Articles in 2011

miR-200 family expression results in highly proliferative ovarian cancer cells. Yet this expression is also linked to longer overall survival in women with ovarian cancer. A new study sheds light into this apparent paradox showing that two members of this family—miR-141 and miR-200a—not only boost tumor growth but also sensitize tumor cells to chemotherapy (pages 1627–1635).

Chemotherapy can save the lives of many individuals with cancer. Unfortunately, it usually causes infertility after treatment, posing a concern for these people who will face a lifetime condition that considerably limits the quality of their lives. Advances in the field of oncofertility have brought hope to cancer survivors who long to plan a family; however, standard approaches only rely on cryopreservation of sperms and eggs before treatment and do not prevent infertility. In 'Bedside to Bench', Min Xu, Mary Ellen Pavone and Teresa Woodruff examine a study where individuals treated with gonadotropin-releasing hormone (GnRH) agonists before cancer therapy showed a decreased risk of infertility. How these agonists work to suppress and protect ovarian function and increase fertility in women after treatment is still unclear and begs further investigation at the bench. In 'Bench to Bedside', Amander Clark, Bart Phillips and Kyle Orwig discuss potential experimental options to preserve and restore male fertility after chemotherapy. These approaches will shed light into mechanisms of male fertility and spermatogenesis and may be the alternative to sperm freezing, which is not suitable for prepubertal boys and men unable to make sperm.

Since its launch in 2001, the Center for Global Development (CGD) has been instrumental in convening working groups and issuing reports that shape the agenda for a range of topics that affect global poverty and people of the developing world. At the helm of its global health effort is Amanda Glassman. In recognition of CGD's ten-year anniversary last month, Elie Dolgin spoke to Glassman about how the think tank turns its words into actions.

The discovery that skin cells from an adult human can be reprogrammed back to their embryonic stage and then differentiated to produce neuron-like cells in culture opens an opportunity to study disease pathogenesis and screen potential therapeutic drugs. A new study provides an example of this approach for the neuropsychiatric disorder Timothy syndrome (pages 1657–1662).

We look back on some of the key insights into biomedicine published this year.

Here we present the in-gene-ious cancer drugs, sanguine blood thinners and others of 2011 as we look back on this year's major headlines related to medications.

Scientists had long assumed that any genetic mutation that does not alter a protein sequence should have no impact on human health. But recent research has shown that such synonymous DNA changes can trigger disease in a number of ways. Alla Katsnelson talks to scientists and biotech companies who are speaking up about 'silent' mutations.

This review provides a guide to the conceptual and practical issues to consider when trying to generate an iPSc model that accurately recapitulates the features of a human genetic disease. The authors highlight recent successes in modeling genetic diseases using iPSCs and offers a perspective on the next steps that will be needed to improve current iPSC-based disease models.

New methods for analyzing ligand-receptor binding under physiologic conditions in cell-based assays and living animals are much needed for the testing and validation of candidate therapeutic agents targeting ligand-receptor binding. Here, Kathryn Luker and her colleagues developed a molecular imaging assay for ligand-receptor binding based on Gaussia luciferase complementation, focusing on chemokine CXCL12 and its chemokine receptors CXCR4 and CXCR7, although the assay could be applied more broadly to any receptor with a protein ligand.

This report uncovers a role for the mRNA binding factor CPEB4 in cancer. CEPB4 is upregulated in human pancreatic adenocarcinomas and glioblastomas, where it supports tumor growth by providing translational activation of normally silent mRNAs, including tPA, an important contributor to malignancy. The findings illustrate that altered post-transcriptional regulation of gene expression may be an important contributing factor to cancer.

The cytokine PDGF has multiple effects on the vasculature and influences tumor growth and progression. Yuan Xue et al. uncover a new role for PDGF as a regulator of hematopoiesis and provide a unifying mechanism by which PDGF induction of the cytokine erythropoietin in stromal cells underlies PDGF's effects on both hematopoiesis and the tumor vasculature.

Steven Artandi and his colleagues have found that dedifferentiation and proliferation of kidney podocytes as a result of TERT or Wnt signaling leads to a collapsing glomerulopathy phenotype in mice, similar to that seen in HIV-associated nephropathy (HIVAN) in humans, and that inhibiting these pathways corrected disease progression. They also found that TERT expression and Wnt activity is elevated in a mouse model of HIVAN and in human HIVAN renal samples, suggesting possible targets to treat this disease.

Graft-versus-host disease (GVHD) can be a life-threatening complication of bone marrow transplantation (BMT). Understanding the mechanisms causing GVHD is important to developing treatments or preventive therapies. In this issue, Koyama et al. report the surprising finding that recipient nonhematopoietic antigen-presenting cells, rather than dendritic cells, are the crucial factor in inducing CD4⁺ T cell–dependent GVHD and death in mice.