Rabbit Anti-Human CCNH Polyclonal antibody

The combined analysis of the CCNH rs2230641 and the ABCG2 rs3114018 SNPs independently predict the development of severe oxaliplatin-induced peripheral neuropathy in early-stage colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy. This pharmacogenetic approach might improve the stratification of patients, enabling specific dosing strategies and the assessment of potential neuroprotective therapies.Oxaliplatin-based chemotherapy (CT), widely used as adjuvant therapy for stage III and selected high-risk stage II colon cancer (CC) patients, is often associated with cumulative peripheral neuropathy. Our aim is to identify single-nucleotide polymorphisms (SNPs) in genes involved in oxaliplatin metabolism, DNA repair mechanisms, cell cycle control, detoxification or excretion pathways to predict severe (grade 2-3) oxaliplatin-induced peripheral neuropathy (OXPN) among CC patients treated with oxaliplatin and fluoropyrimidine-based adjuvant CT. Genomic DNA was extracted from formalin-fixed-paraffin-embedded peritumoral samples from 206 high-risk stage II and stage III CC patients receiving oxaliplatin-based adjuvant CT from January 2004 to December 2009. Genotyping was carried out for 34 SNPs in 15 genes using MassARRAY (SEQUENOM) technology. A total of 181 stage II-III CC patients treated with the same CT regimens were enrolled as a validation set. The rs2230641 cyclin H (CCNH) rs2230641 C/C [odd ratio (OR) = 5.03, 95% confidence interval (CI) 1.061-2.41, P = 0.042] and the ATP-binding cassette subfamily G, member 2 (ABCG2) rs3114018 A/A genotypes (OR = 2.67; 95% CI 0.95-4.41; P = 0.059) were associated with a higher risk of severe OXPN. In addition, patients harboring the combination of CCNH C/C and/or the ABCG2 rs3114018 A/A genotypes had a higher risk of grade 2-3 OXPN than those with the CCNH any T and ABCG2 any C genotypes (37.73% versus 19.42%; OR = 2.46; 95% CI 1.19-5.07; P = 0.014) in the logistic regression analysis using age, gender, adjuvant CT regimen and cumulative dose of oxaliplatin as covariates. The ability to predict severe OXPN of this combined analysis was independently validated in the second cohort (58% versus 33.33%; OR = 2.99; 95% CI 1.45-6.13; P = 0.002). Our results suggest that SNPs in CCNH and ABCG2 can modulate the development of severe OXPN among stage II-III CC patients who received oxaliplatin-based CT, thus enabling the individualization of adjuvant treatment.

The mechanisms underlying the potential for aggressive behavior of prostate cancer (PCa) remain elusive. In this study, whole genome and/or transcriptome sequencing was performed on 19 specimens of PCa, matched adjacent benign prostate tissues, matched blood specimens, and organ donor prostates. A set of novel fusion transcripts was discovered in PCa. Eight of these fusion transcripts were validated through multiple approaches. The occurrence of these fusion transcripts was then analyzed in 289 prostate samples from three institutes, with clinical follow-up ranging from 1 to 15 years. The analyses indicated that most patients [69 (91%) of 76] positive for any of these fusion transcripts (TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67, KDM4-AC011523.2, MAN2A1-FER, and CCNH-C5orf30) experienced PCa recurrence, metastases, and/or PCa-specific death after radical prostatectomy. These outcomes occurred in only 37% (58/157) of patients without carrying those fusion transcripts. Three fusion transcripts occurred exclusively in PCa samples from patients who experienced recurrence or PCa-related death. The formation of these fusion transcripts may be the result of genome recombination. A combination of these fusion transcripts in PCa with Gleason's grading or with nomogram significantly improves the prediction rate of PCa recurrence. Our analyses suggest that formation of these fusion transcripts may underlie the aggressive behavior of PCa.