Molecular diagnosis of endometrial cancer from uterine aspirates.

Rapid and reliable diagnosis of endometrial cancer (EC) in uterine aspirates is highly desirable. Current sensitivity and failure rate of histological diagnosis limit the success of this method and subsequent hysteroscopy is often necessary. Using quantitative reverse transcriptase-polymerase chain reaction on RNA from uterine aspirates samples, we measured the expression level of 20 previously identified genes involved in EC pathology, created five algorithms based on combinations of five genes and evaluated their ability to diagnose EC. The algorithms were tested in a prospective, double-blind, multicenter study. We enlisted 514 patients who presented with abnormal uterine bleeding. EC was diagnosed in 60 of the 514 patients (12%). Molecular analysis was performed on the remnants of aspirates and results were compared to the final histological diagnoses obtained through biopsies acquired by aspiration or guided by hysteroscopy, or from the specimens resected by hysterectomy. Algorithm 5 was the best performing molecular diagnostic classifier in the case-control and validation study. The molecular test had a sensitivity of 81%, specificity of 96%, positive predictive value (PPV) of 75% and negative predictive value (NPV) of 97%. A combination of the molecular and histological diagnosis had a sensitivity of 91%, specificity of 97%, PPV of 79% and NPV of 99% and the cases that could be diagnosed on uterine aspirate rose from 76 to 93% when combined with the molecular test. Incorporation of the molecular diagnosis increases the reliability of a negative diagnosis, reduces the need for hysteroscopies and helps to identify additional cases.

Biomaterials for bone regeneration.

OBJECTIVE: This article reviews the literature on biomaterials used for bone regeneration. MATERIAL AND METHOD: A total of seventeen bibliographic sources were found using the MEDLINE database and to avoid the variability of the search terms the thesaurus Mesh was used. RESULTS: These materials act essentially due to their osteoconductive ability, although their osteoinductive capacity is being improved with the use of growth factors. As to their effectiveness, many differences exist between them and some even affect bone regeneration negatively. CONCLUSIONS: Biomaterials used for bone regeneration are valid when the correct material is used. As yet the osteogenic capacity of autogenous bone has not been equalled by biomaterials. Tissue engineering has caused great interest because of its many possibilities, although more studies are necessary in order to achieve the ambitious expectations when it comes to tissue or organ regeneration in the human body.

Retraction: Evaluation of periimplant bone neoformation using different scanning electron microscope methods for measuring BIC. A dog study.

In relation to the article of the Journal of Clinical and Experimental Dentistry "Calvo-Guirado JL, Aguilar-Salvatierra A, Guardia J, Delgado-Ruiz R, Ramírez-Fernández MP, Pérez-Sánchez C, Gómez-Moreno G. Evaluation of periimplant bone neoformation using different scanning electron microscope methods for measuring BIC. A dog study. J Clin Exp Dent. 2012 Feb 1;4(1):e8-e13", the authors have used three figures that are the same as those published in three different publications (J Pineal Res 2010; COIR 2010; COIR 2012). The copyright of the mentioned publications was consequently not respected. Retraction of the article is therefore decided.

MMP-9 affects gene expression in chronic lymphocytic leukemia revealing CD99 as an MMP-9 target and a novel partner in malignant cell migration/arrest.

We previously showed that MMP-9 contributes to CLL pathology by regulating cell survival and migration and that, when present at high levels, MMP-9 induces cell arrest. To further explore the latter function, we studied whether MMP-9 influences the gene-expression profile in CLL. Microarray analyses rendered 131 differentially expressed genes in MEC-1 cells stably transfected with MMP-9 (MMP-9-cells) versus cells transfected with empty vector (Mock-cells). Ten out of twelve selected genes were also differentially expressed in MEC-1 cells expressing the catalytically inactive MMP-9MutE mutant (MMP-9MutE-cells). Incubation of primary CLL cells with MMP-9 or MMP-9MutE also regulated gene and protein expression, including CD99, CD226, CD52, and CD274. Because CD99 is involved in leukocyte transendothelial migration, we selected CD99 for functional and mechanistic studies. The link between MMP-9 and CD99 was reinforced with MMP-9 gene silencing studies, which resulted in CD99 upregulation. CD99 gene silencing significantly reduced CLL cell adhesion, chemotaxis and transendothelial migration, while CD99 overexpression increased cell migration. Mechanistic analyses indicated that MMP-9 downregulated CD99 via binding to α4ß1 integrin and subsequent inactivation of the Sp1 transcription factor. This MMP-9-induced mechanism is active in CLL lymphoid tissues, since CD99 expression and Sp1 phosphorylation was lower in bone marrow-derived CLL cells than in their peripheral blood counterparts. Our study establishes a new gene regulatory function for MMP-9 in CLL. It also identifies CD99 as an MMP-9 target and a novel contributor to CLL cell adhesion, migration and arrest. CD99 thus constitutes a new therapeutic target in CLL, complementary to MMP-9.

DmFoxF, a novel Drosophila fork head factor expressed in visceral mesoderm.

DmFoxF is a novel Drosophila fork head domain factor, which is expressed in the visceral mesoderm of the embryo. Our data suggest that DmFoxF is the fly orthologue of the vertebrates FOXF1 and FOXF2 transcription factors. DmFoxF shares homology with FOXF1 and FOXF2 in its fork head domain, and it is able to specifically bind DNA sequences recognized by these vertebrate fork head factors. In stage 10-11 embryos, the DmFoxF protein is detected into the nuclei of cells of the presumptive visceral mesoderm. It localizes at the segmental cell clusters of the mesoderm, which will eventually develop to surround the midgut endoderm. DmFoxF is also expressed in the proctodeal mesoderm, which will develop into the visceral mesoderm of the hindgut.

Evaluation of periimplant bone neoformation using different scanning electron microscope methods for measuring BIC. A dog study.

OBJECTIVES: [corrected] The aim of this study was to determine which of three methods for measuring BIC (bone-to-implant contact), using vestibular and lingual scanning electron microscopy (SEM) for different implant systems at 15, 30 and 90 days post-surgery was the most precise. An elemental analysis with SEM was used to evaluate neoformed bone composition for three implant systems at the same study times. MATERIAL AND METHODS: 36 implants were placed in eighteen Beagle dogs mandible about one year old and weighing approximately 12-13 kg in order to evaluate bone apposition to three different implant surfaces. It was used the third and fourth premolar and first molar distal sockets in both quadrants of the mandible (3P3, 4P4 and 1M1). Teeth were hemi-sected and the distal roots were removed. The specimens were prepared for histological examination and each section surface was stained using Masson's trichrome and hematoxylin and eosin stains. BIC evaluations were performed by the three methods, BIC I (the quantity of mineralized bone in direct contact with the implant's titanium surface across the entire threaded area); BIC II (along a line that passes from apex to apex of the implant threads); BIC III (both in areas around and above the threads and in between threads). RESULTS: Both BIC and bone content were analyzed for all implants placed in P3, P4 y M1 alveoli on both, the buccal and palatine sides (elemental analysis quantified Ca, P, O and C). It was seen it was only at the ninety-day mark that high percentages of calcium were present. CONCLUSIONS: This study suggest that BIC III evaluation is the most certain method for establishing the quantity of bone formed as the BIC area. Key words:Bone-to-impant contact, dogs, extraction socket, implants.

Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis.

Rho GTPases control cytoskeletal dynamics through cytoplasmic effectors and regulate transcriptional activation through myocardin-related transcription factors (MRTFs), which are co-activators for serum response factor (SRF). We used RNA interference to investigate the contribution of the MRTF-SRF pathway to cytoskeletal dynamics in MDA-MB-231 breast carcinoma and B16F2 melanoma cells, in which basal MRTF-SRF activity is Rho-dependent. Depletion of MRTFs or SRF reduced cell adhesion, spreading, invasion and motility in culture, without affecting proliferation or inducing apoptosis. MRTF-depleted tumour cell xenografts showed reduced cell motility but proliferated normally. Tumour cells depleted of MRTF or SRF failed to colonize the lung from the bloodstream, being unable to persist after their arrival in the lung. Only a few genes show MRTF-dependent expression in both cell lines. Two of these, MYH9 (NMHCIIa) and MYL9 (MLC2), are also required for invasion and lung colonization. Conversely, expression of activated MAL/MRTF-A increases lung colonization by poorly metastatic B16F0 cells. Actin-based cell behaviour and experimental metastasis thus require Rho-dependent nuclear signalling through the MRTF-SRF network.

Biomaterials for bone regeneration

Objective: This article reviews the literature on biomaterials used for bone regeneration.Material and method: A total of seventeen bibliographic sources were found using the MEDLINE database and toavoid the variability of the search terms the thesaurus Mesh was used.Results: These materials act essentially due to their osteoconductive ability, although their osteoinductive capacityis being improved with the use of growth factors. As to their effectiveness, many differences exist between themand some even affect bone regeneration negatively.Conclusions: Biomaterials used for bone regeneration are valid when the correct material is used. As yet the osteogeniccapacity of autogenous bone has not been equalled by biomaterials. Tissue engineering has caused greatinterest because of its many possibilities, although more studies are necessary in order to achieve the ambitiousexpectations when it comes to tissue or organ regeneration in the human body (AU)

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