Category: Cancer

Research Highlights: Magnesium Helps The Immune System Fight Against Cancer

~ Chromoscience ~ Leave a comment
clevelandclinic.org

Magnesium Helps The Immune System Fight Against Cancer

  • Magnesium is important in maintaining a healthy body.[1]
  • Magnesium is involved in muscle regulation, nerve function, blood sugar levels, blood pressure, protein production, bone maintenance, and genetic stability.[1]
  • Foods that contain magnesium include legumes, nuts, whole grains, green leafy vegetables, breakfast cereals, yogurt, and certain milk products.[1]
  • The role of magnesium outside the cells in regards to cellular immunity remains unclear.
  • Lymphocyte Function Associated Antigen 1 or LFA-1 is a cell-surface protein found on CD8+ T cells.[2]
  • LFA-1 functions as an adhesion molecule promoting contact between two cells or between a cell and the extracellular matrix.
  • Researchers discovered that magnesium activates the LFA-1 on CD8+ T cells, thereby increasing calcium influx, signal transduction, metabolic reprogramming, immunological interface, and cytotoxicity.
  • When LFA-1 detected high levels of magnesium, pathogen and tumor-specific T cell’s performance was improved, effectiveness of bi-specific T cell engaging antibodies was enhanced, and CAR T cell function was improved.
  • CAR T cells are a type of T cells that have been genetically modified to produce an artificial T cell receptor for use in immunological treatment.[3]
  • Low levels of magnesium in the blood were correlated with more rapid disease progression and lower survival rate in patients treated with CAR T cell and immune checkpoint antibody.
  • The findings highlight the relationship between co-stimulation and nutrient sensing, and direct to the magnesium-LFA-1 interaction as a therapeutically amenable biological system.

Sources:

Jonas Lötscher, Adrià-Arnau Martí i Líndez, Nicole Kirchhammer, Elisabetta Cribioli, Greta Giordano, Marcel P. Trefny, Markus Lenz, Sacha I. Rothschild, Paolo Strati, Marco Künzli, Claudia Lotter, Susanne H. Schenk, Philippe Dehio, Jordan Löliger, Ludivine Litzler, David Schreiner, Victoria Koch, Nicolas Page, Dahye Lee, Jasmin Grählert, Dmitry Kuzmin, Anne-Valérie Burgener, Doron Merkler, Miklos Pless, Maria L. Balmer, Walter Reith, Jörg Huwyler, Melita Irving, Carolyn G. King, Alfred Zippelius, Christoph Hess. Magnesium sensing via LFA-1 regulates CD8 T cell effector function. Cell, 2022; DOI: 10.1016/j.cell.2021.12.039

[1] https://ods.od.nih.gov/factsheets/Magnesium-Consumer

[2] https://www.sciencedirect.com/topics/medicine-and-dentistry/lymphocyte-function-associated-antigen-1

[3] https://en.wikipedia.org/wiki/Chimeric_antigen_receptor_T_cell

Research Highlights: Gut Bacteria Promote Therapy Resistant Prostate Cancer

~ Chromoscience
Image by Gerd Altmann from Pixabay

Gut Bacteria Promote Therapy Resistant Prostate Cancer

  • Androgens such as testosterone are important for male sexual and reproductive function.
  • Androgens play a role in the growth of prostate cancer cells.
  • Decreasing androgens by means of castration or hormone suppression is the current treatment for prostate cancer.
  • Castration refers to the process of removing the testicles in males.
  • The microbiota consist of microorganisms that inhabit a particular environment or location in or on the host.
  • Microbiota contains different types of organisms which includes symbiotic, commensal, and pathogenic microorganisms.
  • The role of the gut microbiota to the emergence of castration-resistance prostate cancer has not yet been addressed.
  • Researchers discovered that deprivation of androgen in mice and humans encourages the expansion of some commensal microbiota that helps to begin the castration resistance.
  • They found that when the body was deprived of androgens during the therapy, the gut microbiome could produce androgens from androgen precursors.
  • When the gut microbiota was removed by antibiotic therapy, the emergence of castration resistance was delayed even when mice are immunodeficient.
  • Fecal microbiota transplantation from castration-resistance prostate cancer mice and patients gave mice harboring prostate cancer resistant to castration.
  • In contrast, the growth of tumor was controlled by fecal microbiota transplantation from patients with hormone-sensitive prostate cancer.
  • Fecal microbiota transplantation, also known as a stool transplant, is the process of transferring fecal bacteria from a healthy individual into another individual.
  • The results suggest that the commensal gut bacteria contributes to endocrine resistance in castration-resistance prostate cancer by providing an alternative source of androgens.

Sources:

Pernigoni, N., Zagato, E., Calcinotto, A., Troiani, M., Mestre, R. P., Calì, B., Attanasio, G., Troisi, J., Minini, M., Mosole, S., Revandkar, A., Pasquini, E., Elia, A. R., Bossi, D., Rinaldi, A., Rescigno, P., Flohr, P., Hunt, J., Neeb, A., Buroni, L., … Alimonti, A. (2021). Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis. Science (New York, N.Y.), 374(6564), 216–224. https://doi.org/10.1126/science.abf8403

Research Highlights: SRT1720 Experimental Drug Inhibits Bladder Cancer Development

~ Chromoscience
By Created by US government agency National Cancer Institute – http://www.cancer.gov/cancertopics/wyntk/prostate/allpages#ab3d4f20-6ab9-4428-9717-067035d2e691, Public Domain, https://commons.wikimedia.org/w/index.php?curid=837427

SRT1720 Experimental Drug Inhibits Bladder Cancer Development

  • Bladder cancer is the sixth most common malignancy in the United States.[2]
  • The most common clinical presentation of bladder cancer is the presence of blood in the urine.[2]
  • Smoking is a major risk factor for bladder cancer.[3]
  • New therapeutic targets and drugs for bladder cancer are needed in clinical settings.
  • Most of the past research relied on limited bladder cancer cell lines.
  • Tumor heterogeneity and pathology of this disease are not well represented with limited bladder cancer cell lines.
  • An organoid is a small and simplified version of an organ produced in three dimensions that shows realistic micro-anatomy.[4]
  • Cancer organoids can repeat pathological and molecular properties of bladder cancer.
  • Researchers evaluate the first bladder cancer organoid-based molecule, SRT1720, for epigenetic drugs.
  • SRT1720 is a drug that was studied by Sirtris Pharmaceuticals intended as a small-molecule activator of the sirtuin subtype SIRT1.[1]
  • SIRT1 is a gene involved in the deacetylation of histones and a number of nonhistone substrates that can affect multiple signaling pathways.[5]
  • Many studies showed that SIRT1 could act as either a tumor suppressor or tumor promoter depending on its targets in specific cancers.[5]
  • Researchers found that SRT1720 significantly inhibits the development of both mouse and human bladder cancer organoids.
  • SRT1720 also prevents the development of bladder cancer in mouse and human patient-derived xenograft bladder cancer.
  • When SIRT1 is mutated, the growth of cancer organoids is increased and their sensitivity to SRT1720 is decreased.
  • The finding proves that SRT1720 targets the SIRT1 in bladder cancer.
  • Researchers also found that SRT1720 treatment can inhibit the development of hypoxia.
  • Additionally, the SIRT1-repressed gene signature is linked with the hypoxia target gene signature and poor prognosis in human bladder cancer.
  • The study demonstrated the power of drug discovery using cancer organoids and identifies SRT1720 as a new therapy for bladder cancer.

Related Video

Sources:

Tan, P., Wang, M., Zhong, A. et al. SRT1720 inhibits the growth of bladder cancer in organoids and murine models through the SIRT1-HIF axis. Oncogene (2021). https://doi.org/10.1038/s41388-021-01999-9

[1] https://en.wikipedia.org/wiki/SRT-1720

[2] https://pubmed.ncbi.nlm.nih.gov/29094888

[3] https://www.cancer.gov/types/bladder

[4] https://en.wikipedia.org/wiki/Organoid

[5] https://pubmed.ncbi.nlm.nih.gov/24020000

Research Highlights: Cancer Cell Outcompetes T Cell in Methionine Consumption

~ Chromoscience ~ Leave a comment
T cells attacking cancer cells. Credit: Prasad Adusumilli

Original Article: https://doi.org/10.1038/s41586-020-2682-1

  • Abnormal epigenetic patterns is associated with effector T cell malfunction in tumors, but the cause of this correlation is unclear.
  • Methionine is an amino acid that is a component of most proteins, and it is an essential nutrient in the diet of vertebrates.
  • CD8+ T cell is a T lymphocyte that kills cancer cells.
  • The study show that tumor cells alter methionine metabolism in CD8+ T cells.
  • The alteration includes lowering the intracellular levels of methionine inside the cells.
  • The alteration also includes lowering the intracellular levels of methyl donor S-adenosylmethionine (SAM).
  • The result of these alteration is the loss of dimethylation at lysine 79 of histone H3 (H3K79me2).
  • Loss of H3K79me2 resulted in low expression of STAT5 and impaired T cell immunity.
  • STAT5 proteins are involved in cytosolic signalling and in mediating the expression of specific genes.
  • Mechanistically, tumor cells enthusiastically consumed methionine and outcompeted T cells.
  • Tumor cells compete with T cell for methionine by expressing high levels of the methionine transporter.
  • Genetic and biochemical inhibition of tumor methionine transporter restored H3K79me2 in T cells, as a result boosting spontaneous and checkpoint-induced tumor immunity.
  • In addition, methionine supplement improved the expression of H3K79me2 and STAT5 in T cells.
  • The improvement due to methionine supplementation went along with increased T cell immunity in tumor-bearing mice and patients with colon cancer.
  • Clinically, tumor methionine transporter has a negative correlation with T cell histone methylation and functional gene signatures.
  • The study identify a physical connection between methionine metabolism, histone patterns, and T cell immunity in the tumor micro-environment.
  • Cancer methionine consumption can be an immune evasion mechanism.
  • The study suggests that targeting cancer methionine signalling is a potential cancer therapy.

Source:

https://doi.org/10.1038/s41586-020-2682-1

https://languages.oup.com/google-dictionary-en/

https://doi.org/10.1016%2Fb978-0-12-817572-9.00007-0

https://doi.org/10.1093%2Femboj%2F18.17.4754

Keywords: cancer therapy, cancer cure, cancer treatment, cancer immunotherapy, how cancer cell affect t cell, t cell, immune system, immunity

When Cancer Cells Express The Wrong Gene

~ Chromoscience ~ Leave a comment
cancer cells
An Ovarian Teratoma: The photo shows a type of tumor that includes teeth at the bottom part of the ovary. This ovarian tumor expressed the wrong gene which results in the formation of teeth at the wrong location. Source: https://commons.wikimedia.org/wiki/File:Ovarian_teratoma.jpg

When Cancer Cells Express The Wrong Gene

An organism is formed based from an architectural blueprint called DNA. In eukaryotes including human cell, the nucleus holds the DNA. Humans contain 46 chromosomes and for each chromosome, DNA is organized into a strand. Each shorter segment of the DNA strand is called genes. This is analogous to organizing a long paragraph into a different clear sentences. Each gene is an instruction to make a protein. Analogically speaking, DNA in eukaryotic cells are like the apps (application software) in mobile phone. If you want to know the current date, you would only access the calendar app and not run the other programs. The same idea applies in eukaryotic DNA. A cell does not express all the gene stored in the nucleus and only express gene that are needed depending on the type of cell. For example, each cell in the human body regardless of where it is located contains the gene to make the hair, skin, teeth, liver, and ovary, but these genes are turned off in the stomach cells. If genes for making the teeth were turned on in the stomach cells, you will have teeth forming in the stomach.

Source:

Blankenship-Williams, L. (2015). What You Really Need To Know Before Anatomy, Physiology, and Microbiology. Carbohydrates and Nucleic Acids. Accessed November 18, 2019. https://www.amazon.com/really-before-Anatomy-Physiology-Microbiology/dp/0692481923