scholarly journals Anti-Angiogenesis Therapy of Cancer Cells using 153Sm-Bevasesomab

2018 ◽  
Vol 2 (3) ◽  
Author(s):  
Kamal Yavari
Keyword(s):  
Monoclonal Antibody ◽  
Cancer Cell Line ◽  
Chelating Agent ◽  
Colon Cancer Cell Line ◽  
Molar Ratio ◽  
Sds Page ◽  
Layer Chromatography ◽  
In Vitro Stability ◽  
Antibody Labelling

Purpose: Angiogenesis is essential for tumor growth or metastasis. Avastin is a monoclonal antibody that is used in treating angiogenesis. We labelled this monoclonal antibody with samarium153 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical.Material and Methods: For a successful radiolabeling, we chose DOTA-NHS as the bifunctional chelating agent and optimized radiolabeling condition with modifications of the factors such as reaction time and molar ratio which are known to be very critical in radiolabeling. The efficiency and in vitro stability of antibody labelling were determined using thin layer chromatography. The integrity of the radiolabeled antibody was checked by SDS-PAGE. Biodistribution study of 153Sm-DOTA –avastin was carried out in BALB/c mice at 2, 24, 48 and 72 hours after injection. Immunoreactivity and toxicity of the complex were tested on colon cancer cell line by MTT.Results: The efficiency of antibody labelling was more than 99%. The in vitro stability of the labelled product in human serum after 120h was 78 ±2%. There was no fragmentation in the labelled antibody during SDS-PAGE protocol. The highest of %ID/g was observed in the blood, liver, lungs and spleen. The immunoreactivity of the complex was 89±1.4%. At a concentration of 1 nM, the complex killed 70±3% of SW480 cells. At 1.9 nM, 90±5% of the cells were killed.Discussion: The monoclonal antibody avastin against angiogenesis was effectively radiolabeled with 153Sm. The results showed that the new complex could be considered a promising tracer for noninvasive delineation of angiogenesis.

scholarly journals A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1526
Author(s):  
Cristina Ioana Barbălată ◽  
Alina Silvia Porfire ◽  
Alina Sesarman ◽  
Valentin-Florian Rauca ◽  
Manuela Banciu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cell Line ◽  
Colon Cancer Cell Line ◽  
Processing Parameters ◽  
Molar Ratio ◽  
Drug Release Profile ◽  
Optimal Drug ◽  
Formulation Factors ◽  
Murine Colon

An increasing number of studies published so far have evidenced the benefits of Simvastatin (SIM) and Doxorubicin (DOX) co-treatment in colorectal cancer. In view of this, the current study aimed to investigate the pharmaceutical development of liposomes co-encapsulating SIM and DOX, by implementing the Quality by Design (QbD) concept, as a means to enhance the antiproliferative effect of the co-formulation on C26 murine colon cancer cells co-cultured with macrophages. It is known that the quality profile of liposomes is dependent on the critical quality attributes (CQAs) of liposomes (drug entrapped concentration, encapsulation efficiency, size, zeta potential, and drug release profile), which are, in turn, directly influenced by various formulation factors and processing parameters. By using the design of experiments, it was possible to outline the increased variability of CQAs in relation to formulation factors and identify by means of statistical analysis the material attributes that are critical (phospholipids, DOX and SIM concentration) for the quality of the co-formulation. The in vitro studies performed on a murine colon cancer cell line highlighted the importance of delivering the optimal drug ratio at the target site, since the balance antiproliferative vs. pro-proliferative effects can easily be shifted when the molar ratio between DOX and SIM changes.

The Anticoagulant Properties of a Modified Form of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 298-304 ◽  
Author(s):  
C A Mitchell ◽  
S M Kelemen ◽  
H H Salem
Keyword(s):  
Monoclonal Antibody ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Factor Xa ◽  
Protein S ◽  
Human Neutrophil Elastase ◽  
Factor X ◽  
Sds Page

SummaryProtein S (PS) is a vitamin K-dependent anticoagulant that acts as a cofactor to activated protein C (APC). To date PS has not been shown to possess anticoagulant activity in the absence of APC.In this study, we have developed monoclonal antibody to protein S and used to purify the protein to homogeneity from plasma. Affinity purified protein S (PSM), although identical to the conventionally purified protein as judged by SDS-PAGE, had significant anticoagulant activity in the absence of APC when measured in a factor Xa recalcification time. Using SDS-PAGE we have demonstrated that prothrombin cleavage by factor X awas inhibited in the presence of PSM. Kinetic analysis of the reaction revealed that PSM competitively inhibited factor X amediated cleavage of prothrombin. PS preincubated with the monoclonal antibody, acquired similar anticoagulant properties. These results suggest that the interaction of the monoclonal antibody with PS results in an alteration in the protein exposing sites that mediate the observed anticoagulant effect. Support that the protein was altered was derived from the observation that PSM was eight fold more sensitive to cleavage by thrombin and human neutrophil elastase than conventionally purified protein S.These observations suggest that PS can be modified in vitro to a protein with APC-independent anticoagulant activity and raise the possibility that a similar alteration could occur in vivo through the binding protein S to a cellular or plasma protein.

scholarly journals Nimesulide Based Novel Glycolamide Esters: Their Design, Synthesis, and Pharmacological Evaluation

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kavitha Kankanala ◽  
Vangala Ranga Reddy ◽  
Yumnam Priyadarshini Devi ◽  
Lakshmi Narasu Mangamoori ◽  
Khagga Mukkanti ◽  
...  
Keyword(s):  
Cancer Cell Line ◽  
Human Colon ◽  
Colon Cancer Cell Line ◽  
Cytotoxic Activities ◽  
Step Method ◽  
Human Colon Cancer ◽  
Cytotoxic Effects ◽  
Design Synthesis ◽  
First Time

The nimesulide based novel glycolamide esters were designed and synthesized for the first timeviaa three-step method starting from nimesulide. Structures of the synthesized compounds were confirmed by spectroscopic analysis. All the synthesized compounds were examined for their cytotoxic effectsin vitro,some of which showed significant cytotoxic activities against HCT-15 human colon cancer cell line.

scholarly journals A Novel PET Imaging Using64Cu-Labeled Monoclonal Antibody against Mesothelin Commonly Expressed on Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Kazuko Kobayashi ◽  
Takanori Sasaki ◽  
Fumiaki Takenaka ◽  
Hiromasa Yakushiji ◽  
Yoshihiro Fujii ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cancer Cells ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Chelating Agent ◽  
Pancreatic Cancer Cells ◽  
Positron Emission ◽  
Wide Range

Mesothelin (MSLN) is a 40-kDa cell differentiation-associated glycoprotein appearing with carcinogenesis and is highly expressed in many human cancers, including the majority of pancreatic adenocarcinomas, ovarian cancers, and mesotheliomas, while its expression in normal tissue is limited to mesothelial cells lining the pleura, pericardium, and peritoneum. Clone 11-25 is a murine hybridoma secreting monoclonal antibody (mAb) against human MSLN. In this study, we applied the 11-25 mAb toin vivoimaging to detect MSLN-expressing tumors. Inin vitroandex vivoimmunochemical studies, we demonstrated specificity of 11-25 mAb to membranous MSLN expressed on several pancreatic cancer cells. We showed the accumulation of Alexa Fluor 750-labeled 11-25 mAb in MSLN-expressing tumor xenografts in athymic nude mice. Then, 11-25 mAb was labeled with64Cu via a chelating agent DOTA and was used in bothin vitrocell binding assay andin vivopositron emission tomography (PET) imaging in the tumor-bearing mice. We confirmed that64Cu-labeled 11-25 mAb highly accumulated in MSLN-expressing tumors as compared to MSLN-negative ones. The64Cu-labeled 11-25 mAb is potentially useful as a PET probe capable of being used for wide range of tumors, rather than18F-FDG that occasionally provides nonspecific accumulation into the inflammatory lesions.

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