Phase Ib IIT of Heat Shock Protein 90 Inhibitor TAS-116 Combined with Cyclin-dependent Kinase 4/6 Inhibitor Palbociclib in Advanced Breast Cancer Progressing on Palbociclib & Treatment-refractory Solid Tumors with Retinoblastoma Deficiency

The purpose of this study is to evaluate the safety and efficacy of TAS-116 with palbociclib in two groups of patients:
* Patients with advanced breast cancer that has become worse after taking palbociclib alone
* Patients with cancers that have an abnormality in a gene called the "retinoblastoma gene".

开始日期2023-09-12

申办/合作机构

Brown University

CTR20232143 / Recruiting临床1期

一项TAS-116(pimitespib)联合伊马替尼治疗晚期胃肠道间质瘤患者的Ⅰ期研究

这是一项I期、开放性、多国、多中心研究。在中国患者剂量递增部分，将在中国患者中评估pimitespib单药治疗以及与伊马替尼联合治疗的安全性和耐受性。

开始日期2023-09-04

申办/合作机构

Bushu Pharmaceuticals Ltd.

[+2]

100 项与 HSP90A x HSP90B 相关的临床结果

登录后查看更多信息

100 项与 HSP90A x HSP90B 相关的转化医学

登录后查看更多信息

0 项与 HSP90A x HSP90B 相关的专利（医药）

登录后查看更多信息

项与 HSP90A x HSP90B 相关的文献（医药）

2024-11-01·Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Persistent interactive effects of developmental salinity and temperature in Atlantic killifish (Fundulus heteroclitus)

Article

作者: Thapar, Myra ; Blanchard, Tessa S ; Bugg, William S. ; Bugg, William S ; Schulte, Patricia M. ; Earhart, Madison L. ; Earhart, Madison L ; Schulte, Patricia M ; Blanchard, Tessa S.

Climate change alters multiple abiotic environmental factors in aquatic environments but relatively little is known about their interacting impacts, particularly in developing organisms where these exposures have the potential to cause long-lasting effects. To explore these issues, we exposed developing killifish embryos (Fundulus heteroclitus) to 26 °C or 20 °C and 20 ppt or 3 ppt salinity in a fully-factorial design. After hatching, fish were transferred to common conditions of 20 °C and 20 ppt to assess the potential for persistent developmental plasticity. Warm temperature increased hatching success and decreased hatch time, whereas low salinity negatively affected hatching success, but this was only significant in fish developed at 20 °C. Temperature, salinity, or their interaction affected mRNA levels of genes typically associated with thermal and hypoxia tolerance (hif1a, hsp90b, hsp90a, hsc70, and hsp70.2) across multiple developmental timepoints. These differences were persistent into the juvenile stage, where the fish that developed at 26 °C had higher expression of hif1a, hsp90b, hsp90a, and hsp70.2 than fish developed at 20 °C, and this was particularly evident for the group developed at both high temperature and salinity. There were also long-lasting effects of developmental treatments on body size after four months of rearing under common conditions. Fish developed at low salinity or temperature were larger than fish developed at high temperature or salinity, but there was no interaction between the two factors. These data highlight the complex nature of the developmental effects of interacting stressors which has important implications for predicting the resilience of fishes in the context of climate change.

2024-09-26·Reviews on Recent Clinical Trials

Expression of Heat Shock Protein 90 in Testicular Cancer: A Retrospective Cohort Study

Article

作者: Giannakodimos, Ilias ; Tzortzis, Vasileios ; Politis, Vasileios ; Stamatiou, Konstantinos ; Sotiriou, Sotirios ; Mitakidi, Evangelia ; Tzelepis, Konstantinos ; Provatas, Ioannis

Background:The HSP90 marker is believed to play a constructive role in facilitating neoplastic transformation mainly via interaction with multiple pro-survival proteins. Welldesigned studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors.Objective:The current study aimed to investigate the expression of HSP90 in various types of testicular cancer and highlight its expression in embryonal testicular cancer.objective:The current study aims to investigate the expression of HSP90 in various types of testicular cancer and to highlight its expression in embryonal testicular cancer.Material and Methods:Immunohistochemical staining for HSP90 in 84 male patients, with nonmetastatic testicular cancer, who underwent orchiectomy from 2000 to 2023, was retrospectively performed at the Laboratory Department of General Hospital of Nikaia in Greece.Results:A total of 84 males, with a mean age of 36.2 years, who have undergone high-cord radical orchiectomy, were included in this study. Out of the included males, 28.57% had embryonal carcinoma, 23.81% had seminoma, 19.05% had yolk sac tumor, 11.9% had mature teratoma, 9.52% had immature teratoma, and 7.14% had choriocarcinoma. HSP90b was positive in all embryonal carcinoma, seminoma, and choriocarcinoma cases, while it was positive in 75% of the yolk sac tumor, 75% of mature teratoma, and 75% of immature teratoma specimens. HSP90 was found negative in all choriocarcinoma, mature teratoma, and immature teratoma specimens, while it was positive in 25% of yolk sac tumor, 8.33% of embryonal carcinoma, and 10% of seminoma cases. Concerning the expression of HSP90b, a statistically significant relationship was found between excised tumor specimens and normal parenchyma specimens, especially in sac cases (p <0.001). Regarding HSP90a expression, a statistically significant relationship (OR=21.5, p =0.021) was found between excised tumor specimens and normal parenchyma specimens, especially in embryonal carcinoma cases (p <0.001).Conclusion:HSP90b is highly expressed in the majority of the types of testicular tumors, both in tumor and normal parenchyma specimens, while HSP90a staining is negative in resected specimens. Further well-designed studies are needed to elucidate the role of HSP90 as a diagnostic marker and therapeutic target in testicular tumors.

2023-07-01·Journal of thermal biology

Slow heating rates increase thermal tolerance and alter mRNA HSP expression in juvenile white sturgeon (Acipenser transmontanus).

Article

作者: Bugg, William ; Earhart, Madison L ; Brauner, Colin J ; Rost-Komiya, Beatrice ; Penman, Rachael J

Freshwater fish such as white sturgeon (Acipenser transmontanus) are particularly vulnerable to the effects of anthropogenically induced global warming. Critical thermal maximum tests (CT_max) are often conducted to provide insight into the impacts of changing temperatures; however, little is known about how the rate of temperature increase in these assays affects thermal tolerance. To assess the effect of heating rate (0.3 °C/min, 0.03 °C/min, 0.003 °C/min) we measured thermal tolerance, somatic indices, and gill Hsp mRNA expression. Contrary to what has been observed in most other fish species, white sturgeon thermal tolerance was highest at the slowest heating rate of 0.003 °C/min (34.2 °C, and CTmax of 31.3 and 29.2 °C, for rates 0.03 and 0.3 °C/min, respectively) suggesting an ability to rapidly acclimate to slowly increasing temperatures. Hepatosomatic index decreased in all heating rates relative to control fish, indicative of the metabolic costs of thermal stress. At the transcriptional level, slower heating rates resulted in higher gill mRNA expression of Hsp90a, Hsp90b, and Hsp70. Hsp70 mRNA expression was increased in all heating rates relative to controls, whereas expression of Hsp90a and Hsp90b mRNA only increased in the two slower trials. Together these data indicate that white sturgeon have a very plastic thermal response, which is likely energetically costly to induce. Acute temperature changes may be more detrimental to sturgeon as they struggle to acclimate to rapid changes in their environment, however under slower warming rates they demonstrate strong thermal plasticity to warming.