Tag: ATP

Categories : CancerTags :

Suffocating Cancer Cells to Quash Metastasis

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Lung cancer cells metastasising. Source: National Cancer Institute on Unsplash

Researchers have eliminated cells derived from untreatable metastatic cancer by disrupting the cellular components that are responsible for converting oxygen into chemical energy. The results are published in the Journal of the American Chemical Society.

Treatment of cancer is a a long battle because surviving cancer cells often evolve into aggressive, untreatable forms. Hence, treatment plans often involve multiple drug combinations and/or radiation therapy in order to prevent cancer relapse. To combat the variety of cancer cell types, modern drugs have been developed to target specific biochemical processes that are unique within each cell type.

However, cancer cells are highly adaptive and able to develop mechanisms to avoid the effects of the treatment. “We want to prevent such adaptation by invading the main pillar of cellular life – how cells breathe – that means take up oxygen – and thus produce chemical energy for growth,” explained David Ng, group leader at the Max Planck Institute for Polymer Research (MPI-P).

The research team produced a synthetic drug that travels into cells where it reacts to conditions found inside and triggers a chemical process. This allows the drug’s molecules to bind together and form tiny hairs that are a thousand times thinner than human hair. “These hairs are fluorescent, so you can look at them directly with a microscope as they form,” said first author Zhixuan Zhou, an Alexander von Humboldt fellow.

The scientists monitored the oxygen consumption in different cell types and found that these tiny hairs prevent all of them from converting oxygen into the energy deliver molecule ATP. The process worked even for those cells derived from untreatable metastatic cancer, with the cells dying off within four hours. After some more years of research, the scientists hope that they can develop a new method to treat up-to-now untreatable cancer.

Weil, Ng and colleagues have shown an exciting outcome under controlled laboratory culture and will continue to unravel deeper insights on the basis of how these tiny hairs prevent the conversion of oxygen to chemical energy. With further development, these objects could in the future possibly also be manipulated to control other cellular processes to address other important diseases.

Source: Max Planck Institute for Polymer Research

Categories : Lab Tests and ImagingTags :

New Biosensor Rapidly Measures ATP and Lactate in Blood Samples

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The prototype of the ATP and lactate sensor developed in the study (left); and the integrated sensor chip that detects ATP and lactate levels (right). Credit: Akihiko Ishida, Hokkaido University

Scientists at Hokkaido University have developed a prototype sensor that could help doctors rapidly measures levels of adenosine triphosphate (ATP) and lactate in blood samples from patients, aiding in the rapid assessment of the severity of conditions such as sepsis.

The scientists detailed their prototype biosensor in the journal Biosensors and Bioelectronics.

ATP is a molecule found in every living cell that stores and carries energy. In red blood cells, ATP is produced by a biochemical pathway called the Embden–Meyerhof pathway. Severe illnesses such as multiple organ failure, sepsis and influenza reduce the amounts of ATP produced by red blood cells.

As such, the severity of these illnesses could be gauged by monitoring the amounts of ATP and lactates in a patient’s blood. “In 2013, our co-authors at Tokushima University proposed the ATP-lactate energy risk score (A-LES) for measuring ATP and lactate blood levels to assess acute influenza severity in patients,” explained Akihiko Ishida, an applied chemist at Hokkaido University. “However, current methods to measure these levels and other approaches for measuring disease severity can be cumbersome, lengthy or not sensitive enough. We wanted to develop a rapid, sensitive test to help doctors better triage their patients.”

The researchers developed a biosensor that can detect levels of ATP and lactate in blood with great high sensitivity in as little as five minutes. The process is straightforward. Chemicals are added to a blood sample to extract ATP from red blood cells. Enzymes and substrates are then added to convert ATP and lactate to the same product that can be detected by specially modified electrodes on a sensor chip; the amount of by-product present in the sample increases the electrical current measured.

Schematic representation of the proposed sensor for sequentially detecting ATP and lactate levels in the blood. Through a series of chemical reactions, ATP and lactate are converted to hydrogen peroxide, the breakdown of which to water H2O causes the sensor chip to generate a signal that is detected by the sensor.

The team conducted parallel tests and found that other components present in blood, such as ascorbic acid, pyruvic acid, adenosine diphosphate (ADP), urate and potassium ions, don’t interfere with the ability of the electrodes to accurately detect ATP and lactate. They also compared their sensor with those currently available and found it allowed for the relatively simple and rapid measurement of the two molecules.

“We hope our sensor will enable disease severity monitoring and serve as a tool for diagnosing and treating patients admitted to intensive care units,” said Ishida.

The researchers plan to further simplify the measurement process by integrating an ATP extraction method into the chip itself, as well as reducing the size of the sensor system.

Source: Hokkaido University