Selection of down-regulated sequences along the monocytic differentiation of leukemic HL60 cells

In order to dissect the molecular mechanisms of monocytic differentiation we have developed a subtractive hybridisation method based on a simplified 'representational difference analysis'. We have selected 16 sequences and confirmed their down-regulation along the TPA-induced monocytic differentiation of HL60 cells. Among these sequences we have identified the alpha-tubulin, the TaxREB protein and two ribosomal protein sequences which had not been previously described as differentially expressed. These results add to our knowledge about the molecules implicated along the monocytic differentiation and growth arrest of leukemic cells and provide a first step in the study of their respective roles

Direct transport between superconducting subgap states in a double quantum dot

We demonstrate direct transport between two opposing sets of Yu-Shiba-Rusinov (YSR) subgap states realized in a double quantum dot. This bound-state-to-bound-state transport relies on intrinsic quasiparticle relaxation, and the tunable gating of this quantum dot device allows us to explore also an additional relaxation mechanism based on charge transferring Andreev reflections. The transition between these two relaxation regimes is identified in the experiment as a marked gate-induced stepwise change in conductance. We present a transport calculation, including YSR bound states and multiple Andreev reflections alongside quasiparticle relaxation, due to a weak tunnel coupling to a nearby normal metal, and obtain excellent agreement with the dat

Double Nanowires for Hybrid Quantum Devices

Parallel 1D semiconductor channels connected by a superconducting strip constitute the core platform in several recent quantum device proposals that rely, for example, on Andreev processes or topological effects. In order to realize these proposals, the actual material systems must have high crystalline purity, and the coupling between the different elements should be controllable in terms of their interfaces and geometry. A strategy for synthesizing double InAs nanowires by the vapor-liquid-solid mechanism using III-V molecular beam epitaxy is presented. A superconducting layer is deposited onto nanowires without breaking the vacuum, ensuring pristine interfaces between the superconductor and the two semiconductor nanowires. The method allows for a high yield of merged as well as separate parallel nanowires with full or half-shell superconductor coatings. Their utility in complex quantum devices by electron transport measurements is demonstrated

Identification of gene polymorphisms of human DNA topoisomerase I in the National Cancer Institute panel of human tumour cell lines

Topoisomerase 1 (Top1), a nuclear enzyme involved in DNA relaxation, is the target of several anticancer drugs. TOP1 mutations occur in camptothecin-resistant tumour cell lines. We explored, in the NCI panel of 60 human tumour cell lines, whether polymorphic variations in the TOP1 gene could explain differences in drug sensitivity. The 21 exons of the gene were fully studied as well as five intronic domains that had previously been shown to harbour single nucleotide polymorphisms (SNPs) or mutations. PCR products covering the whole exonic sequences or the relevant intronic domains were subjected to denaturing high-performance liquid chromatography. Nucleotide variations were then determined by sequencing. Discrimination between intronic common and variant homozygous samples was performed using a restriction fragment length polymorphism technique. Only one exonic mutation was detected, at the heterozygous state; it occurs in exon 19 of a colon cancer cell line (HCT-15) and consists of a G>A transition at position 75, resulting in a Met675Ile change. The intronic sequences studied harboured the SNPs expected with allelic frequencies between 20 and 40%. Three major haplotypes, generating 92% of the 10 genotypes encountered, were defined as containing none of the intronic SNPs, or three of them, or all of them. No significant relationship was evidenced between Top1 expression and the TOP1 polymorphisms studied. However, when comparing the cytotoxicity of 138 drugs as a function of the genotypes, several drug groups, namely Top1 inhibitors, antifolates and taxanes, had significantly different IC50s as a function of the distribution of the intronic SNPs of the TOP1 gene

Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database

BACKGROUND: The effect of current therapies in improving the survival of lung cancer patients remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities based on informed insights. A molecular pharmacological analysis was undertaken to design an improved chemotherapeutic strategy for advanced lung cancer. METHODS: We related the cytotoxic activity of each of commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin (CDDP), and carboplatin (CBDCA)) to corresponding expression pattern in each of the cell lines using a modified NCI program. RESULTS: We performed gene expression analysis in lung cancer cell lines using cDNA filter and high-density oligonucleotide arrays. We also examined the sensitivity of these cell lines to these drugs via MTT assay. To obtain our reproducible gene-drug sensitivity correlation data, we separately analyzed two sets of lung cancer cell lines, namely 10 and 19. In our gene-drug correlation analyses, gemcitabine consistently belonged to an isolated cluster in a reproducible fashion. On the other hand, docetaxel, paclitaxel, 5-FU, SN-38, CBDCA and CDDP were gathered together into one large cluster. CONCLUSION: These results suggest that chemotherapy regimens including gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug. Gene expression-drug sensitivity correlations, as provided by the NCI program, may yield improved therapeutic options for treatment of specific tumor types