scholarly journals Administration of Beta-Emitting Anti-CD37 Radioimmunoconjugate Lutetium (177Lu) Lilotomab Satetraxetan as Weekly Multiple Injections Increases Maximum Tolerated Activity in Nude Mice with Non- Hodgkin Lymphoma Xenografts

2018 ◽  
Vol 4 (1) ◽  
pp. 181-190
Author(s):  
Helen Heyerdahl ◽  
Ada H.V. Repetto-Llamazares ◽  
Jostein Dahle
Keyword(s):  
Hodgkin Lymphoma ◽  
Nude Mice ◽  
Separate Experiment ◽  
Growth Delay ◽  
Control Group ◽  
Multiple Dosing ◽  
Multiple Injections ◽  
Non Hodgkin Lymphoma

Lutetium (177Lu) lilotomab satetraxetan (177Lu-lilotomab) is a novel anti-CD37 radioimmunoconjugate (RIC) currently in Phase 2b clinical trial for treatment of non-Hodgkin lymphoma (NHL). The aim of the current study was to investigate tolerability and anti-tumor efficacy of multiple dosing of 177Lu-lilotomab in vivo. Nude mice with subcutaneous (s.c.) NHL (Ramos) xenografts were given 2, 3 or 4 weekly injections of 300 MBq/kg 177Lu-lilotomab or NaCl. Treatment tolerability was assessed by body weight, hematology and histopathological evaluation. A separate experiment in mice without xenografts was performed to collect long term toxicity data. Mice in this study were dosed more conservatively with the intention that all mice should survive until end of experiment and were administered 2 or 4 weekly injections of 200 MBq/kg 177Lu-lilotomab or NaCl. Total accumulated activity of 900 MBq/kg 177Lu-lilotomab given as three weekly injections was tolerated by nude mice with s.c. Ramos xenografts, which is 50 % higher than the maximum tolerated activity (MTA) of a single injection of 530-600 MBq/kg. In the long-term toxicity animals, the highest accumulated activity tested, 800 MBq/kg, was also well tolerated. Radioactivity-dependent transient reduction in white blood cell and platelet counts occurred in all treated groups, with nadir 1-3 weeks after last injection. This toxicity was radioactivity dependent and consistent with histopathological changes in hemolymphopoietic tissues. Significant tumor growth delay measured as time to reach 4 times intial tumor volume was observed in all groups given multiple injections of 300 MBq/kg 177Lu-lilotomab compared to NaCl control group (p<0.001). In conclusion, weekly injections of 177Lu-lilotomab increase the accumulated MTA from 530 to 900 MBq/kg in nude mice, allowing the total injected activity and hence the radiation dose to tumor to be increased without increasing the toxicity to normal tissues.

Rapid manufacture of cd19 car t cells in an automated system for treatment of non-hodgkin lymphoma results in long term persistence in vivo

Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S85
Author(s):  
K. Zamborsky ◽  
J. Payne-Schiavone ◽  
S. Kleinsorge-Block ◽  
I. Yevtukh ◽  
K. Oliva ◽  
...  
Keyword(s):  
T Cells ◽  
Hodgkin Lymphoma ◽  
Automated System ◽  
Car T Cells ◽  
Non Hodgkin Lymphoma ◽  
Car T ◽  
Rapid Manufacture

scholarly journals Fluorescent Nanodiamonds Enable Long-Term Detection of Human Adipose-Derived Stem/Stromal Cells in an In Vivo Chondrogenesis Model Using Decellularized Extracellular Matrices and Fibrin Glue Polymer

Polymers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1391 ◽  
Author(s):  
Yi-Chia Wu ◽  
Ya-Chin Wang ◽  
Wei-Ting Wang ◽  
Hui-Min David Wang ◽  
Hsin-Hung Lin ◽  
...  
Keyword(s):  
Fibrin Glue ◽  
Nude Mice ◽  
Stromal Cells ◽  
Histological Analysis ◽  
Control Group ◽  
Efficient Treatment ◽  
Fluorescent Nanodiamonds ◽  
Experimental Group

Clinically available materials, including allogeneic irradiated costal cartilage and fibrin glue polymer, were used as scaffolds for in vivo chondrogenic differentiation of human adipose-derived stem/stromal cells (hASCs) in the attempt to develop a more efficient treatment over current methods. Current studies include the use of growth-factor stimulation, tissue engineering, and biocompatible materials; however, most methods involve complicated processes and pose clinical limitations. In this report, the xenografts in the experimental group composed of a diced decellularized cartilage extracellular matrix (ECM), hASCs, and fibrin glue polymer were implanted into the subcutaneous layer of nude mice, and the results were compared with two groups of controls; one control group received implantation of decellularized cartilage ECM and fibrin glue polymer, and the other control group received implantation of hASCs mixed with fibrin glue polymer. To evaluate whether hASCs had in vivo chondrogenesis in the xenografts, hASCs were labeled with fluorescent nanodiamonds (FNDs), a biocompatible and photostable nanomaterial, to allow for long-term detection and histological analysis. Increased cellularity, glycosaminoglycan, and collagen deposition were found by the histological examination in the experimental group compared with control groups. With the background-free detection technique and time-gated fluorescence imaging, the numbers and locations of the FND-labeled hASCs could be detected by confocal microscopy. The chondrocyte-specific markers, such as aggrecan and type II collagen, were colocalized with cells containing signals of FNDs which indicated in vivo chondrogenesis of hASCs. Taken together, functional in vivo chondrogenesis of the hASCs could be achieved by clinically available decellularized cartilage ECM and fibrin glue polymer in the nude mice model without in vitro chondrogenic induction. The fluorescent signals of FNDs in hASCs can be detected in histological analysis, such as hematoxylin and eosin staining (H&E staining) without the interference of the autofluorescence. Our study may warrant future clinical applications of the combination of decellular cartilage ECM, fibrin glue polymer, and hASCs for cartilage repair.

Lentiviral-Mediated Beclin-1 Overexpression Inhibits Cell Proliferation and Induces Autophagy of Human Esophageal Carcinoma Eca109 Cell Xenograft in Nude Mice

2020 ◽  
Vol 15 (1) ◽  
pp. 70-77
Author(s):  
Junhe Zhang ◽  
Weihua Dong
Keyword(s):  
Growth Rate ◽  
Cell Proliferation ◽  
Esophageal Carcinoma ◽  
Nude Mice ◽  
Beclin 1 ◽  
Control Group ◽  
Vector Group ◽  
Empty Vector ◽  
Empty Vector Group

Background: Esophageal carcinoma is one of the common malignant tumors in digestive tract. BECLIN-1 is a key gene that regulates autophagy, and its abnormal expression may be related with many human tumors. However, the mechanism of BECLIN-1 in esophageal carcinoma remains unknown. Objective: In this study, we explored the effect of BECLIN-1 overexpression on tumor growth in mice with esophageal carcinoma and its mechanism. Methods: Recombined lentiviral vector containing BECLIN-1 was used to transfect human esophageal carcinoma Eca109 cells and establish stable cell line. qRT-PCR was used to detect BECLIN-1 mRNA level in the transfected Eca109 cells, CCK-8 assay was used to detect cell proliferation. Beclin-1, P62 and LC3-II protein expression levels in Eca109 cells were detected using Western blot analysis. Subcutaneous xenograft nude mice model of human esophageal carcinoma was established, and the tumor growths in Beclin-1 group, control group and empty vector group were monitored. Beclin-1 protein expression in vivo was detected by immunohistochemistry. Results: Beclin-1 mRNA and protein were overexpressed in Eca109 cells. Compared with empty vector group, the growth rate of cells transfected with BECLIN-1 decreased significantly. Compared with the control group and empty vector group, the expression level of P62 protein in beclin-1 group was significantly decreased, while the expression level of LC3-II protein was significantly increased. The tumor growth rate in nude mice of Beclin-1 group was significantly lower than that of the control group and empty vector group, and Beclin-1 protein was mainly expressed in Beclin-1 group in vivo. Conclusion: BECLIN-1 can induce autophagy in esophageal carcinoma Eca109 cells, and it can significantly inhibit the growth of esophageal carcinoma.

Persistent fatigue among long-term non-Hodgkin lymphoma survivors

2021 ◽  
pp. 1-9
Author(s):  
Matthew R. LeBlanc ◽  
Sheryl Zimmerman ◽  
Thomas W. LeBlanc ◽  
Ashley Leak Bryant ◽  
Kathryn E. Hudson ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Persistent Fatigue ◽  
Lymphoma Survivors

scholarly journals SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo

2012 ◽  
Vol 158A (9) ◽  
pp. 2204-2213 ◽  
Author(s):  
Alireza Baradaran-Heravi ◽  
Anja Raams ◽  
Joanna Lubieniecka ◽  
Kyoung Sang Cho ◽  
Kristi A. DeHaai ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Genotoxic Agents

scholarly journals Axicabtagene Ciloleucel (axi-cel; KTE-C19) in Patients with Refractory Aggressive Non-Hodgkin Lymphoma (NHL): Long-Term Follow-up of the Pivotal Zuma-1 Trial

2018 ◽  
Vol 24 (3) ◽  
pp. S74-S75 ◽  
Author(s):  
Sattva S. Neelapu ◽  
Frederick L. Locke ◽  
Nancy L. Bartlett ◽  
Lazaros J. Lekakis ◽  
David Miklos ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Long Term Follow Up

Catheter Patency and Peritoneal Morphology and Function in a Rat Model of Citrate-Buffered Peritoneal Dialysis

2010 ◽  
Vol 30 (6) ◽  
pp. 602-610 ◽  
Author(s):  
Nicola Cavallini ◽  
Magnus Braide
Keyword(s):  
Peritoneal Dialysis ◽  
Rat Model ◽  
Fluid Transport ◽  
Separate Experiment ◽  
Control Group ◽  
Vascular Density ◽  
Long Term Effects ◽  
Catheter Patency ◽  
Peritoneal Morphology

BackgroundSingle-dwell studies in rats and humans have shown that supplementing citrate for lactate in peritoneal dialysis (PD) fluids improves ultrafiltration (UF).MethodsThe long-term effects of citrate-substituted PD fluids on PD catheter patency, UF, and peritoneal morphology were evaluated in a rat model over 5 weeks of daily PD fluid exposure. A standard 2.5% glucose 40 mmol/L lactate PD fluid and a corresponding 10/30 mmol/L citrate/lactate PD fluid were compared. In a control group, rats with catheters received no PD fluid.ResultsThe average patency time (% of 36 days) of silicone rubber PD catheters was significantly longer in the citrate PD group (98.8% ± 1.2%) and the control group (100% ± 0%) compared to the lactate PD group (54.7% ± 9.5%). In a separate experiment, heparin-coated polyurethane catheters were used to study peritoneal morphology and fluid transport. The citrate group had a higher net UF than the lactate group at the beginning and at the end of the 5 weeks. During the experiment, both fluid-treated groups suffered from UF loss; the control group showed the highest net UF at the end of the 5 weeks. Peritoneal vascular density and submesothelial thickness, indicators of angiogenesis and fibrosis, were not significantly different among the groups. Fibrosis was significantly negatively correlated to osmotic UF.ConclusionA positive acute effect of citrate on UF was confirmed and conserved over time. Citrate PD strongly improved PD catheter patency time compared with lactate. Both citrate PD and lactate PD induced negative long-term effects on UF compared with control animals.

scholarly journals Expression of the oncofetal ED-B–containing fibronectin isoform in hematologic tumors enables ED-B–targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients

Blood ◽  
2009 ◽  
Vol 113 (10) ◽  
pp. 2265-2274 ◽  
Author(s):  
Stefanie Sauer ◽  
Paola A. Erba ◽  
Mario Petrini ◽  
Andreas Menrad ◽  
Leonardo Giovannoni ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Hodgkin Lymphoma ◽  
Hematologic Malignancies ◽  
Current Treatment ◽  
Cancer Therapies ◽  
Bone Marrow Biopsies ◽  
Normal Tissues ◽  
Non Hodgkin Lymphoma ◽  
Promising Target

Abstract Current treatment of hematologic malignancies involves rather unspecific chemotherapy, frequently resulting in severe adverse events. Thus, modern clinical research focuses on compounds able to discriminate malignant from normal tissues. Being expressed in newly formed blood vessels of solid cancers but not in normal mature tissues, the extradomain B of fibronectin (ED-B FN) is a promising target for selective cancer therapies. Using immunohistology with a new epitope retrieval technique for paraffin-embedded tissues, ED-B FN expression was found in biopsies from more than 200 Hodgkin and non-Hodgkin lymphoma patients of nearly all entities, and in patients with myeloproliferative diseases. ED-B FN expression was nearly absent in normal lymph nodes (n = 10) and bone marrow biopsies (n = 9). The extent of vascular ED-B FN expression in lymphoma tissues was positively correlated with grade of malignancy. ED-B FN expression was enhanced in lymph nodes with severe lymphadenopathy and in some hyperplastic tonsils. The in vivo accessibility of ED-B FN was confirmed in 3 lymphoma patients, in whom the lymphoma lesions were visualized on scintigraphy with 131I-labeled L19 small immunoprotein (131I-L19SIP). In 2 relapsed Hodgkin lymphoma patients131I-L19SIP radioimmunotherapy induced a sustained partial response, qualifying ED-B FN as a promising target for antibody-based lymphoma therapies.

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