Serine, glycine and one-carbon units: cancer metabolism in full circle

One-carbon metabolism involving the folate and methionine cycles integrates nutritional status from amino acids, glucose and vitamins, and generates diverse outputs, such as the biosynthesis of lipids, nucleotides and proteins, the maintenance of redox status and the substrates for methylation reactions. Long considered a 'housekeeping' process, this pathway has recently been shown to have additional complexity. Genetic and functional evidence suggests that hyperactivation of this pathway is a driver of oncogenesis and establishes a link to cellular epigenetic status. Given the wealth of clinically available agents that target one-carbon metabolism, these new findings could present opportunities for translation into precision cancer medicine.

Cell growth and proliferation require the construction of building blocks for new cellular components, including proteins, lipids and nucleic acids, as well the maintenance of cellular redox status, and genetic and epigenetic status. Amino acid metabolism involving serine and glycine, and the carbon units that they provide, satisfies many of these requirements. One-carbon metabolism encompasses a complex metabolic network that is based on the chemical reactions of folate compounds. These reactions proceed in a cyclical nature during which a carbon unit is transferred to other metabolic pathways and is eventually replenished by several sources. Modern cancer therapy partly arose from the hypothesis that antagonists of folates could reduce the proliferation of malignant blood cells. The antagonism of folate metabolism and its downstream effectors, such as nucleotide metabolism, has been used in chemotherapy for more than 60 years.

Read more: Serine, glycine and one-carbon units: cancer metabolism in full circle

Source: NatureReviewsCancer

Targeting Tumor Metastasis

Tumour metastasis, the movement of tumour cells from a primary site to progressively colonize distant organs, is a major contributor to the deaths of cancer patients. Therapeutic goals are the prevention of an initial metastasis in high-risk patients, shrinkage of established lesions and prevention of additional metastases in patients with limited disease. Instead of being autonomous, tumour cells engage in bidirectional interactions with metastatic microenvironments to alter antitumour immunity, the extracellular milieu, genomic stability, survival signalling, chemotherapeutic resistance and proliferative cycles. Can targeting of these interactions significantly improve patient outcomes? In this Review preclinical research, combination therapies and clinical trial designs are re-examined.

Metastases, or the consequences of their treatment, are the greatest contributors to deaths from cancer. Clinical metastatic disease results from several selective forces. Pathways that fuel initial tumorigenesis, described as the 'trunk' of a cancer evolutionary tree, can also endow tumour cells with metastatic properties and de novo drug resistance. Two types of 'limb' pathway emerge from the tree trunk: events that induce acquired resistance to therapy and pathways that induce or accelerate metastasis to distant organs1. Cancer therapy has largely concentrated on druggable targets in the trunk tumorigenesis pathways, such as receptor tyrosine kinases, and uses sequential and combination therapies to minimize drug resistance.

Read more: Targeting Tumor Metastasis

Source: NatureReviewsCancer

How to Reduce Your Risk for Cervical Cancer?

The Latest Information on Vaccines, Tests and Treatments

Find out what you can do to reduce your risk for cervical cancer and whether a diagnosis affects fertility as a top expert discusses advances in treatment…

Cervical cancer, once the leading cause of cancer deaths among U.S. women, is no longer so common. The number of cases has plunged 74% in the past four decades. And the rate of new diagnoses is still dropping 4% each year.

The dramatic turnaround is thanks to Pap smears, which can detect precancerous cells so that they can be treated and cured, according to the National Institutes of Health.

Yet doctors still can’t agree on when you should get your first Pap test, how often you should have it and whether that screening should now be replaced by a human papillomavirus (HPV) screening test. Some experts claim that the new test, recently approved by the FDA, can catch more women at risk for cervical cancer, and earlier, than the Pap smear.

Read more: How to Reduce Your Risk for Cervical Cancer?

Source: lifescript

High troponin levels may account for mental stress ischemia in cardiac patients.

Some people with heart disease experience a restriction of blood flow to the heart in response to psychological stress. Usually silent (not painful), the temporary restriction in blood flow, called ischemia, is an indicator of greater mortality risk.

Cardiologists at Emory University School of Medicine have discovered that people in this group tend to have higher levels of troponin -- a protein whose presence in the blood that is a sign of recent damage to the heart muscle-- all the time, independently of whether they are experiencing stress or chest pain at that moment.

The results are scheduled for presentation by cardiology research fellow Muhammad Hammadah, MD at the American College of Cardiology meeting in Chicago on April 3, as part of the Young Investigator Awards competition. Hammadah works with Arshed Quyyumi, MD, and Viola Vaccarino, MD, PhD, and colleagues at the Emory Clinical Cardiovascular Research Institute.

"Elevated troponin levels in patients with coronary artery disease may be a sign that they are experiencing repeated ischemic events in everyday life, with either psychological or physical triggers," Hammadah says.

Video source: High troponin levels may account for mental stress ischemia in cardiac patients.

Sourse: newsmedia.tasnimnews

New nanoparticle 'cluster bombs' could make chemotherapy less toxic.

Chemotherapy is one of the key weapons in our fight against cancer, but it comes with a whole host of unwanted side effects and damage to the surrounding, healthy areas of the body. So an international team of researchers has come up with what they think could be a much less toxic way of delivering the treatment, and it's based around 'cluster bombs' of nanoparticles.

The new procedure is designed to improve the delivery of the chemotherapy drug cisplatin. It works using tiny nanoparticles, just 100 nanometres wide, which are loaded with drugs and transported to the tumor site through blood vessels. Once they reach their destination, the acidic environment around the cancer cells causes them to break up into 5-nanometre-wide particles, which can then move inside the tumor cells.

At this point, the cisplatin can do its work from inside the tumor cells, damaging the cancerous DNA to effectively kill them off. To give you some idea of the scale, you can fit a million nanometres inside a millimetre.

In tests on lab mice, the teams from Emory University in the US and the University of Science and Technology of China found that the concentration of cisplatin that reached the tumors was seven times higher than normal. And if more of the drug is reaching its intended target, that means less of it is leaking out into the rest of the body, so unwanted side effects are reduced.

Video source: New nanoparticle 'cluster bombs' could make chemotherapy less toxic.

Source: Jovan Vitanovski/Shutterstock

HIV life cycle: How HIV infects a cell and replicates itself using reve...

HIV life cycle -- how HIV infects a cell and replicates itself using reverse transcriptase and the host's cellular machinery.

From the 2007 Holiday Lectures. AIDS -- Evolution and Epidemic.

Howard Hughes Medical Institute, HHMI's BioInteractive Animations.

Video source: http://tinyurl.com/khx39v6

Metabolic Diseases Could be Promoted by 'Unhealthy' Microbiomes.

Trillions of bacteria surround us, permeate us, and bind our bodies together. They affect our immune systems and our brains, they shift and change with our diet, and some researchers suspect that these microbial multitudes may be an important link between our modern lifestyle and ongoing epidemics of diseases such as asthma, obesity, and diabetes.

Leading microbiome researchers recently came to UC San Francisco to share the newest insights about how improving our relationship with our bodies’ microbial ecosystems could be the next big breakthrough in treating metabolic disease. One major theme of the symposium – hosted by theUniversity of California Sugar, Stress, Environment, and Weight (SSEW) Center – was the question of whether the troubling modern epidemic of metabolic disease may arise in part because our civilization has not been kind to our microbes.

“In Western industrialized nations, we have dramatically changed our interaction with microbes in last several decades,” said Susan Lynch, PhD, who studies links between the microbiome and chronic inflammatory diseases at UCSF. “Particularly in urbanized areas, we have less contact with the soil and with animals. We have changed our diets dramatically and waged war on our microbes with antibiotics.”

Read more: Metabolic Diseases Could be Promoted by 'Unhealthy' Microbiomes.

Source: ucsf.edu

Novel Blood Test Diagnoses Alzheimer's At Early Stage.

A blood test has been developed that may potentially facilitate detection of Alzheimer's disease at an early stage and it is based on an immuno-chemical analysis using an infrared sensor. 

A major problem of Alzheimer's disease (AD) diagnosis is the fact that, by the time the first clinical symptoms appear, massive irreversible damage to the brain has already occurred and at that point, symptomatic treatment is the only available option.

Scientists at the Ruhr-University Bochum (Germany) and their colleagues analyzed the secondary structure of Amyloid-beta (Aβ) peptide in cerebrospinal fluid (CSF) and blood plasma of 141 patients which was measured with an immuno-infrared-sensor. The sensor's surface is coated with highly specific antibodies which extract biomarkers for Alzheimer's from the blood or the CSF, taken from the lower part of the back. The infrared sensor analyses of the biomarkers showed pathological changes, which can take place more than 15 years before any clinical symptoms appear.

Read more: Novel Blood Test Diagnoses Alzheimer's At Early Stage.

Source: slideshare, labmedica

Anemia

Anemia is a condition characterized by an inadequate amount of red blood cells, which are produced in your bone marrow. Red blood cells contain hemoglobin, a substance that picks up oxygen from your lungs, carries it throughout your body, and gives it to your cells. Your cells need oxygen to perform the basic functions that generate energy and keep you alive. In addition, hemoglobin picks up some of the carbon dioxide given off by your cells and returns it to the lungs, where it is exhaled when you breathe out. Without enough red blood cells to transport oxygen to your cells and carbon dioxide away from your cells, your body functions at a less than optimal level.

There are many causes of anemia, which can be broadly grouped into three categories:

Blood Loss

If you are bleeding heavily, you will rapidly become anemic and may develop severe symptoms including shock. Slower leakage of blood that you are unaware of, such as bleeding from a stomach ulcer or from colon cancer , can also exceed your bone marrow’s ability to replace blood supplies, eventually resulting in anemia.

Failure to Make Enough Normal Red Blood Cells or Hemoglobin

Dietary intake of iron, folic acid, and vitamin B 12 are necessary for red blood cell formation. Deficiencies of these nutrients can impair bone marrow function, thus reducing production of adequate numbers of red blood cells. In addition, cancers, certain drugs and toxins, allergic reactions to medicines, and chronic illness can cripple the bone marrow so that it makes defective or insufficient red blood cells. Hereditary defects, such as sickle cell disease , also may lead to anemia. When the bone marrow fails completely the condition is known as aplastic anemia.

Read more: Anemia

Source: Nucleus Medical Media

Clinical Chemistry Guide to Scientific Writing

Clinical Chemistry is pleased to present the Clinical Chemistry Guide to Scientific Writing, a series of educational articles on how to design and write scientific research papers for publication. These articles will help authors, educators, researchers, training program directors, and other professionals write more clearly and effectively, thereby improving their chances for success. We encourage educators and training program directors to use them as a teaching aid, and provide a link to them on their own Web sites.

These articles are easy to read and humorous at times, yet are full of useful information and examples to illustrate important points. Because the articles will benefit anyone interested in scientific writing, we are making them available not only to subscribers, but to all scientists. Translations into Chinese and Spanish are available. We welcome your feedback and suggestions regarding aspects of the writing process about which you would like to learn more.

Read more: Clinical Chemistry Guide to Scientific Writing

Source: 123rf