scholarly journals Effect of Snake Venom Metalloprotease Desintegrin in Hepatocarcinoma Tumor Cells

2020 ◽  
Vol 2 (4) ◽  
pp. 112-122
Author(s):  
Amanda Gomes ◽  
Leticia Monica Coimbra Gaziola ◽  
Luciana Knop ◽  
Rosa Andrea Nogueira Laiso ◽  
Durvanei Augusto Maria
Keyword(s):  
Tumor Cells ◽  
Liver Tumor ◽  
Catalytic Domain ◽  
Therapeutic Option ◽  
Antitumor Effects ◽  
Incidence And Mortality ◽  
Murine Liver ◽  
Dietary Toxins ◽  
Endothelial Basement Membrane ◽  
Snake Toxin

Hepatocellular carcinoma is the third leading cause of cancer-related death in the world. This cancer is associated with cirrhosis following the hepatitis B or C virus infection, alcohol addiction, metabolic liver disease and exposure to dietary toxins such as aflatoxins and aristolochic acid. Studies demonstrate the integration of the HBV genome into liver cell DNA, including cases of patients with HBV-negative serology. Despite advances in prevention techniques, screening, and technology in cancer diagnosis and treatments, the incidence and mortality remain worrisome. Therefore, this research is significant due to the contribution of the development of new biological agents that can be used as monotherapy or adjuvant chemotherapy. Jararhagin, a snake toxin isolated from Bothrops jararaca venom, has been the subject of many studies seeking alternatives for the treatment of cancer. This protein contains the cysteine-rich disintegrin-like metalloproteinase domains and desirable functions to combat tumor cells, such as promoting acute inflammation, damaging the vascular endothelium through the zinc-dependent catalytic domain (responsible for hemorrhagic function) and enzymatically degrading the constituents of the endothelial basement membrane. Due to the antitumor effects of jararhagin presented in previous research, this study aimed to describe the possible antitumor effects of this snake metalloprotease in the murine liver tumor, intending to propose a new therapeutic option in the human liver tumor.

Antitumor effects of IL-6 on murine liver tumor cells in vivo

1999 ◽  
Vol 6 (2) ◽  
pp. 142-144 ◽  
Author(s):  
Hyung-Sik Kang ◽  
Dae-Ho Cho ◽  
Sung-Sook Kim ◽  
Kwang-Ho Pyun ◽  
Inpyo Choi
Keyword(s):  
Tumor Cells ◽  
Liver Tumor ◽  
Antitumor Effects ◽  
Murine Liver

scholarly journals Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion

Hepatology ◽  
2010 ◽  
Vol 52 (3) ◽  
pp. 945-953 ◽  
Author(s):  
Wei Ding ◽  
Hanning You ◽  
Hien Dang ◽  
Francis LeBlanc ◽  
Vivian Galicia ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Liver Tumor ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Murine Liver

Virtual screening of potential therapeutic inhibitors against spike, helicase and polymerase of SARS-CoV-2 (COVID-19)

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Ayesha Tazeen ◽  
Farah Deeba ◽  
Aftab Alam ◽  
Rafat Ali ◽  
Romana Ishrat ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Nigella Sativa ◽  
Therapeutic Option ◽  
Natural Compounds ◽  
Host Cells ◽  
Nucleoside Triphosphate ◽  
Symptomatic Management ◽  
Replication Inhibitor ◽  
Inhibitory Potential ◽  
Approved Drugs

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected around 13 million people and has caused more than 5.7 lakh deaths worldwide since December 2019. In the absence of FDA approved drug for its treatment, only symptomatic management is done. Methods: We attempted to uncover potential therapeutic targets of spike, helicase and RNA dependent RNA polymerase (RdRp) proteins of the SARS-CoV-2 employing computational approach. The PDB structure of spike and RdRp and predicted structure of helicase proteins were docked with 100 approved antiviral drugs, natural compounds and some other chemical compounds. Results: The anti-SARS ligands EK1 and CID_23631927, and NCGC00029283 are potential entry inhibitor as it showed affinity with immunogenic receptor binding domain (RBD) of spike protein. This RBD interacts with angiotensin converting enzyme (ACE2) receptor facilitating the entry of virion in the host cells. The FDA approved drugs including Nelfinavir, Saquinavir, Tipranavir, Setrobuvir, Indinavir and Atazanavir showed potential inhibitory activity against targeted domains and thus may act as entry or replication inhibitor or both. Furthermore, several anti-HCoV natural compounds including Amentoflavone, Rutin and Tannin are also potential entry and replication inhibitor as they showed affinity with RBD, Ploop containing nucleoside triphosphate hydrolase and catalytic domain of the respective protein. Dithymoquinone showed significant inhibitory potential against the fusion peptide of S2 domain. Importantly, Tannin, Dithymoquinone and Rutin can be extracted from Nigella sativa seeds and thus may prove to be one of the most potential anti-SARS-CoV-2 inhibitor. Conclusion: Several potential ligands were identified with already known anti-HCoVs activities. Furthermore, as our study showed that some of the ligands acted as both entry or replication inhibitor against SARS-CoV-2, it is envisaged that a combination of either inhibitors with a dual mode of action would prove to be a much desired therapeutic option against this viral infection.

scholarly journals RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen-Chen Huang ◽  
Fang-Rui Liu ◽  
Qiang Feng ◽  
Xin-Yan Pan ◽  
Shu-Ling Song ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Membrane ◽  
Fusion Protein ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Fusion Proteins ◽  
Inhibitory Effect ◽  
Endosomal Escape ◽  
Antitumor Effects ◽  
Sw480 Cells

Abstract Background We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects. Methods RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv. Results RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells. Conclusion The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.

scholarly journals 150 GAIA-102: a new class off-the-shelf allogeneic NK-like cells that can eliminate solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A163-A163
Author(s):  
Yui Harada ◽  
Yoshikazu Yonemitsu
Keyword(s):  
Nk Cells ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Adoptive Immunotherapy ◽  
Nk Cell ◽  
Peritoneal Dissemination ◽  
Checkpoint Inhibitors ◽  
Antitumor Effects ◽  
Car T

BackgroundCancer immunotherapy has been established as a new therapeutic category since the recent success of immune checkpoint inhibitors and a type of adoptive immunotherapy, namely chimeric antigen receptor-modified T cells (CAR-T). Although CAR-T demonstrated impressive clinical results, serious adverse effects (cytokine storm and on-target off-tumor toxicity) and undefined efficacy on solid tumors are important issues to be solved. We’ve developed a cutting-edge, simple, and feeder-free method to generate highly activated and expanded human NK cells from peripheral blood (US9404083, PCT/JP2019/012744, PCT/JP2020/012386), and have been conducting further investigation why our new type of NK cells, named as GAIA-102, are so effective to kill malignant cells.MethodsCryopreserved PBMCs purchased from vendors were mixed and processed by using LOVO and CliniMACS® Prodigy (automated/closed systems). CD3+ and CD34+ cells were depleted, and the cells were cultured with high concentration of hIL-2 and 5% UltraGRO® for 14 days in our original closed system. Then, we confirmed the expression of surface markers, CD107a mobilization and cell-mediated cytotoxicity against various tumor cells and normal cells with or without monoclonal antibody drugs in vitro and antitumor effects against peritoneal dissemination model using SKOV3 in vivo.ResultsImportantly, we’ve found that our GAIA-102 exhibited CD3-/CD56bright/CD57- immature phenotype that could kill various tumor cells efficiently from various origins, including Raji cells that was highly resistant to NK cell killing. More importantly, massive accumulation, retention, infiltration and sphere destruction by GAIA-102 were affected neither by myeloid-derived suppressor cells nor regulatory T-lymphocytes. GAIA-102 was also effective in vivo to murine model of peritoneal dissemination of human ovarian cancer; thus, these findings indicate that GAIA-102 has a potential to be an ‘upward compatible’ modality over CAR-T strategy, and would be a new and promising candidate for adoptive immunotherapy against solid tumors.ConclusionsWe now just started GMP/GCTP production of this new and powerful NK cells and first-in-human clinical trials in use of GAIA-102 will be initiated on 2021.Ethics ApprovalThe animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of Kyushu University (approval nos. A30-234-0 and A30-359-0).

POTENT ANTITUMOR EFFECTS OF CD154 TRANSDUCED TUMOR CELLS IN EXPERIMENTAL BLADDER CANCER

2001 ◽  
Vol 166 (3) ◽  
pp. 1093-1097 ◽  
Author(s):  
ANGELICA LOSKOG ◽  
ANNA BJÖRKLAND ◽  
MICHAEL P. BROWN ◽  
OLLE KORSGREN ◽  
PER-UNO MALMSTRÖM ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Cells ◽  
Antitumor Effects

scholarly journals Mechanical tibial loading remotely suppresses brain tumors by dopamine-mediated downregulation of CCN4

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yao Fan ◽  
Rongrong Zha ◽  
Tomohiko Sano ◽  
Xinyu Zhao ◽  
Shengzhi Liu ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Tumor Cells ◽  
Mechanical Loading ◽  
Tumor Suppression ◽  
Weight Bearing ◽  
Dopamine Synthesis ◽  
Bone Homeostasis ◽  
Antitumor Effects ◽  
Simultaneous Application ◽  
The Brain

AbstractMechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone. However, whether loading to a weight-bearing hind limb can inhibit distant tumor growth in the brain is unknown. We examined the possibility of bone-to-brain mechanotransduction using a mouse model of a brain tumor by focusing on the response to Lrp5-mediated Wnt signaling and dopamine in tumor cells. The results revealed that loading the tibia with elevated levels of tyrosine hydroxylase, a rate-limiting enzyme in dopamine synthesis, markedly reduced the progression of the brain tumors. The simultaneous application of fluphenazine (FP), an antipsychotic dopamine modulator, enhanced tumor suppression. Dopamine and FP exerted antitumor effects through the dopamine receptors DRD1 and DRD2, respectively. Notably, dopamine downregulated Lrp5 via DRD1 in tumor cells. A cytokine array analysis revealed that the reduction in CCN4 was critical for loading-driven, dopamine-mediated tumor suppression. The silencing of Lrp5 reduced CCN4, and the administration of CCN4 elevated oncogenic genes such as MMP9, Runx2, and Snail. In summary, this study demonstrates that mechanical loading regulates dopaminergic signaling and remotely suppresses brain tumors by inhibiting the Lrp5-CCN4 axis via DRD1, indicating the possibility of developing an adjuvant bone-mediated loading therapy.

scholarly journals Sonodynamic Therapy for the Treatment of Intracranial Gliomas

2021 ◽  
Vol 10 (5) ◽  
pp. 1101
Author(s):  
Antonio D’Ammando ◽  
Luca Raspagliesi ◽  
Matteo Gionso ◽  
Andrea Franzini ◽  
Edoardo Porto ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Therapeutic Option ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
High Grade ◽  
Sonodynamic Therapy ◽  
Treatment Protocols ◽  
Ultrasound Waves ◽  
High Grade Gliomas ◽  
Preclinical And Clinical Studies

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas.

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