Navigation Links
JCI table of contents: Aug. 16, 2007
Date:8/16/2007

EDITOR'S PICK: Can cancer drugs combine forces?

Individuals with chronic myeloid leukemia (CML) are treated first with a drug known as imatinib (Gleevec), which targets the protein known to cause the cancer (BCR-ABL). If their disease returns, because BCR-ABL mutants emerge that are resistant to the effects of imatinib, individuals are treated with a drug known as dasatinib (SPRYCEL), which targets BCR-ABL in a different way. However, patients that relapse after treatment with dasatinib, because BCR-ABL mutants emerge that are resistant to the effects of this drug, are now beginning to be seen in the clinic. Researchers from Memorial Sloan-Kettering Cancer Center, New York, now suggest that treating patients with a combination of the drugs might decrease the chance of the cancer returning, or at the very least increase the time before a relapse occurs

In the study, which appears online on August 16 in advance of publication in the September print issue of the Journal of Clinical Investigation, Charles Sawyers and colleagues show that 2 of 12 patients whose cancer had returned after treatment with dasatinib responded to retreatment with imatinib. Analysis of the BCR-ABL proteins from these patients revealed that their BCR-ABL had only the dasatinib-resistance mutation. By contrast, the BCR-ABL proteins of the other patients had either a single mutation that rendered the protein resistant to both dasatinib and imatinib or had two mutations, one rendering the protein resistant to imatinib and one rendering the protein resistant to dasatinib. A third drug that can target dasatinib- and imatinib-resitant BCR-ABL is currently in clinical trials. The authors therefore suggest that rather than treating CML patients with the drugs that target BCR-ABL sequentially, they should receive all the drugs when they are first diagnosed with the disease so that the emergence of the drug-resistant forms of BCR-ABL might be prevented, or at least delayed.

TITLE: Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency

AUTHOR CONTACT: Charles L. Sawyers Memorial Sloan-Kettering Cancer Center, New York, New York, USA. Phone: (646) 888-2138; Fax: (646) 888-2595; E-mail: sawyersc@mskcc.org.

View the PDF of this article at: https://www.the-jci.org/article.php?id=30890


EDITOR'S PICK: Specific antagonism lowers blood pressure

High blood pressure (hypertension) is associated with an increased risk of heart attack and stroke, and the frequent use of drugs known as NSAIDs, for example to treat individuals with rheumatoid arthritis, can cause hypertension. Exactly why NSAIDs cause hypertension is not clear because they inhibit the generation of several soluble factors (known as prostaglandins) that can affect blood pressure and the effects of inhibiting the individual receptors for prostaglandins are not known. In an attempt to address this issue researchers from Vanderbilt University Medical Center identified a novel potential target for the treatment of hypertension.

In the study, which appears online on August 16 in advance of publication in the September print issue of the Journal of Clinical Investigation, Matthew Breyer and colleagues show that inhibitors of the prostaglandin E2 receptor EP1 reduce hypertension in rats. Consistent with this, mice lacking EP1 were protected from the hypertensive effects of angiotensin II and EP1-specific agonists. The authors therefore suggest that targeting the PGE2 receptor EP1 might be a viable approach to treating hypertension.

TITLE: Antihypertensive effects of selective prostaglandin E2 receptor subtype 1 targeting

AUTHOR CONTACT: Matthew D. Breyer Vanderbilt University Medical Center, Nashville, Tennessee, USA. Phone: (615) 343-3764; Fax: (615) 343-4704; E-mail: breyerma@lilly.com.

Youfei Guan Peking University Health Science Center, Beijing, People's Republic of China. Phone: 86-10-8280-1447; Fax: 86-10-8280-1447; E-mail: youfeiguan@bjmu.edu.cn.

View the PDF of this article at: https://www.the-jci.org/article.php?id=29838


OPHTHALMOLOGY: Eyeing up a role for S1P2R in abnormal blood vessel formation

Many millions of individuals worldwide suffer from vision loss as a result of the formation of an abnormal network of blood vessels in the eye. This abnormal blood vessel network forms in response to damage to the retina and often occurs in individuals who are diabetic. Understanding the molecular mechanisms controlling the development of the network of blood vessels in the retina under normal and pathological conditions is therefore an area of intensive research.

In a study appearing online on August 16, in advance of publication in the September print issue of the Journal of Clinical Investigation, Timothy Hla and colleagues from the University of Connecticut School of Medicine, Farmington, show that under normal conditions, blood vessel development is indistinguishable in wild-type mice and in mice lacking a protein known as sphingosine 1–phosphate receptor 2 (S1P2R). By contrast, damage to the retina, in the form of low levels of oxygen, induces the formation of an abnormal network of blood vessels in the eyes of wild-type mice, but not in the eyes of S1P2R-deficient mice. The absence of pathological blood vessel formation in S1P2R-deficient mice was associated with decreased inflammatory cell infiltration of the retina and decreased expression of the proinflammatory enzyme cyclooxygenase-2. This demonstration that S1P2R-driven inflammation is an important event in pathological blood vessel formation in the eye led the authors to suggest that inhibiting S1P2R activation in the retina might provide a new therapeutic approach to treating diseases of the eye caused by the presence of an abnormal blood vessel network.

TITLE: Essential role of sphingosine 1–phosphate receptor 2 in pathological angiogenesis of the mouse retina

AUTHOR CONTACT: Timothy Hla University of Connecticut School of Medicine, Farmington, Connecticut, USA. Phone: (860) 679-4128; Fax: (860) 679-1201; E-mail: hla@nso2.uchc.edu.

Christopher DeFrancesco Office of Communications University of Connecticut Health Center, Farmington, Connecticut, USA. Phone: 860-679-3914; E-mail: cdefrancesco@uchc.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=31123


ONCOLOGY: A winning combination for the treatment of cancer

The immune system does not destroy tumors even though they express molecules that should activate immune cells. The immune system is therefore said to be tolerant of the tumors. Several molecules and cell types have been implicated in the induction of immune system tolerance to tumors, including, in mice, a small population of immune cells known as plasmacytoid dendritic cells (pDCs) that produce the enzyme indoleamine 2,3-dioxygenase (IDO) and that are isolated from the lymph nodes that drain the site of the tumor. Now, researchers from the Medical College of Georgia, Augusta, have identified how these mouse IDO-expressing pDCs induce tumor-specific immune tolerance.

In the study, which appears online on August 16 in advance of publication in the September print issue of the Journal of Clinical Investigation, David Munn and colleagues found that mouse IDO-expressing pDCs from tumor-draining lymph nodes directly activate the suppressive function of a population of regulatory immune cells characterized as CD4+CD25+Foxp3+ and known as Tregs. Suppression by Tregs activated by IDO-expressing pDCs was mediated by interactions between programmed cell death 1 (PD1) and its ligands. This mechanism of suppression is distinct from that used by Tregs activated by other stimuli. Importantly, immune suppression in tumor-draining lymph nodes was abrogated by treating mice with both a chemotherapeutic drug and a chemical inhibitor of IDO, but not either agent alone, leading the authors to suggest that combining IDO inhibitors with chemotherapeutic agents might improve the efficacy of chemotherapeutics in individuals with cancer.

TITLE: Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3,-dioxygenase

AUTHOR CONTACT: David H. Munn Medical College of Georgia, Augusta, Georgia, USA. Phone: (706) 721-7141; Fax: (706) 721-8732; E-mail: dmunn@mail.mcg.edu.

Toni Baker Director of Media Relations Medical College of Georgia, Augusta, Georgia, USA. Phone: 706-721-4421; E-mail: tbaker@mcg.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=31911


ONCOLOGY: How tumors prevent immune cell entry

For a number of cancers the presence of immune cells known as an NKT cells in the tumor is associated with a better prognosis. It has therefore been suggested that more aggressive tumors have developed strategies to prevent them from being infiltrated by NKT cells. A new study, which appears online on August 16 in advance of publication in the September print issue of the Journal of Clinical Investigation, shows that this is the case. The pathway used by tumors to prevent NKT cell infiltration might provide researchers with new targets for the development of new treatments for cancer.

In the study, Leonid Metelitsa and colleague from Childrens Hospital Los Angeles show in vitro that expression of a protein known as MYCN, which has been associated with many different types of cancer, by neuroblastoma cells decreases their secretion of a soluble factor (CCL2) that attracts NKT cells. Similarly, in mice, NKT cells were largely inhibited from invading neuroblastomas overexpressing MYCN. Furthermore, individuals with neuroblastomas that expressed high levels of MYCN and whose cancer had spread to the bone marrow had substantially fewer NTK cells in their bone marrow than individuals with neuroblastomas that expressed low levels of MYCN and whose cancer had spread to the bone marrow. The authors therefore suggest that enhancing NKT cell localization to the tumor should be considered when designing new cancer therapeutics.

TITLE: Oncogene MYCN regulates localization of NKT cells to the site of disease in neuroblastoma

AUTHOR CONTACT: Leonid S. Metelitsa Childrens Hospital Los Angeles, Los Angeles, California, USA. Phone: (323) 671-1839; Fax: (323) 664-9455; E-mail: lmetelitsa@chla.usc.edu.

Steve Rutledge Director of Communications Childrens Hospital Los Angeles, Los Angeles, California, USA. Phone: (323) 361-4121; E-mail: srutledge@chla.usc.edu

View the PDF of this article at: https://www.the-jci.org/article.php?id=30751


GENETICS: 1, 2, 3: third gene responsible for genetic disorder identified

Tumoral calcinosis is an inherited disorder that is characterized by the presence of lumps of calcium at inappropriate sites in the body, such as around the hip, elbow, shoulder, and knee joints. Previously, mutations in two genes (FGF23 and GALNT3) had been shown to cause this disease. Now, researchers from Indiana University School of Medicine have identified in a third gene a mutation that causes tumoral calcinosis.

In the study, which appears online on August 16 in advance of publication in the September print issue of the Journal of Clinical Investigation, Michael Econs and colleagues show that a 13 year old girl with tumoral calcinosis has a mutation in both copies of her KL gene. In vitro analysis revealed that the KL protein resulting from this mutation was expressed and secreted at lower levels than normal KL and that it was unable to help FGF23 mediate its functions. This study provides insight into why mutations in the KL gene cause tumoral calcinosis and gives clinicians a new candidate gene to consider when attempting to determine the etiology of tumoral calcinosis.

TITLE: A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis

AUTHOR CONTACT: Michael J. Econs Indiana University School of Medicine, Indianapolis, Indiana, USA. Phone: (317) 274-1339; Fax: (317) 278-0658; E-mail: mecons@iupui.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=31330


'/>"/>
Contact: Karen Honey
press_releases@the-jci.org
215-573-1850
Journal of Clinical Investigation
Source:Eurekalert

Related biology news :

1. Highly adaptable genome in gut bacterium key to intestinal health
2. Development of portable infectious disease detector
3. Scientists identify genes responsible for black rot disease in vegetables
4. Recombinant DNA technology may enable oral, rather than injectable, delivery of protein drugs
5. Aloe vera coating may prolong freshness, safety of fruits and vegetables
6. Nanotechnology to provide portable genetic risk detection
7. New study shows patients more willing to consider self-injectable HIV therapy than many physicians anticipate
8. Implantable pumps extend lives of patients too sick for transplant
9. Bioengineers create stable networks of blood vessels
10. Portable cocaine sensor developed at UC Santa Barbara
11. Researchers develop portable vein finder for faster, more accurate injections
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/2/2016)... 2016  BioMEMS devices deployed in hospitals ... medical screening and diagnostic applications, such as ... that facilitate and assure continuous monitoring without ... being bolstered through new opportunities offered by ... coupled with wireless connectivity and low power ...
(Date:2/2/2016)... 2016 Technology Enhancements Accelerate Growth of X-ray Imaging ... digital and computed radiography markets in Thailand ... Indonesia (TIM). It provides an in-depth ... well as regional market drivers and restraints. The study ... and market attractiveness, both for digital and computed radiography. ...
(Date:2/1/2016)... Canada , February 1, 2016 ... technological advancements to drive global touchfree intuitive gesture control ... --> Rising sales of consumer electronics coupled ... gesture control market size through ... consumer electronics coupled with new technological advancements to drive ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... Florida , February 11, 2016 ... and Promote Genetic Understanding to Support Research and Discovery ... GenomeAsia 100K, today announced an ambitious plan to sequence 100,000 ... South Asian countries and at least 7 of North and ... In the first phase, the project will focus on ...
(Date:2/11/2016)... Feb. 11, 2016  Bioethics International, a not-for-profit organization focused ... developed, marketed and made accessible to patients around the world, ... had named the publication of the Good Pharma Scorecard ... is also featured as one of BMJ Open ,s ... year that are most frequently read. Ed Sucksmith ...
(Date:2/11/2016)... , Feb. 11, 2016  Dovetail Genomics™ LLC today ... beta program for a planned metagenomic genome assembly service. ... company,s metagenomic genome assembly method in a talk on ... Biology & Technology conference in Orlando, Fla. ... highly complex datasets is difficult. Using its proprietary ...
(Date:2/11/2016)... ... 2016 , ... Global Stem Cells Group, a ... Stem Cells Network (GSCN) to distribute exosome injection and other biological products to ... Rica, Dominican Republic, Colombia, Argentina, Nicaragua, Panama, El Salvador, Venezuela, Peru, Ecuador, Paraguay, ...
Breaking Biology Technology: