Radioimmunotherapy of Xenografts of Human Pancreatic Carcinomas - Intravenous and Intratumoral Application of 131l-Labelled Monoclonal Antibodies

1986 ◽  
Vol 25 (06) ◽  
pp. 235-238 ◽  
Author(s):  
S. Lander ◽  
M. Bahlo ◽  
R. Montz ◽  
R. Klapdor
Keyword(s):  
Irradiation Dose ◽  
Tumor Regression ◽  
Whole Body ◽  
Inhibit Tumor Growth ◽  
Local Irradiation ◽  
Clinical Value ◽  
Direct Radiation ◽  
Intravenous Injections ◽  
Induce Tumor Regression ◽  
High Doses

The effects of radioimmunotherapy were tested in xenografts of 2 different human pancreatic carcinomas comparing the intravenous and intratumoral application. On principle, intravenous injections of high doses of 131l-anti- Ca 19-9 or -BW 494/32 may inhibit tumor growth. In view of the low direct radiation dose (360-2100 rad), however, other factors than direct toxic effects have to be discussed, e. g. systemic effects due to the high whole-body irradiation. Intratumoral application, however, may induce tumor regression or growth inhibition due to the high local irradiation dose. Consequently, this treatment modality might be of clinical value at least in some patients.

Effects of Vancomycin on Platelets, Plasma Proteins and Hepatitis B Surface Antigen

1975 ◽  
Vol 34 (01) ◽  
pp. 083-093 ◽  
Author(s):  
Barry S Coller ◽  
W. B Lundberg ◽  
Harvey R Gralnick
Keyword(s):  
Hepatitis B ◽  
Factor Viii ◽  
Surface Antigen ◽  
Plasma Proteins ◽  
Hepatitis B Surface Antigen ◽  
Infusion Site ◽  
Vancomycin Therapy ◽  
Intravenous Injections ◽  
Low Concentrations ◽  
High Doses

SummaryThe antibiotic vancomycin shares many similarities with ristocetin, an agent noted for its effects on platelets and plasma fibrinogen. Vancomycin did not aggregate platelets as ristocetin, but platelets were incorporated into precipitates induced by vancomycin. Fibrinogen and factor VIII were precipitated from plasma at low concentrations of vancomycin. The precipitated fibrinogen remained clottable. Hepatitis B surface antigen was selectively precipitated from serum and could be recovered from the precipitate. Rabbits receiving bolus intravenous injections of high doses of vancomycin developed hypofibrinogenemia and thrombocytopenia within minutes and often went on to die. Studies with 125I-vancomycin revealed little stable binding of the antibiotic to platelets or fibrinogen. A relationship is suggested between the potent protein precipitating effects and phlebitis at the infusion site commonly associated with vancomycin therapy.

scholarly journals Cabozantinib and dasatinib synergize to induce tumor regression in non-clear cell renal cell carcinoma

2021 ◽  
pp. 100267
Author(s):  
Hui-wen Lue ◽  
Daniel S. Derrick ◽  
Soumya Rao ◽  
Ahna Van Gaest ◽  
Larry Cheng ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumor Regression ◽  
Cell Renal Cell Carcinoma ◽  
Induce Tumor Regression

scholarly journals TLR4/IFNγ pathways induce tumor regression via NOS II-dependent NO and ROS production in murine breast cancer models

2015 ◽  
Vol 5 (5) ◽  
pp. e1123369 ◽  
Author(s):  
Myriam Lamrani ◽  
Nejia Sassi ◽  
Catherine Paul ◽  
Nadhir Yousfi ◽  
Jean-Luc Boucher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Regression ◽  
Ros Production ◽  
Induce Tumor Regression ◽  
Cancer Models

scholarly journals Targeted α particle immunotherapy for myeloid leukemia

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1233-1239 ◽  
Author(s):  
Joseph G. Jurcic ◽  
Steven M. Larson ◽  
George Sgouros ◽  
Michael R. McDevitt ◽  
Ronald D. Finn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Absorbed Dose ◽  
Myelogenous Leukemia ◽  
Whole Body ◽  
Hematopoietic Stem ◽  
Acute Myelogenous ◽  
Antigen System ◽  
High Doses ◽  
Nonspecific Cytotoxicity

Unlike β particle–emitting isotopes, α emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the β-emitters 131I and 90Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of β-emitting constructs, the α-emitting isotope 213Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg 213Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the 213Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with β-emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of 213Bi-HuM195, and it is the first proof-of-concept for systemic targeted α particle immunotherapy in humans.

scholarly journals Protection from Radiation-induced Damage in Rat’s Ileum and Colon by Combined Regimens of Melatonin and Metformin: A Histopathological Study

2020 ◽  
Vol 19 (2) ◽  
pp. 180-189 ◽  
Author(s):  
Masoud Najafi ◽  
Mohsen Cheki ◽  
Gholamreza Hassanzadeh ◽  
Peyman Amini ◽  
Dheyauldeen Shabeeb ◽  
...  
Keyword(s):  
Whole Body ◽  
Gastrointestinal Disorders ◽  
Histopathological Study ◽  
Radiation Toxicity ◽  
Pharmaceutical Treatment ◽  
Tissue Samples ◽  
Melatonin Administration ◽  
Male Wistar Rats ◽  
Radiation Induced ◽  
High Doses

Background: Radiation-induced enteritis and proctitis are common side effects of abdominopelvic cancers among patients that undergo radiotherapy for prostate, colorectal or urinary cancers. Exposure of these tissues to high doses of radiation leads to damage to villous, inflammation, pain, ulcer and bleeding, which may cause malabsorption and gastrointestinal disorders. To date, several procedures such as pharmaceutical treatment have been proposed for protection and mitigation of gastrointestinal toxicity following radiotherapy. Aims: In the current study, we aimed to investigate the possible radioprotection of ileum and colon in rats using a combination of melatonin and metformin. Methods: In this experimental study, 30 male Wistar rats were randomly assigned to six groups: control, melatonin (100 mg/kg) treatment, melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment, radiation (10 Gy to whole body) group, radiation + melatonin (100 mg/kg) treatment, and radiation + melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment. After 3.5 days, rats were sacrificed and their ileum and colon tissues carefully removed. Histopathological evaluations were conducted on these tissue samples. Results: Histological evaluations reported moderate to severe damages to ileum and colon following whole body irradiation. Melatonin administration was able to protect the ileum remarkably, while the combination of melatonin and metformin was less effective. Interestingly, for the colon, melatonin was less effective while its combination with metformin was able to protect against radiation toxicity completely. Conclusion: For the ileum, melatonin was a more effective radioprotector compared to its combination with metformin. However, the combination of melatonin and metformin can be proposed as an ideal radioprotector for the colon.

Changes in 5-HT-mediated pathways in radiation-induced attenuation and recovery of ion transport in rat colon

2000 ◽  
Vol 278 (1) ◽  
pp. G75-G82 ◽  
Author(s):  
A. François ◽  
B. Ksas ◽  
P. Gourmelon ◽  
N. M. Griffiths
Keyword(s):  
Electrical Field Stimulation ◽  
Whole Body ◽  
Rat Colon ◽  
Receptor Subtypes ◽  
Ussing Chambers ◽  
Tissue Responses ◽  
Radiation Induced ◽  
High Doses ◽  
Colonic Transport

Whole body exposure to high doses of ionizing radiation is associated with small intestinal and colonic dysfunction, the etiology of which remains unknown. In this study, we investigated the role of both neural and nonneural 5-hydroxytryptamine (5-HT)-mediated pathways in radiation-induced attenuation and recovery of colonic secretory function. Rats were exposed to whole body 10-Gy gamma irradiation, and distal colonic tissues were studied in Ussing chambers 1, 3, and 7 days after exposure. Tissue responses to exogenously added 5-HT (nonneural pathway) and electrical field stimulation (EFS; neural pathway) were performed, and 5-HT receptor subtypes implicated in both responses were determined using three different 5-HT receptor antagonists: methysergide (5-HT2/1C), granisetron (5-HT3), and SDZ-205,557 (5-HT4). Maximal responses to exogenously added 5-HT were decreased at 1 and 3 days and returned to control values at 7 days. Responses to exogenous 5-HT were insensitive to both 5-HT2/1C and 5-HT3 antagonists and to TTX but were totally inhibited by SDZ-205,557 in both control and irradiated tissues. Responses to EFS were decreased 1 and 3 days after exposure and returned to control values at 7 days. In control tissues and 1 and 3 days after exposure, EFS responses were insensitive to both 5-HT2/1C and 5-HT4 antagonists but reduced by granisetron in control (51%) and at 1 (64%) and 3 days (58%) after exposure. Granisetron was more effective at 7 days (73% inhibition), which was concomitant with the appearance of a 5-HT4antagonist-sensitive pathway (40% inhibition). In conclusion, neural and nonneural 5-HT-mediated pathways involve 5-HT3 and 5-HT4 receptors, respectively, in control as well as in irradiated tissues 1 and 3 days after exposure. Conversely, the recovery of colonic transport is associated with additional 5-HT3-mediated pathways, probably in combination with 5-HT4 receptors.

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