Saturday, April 22, 2017

Hypothesis: virus families bind receptor families (restated from earlier post)

Hypothesis: Virus families bind receptor families

Melanocortin receptors and Flaviviruses (west nile, dengue, zika)

Estrogen receptors (alpha, beta, estrogen-related)  and Herpes viruses (alpha, beta, and gamma)

Dopamine receptors and Flu viruses

Acetlycholine receptors and Enteroviruses (d68, coxsackie)

Cannabinoid receptors and Human Papilloma viruses

serotonin receptors and Polyomaviruses (JC virus/sv40, BK, hepatitis B)

luteinizing hormone receptors and retroviruses (rous sarcoma virus, HIV)

Muscarinic receptors and Paramyxoviridae (measles, mumps, RSV, parainfluenza viruses)

NOTES:

Hepatitis A is an enterovirus
Hepatitis B is a polyomavirus
Hepatitis C is a flavivirus

earlier post on receptor binding

receptor hypothesis: positive or negative

collected references

serotonin receptors and polyomaviruses 2012
https://www.ncbi.nlm.nih.gov/pubmed/24089568

herpes reactivation is estrogen receptor dependent 2010
https://www.ncbi.nlm.nih.gov/pubmed/19846508

HHV8 and the estrogen receptor alpha 2008
http://d-scholarship.pitt.edu/8097/

no direct link dopamine and flu but virus always found in dopamine cells
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0051068

The dopamine 2 receptor is on the pancreas
http://www.jbc.org/content/280/44/36824.full

D2 and the substantia nigra
http://www.ncbi.nlm.nih.gov/pubmed/1825842
http://www.hindawi.com/journals/ijmc/2011/403039/

Frontal lobe and D2
http://www.sciencedirect.com/science/article/pii/S1053811906011049

The flu virus and parkinson's
http://news.sciencemag.org/brain-behavior/2009/08/bird-flu-virus-possible-trigger-parkinsons

Could it be that the flu uses the D2 receptor to infect cells?

The receptor that people have found them using is hemaggluten. Hemaggluten is the antigen on red blood cells that we use to identify blood types.  This had me puzzled.

However the dopamine D2 receptors have a hemogglutin epitope. ( a matching piece)
http://www.jbc.org/content/274/28/19894.abstract

melatonin protects against flaviviruses
http://www.ncbi.nlm.nih.gov/pubmed/14962057

if you assume virus families use receptor families and look at where flaviviruses infect a possible pattern appears

Flaviviruses look like they bind melanocortin receptors

mcr1   Tick borne encephalitis virus/ hepatitis C   (Thrombocytopenia due to red blood cells with mcr1)

mcr2 (ACTH receptor)   Zika (placenta, developing brain)

mcr3  West nile (kidneys)

mcr3 and mcr1  Japanese encephalitis

mcr4  Yellow fever (liver)/ hepatitis C (here too)
                 
mcr5  Dengue (immune system T cells) (which explains the second exposure response)


HIV looks like it causes premature menopause
https://www.ncbi.nlm.nih.gov/pubmed/24303653

Menstrual cycle and HIV
https://books.google.com/books?id=cGUEAAAAMBAJ&pg=PA2&lpg=PA2&dq=Luteinizing+hormone+and+HIV&source=bl&ots=wbfbAocMEP&sig=MYmm4wIjsIpThKZQvDe-2rFI27M&hl=en&sa=X&ved=0ahUKEwiFgtKC25zTAhXLrlQKHbUDCG04ChDoAQgjMAQ#v=onepage&q=Luteinizing%20hormone%20and%20HIV&f=false

HIV surges with LH drops so do they use the same receptor?


feline leukemia virus and thiamine transporter
https://www.ncbi.nlm.nih.gov/pubmed/16537605
https://www.fredhutch.org/en/news/spotlight/imports/feline-leukemia-virus-inhibits-thiamine-uptake--with-pathologica.html

LH and albumin antibody cross-reaction
https://www.ncbi.nlm.nih.gov/pubmed/2102467






Friday, April 21, 2017

Reorganizing the co-carcinogenesis paper based on the 5 nuclear virus families

Evaluation of Hypothesis:

Viruses are 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.  The characteristics of the cancer will also take on attributes of the pathway launched by the receptor.

Since there are only five virus families that infect the nucleus of cells we will attempt to divide all the cancers up into these five families: the human papilloma viruses, the Herpes viruses, the Retroviruses, the polyomaviruses, and the flaviviruses.

The human papilloma virus family use the cannabinoid receptors of which there are two CB1 and CB2.

Clear cell renal carcinoma has been connected to HPV16.  HPV16 appears to use the cannabinoid one receptor which may explain the yellow to clear appearance of the cells. CB1 receptors have been tied to ceramide which can change a cells lipid metabolism. If overstimulated the cell could over produce lipids resulting in the yellow appearance of the cancer.  The expression of the CB1 receptors is controversal.  CB1 receptor has been found to be over expressed and under expressed in these renal tumor cells.  Are they over expressed before becoming under expressed?

Cervical cancer was the first cancer linked to HPV.  There are 2 forms of cervical cancer squamous and adenocarcinoma. The squamous form of has been connect specifically to HPV16 and cannabinoid receptor 2.  The adenocarcinoma has been connected to HPV18 and cannabinoid receptor 1.  Predictable there are exists a squamous form of non-melanoma skin cancer that was connect to HPV16 and a basal form which was connected to HPV18.  Do these non melanoma skin cancers express different cannabinoid receptors?

Triple negative estrogen receptor breast cancers have been found to contain HPV.  Some triple negative breast cancer are basal cells and a few rare ones are squamous in shape.

The Herpes virus family use the estrogen receptors of which there are three types alpha, beta, and estrogen-related receptors.  Only the alpha and estrogen-related receptors cycle to the nucleus.  The beta estrogen receptor cycles to the mitochondria which means the alpha-herpes like herpes zoster cannot cause cancer.

EBV and HHV8 are gamma-herpes that use the alpha estrogen receptors.  EBV has been linked to estrogen receptor positive breast cancers.  CMV use the estrogen-related receptors like progesterone and CMV has been linked to some forms of breast cancer. There are breast cancer cells that are only progesterone positive but it remains unclear that this is the CMV group.

  EBV and HHV8 has been isolated from Papillary renal carcinomas which as herpes viruses would trigger estrogen receptors.

 HHV8 is also known as the Kaposi's virus produce spindle like cancers often seen in aids patients.  The spindle like shape occurs because some of the alpha estrogen receptors stimulate luteinizing hormones.

Luteinizing hormone receptors and spindle cancer cells are strongly linked to the Retrovirus family.

Chrondrosarcomas have spindle cell components of cartilage. HIV patients have increased rates of chrondrosarcoma.   HIV as a retrovirus looks like it triggers spindle cells like other known retroviruses. Spindle cell sarcoma in chickens 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.  When the luteinizing hormone is high during a female patient's cycle the level of HIV drops and the Luteinizing hormone receptor is normally overexpressed in the Theca cells of the ovary which have a spindle cells shape to them. Is the spindle shape connected to the receptor?

HIV patients not only have increased chrondrosarcoma but increased hepatic spindle tumors.

Polyomaviruses use the serotoinin receptors.

Osteosarcomas are the most common type and largest group of bone cancers with a higher rate in African males.  The JC virus, a polyomavirus, 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.

Osteosarcomas have been shown to be induced by x-rays.  Both polyomaviruses and X-rays have also been linked to papillary thyroid carcinomas.  Both of these cancers have been found to have abnormally high DNA levels.  Interestingly serotonin has been shown to have a protective effect against X-rays and that Serotonin receptor antagonists can repair DNA after UV Damage. Apparently with extremely high does of X-ray the DNA repair state spins out of control.  Polyomaviruses binding serotonin receptors apparently triggers DNA regeneration as it infects and if a carcinogen is present with the virus cancer results.

Iron binding proteins have been shown to be regulated by serotonin receptors.  Which is interesting because osterosarcomas have been treated in dogs with artemisinin. Artemisinin is a component of worm wood that binds iron. This treatment of artemisinin seemed to destroy the osterosarcomas in dogs.

Hale's colloidal iron staining is the method of identifying chromophobe renal carcinomas from other renal cancers because these cancer tumors have such a high iron content.

Chromophobe renal cancer has been associated with Birt-hogg-dube because of the appearance of follicular tumors.   The disease and the cancer both have extreme mitochondrial biogenesis occurring.  Interestingly while the burt-hogg-dube form may be genetic the chromophobe type may be due to the triggering of serotonin receptors.  The BK virus which is notorious for infecting Kidney transplants is a polyomavirus which appears to use serotonin receptors and could be the culprit here.

Meninginomas of the brain have been linked to polyomavirus sv40 and with high iron concentrations.

The endocrine pancreatic cancers such as Insulinoma, Glucogonoma, and gastrinoma duct tumors all seem to be linked to polyomaviruses.  Insulinomas with BK polyomavirus, and glucogonoma with SV40.

Flaviviruses use the melanocortin receptor family. Not all of these receptors move to the nucleus only MCR4 does.

In Heptocellular cancer there are two mouse models. One involves a mutated MCR4 receptor creating HCC and the other are mice trangenic for the agouti protein which binds melanocortin receptors producing mice that were not just golden in color but obese with high rates of liver cancer.

 Hepatitis C and yellow fever have both been found connected to heptocellular cancer tumors.  Heptocellular cancers tend to be full of fat deposits.  Note that leptin, the fat cell hormone, has been shown to inhibit HCC growth and the MCR4 has been shown to regulate fat consumption.

It seems likely that Hepatitis C and yellow fever use MCR4 which moves to the nucleus to regulate genes connected to fat metabolism.  If a carcinogen is encountered these genes are stuck activated.

Chronic hepatitis C patients have higher rates of hypothyroidism and thyroid papillary carcinomas which leads to a suspicion that these maybe partially triggered by the virus.

Note that I think there are 3 types of thyroid papillary carcinomas: irregular, cystic, and nodule. Tempted to think that the cystic is EBV, the nodule is HHV8, and the irregular and most common form is the one tied to flaviviruses but this is suspected on very little evidence. (Follicular thyroid would be the polyomavirus family because of the mitochondrial biogenesis associated with it)

These 5 nuclear viruses turn on embryonic Herv genes through the receptors too. Excessive DNA damage, such as damage from UV light, trigger demethylation of DNA.  Only the human papilloma viruses trigger demethylation by using cannabinoid receptors.  Estrogen receptors, serotonin receptors, melanocortin receptors, and luteinizing receptors all methylate the DNA.

Early embryogenesis goes back and forth through extremely high methylation and demethylation states. Think of methyl groups as stickers turning on and off genes.

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

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

In the case of cancer the receptor is activated and magnified thus in these extreme states the cells awaken embryonic genes.

The alpha-estrogen receptors and estrogen-related-receptors cycle to the nucleus which would allow herpes viruses to interact with DNA.  Both estrogen receptors and progesterone receptors methylate genes.   Therefore the Herve genes seen with these estrogen and progesterone breast cancers have the embryonic genes that appear when the DNA is methylated.   Syncytin-1 aka Herv W is over expressed in breast cancer. 

methylation has been linked to pain
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142046

The CB receptors have been studied as possible pain relievers
https://www.ncbi.nlm.nih.gov/pubmed/11164622/

CB2 receptors have negative effects on sperm
https://www.ncbi.nlm.nih.gov/pubmed/26671998

methylation is key for sperm development
https://www.ncbi.nlm.nih.gov/pubmed/21951794


It looks like the cannabinoid receptors used by HPV could be triggering demethylation.

Do the triple negative cancers involving HPV have demethylation involved.  Specifically they can see the demethylation of the estrogen receptor so this is possible and explains why herv E can be found in some breast cancers.

https://www.ncbi.nlm.nih.gov/pubmed/7538900
http://www.ashg.org/genetics/ashg07s/f21242.htm












Apocrine carcinoma, paget's disease, spindle shaped cells, and retroviruses

Looking at the areas of overlap seems to link retroviruses to them

Apocrine breast cancers (1%)

Paget's disease and apocrine breast cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229951/

Her2 spindle cell carcinoma with apocrine carcinoma of breast
https://www.hindawi.com/journals/cripa/2014/310829/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053236/

as spindle cancers are these retroviruses induced?

a protein from apocrine breast cancer related to retroviruses
https://www.ncbi.nlm.nih.gov/pubmed/10713110

Paget's disease and chrondrosarcomas
https://www.ncbi.nlm.nih.gov/pubmed/9297756
https://www.ncbi.nlm.nih.gov/pubmed/15895907
http://www.healio.com/orthopedics/journals/ortho/2004-1-27-1/%7B51abef2f-83dd-4c8e-94a9-e40193aff76e%7D/femoral-chondrosarcoma-complicating-pagets-disease-of-bone

HTLV and Paget's overlap ?
https://www.ncbi.nlm.nih.gov/pubmed/8212554

HTLV and eccrine sweat glands
http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0215(19990301)80:5%3C652::AID-IJC3%3E3.0.CO;2-P/full

bovine leukemia virus and breast cancer
https://wwwnc.cdc.gov/eid/article/20/5/13-1298_article
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134304






Monday, April 17, 2017

Newest update of co-carcinogenesis

Title:  Updating Co-carcinogenesis

Abstract:  Co-carcinogenesis is the synergism between a nuclear virus and a carcinogen to cause cancer.  The receptor used by the virus to enter the cell triggers either methylation or demethylation. Note that severe DNA damage causes demethylation however this co-carcinogenesis hypothesis suggests that cancer can develop merely because of extreme methylation or demethylation even if the DNA has not been damaged.

Cancer cells appear to express the receptors the viruses used to infect them.  This is because when the receptors are used they are activated triggering the pathways they are linked to and then the cell creates replacement receptors.  Some receptors trigger methylation while others trigger demethylation.

This is how without damaging the DNA viral infections awaken Hervs, the embryonic genes characteristic of cancer.  The four stages of embryo genesis switch back and forth between methylation and demethylation. These embryonic genes set the stage for the rapid cell division seen in cancer.

In a cancer cell, the virus opens the DNA up and then can not function to destroy the cell or make new viruses because the carcinogen inhibits the viral polymerase. Polymerases are the transcription vehicles that turn the DNA cookbook into RNA recipes that can be used. The viral polymerases have probably evolved to compete with host polymerases and have stronger binding efficiencies.

It is my contention that cancer occurs because a carcinogen inhibits the viral polymerase better than the human polymerase. Alone a carcinogen would just stunt growth by binding the host's 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 without DNA damage 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.   The receptors expressed by the tumors will be matched up with the corresponding viruses and to validate the match the known methylation or lack there of will be examined.   The most feasible carcinogen for each cancer will also be considered.

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 and radioactive bombs used during the Vietnam war damaged DNA so profoundly that the world view of such cancers and birth defects completely changed.  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 for the first time in years the possible co-carcinogenesis of cervical cancer, hepatocellular carcinoma, and Kaposi's sarcoma using statistics.  Co-carcinogenesis he suggested is the synergistic actions of a virus and a carcinogen together that both must be present just as Rous hypothesized. 

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

Hypotheses:  Only nuclear viruses cause cancer.  Cancer cells 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' receptor uses: methylation or demethylation.  Demethylated cancers are more aggressive.  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.

Kaposi's cancer

The HHV8 virus has been isolated from Kaposi's cancer tumors and has been found in 95%.  HHV8 which has been called the Kaposi's virus is a gamma herpes virus which has been proven to bind the alpha estrogen receptor.  Not only is the alpha estrogen receptor increased in Kaposi's cancer but luteinizing hormone receptors are increased as well.  This is interesting because Kaposi is a spindle shaped cancer.  Spindle shaped cancers much like Theca cells have increased luteinizing hormone receptors expressed.  Since EBV and HHV8 both bind the alpha estrogen receptor there must be different alleles of this gene with each virus favoring a different allele but binding both. This alpha estrogen receptor must be closely linked to the luteinizing hormone.

 Without a carcinogen the HHV8 virus can cause Castleman's disease an infection of the lymph node causing benign tumors.  When a carcinogen is present, such the nitrite inhalents discovered by Haverkos,  the tumors transform to cancers.

Breast cancer

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

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344231/
 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972522/)

Looking first at the herpes viruses first CMV infection has been found to be estrogen-related-receptor dependent. Progesterone as an estrogen related receptor could be what CMV is using to trigger Breast cancer.

CMV and estrogen related receptor
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284536/
Progesterone is an estrogen related receptor

EBV is a gamma-herpes virus which would be using the alpha-estrogen receptor thus creating the estrogen receptor positive form of breast cancer.

 The alpha-estrogen receptors and estrogen-related-receptors which some herpes viruses use cycle to the nucleus which would allow herpes viruses to interact with DNA.  Further both estrogen receptors and progesterone receptors methylate genes. (think of methyl groups as stickers on the DNA helping to change which genes are expressed)  Therefore the Herve genes seen with these estrogen and progesterone breast cancers have the embryonic genes that appear when the DNA is methylated.   Syncytin-1 aka Herv W is over expressed in breast cancer. Normally Herv W is only awakened by methylation in embryo cells.

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

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

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.  Some triple negative breast cancer are basal cells and a few rare ones are squamous in shape.

There are 2 forms of cervical cancer squamous and adenocarcinoma. The squamous form of has been connect specifically to HPV16 and cannabinoid receptor 2.  The adenocarcinoma has been connected to HPV18 and cannabinoid receptor 1.  Predictable there are exists a squamous form of non-melanoma skin cancer that was connect to HPV16 and a basal form which was connected to HPV18.  Do these non melanoma skin cancers express different cannabinoids?

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. An activated cannabinoid receptor demethylate genes.

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.

Unfortunately the carcinogens of the skin that would interact with viruses, are applied as lotions and still available to the public.  Diazolidnyl urea or iodopropynyl butylcarbamate are compounds that release formaldehyde.  Formaldehyde is highly carcinogenic.

Can we 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 heptachlor is not metabolized it merely collects increasing in concentration until the virus is caught.  Hawaii had sprayed heptachlor on the tops of pineapples which were not for human consumption rather fed to cows.  When breast cancer rates skyrocketed they realized the heptachlor was in the milk people were drinking.  Although the procedure of using heptachlor on pineapples has stopped those people with heptachlor could still develop breast cancer.

Heptachlor is a type of organochloride. Organochlorides have long 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.

Bone Cancers:  Ewings, Osteosarcoma, Chondrosarcoma (cartilage) , Chordoma, and Fibrosarcoma

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, a polyomavirus, 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.

Osteosarcomas have been shown to be induced by x-rays.  Both polyomaviruses and X-rays have also been linked to papillary thyroid carcinomas.  Both of these cancers have been found to have abnormally high DNA levels.  Interestingly serotonin has been shown to have a protective effect against X-rays and that Serotonin receptor antagonists can repair DNA after UV Damage. Apparently with extremely high does of X-ray the DNA repair state spins out of control.  Polyomaviruses binding serotonin receptors apparently triggers DNA regeneration as it infects and if a carcinogen is present with the virus cancer results.

Cadmium is a possible carcinogen for bones because 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.

Cadmium has also has been linked to Chrondrosarcomas.

Chrondrosarcomas have spindle cell components of cartilage. HIV patients have increased rates of chrondrosarcoma.   HIV as a retrovirus looks like it triggers spindle cells like other known retroviruses. Spindle cell sarcoma in chickens 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.  When the luteinizing hormone is high during a female patient's cycle the level of HIV drops and the Luteinizing hormone receptor is normally overexpressed in the Theca cells of the ovary which have a spindle cells shape to them. Is the spindle shape connected to the receptor?

HIV patients not only have increased chrondrosarcoma but increased hepatic spindle tumors.

What carcinogens appear with these spindle tumors? 
Nitrites have strong connections to spindle cells. Rats fed sodium nitrate developed spindle tumors and Aids patients who took "poppers" a form of nitrate used for a sexual high tended to develop more cancers than those who didn't.

https://www.omicsonline.org/open-access/highgrade-chondrosarcoma-associated-with-spindle-cell-components-of-the-cricoid-cartilage-2157-7099.S4-020.php?aid=35508
http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S1681-150X2017000100007

Chordoma

These bone cancers express estrogen receptors and progesterone receptors.
https://www.ncbi.nlm.nih.gov/pubmed/11131982  Which would indicate one of the beta herpes viruses: CMV, HHV5, HHV6, HHV7.  (still looking for a paper connecting one...suspect HHV6 because it favors nerves and these bone cancers are of the spine and skull)

Fibrosarcomas have been found in cats and monkeys to be started by retroviruses. Retrovirus by using luteinizing hormone receptors induce these fibrosarcomas to be spindle shaped.  Wolfe's monkey experiments actually transformed cells into fibrosarcomas using a retrovirus.  The carcinogens are polycyclic aromatic compounds. These Polycyclic aromatic hydrocarbons contain aromatic compounds like benzene rings which inhibit polymerases (looking for a direct reference)

Congenital fibrosarcoma from prenatal exposure working at a gas station
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457614/


Pancreatic cancer

There are 2 major 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.

Again, Polyomaviruses use the serotonin receptors to infect cells and these receptors seem to be increased in these endocrine pancreatic cancers. Hepatitis B is sort of strange in that it is not really a polyomavirus and tends to act like a retrovirus using reverse transcription.

The most common pancreatic cancer, adenocarcinomas, are the exocrine cancers. Squamous adenocarcinomas has been connected to HPV16.  Both cannabinoid receptors exist on the pancreas.  Again HPV16 uses CB1 while HPV18 uses CB2.   Is it possible that the most common form of pancreatic cancer is caused by HPV18?

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.

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. Are they caused by hepatitis B or sv40 in humans?

iron and meningiomas
https://www.ncbi.nlm.nih.gov/pubmed/525262

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.

Looking at the 2 most common types of liver cancer, Hepatocellular cancer and cholangocarcinoma, both are connected to the same carcinogen alcohol.   Alcohol abuse has long been linked to increased rates of liver cancer.  Alcohol is a known polymerase inhibitor.

Hepatocellular cancer is the most common form of liver cancer.  Hepatitis C and yellow fever both of which are flaviviruses have been linked to Hepatocellular cancer

yellow fever and Hepatocellular cancer
http://onlinelibrary.wiley.com/doi/10.1002/path.1711090202/abstract
hepatitis C and hepatocellular cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840947/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493352/

Flaviviruses appear to be using melanocortin receptors.  Which seems fitting because the mouse model for hepatocellular cancer involves a mutated melanocortin 4 receptor.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204024/

Cholangocarcinoma and Hepatitis B virus
https://www.ncbi.nlm.nih.gov/pubmed/27999794
https://www.ncbi.nlm.nih.gov/pubmed/22694354
https://www.ncbi.nlm.nih.gov/pubmed/28030846

As a polyomavirus Hepatitis B is linked to serotonin receptors.  Serotonin metabolism is altered in Cholangocarcinoma.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593938/

Increased DNA repair enzymes in Cholangocarcinoma which could be linked to the serotonin receptors being triggered by the Hep B.
https://www.ncbi.nlm.nih.gov/pubmed/23480773

Kidney Cancer

In addition to alcohol and smoking,  nitrosodimmethylamine (NDMA), has been found to accumulate in the Kidney and cause cancer.
http://www.irjponline.com/admin/php/uploads/903_pdf.pdf

There are several types of kidney cancers : clear cell, papillary, and chromophobe are just 3 of them.

Clear cell renal carcinoma has been connected to HPV16.  HPV16 appears to use the cannabinoid one receptor which may explain the yellow to clear appearance of the cells. CB1 receptors have been tied to ceramide which can change a cells lipid metabolism. If overstimulated the cell could over produce lipids resulting in the yellow appearance of the cancer.  The expression of the CB1 receptors is controversal.  CB1 receptor has been found to be over expressed and under expressed in these tumor cells.  Are they over expressed before becoming under expressed?  The state of demethylation supports the notion that the receptors were initially stimulated.

Papillary renal carcinoma has been connected to methylation and the activation of embryonic Herv-w.   EBV and HHV8 has been isolated from Papillary renal carcinomas which as herpes viruses would trigger estrogen receptors and the methylation connected to them.

Chromophobe renal cancer has been associated with Birt-hogg-dube because of the appearance of follicular tumors.   The disease and the cancer both have extreme mitochondrial biogenesis occurring.  Interestingly while the burt-hogg-dube form may be genetic the chromophobe type may be due to the triggering of serotonin receptors.  The BK virus which is notorious for infecting Kidney transplants is a polyomavirus which appears to use serotonin receptors. Note that serotonin receptors have also been found to "regulate" iron containing proteins.  Hale's colloidal iron staining is the method of identifying chromophobe carcinomas from other renal cancers.

https://researchconnect.wayne.edu/en/publications/colloidal-iron-staining-in-renal-epithelial-neoplasms-including-c

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. 

Serotonin receptors, DNA repair, polyomaviruses, and Osteosarcomas

Osteosarcomas have been shown to be induced by x-rays.  Both polyomaviruses and X-rays have also been linked to papillary thyroid carcinomas.  Both of these cancers have been found to have abnormally high DNA levels.  Interestingly serotonin has been shown to have a protective effect against X-rays and that Serotonin receptor antagonists can repair DNA after UV Damage. Apparently with extremely high does of X-ray the DNA repair state spins out of control.  Polyomaviruses binding serotonin receptors apparently triggers DNA regeneration as it infects and if a carcinogen is present with the virus cancer results.

Osteosarcomas have abnormally increased DNA levels
https://www.ncbi.nlm.nih.gov/pubmed/6958350

Serotonin receptors induce DNA repair after UV DNA damage
https://www.ncbi.nlm.nih.gov/pubmed/19829299

Serotonin protects against X-ray damage
https://www.karger.com/Article/Pdf/254512

polyomavirus sv40 and osteosarcoma
https://www.ncbi.nlm.nih.gov/pubmed/9824156?dopt=Abstract
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000733

polyomavirus sv40 and papillary thyroid carcinomas
https://www.ncbi.nlm.nih.gov/pubmed/9482113?dopt=Abstract

x-rays and papillary thyroid carcinomas
http://www.thyroid.org/professionals/ata-publications/clinical-thyroidology/september-2013-volume-25-issue-9/clin-thyroidol-201325201-202/

x-rays and osteosarcoma
https://www.ncbi.nlm.nih.gov/pubmed/21170638

Polyomaviruses look like they are using serotonin receptors

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

Iron binding proteins have been shown to be regulated by serotonin receptors too
http://www.mc.vanderbilt.edu/reporter/index.html?ID=6991

Osteosarcomas and increased iron?

osteosarcomas, dogs, iron, and artemisinin
http://www.dogsnaturallymagazine.com/artemisinin-and-canine-cancer/

Artemisinin binds iron!!

artemisinin a sweet wormwood component




Thursday, April 13, 2017

Dividing up the estrogen positive breast cancers

Breast cancer shapes
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143811

Triple negative has a more round shape (HPV viruses)

epithelial breast cells and CMV
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063230/

EBV and transition in breast to mesenchymal
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972522/



Previous post connected the alpha estrogen receptors to the herpes-gamma viruses and estrogen-related receptors with herpes-beta viruses.

CMV is a beta virus. Progesterone is an ERR.

CMV binds ERR
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284536/

EBV is a gamma virus.

is this possible?

methylation and Estrogen positive breast cancers
http://angelabiggs.blogspot.com/2017/03/breast-cancer-methylation-demethylation.html

syncytin-1 (herv W)
syncytin-2 (herv F)

noticed pattern

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

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

viruses:  HPV/flavivirus    Herpes/ polyomaviruses/ retroviruses
                   demethylation                     methylation


syncytin and breast cancer
https://www.ncbi.nlm.nih.gov/pubmed/17306327

HERVs are considered embyrogenic genes that are turned on during methylation.  Syncytin is the new name given to them when looking their involvement with cell adhesion of breast cancer cells to endothelial cells

Syncytin and Cell adhesion
https://www.ncbi.nlm.nih.gov/pubmed/16871371

transition and Herv K ? are some herv ks with methylation????
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292751/

some Herv Ks seem linked to herpes viruses...during methylation even

Herv-w/ syncytin-1  and EBV in multiple sclerosis
https://virologyj.biomedcentral.com/articles/10.1186/s12985-017-0719-3

EBV and Her2 ?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031896/


Glucocorticoid and HHV8
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708632/

high stress...high levels of cortisone does cause methylation
http://www.sciencedirect.com/science/article/pii/S2352289514000095

so HHV8 might not cause cancer until high stress or another virus methylates the DNA?





Monday, April 10, 2017

Do the receptors reveal how viruses methylate or demethylate?

Here is the pattern I have noticed

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

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

viruses:  HPV/flavivirus    Herpes/ polyomaviruses/ retroviruses
                   demethylation                     methylation

The question is how does methylation or demethylation get triggered.  It has been suggested that the immune reaction to infection must be methylation but how can that be if half the viruses demethylate.
Is it possible that the way a virus infects the cell, the receptor used, triggers the methylation or demethylation?

My previous hypothesis: virus families use receptor families suggested these:

Retroviruses- albumin binding receptors (HIV - luteinizing receptors)  where do these fall?

HPV - cannabinoid receptors
Flaviviruses- melanocortin receptors (only MCR1 goes to the nucleus)

Herpes - Estrogen receptors (only alpha-estrogen receptors and estrogen-like receptors go to the nucleus)
 Polyomaviruses - Serotonin like receptors (they go through the ER)


Things that bind estrogen receptors have been suspects in trigger methylation

http://www.sciencedirect.com/science/article/pii/S0006291X04005029
http://www.jstor.org/stable/3650939?seq=1#page_scan_tab_contents

So do Herpes viruses trigger methylation by binding like estrogen?

If HPV uses Cannabinoid receptors are they the opposite? Do they demethylate?

methylation has been linked to pain
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142046

The CB receptors have been studied as possible pain relievers
https://www.ncbi.nlm.nih.gov/pubmed/11164622/

CB2 receptors have negative effects on sperm
https://www.ncbi.nlm.nih.gov/pubmed/26671998

methylation is key for sperm development
https://www.ncbi.nlm.nih.gov/pubmed/21951794

It looks like the cannabinoid receptors used by HPV could be triggering demethylation.

So what do retroviruses like HIV do?

LH receptor methylates
https://www.ncbi.nlm.nih.gov/pubmed/6315096

HIV and herv W


https://www.ncbi.nlm.nih.gov/pubmed/27885560

It is very possible that the choice of methylation or demethylation made by the cell when infected by a virus is not a defensive choice but rather determined by the receptor used by the virus to infect.

???
The the triple negative cancers involving HPV have demethylation involved.  Specifically they can see the demethylation of the estrogen receptor.

https://www.ncbi.nlm.nih.gov/pubmed/7538900
http://www.ashg.org/genetics/ashg07s/f21242.htm