Introduced the ITGB1-DT as a novel biomarker associated with five potential drugs using bioinformatics analysis of breast cancer proteomics data and RT-PCR.

Article

Author: Hashemi, Mehrdad ; Esfandiari, Negin ; Yousefian Naeini, Zahra ; Arbabian, Sedighe ; Hushmandi, Kiavash ; Entezari, Maliheh

BACKGROUNDBreast cancer (BC) has been identified as a significant contributor to the rising number of female cancer deaths. As, it has become clear that breast cancer development depends on the interplay of several biological factors against a single molecule. This research aimed to use proteomics to gain a regulatory and metabolic understanding of BC pathophysiology.METHODFor the study, a breast cancer proteomics dataset was downloaded from ProteomeXchange and then analyzed by employing MaxQuant and Perseus. Functional enrichment analysis through Metascape and Cytoscape software showed DEPs related biomedical phenomena with potential abruption. The expression of selected lncRNA in terms of the highest connectivity parameters was then quantitatively assessed through RT-PCR in 30 tumor tissues of breast cancer patients, as compared to the adjacent healthy ones.RESULTThe results indicated that among the 3048 identified proteins, 1149 were differentially expressed, which could be mainly enriched in several key terms. Furthermore, the obtained findings revealed that ITGB1-DT was significantly overexpressed in tumor tissues. Moreover, we found five potential compounds that could be attributed to ITGB1-DT targets (ATN-161, Firategrast, SB-683698, dabigatran-etexilate, and tranexamic-acid).CONCLUSIONThese analyses proposed that ITGB1-DT could be employed as a differentiated factor to identify breast tumor tissues in healthy samples. Besides this, Firategrast could be introduced as a potential remedial agent for breast cancer patients. Overall, from the analysis of a proteomics dataset, an integrative map was generated, and a novel biomarker that may have been implicated in the early detection of BC was introduced.

01 Feb 2021·The FASEB JournalQ2 · BIOLOGY

Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV‐infected rhesus macaques

Q2 · BIOLOGY

Article

Author: Connolly, Patrick J. ; Ziani, Widade ; Wang, Xiaolei ; Shao, Jiasheng ; Veazey, Ronald S. ; Fang, Angela ; Xu, Huanbin

Cellular viral reservoirs are rapidly established in tissues upon HIV-1/SIV infection, which persist throughout viral infection, even under long-term antiretroviral therapy (ART). Specific integrins are involved in the homing of cells to gut-associated lymphoid tissues (GALT) and inflamed tissues, which may promote the seeding and dissemination of HIV-1/SIV to these tissue sites. In this study, we investigated the efficacy of prophylactic integrin blockade (α4β7 antibody or α4β7/α4β1 dual antagonist TR-14035) on viral infection, as well as dissemination and seeding of viral reservoirs in systemic and lymphoid compartments post-SIV inoculation. The results showed that blockade of α4β7/α4β1 did not decrease viral infection, replication, or reduce viral reservoir size in tissues of rhesus macaques after SIV infection, as indicated by equivalent levels of plasma viremia and cell-associated SIV RNA/DNA to controls. Surprisingly, TR-14035 administration in acute SIV infection resulted in consistently higher viremia and more rapid disease progression. These findings suggest that integrin blockade alone fails to effectively control viral infection, replication, dissemination, and reservoir establishment in HIV-1/SIV infection. The use of integrin blockade for prevention or/and therapeutic strategies requires further investigation.

02 Dec 2018·Expert Opinion on Therapeutic PatentsQ2 · MEDICINE

α₄β₇ integrin inhibitors: a patent review

Q2 · MEDICINE

Review

Author: Wei, Ji-Fu ; Gu, Zhi-Chun ; Shi, Fang-Hong ; Huang, Shi-Ying ; Li, Hao ; Zhang, Shun-Guo

INTRODUCTIONThe α₄β₇ integrin is heterodimeric cell surface receptors expressed on most leukocytes. Mucosal addressing cell adhesion molecule 1(MAdCAM-1) is an exclusive ligand for α₄β₇ integrin. Areas covered: This article will highlight the progress that has been made in the discovery and development of α₄β₇ integrin inhibitors, and their use in the treatment of inflammatory bowel diseases, multiple sclerosis, asthma, hepatic disorders, human immunodeficiency virus, allergic conjunctivitis and type 1 diabetes. Expert opinion: α₄β₇ integrin inhibitors have attracted much interest for their clinical implication. Natalizumab and Vedolizumab are monoclonal antibodies (mAbs) successfully utilized clinically. Natalizumab is a mAbs of α₄-subunit blocking both α₄β₁ and α₄β₇ integrin. Vedolizumab selectively targets the α₄β₇ integrin. Several mAbs are still in the process of research and development. Among these mAbs, etrolizumab selectively against the β₇-subunit and AMG-181 specifically against the α₄β₇ integrin are the most promising anti-α₄β₇ integrin antibodies. Despite the unclear development stage of TR-14035 and R411, several low molecular compounds show bright future of further development, such as AJM300 and CDP323. In addition, results from laboratory data show that peptide inhibitors, such as peptide X, are effective α₄β₇ integrin inhibitors.

100 Deals associated with TR-14035

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 2	US	Mitsubishi Tanabe Pharma Corp.	-
Asthma	Phase 2	-	GSK Plc	-
Asthma	Phase 2	JP	-	-
Asthma	Phase 2	-	-	-
Irritable Bowel Syndrome	Phase 2	US	Mitsubishi Tanabe Pharma Corp.	-
Multiple Sclerosis	Phase 2	-	GSK Plc	-
Rheumatoid Arthritis	Phase 2	US	Mitsubishi Tanabe Pharma Corp.	-
Rheumatoid Arthritis	Phase 2	-	-	-
Rheumatoid Arthritis	Phase 2	-	GSK Plc	-
Rheumatoid Arthritis	Phase 2	JP	-	-

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