Targeting the hypoxia pathway in malignant plasma cells by using 17-allylamino-17-demethoxygeldanamycin.

Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions. We confirmed that 17-AAG inhibits hypoxic induction of the HIF-1 target genes in malignant plasma cells and demonstrate the concentration range of severe hypoxia-specific cytotoxicity. Next, we selected the malignant plasma cells under severe hypoxia/re-oxygenation culture conditions in the presence or absence of 17-AAG and subsequently, the cells which survived were further expanded and analyzed. Interestingly, we have noticed significant changes in the survival and the response to anti-MM drugs between the parental cell lines and those selected in cyclic severe hypoxia in the presence and absence of 17-AAG. Importantly, we also observed that the lack of oxygen itself, irrespectively of HIF-1 inhibition, is the main/pivotal factor driving the selection process in the experiments presented here.

Spanish Translation of the Anatomical Quality Assurance (AQUA) Checklist: new guidelines for reporting in original anatomical studies

Clear reporting of original studies is an integral part of evidence-based principles, which the basic sciences, including anatomy, have only recently begun to adapt to. Evidence-based anatomy (EBA), is a developing field of anatomical research which employs evidence-based methods such as meta-analyses, systematic reviews, and high-quality original studies. However, there is a lack of standardized reporting checklist within anatomical research, and the Anatomical Quality Assurance (AQUA) Checklist was developed to account for this deficit. The AQUA Checklist serves to guide authors in clear reporting of original anatomical studies and is endorsed by the Federative International Committee for Scientific Publications (FICSP). To assure high quality, comprehensive and unambiguous description of methodology and results, the checklist consists of 29 reporting items that should be addressed by authors of original anatomical studies. The AQUA Checklist has been translated into the Spanish language to remove any language barriers and to allow utilization and reproducibility of Spanish anatomical research. Conforming to the reporting items of the AQUA Checklist will help elevate the standards of future original anatomical research and raise the quality of anatomical studies published in Spanish journals

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