Last update 01 Nov 2024

ICAM-1 x Tubulin

Last update 01 Nov 2024

Basic Info

Related Targets

ICAM-1Tubulin

Drugs associated with ICAM-1 x Tubulin

ICAM1-DM1 ADC (Boston Children's Hospital)

Target

ICAM-1 x Tubulin

Mechanism

ICAM-1 modulators [+1]

Active Org.

The Children's Hospital Corp.

Originator Org.

The Children's Hospital Corp.

Active Indication

Pancreatic Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ICAM-1 x Tubulin

100 Translational Medicine associated with ICAM-1 x Tubulin

0 Patents (Medical) associated with ICAM-1 x Tubulin

Literatures (Medical) associated with ICAM-1 x Tubulin

31 Dec 2024·OncoImmunology

β-Lapachone promotes the recruitment and polarization of tumor-associated neutrophils (TANs) toward an antitumor (N1) phenotype in NQO1-positive cancers

Article

Author: Zhao, Ye ; Huang, Xiumei ; Fu, Yang-Xin ; Jiang, Shu ; Li, Xiaoguang ; Chen, Yaomin ; Chen, Xiang ; Tumbath, Soumya ; Zhou, Hao ; Jiang, Lingxiang ; Yin, Zhijun ; Lu, Tao ; Zhang, Taolan ; Zahid, Kashif Rafiq

NAD(P)H:quinone oxidoreductase 1 (NQO1) is overexpressed in most solid cancers, emerging as a promising target for tumor-selective killing. β-Lapachone (β-Lap), an NQO1 bioactivatable drug, exhibits significant antitumor effects on NQO1-positive cancer cells by inducing immunogenic cell death (ICD) and enhancing tumor immunogenicity. However, the interaction between β-Lap-mediated antitumor immune responses and neutrophils, novel antigen-presenting cells (APCs), remains unknown. This study demonstrates that β-Lap selectively kills NQO1-positive murine tumor cells by significantly increasing intracellular ROS formation and inducing DNA double strand breaks (DSBs), resulting in DNA damage. Treatment with β-Lap efficiently eradicates immunocompetent murine tumors and significantly increases the infiltration of tumor-associated neutrophils (TANs) into the tumor microenvironment (TME), which plays a crucial role in the drug's therapeutic efficacy. Further, the presence of β-Lap-induced antigen medium leads bone marrow-derived neutrophils (BMNs) to directly kill murine tumor cells, aiding in dendritic cells (DCs) recruitment and significantly enhancing CD8⁺ T cell proliferation. β-Lap treatment also drives the polarization of TANs toward an antitumor N1 phenotype, characterized by elevated IFN-β expression and reduced TGF-β cytokine expression, along with increased CD95 and CD54 surface markers. β-Lap treatment also induces N1 TAN-mediated T cell cross-priming. The HMGB1/TLR4/MyD88 signaling cascade influences neutrophil infiltration into β-Lap-treated tumors. Blocking this cascade or depleting neutrophil infiltration abolishes the antigen-specific T cell response induced by β-Lap treatment. Overall, this study provides comprehensive insights into the role of tumor-infiltrating neutrophils in the β-Lap-induced antitumor activity against NQO1-positive murine tumors.

01 Nov 2024·Brain, Behavior, & Immunity - Health

Cardiovascular and kidney diseases are positively associated with neuroinflammation and reduced brain-derived neurotrophic factor in patients with severe COVID-19

Article

Author: Lirio, Pedro.H.C. ; Crippa, Jose A. ; Crippa, Jose A ; Scomparin, Davi S ; Scarante, Franciele F. ; Ferreira, Rafael R ; Hallak, Jaime E C ; Fabro, Alexandre ; Rodrigues, Livia.C.M. ; Costa, Karla C.M. ; Costa, Karla ; Campos, Alline C. ; Scomparin, Davi S. ; Batah, Sabrina S. ; Arruda, Eurico ; Martins, Ronaldo B ; Batah, Sabrina S ; Costa, Karla C M ; Marques, Bruno L ; Marques, Bruno L. ; Lirio, Pedro H.C. ; Hallak, Jaime E.C. ; Rodrigues, Livia C.M. ; Hallak, Jaime.E.C. ; Rodrigues, Livia C M ; Fabro, Alexandre T. ; Tostes, Rita C ; Martins, Ronaldo B. ; Lirio, Pedro H C ; Scarante, Franciele F ; Tostes, Rita C. ; Ferreira, Rafael R. ; Fabro, Alexandre T ; Campos, Alline C ; Pires, Isabela

Even though respiratory dysfunctions are the primary symptom associated with SARS-CoV-2 infection, cerebrovascular events, and neurological symptoms are described in many patients. However, the connection between the neuroimmune profile and the lung's inflammatory condition during COVID-19 and its association with the neurological symptoms reported by COVID-19 patients still needs further exploration. The present study characterizes the SARS-CoV-2 infectivity profile in postmortem nervous and lung tissue samples of patients who died due to severe COVID-19, and the pro-inflammatory factors present in both nervous and lung tissue samples, via a proteomic profiling array. Additionally, Brain-Derived Neurotrophic Factor (BDNF) levels and intracellular pathways related to neuroplasticity/neuroprotection were assessed in the samples. Out of the 16 samples analyzed, all samples but 1 were positive for the viral genome (genes E or N2, but only 3.9% presented E and N2) in the olfactory brain pathway. The E or N2 gene were also detected in all lung samples, with 43.7% of the samples being positive for the E and N2 genes. In the E/N2 positive brain samples, the Spike protein of SARS-CoV-2 co-localized with TUJ-1+ (neuron-specific class III beta-tubulin) and GFAP+ (glial fibrillary acidic protein) astrocytes. IL-6, but not IL-10, expression was markedly higher in most nervous tissue samples compared to the lung specimens. While intracellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF), and plasminogen activator inhibitor 1 (PAI-1) were increased in lung samples from SARS-Cov-2 patients, only MIF and IL-18 were detected in nervous tissue samples. Correlation analysis suggested that high levels of IL-6 are followed by increased levels of IL-10 in the brain, but not in lung samples. Our analysis also demonstrated that the presence of comorbidities, such as cardiovascular disease, hypertension, and hypothyroidism, is associated with neuroinflammation, while chronic kidney conditions predict the presence of neurological symptoms, which correlate with lower levels of BDNF in the brain samples. Our results corroborate the hypothesis that a pro-inflammatory state might further impair neural homeostasis and induce brain abnormalities found in COVID-19 patients.

01 May 2024·Behavioural Brain Research

Transcriptomic analysis to identify genes associated with hypothalamus vulnerability in aging mice with cognitive decline

Article

Author: Tian, Xiaofeng ; Shi, Ying ; Zhao, Zhixing ; Su, Dongmei ; Zhao, Jing ; He, Bin ; Shi, Cuige

The normal aging process is accompanied by cognitive decline, and previous studies have indicated the crucial role of the hypothalamus in regulating both aging and cognition. However, the precise molecular mechanism underlying this relationship remains unclear. Therefore, this present study aimed to identify potential predictors of cognitive decline associated with aging specifically within the hypothalamus. To achieve this, we employed Morris water maze (MWM) testing to assess learning and memory differences between young and aged mice. Additionally, transcriptome sequencing was conducted on the hypothalamus of young and aged mice to identify potential genes. Subsequently, GO and KEGG analyses were performed to investigate the functions of differentially expressed genes (DEGs) and their associated biological pathways. Finally, the results obtained from sequencing analysis were further validated using qRT-PCR. Notably, MWM testing revealed a significant decrease in spatial learning and memory ability among aged mice. According to KEGG analysis, the DEGs primarily encompassed various biochemical signaling pathways related to immune system (e.g., C3; C4b; Ccl2; Ccl7; Cebpb; Clec7a; Col3a1; Cxcl10; Cxcl2; Fosb; Fosl1; Gbp5; H2-Ab1; Hspa1a; Hspa1b; Icam1; Il1b; Itga5; Itgax; Lilrb4a; Plaur; Ptprc; Serpine1; Tnfrsf10b; Tnfsf10), neurodegenerative disease (e.g., Atp2a1; Creb5; Fzd10; Hspa1a; Hspa1b; Il1b; Kcnj10; Nxf3; Slc6a3; Tubb6; Uba1y; Wnt9b), nervous system function (e.g., Chrna4; Chrna6; Creb5; Slc6a3),and aging (e.g., Creb5; Hspa1a; Hspa1b) among others. These identified genes may serve as potential predictors for cognitive function in elderly individuals and will provide a crucial foundation for further exploration into the underlying molecular mechanisms.

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