Medical Bulletin 03/ August/ 2024

A recent published study in the journal of clinical investigation finds a rug that was developed to treat pancreatic cancer has now been shown to increase symptom-free survival in preclinical medulloblastoma models – all without showing signs of toxicity. Medulloblastoma is the most common malignant brain tumour in children. Survival rates vary according to which one of the four subtypes a patient has, but the worst survival rates, historically at about 40%, are for Group 3, which this research focused on.

The research focused on the drug triptolide, which is extracted from a vine used in traditional Chinese medicine, and its water-soluble prodrug version, Minnelide. A prodrug is an inactive medication that the body converts into an active drug through enzymatic or chemical reactions.

To evaluate the efficacy of triptolide in targeting medulloblastoma the researchers utilised an established bioinformatic portal.

MYC is an oncogene, or gene that has the potential to cause cancer. MYC is dysregulated, or out of control, in about 70% of human cancers, and it shows up in much higher levels in Group 3 medulloblastoma than in the other medulloblastoma subgroups. Despite its well-known role in cancer, this oncogene historically has been considered impossible to target with drugs.

The study concludes that the drug, originally designed for treating pancreatic cancer, has the potential to be an effective treatment option for the most aggressive form of medulloblastoma. This finding opens up new avenues for targeted therapies and provides hope for improving outcomes in patients with this challenging brain cancer. Further research and clinical trials are needed to confirm its efficacy and safety in this new application.

References: Curtin SC, et al. Declines in cancer death rates among children and adolescents in the United States, 1999–2014. NCHS Data Brief. 2016;(257):1–8.

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In a study published in The American Journal of Medicine, discovered cardiovascular disease is the leading avoidable cause of premature death and disability. Primarily heart attacks and stroke, cardiovascular disease accounts for more than 900,000 annual deaths nationally and about 10 million deaths globally. Uncontrolled hypertension or high blood pressure is a major risk factor for stroke and heart attacks. Prevention and management of cardiovascular disease involves therapeutic lifestyle changes such as diet and exercise and adjunctive drug therapies of proven benefit.

Before the Hypertension Detection and Follow Up Program, a landmark study conducted in the 1970s, only about 50% of patients were aware of their high blood pressure. Of those, only 50% were actively treated. Of that group, only 50% received effective treatment. Therefore, only one-eighth of all patients were effectively treated.

This research shows that 54% are aware of their high blood pressure, 40% are actively treated and 21% are actively controlled. Many countries worldwide have developed guidelines emphasising the importance of strict blood pressure control. According to the latest recommendations from the American Heart Association and the American College of Cardiology, healthy individuals should aim for a systolic blood pressure of 130 millimetres of mercury (mmHg) or lower and a diastolic blood pressure of 80 mmHg or lower.

This concludes that Making positive lifestyle changes like losing weight, being more physically active, and cutting down on salt intake has been shown to be beneficial for managing blood pressure. For those whose blood pressure is above 130/80, a combination of these lifestyle changes along with medications can safely and effectively lower blood pressure. Medications are typically started for individuals whose pressure remains above 140/90 despite these lifestyle changes.

References: Davis, B. R., et al. (2024) New Clinical Challenges In Hypertension Management. The American Journal of Medicine. doi.org/10.1016/j.amjmed.2024.07.005.

In a recent study published in the journal Cancer Screening and Prevention, researchers reviewed the existing knowledge on the beneficial and detrimental effects of dietary patterns and nutritional supplements on cancer risk.

Diet, alongside lifestyle choices, is a major modifiable risk factor for cancer. An increasing number of studies highlight not only the preventive but also the causal role of diet in cancer development. Unhealthy diets, characterised by high-calorie foods, sugar-sweetened beverages, processed and red meats, and foods high in saturated and trans fats, are known to elevate the risk of obesity, metabolic disorders, and various cancers. Obesity-related cancer deaths account for 14% among men and 20% among women. Additionally, the consumption of alcohol and processed meats has been linked to cancers of the liver, pancreas, oesophagus, and colorectal region.

A substantial body of evidence indicates a causal relationship between diet and cancer. However, the complex nature of cancer has made it challenging to establish direct correlations between dietary factors and cancer risk. Epidemiological studies have demonstrated strong links between the consumption of certain foods and an increased risk of various cancers.

Polyunsaturated fatty acids such as omega-3 have been attributed to anti-cancer properties. Omega-3 fatty acids can be found mainly in marine fish and small quantities in plants such as flaxseed.

The findings highlighted that diet and nutritional supplements are significant modifiable risk factors for cancer. To reduce the risk of various cancers, a healthy diet rich in whole foods and free from processed meats, fried foods, and sugar-sweetened beverages is recommended, along with limiting alcohol intake.

References Khanashyam A.C., Thorakkattu P., Babu K.S., Shah K., Rajput M.S., Nirmal S., et al. (2024). Diet and Supplements in Cancer Prevention. Cancer Screening and Prevention. 2(2):138-147. doi: 10.14218/CSP.2023.00001. https://www.xiahepublishing.com/2835-3315/CSP-2023-00001

A study published in the journal Science, Researchers at Washington University School of Medicine in St. Louis has developed a way to capture the effects of ageing in the development of Alzheimer’s disease. They devised a method to study aged neurons in the lab without a brain biopsy, an advancement that could contribute to a better understanding of the disease and new treatment strategies.

The scientists transformed skin cells taken from patients with late-onset Alzheimer’s disease into brain cells called neurons. Late-onset Alzheimer’s develops gradually over many decades and only starts to show symptoms at age 65 or older. By studying these cells, the researchers identified aspects of cells’ genomes — called retrotransposable elements, which change their activity as we age — in the development of late-onset Alzheimer’s disease. The findings suggest new treatment strategies targeting these factors.

The method to transform easily obtained human skin cells from living patients directly into neurons makes it possible to study Alzheimer’s effects on the brain without the risk of a brain biopsy and in a way that retains the consequences of the patient’s age on the neurons. After transforming skin cells into brain cells, the researchers found that the new neurons can grow in a thin gel layer or self-assemble into small clusters, called spheroids, mimicking the 3D environment of the brain.

The Alzheimer’s disease patients’ spheroids quickly developed amyloid beta deposits and tau tangles between neurons. Activation of genes associated with inflammation also emerged and then the neurons began to die, mimicking what is seen in brain scans of patients.

The study concludes that the identification of an ageing-linked genomic factor in Alzheimer's disease provides crucial insights into the disease's underlying mechanisms. This discovery highlights the potential for developing targeted therapies that address the genomic changes associated with ageing, potentially offering new avenues for treatment and prevention. Further research is necessary to explore the therapeutic implications and to understand how these genomic factors contribute to the progression of Alzheimer's disease.

References: A. Serrano-Pozo, M. P. Frosch, E. Masliah, B. T. Hyman, Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med. 1, a006189 (2011).