In the last post we dealt with the development of cancer and talked about mutation forms and more.
In the 3rd episode of this series, I want to thematize chronic inflammations and its causes as a preliminary stage of cancer. In addition to that different pathogens will be presented that have a more or less high risk of spark cancer. Let’s dive into it!
So first of all, we need to differentiate acute inflammation and chronic inflammation.
Inflammation is the response of vascularized tissues to harmful stimuli such as infectious agents, mechanical damage, and chemical irritants. Inflammation has both local and systemic manifestations and can be either acute or chronic.
Acute inflammation occurs minutes to hours following to the harm and has a short duration usually initiates our immune system.
There are often 5 typical signs:
- Rubor: Redness 🔴
- Calor: Heat 🔥
- Dolor: Pain 憷
- Functio laesa: Loss of function 🗲
- Tumor: Swelling
|Rubor||Redness||Increased blood flow helps to recruit the necessary cells of the immune system|
|Calor||Heat||Due to the increased blood flow and permeability of the blood vessels more heat is being dispensed|
|Dolor||Pain||This leads to the intuitive protection of the injured tissue in our behaviour|
|Functio laesa||Loss of function||e.g. restricted range of movement – this sign is often missing|
|Tumor||Swelling||Caused by the increased permeability of the capillaries water & cells diffuse into the damage tissue|
Not all the signs have to be present!
The aim is to eliminate pathogens, remove debris/waste from the injury and repair the tissue.
Chronic inflammations on the other hand last for months or years. Sometimes the typical sings of inflammation are not fully pronounced. Reason for that might be autoimmune diseases, chronic exposure to harmful substances or organisms, nondegradable pathogens or persistent infections (e.g. with tuberculosis, syphilis, HIV, H. Pylori etc.).
More so often chronic inflammations are autonomous processes meaning their lost their function as a warning signal – they themself are given pathological significance. Often the repair mechanisms lead to damaging the tissue instead of restoration of normal function.
One important aspect in the context of cancer is that acute inflammation is characterized by high levels of TNFα (tumor necrosis factor α) concentrations, which is simply a signal protein (zytokine) for the other cells (e.g. immune cells etc.) and is important for the immune response of the human body. Besides of that NFκB is an inflammation mediator promoting cell growth and inhibiting apoptosis (controlled cell death).
During acute inflammation states you have the balance of high levels of TNFαꜛ & NFκBꜛ, while in chronic inflammation states you have the dysbalance of low levels of TNFαꜜ & high levels of NFκBꜛ resulting into a lower immune activity with increased growth stimulus for e.g. cancer cells.
Apoptosis is the programmed, controlled cell death while necrosis is the result of uncontrolled cell death leading to inflammation! 🔥
Here are some examples of chronic inflammations and related carcinomas:
|Gastroesophageal reflux disease (GERD)||Adenocarcinoma of the oesophagus|
|Cigarette smoke, asbestos etc.||Bronchial carcinoma|
|Chronic pancreatitis||Pancreatic cancer|
|Ulcerative Colitis & Crohn's Disease||Colon cancer|
There are also a couple of infections caused by specific pathogens that can increase the risk of developing cancer immensely.
For example: Due to specific proteins produced by the virus genetic material in the host cells the cell cycle is being manipulated for the benefit of the virus – this includes among other things bypassing the cell's own security systems and repair mechanisms.
If by accident the genetic material of e.g. the Hepatitis B virus or HPV is integrated into the genome of the host cell permanently the carcinogenic potential unfolds.
Here are some examples of pathogens and related carcinomas:
|Hepatitis B & C due to HBV / HCV||Hepatocellular carcinoma|
|HPV infection||Cervical cancer|
|Helicobacter pylori infection||Gastric cancer and / or MALT lymphoma|
|Human herpesvirus 8 (often associated with AIDS)||Kaposi's sarcoma|
|Epstein-Barr-Virus (EBV)||Burkitt Lymphoma, Hodgkin Lymphoma, Nasopharyngeal Carcinoma & Gastric Carcinoma|
|Urocystitis due to schistosomiasis||Bladder cancer|
The HPV (human papillomavirus) is one of the most important risk factors concerning cervical cancer and reproduces itself in epithelia, keratinized skin and mucous membrane. Beside of cervical cancer it causes benign tumours such as skin warts.
There are different subtypes of this virus – it is important to distinguish between “low risk” & “high risk” subtypes. The “low risk” ones include HPV-6 & HPV-11 and the “high risk” group include HPV-16 & HPV-18.
A vaccination against HPV is possible, which is recommended by the STIKO (Standing Committee on Vaccination) for girls and now also for boys aged 9 to 14 years. The neutralizing antibodies can then be detected in the cervical secretion, for example, and are also effective against subtypes of HPV.
By now ...
✅ you know the difference between acute & chronic inflammations
✅ you are aware of chronic inflammations being a risk factor for developing cancer
✅ you are familiar with damage & repair mechanisms of the DNA
✅ you know the hallmarks of cancer cells
✅ you can explain the development of cancer & the Two-hit hypothesis
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See you soon!
In the final episode we will analyse the microcirculation of tumor tissue and talk about metastasis – this will go little more in detail for the geeks!