Targeted Modulation of FAK/PI3K/PDK1/AKT and FAK/p53 Pathways by Cucurbitacin B for the Antiproliferation Effect Against Human Cholangiocarcinoma Cells.

This study aimed to investigate the antiproliferative property of cucurbitacin B on KKU-100 CCA cells. The determination of underlying molecular mechanisms was also carried out. The results revealed that cucurbitacin B suppressed growth and replicative ability to form colonies of CCA cells, suggesting the antiproliferative effect of this compound against the cells. Flow cytometry analysis demonstrated that the interfering effect of cucurbitacin B on the CCA cell cycle at the G2/M phase was accountable for its antiproliferation property. Accompanied with cell cycle disruption, cucurbitacin B altered the expression of proteins involved in the G2/M phase transition including downregulation of cyclin A, cyclin D1, and cdc25A, and upregulation of p21. Additional molecular studies demonstrated that cucurbitacin B suppressed the activation of focal adhesion kinase (FAK) which consequently resulted in inhibition of its kinase-dependent and kinase-independent downstream targets contributing to the regulation of cell proliferation including PI3K/PDK1/AKT and p53 proteins. In this study, the transient knockdown of FAK using siRNA was employed to ascertain the role of FAK in CCA cell proliferation. Finally, the effect of cucurbitacin B on upstream receptor tyrosine kinases regulating FAK activation was elucidated. The results showed that the inhibitory effect of cucurbitacin B on FAK activation in CCA cells is mediated via interference of EGFR and HER2 expression. Collectively, cucurbita...
Source: The American Journal of Chinese Medicine - Category: Complementary Medicine Authors: Tags: Am J Chin Med Source Type: research

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Authors: Zhang W, Zhou H, Wang Y, Zhang Z, Cao G, Song T, Zhang T, Li Q Abstract Biliary tract cancer (BTC) is a disease entity comprising diverse epithelial tumors with features of cholangiocyte differentiation, and it includes cholangiocarcinoma (CCA) and gallbladder cancer (GBC). Depending on its anatomical location, cholangiocarcinoma is categorized as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Nearly two-thirds of patients with biliary tract cancer present with advanced disease at diagnosis and in 68-86% of resections the cancer eventually recurs either locoregionally or at a distance. Chemothera...
Source: BioScience Trends - Category: Biomedical Science Tags: Biosci Trends Source Type: research
CONCLUSIONS: Although many target drugs have been speeded up for approval such as BGJ398 for FGFR2 fusion positive ICC patients in western countries, the beneficiary populations are very small in China. The regular target drug such as trastuzumab for HER2 amplification and Crizotinib for MET amplification may be potential candidates in target treatment based on the Chinese population. PMID: 32825971 [PubMed - as supplied by publisher]
Source: Pathology, Research and Practice - Category: Pathology Authors: Tags: Pathol Res Pract Source Type: research
Conditions:   Colorectal Carcinoma;   Gastric Adenocarcinoma;   Esophageal and GEJ Adenocarcinoma;   Cholangiocarcinoma;   Gallbladder Carcinoma Interventions:   Drug: tucatinib;   Drug: trastuzumab;   Drug: oxaliplatin;   Drug: leucovorin;   Drug: fluorouracil Sponsor:   Seattle Genetics, Inc. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
AbstractBiliary tract carcinomas are divided into intrahepatic, perihilar, distal extrahepatic cholangiocarcinomas, and gallbladder adenocarcinomas. Therapies targetingROS1,ALK,MET, andHER2 alterations are currently evaluated in clinical trials. We assessedROS1 andALK translocations/amplifications as well asMET andHER2 amplifications for each tumor subtype by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) in 73 intrahepatic, 40 perihilar bile duct, 36 distal extrahepatic cholangiocarcinomas, and 45 gallbladder adenocarcinomas (n = 194). By FISH, we detected targetable alterations in 5...
Source: Virchows Archiv - Category: Pathology Source Type: research
Late recurrence of estrogen receptor (ER) positive breast cancer is common. When tissues from a recurrent or metastatic focus are available, re-evaluation of ER, progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status is recommended for treatment selection. This case report describes a 59-year-old woman who underwent surgery for left breast cancer, with a histopathological diagnosis of invasive ductal carcinoma (pathological stage T2N1aM0 Stage IIB, ER positive, PgR positive and HER2 negative). A health check-up 16 years after surgery revealed multiple hepatic mass lesions, and the patient w...
Source: Case Reports in Oncology - Category: Cancer & Oncology Source Type: research
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
We examined the following three conditions: DMEM high glucose which contained 4.5 mg/ml glucose, independent of serum, DMEM low glucose which contained 1.0 mg/ml glucose, independent of serum. And, DMEM no glucose which contained 0.0 mg/ml glucose, independent of serum. DMEM is referred to as glucose “free,” however some glucose was actually present due to the FBS. The glucose concentration in the FBS used was 1.04 mg/ml. We calculate 0.0937 mg/ml glucose was present in the media under all conditions due to the addition of serum. Quantification of ROS Levels ROS are widely evaluated in tissue culture using di...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsT-DM1 exhibited preclinical activity in HER2-overexpressing BTC. Further evaluation in clinical studies is warranted.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
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