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AKT Pathway  

 

 

The Akt Pathway, or PI3K-Akt Pathway is a signal transduction pathway that promotes survival and growth in response to extracellular signals. Key proteins involved are PI3K (phosphatidylinositol 3-kinase) and Akt (Protein Kinase B)

Angiogenesis  

 

The development of new blood vessels, stimulated by VEGF, a growth factor secreted by cancer cells. Angiogenesis helps provide nutrients for cancer to grow.

Apoptosis  

 

 

Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Traditionally the type of cancer cell death that oncologists aim to achieve in their cancer patients. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay. Wikipedia

ATP  

 

ATP stands for adenosine triphosphate. This chemical, discovered in the 1920s, is important to all life. It stores and releases energy for many cellular processes. It is found in mitochondria and provides the energy for cancer growth.

Autophagy  

 

 

 

(or autophagocytosis) (from the Ancient Greek αὐτόφαγος autóphagos, meaning “self-devouring”[1] ) is the natural, regulated mechanism of the cell that removes unnecessary or dysfunctional components.[3] It allows the orderly degradation and recycling of cellular components. In cancer ‘salvage autophagy’ is a route to ingest nutrients and drive further growth. This can be an aggressive feeding pathway in many cancers (e.g. pancreatic).

Bifidobacterium  

 

Bifidobacterium are a group of bacteria called probiotics that normally live in your intestines and stomach. They help your body perform essential functions such as digestion and staving off harmful bacteria.

BRCA Gene  

 

 

The name “BRCA” is an abbreviation for “Breast Cancer gene.” BRCA1 and BRCA2 are two different genes that have been found to impact a person’s chances of developing breast cancer. Every human has both the BRCA1 and BRCA2 genes. Mutations in this gene can cause cancers of breast and ovary.

 

Carcinogens Are substances capable of causing cancer in living tissue.
Caspase Cascade  

 

Caspases are a family of cysteine proteases that act in concert in a cascade triggered by apoptosis signalling. The culmination of this cascade is the cleavage of a number of proteins in the cell, followed by cell disassembly, cell death, and, ultimately, the phagocytosis and removal of the cell debris.

Catabolic  

Marked by or promoting metabolic activity concerned with the breakdown of complex molecules (such as proteins or lipids) and the release of energy within the organism

COC  

 

Care Oncology Clinic – London and now US based cancer clinic prescribing a repurposed combination of existing licenced medicines normally used to treat conditions other than cancer.  This standard of practise is known as off-label use.

Cox 2 inhibitor  

 

An anti-inflammatory drug such as NSAIDs that selectively blocks the Cox-2 enzyme. Blocking this enzyme impedes the production of the chemical messengers that cause pain and swelling. Cox-2 is associated with promoting cancer.

Cytokinesis  

The cytoplasmic division of a cell at the end of mitosis or meiosis, bringing about the separation into two daughter cells.

Cytotoxic  

 

 

Cytotoxic drugs or cytostatic (also cytotoxicchemotherapy) are drugs used to destroy cancercells. Cytotoxic drugs inhibit cell division and in this way cause cancer cells to die. Cytotoxic drugs are transported in the bloodstream throughout the body

 

Daughter Cells  

A cell formed by the division or budding of another

 

Downregulate Turn off gene expression
Endothelium  

 

 

The Endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels, and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall

Epigenetics  

 

The study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself, influenced by the tumour microenvironment.

Endocytosis  

The taking in of matter by a living cell by invagination of its membrane.

Ferroptosis  

 

 

 

 

Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides i.e., oxidised fat, found in membranes including mitochondria. It is genetically and biochemically distinct from other forms of regulated cell death such as apoptosis. Ferroptotic cell death is characterized by cytological changes, including cell volume shrinkage and increased mitochondrial membrane density which limits its ability to produce ATP for cell division causing cell death.

Fibroblast  

 

A cell in connective tissue which produces collagen and other fibres. Found in the ‘stroma’ surrounding cancer cells and capable of glycolysis.

FGF  

 

The fibroblast growth factors (FGF) are a family of cell signalling proteins that are involved in a wide variety of processes. In cancer, these growth factors promote cancer growth.

Genotype  

 

 

genotype is an individual’s collection of genes. The term also can refer to the two alleles inherited for a particular gene. The genotype is expressed when the information encoded in the genes’ DNA is used to make protein and RNA molecules.

Glutathione  

 

 

The master antioxidant used by cancer to protect itself from oxidation therapies such as chemotherapy, radiotherapy and ferroptosis. It is a tripeptide derived from glutamic acid, cysteine, and glycine.

Heterogenous  

 

Tumours are a mix of different types of cells that behave in different ways. If you kill off only one type of cell you can make cancer return more aggressive than before by stimulating another more dominant and potentially more active type of cell. This is why combination therapies are more effective.

Hormesis  

 

Different doses of drugs and supplements will have different effects. E.g. A low dose of vitamin C acts as an antioxidant whereas high doses produce hydrogen peroxide (oxidant).

Hypoxia  

A deficiency in the amount of oxygen reaching the tissues.

IGF-1 and IGF-2  

 

 

 

A protein made by the body that stimulates the growth of many types of cells. Insulin-like growth factor is similar to insulin (a hormone made in the pancreas). There are two forms of insulin-like growth factor called IGF-1 and IGF-2. Higher than normal levels of IGF-1 and in some cancers IGF-2, may increase the risk of several types of cancer.

IL6  

 

 

Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene. Prolonged IL6 stimulating can lead to oncogenesis through stimulation of the STAT3 pathway.

Integrins  

 

 

 

These are the principal receptors used by animal cells to bind to the extracellular matrix. They are heterodimers and function as transmembrane linkers between the extracellular matrix and the actin cytoskeleton. A cell can regulate the adhesive activity of its integrins from within. Integrins hold a tumour together.

Ketogenic  

Traditionally associated with a low-carb, high fat diet although there are modifications of this.

Krebs Cycle or OXPHOS  

 

 

The sequence of reactions by which most living cells generate energy during the process of aerobic respiration. It takes place in the mitochondria, using up oxygen and producing carbon dioxide and water as waste products, and ADP is converted to energy-rich ATP.

Lipoprotein  

Any of a group of soluble proteins that combine with and transport fat or other lipids in the blood plasma

Lipogenesis  

The metabolic formation of fat

Lysosome  

 

 

lysosome is a membrane-bound cell organelle that contains digestive enzymes. Lysosomes are involved with various cell processes. They break down excess or worn-out cell parts. They may be used to destroy invading viruses and bacteria. They are involved in the process of autophagy.

Macrophages

(M1 or M2 type)

 

 

 

‘M2 type‘ macrophages exist in abundance in tumours and help form its protection from your own immune system. The M1 type is a type of white blood cell in contrast surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. The M2 type or tumour associated macrophages (TAMs) are macrophages that have been converted from M1 to assist and protect the cancer cell from cell death. Converting M2 types back to an M1 type assists cancer therapy.

Micropinocytosis  

 

Micropinocytosis or ‘cell drinking’ is a type of endocytosis that involves the nonspecific uptake of extracellular material, such as soluble molecules, nutrients, and antigens. It is used by many cancers (esp. pancreatic) to increase its nutrient availability especially to assist growth. It is part of the autophagy process.

Metastases  

The development of secondary malignant growths at a distance from a primary site of cancer.

Metronomic  

 

 

Treatment in which low doses of anticancer drugs are given on a continuous or frequent, regular schedule (such as daily, every few days or weekly), usually over a long time. Metronomic chemotherapy causes less severe side effects than standard chemotherapy

Microtubule  

 

 

Microtubules are microscopic hollow tubes made of the proteins alpha and beta tubulin that are part of a cell’s cytoskeleton, a network of protein filaments that extends throughout the cell, gives the cell shape, and keeps its organelles in place.

Mitochondria  

 

 

These are known as the powerhouses of the cell. They are organelles that act like a digestive system which takes in nutrients, breaks them down, and creates energy rich molecules for the cell. The biochemical processes of the cell are known as cellular respiration.

MMPs  

 

 

 

Matrix metalloproteinases. MMPs are enzymes involved in a variety of physiological and pathological processes including tumour cell invasion and metastasis. They break down the stroma surrounding a cancer cell allowing the cells to break off and spread to other parts of the body. They play a major role in tumour cell progression.

mTOR  

 

 

 

A protein sensing ‘switchboard’ it senses when conditions are right for cell division e.g. when nutrients are in abundance. mTOR may be more active in some types of cancer than others. Blocking mTOR may cause the cancer cells to die. If you block mTOR you will activate greater autophagy. This pathway may need to be blocked concurrently unless you are activating ferroptosis. Metformin inhibits mTOR.

MUFA  

 

 

 

 

Monounsaturated fatty acids, or MUFAs, are a type of unsaturated fat. “Mono,” meaning one, signifies that monounsaturated fats have only one double bond. There are many different types of MUFAs. Oleic acid is the most common type, comprising around 90% of those found in the diet. Too many MUFAs in the diet may prevent ferroptosis.

Myokine  

 

 

Small molecules secreted by contracting skeletal muscle cells, are an area of active interest in elucidating the anti-neoplastic effects of exercise. Myokines have been shown to act as tumour suppressors in breast and colon cancer

Necrosis  

 

The death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply

NED  

No Evidence of Disease

Notch signalling pathway  

 

Notch pathway plays an important role in linkage between angiogenesis and CSCs self-renewal. CSCs (cancer stem cells) are population of cells that have stem cell properties and invasion capabilities that contribute to cancer oncogenesis and metastasis.

Nucleosides  

 

 

1.    A small section of DNA or RNA.  A compound (e.g. adenosine or cytidine) consisting of a purine or pyrimidine base linked to a sugar.

2.  The difference between Nucleotides and Nucleosides – A building block of DNA or RNA- nucleotide is made up of the sugar, nitrogenous bases, and phosphate while the nucleoside is made up of sugar and base only

Nucleotides  

 

nucleotide is the basic building block of nucleic acids. RNA and DNA are polymers made of long chains of nucleotides. A nucleotide consists of a sugar molecule (either ribose in RNA or deoxyribose in DNA) attached to a phosphate group and a nitrogen-containing base

NSAIDs  

 

 

Nonsteroidal anti-inflammatory drugs are members of a drug class that reduces pain, decreases fever, prevents blood clots, and in higher doses, decreases inflammation. Side effects depend on the specific drug but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease

Oncogenes  

Oncogenes are genes that are closely linked to promoting cancer

Oncogenesis  

How cancer begins

Osteoblasts  

 

 

These are the cells that form new bone. They also come from the bone marrow and are related to structural cells. They have only one nucleus. Osteoblasts work in teams to build bone. They produce new bone called “osteoid” which is made of bone collagen and other protein

Osteoclasts  

A large multinucleate bone cell which absorbs bone tissue during growth and healing

OXPHOS  

 

 

Oxidative phosphorylation is the process in which ATP is formed as a result of the transfer of electrons from NADH or FADH 2 to O 2 by a series of electron carriers. This process, which takes place in mitochondria, is the major source of ATP in aerobic organisms

PGDF  

 

Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division secreted by platelets. PDGF promotes cancer cell growth.

Phenotype  

 

The observable physical or biochemical characteristics of an organism, as determined by both genetic makeup and environmental influences i.e., the tumour microenvironment.

Phospholipid  

Type of fat found in cell membranes.

Pleiotropic  

Producing more than one effect

PUFA  

 

Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond In their backbone. Some PUFAs are important for ferroptosis such as DHA and EPA.

RAS Gene  

 

 

 

Oncogenes are genes that are closely linked to cancer, and the gene that encodes Ras was among the first to be discovered. … Ras is involved in the signals passed between cells that control the amount of growth that is allowed at any time. Cancer-causing mutation of Ras creates a form of the protein that is always on. KRAS, HRAS and NRAS mutations cause aggressive cancers.

Reverse Warburg  

 

 

 

The Reverse Warburg Effect describes when glycolysis in the cancer-associated stroma (e.g. fibroblasts) metabolically supports adjacent cancer cells by producing lactate.  This lactate is then ingested by cancer cells which then convert it to pyruvate to increase OXPHOS. This catabolite transfer from neighbouring cells allows cancer cells to generate more ATP and increase proliferation.

RFA  

 

 

Radiofrequency ablation (RFA), also called fulguration, is a medical procedure in which part of the electrical conduction system of the heart, tumour or other dysfunctional tissue is ablated using the heat generated from medium frequency alternating current (in the range of 350–500 kHz).

RNA  

 

 

Ribonucleic acid, a nucleic acid present in all living cells. Its principal role is to act as a messenger carrying instructions from DNA for controlling the synthesis of proteins, although in some virus’s RNA rather than DNA carries the genetic information.

ROS  

 

 

 

 

 

 

Reactive oxygen species (ROS) are chemically reactive chemical species containing oxygen molecules. ROS are formed as a natural by-product of the normal metabolism of oxygen and have important roles in cell signalling and homeostasis. In cancer more ROS is created due to more metabolic activity in the cell and the cancer creates glutathione to prevent the ROScausing cell death. Excess ROS is used in many traditional treatments to trigger cell death as the cancer is unable to defend itself against high doses of oxygen free radicals, particularly if you block its ability to make glutathione (e.g. blocking xCT antiporter).

Sterols  

 

Any of a group of naturally occurring unsaturated steroid alcohols, typically waxy solids

TACE  

 

 

 

 

Trans arterial chemoembolization or TACE places chemotherapy and synthetic materials called embolic agents into a blood vessel feeding a cancerous tumour to cut off the tumour’s blood supply and trap the chemotherapy within the tumour. It is most often used to treat liver cancer but may also be used in patients whose cancer has spread to other areas of the body. Chemoembolization may be used as a standalone treatment or in combination with surgery, ablation, chemotherapy or radiation therapy.

TLR  

 

 

 

TLRs (toll like receptors) are membrane receptors that recognize cell-surface pathogens like bacteria or lipopolysaccharides (LPS), lipoproteins, lipopeptides and flagellin, among others; immune responses stimulated by TLR activation may result in immune-mediated tumour cell killing, e.g. BCG vaccination for bladder cancer.

TGF – Beta  

 

 

Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation.

TNF  

 

 

TNF as an anticancer agent. Although TNF has cytotoxic, cytostatic, and immunomodulatory effects on malignant tumours, using TNF as a chemotherapeutic drug has been hampered by its deleterious side effects, including systemic shock and widespread inflammatory responses.

Upregulate  

Turn on gene expression

Vacuole  

A space or vesicle within the cytoplasm of a cell, enclosed by a membrane and typically containing fluid

VEGF  

 

Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), is a signal protein produced by cells that stimulates the formation of blood vessels

Warburg Effect  

 

 

The term Warburg effect in oncology describes the observation that cancer cells, and many cells grown in vitro, exhibit glucose fermentation even when enough oxygen is present to properly respire. … The Warburg hypothesis was that the Warburg effectwas the root cause of cancer.

WNT Signalling  

 

 

The Wnt signalling pathway is an ancient and evolutionarily conserved pathway that regulates crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning and organogenesis during embryonic development. It is upregulated in many cancers.

xCT Antiporter  

 

 

 

This membrane transporter exports a molecule of glutamate in exchange for a molecule of cystine to create cysteine which is then used to create glutathione. The more aggressive a cancer, the more this pathway is upregulated. Inhibiting this pathway will starve a cancer of cysteine/glutathione and help trigger ferroptosis.

 

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