Tag: cancer

Categories : CancerTags :

Iron is a ‘Double-edged Sword’ For Cancer Cells

On By ModernMedia

A grant by the American Cancer society will be used to investigate the treatment of certain neuroblastoma by forcing them to overloading on iron.

Neuroblastoma is a cancer that forms in nerve tissue, and most commonly in the glands around the kidneys. It is the most frequently occurring childhood cancer that occurs outside the cranium. MYCN is overexpressed in 20-25% of neuroblastoma, and these cancers contribute to a considerable portion of paediatric cancer-related deaths. Recent research has shown that the MYCN gene introduces a weakness to ferroptosis-inducing drugs because MYCN draws on a lot of iron to help the cancer grow.  

“Iron is a double-edged sword in a cancer cell. It can help the cancer grow and survive, but it also creates these toxic molecules within the cell called reactive oxygen species,” explained Anthony Faber, PhD.

Reactive oxygen species (ROS) are unstable molecules that react with other molecules, causing DNA damage and cell death. This recently discovered form of cell death, largely influenced by iron accumulation, is called ferroptosis. Little is known about ferroptosis, and even less about cancers which may be vulnerable to ferroptosis-inducing drugs. By boosting cellular toxin removal systems, MYCN produces so much iron that it also creates a vulnerability to drugs which prevent cells from eliminating ROS. Blocking these toxin removal systems causes death among MYCN-amplified cells. 

“As MYCN continues to be one of the most important targets in cancer therapeutics, this study highlights a new and clinically important strategy for treating MYCN-associated cancers,” Dr Faber said.

“Fortunately, the Cancer Mouse Models Core run by Jennifer Koblinski, PhD, and Bin Hu, PhD, at Massey is spectacular and will allow us to robustly test these FDA-approved drugs in both patient-derived models and orthotopic models, where the tumors grow atop the adrenal glands similar to the way they grow in patients,” Dr Faber said.

If these models show positive results for the testing of these drugs, they can move on to clinical trials. He added that this study may have far reaching implications, as in certain small cell lung cancers and triple negative breast cancer, whose growth is driven c-MYC, a similar protein .

Source: Medical Xpress

Journal information: Konstantinos V. Floros et al, MYCN-amplified neuroblastoma is addicted to iron and vulnerable to inhibition of the system Xc-/glutathione axis, Cancer Research (2021). DOI: 10.1158/0008-5472.CAN-20-1641

Categories : CancerTags :

Osmium in Cancer Cells May Be a Useful Weapon

On By ModernMedia

Using powerful X-ray beams to probe inside a cancer cell, researchers have determined that osmium could be a viable element for new cancer drugs.

About half of all chemotherapy drugs use platinum, but this has platinum which reacts in the nucleus, possibly leading to undesirable side effects. Osmium is a rare metal which could replace platinum in chemotherapy drugs, but first researchers needed to know where the osmium would wind up. To determine this, the researchers used the Diamond synchrotron to precisely track osmium in human lung cancer cells with a precision of 100 nanometres.

The researchers revealed the functioning of osmium in the cells using synchrotron X-ray Fluorescence (XRF) imaging. This enabled the researchers to observe the osmium in a single lung cancer cell. However, since osmium’s reactivity is determined by its ligand coating, these were labelled with bromine.

Once in the cell, the researchers observed that the osmium stayed in the cytoplasm, while the ligands penetrated into the nucleus, suggesting a twin attack on the cell.

Professor Peter Sadler, from the Department of Chemistry at the University of Warwick explained the use of osmium and their research process: “Osmium is a rare precious metal, however, since it can act as a catalyst, a very little amount is needed for reactions in the cancer cell, therefore it could be a sustainable treatment going forward. We wanted to see how exactly it worked in a single cancer cell, which involved a variety of novel techniques, including taking water molecules out of the cell and rapidly flash-freezing it. Whereas usually cells are chemically altered to see the reactions, in our method they are close to their natural state, making our results more authentic.”

It was hard work, as Dr Elizabeth Bolitho, from the Department of Chemistry and Diamond explained: “We worked 24 hours a day, 5 days a week to collect these exciting data, allowing us to see inside cancer cells to a nanoscale resolution. This has provided crucial insights into potential cellular targets of such Osmium catalysts.

“Not only were we able to track the osmium in a lung cancer cell, but more widely in breast cancer, ovarian and prostate cancer cells, for example, which provides hope that in the future osmium could be used to treat a range of different cancer.”

Source: News-Medical.Net

Journal information: Bolitho, E. M., et al. (2021) Tracking Reactions of Asymmetric Organo‐Osmium Transfer Hydrogenation Catalysts in Cancer Cells. Angewandte Chemie. doi.org/10.1002/anie.202016456.

Categories : Cancer Diet and NutritionTags :

Decreasing Cancer Deaths with Population-wide Vitamin D

On By ModernMedia

Supplementation Scientists have estimated that supplementing the over-50 population in Germany with sufficient vitamin D would save 30 000 lives which would otherwise be lost to cancer, gaining some 300 000 extra years of life, all while reducing healthcare costs.

Vitamin D is created in the body through the interaction of UV-B radiation with dehydrocholesterol, which is produced in the skin, into vitamin D3 (cholecalciferol). In many countries, populations have chronically low vitamin D levels due to more time being spent indoors. Vitamin D supplementation is associated with the prevention and treatment of nutritional rickets and osteomalacia, but it is important for other aspects of health such as prevention of respiratory tract infections and asthma. In countries such as Germany, low sunlight levels for much of the year combined with more time spent indoors results in much of the population having inadequate vitamin D levels. 

Three large meta-analyses had indicated that mortality due to cancer is reduced by 13% with vitamin D supplementation.

“In many countries around the world, the age-adjusted rate of cancer mortality has fortunately declined over the past decade,” said Hermann Brenner, epidemiologist at the German Cancer Research Centre (DKFZ).  However, given the often considerable costs of many new cancer drugs, this success has often come at a high price. Vitamin D, on the other hand, is comparatively inexpensive in the usual daily doses.”

To get their figures, the scientists used a daily administration of 1000 international units of vitamin D, costing 25 Euros per person per year. Since about 36 million people over the age of 50 live in Germany, this results in an annual cost of 900 million Euros.

The researchers calculated the number of years lost to cancer death, and also did not account for testing of vitamin D levels, as the proposed 1000 international units were far short of an overdose danger. The study estimated that if the entire German population over the age 50 were given sufficient supplements to achieve the recommended levels of vitamin D, 30 000 cancers deaths annually would be prevented.

“In view of the potentially significant positive effects on cancer mortality – additionally combined with a possible cost-saving – we should look for new ways to reduce the widespread vitamin D deficiency in the elderly population in Germany. In some countries, foods have even been enriched with vitamin D for many years – for example, in Finland, where cancer mortality rates are about 20 percent lower than in Germany. Not to mention that there is mounting evidence of other positive health effects of adequate vitamin D supply, such as in lung disease mortality rates,” said Brenner, adding, “Finally, we consider vitamin D supplementation so safe that we even recommend it for newborn babies to develop healthy bones.”

Spending about 12 minutes two to three times a week in the sun, with face, hands and parts of the arms and legs all uncovered and without sunscreen is sufficient to provide enough vitamin D.

Source: News-Medical.Net

Journal information: Niedermaier, T., et al. (2021) Vitamin D supplementation to the older adult population in Germany has the cost‐saving potential of preventing almost 30,000 cancer deaths per year. Molecular Oncology. doi.org/10.1002/1878-0261.12924.

Categories : CancerTags :

Tumour Weakened against Radiation by Tweaking a Certain Protein

On By ModernMedia

The vulnerability of specific tissues to ionising radiation has been linked to the time-varying levels of a tumour-suppressing protein, opening new avenues for cancer combination therapy.

The ability for cells to survive radiation damage has been known to be connected to p53, but tissues with vastly different levels of p53 have been shown to have great differences in sensitivity. In the face of this apparent paradox, researchers from Blavatnik Institute at Harvard Medical School, Massachusetts General Hospital, and the Novartis Institutes for BioMedical Research investigated the behaviour of p53 in irradiated tissues.

“Dynamics matter. How things change over time matters,” said co-corresponding author Galit Lahav, the Novartis Professor of Systems Biology at HMS. “Our ability to understand biology is limited when we only look at snapshots. By seeing how things evolve temporally, we gain much richer information that can be critical for dissecting diseases and creating new therapies.”

Ionising radiation randomly damages a cell’s molecular machinery, causing it to initiate cell death if it is too serious. The arbitrator of cellular suicide is p53, which is also involved in tumour suppression. 

The findings opened new avenues for combination cancer therapies, as they discovered that administering a drug that blocks p53 levels from oscillating resulted in tumours in mice being more susceptible to radiation. 
Administering to the mice an experimental anti-cancer drug that inhibits MDM2, a protein which degrades p53, they forced p53 to stay elevated. The large intestine, which is normally radiation resistant, showed increased vulnerability.

Testing out this enhanced vulnerability on human tumours transplanted into mice, a significant tumour shrinkage was seen following radiation and then MDM2 inhibitor administration.

Co-corresponding author Galit Lahav, Novartis Professor of Systems Biology, Harvard Medical School explained: “By irradiating first, we force the cancer cells to activate p53, and by adding MDM2 inhibitor on top of that, we can keep p53 active longer. This combination has a much stronger effect than either alone.”

The findings showed the importance of understanding the role of p53 in cancer, the dynamic nature of which is not being looked at in studies testing MDM2. More research into the biological pathways of p53 is called for. 
“For a lab studying p53, cancer is always a major motivation. Our goal is to acquire knowledge to help develop better and more efficient therapies,” Lahav said. “Understanding how p53 behaves over time in different conditions is a critical piece of the puzzle.”

Source: News-Medical.Net

Journal information: Stewart-Ornstein, J., et al. (2021) p53 dynamics vary between tissues and are linked with radiation sensitivity. Nature Communications.doi.org/10.1038/s41467-021-21145-z

Categories : Cancer Immune SystemTags :

Immune Cells in Prostate Tumours Boost Survival with Immunotherapy

On By ModernMedia

A new Northwestern Medicine study discovered the reason why black men are more likely to survive prostate cancer when given immunotherapy. 

Black men die more often from prostate cancer, yet are more likely to respond to immunotherapy. The increased presence of a type of immune cell in the tumours of black men appears to be related to their increased odds of survival with immunotherapy. The findings will be published on February 10 in Nature Communications.

A research team by Dr Edward Schaeffer, chair of urology at Northwestern University Feinberg School of Medicine and Northwestern Medicine, found that men who survive prostate cancer with immunotherapy have been found to have more plasma cells. Plasma cells are a type of specially differentiated B cell, which secrete antibodies and play a key role in the adaptive immune response.

“If a man’s prostate cancer has numerous plasma cells, we found he had improved cancer survival,” Schaeffer said. “Our study suggests plasma cells are important in the body’s response to cancer.”

Recent studies have shown that black men with advanced prostate cancer have on average better response to immunotherapy than white men. However, there has been no way to determine which individuals would have a better response, regardless of race.

Schaeffer’s team went through the genomics of 1300 tumour samples classified to genetic ancestry or self-identified race, and found more plasma cells in the tumours of black men than those of white men. However, the finding was not unique to black men alone, as elevated plasma cells in all men raised the odds of cancer-free survival after surgery.

“The finding comes at a time as researchers are discovering plasma cells may play a greater role in cancer immunotherapy than previously thought,” said first author Dr. Adam Weiner, a Northwestern Medicine urology resident. “Testing for plasma cells in prostate cancer may help identify men who will benefit from immune-based treatments.”

Source: Medical Xpress

Categories : Cancer GeneticsTags :

RNA Knockout Halts the Spread of Triple-negative Breast Cancer

On By ModernMedia

The University of Westminster has released a new study showing that taking out small chunks of human DNA called microRNA can reverse the spread of triple negative breast cancer cells.

The study also suggested that microRNAs could be targeted to spot and treat triple negative breast cancer. Breast cancer is the most common cancer in women, and triple negative breast cancer makes up 10-20% of cases.

MicroRNAs (miRs) have important roles in cellular functioning and signalling, and are heavily involved in the growth and metastasis of cancers. The researchers found that miR-21, a major breast cancer-related RNA, is increased in triple negative breast cancer and is also associated with metastasis.

Using CRISPR/Cas9, the researchers knocked out miR-21 from the cancer cells, and discovered that the cancer cells’ metastatic properties were reversed. They also observed that they released smaller vesicles, which release lipid blobs that play an important part in cancer spread. There was also less miR-21 carried in the vesicles, which also carry disease-related molecules to other cells.

Lead researcher Dr Pinar Uysal-Onganer of the University of Westminster, said: “This is an important study which contributes to better understanding of roles of miRs in aggressive cancer types such as triple negative breast cancer. We are now aiming to clarify the relationships between miR-21 and cancer drug resistance, which is another important factor that limits cancer cure.”

Source: Medical Xpress

Journal information: Elif Damla Arisan et al. MiR-21 is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells, International Journal of Molecular Sciences (2021). DOI: 10.3390/ijms22041557

Categories : CancerTags :

New Ultrasonic Tumour Therapy

On By ModernMedia

A new technique has been developed that uses ultrasound to vapourise encased nano-droplets, at the tumour site. This technology could be used to image the tumour, damage it or even deliver chemotherapy drugs with precision.

Existing applications of ultrasound therapy include thermal excitation of tissues, for example to dilate blood vessels, and creating cavitation to break up kidney stones. Ultrasonic toothbrushes have also been shown to remove dental plaque with better efficiency than conventional toothbrushes, and about the same as that of mechanical electrical toothbrushes. Micrometre-sized droplets, encased in a stabilising shell, can already be visualised with ultrasound, but these are too large to enter tumours. Nanometre-sized droplets can do so, however.

Vapourisation is tricky to control in reality, since the process requires a point of nucleation. The researchers demonstrated an efficient way to achieve vapourisation: by applying a frequency at the exact resonant frequency of the droplet, the pressure inside suddenly drops and the liquid vapourises. This is much the same principle as shattering a crystal glass by bombarding it with sound at its resonant frequency.

The researchers used hydrofluorocarbons,  which have a very low boiling point,   for the droplets. The resonance of the droplet being six times higher makes vapourisation much easier. The speed of sound of the droplet fluid being lower than the speed of sound in the bodily fluids surrounding it.
This resonant droplet vapourisation technology has a number of possible medical applications. The bubbles from the bursting droplets could be used to physically damage the tumour. Or, the droplets could contain chemotherapy drugs and made to break open precisely inside the tumour and reducing exposure of the rest of the body.

Source: News-Medical.Net

Journal information: Lajoinie, G. et al. (2021) High-Frequency Acoustic Droplet Vaporization is Initiated by Resonance’ by Guillaume Lajoinie, Tim Segers, and Michel Versluis. Physical Review Letters. doi.org/10.1103/PhysRevLett.126.034501.

Categories : Cancer GeneticsTags :

New Method to Pick up Mutations Behind Colorectal Cancer Risks

On By ModernMedia

University of Michigan researchers have developed a method to detect mutations which give rise to colorectal cancer.

Colorectal cancer is the third most common cancer type, and the second most common cause of cancer-related deaths in the United States. Although most cases occur sporadically, some 5 to 10% of cases are hereditary, the most common cause of which is Lynch syndrome. Lynch syndrome results in an 80% increase in the lifetime risk of developing colorectal cancer. Those with a family history of colorectal cancer are advised to start screening before age 45. However, genetic testing for cancer risk does not always provide useful information for those with family history.  

To address this, a new method of genetic testing was developed by Jacob Kitzman, PhD, of the Department of Human Genetics at Michigan Medicine plus together with other colleagues. Since mutations are rare in the human population, determining which one is responsible is difficult, and simply studying one in the lab is too time consuming to be practical.
With deep mutational scanning, the researchers measured the effect of MSH2 mutations, which is one major cause of Lynch syndrome

They deleted the normal copy of MSH2 from human cells with CRISPR-Cas, replacing it with a library of every possible mutation in the MSH2 gene. Each cell in the mix then carried a unique MSH2 mutation. Chemotherapy then killed off only the cells that had a functional variant of MSH2.

The counterintuitive idea, noted Kitzman, is that the surviving cells do not have functioning MSH2—which have mutations that are most likely to cause disease.

“We were basically trying to sit down and make the mutations we could so they could serve as a reference for ones that are newly seen or are amongst the thousands of variants of unknown significance identified in people from clinical testing,” says Kitzman. “Until now, geneticists could not be sure whether these are benign or pathogenic.”

It is hoped that with other patient-specific information, some of these variants could be reclassified, and those individuals advised to undergo more intense screening.

Kitzman said: “One of the next areas that will need some focus in the field of human genetics is to create these sorts of maps for many different genes where there is a clinical connection, so we can be more predictive when variants are found in an individual.”

Source: Medical Xpress

Journal information: Xiaoyan Jia et al, Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk, The American Journal of Human Genetics (2020). DOI: 10.1016/j.ajhg.2020.12.003

Categories : Cancer Diet and NutritionTags :

Breast Cancer in Mice Inhibited by Restricted Feeding Times

On By ModernMedia

Restricting calorie intake to an eight-hour window coinciding with physical activity reduced breast cancer risk in female mouse models.

Researchers from University of California San Diego School of Medicine, Moores Cancer Center and Veterans Affairs San Diego Healthcare System (VASDSH) found that the restricted feeding times, which are kind of circadian rhythm-linked intermittent fasting, enhanced metabolic health and tumour circadian rhythms in female mice with obesity-driven postmenopausal breast cancer. Breast cancer is the second most common cancer in US women, after skin cancer.

“Previous research has shown that obesity increases the risk of a variety of cancers by negatively affecting how the body reacts to insulin levels and changing circadian rhythms,” explained senior author Nicholas Webster, PhD. professor at UC San Diego School of Medicine and senior research career scientist at VASDSH. “We were able to increase insulin sensitivity, reduce hyperinsulinemia, restore circadian rhythms and reduce tumor growth by simply modifying when and for how long mice had access to food.”

Female mouse models mimicking postmenopausal hormone conditions were used to investigate if time-restricted feeding of obese mice affected the tumour growth and development, and reduced metastasis to the lungs. The mice were split into three groups, one with constant access to food, one with access for eight hours at night when they have the greatest activity, and the last was fed an unrestricted low-fat diet.

Obesity and menopause disrupt the circadian rhythm, with increased risk of insulin resistance and thereby chronic diseases such as cancer. A number of cancers are known to be associated with insulin resistance, such as breast cancer and pancreatic cancer. High insulin levels in obese mice drive tumour growth. Artificially increasing insulin levels has been shown to accelerate tumour growth whilst lowering them is similar to the effect of limiting eating.
Manasi Das, PhD, postdoctoral fellow in the Webster lab and first author, said: “Time-restricted eating has a positive effect on metabolic health and does not trigger the hunger and irritability that is associated with long-term fasting or calorie restriction. Through its beneficial metabolic effects, time-restricted eating may also provide an inexpensive, easy to adopt, but effective strategy to prevent and inhibit breast cancer without requiring a change in diet or physical activity.”

Webster believes that time-restricting eating warrants further investigations as it may present a way to reduce breast cancer risk, or that of cancer in general.

“The increase in risk of breast cancer is particularly high in women who are overweight and have been through menopause. For this reason, doctors may advise women to adopt weight loss strategies to prevent tumor growth,” said Das. “Our data suggests that a person may benefit from simply timing their meals differently to prevent breast cancer rather than changing what they eat.”

Source: Medical Xpress

Journal information: Manasi Das et al. Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models, Nature Communications (2021). DOI: 10.1038/s41467-020-20743-7

Categories : Ageing CancerTags :

Aspirin Protects against Colorectal Cancer

On By ModernMedia

Aspirin is known to reduce the risk of colorectal cancer in middle-aged adults and up until age 70, but has some risky side effects, such as colorectal bleeding. 

It was not known at what stage it was still worth it to start taking aspirin. Indeed, the recent Aspirin in Reducing Events in the Elderly (ASPREE) trial reported that participants taking a daily dose of aspirin (100mg) after the age of 70 for five years had a 30% increased risk of cancer mortality.
It is also currently recommended by the US Preventive Services Task Force that people aged 50-59 years with specific cardiovascular risk profiles take aspirin for its protective effect against heart disease.

To answer the question of whether aspirin was beneficial or harmful after age 70, Andrew T Chan MD, MPH, a gastroenterologist and chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital (MGH), led a team of researchers that analysed a pair of large cohort studies.These were The Nurses’ Health Study (January 1980 – June 2014) and the Health Professionals Follow-up Study (January 1986 – January 2014), giving them a total of 94 500 participants over 35 years.

Their findings showed that aspirin could indeed protect adults over 70 from colorectal cancer – with the caveat that the protection only applied if they started taking aspirin before the age of 70.”There is considerable evidence that aspirin can prevent colorectal cancer in adults between 50 and 70 years old,” commented Chan. “But it has not been clear whether the effect is similar in older adults.”

The researchers concluded that their results “strongly suggest that there is a potential biological difference in the effect of aspirin at older ages which requires further research.”

Source: News-Medical.Net