Recombinant Snake Venom Cystatin Inhibits Tumor Angiogenesis in vitro and in vivo Associated with Downregulation of VEGF-A165, Flt-1 and bFGF

Snakebite is a life-threatening medical emergency, and globally responsible for millions of deaths. In snakebites accidents only deaths are not a concern, it leads to more morbidities. Due to scanty healthcare facilities in rural areas of India, many people seek alternative treatment available in ethnic practices. Tamarindus Indica (TI) plant is rich in medicinal value and used to treat many diseases including snakebite treatment traditionally. In view of this TI seed coat extract (TISCE) was evaluated for antivenom activity. The phytochemical screening of TISCE was performed to understand its chemical composition. TISCE was evaluated for antivenom activity against Indian cobra venom (ICV), common krait venom (CKV), Russells viper venom (RVV), and saw-scaled viper venom (SCV) for phospholipase A2 (PLA-2), haemorrhagic in vitro and in vivo, procoagulant, proteolytic activity, and lethality studies. TISCE majorly contains saponins, glycosides, alkaloids, and phenolic compounds. Minimum indirect haemorrhagic dose (MIHD) observed for ICV (12.5 Âµg), CKV (5.0 Âµg),RVV (10.0 Âµg), and SVV (12.5 Âµg). TISCE inhibits the procoagulant activity of all venoms at a concentration of 18.0 Âµg. It also shows the neutralization of proteolytic enzymes of venom in a dose-dependent manner. A pre-incubated mixture containing five lethal dose 50 (LD50) of venom and TISCE was injected intravenously, all mice survived as venom neutralized by TISCE. The present study demonstrates the ability of TISCE to neutralize snake venom using suitable in vivo and in vitro methods. Further studies required to unravelling the speciï¬c active chemical constituent of TISCE that may used as novel alternative snakebite treatment. TISCE was able to prolong the deaths during the simulation study and may be used in the topical pharmaceutical formulation that will reduce local venom reactions causing much morbidity, which will collectively with Anti-snake venom (ASV), used to treat envenomed patients more effectively.

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Preclinical Immuno-recognition and Neutralization of Lethality Assessment of a New Polyvalent Antivenom, VINS Snake Venom Antiserum – African IHS®, against Envenomation of Ten African Viperid and Elapid Snakes

Journal of Scientific Research and Reports ◽

10.9734/jsrr/2021/v27i1130456 ◽

2021 ◽

pp. 25-43

Author(s):

Djameh, Georgina I. ◽

Nyarko, Samuel ◽

Tetteh-Tsifoanya, Mark ◽

Marfo, Frances M. ◽

Adjei, Samuel ◽

...

Keyword(s):

Snake Venom ◽

Sub Saharan Africa ◽

In Vivo Studies ◽

Health Concern ◽

Major Protein ◽

Snake Species ◽

Neutralizing Capacity ◽

Preclinical Efficacy

Snakebite envenomation is a major health concern in developing countries causing significant mortality and morbidity. With over 1.2 million cases annually caused by medically important snake species belonging to the two families Viperidae (Echis spp. and Bitis spp.) and Elapidae (Naja spp. and Dendroaspis spp.). Several antivenoms are being produced and distributed to western sub-Saharan Africa for treatment of envenomation with the absence of preclinical efficacy studies. The present study evaluated the preclinical efficacy of venoms from Echis leucogaster, Echis ocellatus, Bitis arietans, Bitis gabonica, Naja haje, Naja melanoleuca, Naja nigricollis, Dendroaspis jamesoni, Dendroaspis polylepis and Dendroaspis viridis against a polyvalent Snake Venom Antiserum - African IHS (lyophilised), manufactured by VINS Bioproducts Limited (Telangana, India). Our in vitro results showed that, the SVA- AIHS contains antibodies that are capable of recognizing and binding majority of protein components representative of all eight major protein families of venoms of the snake species tested by double immunodiffusion assay and confirmed by western blot. The venom antiserum exhibited high neutralization efficacy against all the viperid and elapid snake species venoms in in vivo studies and confirmed the manufacturer’s recommended neutralization capacity. This is clear evidence that the VINS polyvalent SVA-AIHS batch tested has strong neutralizing capacity and will be useful in treating envenoming by most African viperid and some elapid snake species.

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Zr-89 Immuno-PET Targeting Ectopic ATP Synthase Enables In-Vivo Imaging of Tumor Angiogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms20163928 ◽

2019 ◽

Vol 20 (16) ◽

pp. 3928

Author(s):

Bok-Nam Park ◽

Ga-Hee Kim ◽

Seung-A Ko ◽

Ga-Hee Shin ◽

Su-Jin Lee ◽

...

Keyword(s):

Cancer Cells ◽

Cellular Uptake ◽

Tumor Angiogenesis ◽

Breast Cancer Cells ◽

Xenograft Model ◽

Tumor Uptake ◽

Positron Emission ◽

Pc3 Cells

In this study, we synthesized a Zr-89-labeled anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) for applications in immuno-positron emission tomography (PET) and evaluated its feasibility for angiogenesis imaging. The cellular uptake of Zr-89 ATPS mAb was measured after treatment of cancer cell lines in vitro, and its biodistribution was evaluated at 4, 24 and 48 h in vivo in mice bearing xenografts. PET images were acquired at 4, 24, 48, and 96 h after Zr-89 ATPS mAb administration. Tumor angiogenesis was analyzed using anti-CD31 immunofluorescence staining. The cellular uptake of Zr-89 ATPS mAb increased over time in MDA-MB-231 breast cancer cells but did not increase in PC3 prostate cancer cells. The tumor uptake of Zr-89 ATPS mAb at 24 h was 9.4 ± 0.9% ID/g for MDA-Mb-231 cells and was 3.8 ± 0.6% ID/g for PC3 cells (p = 0.004). Zr-89 ATPS mAb uptake in MDA-MB-231 xenografts was inhibited by the administration of cold ATPS mAb (4.4 ± 0.5% ID/g, p = 0.011). Zr-89 ATPS mAb uptake could be visualized by PET for up to 96 h in MDA-MB-231 tumors. In contrast, there was no distinct tumor uptake detected by PET in the PC3 xenograft model. CD31-positive tumor vessels were abundant in MDA-MB-231 tumors, whereas they were scarcely detected in PC3 tumors. In conclusion, ATPS mAb was successfully labeled with Zr-89, which could be used for immuno-PET imaging targeting tumor angiogenesis.

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Angiostatic activity of the antitumor cytokine interleukin-21

Blood ◽

10.1182/blood-2007-09-113878 ◽

2008 ◽

Vol 112 (13) ◽

pp. 4940-4947 ◽

Cited By ~ 36

Author(s):

Karolien Castermans ◽

Sebastien P. Tabruyn ◽

Rong Zeng ◽

Judy R. van Beijnum ◽

Cheryl Eppolito ◽

...

Keyword(s):

Immune Response ◽

Tumor Angiogenesis ◽

Chorioallantoic Membrane ◽

Antitumor Immune Response ◽

In Vivo Studies ◽

Type I ◽

Stat3 Phosphorylation ◽

Interleukin 21

Abstract Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immunotherapeutic agent in several cancer types in animal models, and clinical studies are ongoing. IL-21 belongs to the type I cytokine family of which other members, ie, IL-2, IL-15, and IL-4, have been shown to exert activities on vascular endothelial cells (ECs). We hypothesized that IL-21, in addition to inducing the antitumor immune response, also inhibits tumor angiogenesis. In vitro experiments showed a decrease of proliferation and sprouting of activated ECs after IL-21 treatment. We found that the IL-21 receptor is expressed on vascular ECs. Furthermore, in vivo studies in the chorioallantoic membrane of the chick embryo and in mouse tumors demonstrated that IL-21 treatment disturbs vessel architecture and negatively affects vessel outgrowth. Our results also confirm the earlier suggested angiostatic potential of IL-2 in vitro and in vivo. The angiostatic effect of IL-21 is confirmed by the decrease in expression of angiogenesis-related genes. Interestingly, IL-21 treatment of ECs leads to a decrease of Stat3 phosphorylation. Our research shows that IL-21 is a very powerful antitumor compound that combines the induction of an effective antitumor immune response with inhibition of tumor angiogenesis.

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