Influence of Cyclosporine A on Small-Bowel Grafts and Subsequent in Vitro Immune Reactions

1986 ◽  
pp. 161-165
Author(s):  
K. Ulrichs ◽  
E. Deltz ◽  
B. Friedrichs ◽  
G. Leimenstoll ◽  
A. Thiede ◽  
...  
2019 ◽  
Vol 19 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Ling Gao ◽  
Jianwei Dong ◽  
Nanyang Zhang ◽  
Zhanxian Le ◽  
Wenhao Ren ◽  
...  

Background:The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC.Methods:Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR.Results:In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings.Conclusion:The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.


1986 ◽  
Vol 39 (2) ◽  
pp. 308-318 ◽  
Author(s):  
Christopher J. Krco ◽  
Amy Gores ◽  
Vay Liang W. Go

2021 ◽  
Vol 3 (1) ◽  
pp. e000084
Author(s):  
Amanda Farah Khan ◽  
Matthew Kenneth MacDonald ◽  
Catherine Streutker ◽  
Corwyn Rowsell ◽  
James Drake ◽  
...  

ObjectivesWe aim to determine what threshold of compressive stress small bowel and colon tissues display evidence of significant tissue trauma during laparoscopic surgery.DesignThis study included 10 small bowel and 10 colon samples from patients undergoing routine gastrointestinal surgery. Each sample was compressed with pressures ranging from 100 kPa to 600 kPa. Two pathologists who were blinded to all study conditions, performed a histological analysis of the tissues. Experimentation: November 2018–February 2019. Analysis: March 2019–May 2020.SettingAn inner-city trauma and ambulatory hospital with a 40-bed inpatient general surgery unit with a diverse patient population.ParticipantsPatients were eligible if their surgery procured healthy tissue margins for experimentation (a convenience sample). 26 patient samples were procured; 6 samples were unusable. 10 colon and 10 small bowel samples were tested for a total of 120 experimental cases. No patients withdrew their consent.InterventionsA novel device was created to induce compressive “grasps” to simulate those of a laparoscopic grasper. Experimentation was performed ex-vivo, in-vitro. Grasp conditions of 0–600 kPa for a duration of 10 s were used.ResultsSmall bowel (10), M:F was 7:3, average age was 54.3 years. Colon (10), M:F was 1:1, average age was 65.2 years. All 20 patients experienced a significant difference (p<0.05) in serosal thickness post-compression at both 500 and 600 kPa for both tissue types. A logistic regression analysis with a sensitivity of 100% and a specificity of 84.6% on a test set of data predicts a safety threshold of 329–330 kPa.ConclusionsA threshold was discovered that corresponded to both significant serosal thickness change and a positive histological trauma score rating. This “force limit” could be used in novel sensorized laparoscopic tools to avoid intraoperative tissue injury.


2005 ◽  
Vol 114 (4) ◽  
pp. 279-288 ◽  
Author(s):  
Satish Govindaraj ◽  
Elena Fedorova ◽  
Eric M. Genden ◽  
Houtan Chaboki ◽  
Jonathan S. Bromberg ◽  
...  

Prior work has demonstrated that immunosuppressed orthotopic tracheal allografts undergo progressive reepithelialization over a 48-day period with recipient-derived tracheal epithelium. We hypothesized that reepithelialization of tracheal allografts would prevent rejection after withdrawal of immunosuppression. BALB/c murine tracheal grafts were transplanted orthotopically into either syngeneic or allogeneic C57/BL6 recipients. The recipients were either not immunosuppressed, immunosuppressed with cyclosporine A (10 mg/kg per day) continuously, or immunosuppressed for 48 days and then withdrawn from immunosuppression. The grafts were assessed for acute and chronic rejection 10 days and 50 days after immunosuppression withdrawal. The immunosuppressed allograft recipients maintained a ciliated epithelium acutely and chronically after immunosuppression withdrawal. Ten days after immunosuppression withdrawal, there was a mild cellular infiltrate, which resolved 50 days after withdrawal. Electron microscopy, lymphocyte subpopulation assays, and lamina propria analysis demonstrated that immunosuppression withdrawal did not result in tracheal allograft rejection. In vitro and in vivo assessments did not demonstrate evidence of systemic or local immune tolerance. We conclude that reepithelialization of orthotopic tracheal allografts with recipient-derived mucosa prevents rejection of allograft segments. Tracheal transplantation may require only transient immunosuppression, which can be withdrawn after tracheal reepithelialization.


1975 ◽  
Vol 32 (2) ◽  
pp. 240-240
Author(s):  
M Zäller ◽  
A M Dickinson ◽  
M J Embleton,

1991 ◽  
Vol 13 (1) ◽  
pp. 32-36 ◽  
Author(s):  
Rosalind L. Russell ◽  
James G. Donnelly ◽  
Edmund W. Palaszynski ◽  
Maria M. Chan ◽  
Steven J. Soldin

1997 ◽  
Vol 29 (5) ◽  
pp. 2494-2497
Author(s):  
J. Mendola ◽  
H. Corominola ◽  
E. Esmatjes ◽  
A. Saenz ◽  
L. Fernandez-Cruz ◽  
...  

2014 ◽  
Vol 50 (3) ◽  
pp. 591-597
Author(s):  
Xiping Li ◽  
Ping Gao ◽  
Chengliang Zhang ◽  
Tao Wu ◽  
Yanjiao Xu ◽  
...  

Mung bean seed coat (MBSC) is a healthcare product in Asian countries. The aim of this study was to investigate the effect of an MBSC ethanol extract on the bioavailability of cyclosporine A (CsA) in rats. Rats were orally dosed with CsA alone or in combination with MBSC ethanol extracts (500 mg/kg, p.o.). The blood levels of CsA were assayed by liquid chromatography with an electrospray ionization source and tandem mass spectrometry (LC-MS/MS). The everted rat intestinal sac technique was used to determine the influence of MBSC on the absorption of CsA. The results reveal that combined CsA intake with MBSC decreased the Cmax, AUC0-t, t1/2z and MRT0-t values of CsA by 24.96%, 47.28%, 34.73% and 23.58%, respectively (P<0.05), and significantly raised the CL/F by 51.97% (P<0.01). The in vitro results demonstrated that significantly less CsA was absorbed (P<0.05). The overall results indicate that after being concomitantly ingested, MBSC reduced the bioavailability of CsA, at least partially, in the absorption phase.


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