Down-Regulated Expression of HSP70 in Correlation with Clinicopathology of Cholangiocarcinoma
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.Pathology & Oncology Research (Impact Factor: 1.86). 07/2011; 18(2):227-37. DOI: 10.1007/s12253-011-9432-5
Cholangiocarcinoma is a crucial health problem in northeast Thailand. Although rare, it is a highly fatal disease and the prognosis of CCA patients is very poor. To determine if expression of specific genes is useful for diagnosis and prognosis for CCA. We examined the expression of HSP70, HSP90, RB1, cyclin D1, and HDAC6 in 50 resections of human CCA tissues by quantitative real-time PCR. The expression of HSP70, RB1, and HDAC6 was "dominant down-regulation," while the expression of cyclin D1 and HSP90 was "dominant up-regulation." There were no correlations between RB1, cyclin D1, HSP90, and clinicopathological parameters such as status, histology type, histological grading, stage of CCA, and metastasis. A significant association was found between HDAC6 and CCA staging (p = 0.000), CCA gross type and HSP70 (p = 0.046) as well as RB1 expression (p = 0.046). Patients with down-regulation of HSP70 had significantly poorer prognosis than those in the up-regulation group (p = 0.002). Expression of HSP70 may be useful as a new prognostic marker for CCA.
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ABSTRACT: Lokal nichtresektable hiläre Cholangiokarzinome können durch Lebertransplantation kurativ therapiert werden. Die ursprünglich schlechten Ergebnisse nach Transplantation haben sich durch die Etablierung neoadjuvanter Therapieprotokolle und veränderte Strategien in der immunsuppressiven Therapie deutlich verbessert, sodass perihiläre Cholangiokarzinome nun wieder als Transplantationsindikation anerkannt werden. Geeignete Patienten sollten streng selektioniert werden. Die vorliegende Arbeit fasst den aktuellen Stand, Empfehlungen und die Ergebnisse der Lebertransplantation bei diesen Patienten zusammen.
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ABSTRACT: To investigate the expressions of casein kinase II β(CK2β) and X-Linked inhibitor of apoptosis protein (XIAP) in cholangiocarcinoma (CCA) and evaluated their correlations with major clinicopathologic features and patients' survival. Fifty CCA specimens and 20 normal liver tissues were included in the study. Immunohistochemical staining was used to determine the expression levels of CK2β, XIAP in normal and CCA tissues. The relationships of CK2β and XIAP expressions with clinicopathologic parameters and clinical outcome were evaluated. High immunostaining of CK2β and XIAP were observed in 66 % (33/50) and 68 % (34/50) of CCA tissues, which were significantly higher than that of normal liver tissues 0 % (0/20) and 25 % (5/20). The high expression of CK2β was significantly associated with TNM stage (P = 0.036), histological grade (P = 0.020) and high serum CEA level(P = 0.010), while high expression of XIAP was only associated with TNM stage(P = 0.014) and high serum CEA level(P = 0.001). By univariant analysis, patients with high expression of CK2β and XIAP demonstrate significantly poorer overall survival (P = 0.003 vs P = 0.018). Cox regression model showed that positive expression of CK2βis an independent factor of prognosis (P = 0.004). The expressions of CK2β and XIAP in CCA tissues showed strong correlations with the tumor progression, CK2β may be applied as a potential prognostic marker for CCA.
Article: Hsp70 in cancer: Back to the future[Show abstract] [Hide abstract]
ABSTRACT: Mechanistic studies from cell culture and animal models have revealed critical roles for the heat shock protein Hsp70 in cancer initiation and progression. Surprisingly, many effects of Hsp70 on cancer have not been related to its chaperone activity, but rather to its role(s) in regulating cell signaling. A major factor that directs Hsp70 signaling activity appears to be the co-chaperone Bag3. Here, we review these recent breakthroughs, and how these discoveries drive drug development efforts.Oncogene advance online publication, 27 October 2014; doi:10.1038/onc.2014.349.
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