ◽  
pp. 197140092098356
Author(s):  
Marwan Alkrenawi ◽  
Michael Osherov ◽  
Azaria Simonovich ◽  
Jonathan Droujin ◽  
Ron Milo ◽  
...  

Background Cervical discopathy and demyelinating lesions often co-exist in patients with multiple sclerosis (MS). Our study examines the possible association between these two pathologies. Methods Medical records and cervical magnetic resonance imaging scans of MS patients with cervical discopathy who were seen at our MS clinic during 2018 were retrospectively reviewed. The severity of the disc disease was classified as grade I (no compression), grade II (compression of the dural sac) and grade III (cord compression). The spinal cord in each scan was divided into six segments corresponding to the intervertebral space of the spine (C1–C6). Each segment was defined as containing demyelinating lesion and disc pathology (group 1), demyelinating lesion without disc pathology (group 2), disc pathology without demyelinating lesion (group 3) and no demyelinating lesion or disc pathology (group 4). Fisher’s exact test was used to test the association between demyelinating lesions and disc pathology. Results Thirty-four MS patients with cervical discopathy were included in the study (26 females; average age 42.9 ± 13.7 years; average disease duration 8.4 ± 5.4 years). A total of 204 spinal cord segments were evaluated. Twenty-four segments were classified as group 1, 27 segments as group 2, 52 segments as group 3 and 101 segments as group 4. There was no association between demyelinating lesions and the grade of disc disease ( p = 0.1 for grade I, p = 0.3 for grade II and p = 1 for grade III disc disease). Conclusion Our study did not find any association between cervical disc disease and demyelinating spinal cord lesion.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii406-iii406
Author(s):  
Julien Masliah-Planchon ◽  
Elodie Girard ◽  
Philipp Euskirchen ◽  
Christine Bourneix ◽  
Delphine Lequin ◽  
...  

Abstract Medulloblastoma (MB) can be classified into four molecular subgroups (WNT group, SHH group, group 3, and group 4). The gold standard of assignment of molecular subgroup through DNA methylation profiling uses Illumina EPIC array. However, this tool has some limitation in terms of cost and timing, in order to get the results soon enough for clinical use. We present an alternative DNA methylation assay based on nanopore sequencing efficient for rapid, cheaper, and reliable subgrouping of clinical MB samples. Low-depth whole genome with long-read single-molecule nanopore sequencing was used to simultaneously assess copy number profile and MB subgrouping based on DNA methylation. The DNA methylation data generated by Nanopore sequencing were compared to a publicly available reference cohort comprising over 2,800 brain tumors including the four subgroups of MB (Capper et al. Nature; 2018) to generate a score that estimates a confidence with a tumor group assignment. Among the 24 MB analyzed with nanopore sequencing (six WNT, nine SHH, five group 3, and four group 4), all of them were classified in the appropriate subgroup established by expression-based Nanostring subgrouping. In addition to the subgrouping, we also examine the genomic profile. Furthermore, all previously identified clinically relevant genomic rearrangements (mostly MYC and MYCN amplifications) were also detected with our assay. In conclusion, we are confirming the full reliability of nanopore sequencing as a novel rapid and cheap assay for methylation-based MB subgrouping. We now plan to implement this technology to other embryonal tumors of the central nervous system.


Author(s):  
Joanna Cwykiel ◽  
Arkadiusz Jundzill ◽  
Aleksandra Klimczak ◽  
Maria Madajka-Niemeyer ◽  
Maria Siemionow

AbstractThis study evaluated the efficacy of donor recipient chimeric cell (DRCC) therapy created by fusion of donor and recipient derived bone marrow cells (BMC) in chimerism and tolerance induction in a rat vascularized composite allograft (VCA) model. Twenty-four VCA (groin flaps) from MHC-mismatched ACI (RT1a) donors were transplanted to Lewis (RT1l) recipients. Rats were randomly divided into (n = 6/group): Group 1—untreated controls, Groups 2—7-day immunosuppression controls, Group 3—DRCC, and Group 4—DRCC with 7-day anti-αβTCR monoclonal antibody and cyclosporine A protocol. DRCC created by polyethylene glycol-mediated fusion of ACI and Lewis BMC were cultured and transplanted (2–4 × 106) to VCA recipients via intraosseous delivery route. Flow cytometry assessed peripheral blood chimerism while fluorescent microscopy and PCR tested the presence of DRCC in the recipient’s blood, bone marrow (BM), and lymphoid organs at the study endpoint (VCA rejection). No complications were observed after DRCC intraosseous delivery. Group 4 presented the longest average VCA survival (79.3 ± 30.9 days) followed by Group 2 (53.3 ± 13.6 days), Group 3 (18 ± 7.5 days), and Group 1 (8.5 ± 1 days). The highest chimerism level was detected in Group 4 (57.9 ± 6.2%) at day 7 post-transplant. The chimerism declined at day 21 post-transplant and remained at 10% level during the entire follow-up period. Single dose of DRCC therapy induced long-term multilineage chimerism and extended VCA survival. DRCC introduces a novel concept of customized donor-recipient cell-based therapy supporting solid organ and VCA transplants.


Sign in / Sign up

Export Citation Format

Share Document