Hypoxia (environmental), reduced oxygen content of air or a body of water detrimental to aerobic organisms

Hypoxia (medical), a pathological condition in which the body or a region of the body is deprived of an adequate oxygen supply

Autoerotic hypoxia or erotic asphyxiation, intentional restriction of oxygen to the brain for sexual arousal

Cerebral hypoxia or cerebral anoxia, a reduced supply of oxygen to the brain

Diffusion hypoxia or Fink effect, a factor that influences ...

hypoxia

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Cancer is seen as a complex disease that proceeds with numerous genetic changes, including oncogenes, tumor suppressors, DNA repair, cancer metabolism, and genetic origin, leading to excessive growth, metastasis, and drug resistance. Medicine knows various methods for cancer treatment and therapy, such as chemotherapy, interventional oncology, radiotherapy, surgery, hematological oncology, and others. In fact, some of the most promising methods are aimed at destroying tumor cells and deterring their metastasization.

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The modern era of cancer treatment is constantly evolving, with new breakthroughs and discoveries changing the course of treatment and therapy. It is these innovative approaches that we look at in today's article.

What-is-cancer

What is cancer

What-is-cancer_0_0

Cells are the main units that make up the human body. They grow and divide to create new cells, as the body needs them. Usually, cells die when they become too old or damaged. Then new cells appear in their place.

What-is-cancer_0_1

Cancer begins when genetic changes interfere with this consistent and rigorous process. Cells begin to grow uncontrollably and can form a mass called a "tumor". The tumor can be cancerous or benign. A cancerous tumor is a malignant formation, which means it can grow and spread to other parts of the body. A benign tumor means that the tumor can grow, but it will not spread.

What-is-cancer_0_2

Generally speaking, cancer refers to cells that grow uncontrollably and invade other tissues. Cells can become cancerous due to the accumulation of defects or mutations in their DNA. Most of the time, cells are able to detect and repair DNA damage. If a cell is severely damaged and cannot recover, it usually undergoes so-called programmed cell death or apoptosis. Cancer occurs when damaged cells grow, divide and spread unusually, instead of self-destruct.

What-is-cancer_0_3

As cancer develops in the body, it uses different mechanisms to progress and affect various organs and tissues. One of these mechanisms involves blood supply - large tumor formations rely on it to deliver oxygen and nutrients to help them grow. As tumors grow, these blood vessels are unable to provide oxygen and nutrients to any part of the tumor, leading to areas with decreased oxygen levels. However, this environment over time leads to the accumulation of acid in tumor cells.

What-is-cancer_0_4

British-Columbia-researchers'-discovery

British Columbia researchers' discovery

British-Columbia-researchers'-discovery_1_0

To cope with the stress that arises, cells adapt by releasing enzymes that neutralize the acidic conditions of their environment, allowing the cells not only to survive but also to become a more aggressive form of tumor, capable of spreading to other organs. One of these enzymes is called "carboanhydrase IX" (CAIX). A team of researchers from the Faculty of Medicine and the Institute of Cancer Research at the Тhe University of British Columbia discovered the anticancer effect of this enzyme and found that it inhibits cell growth. This is exactly what makes it the "Achilles heel" of cancer cells.

British-Columbia-researchers'-discovery_1_1

In the same study, the research team looked at cell properties and identified the weaknesses of the enzyme "CAIX". They found that the enzyme works through a powerful mechanism known as the 'genome-wide synthetic lethal screen'. This tool looks at the genetics of a cancer cell and systematically erases one gene at a time to determine whether it can be destroyed by eliminating the CAIX enzyme along with another specific gene. [<a href="https://www.science.org/doi/10.1126/sciadv.abj0364" target="_blank" rel="noopener">ref.1</a>]

British-Columbia-researchers'-discovery_1_2

According to Dr. Dedhar - a professor in the faculty and one of the authors of the study, this form of cell death occurs when iron accumulates and weakens the metabolism of the tumour and cell membranes. In June 2021 “Kojin Therapeutics” raised $60 million to accelerate research started at Harvard University and the Dana-Farber Cancer Institute, which involves the use of small molecules to destroy cells that are most vulnerable to ferroptosis. [<a href="https://www.fiercebiotech.com/biotech/kojin-bags-60m-to-exploit-weakness-drug-resistant-cancers" target="_blank" rel="noopener">ref.5</a>]

British-Columbia-researchers'-discovery_1_3

Dr. Dedhar's research team has also found that combining CAIX inhibitors, including SLC-0111, with compounds known to cause ferroptosis, leads to catastrophic cell death and debilitates tumor growth. [<a href="https://www.science.org/doi/10.1126/sciadv.abj0364" target="_blank" rel="noopener">ref.1</a>][<a href="https://pubmed.ncbi.nlm.nih.gov/21606941/" target="_blank" rel="noopener">ref.3]</a>

British-Columbia-researchers'-discovery_1_4

New-strategies-for-cancer-treatment---what-are-the-horizons

New strategies for cancer treatment - what are the horizons

New-strategies-for-cancer-treatment---what-are-the-horizons_2_0

The results of the study, published August 27, 2021 in the multidisciplinary journal Science Advances, are expected to help researchers develop new cancer treatment strategies. [<a href="https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abj0364" target="_blank" rel="noopener">ref.2]</a> Their goal is to limit the progression of solid cancerous tumor formations, which represent the majority of tumor species occurring in the human body.

New-strategies-for-cancer-treatment---what-are-the-horizons_2_1

Dr. Shoukat Dedhar said another unique compound known as "SLC-0111" had previously been identified. It is currently being investigated in phase 1 clinical trials (initial human testing) as a potent inhibitor of the CAIX enzyme. While preclinical models of breast, pancreatic, and brain cancer have shown the effectiveness of this compound in suppressing tumor growth and spread, other cellular properties reduce its effectiveness. Therefore, more research is needed to confirm its potential and dependence on other factors.

New-strategies-for-cancer-treatment---what-are-the-horizons_2_2

In other studies on the topic, scientists looked at methods of targeting hypoxia in cancer therapy and destroying cancerous tumors. [<a href="https://pubmed.ncbi.nlm.nih.gov/21606941/" target="_blank" rel="noopener">ref.3</a>] The two main approaches to this are bioreductive&nbsp;(hypoxia-activated) prodrugs (modified drugs that are transformable before they become pharmacologically active) and inhibitors of molecules on which the survival of hypoxic cells depends.&nbsp;

New-strategies-for-cancer-treatment---what-are-the-horizons_2_3

In short, this is a new type of programmed cell death and is closely related to both the maintenance of homeostasis and the development of diseases, especially cancers. [<a href="https://www.frontiersin.org/articles/10.3389/fonc.2020.571127/full" target="_blank" rel="noopener">ref.4</a>]

New-strategies-for-cancer-treatment---what-are-the-horizons_2_4

It is worth mentioning another step in the progress of cancer treatment. A new drug that can stop tumour growth will be offered to National Health Service patients with lung cancer - the first in Europe to receive the drug. The drug is aimed at the mutation of the KRAS gene found in a quarter of all tumours, which has become known as the "Death Star" mutation due to its spherical appearance. National Health Service researchers have spent 40 years looking for the key to this mutation, and if the treatment works, it could represent a major breakthrough in the fight against other cancers, such as pancreatic cancer and colorectal cancer. [<a href="https://www.independent.co.uk/news/uk/home-news/lung-cancer-drug-tumour-nhs-b1917632.html" target="_blank" rel="noopener">ref.6</a>]

New-strategies-for-cancer-treatment---what-are-the-horizons_2_5

New-strategies-for-cancer-treatment---what-are-the-horizons_2_6

We should remember that cancer belongs to the group of treatable diseases, and every step in the process of diagnosis and treatment is crucial for a favorable development. Our team will keep you up to date on the latest discoveries and achievements in the field, as always at <a href="../../" target="_blank" rel="noopener">&nbsp;Sanat.io.</a>

Cancer is a treacherous and severe disease that is detrimental not only to the body but also to the human spirit. When it is malignant (in very rare cases benign tumors are also life-threatening), it can mean years of struggle and survival attempts. New immunological cancer therapies offer hope for a better outcome, years of survival, and successful recovery therapy.

A light at the end of the tunnel - cancerous tumors and their "Achilles heel"

https://d20hztklr4qnvi.cloudfront.net/68279ed8-fde0-4bc7-9278-c5eaadec7a6e_middle.jpg

 A light at the end of the tunnel - cancerous tumors and their

Бетина Цветкова

Author: Silvia Marinova, PhD student in the Genomic Stability Laboratory at BAS

Thalassemia is a <a href="/p/kak_ghienitie_opriedieliat_prilikata_s_roditielitie_ni_2256bb0a_9ee8_4d00_8f3e_7ca44b90aa45" target="_blank" rel="noreferrer">rare genetic inherited blood disease</a> in which the body does not produce enough of the hemoglobin <a href="/p/kakva_ie_razlikata_miezhdu_bieltk_i_protiein_b1b6b96e_e340_46d2_9768_ac9fa8cd6adc" target="_blank" rel="noreferrer">protein</a>. It is an essential part of red blood cells and is responsible for the transfer of oxygen between individual tissues in the body. When not producing a sufficient amount of it, this leads to the malfunctioning of red blood cells and shortens their lifes.

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As a result, a smaller proportion of them circulate in the bloodstream, and oxygen that reaches the cells is not enough. This leads to <a href="/p/aniemiia_kolko_vida_sshchiestvuvat_kakvo_da_iadiem_kak_da_kombiniramie_khranitie" target="_blank" rel="noreferrer">anemia</a>, a feeling of fatigue and other symptoms, which we will consider in more detail in the article. We will also pay attention to the types of thalassemia, how it is diagnosed and what treatment there is.

Types-of-thalassemia

Types of thalassemia

Types-of-thalassemia_0_0

Thalassemia <a href="https://www.bioseek.eu/us/eng/research/pubmed/Global_epidemiology_of_hemoglobin_disorders_9668547" target="_blank" rel="noopener"></a> is most common in people from Mediterranean, African and South-Eastern Asian populations. However, due to increased migration, it is already found in other areas [<a href="https://www.bioseek.eu/us/eng/research/pubmed/Global_epidemiology_of_hemoglobin_disorders_9668547" target="_blank" rel="noopener">ref.1</a>].

Types-of-thalassemia_0_1

When talking about different types of thalassaemia, <a href="https://www.bioseek.eu/us/eng/research/search?q=DISEASE%3AMESH%3AD017085%2BDISEASE%3AMESH%3AD017086&amp;t=22&amp;o=00&amp;p=1&amp;st=1&amp;tp=9" target="_blank" rel="noopener"></a> we may consider two main things. If it is the part of hemoglobin that is affected, then two main types are recognized - alpha or beta thalassemia [<a href="https://www.bioseek.eu/us/eng/research/search?q=DISEASE%3AMESH%3AD017085%2BDISEASE%3AMESH%3AD017086&amp;t=22&amp;o=00&amp;p=1&amp;st=1&amp;tp=9" target="_blank" rel="noopener">ref.2</a>]. They, in turn, can be divided into subtypes depending on the severity of the disease - thalassemia minor, intermediate or major.

Types-of-thalassemia_0_2

Hemoglobin is an iron-containing protein that carries oxygen into our body. Its main form is composed of the so-called alpha and beta globlin chains and contains two of them. If one of the chains is produced in a smaller amount or is not produced at all, then thalassemia occurs. Depending on which of the two is affected, we distinguish the alpha and beta form of the disease.

How-is-thalassaemia-inherited

How is thalassaemia inherited

How-is-thalassaemia-inherited_1_0

Thalassemia is inherited from parents to children, and because of this it is said that it is an inherited disease. In general, inheritance is autosomal recessive, which means that we need to <a href="/p/kak_ghienitie_opriedieliat_prilikata_s_roditielitie_ni_2256bb0a_9ee8_4d00_8f3e_7ca44b90aa45" target="_blank" rel="noreferrer">inherit</a> a defective allele of the gene from both parents in order to develop the disease. If, however, we inherit such a gene from only one parent, then we are carriers of the disease and more often symptomatology does not develop.

How-is-thalassaemia-inherited_1_1

How-is-thalassaemia-inherited_1_2

The HBB gene [<a href="https://ghr.nlm.nih.gov/gene/HBB" target="_blank" rel="noopener">ref.3</a>] is responsible for the synthesis of beta globrin chains. When there is an error in it, our cells receive incorrect instructions and this leads either to their reduced amount or to the lack of their synthesis.

How-is-thalassaemia-inherited_1_3

The gene is represented in two copies (allels) in our genome - one from each parent, and since the disease is inherited autosomally recessively, upon receiving two mutant copies, then a disease with severe symptoms develops - beta thalassemia intermedia or major.

How-is-thalassaemia-inherited_1_4

If we are carriers with only one damaged gene, then in most cases there is no symptomatology, but it is possible in some cases to develop the mild "minor" form&nbsp;[<a href="https://www.bioseek.eu/us/eng/research/pubmed/Beta_thalassemia_20492708" target="_blank" rel="noopener">ref.4</a>].

How-is-thalassaemia-inherited_1_5

How genes determine resemblance to our parents

How-is-thalassaemia-inherited_1_6

Inheritance in alpha thalassaemia is a little more complicated, since alpha globine chains need two <a href="https://ghr.nlm.nih.gov/gene/HBA1" target="_blank" rel="noopener">genes HBA1</a> [ref.5] and <a href="https://ghr.nlm.nih.gov/gene/HBA2" target="_blank" rel="noopener">HBA2</a> [ref.6]. For each gene, one copy is inherited from the mother and the other from the father. If at least one copy of the gene is divided (missing) in both parents, then there is a risk that their children will develop alpha thalassaemia. The severity of the disease depends on how many copies are divided and in what combination.

How-is-thalassaemia-inherited_1_7

<ul>
<li style="font-weight: 400;">One deleted copy - this is the mildest form of alpha thalassemia, and more often individuals with this type <a href="/p/mutatsii_srieshchu_iestiestvien_podbor_e4a316a0_b5fd_4a51_8dc0_12a14405f8f2" target="_blank" rel="noreferrer">of mutation</a> are only carriers. In rare cases, non-severe <a href="https://www.nature.com/articles/gim9201117" target="_blank" rel="noopener">microcytosis</a> [ref.7] develops, which is characterized by smaller than normal red blood cells (erythrocytes).</li>
<li style="font-weight: 400;">Two deleted copies - when two copies are missing, this also leads to a mild state of alpha thalassemia minor.</li>
<li style="font-weight: 400;">Three deleted copies - then an average disease develops in severity, which is known by the name HbH thalassemia. The result of it is an excess of beta globin chains and their aggregation in the form of abnormal aggregates in red blood cells.</li>
<li style="font-weight: 400;">Four deleted copies - this is the most severe form in which alpha chains are not produced at all. The disease is called Hb Barth syndrome and leads to severe changes during fetal development. In most cases, this causes premature birth, and even if not - the baby rarely survives more than a few months after birth.</li>
</ul>

What-are-the-symptoms-of-thalassemia

What are the symptoms of thalassemia

What-are-the-symptoms-of-thalassemia_2_0

The clinical picture of the disease depends on the type of thalassemia, as well as its severity.

What-are-the-symptoms-of-thalassemia_2_1

Symptoms may include:

What-are-the-symptoms-of-thalassemia_2_2

<ul>
<li style="font-weight: 400;">general fatigue</li>
<li style="font-weight: 400;">weakness</li>
<li style="font-weight: 400;">pale or yellowish skin</li>
<li style="font-weight: 400;">enlarged and deformed bones, especially facial</li>
<li style="font-weight: 400;">dark urine</li>
<li style="font-weight: 400;">oxygen deficiency (hypoxia)</li>
<li style="font-weight: 400;">delayed growth and development, etc.</li>
</ul>

What-are-the-symptoms-of-thalassemia_2_3

Often the symptoms are visible at birth or develop in the first and second year of the baby's life. In milder forms, symptoms may also appear in later childhood or adolescence.

Diagnosis-and-prevention-of-thalassemia

Diagnosis and prevention of thalassemia

Diagnosis-and-prevention-of-thalassemia_3_0

Diagnosis-and-prevention-of-thalassemia_3_1

Diagnosis usually begins with a blood test. The doctor will monitor indicators such as amount of hemoglobin, erythrocyte size, bilirubin level, iron in the blood and others. To confirm the diagnosis, the so-called hemoglobin electrophoresis is performed, which can indicate the ratio between the different globin chains.

Diagnosis-and-prevention-of-thalassemia_3_2

There are also genetic tests that can confirm the type of thalassemia. If it is known that there is a family history of the disease, then such a test can be done to future parents who plan to have a child in order to assess the risk to offspring.

Treatment-of-thalassemia

Treatment of   thalassemia

Treatment-of-thalassemia_4_0

Methods of treatment are again directly dependent on the severity of the condition. People who suffer from this disease should be treated by doctor whose specialty is associated with blood diseases - a hematologist.

Treatment-of-thalassemia_4_1

In severe forms of the disease, patients usually need frequent blood transfusions and/or iron-chelating therapy [<a href="https://www.bioseek.eu/us/eng/research/pubmed/Iron_chelation_therapy_in_transfusion_dependent_thalassemia_patients_current_strategies_and_future_directions_26124688" target="_blank" rel="noopener">ref.8</a>] to bind excess iron in the blood and thus prevent serious organ damage. People suffering from milder forms often do not need specific treatment. <a href="https://www.bioseek.eu/us/eng/research/pubmed/Iron_chelation_therapy_in_transfusion_dependent_thalassemia_patients_current_strategies_and_future_directions_26124688" target="_blank" rel="noopener"></a>

Treatment-of-thalassemia_4_2

It should be noted that it is extremely important for all patients with thalassemia to make "healthy" choices, because for them this means dealing with the disease and improving their quality of life. It is advisable to observe a specific diet in which to avoid iron-rich foods, to do exercises tailored to the severity of the disease and to make all mandatory and recommended immunizations, since people with thalassemia have a higher risk of developing certain infections.

Treatment-of-thalassemia_4_3

Treatment-of-thalassemia_4_4

<a href="/p/kak_ghienitie_opriedieliat_prilikata_s_roditielitie_ni_2256bb0a_9ee8_4d00_8f3e_7ca44b90aa45" target="_blank" rel="noreferrer">How genes determine resemblance to our parents</a>

Treatment-of-thalassemia_4_5

<a href="/p/kak_nuklieinovitie_kisielini_dnk_i_rnk_dirizhirat_zhivota_7b8f007a_0254_40cb_8d72_36410852722e" target="_blank" rel="noreferrer">How nucleic acids DNA and RNA orchestrate life</a>

Treatment-of-thalassemia_4_6

<a href="/p/ima_li_smisl_da_si_napravish_ghienietichien_tiest_0a6b928b_e726_4246_be6a_2ef32f93ccf0" target="_blank" rel="noreferrer">Does it make sense to take a genetic test?</a>

Treatment-of-thalassemia_4_7

<a href="/p/iepighienietikata_ili_kak_nachint_na_zhivot_upravliava_ghienitie_ni_8ec805d0_069f_4823_89cd_c55d051a9610" target="_blank" rel="noreferrer">Epigenetics or how lifestyle governs our genes</a>

Treatment-of-thalassemia_4_8

<a href="/p/mutatsii_srieshchu_iestiestvien_podbor_e4a316a0_b5fd_4a51_8dc0_12a14405f8f2" target="_blank" rel="noreferrer">Mutations vs. Natural Selection</a>

hypoxia

What is thalassemia - types, symptoms and treatment