主要研究目的： Ⅰb期：评价JC-5411-L在晚期实体瘤患者的安全性和耐受性，探索JC-5411-L的最大耐受剂量（MTD），确定II期临床研究推荐剂量（RP2D）。 Ⅱ期：评价JC-5411-L在卵巢癌患者中的有效性和安全性。次要研究目的：评价JC-5411-L的药代动力学（PK）特征。初步评价JC-5411-L治疗晚期实体瘤患者的疗效。探索性研究目的评价晚期实体瘤患者的肿瘤标本或外周血中的生物标记物水平（包括但不限于p53 蛋白表达水平）与疗效的关系。评价晚期实体瘤患者的GST基因型与疗效的关系。

开始日期2023-12-13

申办/合作机构

无锡杰西医药股份有限公司

NCT00691132 / Completed临床2期IIT

Randomized Trial of PEITC as a Modifier of NNK Metabolism in Smokers

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of phenethyl isothiocyanate may prevent lung cancer in people who smoke cigarettes.
PURPOSE: This randomized clinical trial is studying phenethyl isothiocyanate to see how well it works in preventing lung cancer in smokers.

开始日期2009-02-01

申办/合作机构

University of Minnesota

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100 项与 Nrf2 x HSF1 相关的临床结果

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100 项与 Nrf2 x HSF1 相关的转化医学

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0 项与 Nrf2 x HSF1 相关的专利（医药）

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项与 Nrf2 x HSF1 相关的文献（医药）

2024-10-01·Aging Cell

Age‐dependent heat shock hormesis to HSF‐1 deficiency suggests a compensatory mechanism mediated by the unfolded protein response and innate immunity in young Caenorhabditis elegans

Article

作者: Hotzi, Bernadette ; Kovács, Dániel ; Vincze, Viktor Vázsony ; Ahmed, Saqib ; Kovács, Márton ; Barna, János ; Varga, Máté ; Biró, János Barnabás ; Mohammad, Umar ; Sigmond, Tímea ; Vellai, Tibor

AbstractThe transcription factor HSF‐1 (heat shock factor 1) acts as a master regulator of heat shock response in eukaryotic cells to maintain cellular proteostasis. The protein has a protective role in preventing cells from undergoing ageing, and neurodegeneration, and also mediates tumorigenesis. Thus, modulating HSF‐1 activity in humans has a promising therapeutic potential for treating these pathologies. Loss of HSF‐1 function is usually associated with impaired stress tolerance. Contrary to this conventional knowledge, we show here that inactivation of HSF‐1 in the nematode Caenorhabditis elegans results in increased thermotolerance at young adult stages, whereas HSF‐1 deficiency in animals passing early adult stages indeed leads to decreased thermotolerance, as compared to wild‐type. Furthermore, a gene expression analysis supports that in young adults, distinct cellular stress response and immunity‐related signaling pathways become induced upon HSF‐1 deficiency. We also demonstrate that increased tolerance to proteotoxic stress in HSF‐1‐depleted young worms requires the activity of the unfolded protein response of the endoplasmic reticulum and the SKN‐1/Nrf2‐mediated oxidative stress response pathway, as well as an innate immunity‐related pathway, suggesting a mutual compensatory interaction between HSF‐1 and these conserved stress response systems. A similar compensatory molecular network is likely to also operate in higher animal taxa, raising the possibility of an unexpected outcome when HSF‐1 activity is manipulated in humans.

2024-08-01·Apoptosis

The significant mechanism and treatments of cell death in heatstroke

Review

作者: Wang, Zixin ; Lv, Jinke ; Liu, Zhifeng ; Zhu, Jie ; Wu, Liangping ; Zhang, Dingshun

With global warming, extreme environmental heat is becoming a social issue of concern, which can cause adverse health results including heatstroke (HS). Severe heat stress is characterized by cell death of direct heat damage, excessive inflammatory responses, and coagulation disorders that can lead to multiple organ dysfunction (MODS) and even death. However, the significant pathophysiological mechanism and treatment of HS are still not fully clear. Various modes of cell death, including apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis are involved in MODS induced by heatstroke. In this review, we summarized molecular mechanism, key transcriptional regulation as for HSF1, NRF2, NF-κB and PARP-1, and potential therapies of cell death resulting in CNS, liver, intestine, reproductive system and kidney injury induced by heat stress. Understanding the mechanism of cell death provides new targets to protect multi-organ function in HS.

2024-04-01·Biomedicine & Pharmacotherapy

Paeonol promotes longevity and fitness in Caenorhabditis elegans through activating the DAF-16/FOXO and SKN-1/Nrf2 transcription factors

Article

作者: Tao, Mingfang ; Miao, Yuanxin ; Wang, Jinsong ; Chen, Qingchan ; Yi, Qingping ; Li, Rong ; Xu, Yan

Paeonol, as one of the most abundant plant-derived polyphenols, has multiple bioactivities including anti-inflammatory, anti-tumor, and anti-cardiovascular diseases. Nevertheless, the anti-aging effects and related mechanisms of paeonol are rarely reported. In this study, we found that paeonol significantly prolonged the mean lifespan of Caenorhabditis elegans (C. elegans) by 28.49% at a dose of 200 μM. Moreover, paeonol promoted the health of C. elegans by increasing the body bending and pharyngeal pumping rates and reducing the lipofuscin accumulation level. Meanwhile, paeonol induced the expression of stress-related genes or proteins by activating the transcription factors DAF-16/FOXO, SKN-1/Nrf2, and HSF-1, which in turn enhanced oxidative and thermal stress tolerance. The mechanism behind the anti-aging effect of paeonol occurred by down-regulating the insulin/IGF-1 signaling (IIS) pathway. Our findings shed new light on the application of paeonol for longevity promotion and human health.