Author: SD

Pillalamarri Srikrishnarka

Chennai, India

Researchers from three different nations concluded in a recent study that air pollution, particularly PM2.5, could be a serious concern for increasing lung cancer patients. They found that ambient air pollution was related to an increased risk of EGFR-driven lung cancer in 32,957 non-smokers and light smokers. In addition, they also discovered that there was a considerable flow of macrophages into the lungs of the mice when the mices were subjected to simulated air pollution. One of their key findings is that even three years of exposure to PM2.5 are enough for a person affected by EGFR-driven lung cancer without DNA damage. This finding has alarmed researchers.

Let’s take a quick look at a few of the fundamental notes I’ve taken to grasp better what cancer is and to study a few of the terms used in the post before we go right into pieces themselves.

Since we know that mutations in healthy cells can cause cancer, the first step in treating the disease is determining what causes these mutations. The initial stage of cancerous development is a step known as the promoter step.

“Epidermal growth factor receptor (EGFR) is a transmembrane protein; overexpression of this factor suggests the presence of cancer, and under expression suggests the possibility of Alzheimer’s. For the identification of this protein, the Nobel Prize in Medicine was conferred.”

Figure 1. (A and B) Representative immunohistochemistry (IHC) images of human EGFRL858R in ET mice exposed to PBS or PM at 10 weeks. C Representative diagram of spatially segmented human EGFRL858R-positive clusters in lung lobes, with the size of clusters proportional to EGFRL858R cell number at 10 weeks. Copyright © 2023, The Author(s), under exclusive license to Springer Nature Limited.

In a credible study, researchers found that the risk of developing lung cancer rose directly to PM2.5 in the air. They also found that this pattern held throughout all of the East Asian nations studied, in contrast to the native population of the UK.

For researchers to obtain further clinical insights into the progression of lung cancer, they genetically changed a few mice, caused cells to begin the mutation process, and then subjected the animals to ambient air pollution for ten weeks. Due to the exposure to PM, they observed an increase in the adenocarcinomas and aggressive CCSP-rtTa; TetO-EGFR model of doxycycline inducive hyperplasias in an adenoviral-CMV-Cre Kras model of lung cancer.

“They eventually concluded that exposure to PM promotes tumour progression in both oncogenic Kras and EGFR models of lung adenocarcinoma tumours.”

In addition, the evidence that was provided about the clonal dynamics shows that because of PM exposure, EGFR mutant cells grow with the capacity to form a tumour, and an increase in the proliferation rate of EGFR mutant cells demonstrates this.

The IL-6-JAK-STAT pathway is responsible for the mutation, which begs the question, “How does the mutation take place?” Only after exposure to PM were the immune response pathways of inflammation and the allograft response pathway shown to be elevated. Because of the exposure to PM, the expression of the genes for interleukin-1beta (IL-1beta), GM-CSF, CCL6, NK-kB, and epithelial-derived alarmin IL-33 increased. AT2 cells are a candidate cells for the beginning of the adenocarcinoma process in the lung.

“When exposed to PM, lung macrophages release inflammatory cytokines, which is central for tumour promotion. In addition, the IL-1beta signaling is required to promote PM-mediated EGFR-driven lung adenocarcinoma.”

The researchers went on to verify this notion using human lung tissue from 195 people who did not have cancer. They discovered that EGFR-driven mutations might be present in histologically normal lung tissues, even in patients who did not have the same mutations picked during the NSCLC carcinogenesis process. This suggests that EGFR can cause mutations in lung tissue.

The presented data is extremely concerning, and immediate urban replanning is required to stop the further growth in air pollution. However, it is not a sustainable solution to protect oneself from air pollution by donning a mask; rather, a concerted effort by scientists, engineers, city planners, medics, and people in general to battle air pollution is the way ahead.

Reference:

Hill, W., Lim, E.L., Weeden, C.E. et al. Lung adenocarcinoma promotion by air pollutants. Nature 616, 159–167 (2023). https://doi.org/10.1038/s41586-023-05874-3

Pillalamarri Srikrishnarka

Chennai, India: Circulating tumor cells travel from tumor throughout the body and create colonies in different parts of the body leading to recurrence of cancer. This process is also known as metastasis. Imaging these traversing cancer cells and in vivo destroying them without affecting the other cells of the body could potentially prevent the recurrence of cancer.

In this regard there are reported routes of in-vivo capturing these CTC and preventing them from traveling. Of which, inserting of a temporary microchip inside the body which harvests these CTs for extended periods of time. Since the chip is very small in size, the amount of blood harvesting is very small and is time consuming. The other method is by injecting magnetic nanoparticles which interact with these CTs and subsequently captured by controlling the magnetic field. In the third method, an implant typically that has been biofunctionalized is placed inside the body that can capture these CTs and prevent them from spreading throughout the body and initiate the formation of colonies.

To address some of the difficulties faced during the capturing of CTs, recently Wang and co-workers from the Southern University of Science and Technology utilized a functionalized flexible catheter having electrospun nanofibers for capturing these CTs. A liquid metal-polymer conductor was first sprayed onto the catheter and was the surface was sealed using a sealant which helped in making the surface conducting. The top surface of the catheter was given positive potential and the bottom layer was applied with a negative potential. This catheter was used a substrate for collecting electrospun nanofibers in such a way that, as the catheter enters the body, the fiber coating dosen’t get damaged.

The surface of the nanofibers were further functionalized to make them biosafe. These fibers acted as a net to capture all the floating CTs and they were killed by applying potential. They found that around 48 % of the CTs were captured in the presence of the electrospun nanofibers and without the coating it was just 2 %.

“The blood vessel in the LM/NF-catheter group still remained unobstructed and was functioning well. No noticeable morphological changes of the major organs were observed, indicating that there was no observable toxicity or side effects.” claimed the authors.

​​”As we have set the voltage for IRE at a low level, only the cells on the surface of the catheter can be killed, and the IRE could not damage the cells 1 mm away from the catheter. Even though some blood cells are on the surface of the catheter and killed by IRE, this small amount of hemolysis will not significantly affect the normal physiological function of the body.”- was observed by the authors.

This work was concluded by “this project can provide an alternative method for reducing the load of CTCs and other harmful exosomes in patients and has a broad prospect in clinical application to prevent tumor metastasis and recurrence.”

These results were published in ACS NANO (10.1021/acsnano.1c09807)

Pillalamarri Srikrishnarka,

Chennai, India: “Plastics have become an integral part of our life” is an understatement, with a global market worth 430 Billion USD! is one of the richest industries and is expected to grow to 600 USD by 2026. In view of current times where wearing of masks and protecting oneself from COVID has become a basic necessity, these number can easily skyrocket.

After it’s purpose has been solved, plastics generally end up as debris both in landfills and the oceans. With is inertness and high half-life, these plastics don’t degrade, however they break down into tiny fragments forming micro and nano plastics. With potential health risks from these nanoplastics, the health and environmental factors need to be understood ASAP.

Recent evidences on the presence of these micro plastics in fish(Accumulation, Tissue Distribution, and Biochemical Effects of Polystyrene Microplastics in the Freshwater Fish Red Tilapia (Oreochromis Niloticus). Environ. Pollut. 2018, 238, 1−9, Brain Damage and Behavioural Disorders in Fish Induced by Plastic Nanoparticles Delivered through the Food Chain. Sci. Rep. 2017, 7, 11452.) and the human fetus is alarming, major reforms are needed for the safe disposal of plastics globally.

Liu et al., investigated the interaction of nanoplastics with the brain and for the first time they observed the deposition of plastics in the brain by inhalation. For this study, they chose polystyrene beads of the size range 80-200 nm and functionalized with acid and amine groups and their bio interactions were studied. With 7-day exposure to nanoplastics aerosols, these plastics have successfully penetrated the blood brain barrier and liver. Amine-functionalized polystyrene particles absorbed easily through the nasal mucosa compared to that of acid-functionalized polystyrene beads. Such accumulation in the brain could lead to inflammation that could further cause brain disorders and cognitive delusions. In controlled environment, they observed that mice under exposure to plastic aerosols had reduced average movement speed when compared to that of control.

They have concluded that with an understanding of the pathway of plastics into the brain, the focus could be on the block of these pathways and prevention of the internalization and deposition in the brain can be done. 

These results have been published in ACS Nanoletters ( Nano Lett. 2022, 22, 1091−1099)