2-deoxy glucose reprograms tumor microenvironment and synergizes with anti-angiogenesis antibody in metastatic breast cancer
Biomedicine & Pharmacotherapy. Under review. 2021
Manasik Gumah Ali#, Zhening Zhang#, Huang Linhua, Nan Lidi, Mingzhu Pan, Kamal Hezam and Juan Zhang*
#: These authors contribute equally to this work.
Abstract
Background: Targeting VEGF/VEGFR2 has been an effective anti-angiogenic therapy for the treatment of solid tumors. However, long-term use of anti-angiogenesis may lead to tumor hypoxia, which enhances tumor invasiveness and distant metastasis. Preclinical investigations have demonstrated the potent effectiveness of glycolysis inhibitors for tumor therapy. Here, we proposed that the VEGFR2 inhibitor in combination with 2-deoxy glucose could inhibit breast cancer metastasis.
Methods: A series of in vitro and in vivo experiments were conducted to reveal the efficacy and combinatorial effects of VEGFR2 inhibitor and 2-DG in the invasion and metastasis of breast cancer.
Results: Data indicated that a low dose (50 uM of 2-DG) effectively synergized with the anti-angiogenesis effect of the VEGFR2 antibody in vitro via downregulation of PI3K/AKT pathway, and inhibiting tumor proliferation and migration. In vivo results showed that the combination contributed significantly to the inhibition of primary tumor and metastasis. Further study revealed the combination reprogrammed tumor microenvironment by converting the epithelial mesenchymal transition (E.M.T.) markers (E-cadherin, N-cadherin, Vimentin), CD31, VEGF and HIF-1α.
Conclusion: Our findings illustrate a novel combination therapy of a low dose 2-DG with angiogenesis inhibitor for metastatic breast cancer and provide an effective and safe combination for treating metastatic breast cancer.
Keywords
VEGFR2 antibody, 2-deoxy glucose, Tumor angiogenesis, Metastatic breast cancer, Epithelial-mesenchymal transition.
Recent advances in therapeutic applications of neutralizing antibodies for virus infections: an overview
Published in Immunologic Research, 2020
Manasik Gumah Ali, Zhening Zhang, Qi Gao, Mingzhu Pan, Edward G Rowan, Juan Zhang
Abstract
Antibodies are considered as an excellent foundation to neutralize pathogens and as highly specific therapeutic agents. Antibodies are generated in response to a vaccine but little use as immunotherapy to combat virus infections. A new generation of broadly cross-reactive and highly potent antibodies has led to a unique chance for them to be used as a medical intervention. Neutralizing antibodies (monoclonal and polyclonal antibodies) are desirable for pharmaceutical products because of their ability to target specific epitopes with their variable domains by precise neutralization mechanisms. The isolation of neutralizing antiviral antibodies has been achieved by Phage displayed antibody libraries, transgenic mice, B cell approaches, and hybridoma technology. Antibody engineering technologies have led to efficacy improvements, to further boost antibody in vivo activities. “Although neutralizing antiviral antibodies have some limitations that hinder their full development as therapeutic agents, the potential for prevention and treatment of infections, including a range of viruses (HIV, Ebola, MERS-COV, CHIKV, SARS-CoV, and SARS-CoV2), are being actively pursued in human clinical trials.”
Keywords
Humoral immune response, Epitope, Neutralizing antibodies, Monoclonal, Polyclonal, Phage display, Glycoprotein
A carbon-rich nanofiber framework based on a conjugated arylacetylene polymer for photocathodic enzymatic bioanalysis
Published in RSC Advances, 2019
Junyan Tang, Xiaoya Liu, Chengwei Yang, Zhening Zhang, Rui Sun, Hongmei Li, Caolong Li* and Fei Wang
Abstract
Poly(1,3,5-triethynylbenzene) (PTEB), a newly developed conjugated arylacetylene polymer, was utilized for photoelectrochemical (PEC) enzymatic bioanalysis in this work. The porous nanofiber framework of PTEB film which produced an apparent cathodic photocurrent under visible light illumination was fabricated on an indium tin oxide (ITO) electrode via copper-surface mediated interface Glaser polycondensation. As the photocurrent density of the metal-free photocathode displayed a characteristic O2 dependency, the consumption of dissolved oxygen caused by the modified glucose oxidase (GOx) in biocatalysis induced a depressed photoresponse in the presence of glucose. The fabricated PEC transducer exhibited favorable glucose sensing performances in the linear range of 5 mM to 8 mM and with the detection limit of 1.7 mM; it could also be employed in glucose monitoring in human serum. Moreover, the acetylenic carbon-rich polymer possessed the superior features of being cost-effective in preparation and machinable in device development, which sheds light on the exploration of an advanced PEC sensing platform based on conjugated organic polymers for the bioanalysis of valuable analytes.
A brief discussion on the precise treatment of hypertension with rheumatic heart disease and diabetes mellitus: inspired by a clinical case
Chinese Medical Journal. Under review. 2021
Yuanyuan Li, Ling Xu, Tian Sang, Zhening Zhang, Xianhui Zhu, Yulin Tang
Abstract
Hypertension is a clinical syndrome characterized by increased systemic arterial pressure, which can be accompanied by lesion and dysfunction of multiple organs such as heart, brain and kidney. It is very common of patients with hypertension who have concomitant diseases like diabetes and rheumatic heart disease, all of which are among the most common chronic diseases in clinical practice, especially among the middle-aged and elderly people. In this paper, the importance of precise treatment for these diseases will be briefly discussed through a clinical case of hypertension with rheumatic heart disease and diabetes.
Key words
Hypertension, Concomitant diseases, Precise treatment, Clinical case