Volume 16 Issue 5, May 2010

A growing number of clinics are offering cell therapies that remain untested in rigorous clinical trials. Although the scientific community has chided the use of unproven treatments, we need less talk and more action in regulating stem cell therapies.

At the start of this year Melinda Moree officially became chief executive of the Washington, DC–based not-for-profit BIO Ventures for Global Health (BVGH). Christian Torres spoke with Moree about how BVGH engenders partnerships between biotech and global health and how it might produce the next big achievement for both.

This month marks the fiftieth anniversary of the approval of oral contraception in the US, and the Pill's age is starting to show. Problems abound with its delivery, dosage and side effects. Ellen Friedrichs investigates how researchers have conceived of new ways to deliver birth control.

The causes underlying unintended pregnancies are many and complex. But there is no doubt that the vast majority could be prevented by contraceptives that are already available and easily accessible. People just need to stick with them.

Mammalian genomes harbor regulatory elements from ancient retroviral infections. These retroviral remnants are normally silenced by DNA methylation—but this can change. Reactivation of one such element triggers the expression of a nearby oncogene during the development of Hodgkin's lymphoma (571–579).

Pain caused by chronic inflammation is a serious health problem. But the currently available analgesic drugs cause major side effects when taken long term. A new study points to a class of molecules, resolvins, which not only provide analgesia and are well tolerated but may also reduce inflammation (pages 592–597).

T lymphocytes engineered to produce T cell receptors specific for tumor antigens lead to an antitumor immune response. New findings draw attention to a potentially deadly problem with this strategy. The transgenic T cell receptors can shuffle components with native receptors to produce hybrid molecules with specificity against self antigens (pages 565–570).

Many parasites vary their surface molecules to avoid the host's immune response, thereby perpetuating long-term infections. Disrupting this process in the intestinal parasite Giardia lamblia now provides a useful tool for vaccination (pages 551–557).

Approximately 5% of people that are hospitalized for any reason develop acute kidney failure, which, in some cases, progresses to a chronic condition resulting in fibrosis of the kidney and permanent changes in the organ's function. Two new studies suggest that cell cycle arrest of epithelial cells and epigenetic modifications have key roles in the switch to chronic disease (pages 535–543 and 544–550).

Much can go wrong during the nine-month journey from single cell to birth—with infertility stopping the process as it begins and premature birth completing it before its time. These two major problems in reproductive biology are examined by Bruce D. Murphy, Yasushi Hirota, Jeeyeon Cha and Sudhansu K. Dey. In 'Bench to Bedside', Murphy analyzes studies showing how a single gene, FOXL2, may mediate many processes required for fertility. In 'Bedside to Bench', Dey and colleagues take a look at conflicting clinical findings testing progesterone as a therapy for premature birth: they conclude that much more work needs to be done at the bench, particularly in developing mouse models of parturition, before clinicians can successfully intervene to prevent birth from occurring prematurely.

Inappropriate wound healing can lead to fibrosis of an organ and interference with its proper function. Joseph Bonventre and his colleagues have found that G2/M cell cycle arrest of tubular epithelial cells in the kidney after acute injury leads to fibrosis and that targeting this arrest, or the signaling that results from this arrest, is ameliorative for disease progression (pages 523–525 and 544–550).

Wound repair involves the proper regeneration of the extracellular matrix. When this process goes awry, organ fibrosis results, damaging the organ's function. Now, Michael Zeisberg and his colleagues have uncovered an epigenetic mechanism by which kidney fibrosis occurs, as well as a potential new therapeutic target to prevent it (pages 523–525 and pages 535–543).

Giardia lamblia is a major intestinal pathogen causing acute or chronic diarrhea. It is thought to evade the immune system by switching its expression of the variant-specific surface protein (VSP), resulting in antigenic variation. Rivero et al. now report that by interfering with the machinery that restricts VSP expression, they can subvert antigenic variation and generate trophozoites that simultaneously express many VSPs and induce broadly reactive immunity against infection with various G. lamblia isolates (pages 522–523).

Innate immune responses markedly affect subsequent adaptive responses. Here the authors show that adaptive immunity in the form of memory CD4⁺ T cells can also affect the magnitude of innate inflammatory responses.

T cell receptor (TCR) gene therapy is a promising immunotherapy for cancer and infectious disease. But introducing exogenous TCR α and β chains into T cells may have unintended consequences. In this issue, Bendle et al. show that the transfer of TCR-transduced T cells into mice triggered a lethal pathology that resembles graft-versus-host disease and is caused by the pairing of endogenous and exogenous TCR chains resulting in autoreactive T cells (pages 520–521).

In this work, Björn Lamprecht et al. found that survival of Hodgkin's lymphoma cells requires activity of the growth factor receptor CSF1R. Transcription of the gene encoding CSF1R was unexpectedly discovered to originate in a specific class of long terminal repeat, a type of repetitive element present in the genome. Transcriptional initiation from this class of long terminal repeats was widely activated in Hodgkin's lymphoma cells, which the authors traced to defects in epigenetic silencing (517–518).

Chromosomal translocations involving the gene encoding MOZ, a transcriptional regulator, can result in the production of fusion proteins that promote acute myeloid leukemia. In a mouse model of acute myeloid leukemia induced by a MOZ-containing fusion protein, Yukiko Aikawa et al. now identify a potential new therapeutic target, the cytokine receptor CSF1R, which is present on leukemia stem cells and is needed for leukemia induction and progression.

A three-gene expression signature can predict long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody-associated vasculitis and systemic lupus erythematosus.

The omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid alleviate inflammatory pain in patients. Ru-Rong Ji and his colleagues find that the resolvins RvE1 and RvD1, which are derived from omega-3 fatty acids, potently reduce pain in a number of animal models of inflammatory pain. These effects are mediated by both peripheral and central mechanisms and suggest that resolvins may represent a new class of analgesics for inflammatory pain (pages 518–520).

Individuals with obsessive-compulsive disorder (OCD) perform obsessive repetitive actions. Shahin Rafii and his colleagues show that mice lacking the gene Slitrk5 show OCD-like behavioral phenotypes and have deficits in corticostriatal communication in the brain.

Most cases of esophageal cancer can be prevented if detected early at the precancerous high-grade dysplasia stage in patients presenting with Barrett's esophagus, a condition that almost always precedes this form of cancer. Here, Qiu and colleagues have developed a multispectral imaging system that uses endoscopic polarized scanning spectroscopy to perform rapid optical scanning and imaging of the entire esophageal surface, providing a diagnosis in near real time.