Login with your Social Account

Cutting-edge needles promise more accuracy in medical procedures

Cutting-edge needles promise more accuracy in medical procedures

Scientists at Washington State University are creating waterjet-based, steerable needles that could give doctors more accuracy and control and reduce tissue damage in many common, non-invasive medical procedures.

John Swensen, an assistant professor in the School of Mechanical and Materials Engineering, and graduate students Mahdieh Babaiasl and Fan Yang were part of a WSU team that recently co-authored a paper on steerable needles, which was published in the 2019 International Symposium on Medical Robotics (ISMR)

“Our needles have the potential to improve treatments that you can’t reach with traditional straight needles,” Babaiasl said.

For many medical procedures, doctors would like to have bendable, steerable needles to get to their targets. In fact, in a little trick of the trade, doctors will sometimes bend their needles by hand when trying to access a tricky spot, such as when giving a nerve block for back pain. Another problematic procedure for doctors is liver biopsies. When the area to be biopsied lies under the lungs, for instance, the needle must go through the chest cavity.

Waterjet technology has been used for decades in many industries, such as mining and manufacturing.

Swensen’s team developed a technology that uses a controllable waterjet nozzle at the tip of the needle to delicately cut through tissue. After the tissue is cut by the water jet, the bendable, flexible needle can follow the tissue fracture to its destination. In their study, the researchers looked at how the waterjet-based system performed using different nozzle widths, water pressures, and with different tissue stiffness. They recently filed for a patent.

Researchers testing a waterjet-based steerable needle. Their technique could decrease time taken for procedures, in some cases reducing the time taken for procedures by more than half. In addition, the accuracy generated by this technology means the needles can cut through tissue while keeping surrounding blood vessels intact.

In addition to allowing doctors to make turns, the waterjet needles create less friction than straight needles and cause less buckling of the needle and tearing of the surrounding tissue. Check out a video of the needle in action.

In the future, a nurse or doctor sitting in another room could control the needles with something like a video game console, Swensen said.

“Such needles also reduce the need to have precise manual hand-eye coordination,” he added.

Swensen and his team are currently testing their needle technology on artificial tissue made from an elastic polymer that mimics many of the physical properties of biological tissues and will soon begin experiments on real tissue.

Materials provided by Washington State University

Cancer biologists identify new drug combo

Cancer biologists identify new drug combo

When it comes to killing cancer cells, two drugs are often better than one. Some drug combinations offer a one-two punch that kills cells more effectively, requires lower doses of each drug, and can help to prevent drug resistance.

MIT biologists have now found that by combining two existing classes of drugs, both of which target cancer cells’ ability to divide, they can dramatically boost the drugs’ killing power. This drug combination also appears to largely spare normal cells, because cancer cells divide differently than healthy cells, the researchers say. They hope a clinical trial of this combination can be started within a year or two.

“This is a combination of one class of drugs that a lot of people are already using, with another type of drug that multiple companies have been developing,” says Michael Yaffe, a David H. Koch Professor of Science and the director of the MIT Center for Precision Cancer Medicine. “I think this opens up the possibility of rapid translation of these findings in patients.”

The discovery was enabled by a new software program the researchers developed, which revealed that one of the drugs had a previously unknown mechanism of action that strongly enhances the effect of the other drug.

Yaffe, who is also a member of the Koch Institute for Integrative Cancer Research, is the senior author of the study, which appears in the July 10 issue of Cell Systems. Koch Institute research scientists Jesse Patterson and Brian Joughin are the first authors of the paper.

Unexpected synergy

Yaffe’s lab has a longstanding interest in analyzing cellular pathways that are active in cancer cells, to find how these pathways work together in signaling networks to create disease-specific vulnerabilities that can be targeted with multiple drugs. When the researchers began this study, they were looking for a drug that would amplify the effects of a type of drug known as a PLK1 inhibitor. Several PLK1 inhibitors, which interfere with cell division, have been developed, and some are now in phase 2 clinical trials.

Based on their previous work, the researchers knew that PLK1 inhibitors also produce a type of DNA and protein damage known as oxidation. They hypothesized that pairing PLK1 inhibitors with a drug that prevents cells from repairing oxidative damage could make them work even better.

To explore that possibility, the researchers tested a PLK1 inhibitor along with a drug called TH588, which blocks MTH1, an enzyme that helps cells counteract oxidative damage. This combination worked extremely well against many types of human cancer cells. In some cases, the researchers could use one-tenth of the original doses of each drug, given together, and achieve the same rates of cell death of either drug given on its own.

“It’s really striking,” Joughin says. “It’s more synergy than you generally see from a rationally designed combination.”

However, they soon realized that this synergy had nothing to do with oxidative damage. When the researchers treated cancer cells missing the gene for MTH1, which they thought was TH588’s target, they found that the drug combination still killed cancer cells at the same high rates.

“Then we were really stuck, because we had a good combination, but we didn’t know why it worked,” Yaffe says.

To solve the mystery, they developed a new software program that allowed them to identify the cellular networks most affected by the drugs. The researchers tested the drug combination in 29 different types of human cancer cells, then fed the data into the software, which compared the results to gene expression data for those cell lines. This allowed them to discover patterns of gene expression that were linked with higher or lower levels of synergy between the two drugs.

This analysis suggested that both drugs were targeting the mitotic spindle, a structure that forms when chromosomes align in the center of a cell as it prepares to divide. Experiments in the lab confirmed that this was correct. The researchers had already known that PLK1 inhibitors target the mitotic spindle, but they were surprised to see that TH588 affected the same structure.

“This combination that we found was very nonobvious,” Yaffe says. “I would never have given two drugs that both targeted the same process and expected anything better than just additive effects.”

“This is an exciting paper for two reasons,” says David Pellman, associate director for basic science at Dana-Farber/Harvard Cancer Center, who was not involved in the study. “First, Yaffe and colleagues make an important advance for the rational design of drug therapy combinations. Second, if you like scientific mysteries, this is a riveting example of molecular sleuthing. A drug that was thought to act in one way is unmasked to work through an entirely different mechanism.”

Disrupting mitosis

The researchers found that while both of the drugs they tested disrupt mitosis, they appear to do so in different ways. TH588 binds to microtubules, which form the mitotic spindle, and slows their assembly. Many similar microtubule inhibitors are already used clinically to treat cancer. The researchers showed that some of those microtubule inhibitors also synergize with PLK1 inhibitors, and they believe those would likely be more readily available for rapid use in patients than TH588, the drug they originally tested.

While the PLK1 protein is involved in multiple aspects of cell division and spindle formation, it’s not known exactly how PLK1 inhibitors interfere with the mitotic spindle to produce this synergy. Yaffe said he suspects they may block a motor protein that is necessary for chromosomes to travel along the spindle.

One potential benefit of this drug combination is that the synergistic effects appear to specifically target cancer cell division and not normal cell division. The researchers believe this could be because cancer cells are forced to rely on alternative strategies for cell division because they often have too many or too few chromosomes, a state known as aneuploidy.

“Based on the work we have done, we propose that this drug combination targets something fundamentally different about the way cancer cells divide, such as altered cell division checkpoints, chromosome number and structure, or other structural differences in cancer cells,” Patterson says.

The researchers are now working on identifying biomarkers that could help them to predict which patients would respond best to this drug combination. They are also trying to determine the exact function of PLK1 that is responsible for this synergy, in hopes of finding additional drugs that would block that interaction.

Materials provided by Massachusetts Institute of Technology

Situs Inversus Totalis

Bizarre case study reveals man with his body organs on the wrong side

A medical emergency room with the patient turned into a tale of an unexpected tale in the case of a 66-year-old man who turned up at the hospital with coughs and chest pains. Only for the doctors to realize that the internal organs of the patients were on the wrong side of the body like the heart was on the right, liver on the left, etc. The report was published in the New England Journal of Medicine.

This condition is named as Situs inversus totalis and it is not life changing as it sounds. This was discovered due to modern medical scanning tools and many people had lived their lives without any diagnosis. The doctors have said that the patient was migrated to the United States after being in a refugee camp for 20 years. The findings as shown by the chest radiograph were dextrocardia in which the heart is situated on the right rather than on the left and a mirror image transposition for the abdominal organs. The symptoms of the man included chest pain, congestion and coughing and a little pain on the left of the abdomen as seen on the medical reports.

This case is very rare but not unheard. Donny Osmond is a well-known case of Situs Inversus Totalis where all internal organs are flipped like a mirror image and this common type affects close to 1 in 10,000 people. Such people are generally seen wearing a bracelet that declares and signals the doctor of this disorder in case of an emergency surgery where the doctor might mistakenly open the wrong part of the body. The heart is the part where most of the complication occurs in the case of Situs Inversus and dextrocardia in which the key important arteries can end up lying in parallel rather than crisscrossing which makes the heart surgery and transplants very difficult to operate.

The name of this abnormality was coined by Matthew Baillie in 1788 which is “location” and “opposite” in Latin and this terminology is continued by doctors and scientists even today. One recent case was reported of Rose Marie Bentley who lived up to the age of 99 years and no one knew about this abnormal condition until her death report came. Her heart was on the correct side of the body which makes Situs Inversus much more dangerous.

Situs Inversus is often dismissed as an X-ray error after the reports when the baby is born and is the reason why people aren’t diagnosed until many years later.

Pseudomonas aeruginosa SEM

Scientists turn bacteria as an instrument for measuring fluid speeds

A group of researchers from Princeton University has detected bacteria which has the ability to find the speed of fluids in motion. There are many different types of cells which can sense flow similar to the skin cells in human beings. The research has been published in Nature journal.

Zemer Gitai, a biology professor and a senior author on the research paper of Princeton’s Edwin Grant Conklin University said that they have discovered that bacteria can also be used for detecting speed and also added that there’s an application where we can use the bacteria as a flow sensor and we can know the speed in real time. Pseudomonas aeruginosa is that bacteria which have a built-in speedometer.

Pseudomonas is the bacteria which is responsible for health issues and healthcare-related infections per year and this ubiquitous pathogen is found in and on the bodies, in the soil, in the streams of water and throughout the hospitals. This bacteria was found as a serious threat in the centre for disease control and prevention.

Gitai said that chemical disinfection is used instead of scrubbing in some hospitals since pseudomonas loves to grow in pipes. Pseudomonas is said to be surrounded by flowing fluids like the bloodstream, the urinary tract, the gastrointestinal tract as well as in the lungs or in plumbing systems or in medical equipment too like catheters which is one of the primary vectors used for post-surgical infections. Gitai also added that they have found something new about pseudomonas that they can also detect the flow and respond to it and they can change their attitude too.

A postdoctoral research associate in Gitai’s lab, Joseph Sanfilippo and a 2017 graduate alumnus Alexander Lorestani are the main authors on this paper. They together found out that the bacteria can detect the nearby flow of the genes too and those genes are known as fro which stands for flow-regulated operon. Sanfilippo said that fro is tuned as per the speed and it’s not just a switch to on and off but it’s more like a dimmer switch than a light switch.

The researchers created a link between the fro and gene so that they can see in the microscope and thus ended up creating visual speedometer and it is visualized using the light of the flow that is the brighter the glow the faster the flow and Gitai said that they found out something interesting that the speed range matched with the fluids present in the bloodstream of urinary tract.

The scientists found out that the rate of flow in average sized human veins are about 100 per second and they also found that the fro was not able to detect flows below 8 per second but it responded to the flow between 40 and 400 per-second and stay above that.