Formation and repair kinetics of Pt-(GpG) DNA adducts in extracted circulating tumour cells and response to platinum treatment.

BACKGROUND: Pt-(GpG) intrastrand crosslinks are the major DNA adducts induced by platinum-based anticancer drugs. In the cell lines and mouse models, the persistence of these lesions correlates significantly with cell damage. Here we studied Pt-(GpG) DNA adducts in circulating tumour cells (CTC) treated with cisplatin in medium upfront to systemic therapy from patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Blood was drawn before systemic treatment and the CD45/CD15-depleted fraction of mononuclear cells was exposed to cisplatin, verified for the presence of CTC by pan-cytokeratin (pCK) staining and immunoanalysed for the level of Pt-(GpG) in DNA. RESULTS: Immunostaining for pCK, CD45 and subsequently for Pt-(GpG) adducts in the cisplatin-exposed cells (ex vivo) at different time points depicted distinct differences for adduct persistence in CTC between responders vs non-responders. CONCLUSION: Pt-(GpG) adducts can be detected in CTC from NSCLC patients and assessing their kinetics may constitute a clinically feasible biomarker for response prediction and dose individualisation of platinum-based chemotherapy. This functional pre-therapeutic test might represent a more biological approach than measuring protein factors or other molecular markers.

[Host's genetics in HIV disease]. / L'apport de la génétique de l'hôte dans la maladie VIH.

In the 1990 s, the variability of responses to human immunodeficiency virus (HIV) could only be tracked by phenotypic criteria such as the number of CD4T lymphocytes, the occurrence of opportunistic infection, the disease free survival without treatment. In 1996, the viral load is the leading phenotype for genetic studies. Ever since, thanks to a better understanding of the HIV infection pathophysiology, numerous studies helped to highlight the influence of genetic variability on inter-individual response to this virus. Among the genes having an impact, we can quote the following examples: CCR5, HLA-B and HLA-C genes. Practical applications of genetics in clinical medicine include search for HLA-B*57:01 before abacavir introduction. Recently, an eradicating treatment for HIV disease after bone marrow transplantation with a donor homozygote for a CCR5 gene non-functional variant (CCR5Δ32) has been reported. Interest in genetics of chronic viral infection is not specific to HIV. It has also been used on other viral diseases and it has gained a major place on the management of diseases.

Penta-carbonyl-2κC-chlorido-1κCl-bis-[1(η)-cyclo-penta-dien-yl][µ-oxido(phenyl)methylene-1:2κO:C]hafnium(IV)tungsten(0).

The title compound, [HfW(C(5)H(5))(2)(C(7)H(5)O)Cl(CO)(5)] or [W(CO)(5)(C(7)H(5)O){Hf(C(5)H(5))(2)Cl}], contains two metal centres, with a (tungstenpenta-carbon-yl)oxy-phenyl-carbene unit coordinated to a hafnocene chloride. The Hf-O-C angle is nearly linear, and the C=O distance is slightly shorter than for equivalent alkoxy-carbenes. One of the cyclo-penta-dienyl (Cp) rings undergoes an offset face-to-face π-π inter-action [3.495 (7) Å] with the symmetry-related Cp ring of a neighbouring mol-ecule.

Penta-carbonyl-2κC-chlorido-1κCl-bis-[1(η)-cyclo-penta-dien-yl](µ-α-oxido-benzyl-idene-1:2κO:C)titanium(IV)tungsten(0).

The title compound, [TiW(C(5)H(5))(2)(C(7)H(5)O)Cl(CO)(5)], consists of two metal centres, with a (tungstenpenta-carbon-yl)oxy-phenyl-carbene unit coordinated by a titanocene chloride. The oxycarbene group is nearly planar, with the phenyl ring twisted by an angle of 39.1 (2)° with respect to this plane. One of the cyclo-penta-dienyl rings undergoes an offset face-to-face π-π inter-action [3.544 (6) Å] with the symmetry-related cyclo-penta-dienyl ring of a neighbouring mol-ecule.