Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes

ABCB6, a member of the adenosine triphosphate–binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria

Exclusion of ABCB8 and ABCB10 as cancer candidate genes in acute myeloid leukemia.

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Sequential therapy with bevacizumab and EGFR inhibitors for metastatic colorectal carcinoma: a national registry-based analysis

Tomas Buchler,1 Renata Chloupkova,2 Alexandr Poprach,3 Ondrej Fiala,4,5 Igor Kiss,3 Katerina Kopeckova,6 Ladislav Dusek,2 Veronika Veskrnova,1 Lubomir Slavicek,7 Milan Kohoutek,8 Jindrich Finek,4 Marek Svoboda,3 Lubos Petruzelka,9 Bohuslav Melichar10 1Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, 140 59 Prague, Czech Republic; 2Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic; 3Department of Comprehensive Cancer Care and Faculty of Medicine, Masaryk Memorial Cancer Institute and Masaryk University, Brno 656 53, Czech Republic; 4Department of Oncology, University Hospital, 304 60 Pilsen, Czech Republic; 5Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic; 6Department of Oncology, Motol University Hospital and Second Faculty of Medicine, Charles University, 150 00 Prague, Czech Republic; 7Department of Oncology, Jihlava Hospital Comprehensive Cancer Centre, Jihlava, Czech Republic; 8Department of Oncology, T Bata Hospital and Comprehensive Cancer Centre, Zlin, Czech Republic; 9Department of Oncology, General University Hospital and Charles University First Faculty of Medicine, 128 08 Prague, Czech Republic; 10Department of Oncology, Palacky University Medical School and Teaching Hospital, 775 20 Olomouc, Czech Republic Purpose: Although inhibitors of vascular endothelial growth factor and inhibitors of epidermal growth factor receptor (EGFRi) are commonly used for the treatment of metastatic colorectal cancer (mCRC), the optimal sequencing of these agents is currently unclear. Methods: A national registry of targeted therapies was used to analyze baseline ­characteristics and outcomes of patients with mCRC and wild-type KRAS exon 2 status who received ­bevacizumab and EGFRi (cetuximab or panitumumab) as a part of first- and second-line ­treatment in either sequence. Results: The cohort included 490 patients (181 patients treated with first-line EGFRi and second-line bevacizumab and 309 patients treated with first-line bevacizumab and second-line EGFRi). Median overall survival (OS) from the initiation on first-line therapy was similar for patients treated with either sequence, reaching 31.8 (95% CI 27.5–36.1) vs 31.4 months (95% CI 27.8–35.0) for EGFRi → bevacizumab vs bevacizumab → EGFRi cohort, respectively. Time from first-line initiation to progression on the second-line therapy [progression-free survival (PFS)] was 21.1 (95% CI 19.3–23.0) vs 19.3 months (95% CI 17.3–21.3) for bevacizumab → EGFRi vs EGFRi → bevacizumab cohort, respectively (P=0.016). Conclusion: This retrospective analysis of real-world data of patients with wild-type KRAS exon 2 mCRC showed no differences in OS between cohorts treated with bevacizumab → EGFRi vs the reverse sequence while combined PFS favored the bevacizumab → EGFRi sequence. Keywords: colorectal carcinoma, bevacizumab, panitumumab, cetuximab, sequenc

Equal Numbers, Equal Chances? A Case Study of Gender Differences in the Distribution of Social Capital in Smallholder Farmer Groups in B�zi District, Mozambique

Despite the potential for local groups to contribute to rural development, it remains questionable whether social capital – as the ‘missing link’ in development – is compatible with the idea of gender equity strived for in ‘gender mainstreamed’ development projects. This paper examines engendered differences in smallholder farmer groups in Búzi district, and how social capital is generated and distributed. Although men and women equally invest in groups, in terms of participation in group activities or contribution of communal work, the benefits of social capital are significantly unequally distributed. Women find it harder to transform the number of social relations into improved information, access to markets or help in case of need.Malgré le potentiel des groupes locaux pour contribuer au développement rural, il n'est pas certain que le capital social, en tant que chaînon manquant du développement, soit compatible avec le principe d'équité de genre recherchée par les projets de développement sensibles à la question du genre. Cet article examine les différences générées par des groupes de petits exploitants agricoles dans le district de Búzi et comment le capital social est créé et distribué. Alors qu'hommes et femmes investissent de façon équivalente, en termes de participation aux activités des groupes ou de contribution au travail communautaire, les bénéfices du capital social sont distribués de façon sensiblement inégale. Les femmes ont plus de difficultés à transformer les relations sociales en un meilleur accès à l'information, aux marchés ou en aide en cas de besoin.European Journal of Development Research (2009) 21, 264–282. doi:10.1057/ejdr.2008.20