The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
A. M. M. Eggermont - One of the best experts on this subject based on the ideXlab platform.
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In vivo isolated Kidney Perfusion with tumour necrosis factor α (TNF- α ) in tumour-bearing rats
British Journal of Cancer, 1999Co-Authors: A H Van Der Veen, Ann L.b. Seynhaeve, J Breurs, P.t.g.a. Nooijen, Richard L. Marquet, A. M. M. EggermontAbstract:Isolated Perfusion of the extremities with high-dose tumour necrosis factor α (TNF-α) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ Perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated Kidney Perfusion. We studied the feasibility of a Perfusion with TNF-α and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 μg TNF-α. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-α and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated Kidney Perfusion, with TNF-α alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the Kidney to Perfusion with TNF-α, the minimal threshold concentration of TNF-α to exert its anti-tumour effects was not reached. The applicability of TNF-α in isolated Kidney Perfusion for human tumours seems, therefore, questionable. © 1999 Cancer Research Campaign
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In vivo isolated Kidney Perfusion with tumour necrosis factor alpha (TNF-alpha) in tumour-bearing rats.
British journal of cancer, 1999Co-Authors: A H Van Der Veen, Ann L.b. Seynhaeve, J Breurs, P.t.g.a. Nooijen, Richard L. Marquet, A. M. M. EggermontAbstract:Isolated Perfusion of the extremities with high-dose tumour necrosis factor alpha (TNF-alpha) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ Perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated Kidney Perfusion. We studied the feasibility of a Perfusion with TNF-alpha and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 microg TNF-alpha. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-alpha and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated Kidney Perfusion, with TNF-alpha alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the Kidney to Perfusion with TNF-alpha, the minimal threshold concentration of TNF-alpha to exert its anti-tumour effects was not reached. The applicability of TNF-alpha in isolated Kidney Perfusion for human tumours seems, therefore, questionable.
A H Van Der Veen - One of the best experts on this subject based on the ideXlab platform.
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In vivo isolated Kidney Perfusion with tumour necrosis factor α (TNF- α ) in tumour-bearing rats
British Journal of Cancer, 1999Co-Authors: A H Van Der Veen, Ann L.b. Seynhaeve, J Breurs, P.t.g.a. Nooijen, Richard L. Marquet, A. M. M. EggermontAbstract:Isolated Perfusion of the extremities with high-dose tumour necrosis factor α (TNF-α) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ Perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated Kidney Perfusion. We studied the feasibility of a Perfusion with TNF-α and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 μg TNF-α. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-α and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated Kidney Perfusion, with TNF-α alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the Kidney to Perfusion with TNF-α, the minimal threshold concentration of TNF-α to exert its anti-tumour effects was not reached. The applicability of TNF-α in isolated Kidney Perfusion for human tumours seems, therefore, questionable. © 1999 Cancer Research Campaign
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In vivo isolated Kidney Perfusion with tumour necrosis factor alpha (TNF-alpha) in tumour-bearing rats.
British journal of cancer, 1999Co-Authors: A H Van Der Veen, Ann L.b. Seynhaeve, J Breurs, P.t.g.a. Nooijen, Richard L. Marquet, A. M. M. EggermontAbstract:Isolated Perfusion of the extremities with high-dose tumour necrosis factor alpha (TNF-alpha) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ Perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated Kidney Perfusion. We studied the feasibility of a Perfusion with TNF-alpha and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 microg TNF-alpha. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-alpha and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated Kidney Perfusion, with TNF-alpha alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the Kidney to Perfusion with TNF-alpha, the minimal threshold concentration of TNF-alpha to exert its anti-tumour effects was not reached. The applicability of TNF-alpha in isolated Kidney Perfusion for human tumours seems, therefore, questionable.
Rohan John - One of the best experts on this subject based on the ideXlab platform.
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Significant Dysfunction of Kidney Grafts Exposed to Prolonged Warm Ischemia Is Minimized Through Normothermic Ex Vivo Kidney Perfusion.
Transplantation direct, 2020Co-Authors: Peter Urbanellis, Ivan Linares, Sujani Ganesh, Rohan John, Dagmar Kollmann, Laura Mazilescu, Fabiola Oquendo, Toru Goto, Yuki Noguchi, Ana KonvalinkaAbstract:Normothermic ex vivo Kidney Perfusion (NEVKP) is an emerging technique for renal graft preservation. We investigated whether NEVKP could improve early function of severely injured grafts and reduce the incidence of significant renal dysfunction (SRD) similar to delayed graft function in a model of donation after circulatory death. Methods Kidneys from 30-kg Yorkshire pigs were removed following 120 minutes of warm ischemia (WI). These grafts were then preserved in static cold storage (SCS, n = 6) or subjected to NEVKP (n = 5) for 8 hours before heterotopic autotransplantation. SRD was defined as postoperative day (POD) 4 oliguria 6.0 mmol/L. Results All 4 surviving animals with 120 minutes WI grafts stored with SCS developed SRD, compared with 1/5 in the NEVKP group (P = 0.02). The NEVKP group, when compared with SCS, also demonstrated significantly decreased serum creatinine peak values (1118.51 ± 206.90 µmol/L versus 1675.56 ± 98.15 µmol/L; P = 0.002) and higher creatinine clearance (POD4: 9.05 ± 6.97 mL/min versus 0.89 ± 0.56 mL/min; P = 0.05). By POD7, serum creatinine was not significantly different than baseline in the NEVKP (431.49 ± 492.50 µmol/L versus 90.19 ± 14.15 µmol/L, respectively; P = 0.20) but remained elevated following SCS (1189.25 ± 309.47 µmol/L versus 97.26 ± 29.18 µmol/L, respectively; P < 0.01). Histology demonstrated significantly decreased tubular injury scores compared with SCS grafts (P = 0.03). Conclusions Kidney grafts subjected to 120 minutes WI before retrieval showed significant improvement in function, prevention of SRD, and decreased injury following 8 hours of NEVKP.
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normothermic ex vivo Kidney Perfusion improves early dcd graft function compared with hypothermic machine Perfusion and static cold storage
Transplantation, 2020Co-Authors: Peter Urbanellis, J. M. Kaths, Ivan Linares, Sujani Ganesh, Matyas Hamar, Paul Yip, Dagmar Kollmann, Laura Mazilescu, Aryn Wiebe, Rohan JohnAbstract:BACKGROUND Better preservation strategies for the storage of donation after circulatory death grafts are essential to improve graft function and to increase the Kidney donor pool. We compared continuous normothermic ex vivo Kidney Perfusion (NEVKP) with hypothermic anoxic machine Perfusion (HAMP) and static cold storage (SCS) in a porcine Kidney autotransplantation model. METHODS Porcine Kidneys were exposed to 30 minutes of warm ischemia and then reimplanted following either 16 hours of either SCS, HAMP (LifePort 1.0), or NEVKP before autotransplantation (n = 5 per group). The contralateral Kidney was removed. Animals were followed for 8 days. RESULTS Grafts preserved by NEVKP demonstrated improved function with more rapid recovery compared with HAMP and SCS (mean peak serum creatinine: 3.66 ± 1.33 mg/dL [postoperative d 1 [(POD1)], 8.82 ± 3.17 mg/dL [POD2], and 12.90 ± 2.19 mg/dL [POD3], respectively). The NEVKP group demonstrated significantly increased creatinine clearance calculated on POD3 (63.6 ± 19.0 mL/min) compared with HAMP (13.5 ± 10.3 mL/min, P = 0.001) and SCS (4.0 ± 2.6 mL/min, P = 0.001). Histopathologic injury scores on POD8 were lower in both perfused groups (NEVKP and HAMP, score: 1-1.5) compared with SCS (score: 1-3, P = 0.3), without reaching statistical significance. CONCLUSIONS NEVKP storage significantly improved early Kidney function compared with both cold preservation strategies, although HAMP also demonstrates improvement over SCS. NEVKP may represent a novel, superior preservation option for donation after circulatory death renal grafts compared with conventional hypothermic methods.
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Normothermic Ex Vivo Kidney Perfusion Reduces Warm Ischemic Injury of Porcine Kidney Grafts Retrieved After Circulatory Death.
Transplantation, 2018Co-Authors: Matyas Hamar, Ivan Linares, Jun Yu Cen, Sujani Ganesh, Peter Urbanellis, Dagmar Kollmann, Aryn Wiebe, Paul M. Yip, Moritz Kaths, Rohan JohnAbstract:BACKGROUND Cold storage is poorly tolerated by Kidney grafts retrieved after donation after circulatory death. It has been determined that normothermic ex vivo Kidney Perfusion (NEVKP) preservation decreases injury by minimizing cold ischemic storage. The impact of NEVKP on warm ischemic injury is unknown. METHODS We compared pig Kidneys retrieved after 30 minutes warm ischemia and immediate transplantation (no-preservation) with grafts that were exposed to 30 minutes of warm ischemia plus 8-hour NEVKP or plus 8-hour static cold storage (SCS). RESULTS After transplantation, the NEVKP group demonstrated lower daily serum creatinine levels indicating better early graft function compared with no-preservation (P = 0.02) or SCS group (P < 0.001). In addition, NEVKP preserved grafts had a significantly lower grade of tubular injury and interstitial inflammation 30 minutes after rePerfusion compared to grafts without any storage (injury score, NEVKP 1-2 vs no-preservation, 2-2, P = 0.029; inflammation score, NEVKP, 0-0.5 vs no-preservation, 1-2; P = 0.002), although it did not reach significance level when compared to the SCS group (injury score, 1-2, P = 0.071; inflammation score, 1-1; P = 0.071). Regeneration was assessed 30 minutes after rePerfusion by Ki-67 staining. The NEVKP group demonstrated significantly higher number of Ki-67-positive cells: 9.2 ± 3.7 when compared with SCS group (3.9 ± 1.0, P = 0.015) and no-preservation group (4.2 ± 0.7, P = 0.04). CONCLUSIONS In this porcine model of donation after circulatory death Kidney transplantation NEVKP reduced Kidney injury and improved graft function when compared with no-preservation. The results suggest that NEVKP does not cause additional damage to grafts during the preservation period, but may reverse the negative effects of warm ischemic insult itself and promotes regeneration.
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Normothermic ex vivo Kidney Perfusion for graft quality assessment prior to transplantation.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2017Co-Authors: J. M. Kaths, Juan Echeverri, Ivan Linares, Jun Yu Cen, Sujani Ganesh, Matyas Hamar, Peter Urbanellis, Luke S. Dingwell, Paul M. Yip, Rohan JohnAbstract:Normothermic ex vivo Kidney Perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in Kidney transplantation. We investigated whether NEVKP also allows graft quality assessment before transplantation. Kidneys from 30-kg pigs were recovered in a model of heart-beating donation (group A) after 30 minutes (group B) or 60 minutes (group C) (n = 5/group) of warm ischemia. After 8 hours of NEVKP, contralateral Kidneys were resected, grafts were autotransplanted, and the pigs were followed for 3 days. After transplantation, renal function measured based on peak serum creatinine differed significantly among groups (P
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Normothermic Ex Vivo Kidney Perfusion Following Static Cold Storage-Brief, Intermediate, or Prolonged Perfusion for Optimal Renal Graft Reconditioning?
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2017Co-Authors: J. M. Kaths, Juan Echeverri, Ivan Linares, Jun Yu Cen, Sujani Ganesh, Matyas Hamar, Peter Urbanellis, Paul Yip, Rohan John, Darius J. BägliAbstract:Normothermic ex vivo Kidney Perfusion (NEVKP) demonstrated superior results compared to hypothermic storage in donation after circulatory death (DCD) Kidney transplantation. It is unknown whether an optimal Perfusion time exists following hypothermic storage to allow for the recovery of renal grafts from cold ischemic injury. In a porcine model of DCD Kidney autotransplantation, the impact of initial static cold storage (SCS) (8 h) followed by various periods of NEVKP recovery was investigated: group A, 8 hSCS only (control); group B, 8 hSCS + 1 hNEVKP (brief NEVKP); group C, 8 hSCS + 8 hNEVKP (intermediate NEVKP); and group D, 8 hSCS + 16 hNEVKP (prolonged NEVKP). All grafts were preserved and transplanted successfully. One animal in group D was sacrificed and excluded by postoperative day 3 due to hind limb paralysis, but demonstrated good renal function. Postoperative graft assessment during 8 days' follow-up demonstrated lowest levels of peak serum creatinine for intermediate (C) and prolonged (D) NEVKP (p = 0.027). Histological assessment on day 8 demonstrated a significant difference in tubular injury (p = 0.001), with highest values for group B. These results suggest that longer periods of NEVKP following SCS are feasible and safe for postponing surgical transplant procedure and superior to brief NEVKP, reducing the damage caused during cold ischemic storage of renal grafts.
Guillaume Duhamel - One of the best experts on this subject based on the ideXlab platform.
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Fast imaging strategies for mouse Kidney Perfusion measurement with pseudocontinuous arterial spin labeling (pCASL) at ultra high magnetic field (11.75 tesla)
Journal of Magnetic Resonance Imaging, 2015Co-Authors: Valentin H. Prevost, Olivier M. Girard, Virginie Callot, Patrick J. Cozzone, Guillaume DuhamelAbstract:Background To derive an adapted protocol at ultra high magnetic field for mouse Kidney Perfusion measurements using pCASL in combination with three widely available fast imaging readouts: segmented SE EPI (sSE EPI), RARE, and TrueFISP. Methods pCASL sSE EPI, pCASL RARE, and pCASL TrueFISP were used for the acquisition of mouse Kidney Perfusion images in the axial and coronal planes at 11.75T. Results were compared in terms of Perfusion sensitivity, signal-to-noise ratio (SNR), blood flow values, intrasession and intersession repeatability, and image quality (subjectively classified into three grades: good, satisfactory, and unacceptable). Results Renal cortex Perfusion measurements were performed within 2 min with pCASL RARE/pCASL TrueFISP and 4 min with pCASL sSE EPI. In an axial direction, SNR values of 6.6/5.6/2.8, Perfusion sensitivity values of 16.1 ± 3.7/13.6 ± 2.4/13.4 ± 1.0 %, blood flow values of 679 ± 149/466 ± 111/572 ± 46 mL/100 g/min and in-ROI variations values of 192/161/181 mL/100 g/min were obtained with pCASL sSE EPI/pCASL RARE/pCASL TrueFISP. Highest SNR per unit of time (1.8) and highest intra/intersession reliability (92.9% and 95.1%) were obtained with pCASL RARE, which additionally presented highly reproducible satisfactory image quality. In coronal plane, significantly lower SNR, Perfusion sensitivity and Perfusion values were obtained for all techniques compared with that in the axial plane (P \textless 0.05) due to magnetization saturation effects. Conclusion pCASL RARE demonstrated more advantages for longitudinal preclinical Kidney Perfusion studies at ultra high magnetic field. J. Magn. Reson. Imaging 2015;42:999–1008.
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Fast imaging strategies for mouse Kidney Perfusion measurement with pseudocontinuous arterial spin labeling (pCASL) at ultra high magnetic field (11.75 tesla).
Journal of magnetic resonance imaging : JMRI, 2015Co-Authors: Valentin H. Prevost, Olivier M. Girard, Virginie Callot, Patrick J. Cozzone, Guillaume DuhamelAbstract:Background To derive an adapted protocol at ultra high magnetic field for mouse Kidney Perfusion measurements using pCASL in combination with three widely available fast imaging readouts: segmented SE EPI (sSE EPI), RARE, and TrueFISP. Methods pCASL sSE EPI, pCASL RARE, and pCASL TrueFISP were used for the acquisition of mouse Kidney Perfusion images in the axial and coronal planes at 11.75T. Results were compared in terms of Perfusion sensitivity, signal-to-noise ratio (SNR), blood flow values, intrasession and intersession repeatability, and image quality (subjectively classified into three grades: good, satisfactory, and unacceptable). Results Renal cortex Perfusion measurements were performed within 2 min with pCASL RARE/pCASL TrueFISP and 4 min with pCASL sSE EPI. In an axial direction, SNR values of 6.6/5.6/2.8, Perfusion sensitivity values of 16.1 ± 3.7/13.6 ± 2.4/13.4 ± 1.0 %, blood flow values of 679 ± 149/466 ± 111/572 ± 46 mL/100 g/min and in-ROI variations values of 192/161/181 mL/100 g/min were obtained with pCASL sSE EPI/pCASL RARE/pCASL TrueFISP. Highest SNR per unit of time (1.8) and highest intra/intersession reliability (92.9% and 95.1%) were obtained with pCASL RARE, which additionally presented highly reproducible satisfactory image quality. In coronal plane, significantly lower SNR, Perfusion sensitivity and Perfusion values were obtained for all techniques compared with that in the axial plane (P
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High-resolution mouse Kidney Perfusion imaging by pseudo-continuous arterial spin labeling at 11.75T
Magnetic resonance in medicine, 2013Co-Authors: Guillaume Duhamel, Valentin H. Prevost, Olivier M. Girard, Virginie Callot, Patrick J. CozzoneAbstract:Purpose Quantitative measure of blood flow provides important information regarding renal function, nephropathies and viability of Kidney transplantation. Therefore, a method that would allow quantitative and reliable assessment of the renal microvascular Perfusion would be very valuable. Arterial spin labeling Magnetic Resonance Imaging has started to be widely used for human studies. For rodents though, despite the increasing number of transgenic mouse models, renal Perfusion Magnetic Resonance Imaging has been only sparsely reported. This study investigated the use of FAIR (flow-sensitive alternating inversion recovery) and pseudo-continuous arterial spin labeling (pCASL) for mouse renal blood flow measurements. Methods FAIR and pCASL were compared in terms of sensitivity, absolute quantification, reproducibility and flexibility of implementation. Multislice and coronal imaging were also investigated. Studies were performed at 11.75 T with volumic transmitter/receiver radiofrequency coils and fast imaging. Results pCASL demonstrated better experimental flexibility and higher sensitivity compared to FAIR (> +20%). Renal blood flow values in the range of 550–750 mL/100 g/min for the cortex and of 140–230 mL/100 g/min for the medulla, consistent with literature data, were measured. Conclusion pCASL was successfully applied at very high field for mouse renal blood flow measurements, demonstrating high sensitivity, flexibility and multislice imaging capability. pCASL may be considered as a method of choice for mouse Kidney Perfusion studies. Magn Reson Med 71:1186–1196, 2014. © 2013 Wiley Periodicals, Inc.
Richard L. Marquet - One of the best experts on this subject based on the ideXlab platform.
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In vivo isolated Kidney Perfusion with tumour necrosis factor α (TNF- α ) in tumour-bearing rats
British Journal of Cancer, 1999Co-Authors: A H Van Der Veen, Ann L.b. Seynhaeve, J Breurs, P.t.g.a. Nooijen, Richard L. Marquet, A. M. M. EggermontAbstract:Isolated Perfusion of the extremities with high-dose tumour necrosis factor α (TNF-α) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ Perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated Kidney Perfusion. We studied the feasibility of a Perfusion with TNF-α and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 μg TNF-α. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-α and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated Kidney Perfusion, with TNF-α alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the Kidney to Perfusion with TNF-α, the minimal threshold concentration of TNF-α to exert its anti-tumour effects was not reached. The applicability of TNF-α in isolated Kidney Perfusion for human tumours seems, therefore, questionable. © 1999 Cancer Research Campaign
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In vivo isolated Kidney Perfusion with tumour necrosis factor alpha (TNF-alpha) in tumour-bearing rats.
British journal of cancer, 1999Co-Authors: A H Van Der Veen, Ann L.b. Seynhaeve, J Breurs, P.t.g.a. Nooijen, Richard L. Marquet, A. M. M. EggermontAbstract:Isolated Perfusion of the extremities with high-dose tumour necrosis factor alpha (TNF-alpha) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ Perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated Kidney Perfusion. We studied the feasibility of a Perfusion with TNF-alpha and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 microg TNF-alpha. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-alpha and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated Kidney Perfusion, with TNF-alpha alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the Kidney to Perfusion with TNF-alpha, the minimal threshold concentration of TNF-alpha to exert its anti-tumour effects was not reached. The applicability of TNF-alpha in isolated Kidney Perfusion for human tumours seems, therefore, questionable.
