Gender-related invasion differences associated with mRNA expression levels of melatonin membrane receptors in colorectal cancer

2011 ◽  
Vol 51 (8) ◽  
pp. 608-618 ◽  
Author(s):  
Josefa León ◽  
Jorge Casado ◽  
Ángel Carazo ◽  
Laura Sanjuán ◽  
Ana Maté ◽  
...  
2020 ◽  
Vol 75 ◽  
pp. 62-69 ◽  
Author(s):  
Pinelopi I. Artemaki ◽  
Aimilia D. Sklirou ◽  
Christos K. Kontos ◽  
Aikaterini-Anna Liosi ◽  
Despoina D. Gianniou ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13065-13065
Author(s):  
K. Uchida ◽  
K. Hayashi ◽  
H. Kuramochi ◽  
K. Kudo ◽  
S. Miyakura ◽  
...  

13065 Background: To test the hypotheses of whether the relative mRNA expression of excision cross complement-1 (ERCCI) are associated with response to CDDP+S-1 chemotherapy in recurrent colorectal cancer (CRC). We assessed the relationship between ERCC1 mRNA expression levels and the response. Methods: Thirty four patients with relapsed CRC were treated with cisplatin 30 mg/m2 on Day 1 and Day 8, and S-1 twice daily (BSA = 1.5 m2, 60 mg/day) for 21 days, followed by a 2-week period of no treatment. cDNA was derived from paraffin-embeded tumor specimens to determine ERCC1 mRNA expression relative to the internal reference gene beta-actin using fluorescence-based, real-time reverse transcriptase polymerase chain reaction (Taqman) system. Results: Among 34 CRC patients, 4 patients were evaluated as CR, 13 as PR, and 17 as NC/PD. Relative ERCC1 mRNA gene expression level showed significant difference by the response with median expression levels of 0.70/1.33/1.80 in CR/PR/NC+PD patients respectively (P = 0.04). Conclusions: These data suggest that intratumoral ERCC1 mRNA expression levels are independent predictive markers of response to CDDP+S-1 chemotherapy in colorectal cancer. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 383-383
Author(s):  
Martin K. H. Maus ◽  
Craig Stephens ◽  
Stephanie H. Astrow ◽  
Peter Philipp Grimminger ◽  
Dongyun Yang ◽  
...  

383 Background: Gene expression levels of ERCC1, TS, EGFR and VEGFR2 may have predictive value for the personalized use of standard chemotherapeutics as well as agents targeting the EGFR and VEGF pathways and the efficacy of EGFR directed monoclonal antibodies like panitumumab and cetuximab has been confirmed to be dependent on wt KRAS and wt BRAF in patients with advanced colorectal cancer. We investigated the correlations between KRAS/BRAF mutational status and the mRNA expression levels of these genes. Methods: Formalin-fixed paraffin-embedded tumor specimens from 600 patients with advanced colorectal adenocarcinoma were microdissected and DNA and RNA was extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. Results: Mt KRAS tumors had significantly lower TS and EGFR gene expression levels compared with wt KRAS (p<0,001), whereas mt BRAF tumors showed significantly increased TS and EGFR mRNA levels compared to wt BRAF (p<0,001). Mt BRAF tumors showed significantly higher mRNA levels than mt KRAS tumors (p<0,001). ERCC1 and VEGFR2 mRNA levels were significantly down-regulated in mt KRAS specimen (p<0,001), but showed no significant correlation with BRAF mutational status. Conclusions: KRAS and BRAF mutations are associated with opposite mRNA expression levels for TS and EGFR. Recently, resistance to BRAF inhibition in mt BRAF colorectal tumors has been shown in preclinical models to be associated with up-regulation of EGFR. Our data suggests that BRAF mutants are associated with high EGFR levels at the time of diagnosis, and not necessarily part of an acquired mechanism of resistance. Significantly lower mRNA expression levels of VEGFR2 in mt KRAS tumors may explain lower response to angiogenesis inhibition seen in the TML study.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15071-e15071
Author(s):  
H. Kuramochi ◽  
K. Hayashi ◽  
G. Nakajima ◽  
H. Kamikozuru ◽  
M. Yamamoto

e15071 Background: Oxaliplatin has been widely used for the treatment of colorectal cancer. The mechanism of action of platinum compounds such as oxaliplatin is to bind to a DNA molecule in the form of a platinum-DNA-adduct. Excision repair cross complementation group 1 (ERCC1), which plays a major role in the nucleotide excision pathway, has a polymorphism in codon 118, and is reported to be associated with a resistance to platinum-based therapy. Thymidylate synthase (TS) and dehydropyrimidine dehydrogenase (DPD) are key enzymes of 5-FU metabolism and are well known to be associated with a response to 5-FU-based therapy. Methods: Twenty-one colorectal cancer patients (male:female = 7:14; median age, 65) treated with a combination of oxaliplatin and S-1 as a first-line therapy were analyzed for ERCC1 codon 118 polymorphism and the mRNA expression levels of TS, ERCC1, and DPD. Formalin-fixed paraffin- embedded surgical specimens were used and t-RNA and DNA were extracted. The mRNA expression levels were measured using real-time RT-PCR, and the polymorphism was analyzed using the allelic discrimination method together with real-time PCR. Results: No correlation was observed between ERCC1 codon118 polymorphism and any response to the chemotherapy. ERCC1 mRNA levels tended to be higher in the patients with wild-type homozygous alleles in codon 118 than in those with at least one mutant allele(1.19 vs.0.68: p= 0.15). Patients with both high TS and ERCC1 mRNA levels showed a significantly lower response rate than the others (25% vs. 67%, p=0.02). No relationship was seen between DPD mRNA expression levels and the response. Conclusions: The mRNA expression levels of TS and ERCC1 appear to be useful markers for the treatment of S-1 and oxaliplatin. No particular usefulness of ERCC1 codon 118 polymorphism was verified. No significant financial relationships to disclose.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Meng-Lu Zeng ◽  
Xian-Jin Zhu ◽  
Jin Liu ◽  
Peng-Chong Shi ◽  
Yan-Li Kang ◽  
...  

Background. S100 family genes exclusively encode at least 20 calcium-binding proteins, which possess a wide spectrum of intracellular and extracellular functions in vertebrates. Multiple lines of evidences suggest that dysregulated S100 proteins are associated with human malignancies including colorectal cancer (CRC). However, the diverse expression patterns and prognostic roles of distinct S100 genes in CRC have not been fully elucidated. Methods. In the current study, we analyzed the mRNA expression levels of S100 family genes and proteins and their associations with the survival of CRC patients using the Oncomine analysis and GEPIA databases. Expressions and mutations of S100 family genes were analyzed using the cBioPortal, and protein-protein interaction (PPI) networks of S100 proteins and their mutation-related coexpressed genes were analyzed using STRING and Cytoscape. Results. We observed that the mRNA expression levels of S100A2, S100A3, S100A9, S100A11, and S100P were higher and the level of S100B was lower in CRC tissues than those in normal colon mucosa. A high S100A10 levels was associated with advanced-stage CRC. Results from GEPIA database showed that highly expressed S100A1 was correlated with worse overall survival (OS) and disease-free survival (DFS) and that overexpressions of S100A2 and S100A11 were associated with poor DFS of CRC, indicating that S100A1, S100A2, and S100A11 are potential prognostic markers. Unexpectedly, most of S100 family genes showed no significant prognostic values in CRC. Conclusions. Our findings, though still need to be ascertained, offer novel insights into the prognostic implications of the S100 family in CRC and will inspire more clinical trials to explore potential S100-targeted inhibitors for the treatment of CRC.


2019 ◽  
Vol 13 (3) ◽  
pp. 80 ◽  
Author(s):  
Ajoedi Ajoedi ◽  
Muhammad Al Azhar ◽  
Siti Nadliroh ◽  
Sri Hartini ◽  
Rizka Andalusia ◽  
...  

Background: Immunotherapy using immune checkpoint inhibitors has currently emerged as an effective treatment for a subset of colorectal cancer (CRC) patients. The roles of PD-1 and PD-L1 expression levels in peripheral blood to predict patient’s response to immune checkpoint inhibitors are not well established. Therefore, we analyzed PD-1 and PD-L1 mRNA expression levels of peripheral blood in Indonesian CRC patients and explored the association with the clinicopathological features.Methods: Peripheral blood of 25 CRC patients and 10 healthy individuals were collected in Dharmais Hospital-National Cancer Center from 2017 to 2018. PD-1 and PD-L1 mRNA expression levels were analyzed using real time PCR. The associations with clinicopathological variables were analyzed with fisher-exact test or chi square test.Results: PD-1 mRNA expression levels were significantly lower in CRC patients compared to healthy individuals (HI) (mean: 0.0015 ± 0.0013 and 0.017 ± 0.010 respectively, p < 0.001). Although PD-L1 mRNA expression levels were lower in CRC patients, the difference was not statistically significant (mean in CRC and HI: 0.021 ± 0.013 and 0.034 ± 0.028 respectively, p = 0.125). The expression of PD-L1 was higher in CRC females compared to males (p = 0.03). The expression levels of PD-L1 were not associated with different ages (p = 0.673), stages (p = 0.298), histological type of colorectal cancer (p=0.852), patient status (p = 1.000), and body mass index (p = 0.514).Conclusions: The mRNA expression levels of PD-1 and PD-L1 were lower in CRC patients compared to healthy controls. Expression of PD-L1 were correlated with sex, but not correlated with ages, stages, histological type of CRC, patient status, and body mass index.


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