1.
Roles of genetic variants in the PI3K/PTEN pathways in susceptibility to colorectal carcinoma and clinical outcomes treated with FOLFOX regimen.
Lin, L, Zhang, Z, Zhang, W, Wang, L, Wang, J
International journal of clinical and experimental pathology. 2015;(10):13314-22
Abstract
UNLABELLED The genetic or abnormal activation of PI3K/PTEN signaling pathway play an important role with regard to disease progression in variety of human malignancies. Experimental and epidemiologic studies indicated that the genetic polymorphisms in the PTEN, PI3K genes are associated with cancer risk, yet little evidence exists for those 2 genes and colorectal cancer (CRC) risk. To address this, we evaluated whether PTEN rs701848, PIK3CA rs2699887 variants are associated with CRC susceptibility, clinicopathological parameters and clinical outcomes in CRC patients treated with FOLFOX (Oxaliplatin, Leucovorin, 5-Fluorouracil) regimen. A case-control study was performed in 780 CRC patients and 764 healthy controls using the TaqMan assay method. A significant increased risk of CRC was observed in patients carrying PTEN rs701848 TC or CC genotype (adjusted OR=1.306, 95% CI=1.030-1.655, P=0.027; adjusted OR=1.543, 95% CI=1.148-2.075, P=0.004, respectively), TC/CC genotype (adjusted OR=1.367, 95% CI=1.090-1.714, P=0.043) in the dominant model, and C allele (adjusted OR=1.229, 95% CI=1.067-1.416, P=0.004). However, no association was detected between rs2699887 in the PIK3CA gene and CRC risk. A significant association was found between pathological grade (Dukes A and B vs. Dukes C and D) and PIK3CA rs2699887 genotypes. Furthermore, Kaplan-Meier analysis revealed that PTEN rs701848 genotypes were significantly associated with the overall survival (OS) of CRC patients treated with FOLFOX regimen (n=780). Individuals carrying PTEN rs701848 TC or TC/CC genotypes showed significantly longer median survival time (MST) than TT genotype and significant hazard ratio (TC: adjusted HR=0.523, 95% CI=0.325-0.840, P=0.007; TC/CC: adjusted HR=0.545, 95% CI=0.351-0.845, P=0.007). Therefore, rs701848 polymorphism in the PTEN gene is associated with susceptibility to CRC, and C allele of rs701848 showed significant independent better prognosis of CRC patients treated with FOLFOX regimen. These results indicate that rs701848 in the PTEN gene might be a candidate pharmacogenomic factor to assess the susceptibility and prognosis in CRC patients.
2.
Magnetic resonance spectroscopy as an early indicator of response to anti-angiogenic therapy in patients with recurrent glioblastoma: RTOG 0625/ACRIN 6677.
Ratai, EM, Zhang, Z, Snyder, BS, Boxerman, JL, Safriel, Y, McKinstry, RC, Bokstein, F, Gilbert, MR, Sorensen, AG, Barboriak, DP
Neuro-oncology. 2013;(7):936-44
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Abstract
BACKGROUND The prognosis for patients with recurrent glioblastoma remains poor. The purpose of this study was to assess the potential role of MR spectroscopy as an early indicator of response to anti-angiogenic therapy. METHODS Thirteen patients with recurrent glioblastoma were enrolled in RTOG 0625/ACRIN 6677, a prospective multicenter trial in which bevacizumab was used in combination with either temozolomide or irinotecan. Patients were scanned prior to treatment and at specific timepoints during the treatment regimen. Postcontrast T1-weighted MRI was used to assess 6-month progression-free survival. Spectra from the enhancing tumor and peritumoral regions were defined on the postcontrast T1-weighted images. Changes in the concentration ratios of n-acetylaspartate/creatine (NAA/Cr), choline-containing compounds (Cho)/Cr, and NAA/Cho were quantified in comparison with pretreatment values. RESULTS NAA/Cho levels increased and Cho/Cr levels decreased within enhancing tumor at 2 weeks relative to pretreatment levels (P = .048 and P = .016, respectively), suggesting a possible antitumor effect of bevacizumab with cytotoxic chemotherapy. Nine of the 13 patients were alive and progression free at 6 months. Analysis of receiver operating characteristic curves for NAA/Cho changes in tumor at 8 weeks revealed higher levels in patients progression free at 6 months (area under the curve = 0.85), suggesting that NAA/Cho is associated with treatment response. Similar results were observed for receiver operating characteristic curve analyses against 1-year survival. In addition, decreased Cho/Cr and increased NAA/Cr and NAA/Cho in tumor periphery at 16 weeks posttreatment were associated with both 6-month progression-free survival and 1-year survival. CONCLUSION Changes in NAA and Cho by MR spectroscopy may potentially be useful as imaging biomarkers in assessing response to anti-angiogenic treatment.