Friday, March 24, 2017

Updating Co-carcinogenesis

Title:  Updating Co-carcinogenesis

Abstract:  Co-carcinogenesis is the synergism between a nuclear virus and a carcinogen to cause cancer.

Cancer cells appear to express the receptors the viruses used to infect them.  Cancer cells also have specific embryonic Hervs that have been activated by these viruses based on their methylation preferences.

The virus opened the DNA up and then could not function because the carcinogen inhibited the viral polymerase. The viral polymerases have probably evolved to compete with host polymerases and have stronger binding efficiencies.

Cancer occurs because a carcinogen inhibits the viral polymerase better than the human polymerase. When a virus infects the same cell as a carcinogen they interact.  Instead of the virus making what it wants in the host the infected cell is transformed into a cancer cell by the carcinogen. 

 These hypotheses supports Co-carcinogenesis as the cause of cancer where it is the synergism between a carcinogen and a virus that causes cancer. Both have to be present in the nucleus of a cell.

This paper will go through several types of cancer looking at the patterns of receptors on tumors, of the cancers that tend to appear together, looking for the viruses that have been isolated from tumors and the Hervs expressed by the cancer tumors. The most likely carcinogen for each cancer will also be examined.

Introduction:
 Francis Peyton Rous challenged the oncology world first when he suggested that tumors and cancers did not spontaneously occur but could be triggered by something in a contagious way.  He could see that he was transferring some agent from one chicken to another and triggering the tumors.  Unbeknownst to him he was working with the Rous Sarcoma virus. (when the virus was discovered it was named after him) The oncology world seemed to believe that this was strictly a chicken pattern.  Unsuccessfully he alone attempted to isolate this and other viruses from mammalian tumors for years.

In 1933 fellow researcher Richard Shope finally isolated HPV from mouse tumors. They now had a mammalian virus.  Fervently Rous and his coworker Friedewald studied the HPV virus attempting to prove that this virus triggered the tumors in mammals.

Rous and Shope then joined forces and went on to demonstrate that cold tar could synergistically with a rabbit papilloma virus cause squamous cell cancers.  Viruses did not just cause tumors they could cause cancer. These experiments were reproduced and copied using other viruses and other carcinogens and the idea of synergism had just started to take off when I believe we became distracted with the horrific results of war. The agent orange used during the Vietnam war damaged DNA so profoundly that the world saw such cancers and birth defects completely differently.  The general public and even most researchers now will say that cancer is caused by DNA damage. Co-carcinogenesis was quickly forgotten as we embraced anti-oxidants in attempts to protect our DNA from damage.

Even in the 1966 nobel prize speech Rous gave for work on HPV he expressed how most cancer was not a transformed gene from DNA damage rather from viruses but the world didn't listen.

In 2004 Harry Haverkos wrote a paper on viruses, chemicals, and co-carcinogenesis. He demonstrated the possible co-carcinogenesis of cervical cancer, hepatocellular carcinoma, and Kaposi's sarcoma.  Co-carcinogenesis he suggested is the synergistic actions of a virus and a carcinogen together on a host cell that causes cancer; that both must be present as Rous hypothesized. 

Based on what we know today this paper will attempt to suggest possible pathways to explain the mechanism of cancer development.

Hypotheses:  Only nuclear viruses cause cancer.  Cancer cells, the tumors, express the receptors the virus used to infect them.  Carcinogens inhibit the host's polymerases until the viral polymerases are present.  Which embryonic hervs that are expressed in the cancer reveals which method the virus uses: methylation or demethylation.  All of these hypotheses come together to support Co-carcinogenesis as the common cause of cancer. 

Evaluation of Hypothesis:

Viruses are now known to make proteins that interact with the telomeres which are the ends of our chromosomes. The condition of the telomeres, how frayed or pristine, determines how many times the chromosomes can be copied.  Viruses are therefore making our DNA, the cookbooks of our cells, immortal and open for use.  Carcinogens, such as benzene and phenols, are now known to have multiple actions including inhibiting polymerases which are the DNA readers.  Viruses typically make their own polymerases which have a stronger affinity for binding in order to compete with the host's polymerase. Now imagine them coexisting as Co-carcinogenesis suggests.  The DNA has been opened up but the viral polymerases are inhibited by the carcinogen and a cancer cell has been created.  Is this possible? The virus when it enters a cell uses a specific receptor thus stimulates the production of more of those specific receptors to be made.  It is my contention that when we look at the cancerous tumors they will be over expressing the receptor which tells us which virus triggered them. So let's look at a few cancers and see.

Breast cancer

Breast cancer has two major types. An estrogen receptor positive type and the triple negative type.  Interestingly enough two viruses have been isolated from breast cancer; the HPV virus and the Epstein-barr virus.

 The Epstein Barr virus is likely using estrogen receptors 

 In adrenal cells alpha-estrogen receptors which some herpes viruses use cycle to the nucleus which would allow herpes viruses to interact with DNA.  EBV has been suspected of triggering breast cancer.  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972522/)   In Breast cancer the herpes virus would be carried to the nucleus by the estrogen receptor and if a carcinogen was there cause cancer.

 A virus in the mitochondria does not cause cancer.  This is why viral polymerase inhibitors can be given to patients with the shingles without causing cancer but this is not true for EBV herpes infections in other cell types. The herpes zoster virus uses the beta-estrogen receptors which cycle to the mitochondria.  Cancer viruses cycle to the nucleus.

If the herpes virus Epstein-barr triggers the estrogen receptor positive tumors of breast cancer then the HPV virus could be the trigger of the other type of breast cancer tumor.  Triple negative estrogen receptor breast cancers have been found to contain HPV.  HPV could be using cannabinoid receptors.  Cannabinoid receptors are on triple negative tumors and cannabinoid treatments have been considered as a form of treatment for triple negative breast cancers.

Cannabinoids inhibited cervical cancer cells migration, a known HPV cancer.  Interestingly enough cannabinus oil has also been a suggested remedy for non-melanoma cancers.  Non-melanoma skin cancer has associations with HPV.  Non-melanoma skin cancer has increased cannabinoid receptors.  Triple negative receptor breast cancers and cervical cancers should be examined for increased cannabinoid receptors.

For the two types of breast cancer we can connect 2 types of viruses but an increase in receptors is only known for the herpes and estrogen type.  Can we now connect a specific carcinogen to breast cancer?

The carcinogen has to collect at the target tissue which in this case is the breast.  Heptachlor which was an insecticide of the 1980s and is still currently used on fire ants has been found to collect in the breast.  Since heptochlor is not metabolized it merely collects increasing in concentration until the virus is caught. Organochlorides have  been suspected of triggering breast cancer but studies seem to indicate the mere collection of the compounds do not cause cancer. However Co-carcinogenesis could explain the data.  Chlorine has been shown to inhibit adenovirus DNA synthesis.  If chlorine inhibits the polymerase of the viruses found in the breast which are HPV and Herpes Zoster then it is highly likely that heptachlor and the other organochlorides do too.

Another cancer associated with heptachlor is prostate cancer. If we look at prostate cancer we find 2 types there too.  An estrogen receptor form triggered by a herpes virus and a melanocortin receptor form. What virus uses the melanocortin receptor? The flavivirus called chikungunya virus has been isolated from prostate tumors. Prostate cancer patients have an increased risk of melanoma, skin cancer.  Melanoma cells over express melanocortin receptors too. Interestingly most people who have been bitten by a mosquito carrying west nile or other flaviviruses do not realize they are infected.  Flaviviruses could be the cause melanoma. It is not clear if these melanocortin receptors have been increased in the tumors of prostate cancers but they have been associated with an increased proliferation of the cancer cells.

Bone Cancers

Ewings has been associated with CMV and Epstein barr. Interestingly Ewings has also been associated with the hormone swings of pregnancy which would elevate estrogen levels. As herpes viruses they would be using estrogen receptors and the tumors would have increased estrogen receptors.

 Osteosarcomas are the most common type and largest group of bone cancers with a higher rate in African males.  The JC virus being of African origin is found in slightly higher rates in african americans.  Can JC be found in osteosarcomas? Simian virus 40 specifically has been found in dozens of osterosarcomas in monkeys could JC be the human version.

Osterosarcomas have increased serotonin receptors supporting the notion that the receptor used by the virus to infect increases. BK viruses use serotonin receptors.

Spindle cell sarcoma has already been documented and accepted to be caused by the Rous sarcoma virus. Rous sarcoma viruses are a type of retrovirus.  Retroviruses, like HIV, might be binding albumin-binding receptors which includes the luteinizing hormone receptor.

Luteinizing hormone receptor and Kaposi's sarcoma
https://www.ncbi.nlm.nih.gov/labs/articles/9302442/

Kaposi and HIV
http://www.sciencedirect.com/science/article/pii/S1741940905000518

as the lymph node is the carcinogen tattoo ink?


HIV and hepatic spindle cells
https://www.ncbi.nlm.nih.gov/pubmed/8008509


 Cadmium is the possible carcinogen for bones it collects at the growth tip of the bones and has strong associations with the cancer. Further because teen boys tend to grow rapidly and taller than girls they would have more cadmium added which could explain why they have higher rates of bone cancers. Occupations dealing with cadmium have higher rates of osteosarcoma and heavy metal implants have been found associated with sarcomas. Cadmium is found in cigarettes, and cigarette smoke. Cadmium can be found with fertilizers and in Africa the cadmium has been found to contaminate the hot chocolate of Africa because of this.  Cadmium has also been found in shellfish and oysters in high levels which could explain the clusters of cases in the northeast coast. Toxic levels of cadmium were also dumped into Tampa Bay in 2011 and there are clusters there too.  Osterosarcoma case clusters should appear near high cadmium areas. Cadmium can inhibit DNA polymerases directly.  This fits with our theme of a carcinogen present at the site which can inhibit the viral polymerases.

How about pancreatic cancer? There are 2 types of pancreatic cancer, exocrine and endocrine.
Endocrine cells secrete enzymes into the bloodstream whereas exocrine cells secrete into the intestine. The exocrine form is the most common so this must be a common virus. There seem to be multiple types of endocrine cancers which might match up with the different viral infections.

First the endocrine pancreatic cancers such as Insulinoma, Glucogonoma, and gastrinoma duct tumors all seem to be linked to polyomaviruses.

Insulinomas with BK polyomavirus, glucogonoma with SV40, and gastrinoma with Hepatitis B.

Polyomaviruses use the vit D receptors to infect cells and these seem to be increased in endocrine pancreatic cancers.

The most common pancreatic cancer, adenocarcinomas are the exocrine pancreatic cancers triggered by HPVs or retroviruses.

2/3 of pancreatic cancers occur in alcoholics.  Alcohol does inhibit polymerases and could easily inhibit a viral polymerase. The other pancreatic carcinogen could be N-nitros also known as nitrates or nitrites in foods. Highly processed foods like meat, cheese, and beer have high quantities and it's impact has been questioned. Viral polymerases can be inhibited by nitrogen oxides which nitrates and nitrites are and this feature fits with the co-carcinogen hypothesis. The influenza replication has been halted by nitric oxide in mouse models. So does this mean people with the flu should not have processed meats because of the pancreatic cancer risk? Alcohol is the more likely carcinogen candidate.

When we look for carcinogens of the brain the alcohol and benzodiazepine are the most likely candidates.   Again, alcohol can and does inhibit polymerases contributing to the stunting of growth and likely inhibits viral polymerases if they are there.   Benzodiazepine which is an anxiety medication can be absorbed into the fats in the brain when in high concentrations.  Benzodiazepine has be proven to inhibit the polymerases of Hepatits C specifically. The benzene ring of the these medications could be what inhibits the viral polymerases when alcohol is not involved. This is a side effect of an anxiety drug.

 Acyclovir is a medicine prescribed  for it's ability to inhibit the polymerase of herpes viruses and is currently used as a treatment to stop viral infections. There are cases where herpes encephalitis was diagnosed, acyclovir was prescribed and then the patient was discovered to have gliomas tumors. The question is were they misdiagnosed or did the viral infections become high grade glioma tumors.  Acyclovir is not consider carcinogenic because when fed to rats and mice log term no tumors developed. What if the rats had herpes infections at the same time? The reason that acyclovir does not cause cancer in shingles patients has to do with where the virus is.  Herpes viruses use estrogen receptors. The estrogen receptors of nerves cycle to the mitochondria and use the mitochondria's little DNA.  Cancer only occurs when the virus is at the nuclear DNA which is the huge cookbook. In the breast or in the glial cells of the brain acyclovir would be a carcinogen and should never be used in those cases.

 Gliomas, brain cancers of glial cells, are also associated with Alzheimer's disease. If some forms of Alzheimer's are due to a herpes virus infecting and destroying a neuron's mitochondria then gliomas would the herpes virus infecting the nucleus of the glial cells when the carcinogen such as nitrates was there.  The overlap of the gliomas and Alzheimer's is the herpes virus. Herpes simplex virus encephalitis has been found in glioma patients. Cmv has also been connected to gliomas especially in children. Herpes zoster has been connect to gliomas too. With all the connections to herpes viruses it is not surprising that some gliomas express estrogen receptors.

Meningiomas, the brain cancers of the meninge cells, are associated with polyomaviruses like sv40 in monkeys.



As for my original carcinogen example of simple benzene, it has been associated with Leukemia when consumed, which means it goes to the bone marrow.  Viruses that infect the bone marrow like respiratory syncytial virus have been associated with the disease too.  Children with acute lymphoblastic leukemia have often been exposed to RSV in the first nine to 12 months of life. Was it a combination of RSV and benzene exposure? Benzene appears in the waste water of fracking and could be contaminating the well waters of people living near them.

Ovarian cancer HPV18 and  CMV herpes viruses.

HPV18
http://www.nature.com/articles/srep08645

The carcinogen of ovarian cancer is asbestos or talc powder. The asbestos fibers were found in the ovaries and fallopian tubes in addition to asbestos workers having increased rates of ovarian cancer. The association of talc has not been proven but is suspected.



There is not enough evidence to prove that cancers wear the receptors that the viruses used to infect them but there is enough to investigate the possibility. With luck this will prove Co-carcinogenesis and we can prevent most cancer with vaccines. Assuming we figure out how to make vaccines for all of these viruses.  One can only hope. 

Thursday, March 23, 2017

Polyomaviruses and their receptors: serotonin and gangliosides at the ER and not the VDR????

Polyomaviruses go through the Endoplasmic reticulum before getting to the nucleus.  Polyomaviruses cause cancer so we know they get to the nucleus and we know they pass through the ER because the viruses have both been found there and trigger HLA-C.

The receptors polyomaviruses use must therefore travel through the ER.

JC and serotonin receptors
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838264/
https://www.ncbi.nlm.nih.gov/pubmed/15550673

Serotonin receptors localized at the smooth endoplasmic reticulum
http://www.sciencedirect.com/science/article/pii/S000689930002062X

Bk and ganglioside receptors which pass through the Endoplasmic reticulum
https://experts.umich.edu/en/publications/identification-of-gangliosides-gd1b-and-gt1b-as-receptors-for-bk-

Gangliosides and sv40 virus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC202381/

serotonin was once considered an ganglioside?

Both serotonin and gangliosides are stored in the smooth ER

antibodies overlap for serotonin and gangliosides
http://www.sciencedirect.com/science/article/pii/0306453092900172





Wednesday, March 22, 2017

Co-carcinogenesis and Liver cancer

Francis Peyton Rous' Co-carcinogenesis hypothesis: that a virus and a carcinogen together cause cancer. (1966 Nobel prize for HPV work)  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135410/

My co-carcinogenesis takes his further because carcinogens inhibit polymerases.

What I surmise from his hypothesis:

Cancer occurs because a carcinogen inhibits the viral polymerase better than the human polymerase. When a virus infects the same cell as a carcinogen they interact.  Instead of the virus making what it wants in the host the infected cell is transformed into a cancer cell by the carcinogen. 

Alcohol as the carcinogen in liver cancer
http://www.telegraph.co.uk/news/health/news/11492075/Just-three-alcoholic-drinks-a-day-can-cause-liver-cancer-warns-a-new-study..html

Cholangiocarcinoma is a slow growing cancer

I am looking for the embryonic methylation hervs, herv-w and herv-h,  since polyomaviruses and herpes viruses look like they methylate.
http://angelabiggs.blogspot.com/2017/03/hervs-viruses-demethylation-and.html

hepatitis B and cholangiocarcinoma
https://www.ncbi.nlm.nih.gov/pubmed/28030846

(as a polyomavirus Hepatitis B might use vit D receptors VDRs)

VDR and cholangiocarcinoma
https://www.ncbi.nlm.nih.gov/pubmed/17487855

Heptocellular is a aggressive and fast growing cancer

Hepatitis C and Heptocellular carcinoma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840947/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493352/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554798/

herv K and Heptocellular carcinoma
https://www.hindawi.com/journals/bmri/2016/8201642/

HervK is an embryonic gene that appears during demethylation which flaviviruses apparently use. (the demethylation states of embryogenesis have very fast divisions/growth)

As a flavivirus Hepatitis C might use melanocortin receptors. MCR1 is the only one that goes to the nucleus.

MCR5 increased with heptocellular carcinoma...the other receptors are unknown
http://www.proteinatlas.org/ENSG00000176136-MC5R/cancer#top

I can't tell if the MCR1 which is used by the virus to infect has increased.

Yellow fever...a flavivirus infects the liver through MCR4 but ends up in the cytosol

HIV and Hepatic spindle cancer
https://www.ncbi.nlm.nih.gov/pubmed/8008509

HIV as a retrovirus uses albumin/ LH receptors. (hypothesis on this blog). They end up in the nucleus and retroviruses appear to use demethylation causing fast growing cancers.

Are spindle cancers typically retroviruses no matter where in the body?




Tuesday, March 21, 2017

Attempting to link the demethylation and methylation directly to the viruses (as the orchestrator)

Attempting to link the demethylation and methylation directly to the viruses (as the orchestrator)

breast cancer and DNA methyltransferase 1 (DNMT1)
https://www.ncbi.nlm.nih.gov/pubmed/15755728

DNA methyltransferase expression EBV (herpes) and JC virus (polyomavirus)
https://www.ncbi.nlm.nih.gov/pubmed/25341997

Demethylation and TET
https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-015-0134-6
https://academic.oup.com/nsr/article/2/3/318/1426818/Oxidative-DNA-demethylation-mediated-by-Tet
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308928/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960967/

Melanoma and TET2 ( ten-eleven translocation methylcytosine dioxygenase)
https://www.ncbi.nlm.nih.gov/pubmed/27102770

HIV, TET, and demethylation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158049/

Zygote - demethylation- Blastocyte- methylation- Epiblast (pluripotent cells)
       awakens Herv K                                Herv H

Epiblast  -demethylation  - PGCs  -  methylation -Fetus
                    Herv E                              Herv W

viruses: Retrovirus / HPV/flavivirus    Herpes/ polyomaviruses
                   demethylation                     methylation
                      Aggressive cancers           Slow cancers


Monday, March 20, 2017

Osteoarthritis methylation is not caused by a viral infection rather Stenotrophomaonas making gaba or taking sleeping pills?

Is it possible that the methylation seen in osteoarthritis is caused by the high levels of gaba/ GHB produced by stenotrophomona infections or sleeping pills?

osteoarthritis and methylation
https://plus.google.com/+WardPlunet/posts/EveozNYj4BB
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765529/
http://www.sciencedirect.com/science/article/pii/S1063458412000179

Osteoarthritis, fibromylagia, bone spurs, dyspnea, and bone spurs
http://angelabiggs.blogspot.com/2015/02/fibromyalgia-is-it-autoimmune-no-right.html

gaba receptor, hypermethylation, and suicide
https://www.ncbi.nlm.nih.gov/pubmed/18639864
https://autoimmunethyroid.wordpress.com/2008/10/29/dna-hypermethylation-and-gaba/

fibromyalgia and suicide risk
http://www.reuters.com/article/us-fibromyalgia-suicide-idUSTRE66F3JJ20100716
http://fibromyalgia.newlifeoutlook.com/fibromyalgia-and-suicide-risk/

high gaba, stenotrophomonas, and fibromyalgia
http://angelabiggs.blogspot.com/2015/11/stenotrophomonas-possible-connection-to.html

GHB gamma-hydroxybutyrate as a sleeping pill can when overdosed cause pituitary tumors, osteroarthritis ?

Are Atherosclerotic plaques caused by a herpes virus like CMV methylating the DNA?

Marek's disease virus (the chicken's herpes virus) caused atherosclerosis in chickens
Chickens had only mild deposits on a high fat diet unless exposed to the Marek's virus then they had severe hardening of the arteries (1968)
https://www.ncbi.nlm.nih.gov/pubmed/5686036

Herpes virus causing the methylation in cancer hypothesis
http://angelabiggs.blogspot.com/2017/03/hervs-viruses-demethylation-and.html

DNA methylation and atherosclerosis
https://www.ncbi.nlm.nih.gov/pubmed/25091541
https://www.ncbi.nlm.nih.gov/pubmed/27082829

(no carcinogen in this situation)

platelet mito methylation and CVD
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-015-0078-0




Friday, March 17, 2017

Melanoma, demethylation, and herv K

Francis Peyton Rous' Co-carcinogenesis hypothesis: that a virus and a carcinogen together cause cancer. (1966 Nobel prize for HPV work)  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135410/

My co-carcinogenesis takes his further because carcinogens inhibit polymerases.

What I surmise from his hypothesis:

Cancer occurs because a carcinogen inhibits the viral polymerase better than the human polymerase. When a virus infects the same cell as a carcinogen they interact.  Instead of the virus making what it wants in the host the infected cell is transformed into a cancer cell by the carcinogen. 

what causes melanoma? a virus demethylating the DNA or the sun?

Sun exposure and demethylation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877750/

melanoma and herv-K
https://www.ncbi.nlm.nih.gov/pubmed/23311654

demethylation and melanoma
http://cancerdiscovery.aacrjournals.org/content/5/8/OF6
http://www.sciencedirect.com/science/article/pii/S0014579315010248
https://www.scholars.northwestern.edu/en/publications/clinically-relevant-genes-and-regulatory-pathways-associated-with

melanocortin receptor 1 and melanoma
https://www.ncbi.nlm.nih.gov/pubmed/24460937
https://www.ncbi.nlm.nih.gov/pubmed/25017567

prostate cancer increased risk melanoma
http://www.medscape.com/viewarticle/813922

Hepatitis C (a flavivirus) and prostate cancer
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1677-55382011000200009

Melanoma 4x higher in parkinon's patients
http://www.medscape.com/viewarticle/806837

Hepatitis C and parkinson's disease risk
https://www.ncbi.nlm.nih.gov/pubmed/25608223

Looks like hepatitis C uses melanocortin receptor one and that hepatitis C is a risk factor for melanoma which would explain the overlap of prostate cancer and parkinson's disease with melanoma.