Mechanistically, TBK1 deletion or inhibition by amlexanox or GSK8612 reduced the expression of the transcription factor interferon-regulatory factor (IRF)4 and increased the level of IRF5 activation in macrophages stimulated with M-CSF, leading to an M1-like profile with highly proinflammatory factors. IRF5 deletion reversed the effect of TBK1 inhibition on M-CSF-mediated macrophage polarization. Our findings suggest that TBK1 contributes to the regulation of macrophage polarization in response to M-CSF stimulation partly through the IRF5/IRF4 axis.

In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD.

The importance serpin E2 is clear from its involvement in numerous physiological and pathological processes. In this review, we summarize the structural characteristics of the Serpin E2 gene and protein, as well as its roles physiology and disease.

In vitro studies revealed that SERPINE2 knockdown significantly reduced cell proliferation, migration, and invasion in OSCC cell lines. This study suggests that SERPINE2 may serve as a prognostic biomarker and potential therapeutic target for oral cancer.

P2, N=7, Terminated, University of Michigan | N=15 --> 7 | Suspended --> Terminated; Due to limited funding, trial was suspended, intending to restart with additional funds; then preliminary results were obtained, and research moved on to placebo controlled trial. Results for both have been published.

Overall, the data from this study suggests that targeting the LTB4/Ltb4r1 axis in highly inflammatory and pro-fibrotic conditions of chronic liver disease should be considered with caution.

IKBKE can activate AKT independent of PI3K by directly phosphorylating AKT Ser473 and Thr308, thus increasing the phosphorylation of FOXO3a. Phosphorylated FOXO3a promoted its ubiquitin degradation, and inhibited its transportation into the nucleus, causing radioresistance in glioblastoma. IKBKE inhibitor Amlexanox can pass through the blood-brain barrier and increase the radiosensitivity of intracranial tumor cells.

Our study highlights the high expression of SERPINA1 in PTC and its potential role in shaping the immune microenvironment, thereby promoting disease progression. These findings suggest that SERPINA1 could serve as a promising therapeutic target for intervention in PTC.

Recently, irreversible BTK inhibitors, ibrutinib, acalabrutinib and zanubrutinib have been proven to inhibit malignant B-cell survival through hindering tumor-microenvironment interactions. Our results suggest that 5-LOX has potential as a putative novel therapeutic target for development of new strategies for treatment of CLL. B cell chronic lymphocytic leukemia, Chronic lymphocytic leukemia

Overall, our bioinformatics analyses comprehensively described the networks involved SERPINE1 in colon cancer and the potentially associated molecular mechanisms.

SERPINA3 and ELABELA are poor prognostic biomarkers in CLL patients associated with dismal outcomes. SERPINA3 and ELABELA may be a promising therapeutic target for CLL treatment in the future.

The CLL patients indicated for therapy received Fludarabine, Cyclophosphamide, and Rituximab (FCR) for 17 p deletion (del.17p) negative eligible patients, Chlorambucil for del.17p negative non-eligible patients, and Ibrutinib or highdose Methylprednisolone (HDMP) for del.17p positive patients. SERPINA3 and ELABELA are poor prognostic biomarkers in CLL patients associated with dismal outcomes. SERPINA3 and ELABELA may be a promising therapeutic target for CLL treatment in the future.

We also found that Serpinc1 overexpression promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of LLC cells in vitro, possibly regulating the associated factors via the Pi3K/AKT pathway. In summary, our results reveal the synergistic antitumor responses of nab-PTX combined with anti-PD-1 antibody, in which Serpinc1 may play an important role, providing a target gene for combination treatment strategy.

Our mouse model also showed that Amlexanox combined with Olaparib inhibited tumor growth of CRPC xenografts. Our study highlights a new role for IKKε in DNA damage repair through the regulation of Rad51 transcription and provides a rationale for the combination of Amlexanox and Olaparib in the treatment of patients with CRPC.

No abstract available

However, to this point, only momelotinib (MMB)/CYT387 has been evaluated as a cancer therapy in clinical trials, while amlexanox (AMX) has been evaluated clinically for treatment of type II diabetes, nonalcoholic fatty liver disease, and obesity. We also discuss the potential molecular mechanisms of targeting TBK1 for cancer treatment. We hope that our effort can help to stimulate the development of novel strategies for targeting TBK1 signaling in future approaches to cancer therapy.

We found many codifferentially expressed genes and important pathways between SRC and ITGC. THBS1 and SERPINE1 were significantly differentially expressed in the two types of gastric cancer, and may have potentially important functions.

The anticancer potency is generally modest but largely enhanced upon combination with cytotoxic (temozolide, docetaxel), targeted (selumetinib) or biotherapeutic agents (anti-PD-1 and anti-CTLA4 antibodies). Altogether, the analysis provides a survey of the anticancer action of AMX, with the implicated protein targets. The use of this well-tolerated drug to treat cancer should be further considered and the design of newer analogues encouraged.

The result of immunohistochemistry verification shown that SERPINH1 staining was higher in tumor samples than in normal tissue in colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma and cervical squamous cell carcinoma, which was consistent with the result of OS. Overall, these results indicate that SERPINH1 may serve as an important prognostic biomarker and correlate with tumor immunity in human pan-cancer.

Our study suggests that targeting IKKε with BX795 or Amlexanox in androgen-independent-PC cells induces a senescence phenotype and demonstrates in vivo anti-tumor activity. These results strengthen the potential of exploiting IKKε as a therapeutic target.

Collectively, our results highlight the critical contribution of SERPINE1 in a series of malignant characteristics of GBM via regulating the expression of HES1, which shed new light on a new direction to develop a more effective therapeutic management of malignant tumors like GBM.

In addition, miR-29c overexpression inhibited the proliferation and metastasis of OSCC cells, and the subsequent rescue experiment showed that SERPINH1 overexpression can reverse the inhibitory effect of miR-29c in OSCC cell proliferation, migration, apoptosis, and cell cycle arrest. The miRNA, miR-29c can regulate the proliferation, migration, invasion, and cell cycle of OSCC cells by targeting SERPINH1.

In conclusion, our study showed that Amlexanox or GSK8612 was effective in inhibiting TBK1 expression leading to decreased cell proliferation and colony formation in GBM cell lines. A synergistic effect was observed with each of these TBK1 inhibitors plus radiation and/or TMZ. These results suggest that TBK1 may be a potential candidate to pursue as novel therapeutic target in IDH wild-type gliomas. Future work will focus on in vivo studies with Amlexanox or GSK8612 alone and in combination with TMZ and radiation AUTHOR DISCLOSURE: Z. Tong: None.

These results suggest that SRPX2 might be a useful tumor marker for OSCC.

SERPINA3 may play a key role in the biological process of glioma cells especially in immune suppression activities. SERPINA3 may serve as an independent survival prediction factor in glioma patients.

This work highlights further molecular-based patient selection strategies in clinical trials and suggests the mesenchymal subtype as well as SERPINH1 to be associated with response to dasatinib. Our findings indicate that stratification based on gene expression subtyping should be considered in future dasatinib trials.

Besides, an EGFR inhibitor blocked the effects of SERPINE2 overexpression on the aforementioned biological processes. Therefore, the present study confirmed that SERPINE2 formed a positive feedback with EGF/EGFR to regulate the proliferation, invasion and migration of TPC cells, possibly providing novel insights into potential therapeutic targets of papillary TC.

In vivo mouse xenograft studies and patient clinical trials are warranted to understand the functional mechanism of bleomycin towards PDAC and optimize its therapeutic efficacy. Furthermore, we will evaluate the antitumor activity of the other identified drugs in our future studies.

These results suggest that amlexanox sensitized the primary glioma cells and U87 MG cells to TMZ at least partially through the suppression of IKBKE activation and the attenuation of TMZ-induced Akt activation. Overall, combined treatment with TMZ and amlexanox may provide a promising possibility for improving the prognosis of glioblastoma patients in clinical practice.

SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

This is the first case of patient with systemic mastocytosis and myeloid sarcoma simultaneously presenting extensive skin involvements. Mutations of Kit and Arid1a emphasis the importance to notice possibility of various tumors occurring in patients with multiple mutations. In addition, cysteine-leukotrienes-receptor antagonists should always be used to prevent anaphylactic shock due to mast cell activation.

Moreover, SERPINA1 overexpression increased the protein levels of SMAD4, which is a key regulator of the transforming growth factor (TGF)-β signaling pathway. Taken together, the present data demonstrated that SERPINA1 promotes gastric cancer progression through TGF-β signaling, and suggested that SERPINA1 may be a novel prognostic biomarker from tumor tissue biopsy in gastric cancer.

Our study indicated that the immune-related prognostic signature could serve as a novel biomarker for predicting patients' prognosis and providing new immunotherapy targets in ESCA.

In an in vivo xenograft model in nude mice, amlexanox treatment significantly reduced tumor growth. In conclusion, amlexanox was able to suppress tumor progression potentially by the inhibition of autophagy as well as NF-кB and MAP kinase pathways and might therefore constitute a promising candidate for melanoma therapy.

Furthermore, targeting M-MDSCs with Ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, reduced MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. These findings demonstrate the MDSC subsets differentially express MIF receptors and may be leveraged for specific MDSC targeting.