scholarly journals The effect of adenovirus expressing wild-type p53 on 5-fluorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines

2004 ◽  
Vol 10 (24) ◽  
pp. 3583 ◽  
Author(s):  
Sven Eisold
2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15007-e15007
Author(s):  
Arturo Loaiza-Bonilla ◽  
Muaiad Kittaneh ◽  
Victor Daniel Guardiola Amado ◽  
Krisztina Kovacs ◽  
Jaime R. Merchan

e15007 Background: Targeting the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) (PI3K-AKT-mTOR) pathway could arrest tumor growth and induce cell death in cancers that are resistant to currently available therapies. NVP-BEZ235 is an oral, targeted anticancer agent which exerts its potential activity through PI3K/mTOR dual inhibition. The paradoxical feedback activation of the PI3K/Akt pathway may compromise the efficacy of TORC1 inhibitors and provide the rationale for generating dual inhibitors in human pancreatic cancer. Methods: Kras mutant and wild-type human pancreatic cell lines were treated in vitro with BEZ235 and its combination with nab-paclitaxel. Antiproliferative effect per WST-1 assay was measured. Western blot analysis of S235/S236P-RPS6 and Akt (S473P-Akt, T308P-Akt) after exposure to BEZ235 was also performed. The potential synergistic and time-dependent effect at different concentrations of experimental agents was measured at different intervals. Results: BEZ235 reduced S473P-Akt, T308P-Akt and S235/S236P-RPS6 levels in a dose-dependent manner. Nab-paclitaxel at higher concentration exerts significant antiproliferative effects in a time-dependent fashion in pancreatic cell lines irrespective of Kras mutation status. BEZ235 in combination with nab-paclitaxel showed significant synergistic effect in a time and dose-dependent manner compared with the corresponding single drug treatments in pancreatic cancer cell lines with wild-type Kras (BxPC-3) but not in cell lines with mutant Kras (MIA PaCa-2 and PANC-1), the latter leading to a paradoxical increase in proliferation in comparison with controls, suggesting an escape pathway. Conclusions: These results provide the preclinical rationale for studies examining the synthetic lethality and escape pathways of PI3K/mTOR dual inhibition in particular subtypes of pancreatic cancer cell lines. Kras may be studied as a potential predictive biomarker of response to these agents and their combination with standard chemotherapy.


1996 ◽  
Vol 270 (5) ◽  
pp. R1078-R1084 ◽  
Author(s):  
J. P. Smith ◽  
A. Shih ◽  
Y. Wu ◽  
P. J. McLaughlin ◽  
I. S. Zagon

The gastrointestinal peptides gastrin and cholecystokinin (CCK) stimulate growth of human pancreatic cancer through a CCK-B/gastrin- like receptor. In the present study we evaluated whether growth of human pancreatic cancer is endogenously regulated by gastrin. Immunohistomical examination of BxPC-3 cells and tumor xenografts revealed specifc gastrin immunoreactivity. Gastrin was detected by radioimmunoassay in pancreatic cancer cell extracts and in pancreatic cancer cell extracts and in the growth media. With use of reverse-transcriptase polymerase chain reaction gastrin gene expression was detected in both cultured BxPC-3 cancer cells and transplanted tumors, as well as seven addition human pancreatic cancer cell lines. Growth of BxPC-3 human pancreatic cancer cell in serum-free medium was inhibited by the addition of the CCK-B/gastrin receptor antagonist L-365,260, and gastrin treatment reversed the inhibitory effect of the antagonist. A selective gastrin antibody (Ab repressed growth of BxPC-3 cells. Gastrin immunoreactivity was detected in fresh human pancreatic cancer specimens but not in normal human pancreatic tissue. These data provide the first evidence that growth of a human pancreatic cancer is tonically stimulated by the autocrine production of gastrin. Evidence for the ubiquity of this system was provided by the detection of gastrin gene expression in multiple human pancreatic cancer cell lines and detection of gastrin in cell lines and fresh pancreatic tumors.


2011 ◽  
Vol 43 (7) ◽  
pp. 565-574 ◽  
Author(s):  
Jonathan P. Celli ◽  
Nicolas Solban ◽  
Alvin Liang ◽  
Stephen P. Pereira ◽  
Tayyaba Hasan

Oncotarget ◽  
2017 ◽  
Vol 8 (17) ◽  
pp. 29233-29246 ◽  
Author(s):  
Wan-Chi Tsai ◽  
Li-Yuan Bai ◽  
Yi-Jin Chen ◽  
Po-Chen Chu ◽  
Ya-Wen Hsu ◽  
...  

FEBS Letters ◽  
2005 ◽  
Vol 579 (7) ◽  
pp. 1587-1590 ◽  
Author(s):  
Ze-Jun Liu ◽  
Xin Lu ◽  
Yun Zhang ◽  
Shan Zhong ◽  
Shou-Zhi Gu ◽  
...  

Author(s):  
Nazia Hoque ◽  
Choudhury Mahmood Hasan ◽  
Md. Sohel Rana ◽  
Amrit Varsha ◽  
Md. Hossain Sohrab ◽  
...  

As a part of our ongoing research on endophytic fungi, we have isolated a sesterterpene mycotoxin, fusaproliferin (FUS), from Fusarium solani strain associated with the plant Aglaonema hookerianum Schott. FUS showed rapid and sub-micromolar IC50 against pancreatic cancer cell lines. Time dependent survival analysis and microscopy imaging showed rapid morphological changes in cancer cell lines 4 hours after incubation with FUS. This provides a new chemical scaffold that can be further developed to obtain more potent synthetic agents against pancreatic cancer.


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