The lower pH is because the high glycolytic activity that produces acids equivalents in the cell, the higher T° is because the cell is continously replicating, this process needs and releases energy. Also, the increased glycolytic flux araises the T° of the cell.

Greetings.

Probably because they have higher glycolytic activity.

Exist more replication of DNA and all organelles,(increased mitosis), and it need more energy.

The lower pH is because the high glycolytic activity that produces acids equivalents in the cell, the higher T° is because the cell is continously replicating, this process needs and releases energy. Also, the increased glycolytic flux araises the T° of the cell.

Greetings.

@Paul Jennings.

Hi Mr Paul Jennings,

Thank you very much for initiating the discussion and also for your valuable suggestion.

@Ana Maria,

Thank you very much for valuable answer.

Higher temperature is due to faster proliferation and increased metabolic activity.

Thanx for opening an interesting topic. Regarding the acidic environment i would like to mention about the aerobic glycolysis that occurs in rapidly growing cell. This effect was first described by Otto Warburg in 1930. This low pH provides potection to tumor growth even from immune system! And regarding high temperature i would like to mention about the increase synthetic reaction such as DNA replication, Amino acid metabolism, increased transcription & translation, etc. That is there is an over all increased metabolic rate.

Tumor environment, in solid tumor is acid of course for the metabolic switch but also because, generally, vascularization of blood vessels and lymphatic vessels inside tumor are defective. This results either in poor oxigen supply, which leads to anaerobic metabolism initially, and to defective cleaning of anaerobic metabolism byproduct, which in turn leads to tumor milieu acidification. Temperature is higher either for the metabolic rate but also for the vasculature architecture inside tumor: it is defective and so no properly functional for vasodilatation/costriction and blood exchange with normal circulation. In this way liquids are retained and heat cannot be dissipated, increasing temperature locally.

Hope it will be of help!

Hi Shakila Mahalakshmi... Thank you very much.. Faster proliferation and increased metabolic activity may be reasons for the low ph and high Temp..

Hi Ahasanul...

Thank you very much .. For nice explaination. As you suggested, low pH might be involved in the protection for tumor cell from immune system. Rapid DNA replications might be the reason for the higher temperature.

Hi Mr Marco,

Thank you very much for nice explanation.

Hi, Chandrasekhar..............................................................................

Cancer is a perfectly natural process. A very small percentage of cells in every person who has ever lived turn cancerous. And the body usually gets rid of those cancerous cells before they do harm. This process has been going on for eons. It is only when more cancer cells are being created than the body can get rid of that the problem comes. With increased toxins, viruses, carcinogens, etc. our immune systems have become significantly overworked and weakened. In this situation, the low pH provides potection to tumor growth even from immune system. Increase metabolic reaction such as DNA replication, Amino acid metabolism, etc were leads to high temperature. There is an over all increased metabolic rate.

Ya Bhargav, according to your discussion.... rapid metabolic activities were one of the major cause for higher temperature and lower pH of the tumor cells. Thank you.

For further details you can follow some good literature. The underlying cause of all cancer, no matter what type, may have been discovered by Otto Warburg over 50 years ago. He actually won two Nobel Prizes for work proving cancer is caused by a lack of oxygen respiration in cells. He stated in "The Prime Cause and Prevention of Cancer" that the cause of cancer is no longer a mystery, we know it occurs whenever any cell is denied 60% of its oxygen requirements.

increase in pH is due to production of Lactic acid...

A wealth of experiential evidence exists through tissue culture, in that we know that the same cell type in different species will metabolize at a different rate and with different byproducts; pH in tissue culture media is obvious and instantly assessed through a color change from pink to yellow. For instance, rat fibroblasts are very acidic compared to mouse, and media need to be changed more frequently.

A more rapidly expanding culture also will deplete nutrients (including oxygen) more quickly -- naturally, if oxygen is limited the Krebs cycle in the cell breaks down glucose incompletely to produce lactic acid. Also, an overseeded population (too many cells plated) will produce the same effect. Once a population plateaus and reaches confluence, its metabolic demand also decreases. Most tissues in the body are stable and aren’t constantly dividing and growing; a tumor, on the other hand, is highly active, with the associated heat and byproducts.

Furthermore, a tumor in situ may be recognized by the immune system (e.g. by cytolytic T-lymphocytes) which can react to it with leukocyte infiltration causing inflammation. And lastly, a tumor is likely to have caused intense neovascularization (see Judah Folkman’s research on angiogenesis), and perfusion through the microvasculature is the body’s principal means of heat transfer.

So, overall at least three major scenarios exist: the fundamental cell metabolism of rapidly dividing cells; the immune response of inflammation; and tumor angiogenesis.

Hypoxic, ischemic and acidotic conditions of tumor cells due to their faster and accelerated growth. These conditions are secondary for protection from immune cells.

Dear prakash,

Thank you very much for you suggestions.

@Kristine

Respected Kristine,

Thank you very much for you such a detailed and valuable discussion and suggestions regarding abnormal behavior of tumor cell.

@Ospan Mynbaev

Respected Ospan Mynbaev,

Thank you very much for you valuable discussion and suggestions regarding abnormal behavior of tumor cell and how it will protect from the immune system.

Hi chandrasekhar,

You must change your internal environment to one in which cancer cannot thrive. Just as we couldn't live on Mars with no oxygen, cancer can't exist in cells where there is enough oxygen.

@Sawsan,

Thank you Sawsan,

Voltage gated sodium channels upregulation in metastatic cells also contributes to lower pH since the subsequent increase in intracellular sodium concentration activates the Na+/H+ exchanger.

cancer cell grow rapidally but at the same time blood vesscles fail to supply a lot of blood so there is partial deficiency of oxygen to cancerous cell. So anaerobic glycolysis is main pathway which supply energy which produce lactic acid as end product so cause acidic medium and decrease pH

A change in the Sodium level will not affect much when compared to a change in the pH level because concentration of Na is measured in micro equivalents / L and concentration of pH is measured in nano equivalents / L. Rise and fall of the pH depends on the proton ion concentration. More the proton ion conc. pH level will decrease and less the proton ion concentration pH level will increase. Because of the glycolytic activity normally cancer cells will have a lower pH value.

@Joffrey Ducroq

Thank you Joffrey Ducroq for valuable suggestion.

@Dr.Suhasini Bhatnagar,

Thank you Dr.Suhasini Bhatnagar for valuable suggestion.

@Madhuram Khandelwal ,

Thank you for valuable suggestions.

According to your suggestion, Partial deficiency of oxygen to cancerous cell might be the probable reason which leads to lactic acid.

@Ramesh Babu ...

Dear Ramesh Babu , thank for your valuable contribution regarding my question.

@Andrew Lane ...

Dear Andrew Lane, thank for your valuable contribution regarding my question.

@Salvador Harguindey ...

Dear Salvador Harguindey, thank for your valuable contribution regarding my question with use full references.

@Andrew Lane...

Dear Andrew Lane, thank for your valuable contribution regarding my question with use full references.

In cancer cells, glycolytic pathway leads to increased acidity rate, due in part to production of lactic acid, which is dependent on HIF (hypoxic inducible factor) activity.

Hyperthermia , i think, is a reaction which has as a consequence the death of cancer cells.

In chemistry, alkali solutions (pH over 7.0) tend to absorb oxygen, while acids (pH under 7.0) tend to expel oxygen. For example, a mild alkali can absorb over 100 times as much oxygen as a mild acid. Therefore, when the body becomes acidic by dropping below pH 7.0 (note: all body fluids, except for stomach and urine, are supposed to be mildly alkaline at pH 7.4), oxygen is driven out of the body thereby, according to Nobel Prize winner Otto Warburg, inducing cancer. Stomach fluids must remain acidic to digest food and urine must remain acidic to remove wastes from the body. Blood is the exception. Blood must always remain at an alkaline pH 7.4 so that it can retain its oxygen. When adequate mineral consumption is in the diet, the blood is supplied the crucial minerals required to maintain an alkaline pH of 7.4.

However when insufficient mineral consumption is in the diet, the body is forced to rob Peter (other body fluids) to pay Paul (the blood). In doing so, it removes crucial minerals, such as calcium, from the saliva, spinal fluids, kidneys, liver, etc., in order to maintain the blood at pH 7.4. This causes the de-mineralized fluids and organs to become acidic and therefore anaerobic, thus inducing not only cancer, but a host of other degenerative diseases, such as heart disease, diabetes, arthritis, lupus, etc.. Everyone knows that the human body is made up of 78% water by weight, and that water is hydrogen and oxygen gases. When nitrogen gas and carbon in the form of carbon dioxide and methane gases are added, the total gas in the body by weight becomes over 95%. Almost half of the remaining 5% that makes up the human body and controls all biological functions is the mineral calcium. No other mineral is capable of performing as many biological functions as is calcium. Calcium is involved in almost every biological function. This amazing mineral provides the electrical energy for the heart to beat and for all muscle movement. It is the calcium ion that is responsible for feeding every cell. It does this by latching on to seven nutrient molecules and one water molecule and pulls them through the nutrient channel. It then detaches its load and returns to repeat the process. Another important biological job for calcium is DNA replication, which is crucial for maintaining youth and a healthy body. DNA replication is the basis for all body repair and can only occur on a substrate of calcium.

Thus, low calcium means low body repair and premature aging. As important as all these and hundreds of other biological functions of calcium are to human health, none is more important than the job of pH control. Calcium to acid, is like water to a fire. Calcium quickly destroys oxygen robbing acid in the body fluids. Thus, the more calcium, the more oxygen, and therefore, the less cancer and other degenerative disease.In chemistry, alkali solutions (pH over 7.0) tend to absorb oxygen, while acids (pH under 7.0) tend to expel oxygen. For example, a mild alkali can absorb over 100 times as much oxygen as a mild acid. Therefore, when the body becomes acidic by dropping below pH 7.0 (note: all body fluids, except for stomach and urine, are supposed to be mildly alkaline at pH 7.4), oxygen is driven out of the body thereby, according to Nobel Prize winner Otto Warburg, inducing cancer. Stomach fluids must remain acidic to digest food and urine must remain acidic to remove wastes from the body. Blood is the exception. Blood must always remain at an alkaline pH 7.4 so that it can retain its oxygen. When adequate mineral consumption is in the diet, the blood is supplied the crucial minerals required to maintain an alkaline pH of 7.4.

However when insufficient mineral consumption is in the diet, the body is forced to rob Peter (other body fluids) to pay Paul (the blood). In doing so, it removes crucial minerals, such as calcium, from the saliva, spinal fluids, kidneys, liver, etc., in order to maintain the blood at pH 7.4. This causes the de-mineralized fluids and organs to become acidic and therefore anaerobic, thus inducing not only cancer, but a host of other degenerative diseases, such as heart disease, diabetes, arthritis, lupus, etc.. Everyone knows that the human body is made up of 78% water by weight, and that water is hydrogen and oxygen gases. When nitrogen gas and carbon in the form of carbon dioxide and methane gases are added, the total gas in the body by weight becomes over 95%. Almost half of the remaining 5% that makes up the human body and controls all biological functions is the mineral calcium. No other mineral is capable of performing as many biological functions as is calcium. Calcium is involved in almost every biological function. This amazing mineral provides the electrical energy for the heart to beat and for all muscle movement. It is the calcium ion that is responsible for feeding every cell. It does this by latching on to seven nutrient molecules and one water molecule and pulls them through the nutrient channel. It then detaches its load and returns to repeat the process. Another important biological job for calcium is DNA replication, which is crucial for maintaining youth and a healthy body. DNA replication is the basis for all body repair and can only occur on a substrate of calcium.

Thus, low calcium means low body repair and premature aging. As important as all these and hundreds of other biological functions of calcium are to human health, none is more important than the job of pH control. Calcium to acid, is like water to a fire. Calcium quickly destroys oxygen robbing acid in the body fluids. Thus, the more calcium, the more oxygen, and therefore, the less cancer and other degenerative disease.

Rapid metabolism of growth cell might be the reason,...

One factor you have to take into account is that tumors are recognized as being wounds that have to close. So the tumor microenvironment is inflamed with high vascularity and secreted cytokines and chemokines. This is leading to the increased temperature of the tissue as it happens with any inflamed tissue.

In short it is related to its high glycolitic activity that maintains a high metabolic rate and the production of lactic acid.

PHi less or higher in cancer cell? More acid?

Than you very much Salvador....

pH will be higher in cancer cell......................

@Salvador...

Than you very much...

Because the cell through out more H+?

I think the fact that solid tumors end to be hypoxic should also be taken into acount: In hypoxia, the mitochondrial O2 consumption rate and ATP production are reduced, which hinders inter alia active transport in tumor cells. Specifically, major effects of the reduced production of ATP are 1) collapse of Na+ and K+ gradients, 2)

depolarization of membranes, 3) cellular uptake of Cl−, 4) cell swelling, 5) increased cytosolic Ca2+ concentration, and finally, 6) decreased cytosolic pH, resulting in intracellular acidosis in tumor cells.

This was described by Warburg back in 1920s but has been put on the shelf alot of the time due to him being funded by the third reich and describes how tumor cells are more glycolytic active than normal cells and TCA cycle activity is reduced. This would have several benefits to the tumor cells as pyruvate would, instead of entering TCA cycle, be shunted towards purine/pyrimadine synthesis thus driving DNA replication and inturn proliferation. The inactivity of the mitochondria could also play an inhibitory role in instrinsic apoptosis as the loss of mitochrondrial membrane potential COULD inhibit the release of Cytochrome C.

There is a new paradigm shift as its been demonstrated that in BCC it appears the stromal fibroblasts are removing their mitochondria via autophagy, undergoing glycolitic pathway but then passing high energy metabolites onto the tumor cells, coined the "reverse Warburg effect". http://www.breastcentre.manchester.ac.uk/Michael_Lisanti/Reverse_warburg_effect

How do we demonstrate this in situ?

Andrew, I repeat by error the vote up and was subtracted my vote, and I cannot repair this.

The cancer cell lost (or no acquire) the proteins and RNA of functionality. Haven´t hypertrophy and haven´t specialization. Only use DNA and RNA for replication. Not developed RNA and proteins of complete functions (because the relationship of functionality with rest of body, (secretory activity, development of the cell periphery, contraction, complete metabolism because the functionality, apoptosis, etc.)).

They have progression of G1 phase without control. (No inhibition of Rho, and no proteins of complete functions).

The link between cancer and oxygen is clear. In fact an underlying cause of cancer is low cellular oxygenation levels. In newly formed cells, low levels of oxygen damage respiration enzymes so that they cells cannot produce energy using oxygen. These cells can then turn cancerous.

The cancers with the highest growth rates had the highest fermentation rates. The slower a cancer grew, the less it used fermentation to produce energy.

Due to higher rate of cell differentiation, there is irratic and uncontrolled growth where the oxygen supply is lower. Hence the tumor cells undergo anearobic respiration resulting into formation of lactic acid. This event changes the pH profile of tumor cells (acidic i.e., lower pH) when compared to the normal cells. Moreover, the temperature also rises due to continuous cell growth and differentiation to liberate energy.    

Dear all, as clinician -ignorant of molecular issues- I have a naive question to ask. O2 tension in capillaries is quite low in many tissues: at enterocyte in colon (I read) it is 4%, and in cartilage 0,1%, far lower than the 1% I read for  tumor (which ones?). Hence, it is low O2 by definition. I have difficultis  finding NORMAL/usual concentration in non-tumoral tissues. Moreover, I read that stem cells proliferate preferably in low O2 tension, and that cartilage growth requires high glucose. Malignancy in cartilage is not frequent, in my experience (I'm not a specialist). [email protected]

Dear all, your discussion has been very interesting. Can somebody refer me to suitable literature on what type of cancer tissues show increased temperature and to what extent? Also if there is any source of temperature of different cancer types.