| 1. |
|
|
| 2. |
|
|
| 3. |
- Sclafani, F., et al.
(författare)
-
Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer : results of the EXPERT-C trial
- 2015
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 26:9, s. 1936-1941
-
Tidskriftsartikel (refereegranskat)abstract
- Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit.
|
|
| 4. |
|
|
| 5. |
- Lampis, Michael, et al.
(författare)
-
Quantum Data and Control Made Easier
- 2008
-
Ingår i: Electronic Notes in Theoretical Computer Science. - : Elsevier BV. - 1571-0661. ; 210:C, s. 85-105
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper we define nQML, a functional quantum programming language that follows the “quantum data and control” paradigm. In comparison to Altenkirch and Grattage's QML, the control constructs of nQML are simpler and can implement quantum algorithms more directly and naturally. We avoid the unnecessary complexities of a linear type system by using types that carry the address of qubits in the quantum state. We provide a denotational semantics over density matrices and unitary transformations, inspired by Selinger's semantics for QPL. Our semantics leads naturally to an interpreter for nQML, written in Haskell. We also explore the extension of nQML with polymorphic higher-order functions.
|
|
