Medical Bulletin 31/ August/ 2024

Research published in the Journal Science Advances indicates that prostate cancer treatment may increase the risk of developing Alzheimer’s disease in men.

Scientists were actively exploring the origins of Alzheimer’s disease in men with prostate cancer to determine whether it is primarily caused by the standard hormone therapy treatments they receive or by an overactive immune response.

Androgen deprivation therapy (ADT), a form of hormone treatment for cancer, works by lowering testosterone levels, which are essential for cancer growth. However, since androgens play a crucial role in regulating amyloid metabolism, their reduction can lead to an accumulation of amyloid, contributing to the formation of plaques that are characteristic of Alzheimer’s disease.

The research team hypothesized that an overactive immune response and resulting inflammation might be contributing factors. To investigate further, they created an animal model that combined Alzheimer’s disease and cancer, administering androgen deprivation therapy (ADT) for eight weeks while tracking androgen levels and tumour size.

They also developed additional models: a wild type (without Alzheimer’s or cancer), a group with only Alzheimer’s, and another group with only cancer that underwent androgen deprivation therapy. This approach helped the team better understand the complex interactions between these conditions. Additionally, they frequently analyzed blood samples for immune markers to monitor changes.

Researchers found an increase in pro-inflammatory cytokines, small proteins that trigger an increase in inflammation throughout the body, and a decrease in anti-inflammatory cytokines, particularly in the animals with Alzheimer’s and cancer that received ADT.

To intervene and stop the immune cell infiltration, researchers choose the drug Natalizumab for the management. Treating mice with both cancer and Alzheimer’s disease using a combination of ADT and natalizumab not only decreased immune cell infiltration but also enhanced the integrity of the blood-brain barrier.

Reference: Chao Zhang et al.,Androgen deprivation therapy exacerbates Alzheimer’s-associated cognitive decline via increased brain immune cell infiltration.Sci. Adv.10,eadn8709(2024).DOI:10.1126/sciadv.adn8709

Women with endometriosis have a 20% greater risk of significant cardiac outcomes compared with women without endometriosis, the results of a recent Danish study has pointed out.

The study results presented at the ESC Congress 2024 have heightened concerns for women with endometriosis. Endometriosis, a chronic systemic gynaecological condition affecting 10% of women of reproductive age, exhibits pathophysiological traits similar to those of cardiovascular disease.

The study used Danish nationwide registries of all women with a diagnosis of endometriosis between 1977 and 2021. They were matched with women from the background population without endometriosis in a 1:4 ratio based on year of birth. The primary outcome was a composite of acute myocardial infarction and ischaemic stroke. The secondary outcomes were the individual components of the primary outcome, as well as arrhythmias, heart failure and mortality.

There were 60,508 women with endometriosis and 242,032 matched controls included in the analysis (median age, 37.3 years) who were followed for a median of 16 years and a maximum of 45 years.

At the end of the study, it was found that Women with endometriosis had around a 20% increased risk of the composite endpoint of acute myocardial infarction and ischaemic stroke compared with those without endometriosis.

Scientists concluded that the high prevalence of endometriosis highlights the significance of these findings and stresses the need for a deeper understanding and better prevention of its long-term cardiovascular effects.

Reference: The abstract “Endometriosis, a prevalent disease, is associated with significant cardiac disease” will be presented at the session ‘Cardiovascular disease in women (5)’, which takes place on 2 September 2024, Station 6 in the Research Gateway.

Research published in the journal Cell Systems has identified novel molecular and cellular markers in the development of one of the most aggressive, deadly pancreatic cancers: pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma arises from precancerous lesions in the pancreas. One of these lesion types, pancreatic intraepithelial neoplasias (PanINs), can appear in the pancreas years before they progress to invasive cancer. Because pancreatic intraepithelial neoplasias are so small, they cannot be detected by conventional clinical imaging tests.

By employing spatial transcriptomics a method for measuring and mapping gene expression within tissue sections the researchers created a three-part analysis pipeline to track changes in gene expression across samples from nine patients, including 14 pancreatic intraepithelial neoplasias and five rare, high-grade pancreatic intraepithelial neoplasias. They developed machine learning tools for imaging analysis (CODA) and for integrating these findings with single-cell datasets from pancreatic ductal adenocarcinoma, using innovative multi-omics integration methods such as CoGAPS (coordinated gene activity in pattern sets) and project R. The researchers have made their data and code publicly available to assist others in further exploring pancreatic cancer.

The results of their work provide new insights into the gene expression and spatial distribution of different types of cells in the precancerous environment around PanINs. These cells are cancer-associated fibroblasts (CAFs), including antigen-presenting cancer-associated fibroblasts CAFs.

Scientists also observed a shift from CAF-associated inflammatory signalling to increased cellular proliferation as pancreatic intraepithelial neoplasia progressed.

The three-way analysis revealed that some key features of pancreatic cancer were present in pancreatic intraepithelial neoplasias.

Reference: Bell, A. T. F., Mitchell, J. T., Kiemen, A. L., Lyman, M., Fujikura, K., Lee, J. W., Coyne, E., Shin, S. M., Nagaraj, S., Deshpande, A., Wu, P.-H., Sidiropoulos, D. N., Erbe, R., Stern, J., Chan, R., Williams, S., Chell, J. M., Ciotti, L., Zimmerman, J. W., Wirtz, D., Ho, W. J., Zaidi, N., Thompson, E., Jaffee, E. M., Wood, L. D., & Fertig, E. J. (2024). PanIN and CAF transitions in pancreatic carcinogenesis revealed with spatial data integration. Cell Systems. https://doi.org/10.1016/j.cels.2024.07.001

Recent cases of amoebic meningoencephalitis have been reported in Kerala. In response, Health Minister Veena George has announced that the state will initiate research on amoebic encephalitis and develop an action plan to address the issue.

According to a PTI report, the Kerala Health Department organized a technical workshop as the first step, featuring participation from experts both within the state and from institutions such as the Indian Council of Medical Research (ICMR), Indian Association of Virology (IAV), Pondicherry EV Institute, Indian Institute of Science, and the Pollution Control Board.

Health Minister Veena George inaugurated the workshop, announcing that Kerala will embark on research into amoebic meningoencephalitis.

“This will be the first such effort at the global level. When a cluster was formed in Thiruvananthapuram, we were able to detect the first case and subsequently identify other infected individuals. All of them are recovering,” the minister said.

Health Minister Veena George said the Health Department has decided to find out why cases are increasing in the state.

“Based on this, we have decided to launch research activities in collaboration with expert organisations like Indian Council of Medical Research and the Indian Institute of Science,” the minister said, news agency PTI reported.

In an official statement, the Health Department noted that workshop participants commended Kerala’s efforts. According to their assessment, the state’s proactive measures successfully identified rare diseases such as amoebic meningoencephalitis at an early stage, helping to save some individuals from a condition with a 97 per cent mortality rate.

The team expressed full support for Kerala’s initiatives to combat amoebic meningoencephalitis. Globally, only 11 people have recovered from this illness, and in 2024, Kerala reported 19 cases, including five fatalities.

“Kerala has managed to increase the recovery rate. So far, four people in the state have recovered. All those who contracted the disease in Kerala had contact with contaminated water, either directly or indirectly,” the Minister said.

To determine why only some people who used the same water source contracted the disease, a case-control study will be conducted with the help of Indian Council of Medical Research and the National Institute of Epidemiology, it said.