scholarly journals The Predictive and Prognostic Value of Sex in Early-Stage Colon Cancer: A Pooled Analysis of 33,345 Patients from the ACCENT Database

2013 ◽  
Vol 12 (3) ◽  
pp. 179-187 ◽  
Author(s):  
Winson Y. Cheung ◽  
Qian Shi ◽  
Michael O'Connell ◽  
James Cassidy ◽  
Charles D. Blanke ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Value ◽  
Early Stage ◽  
Pooled Analysis ◽  
Early Stage Colon Cancer ◽  
Predictive And Prognostic Value

Association of high microsatellite instability (MSI-H) with a high immunoscore (IS) compared to PD-L1 expression and increased survival in patients (pts) with metastatic colorectal cancer (mCRC) treated with oxaliplatin (Ox) and fluoropyrimidine (FP): A pooled analysis of the AIO KRK 0207 and RO91 trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3595-3595
Author(s):  
Stefanie Noepel-Duennebacke ◽  
Hendrik Juette ◽  
Karsten Schulmann ◽  
Ullrich Graeven ◽  
Rainer Porschen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune Cell ◽  
Early Stage ◽  
Predictive Biomarkers ◽  
Lymphocytic Infiltration ◽  
Pooled Analysis ◽  
Protein Loss ◽  
Early Stage Colon Cancer ◽  
Length Analysis ◽  
Clinical Trial Information

3595 Background: MSI-H is an established prognostic marker in early colon cancer. Moreover, MSI-H, tumor immune cell infiltration and PD-L1 expression are also discussed as potential predictive biomarkers for immunotherapy. However, little is known about the prognostic value of these biomarkers and their association among each other in mCRC. Methods: We analyzed samples from pts. with mCRC uniformly treated with a FP and Ox within two randomized AIO trials (KRK 0207 and RO91). MS status was assessed by immunohistochemistry (IHC) of mismatch repair proteins and subsequent fragment length analysis in case of protein loss or incoherent results. PD-L1 expression was determined by IHC (1% expression threshold). Tumor lymphocytic infiltration (CD8 and CD45RO) was scored according to the immunoscore (IS) concept by Galon et al (J Transl Med 2016). Results: 41/550 cases (7.5%) displayed MSI-H. The mean IS of the total population was 0.57 (SD 0.97), the IS of MSI-H pts. was significantly higher (mean of 2.4; SD 1.4; p≤0.0001). 17 cases were PD-L1 positive (pos.) (3 %), only four of these were MSI-H. MSI-H status was significantly correlated with a higher IS, but not with PD-L1 expression (table 1). There was no difference in median overall survival (mOS) between MSI-H and MS stable (MSS) pts. (mOS MSI-H/MSS: 17.6/22.5 months (mos.), log rank: p=0.85), PD-L1 negative (neg.) and pos. pts. (mOS PD-L1 neg./pos.: 22.1/28.9 mos., log rank: p=0.49) and IS high or low pts. (mOS IS high/low: 21.1/22.1mo., log rank: p=0.25). Conclusions: In contrast to early stage colon cancer, none of these parameters was prognostic in mCRC patients. Panel-sequencing with a total of 35 genes including RAS, BRAF and POL-E on cases with PD-L1 expression, high IS or MSI-H status to further characterize these cases will be reported. Clinical trial information: AIO-R091, AIO-KRK-0207: EudraCT-Nr: 2008-007974-39. [Table: see text]

scholarly journals Nivolumab, ipilimumab and COX2-inhibition in early stage colon cancer

2017 ◽  
Vol 28 ◽  
pp. v207
Author(s):  
M. Chalabi ◽  
M. Van Leerdam ◽  
A. Aalbers ◽  
J. Van den Berg ◽  
G. Beets ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Early Stage ◽  
Early Stage Colon Cancer

scholarly journals Early stage colon cancer

2013 ◽  
Vol 19 (46) ◽  
pp. 8468 ◽  
Author(s):  
Hugh James Freeman
Keyword(s):  
Colon Cancer ◽  
Early Stage ◽  
Early Stage Colon Cancer

scholarly journals Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon Cancer

2017 ◽  
Vol 17 (2) ◽  
pp. 248-262 ◽  
Author(s):  
Babak Esmaeelian ◽  
Kirsten Benkendorff ◽  
Richard K. Le Leu ◽  
Catherine A. Abbott
Keyword(s):  
Colon Cancer ◽  
Natural Products ◽  
Liver Toxicity ◽  
Early Stage ◽  
Blood Biochemistry ◽  
In Vivo Model ◽  
Liver Histopathology ◽  
Genotoxic Carcinogens ◽  
Early Stage Colon Cancer

The acute apoptotic response to genotoxic carcinogens animal model has been extensively used to assess the ability of drugs and natural products like dietary components to promote apoptosis in the colon and protect against colorectal cancer (CRC). This work aimed to use this model to identify the main chemopreventative agent in extracts from an Australian mollusc Dicathais orbita, while simultaneously providing information on their potential in vivo toxicity. After 2 weeks of daily oral gavage with bioactive extracts and purified brominated indoles, mice were injected with the chemical carcinogen azoxymethane (AOM; 10 mg/kg) and then killed 6 hours later. Efficacy was evaluated using immunohistochemical and hematoxylin staining, and toxicity was assessed via hematology, blood biochemistry, and liver histopathology. Comparison of saline- and AOM-injected controls revealed that potential toxic side effects can be interpreted from blood biochemistry and hematology using this short-term model, although AOM negatively affected the ability to detect histopathological effects in the liver. Purified 6-bromoisatin was identified as the main cancer preventive agent in the Muricidae extract, significantly enhancing apoptosis and reducing cell proliferation in the colonic crypts at 0.05 mg/g. There was no evidence of liver toxicity associated with 6-bromoisatin, whereas 0.1 mg/g of the brominated indole tyrindoleninone led to elevated aspartate aminotransferase levels and a reduction in red blood cells. As tyrindoleninone is converted to 6-bromoisatin by oxidation, this information will assist in the optimization and quality control of a chemopreventative nutraceutical from Muricidae. In conclusion, preliminary data on in vivo safety can be simultaneously collected when testing the efficacy of new natural products, such as 6-bromoisatin from Muricidae molluscs for early stage prevention of colon cancer.

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