scholarly journals In silico analysis identifies neuropilin-1 as a potential therapeutic target for SARS-Cov-2 infected lung cancer patients

Aging ◽  
2021 ◽  
Author(s):  
Song Hu ◽  
Zheyu Hu ◽  
Jiajia Qin ◽  
Chuwen Lin ◽  
Xuan Jiang
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Therapeutic Target ◽  
In Silico ◽  
In Silico Analysis ◽  
Potential Therapeutic Target ◽  
Lung Cancer Patients ◽  
Neuropilin 1 ◽  
Silico Analysis

scholarly journals Identifying new COVID-19 receptor Neuropilin-1 in severe Alzheimer’s diseases patients group brain using genome-wide association study approach

2021 ◽  
Author(s):  
Key-Hwan Lim ◽  
Sumin Yang ◽  
Sung-Hyun Kim ◽  
Jae-Yeol Joo
Keyword(s):  
In Silico ◽  
Genome Wide Association Study ◽  
Transmembrane Protein ◽  
In Silico Analysis ◽  
Therapeutic Drug ◽  
Rna Seq ◽  
Total Rna ◽  
Neuropilin 1 ◽  
Silico Analysis ◽  
Brain Tissues

Abstract Background Numerous studies have been conducted on different aspects of the COVID-19 (coronavirus disease 2019) pandemic, which is caused by SARS-CoV-2, since its emergence in late 2019. Mutual relations among SARS-CoV-2 and neuro-pathophysiological phenomena are continuously being demonstrated, and several underlying diseases, such as those in the elderly, are positively correlated with susceptibility to SARS-CoV-2 infection. The expression of angiotensin converting enzyme 2 (ACE2), which is required for SARS-CoV-2 infection, was recently demonstrated to be increased in Alzheimer’s disease (AD) patients. Methods Recent preclinical studies have shown that Neuropilin-1 (NRP1), which is a transmembrane protein with roles in neuronal development, axonal outgrowth, and angiogenesis, also plays a role in the infectivity of SARS-CoV-2. Thus, we hypothesized that NRP1 may be upregulated in AD patients and that a correlation between AD and SARS-CoV-2 NRP1-mediated infectivity may exist. We used an AD mouse model that mimics AD and performed high throughput total RNA-seq with brain tissue and whole blood. For quantification of NPR1 in AD, brain tissues and blood were subjected to western blotting and RT-qPCR analysis. In silico analysis for NRP1 expression in AD patients has been performed on the human hippocampus data sets (GSE4226, GSE1297). Results Many cases of severe symptom of COVID-19 are concentrated in elderly group who have complications such as diabetes, degenerative disease, and brain disorders. Total RNA-seq analysis showed that Nrp1 gene was commonly overexpressed in AD model. Similar to ACE2, NRP1 protein also strongly expressed in the AD brain tissues. Interestingly, in silico analysis revealed that the level of expression for NRP1 was distinct at age and AD progression. Conclusions Given that the NRP1 is highly expressed in AD, it will be important to understand and predict that NRP1 may a risk factor for SARS-CoV-2 infection in AD patients. This will support to development of potential therapeutic drug to reduce SARS-CoV-2 transmission.

Comprehensive cancer genomics-based screening of new therapeutic targets and biomarkers for lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21031-e21031
Author(s):  
Yataro Daigo ◽  
Atsushi Takano ◽  
Yusuke Nakamura
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Therapeutic Target ◽  
Cancer Genomics ◽  
Cancer Biomarkers ◽  
Lung Cancer Cells ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Target Molecules

e21031 Background: Since the clinical outcome of advanced lung cancer patients is still poor after standard therapies, development of new anti-cancer drugs with minimum risk of adverse effects and cancer biomarkers for precision medicine is urgently required. Methods: We have been screening new therapeutic target molecules and molecular biomarkers for lung cancers as follows; i) To identify overexpressed genes in lung cancers by the gene expression profile analysis, ii) To verify the target genes for their scarce expression in normal tissues, iii) To validate the clinicopathologic importance of their protein expression by tissue microarray covering 263 lung cancers, and iv) To confirm their function for the growth and/or invasive ability of the lung cancer cells by siRNAs and gene transfection assays. Results: We identified dozens of candidate target molecules and selected a gene encoding protein with a GAP domain, LAPG1 (lung cancer-associated protein with Gap domain 1). Immunohistochemical analysis showed that LAPG1 expression was observed in 69.9% of lung cancers. Moreover positivity of LAPG1 expression was associated with poor prognosis of lung cancer patients. Knockdown of LAPG1 expression by siRNAs suppressed growth of lung cancer cells. Introduction of LAPG1 increased the invasive activity of mammalian cells, indicating that LAPG1 could be a prognostic biomarker and therapeutic target for lung cancers. Conclusions: Comprehensive cancer genomics-based screening could be useful for selection of new cancer biomarkers and molecular targets for developing small molecules, antibodies, nucleic acid drugs, and immunotherapies.

Assessment of epigenetic alterations and in silico analysis of mutation affecting PTEN expression among Indian cervical cancer patients

2019 ◽  
Vol 120 (9) ◽  
pp. 15851-15866 ◽  
Author(s):  
Afreen Naseem ◽  
Zafar Iqbal Bhat ◽  
Ponnusamy Kalaiarasan ◽  
Bhupender Kumar ◽  
Zubair Bin Hafeez ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
In Silico ◽  
In Silico Analysis ◽  
Pten Expression ◽  
Epigenetic Alterations ◽  
Silico Analysis

An “in silico” clinical trial comparing free breathing, slow and respiration correlated computed tomography in lung cancer patients

2006 ◽  
Vol 81 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Geert Bosmans ◽  
Jeroen Buijsen ◽  
André Dekker ◽  
Marije Velders ◽  
Liesbeth Boersma ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Clinical Trial ◽  
Cancer Patients ◽  
In Silico ◽  
Free Breathing ◽  
Lung Cancer Patients

869 Anti-LunX targeting therapy for lung cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A921-A921
Author(s):  
Xiaohu Zheng ◽  
Weihua Xiao ◽  
Zhigang Tian
Keyword(s):  
Lung Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Therapeutic Target ◽  
Xenograft Model ◽  
Therapeutic Antibody ◽  
Antibody Treatment ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Novel Therapeutic

BackgroundThe identification of novel therapeutic targets in lung cancer for the generation of targeted drugs is an urgent challenge. Lung-specific X (LunX) is a member of the palate, lung, and nasal epithelium clone (PLUNC) protein family. Some reports have suggested that the human PLUNC gene (also named LUNX) might be a potential marker for NSCLC, and PLUNC mRNA has been identified in peripheral blood and mediastinal lymph nodes from NSCLC patients.It is unclear whether LunX expression is associated with the pathological type and pathological severity in lung cancer patients. The utility of LunX as a potential therapeutic target in NSCLC is uncertain.MethodsClinically, 80% of lung cancers are non-small-cell lung cancers (NSCLCs). Here, we analyzed 158 NSCLC samples and detected LunX expression.ResultsIt showed that the expression of LunX were elevated in 90% (108/150) lung cancers by IHC staining, which accompanied with significantly lower rate of postsurgery survival. Further evaluation of LunX expression in invasive tumor cells in subclavicular lymph nodes, draining lymph nodes, hydrothorax of lung cancer patients, turned out that LunX is highly expressed in invasive lung cancer cells. These data indicated that LunX overexpresses in lung cancer and associates with tumorigenesis and tumor progression.Mechanistically, we discovered that LunX bound to 14-3-3 protein and facilitated their activation by maintaining these proteins in a dephosphorylated state, thereby contributing to the activation of pathways downstream of 14-3-3 protein, such as the Erk1/2 and JNK pathways. Thus, LunX promoted tumor growth and metastasis.Furthermore, we generated a therapeutic antibody specific for lung cancer, which not only inhibited lung cancer growth and reduced Ki67 staining and angiogenesis in xenograft model of subcutaneously transplanted tumor, but also blocked tumor metastasis and invasion, improved the survival of these mice. We also detected that antibody treatment induces LunX antigen-antibody complex endocytosis and the degradation of LunX protein.ConclusionsOur study suggests that LunX is a novel therapeutic target in lung cancer and that the LunX-targeted therapeutic antibody may have considerable clinical benefit.

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