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Shajedul Islam

Publications and source records attributed to Shajedul Islam.

2 recordsLinked to original sources

Casein Kinase 1 Alpha 1 Is Over-expressed in Pancreatic Adenocarcinoma Tissues and Correlates With Shorter Patient Survival.

BACKGROUND/AIM: A quarter of a century has passed since the start of the 21st century, and cancer, once considered an incurable disease, has become manageable thanks to the development of various treatments. However, pancreatic adenocarcinoma (PAAD) remains one of the deadliest cancers in the world, with over 95% of patients dying within five years. This is because the anatomical location of the pancreas makes it very difficult to detect with imaging, and symptoms often do not appear until the cancer invades the nerve plexus in its terminal stages, meaning that by the time it is diagnosed, it is often too late. Therefore, the development of prognostic markers is an urgent task. Casein kinase 1 alpha 1 (CSNK1A1) is a serine/threonine protein kinase deeply involved in Wnt signaling and the tumor suppressor mechanisms of p53. While the association between increased or decreased CSNK1A1 expression and prognosis has been reported in many types of cancer tissue, its association in PAAD is not yet fully understood. This study investigated the potential of CSNK1A1 as a prognostic marker for PAAD. MATERIALS AND METHODS: We used Gene Expression Profiling Interactive Analysis (GEPIA) and the University of Alabama Birmingham Cancer Data Analysis Portal (UALCAN) bioinformatics platforms to analyze CSNK1A1 mRNA expression, protein levels, and survival rates of patients with PAAD obtained from The Cancer Genome Atlas (TCGA) database. RESULTS: CSNK1A1 mRNA and protein levels were significantly higher in PAAD tissue compared to normal pancreatic tissue, and this increase was associated with a poor prognosis in patients with PAAD. CONCLUSION: In PAAD tissue, increased expression of CSNK1A1 mRNA and protein was observed compared to normal pancreatic tissue, and this increased expression correlated with poor patient prognosis. Therefore, CSNK1A1 is considered a promising prognostic biomarker in PAAD.

CSNK1A1

Cancer-induced nerve injury promotes resistance to anti-PD-1 therapy.

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated inflammation to promote nerve healing and regeneration. As the tumour grows, the CINI burden increases, and its associated inflammation becomes chronic and skews the general immune tone within the tumour microenvironment into a suppressive and exhaustive state. The CINI-driven anti-PD-1 resistance can be reversed by targeting multiple steps in the CINI signalling process: denervating the tumour, conditional knockout of the transcription factor mediating the injury signal within neurons (Atf3), knockout of interferon-α receptor signalling (Ifnar1-/-) or by combining anti-PD-1 and anti-IL-6-receptor blockade. Our findings demonstrate the direct immunoregulatory roles of CINI and its therapeutic potential.

Animals