High c-MET expression defines a subset of pancreatic adenocarcinoma patients with poor prognosis following surgical resection: Exploration of mechanisms driving c-MET overexpression, transcriptomic analyses, and in vitro effects of c-MET inhibitors

Pancreatology ◽  
2016 ◽  
Vol 16 (3) ◽  
pp. S27
Author(s):  
Jerome Cros ◽  
Cindy Neuzillet ◽  
Jerome Raffenne ◽  
Alice Boyez ◽  
Annemilai Tijeras-Raballand ◽  
...  
2020 ◽  
Vol 9 (8) ◽  
pp. 2440
Author(s):  
Natalia Gablo ◽  
Karolina Trachtova ◽  
Vladimir Prochazka ◽  
Jan Hlavsa ◽  
Tomas Grolich ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and aggressive cancers with a less than 6% five-year survival rate. Circulating microRNAs (miRNAs) are emerging as a useful tool for non-invasive diagnosis and prognosis estimation in the various cancer types, including PDAC. Our study aimed to evaluate whether miRNAs in the pre-operative blood plasma specimen have the potential to predict the prognosis of PDAC patients. In total, 112 PDAC patients planned for surgical resection were enrolled in our prospective study. To identify prognostic miRNAs, we used small RNA sequencing in 24 plasma samples of PDAC patients with poor prognosis (overall survival (OS) < 16 months) and 24 plasma samples of PDAC patients with a good prognosis (OS > 20 months). qPCR validation of selected miRNA candidates was performed in the independent cohort of PDAC patients (n = 64). In the discovery phase of the study, we identified 44 miRNAs with significantly different levels in the plasma samples of the group of good and poor prognosis patients. Among these miRNAs, 23 showed lower levels, and 21 showed higher levels in plasma specimens from PDAC patients with poor prognosis. Eleven miRNAs were selected for the validation, but only miR-99a-5p and miR-365a-3p were confirmed to have significantly lower levels and miR-200c-3p higher levels in plasma samples of poor prognosis cases. Using the combination of these 3-miRNA levels, we were able to identify the patients with poor prognosis with sensitivity 85% and specificity 80% (Area Under the Curve = 0.890). Overall, 3-miRNA prognostic score associated with OS was identified in the pre-operative blood plasma samples of PDAC patients undergoing surgical resection. Following further independent validations, the detection of these miRNA may enable identification of PDAC patients who have no survival benefit from the surgical treatment, which is associated with the high morbidity rates.


2013 ◽  
Vol 216 (2) ◽  
pp. 312-319 ◽  
Author(s):  
Sha'Shonda L. Revels ◽  
Mousumi Banerjee ◽  
Huiying Yin ◽  
Christopher J. Sonnenday ◽  
John D. Birkmeyer

2012 ◽  
Vol 215 (3) ◽  
pp. S106
Author(s):  
Sha'Shonda L. Revels ◽  
Mousumi Banerjee ◽  
Huiying Yin ◽  
Christopher J. Sonnenday ◽  
John D. Birkmeyer

2020 ◽  
Vol 6 (1) ◽  
pp. 205511692092491
Author(s):  
Johanna E Todd ◽  
Sandra M Nguyen

Case summary Primary pancreatic adenocarcinoma is an uncommon neoplasm seen in cats and often has a poor prognosis. We report a case of an 8-year-old male neutered domestic shorthair cat weighing 5.8 kg diagnosed with pancreatic adenocarcinoma treated with surgical resection and toceranib phosphate, which had a progression-free interval of 1148 days and survived for more than 1436 days. The treatment was well tolerated; however, the cat developed generalised coat hypopigmentation. Relevance and novel information To our knowledge, the cat in our report has the longest progression-free interval and survival time post-surgical resection of pancreatic carcinoma treated with toceranib. Hypopigmentation as a side effect of toceranib has been reported in dogs, but this is the first case reported in cats.


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  

1990 ◽  
Vol 64 (03) ◽  
pp. 402-406 ◽  
Author(s):  
M D Oethinger ◽  
E Seifried

SummaryThe present in vitro study investigated dose-, time- and temperature-dependent effects of two-chain urokinase plasminogen activato(u-PA, urokinase) on normal citrated plasma. When 10 μg/ml u-PA wereadded to pooled normal plasma and incubated for 30 min at an ambient temperature (25° C), α2-antiplas-min decreased to 8% of the control value. Incubation on ice yielded a decrease to 45% of control,whereas α2-antiplasmin was fully consumed at 37° C. Fibrinogen and plasminogen fell to 46% and 39%, respectively, after a 30 min incubation at 25° C. Thrombin time prolonged to 190% of control.Various inhibitors were studied with respect to their suitability and efficacy to prevent these in vitro effects. Aprotinin exhibited a good protective effect on fibrinogen at concentrations exceeding 500 KlU/ml plasma. Its use, however, was limited due to interferences with some haemostatic assays. We could demonstrate that L-Glutamyl-L-Glycyl-L-Arginyl chloromethyl ketone (GGACK) and a specific polyclonal anti-u-PA-antibody (anti-u-PA-IgG) effectively inhibited urokinase-induced plasmin generation without interfering with haemostatic assays. The anti-u-PA-antibody afforded full protection ofα2-antiplasmin at therapeutic levels of u-PA.It is concluded that u-PA in plasma samples from patients during thrombolytic therapy may induce in vitro effects which should be prevented by the use of a suitable inhibitor such as GGACK or specific anti-u-PA-antibody.


1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.


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