JCI early table of contents for October 1, 2012

October 01, 2012

Sphingolipid metabolism contributes to diabetes-associated heart disease

Patients with type 2 diabetes are subject to a number of major health risks, including a greatly increased risk of heart failure. This is due in part to the development of diabetic cardiomyopathy (DbCM), a condition that significantly impairs heart function. In this issue of the Journal of Clinical Investigation, Ashley Cowart and colleagues at the Medical University of South Carolina report that an increase in specific types of saturated fatty acids (SFAs) and fatty acid metabolic pathways cause lipid overload and symptoms of DbCM in mice. Mice fed a diet high in SFAs developed alterations in the walls of the heart and heartbeat that are characteristic cardiomyopathy symptoms in humans. This study reveals the underlying metabolic mechanisms of DbCM and successfully models diabetes-associated heart disease in mice without genetic manipulation.

TITLE:

Ceramide Synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomycoytes

AUTHOR CONTACT:

L. Ashley Cowart

Medical University of South Carolina, Charleston, SC, USA

Phone: 843-437-3539; E-mail: cowartl@musc.edu

View this article at: http://www.jci.org/articles/view/63888?key=c24d3456fa8201bdc62a

Altered triglyceride metabolism in mice causes non-alcoholic fatty liver disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is a condition in which triglycerides accumulate in liver cells. Individuals who develop NAFLD frequently have a mutation in a protein known as PNPLA3. In this issue of the Journal of Clinical Investigation, researchers led by Helen Hobbs at the University of Texas Southwestern Medical Center report on the contribution of this mutation to NAFLD in mice. Mice overexpressing mutant PNPLA3 did not metabolize triglycerides as well as normal mice indicating that mutation of PNPLA3 and the subsequent loss of appropriate triglyceride metabolism may underlie human NAFLD.

TITLE:

Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis

AUTHOR CONTACT:

Helen H. Hobbs

University of Texas Southwestern Medical Center, Dallas, TX, USA

Phone: 214 648 6724; Fax: 214 648 7539; E-mail: helen.hobbs@utsouthwestern.edu

View this article at: http://www.jci.org/articles/view/65179?key=96916004cc745c3dacf1

Researchers identify inflammatory mediators in pancreatic cancer

Pancreatic ductal adenocarcinoma is an aggressive cancer that feeds off inflammation in the tumor microenvironment. Current research is directed at determining how the tumor interacts with the surrounding tissue to drive inflammation and tumor growth. In this issue of the Journal of Clinical Investigation researchers led by George Miller at the New York University School of Medicine report that pancreatic cancer is driven by activation of a pro-inflammatory cell surface receptor known as TLR7. In a mouse model of pancreatic cancer, TLR7 activation accelerated tumor progression and drove the activation of oncogenic pathways. TLR7-deficient mice or mice that had been treated with a drug to block TLR7 activation had lower levels of inflammation and did not develop pancreatic cancer. These findings suggest that therapeutics targeting TLR7 may be an effective treatment for human pancreatic cancer.

TITLE:

Toll-Like Receptor 7 regulates pancreatic carcinogenesis in mice and humans

AUTHOR CONTACT:

George Miller

New York University School of Medicine, New York, NY, USA

Phone: 201-446-3608; E-mail: george.miller@med.nyu.edu

View this article at: http://www.jci.org/articles/view/63606?key=140bcf86df56061e2bb9

Putting a 'HEX' on muscle regeneration

A complex genetic regulatory network mediates the regeneration of adult skeletal muscles. In this issue of the Journal of Clinical Investigation, researchers at the State University of New York Downstate Medical Center in Brooklyn report that HEXIM1, a protein that regulates gene transcription, is important for skeletal muscle regeneration in mice. M.A.Q. Saddiqui and colleagues found that HEXIM1 blocks gene expression that is required for muscle regeneration after injury. Mice with a 50% reduction in HEXIM1 exhibited greater muscle mass and function after injury compared to mice with a normal amount of the gene. These results indicate that HEXIM1 may be a therapeutic target in degenerative muscle diseases.

TITLE:

HEXIM1 controls satellite cell expansion to regulate skeletal muscle regeneration

AUTHOR CONTACT:

M.A.Q. Siddiqui

SUNY Downstate Medical Center, Brooklyn, NY, USA

Phone: 718-270-1014; E-mail: maq.siddiqui@downstate.edu

View this article at: http://www.jci.org/articles/view/62818?key=81f201478a6fa71c020f

Untangling the cause of congenital lung disease

Alveolar Capillary Dysplasia (ACD) is a rare, lethal congenital malformation of the small blood vessels surrounding the alveoli of the lungs. Newborns with this disease develop respiratory distress and pulmonary hypertension within minutes to hours after birth. In this issue of the Journal of Clinical Investigation researchers led by Parviz Minoo at the University of Southern California report that loss of the protein Pten causes an ACD-like disease in mice. Mice pups that did not express Pten in the lung could not oxygenate their blood supply and died shortly after birth. Analysis of the lung cells showed that these mice did not develop the cells required for formation of the blood vessels that mediate gas exchange. These studies demonstrate a role for Pten in the development of alveoli-associated capillaries and suggest that Pten-mutant mice could serve as a model of human ACD.

TITLE:

Mesodermal Pten inactivation leads to alveolar capillary dysplasia-like phenotype

AUTHOR CONTACT:

Parviz Minoo

University of Southern California, Los Angeles, CA, USA

Phone: 323-226-4340; Fax: 213-236-5049; E-mail: minoo@usc.edu

View this article at: http://www.jci.org/articles/view/61334?key=6dab548111403637315b

Seeing the light: researchers track oncogenesis in the liver bile ducts

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver cancer originating in the bile ducts. Based on studies of tumor tissue, ICC was originally classified as a cancer of the cells that line the bile ducts, known as cholangiocytes; however, ICC frequently co-occurs in patients with chronic hepatitis C infections, suggesting that ICC originates in liver cells (hepatocytes). To determine how ICC begins, In this issue of the Journal of Clinical Investigation, researchers led by Atsushi Suzuki at Kyushu University in Japan studied ICC progression in a mouse with fluorescently labeled liver cells. They demonstrated that ICC can arise from hepatocytes and identified signaling pathways that were required for oncogenesis in this cell type. This study will help define the pathology of ICC and, eventually, the design of new and more effective therapies.

TITLE:

Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes

AUTHOR CONTACT:

Atsushi Suzuki

Medical Institute of Bioregulation, Kyushu University, Fukuoka, , JPN

Phone: +81-92-642-6793; E-mail: suzukicks@bioreg.kyushu-u.ac.jp

View this article at: http://www.jci.org/articles/view/63065?key=281f33976ea6d1bd57f6

ACCOMPANYING ARTICLE

TITLE:

Cholangiocarcinomas can originate from hepatocytes in mice

AUTHOR CONTACT:

Holger Willenbring

University of California San Francisco, San Francsico, CA, USA

Phone: 415 476 2417; Fax: ; E-mail: willenbringh@stemcell.ucsf.edu

View this article at: http://www.jci.org/articles/view/63212?key=dbae1e72b11c2671f0dd

In myelofibrosis, it's all about location

In myelofibrosis (MF), hematopoietic stem cells become malignant. As the HSCs begin to grow out of control, they produce immature blood cells and fibrous tissue that destroy the bone marrow. Because the blood cells made in the marrow are of poor quality, HSCs in other organs such as the liver and spleen begin making blood cells to compensate. HSC behavior is determined by intrinsic properties as well as their environment. In a study published in the Journal of Clinical Investigation, Ronald Hoffman and colleagues at the Mount Sinai School of Medicine used HSCs isolated from the spleens and peripheral blood (PB) of human MF patients to determine how location influences HSC behavior. By transplanting the MF patient HSCs into mice, Hoffman and colleagues found that splenic HSCs were able to generate red and white blood cells for a prolonged period of time and behaved similarly to the normal HSCs found in bone marrow. In contrast, HSCs isolated from PB were not able to produce the full complement of white blood cells. These results suggest that the environment in the spleen may lead to the production of a greater number of malignant blood cells and contribute to disease progression.

TITLE:

Spleens of myelofibrosis patients contain malignant hematopoietic stem cells

AUTHOR CONTACT:

Xiaoli Wang

Mount Sinai School of Medicine, New York, NY, USA

Phone: 2122412284; E-mail: xiaoli2004osaka@gmail.com

View this article at: http://www.jci.org/articles/view/64397?key=535290f9b80230c57e59
-end-


JCI Journals

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.