Multiple Primary Lung Cancers: Treatment Outcomes After ...
Comparing Small Cell And Non-Small Cell Lung Cancer
There are two different types of lung cancer — small cell and non-small cell lung cancer — that behave differently and therefore require different treatments, an expert explained.
Lung cancer is the second most common cancer in the country, accounting for about 1 in every 5 cancer related deaths, according to the American Cancer Society. While "lung cancer" is an umbrella term, the malignancy can be looked at as separate diseases with non-small cell lung cancer being the most common.
About 85 to 87% of lung all lung cancers are non-small cell and with a much smaller portion being small cell lung cancer," Joelle Fathi, a nurse practitioner and Chief Healthcare Delivery Officer at GO2 For Lung Cancer, said in an interview with CURE®.
Non-small cell and small cell lung cancer cells look different under a microscope, and must be treated differently, Fathi said.
"It's really critical to understand what the genetic makeup of those tumors are in order to direct therapy that will target that type of lung cancer and how it's mutated," Fathi said.
"Lung cancer cells behave in different ways, so naturally, they respond to different remedies.
Small cell lung cancer, which is commonly associated with tobacco smoke exposure, tends to be treated with chemotherapy and radiation, but treatment for non-small cell lung cancer depends on the subtype and observable mutations of the cancer.
And what we know about small cell lung cancer is that it tends to be a very fast-growing disease; it'sdifficult to catch it in the natural environment of lung cancer screening.
Because I could screen you today, and you may not have any evidence of lung cancer, and two months later, a small cell (lung cancer) could develop. Because it grows so quickly, we may not have the opportunity to catch it in an early stage by your next annual screen — it grows that fast," Fathi explained.
"There are families and groups with long lineages of lung cancer, including people who have never smoked, who still develop lung cancer without other known risk factors. Why do these people develop lung cancer? Why is it so prevalent in certain families and groups of people remains a mystery, highlighting the need for continued research in the field". Fathi explained.
The genetic and molecular factors behind a lung cancer diagnosis can be instrumental in determining how it is treated, as targeted therapies and immunotherapy agents continue to personalize care for patients with non-small cell lung cancer.
As new lung cancer discoveries and therapies continue to emerge, keeping patients updated on these new findings is critical, Fathi emphasized.
"One of the best things that we can do for our patients is empower them with knowledge. And when people have information, they can make informed decisions about how they approach their health care — and perhaps even more important how they can advocate for themselves," Fathi stated.
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Could A Molecule In Cruciferous Veggies Help Protect Against Lung Infection?
For a very long time, doctors have urged people to eat more vegetables.
Not only are they nutritious, but previous research shows adding more veggies to a person's diet can help reduce obesity risk, improve mental health, lower heart disease risk, and boost gut health.
In a recent study, researchers from the Francis Crick Institute in London have found that molecules naturally found in cruciferous vegetables — such as broccoli and cauliflower — can boost the activity of a protein called aryl hydrocarbon receptor (AHR), helping the lungs to maintain a healthy barrier against viral and bacterial infection.
The findings were recently published in the journal Nature.
Aryl hydrocarbon receptor (AHR) is a type of cellular protein. In the body, it assists with gene regulation and the metabolism of certain enzymes.
Previous research also shows AHR plays a role in regulating the immune system and plays an active role in stem cells.
Because of its relation to the immune system, scientists have studied the use of AHR as a potential target for prevention and therapies for a number of diseases, including:
In this study, researchers focused on the natural lung barrier that helps protect the lungs from pollution and infection.
The lung barrier includes two layers — one of endothelial cells and one of epithelial cells. This allows the barrier to keep out viruses and bacteria but still lets oxygen enter.
According to Dr. Andreas Wack, PhD, principal group leader of the Wack Lab Immunoregulation Laboratory at the Francis Crick Institute and lead author of this study, they decided to study the effect of AHR on lung barriers because it has been studied extensively at other barrier sites such as the skin and the gut, but much less so in the lung.
"AHR is an environmental sensor that can be activated by ligands found in food or produced by bacteria living in our gut — but some toxic ligands are also derived from air pollution. AHR protects the lung by inducing gene programs known to support barrier integrity and barrier function. Which genes are directly targeted by AHR and which ones are triggered indirectly is unclear."
— Dr. Andreas Wack, PhD, lead study author
For the present study, Dr. Wack and his team performed a variety of experiments using a mouse model.
When mice were infected with the flu virus, scientists found blood in the airspaces in the lungs as it had leaked across the damaged lung barrier.
When AHR was overactivated, there was less blood in the lung spaces, indicating that it helped prevent the lung barrier from leaking.
During the study, scientists observed mice with increased AHR activity did not lose as much weight when infected with the flu virus. Additionally, the AHR-enhanced mice could better fight off bacterial infection and the already-introduced flu virus.
Researchers also found the flu infection caused a decrease in protective lung AHR activity only in mice fed AHR ligands in their diet before the illness.
Mice that consumed an AHR ligand-rich diet during infection had better lung barrier integrity and less lung damage than those on a control diet.
"In mice without ligands in the diet, their AHR activity levels were low to start with, so if you don't eat ligands, you have little AHR activity," Dr. Wack explained to Medical News Today.
"When you eat them, then AHR activity increases. This activity can be dampened by sick behavior, i.E., not eating for some days."
"This is probably not a good idea, so keep eating a healthy diet to upkeep AHR activity," he added. "What is good for your gut — a healthy, rich, (and) varied diet containing AHR ligands — is probably also good for your lungs."
After reviewing this study, Dr. Elliot Eisenberg, assistant professor of medicine (pulmonary, critical care, and sleep medicine) at the Icahn School of Medicine at Mount Sinai, told MNT that the data was encouraging and demonstrated a potential protective effect of dietary intake on lung endothelial cell response to infection.
"As this is preclinical data, dietary recommendations for patients with influenza cannot be made," Dr. Eisenberg said.
"[The study data] does provide biological plausibility to support future clinical and translational endeavors assessing diet and clinical outcomes and adds to the growing body of literature supporting the role of diet and lung health."
"Prior clinical research, including studies by Mount Sinai, have demonstrated healthy diet attenuates wheezing among teens with secondhand smoke exposure, and is associated with (a) slower decline in lung function amongst young adults."
— Dr. Elliot Eisenberg, pulmonary and internal physician
Cruciferous vegetables are part of a family of vegetables known as brassicas.
There are more than 3,000 different types of cruciferous vegetables. The most commonly known are:
In addition to providing the nutritional benefits all vegetables are known for, these veggies are also high in dietary fiber and rich sources of specific vitamins, including vitamins C, E, K, and B9 (folate).
Cruciferous vegetables also contain phytonutrients, which are compounds known to help lower inflammation. Previous studies have also linked phytonutrients to cancer treatment and prevention.
And these types of veggies naturally have chemicals called glucosinolates. Past studies have linked glucosinolates to potential cancer protection, such as gastrointestinal cancers.
Additionally, other studies have looked at using glucosinolates to help protect against cardiovascular and neurodegenerative diseases.
Health and nutrition experts recommend consuming 2 to 3 cups of vegetables daily as part of a healthy, balanced diet.
Researchers Create New Model Of Lung Mesenchymal Cells
In vitro differentiation of iPSCs toward the lung mesenchyme lineage through a mesodermal progenitor. A Schematic of the Tbx4 lung enhancer reporter/tracer (LER) line, and image of an E10 embryo (dox from E6.5 to E10). Scale bar = 0.5 mm. Created with BioRender.Com. B Directed differentiation of iPSCs into lung mesenchyme through a mesodermal progenitor. CSFDM = complete serum-free differentiation medium, LIF = Leukemia inhibitory factor. Created with BioRender.Com. C Expression relative to day 0 iPSCs of Foxf1 (lateral plate mesoderm), Pax2 (intermediate mesoderm) and Tbx6 (paraxial mesoderm) in KDR± cells on day 5. N = 3. D Image and flow cytometry plot showing expression of GFP (green) in the Tbx4-LER iPSC line on day 13. Red = Tomato in non-recombined cells. Scale bar = 100 μm. E GFP percentage on day 13 using all 4 medium factors (RA, PMA, BMP4, WNT3A), or one or two factors removed at a time. Dox from day 5 on. N = 9. F Day 13 GFP percentage in RA&PMA medium, with either the XAV or recombinant mouse WNT3A. Dox from day 5 on. N = 3. G GFP percentage on day 13 in RA&PMA medium, in RA or PMA only medium, or upon addition of Cyclopamine. Dox from day 5 on. N = 4 for "RA&PMA" and "RA", N = 3 for "PMA" and "RA&Cyclo". h GFP percentage over time from day 5 to 13 of differentiation. Dox from day 5 on. N = 4 for day 8-12, N = 3 for day 13. i GFP percentage on day 13 in RA&PMA medium after sorting for KDR± on day 5 of differentiation. N = 3. Created with BioRender.Com. J Representative image showing reporter activation on day 13 of lung epithelial differentiation and GFP percentage in the mesenchymal versus epithelial (i.E., co-development, cLM) differentiation protocol. Dox from day 5 on in the mesenchymal differentiation protocol, and from day 6 (anterior foregut endoderm stage) on in the epithelial (co-development) protocol. Scale bar = 100 μm. N = 4 for "Mesenchymal", N = 5 for "Co-development". All bars show mean ± sd. P values were determined by unpaired, two-tailed Student's t test. Significant (p p values are highlighted in bold font. Credit: Nature Communications (2023). DOI: 10.1038/s41467-023-39099-9 Lung mesenchymal cells, which are critical components of the lung's unique structure, also play important roles in disease and recovery from injury, yet knowledge is limited about their biology or how they initiate diseases like pulmonary fibrosis. While experimental models have helped to identify some regulators of lung mesenchyme behavior, the understanding of how the lung mesenchyme is identified during human development is unknown.
To better understand these processes, researchers from Boston University Chobanian & Avedisian School of Medicine have developed an in-vitro induced pluripotent stem cell (iPSC)-based model system for the derivation and study of early lung-specific mesenchyme with potential benefit for comprehending basic mechanisms regulating tissue-specific mesenchymal fate decisions and future applications for regenerative medicine.
"Our study has implications for the study of lung diseases, such as pulmonary fibrosis and interstitial lung diseases that arise from dysfunction of the part of the lung known as mesenchyme. These diseases currently have very limited treatment options and we hope our model system will provide new tools to understand what goes wrong in these diseases and to screen for better drugs," said corresponding author Darrell Kotton, MD, the David C. Seldin Professor of Medicine and director of the BU/Boston Medical Center Center for Regenerative Medicine (CReM).
The researchers used an experimental model with an iPSC line carrying a lung mesenchyme-specific fluorescent reporter, meaning that cells that become lung mesenchymal were marked by green fluorescence. Using this model, they tested several growth factors and small molecules to stimulate pathways with known roles in lung development.
They found that stimulating the retinoic acid and hedgehog signaling pathways, both known to play essential roles in embryonic development, resulted in the maximum percentage of green fluorescent cells indicative of the potential presence of lung mesenchyme. They then isolated those cells and compared their gene expression profile to primary cells from embryonic lungs of the experimental model to determine how similar these cells are to primary lung mesenchymal cells.
Finally, they used their recombinant organoid system to test whether these cells can actually function as lung mesenchyme.
"An important role of the developing lung mesenchyme in the experimental model is their ability to interact with and signal to the neighboring epithelium. We found that our engineered cells can recapitulate some of those signaling interactions, suggesting that they have functional capacity," explained first author Andrea Alber, Ph.D., a postdoctoral fellow in Kotton's laboratory.
According to the researchers, the part of the study where the engineered lung mesenchymal cells are combined with lung epithelial cells in culture dishes (so called "recombinants") is particularly exciting as this resulted in organoids, living cells assembled together in a 3D culture gel that helps scientists understand how cells are organized and communicate. "We are now working to apply these types of new organoid models to better understand pulmonary fibrosis," added Alber.
These findings appear in the journal Nature Communications.
More information: Andrea B. Alber et al, Directed differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme, Nature Communications (2023). DOI: 10.1038/s41467-023-39099-9
Citation: Researchers create new model of lung mesenchymal cells (2023, June 13) retrieved 18 August 2023 from https://medicalxpress.Com/news/2023-06-lung-mesenchymal-cells.Html
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