Day: March 2, 2022

Categories : CancerTags :

Statins Could Slow Metastases, Study Finds

On By ModernMedia
Melanoma cells. Source: National Cancer Institute.

By screening various drugs to inhibit a cancer-driving gene, researchers have hit upon a familiar drug – statins.

Cancer patients rarely die from the primary tumour, but rather from the metastases – even after successful tumour surgery. This is because cancer cells sometimes metastasise when the tumour is still very small and may not have even been discovered yet. To do this, they must break away from the extracellular matrix and migrate into neighbouring lymphatic vessels or blood vessels that transport them to new tissue, where they settle and proliferate.

Understanding the molecular mechanisms of metastasis is therefore a key piece of the puzzle in the fight against cancer. More than a decade ago, Professor Ulrike Stein and her lab discovered an important driver of this process in human colorectal cancer: the metastasis-associated in colon cancer 1 (MACC1) gene.

When cancer cells express MACC1, their ability to proliferate, move around the body, and invade other tissues is enhanced. “Many types of cancers spread only in patients with high MACC1 expression,” Prof Stein explained. MACC1’s role as a key factor and biomarker of tumour growth and metastasis – in many solid tumours beside colorectal cancer – has since been studied by many other researchers worldwide and confirmed in more than 300 publications. Now together with Dr Robert Preißner of Charité, Stein has discovered what could disrupt metastatic progression in such cases: statins, normally prescribed for lowering cholesterol, can inhibit MACC1 expression in tumour cells. The scientists are presenting their findings in the journal Clinical and Translational Medicine.

In their search for MACC1 inhibitors, the researchers conducted high-throughput drug screening, and independently arrived at statins. Tests on various tumour cell lines were favourable: All seven drugs tested reduced MACC1 expression in the cells, but to varying degrees. The scientists then administered the cholesterol inhibitors to genetically modified mice with increased MACC1 expression. This almost completely suppressed the formation of tumours and metastases in the animals. “What is particularly remarkable is that the benefits continued in the animals even after we reduced the animal dose to a human equivalent dose,” Stein said.

Dr Preißner and collaborators also examined data from a total of 300 000 patients who had been prescribed statins. This analysis found a correlation: “Patients taking statins had only half the incidence of cancer compared to the general population,” Preißner explains.

Prof Stein warned against taking statins as a preventive measure without consulting a doctor and having their lipid levels checked.

“We are still at the very beginning,” Dr Stein cautioned. “Cell lines and mice are not human beings, so we cannot directly transfer the results.” The experimental studies and retrospective data analysis will now be followed up by a clinical trial, she said. Only after that will it be possible to say with certainty whether statins actually prevent or reduce metastasis in patients with high MACC1 expression.

Source: Max Delbrück Center for Molecular Medicine

Categories : PaediatricsTags :

Invasive Mechanical Ventilation in PICU has Lasting Neurocognitive Impacts

On By ModernMedia
Photo by Margaret Weir on Unsplash

Children in paediatric ICUs (PICUs) that undergo invasive mechanical ventilation for acute respiratory failure are left with lasting neurocognitive effects, according to a study published in JAMA.

Little is known about whether children undergoing invasive mechanical ventilation worse long-term neurocognitive function than children who do not undergo such procedures. There are concerns about neurotoxic effects of critical illness and its treatment on the developing brain. Therefore, infants and young children may be uniquely susceptible to adverse neurocognitive outcomes after invasive mechanical ventilation.

Researchers conducted a four-year sibling-matched cohort study conducted at 31 PICUs and associated neuropsychology testing centres. Children who survived PICU hospitalisation for respiratory failure and were discharged without severe cognitive dysfunction were found to have significantly lower subsequent IQ scores than their matched siblings.

“While the difference in IQ scores between patients and unexposed siblings was small, the data provide strong evidence of the existence and epidemiology of paediatric post-intensive care syndrome (PICS-p) after a single typical episode of acute respiratory failure necessitating invasive ventilation among generally healthy children,” said Martha A.Q. Curley, PhD, RN, FAAN, Professor of Nursing at the University of Pennsylvania School of Nursing (Penn Nursing) and the study’s lead researcher.

The study reaffirms the importance of assessing long-term outcomes as part of any trial evaluating acute interventions in pediatric critical care. It also underscores the importance of further study to understand which children may be at highest risk, what modifiable factors could cause it, and how it can be prevented.

Source: University of Pennsylvania

Categories : CancerTags :

Study Suggests Caution when Prescribing Metformin for Cancer Cases

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Source: National Cancer Institute on Unsplash

By making computer simulations of drugs, researchers have found that doctors need to be wary of prescribing metformin for all types of cancer and patients. Their findings are published in BioMed Central Cancer.

The diabetes drug metformin has been used in clinical settings as a cancer treatment in recent years. The researchers say while metformin shows great promise, it also has negative consequences for some types of cancers.

“Metformin is a wonder drug, and we are just beginning to understand all its possible benefits,” said Mehrshad Sadria, a PhD candidate in applied mathematics at the University of Waterloo. “Doctors need to examine the value of the drug on a case-by-case basis, because for some cancers and some patient profiles, it may actually have the opposite of the intended effect by protecting tumour cells against stress.”

The computer-simulated treatments use models that replicate both the drug and the cancerous cells in a virtual environment. Such models can give clinical trials in humans a considerable head-start and can provide insights to medical practitioners that would take much longer to be discovered in the field.

“In clinical settings, drugs can sometimes be prescribed in a trial and error manner,” said Anita Layton, professor of applied mathematics and Canada 150 Research Chair in mathematical biology and medicine at Waterloo. “Our mathematical models help accelerate clinical trials and remove some of the guesswork. What we see with this drug is that it can do a lot of good but needs more study.”

The researchers say their work shows the importance of precision medicine when considering the use of metformin for cancer and other diseases. Precision medicine is an approach that assumes each patient requires individualised medical assessment and treatment.

“Diseases and treatments are complicated,” Sadria said. “Everything about the patient matters, and even small differences can have a big impact on the effect of a drug, such as age, gender, genetic and epigenetic profiles. All these things are important and can affect a patient’s drug outcome. In addition, no one drug works for everyone, so doctors need to take a close look at each patient when considering treatments like metformin.”

Source: EurekAlert!

Categories : AgeingTags :

Factors that Affect Disability after Surgery in Older Adults

On By ModernMedia
old man walking with canes
Source: Miika Luotio on Unsplash

In an analysis of older adults who underwent surgery, published in the Journal of the American Geriatrics Society, more who had non-elective surgery were found to experience disabilities than those who had elective surgery, and factors such as age increased this vulnerability.

The study included 247 adults aged 70 years or older who were discharged from the hospital after major surgery from 1997 to 2017, patients who had non-elective surgery had more disabilities in daily activities over the following 6 months than those who had elective surgery.  

Researchers identified 10 factors that were associated with greater disability burden: age 85 years or older, female sex, Black race or Hispanic ethnicity, neighbourhood disadvantage, multimorbidity, frailty, one or more disabilities, low functional self-efficacy, smoking, and obesity. The burden of disability increased with each additional “vulnerability” factor.

“The results from this study can be used by clinicians to identify older adults who are particularly susceptible to poor functional outcomes after major surgery, and a subset of the factors identified could serve as the basis for new interventions to improve functional outcomes in vulnerable older surgical patients,” said lead author Thomas M. Gill, MD, of the Yale School of Medicine.

Source: Wiley

Categories : CancerTags :

Report Shows a Long Road Ahead for Cancer Treatment in South Africa

On By ModernMedia
Source: National Cancer Institute

In their recently released Middle East and Africa regional report on cancer, the Swedish Institute for Health Economics (IHE) highlighted challenges for the country’s under-resourced healthcare system. It also highlighted the need to provide training for South African GPs in early detection of cancer.

Cancer is a growing challenge for South Africa. The incidence of cancer cases in South Africa is predicted to double over the next two decades, from 110 per 100 000 in 2018 to 226 per 100 000 in 2040. It is also gradually becoming one of the leading causes of death, from 9% in 2000 to 10% in 2016, even as the share of deaths from cardiovascular diseases and diabetes grows as well. Prostate cancer is the most common (31%) in men by far, while in women breast cancer (27%) was closely followed by cervical cancer (22%).

The COVID pandemic has largely overshadowed the Department of Health’s 207-2022 cancer plan, though successes with HIV have allowed it to move up in priority. A major challenge will be getting it moved up in priority.

The direct costs to the healthcare system from cancer are USD11 (R165) per capita and USD19 (R285) per capita in indirect costs to society (premature death, early retirement, sick leave etc). Yet South Africa’s public healthcare spending is only 4% of GDP, below the World Health Organization informal target of 5%.

In terms of prevention, anti-smoking campaigns have had some effect, though more work needs to be done on tackling obesity. The HPV vaccination campaign is a step in the right direction, the report says, though the hepatitis B vaccination programme is flagging.

In early detection, GPs need better training in recognising the early signs of cancer. Public health literacy is also a priority, along with expanding breast and cervical cancer screening. Given rising incidence, colorectal cancer screening should also be considered, the IHE recommended.

Universal health care continues to be a priority, with the proportion of the population covered by medical schemes remaining static at 17% from 2012 to 2019. Public healthcare, which only offers a defined set of services, suffers from a lack of resources and personnel.

As far as cancer treatment in South Africa goes, public healthcare resembles global standards 20 years ago. Though radiation machines adequately serve the population on a national level, there are significant disparities with long waiting times and machines that can provide modern radiation techniques are limited and not listed in prescribed minimum benefits. Targeted drugs and immunotherapy remain almost exclusively the province of private healthcare, with a lengthy procedure to get drugs listed on the EML. Streamlining this should be a priority, the report recommends.

Categories : CancerTags :

Ultrasound Scans Proven Effective in Prostate Cancer Diagnosis

On By ModernMedia
Photo by MART PRODUCTION from Pexels

Results from a clinical trial showed that ultrasound scans are effective in prostate cancer diagnosis, which would be a cheaper option than MRI for low- and middle income countries. The study is published in Lancet Oncology.

“MRI scans are one of the tests we use to diagnose prostate cancer,” said Professor Hashim Ahmed, lead author of the study and Chair of Urology at Imperial College London. “Although effective, these scans are expensive, take up to 40 minutes to perform and are not easily available to all. Also, there are some patients who are unable to have MRI scans such as those with hip replacements or claustrophobia fears.  As cancer waiting lists build as a result of the COVID pandemic, there is a real need to find more efficient and cheaper tests to diagnose prostate cancer.

“Our study is the first to show that a special type of ultrasound scan can be used as a potential test to detect clinically significant cases of prostate cancer.  They can detect most cases of prostate cancer with good accuracy, although MRI scans are slightly better.

“We believe that this test can be used in low and middle income settings where access to expensive MRI equipment is difficult and cases of prostate cancer are growing.”

Prostate cancer develops slowly and symptoms such as the blood in the urine do not appear until the disease has developed. It usually affects men over 50 and often men with a family history of the disease. Black men are disproportionately impacted by the disease and prostate cancer deaths now exceed those from breast cancer.

One of the principal means of prostate cancer diagnosis is a multi-parametric MRI (mpMRI) scan. However, the 40-minute scan costs £350–450 (R7000-9000).

This new study tested multiparametric ultrasound (mpUSS) to image the prostate. Elastography examines tissue hardness, doppler and contrast-enhancement with microbubbles measures blood flow. As cancers are denser and have greater blood supply, they show up more clearly.
While mpUSS is more widely available than mpMRI, no large-scale studies have been done thus far to validate its effectiveness as a test to detect prostate cancer cases.

For the trial the team recruited 370 men at risk of prostate cancer. They were identified following initial tests such as a prostate-specific antigen (PSA) test and/or an abnormal digital rectal examination.

The men underwent both mpUSS and mpMRI scans at separate visits. This was then followed by biopsies for 257 patients who had a positive mpUSS or mpMRI test result. Cancer was detected in 133 men, with 83 men diagnosed with clinically significant cancer.

Individually, mpUSS detected 66 cases of clinically significant cancer compared to mpMRI which detected 77 cases.

Although mpUSS detected 4.3% fewer clinically-important prostate cancers compared to mpMRI, this method would lead to 11.1% more patients being biopsied as a result of false positives from the mpUSS.

The researchers believe that mpUSS could be an alternative to mpMRI as a first test for patients at risk of prostate cancer, particularly where mpMRI cannot be carried out. As both imaging tests missed clinically-important cancers detected by the other, using both would increase the detection of clinically-important prostate cancers overall.

Source: Imperial College London