Response of vertebral fractures to treatment with denosumab in a patient with postpartum osteoporosis: a case report and literature review.

Postpartum osteoporosis (PO) is a rare condition characterized by low bone mineral density (BMD) and an increased risk of vertebral fragility fracture. We encountered a 34-year-old woman who developed back pain 1 week after delivery. Magnetic resonance imaging of the lumbar spine revealed three vertebral compression fractures. Pretreatment BMD evaluation by dual-energy X-ray absorptiometry revealed a low T-score and Z-score (-2.0 and -2.0, respectively; BMD, 0.876 g/cm2) in the affected region of the spine. The patient was diagnosed with PO and treated with subcutaneous injection of denosumab 60 mg (Prolia; Amgen, Inc., Thousand Oaks, CA, USA) every 6 months. After two treatments, the BMD had significantly increased and the back pain was improved; the patient therefore decided to terminate the treatment. Two months later, her back pain worsened and BMD decreased as measured by dual-energy X-ray absorptiometry examination of the lumbar spine. Therefore, the patient resumed treatment with denosumab, and the BMD of the lumbar spine increased after another two treatments. Therefore, we consider denosumab to be promising in the management of PO with respect to increased BMD and decreased pain.

Carbon ion radiotherapy for synchronous choroidal melanoma and lung cancer: A case report.

BACKGROUND: Despite being the most common intraocular malignancy among adults, choroidal melanoma is a rare cancer type, even more so when accompanied by lung cancer. We report a patient with synchronous choroid melanoma and lung cancer treated with carbon ion radiotherapy (CIRT). CASE SUMMARY: A 41-year-old woman was transferred to our center with a diagnosis of choroidal melanoma in her right eye. During the examination, we found a right lung tumor that was histologically diagnosed as lung cancer. The patient was treated with CIRT for both malignant neoplasms. The CIRT dose was 70 photon equivalent doses (GyE) in five fractions for the right eye choroidal melanoma and 72 GyE in 16 fractions for the right lung cancer. At 3 mo after CIRT, the choroidal melanoma completely disappeared, as did the right lung cancer 7 mo after; the patient was in complete remission. CONCLUSION: CIRT may be an effective treatment for double primary lung cancer and choroid melanoma.

Eliciting gastric cancer survivors' preferences for follow-up services: a discrete choice experiment protocol.

INTRODUCTION: Follow-up care is important for gastric cancer survivors, but follow-up strategies for gastric cancer survivors remain inconsistent, and compliance of gastric cancer survivors with follow-up care is very low. Understanding the needs and preferences of gastric cancer survivors is conducive to developing appropriate and acceptable follow-up strategies, thereby improving patient compliance. Discrete choice experiments can quantify individual needs and preferences. However, to date, there is no discrete choice experiment on the preferences of gastric cancer survivors, and no studies have examined how gastric cancer survivors make choices based on different characteristics of follow-up. This paper outlines an ongoing discrete choice experiment that aims to (1) explore follow-up service-related characteristics that may affect gastric cancer survivors' choices about their follow-up, (2) elicit how gastric cancer survivors consider the trade-offs among different follow-up service options using discrete choice experiment, (3) determine whether gastric cancer survivors' needs and preferences for follow-up vary due to the economy, politics, technology and culture in different regions. METHODS AND ANALYSIS: Six attributes were developed through a literature review, semistructured interviews and experts and focus group discussions. A fractional factorial design was used to evaluate the interaction between attributes. A multiple logit model will be used to understand the trade-off between the follow-up characteristics of gastric cancer survivors. A mixed logit model will be used to explore the willingness to pay and uptake rate of gastric cancer survivors for follow-up attributes and further explore the preferences of different groups. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of the School of Nursing, Jilin University. The results of this study will be shared through online blogs, policy briefs, seminars and peer-reviewed journal articles and will be used to modify the current strategy of gastric cancer survivors' follow-up services according to economic development and regional culture.

Genistein exerts anti-leukemic effects on genetically different acute myeloid leukemia cell lines by inhibiting protein synthesis and cell proliferation while inducing apoptosis - molecular insights from an iTRAQ™ quantitative proteomics study.

Acute myeloid leukemia (AML) is a form of cancer that affects the hematopoietic precursor cells with lethal effects. We investigated the prospect of using genistein as an effective alternate therapy for AML. A two-cell line model, one possessing the FLT3 gene with the ITD mutation (MV4-11) and the other with the wildtype FLT3 gene (HL-60) has been employed. Our 8-plexed iTRAQ™-based quantitative proteomics analysis together with various functional studies demonstrated that genistein exerts anti-leukemic effects on both the AML cell lines. Genistein treatment on the AML cells showed that the drug arrested the mTOR pathway leading to down-regulation of protein synthesis. Additionally, genistein treatment is found to induce cell death via apoptosis. Contrasting regulatory effects of genistein on the cell cycle of the two cell lines were also identified, with the induction of G2/M phase arrest in HL-60 cells but not in MV4-11 cells. Hence, our study highlights the potent anti-leukemic effect of genistein on AML cells irrespective of their genetic status. This suggests the potential use of genistein as an effective general drug therapy for AML patients.

Global identification of DELLA target genes during Arabidopsis flower development.

Gibberellin (GA) plays important roles in regulating many aspects of plant development. GA derepresses its signaling pathway by promoting the degradation of DELLA proteins, a family of nuclear growth repressors. Although the floral organ identity is established in flowers of the GA-deficient mutant ga1-3, the growth of all floral organs is severely retarded. In particular, abortive anther development in ga1-3 results in male sterility. Genetic analysis has revealed that various combinations of null mutants of DELLA proteins could gradually rescue floral organ defects in ga1-3 and that RGA is the most important DELLA protein involved in floral organ development. To elucidate the early molecular events controlled by RGA during flower development, we performed whole-genome microarray analysis to identify genes in response to the steroid-inducible activation of RGA in ga1-3 rgl2 rga 35S:RGA-GR. Although DELLA proteins were suggested as transcriptional repressors, similar numbers of genes were down-regulated or up-regulated by RGA during floral organ development. More than one-third of RGA down-regulated genes were specifically or predominantly expressed in stamens. A significant number of RGA-regulated genes are involved in phytohormone signaling or stress response. Further expression analysis through activation of RGA by steroid induction combined with cycloheximide identified eight genes as immediate targets of RGA. In situ hybridization and transgenic studies further showed that the expression pattern and function of several selected genes were consistent with the predictions from microarray analysis. These results suggest that DELLA regulation of floral organ development is modulated by multiple phytohormones and stress signaling pathways.

Direct interaction of AGL24 and SOC1 integrates flowering signals in Arabidopsis.

During the transition from vegetative to reproductive growth, the shoot meristem of flowering plants acquires the inflorescence identity to generate flowers rather than vegetative tissues. An important regulator that promotes the inflorescence identity in Arabidopsis is AGAMOUS-LIKE 24 (AGL24), a MADS-box transcription factor. Using a functional estradiol-inducible system in combination with microarray analysis, we identified AGL24-induced genes, including SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1), a floral pathway integrator. Chromatin immunoprecipitation (ChIP) analysis of a functional AGL24-6HA-tagged line revealed in vivo binding of AGL24-6HA to the regulatory region of SOC1. Mutagenesis of the AGL24 binding site in the SOC1 promoter decreased Pro(SOC1):GUS expression and compromised SOC1 function in promoting flowering. Our results show that SOC1 is one of the direct targets of AGL24, and that SOC1 expression is upregulated by AGL24 at the shoot apex at the floral transitional stage. ChIP assay using a functional SOC1-9myc-tagged line and promoter mutagenesis analysis also revealed in vivo binding of SOC1-9myc to the regulatory regions of AGL24 and upregulation of AGL24 at the shoot apex by SOC1. Furthermore, we found that as in other flowering genetic pathways, the effect of gibberellins on flowering under short-day conditions was mediated by the interaction between AGL24 and SOC1. These observations suggest that during floral transition, a positive-feedback loop conferred by direct transcriptional regulation between AGL24 and SOC1 at the shoot apex integrates flowering signals.

Synergistic antileukemia effect of genistein and chemotherapy in mouse xenograft model and potential mechanism through MAPK signaling.

We investigated the antiproliferative effect of genistein, and its antileukemia effect in combination with cytosine arabinoside (ara-C) in acute myeloid leukemia (AML). Optimal dosage of genistein as single agent and in combination with ara-C was first determined in vitro. Genistein demonstrated a dose- and time-dependent inhibition of cell proliferation, induction of apoptosis, and cell-cycle arrest at G(2)/M phase. Gene-expression profiles revealed mitogen-activated protein kinase (MAPK) signaling as one of the most affected biological pathways. Phosphatidylinositol 3 kinase, protein kinase A, protein kinase C, MAPK kinase 4, KIT, PIM1, and transforming growth factor-beta receptor 1, were significantly downregulated by genistein. To test whether genistein could augment the antiproliferation activity of ara-C, two groups of severe combined immunodeficient mice were inoculated with NB4 and HL-60 cells, respectively, followed by treatment with either genistein or combination of genistein and ara-C. The combination treatment significantly inhibited tumor growth, and improved survival of NB4 (p = 0.0031) and HL-60 (p = 0.0007) xenograft mice. Our present study highlighted the schedule-dependent synergistic antileukemia effect of genistein with chemotherapy in both in vitro and in vivo models. This novel combination could potentially be a promising regimen for treatment of AML.

MicroRNA: biological and computational perspective.

MicroRNAs (miRNAs) are endogenously expressed non-coding RNAs of 20-24 nucleotides, which post-transcriptionally regulate gene expression in plants and animals. Recently it has been recognized that miRNAs comprise one of the abundant gene families in multicellular species, and their regulatory functions in various biological processes are widely spread. There has been a surge in the research activities in this field in the past few years. From the very beginning, computational methods have been utilized as indispensable tools, and many discoveries have been obtained through combination of experimental and computational approaches. In this review, both biological and computational aspects of miRNA will be discussed. A brief history of the discovery of miRNA and discussion of microarray applications in miRNA research are also included.