Blocking PLK-1 to beat bladder cancer
Surgical removal of part of, or the entire, bladder is commonly used to treat bladder cancer, causing loss of urinary and sexual functions. Thus, novel therapeutic approaches are needed. In a study appearing online on March 10 in advance of publication in the April 1 print edition of the Journal of Clinical Investigation, Takeshi Yuasa and colleagues from Kyoto University hospital use small interfering RNA (siRNA) technology to silence a gene that they believe to be involved in cancer progression.
The researchers have investigated the efficacy of polo like kinase-1 (PLK-1) siRNA against bladder cancer in mice. PLK-1 regulates cell division and its expression is correlated with a variety of human tumors. The authors put the siRNA into vesicles that can enter cells via their membranes to suppress the expression of PLK-1 in bladder cancer cells in a time and dose dependent fashion.
Intravesical administration of the PLK-1 inhibitor reduced cell proliferation and killed cancer cells. To validate the efficacy of the treatment in vivo, mice were implanted with bladder cancer cells, and PLK-1 siRNA prevented the growth of bladder cancer in this mouse model.
This interesting study shows that therapy to inhibit expression of PLK-1 could be an important strategy for the management of bladder cancer.
TITLE: Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer
AUTHOR CONTACT: Takeshi Yuasa
Kyoto University Hospital, Kyoto, Japan
Phone: 81-75-751-3630; Fax: 81-75-751-3631; E-mail: firstname.lastname@example.org
Preventing SCD1 expression prevents obesity
Metabolic syndrome is a clustering of certain metabolic-related heart disease risk factors including obesity, and has become one of the greatest health problems worldwide. Effective therapies to treat obesity and metabolic syndrome are urgently needed but are currently lacking. In a study appearing online on March 10 in advance of publication in the April 1 print edition of the Journal of Clinical Investigation, Bei Zhang and colleagues from Merck Research Laboratories demonstrate a new therapeutic approach to treat obesity and metabolic syndrome.
The researchers block stearoyl-CoA desaturase-1 (SCD1) – a protein that regulates the synthesis of fats in the blood – by using specific small molecules to interfere with synthesis of SCD1 in liver cells and in mice. Inhibiting SCD1 decreased body fat, and prevented obesity and development of metabolic syndrome. Blocking SCD1 also increased expression of genes involved in energy expenditure.
The results aid in our understanding of the role of SCD1 in metabolism and validate SCD1 as a potential target for pharmacological intervention for obesity and related metabolic disorders.
TITLE: Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1
AUTHOR CONTACT: Bei Zhang
Merck Research Laboratories, Rahway, NJ USA
Phone: (732) 594-1926; Fax: (732) 594-3750; E-mail: email@example.com
Thyroid cancer genes share common cellular networks
Thyroid cancer is associated with different genetic mutations. In particular, rearrangement of the RET receptor gene, and activation of Ras and B-Raf genes are common events in thyroid cancer, labeling these three as oncogenes (genes that contribute to cancer). In a study appearing online on March 10 in advance of publication in the April 1 print edition of the Journal of Clinical Investigation, Massimo Santoro and colleagues from University Federico II explored which common genes regulated by these oncogenes participate in tumor formation. The researchers demonstrate that the three oncoproteins involved in thyroid cancer activate a common signaling network in thyroid cells that stimulates cell proliferation and motility. The study provides insights into the genes relevant in thyroid tumors.
TITLE: A genetic program driven by the RET/PTC-RAS-BRAF linear signaling cascade that mediates the motile and mitogenic phenotype of thyroid cancer cells
AUTHOR CONTACT: Massimo Santoro
University Federico II, Naples, Italy
Phone: 39-081-7463056; Fax: 39-081-7463037; E-mail: firstname.lastname@example.org
MLL triggers leukemia
Infant acute leukemia is often associated with in utero events that cause chromosomal abnormalities involving the mixed-lineage leukemia (MLL) gene. However little is known regarding how these events lead to leukemia. In a study appearing online on March 10 in advance of publication in the April 1 print edition of the Journal of Clinical Investigation, Tetsuya Nosaka and colleagues from the University of Tokyo investigate how MLL induces leukemia in mice. The researchers provide direct evidence for a two-step program of leukemia by MLL, where MLL cooperates with other proteins SEPT6 and Flt3. This may contribute to the development of MLL fusion-targeted therapy.
TITLE: Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple lineage leukemogenesis
AUTHOR CONTACT: Tetsuya Nosaka
The University of Tokyo, Tokyo Japan
Phone: 81-3-5449-5399; Fax: 81-3-5449-5453; E-mail: email@example.com
Leptin swings both ways to regulate energy balance
Activity of neurons in the hypothalamus that express neuropeptides proopiomelanocortin (Pomc) or agouti-related peptide (Agrp) is controlled by insulin and also by leptin, a hormone made by fat cells that regulates feeding behavior. Leptin can reduce weight and food intake by inhibiting Agrp neurons and stimulating Pomc neurons. The alternate paradigm increases food intake and leads to obesity. In a study appearing online on March 10 in advance of publication in the April 1 print edition of the Journal of Clinical Investigation, Gregory Barsh and colleagues from Stanford University examine how leptin regulates these neurons in opposite directions. The authors monitor phosphatidylinositol 3-kinase (PI3K) activity in single hypothalamic neurons of mice. PI3K was thought to lie downstream of leptin and insulin signaling. They demonstrate that insulin and leptin can directly activate PI3K in Pomc neurons. In Agrp neurons, leptin represses PI3K while insulin maintains PI3K activation. This study advances our understanding of the mechanisms regulating critical Pomc/Agrp circuits of the hypothalamus and provides experimental support to the model that PI3K signaling is required for the actions of leptin.
TITLE: Phosphatidylinositol 3–kinase integrates the action of insulin and leptin on hypothalamic neurons
AUTHOR CONTACT: Greg Barsh
Stanford University School of Medicine, Stanford, CA USA
Phone: (650) 723-5035; E-mail: firstname.lastname@example.org
Blocking inflammation protects against HIV
Activation of the immune system can predict HIV progression in humans. African green monkeys (AGM) are the natural hosts of SIV (the simian equivalent of HIV), where infection is not pathogenic. In a study appearing online on March 10 in advance of publication in the April 1 print edition of the Journal of Clinical Investigation, Michaela Muller-Trutwin and colleagues from the Pasteur Institute, address a central question in HIV/SIV research: why don't the natural hosts of SIV exhibit disease progression despite high levels of viral replication? The researchers compare 9 AGM without disease progression to 2 macaques with progression. They show that AGM are protected from SIV-mediated disease because they have a protective down regulation of immune cell activation and upregulation of proteins called cytokines that block inflammation. This suggests that an early induction of an anti-inflammatory environment and regulatory T cells may protect against AIDS. These new insights could help in the development of novel immune intervention strategies against AIDS.
TITLE: Antiinflammatory profiles during primary SIVagm infection are associated with protection against AIDS
AUTHOR CONTACT: Michaela Muller-Trutwin
Pasteur Institute, Paris, France
Phone: 33-1-40-613969; Fax: 33-1-45-688957; E-mail: email@example.com
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
Published on PsychCentral.com. All rights reserved.
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-- John D. Rockefeller