AbstractBackgroundLet-7a-5p is demonstrated to be a tumor inhibitor in nasopharyngeal carcinoma. However, the role of let-7a-5p in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been reported. This study is designed to determine the pattern of expression and role of let-7a-5p in CRSwNP.MethodsThe expression level of let-7a-5p, TNF-α, IL-1β, and IL-6 in CRSwNP tissues and cells were detected by RT-qPCR. Western blot assay was carried out to measure the protein expression of the Ras-MAPK pathway. Dual luciferase reporter assay and RNA pull-down assay were used to explore the relationship between let-7a-5p and IL-6.ResultsLet-7a-5p was significantly downregulated in CRSwNP tissues and cells. Moreover, the mRNA expression of TNF-α, IL-1β and IL-6 was increased in CRSwNP tissues, while let-7a-5p mimic inhibited the expression of TNF-α, IL-1β and IL-6. Besides that, let-7a-5p was negatively correlated with TNF-α, IL-1β and IL-6 in CRSwNP tissues. In our study, IL-6 was found to be a target gene of let-7a-5p. Additionally, let-7-5p mimic obviously reduced the protein levels of Ras, p-Raf1, p-MEK1 and p-ERK1/2, while IL-6 overexpression destroyed the inhibitory effect of let-7a-5p on the Ras-MAPK pathway in CRSwNP.ConclusionWe demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway in CRSwNP.

1996-04-01·Current Opinion in Cell Biology

Targeting signal transduction for disease therapy

Review

作者: Levitzki, A

With the advance in the molecular understanding of disease processes, it has been appreciated that many diseases result from the malfunctions of signaling pathways. This recognition has led to intensive research and the development of therapies based on the interception of cellular signaling in diseased cells. In the past two years, success has been achieved using a blocker of the farnesylation of Ras as a tumor inhibitor, a JAK-2 blocker as an efficient inhibitor of recurrent pre-B cell acute lymphoblastic leukemia, and a platelet-derived growth factor receptor kinase as a blocker of restenosis.

项与 Brain tumor (Kidswell Bio) 相关的新闻（医药）

2024-07-17

·BioPharmaDive

In strengthening Spravato sales, a positive sign for psychedelic drugs

Dive Brief:Sales of Johnson & Johnsons depression drug Spravato accelerated in the second quarter, putting the medicine on pace to eclipse $1 billion in annual revenue this year.Globally, Spravato sales totaled $271 billion between April and June, a 61%increase from the same period one year before and a 20% jump from the first quarter. The numbers, disclosed by J&J alongside second quarter earnings Wednesday, reflected increased physician and patient confidence, Jessica Moore, the companys head of investor relations, said on a conference call.Approved for treatment-resistant depression in 2019, Spravato is a form of ketamine thats given as a nasal spray. Its also cleared to treat depressive symptoms in people with major depressive disorder who show acute suicidal ideation or behavior.Dive Insight:Spravato remains a comparatively small product by sales for J&J, which reported more than $22 billion in revenue during the second quarter. But the pharmaceutical giant has high expectations for its growth, telling investors in December that it anticipates sales will grow to between $1 billion and $5 billion annually.Wednesdays numbers are encouraging evidence in support of that forecast. And they could also bode well for brain drugs like Spravato that work in ways that can also cause dissociation and hallucination.Spravato's strong sales trajectory supports the notion psychedelics can become commercially viable for mental health, wrote Jefferies analyst Andrew Tsai in a client note Wednesday.The field is in particular focus as the Food and Drug Administration decides whether to approve MDMA as part of a psychedelic-assisted therapy tested by biotechnology company Lykos Therapeutics. While two late-stage studies run by Lykos showed the therapy could help people with post-traumatic stress disorder, advisers to the FDA last month recommended the agency hold off on an approval, citing issues with how the trials were conducted and MDMAs safety. The FDA is expected to make its verdict by Aug. 11.Experts viewed the negative vote as having a sobering effect on the psychedelic field, although the FDA could still surprise and grant Lykos an approval in some fashion.Behind Lykos are several other companies, including Compass Pathways, which is developing psilocybin for treatment-resistant depression, and Atai Life Sciences, which is working on a form of dimethyltryptamine in the same setting.Spravato's continued sales acceleration ... provides evidence that psychedelics can generate meaningful sales in hard-to-treat [central nervous system] disorders, even if their ultimate use [is] restricted to hospitals or treatment clinics, wrote Tsai.Due to the risk of dissociation and suicidal thoughts, Spravato is only available for use under the supervision of a healthcare professional in a medical office or clinic.Unlike many of its pharmaceutical peers, J&J has maintained neuroscience as a research focus, and is developing two depression drugs behind Spravato that work in new ways. One, seltorexant, showed positive results in a Phase 3 study J&J read out in late May, while the company is awaiting important data on the other, called aticaprant. '

临床结果上市批准临床3期

100 项与 Brain tumor (Kidswell Bio) 相关的药物交易

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