Cases of HPV-related oral cancers have risen significantly in Canada, study finds
Incidence of HPV-related oral cancers increased by about 50% between 2000 and 2012
The Canadian Press · Posted: Aug 13, 2017 10:46 PM PDT | Last Updated: August 14, 2017
Statistics from a Canadian Cancer Society report last fall showed 1,335 Canadians were diagnosed in 2012 with HPV-related oropharyngeal cancer and 372 died from the disease. (CBC)
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The proportion of oral cancers caused by the human papillomavirus has risen significantly in Canada, say researchers, who suggest the infection is now behind an estimated three-quarters of all such malignancies.
In a cross-Canada study, published Monday in the Canadian Medical Association Journal, the researchers found the incidence of HPV-related oropharyngeal cancers increased by about 50 per cent between 2000 and 2012.
“It’s a snapshot of looking at the disease burden and the time trend to see how the speed of the increase of this disease (is changing),” said co-author Sophie Huang, a research radiation therapist at Princess Margaret Cancer Centre in Toronto.
Researchers looked at data from specialized cancer centres in British Columbia, Alberta, Ontario and Nova Scotia to determine rates of HPV-related tumours among 3,643 patients aged 18 years or older who had been diagnosed with squamous cell oropharyngeal cancer between 2000 and 2012.
“In 2000, the proportion of throat cancer caused by HPV was estimated at 47 per cent,” said Huang. “But in 2012, the proportion became 74 per cent … about a 50 per cent increase.”
Statistics from a Canadian Cancer Society report last fall showed 1,335 Canadians were diagnosed in 2012 with HPV-related oropharyngeal cancer and 372 died from the disease.
Most cases linked to oral sex
HPV is the most common sexually transmitted infection worldwide. Most people never develop symptoms and the infection resolves on its own within about two years. But in some people, the infection can persist, leading to cervical cancer in women, penile cancer in men and oropharyngeal cancer in both sexes.
Most cases of HPV-related oral cancer are linked to oral sex, said Huang, noting that about 85 per cent of the cases in the CMAJ study were men.
HPV-related tumours respond better to treatment and have a higher survival rate than those linked to tobacco and alcohol use, the other major cause of oral cancer, she said, adding that early identification of a tumour’s cause is important to ensure appropriate and effective treatment.
While some centres in Canada routinely test oral tumours to determine their HPV status, such testing is not consistent across the country, the researchers say.
In the past, physicians generally tended to reserve tumour testing for cases most likely to be caused by HPV — among them younger males with no history of smoking and with light alcohol consumption — to prevent an unnecessary burden on pathology labs.
“Only as accumulating data have supported the clinical importance of HPV testing has routine testing been implemented in most (though not all) Canadian centres,” the researchers write.
Vaccine for boys in all 10 provinces
The study showed that the proportion of new HPV-related oral cancers rose as those caused by non-HPV-related tumours fell between 2000 and 2012 — likely the result of steadily declining smoking rates.
HPV vaccines given to young people before they become sexually active can prevent infection — and the researchers say both boys and girls should be inoculated.
Currently, six provinces provide HPV immunization to Grade 6 boys as well as girls, with the other four provinces set to add males to vaccination programs this fall, said Huang.
“So vaccinating boys is very important because, if you look at Canadian Cancer Society statistics (for 2012), HPV- related oropharyngeal cancer in total numbers has already surpassed cervical cancers,” she said.
“The increase of HPV-related cancer is real, and it’s striking that there’s no sign of a slowdown.”
It’s not clear why males seem to be at higher risk of this cancer than females, said Leah Smith, an epidemiologist with the Canadian Cancer Society. Smith was not involved in the study.
“The research does suggest that the female immune system seems to respond differently to HPV infections in the mouth and throat than the male immune system,” Smith said. “In females for example, oral HPV infections seem to occur less often and clear more quickly than they do in males, and it’s the persistence of an infection in the mouth and throat that can ultimately lead to cancer.”
Smith called for more research to understand better exactly how HPV is passed on and why some people are more likely to develop these cancers than others.
Human papillomavirus (HPV)-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The most recent (8th) edition of the UICC/AJCC staging system separates HPV+ OPSCC from its HPV-negative (HPV−) counterpart to account for the improved prognosis seen in the former. Indeed, owing to its improved prognosis and greater prevalence in younger individuals, numerous ongoing trials are examining the potential for treatment de-intensification as a means to improve quality of life while maintaining acceptable survival outcomes. In addition, owing to the distinct biology of HPV+ OPSCCs, targeted therapies and immunotherapies have become an area of particular interest. Importantly, OPSCC is often detected at an advanced stage owing to a lack of symptoms in the early stages; therefore, a need exists to identify and validate possible diagnostic biomarkers to aid in earlier detection. In this Review, we provide a summary of the epidemiology, molecular biology and clinical management of HPV+ OPSCC in an effort to highlight important advances in the field. Ultimately, a need exists for improved understanding of the molecular basis and clinical course of this disease to guide efforts towards early detection and precision care, and to improve patient outcomes.
Key points
The incidence of human papillomavirus-associated oropharyngeal cancer (HPV+ OPSCC) is expected to continue to rise over the coming decades until the benefits of gender-neutral prophylactic HPV vaccination begin to become manifest.
The incidence of HPV+ OPSCC appears to be highest in high-income countries, although more epidemiological data are needed from low- and middle-income countries, in which HPV vaccination coverage remains low.
The substantially better prognosis of patients with HPV+ OPSCC compared to those with HPV– OPSCC has been recognized in the American Joint Committee on Cancer TNM8 staging guidelines, which recommend stratification by HPV status to improve staging.
The molecular biology and genomic features of HPV+ OPSCC are similar to those of other HPV-associated malignancies, with HPV oncogenes (E6 and E7) acting as key drivers of pathogenesis.
Treatment de-intensification is being pursued in clinical trials, although identifying the ~15% of patients with HPV+ OPSCC who have recurrent disease, and who therefore require more intensive treatment, remains a key challenge.
Synopsis
These findings suggest men are vulnerable to HPV linked oropharyngeal cancers (SCC) related most likely to oral sex and the fact is we don’t know how many cases are out there. Test kits for men with chronic problems with their throats suggests a way to improve our epidemiological understanding of the extent of the problem and also provide earlier treatment opportunities for those who get a positive diagnosis. I therefore recommend Canadian men be given the option for a test kit for HPV also. Chances are that some portion of women with HPV cancers contracted it from oral sex and vice versa.
My summary of cancers from infectious agents was presented at a Genetics and Genetics Disorders and Stem Cells Symposium in Stockholm and HPV was one of my presentation topics. May 13-14, 2019.
I have summarized cancers that one can catch from sharing infectious agents below. The problem world wide is much bigger than just HPV and SCC cancers. In fact it can be viewed as a silent pandemic which is little discussed.
Cancer causing viruses and bacteria potentially acquired from other peoples’ by association and worms associated with food production.
THESE INFECTIOUS AGENTS CAN BE TRANSMITTED PERSON TO PERSON ERGO THEIR CANCERS ARE A SILENT SLOW PANDEMIC.
PRESENTATION I GAVE IN PPT TO THE WORLD CONGRESS ON GENETICS, GENETIC DISORDERS AND STEM CELLS IN STOCKHOLM SWEDEN MAY 13-14 2019
Jorma Jyrkkanen, BSc (zoology), PDP (education)
Biologist
26 Dec 2017
jjyrkkanen76@outlook.com
Catching Cancer. Infections that can transform into cancer. Jorma A. Jyrkkanen, 250-859-5330,Viruses, bacteria and worms linked to cancerMechanisms of carcinogenesisPotentially synergistic residues mothers mik, diet, air, drink, on skinPrevention by education, policy, hygiene, clinical practiceConflicts between antibiotics, pesticides and mitochondrial alteration to promote carcinogenesisPre-approval testing of chemicals, biological pesticides, GMOs, antibiotics; for carcinogenicity, epigenetic profiles, impact on mitochondria, LGT potential of introduced or altered genes, effects on tumor suppressor genes, DNA methylation, DNA repair genes, promoters, microRNA up or down regulation, hypomethylation, hypermethylation, genes found silenced in cancer or deleterious genes activated, impacts on the ubiquitin-proteasome pathway(UPP)General regulatory needs
Dedication Son Jeff 1968-2000
Review Preamble
Life-time exposures to pathogens, carcinogens, mutagens, methylators, alkylators, phosphorylators, damage to our bodies is often multi-factorial, cumulative, synergistic, genetic, epigenetic, potentially heritable, different for everybody.
There will be folks whose immune systems having been compromised who will be susceptible to these diseases much more than others and genetics plays a large role as well. Example AIDS patients, scleroderma pigmentosum patients, patients with genetic defects, epigenetic defects
Synergies exist between drugs, pesticides, pathogens and the strength of these will vary also from person to person depending on history of exposure. Cancers exhibit epigenetic on/off switching.
Two anti-cancer drugs today treat epigenetic cancers.
Organisms associated with or causative agents of cancer I identified many of these in 2001
PATHOGENS that are linked to cancers at these specific sites can be expected to interact with CANCER CAUSING CHEMICALS that are linked to cancers at the same sites.
They may do this by contributing to one or mores steps in the progression sequence to cancer.
Epigenetic factors can turn linked genes on or off contributing to progression. I consider them risk multipliers.
IARC GROUP 1 DEFINITE HUMAN CARCS /CALIFORNIA Proposition 65 Carcs
Begs the question, what effect do antibiotics have on mitochondria?
BO Pr
ROS p53
Mechanisms of Viral carcinogenesis
Normally, wild type proto-oncogenes turn on the cell cycle to divide and tumor suppressor genes tell it to stop. A transforming virus wants to get around that.
Rb restriction point
Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes don’t work properly, cells can grow out of control, which can lead to cancer.Jun 25, 2014
Left. Mitogenic pathway using the retrovirus transducing genes. Protein attached to a growth factor receptor form a signaling pathway with bindings. Rb forms a restriction point in cell cycle and if you phosphorylate it, it pushes the cell past the cell check point for division. Right. Rb forms a complex with transcription proteins and that activates E2f needed to activate cell division and DNA synthesis. Viral T factor can also free up the E2f. Freed E2F binds and activates the proteins needed for cell division. The mitogenic signal comes down the pipe from the receptor top L from proto-oncogenes to phosphorylate Rb. If you take both copies of the recessive Rb gene away, you get uncontrolled replication.***
Viral T antigens kick division into S phase
Transformation doesn’t produce virions nor does it kill the cell. It prevents it from dying ie apoptosis, it becomes immortal like HeLa cells.
E1A, LT, E7 are viral tumor proteins ie antigens that can also free Rb from E2f and kick the cell cycle into mitosis.
Final step in transformation mediated by P53. P53 senses DNA damage or unscheduled replication.
Viral deactivation of P53 Police subsequently triggers the eternal division of the cell ie it continues dividing, it is transformed. Adenovirsues, papilloma V 16,18 E6 Protein, polyomaV infections attack P53 gene, proteasome breaks it down.
P53 Gene, Tumor Suppressor, Mr Fixit
P53 Modus Operandi
Hazards to Mr Fix-It P53; Note especially DNA SB, TF, ROS, RS, Viral infection, oncogenes/hyper-proliferation
Why we need to protect our P53 Mr. Fixit
EX: Action of Carcinogenic Viruses; Epstein-Barr virus (EBV) is a major cause of immunosuppression-related B-cell lymphomas and Hodgkin lymphoma (HL). In these malignancies, EBV latent membrane protein 1 (LMP1) and LMP2A provide infected B cells with surrogate CD40 and B-cell receptor growth and survival signals. T- and NK-cell depletion, LMP1/2A caused massive plasmablast outgrowth, organ damage, and death. Minamitani T1, Ma Y2,3, Zhou H2,3, Proc Natl Acad Sci U S A. 2017 May 2;114(18):4751-4756.
MTOR->mRNA Translation
AKT->apoptosis, transcription
P13K->Growth, prolifer, survival ie cancer
Tumor suppressor
MrFixit
Immune booster
Increase gene expression
BAD BOYS
BAD BOYS
Oncogenes are cellular c-ONC genes that regulate cell Growth. Tagged to a cancer V gene, they transform a cell. Become immortal, to lose limits to growth and become v-ONC, ex:v-SRC, v-MYC, v-RAS
Epigenetically active organisms or chemicals/pesticides can affect many cancers ex:
RAS Proto oncogene mutation leads to proliferation and genomic instability
P13K->Growth, proliferation,
survival ie cancer
Cyclin dependent
Kinase inhibitor
RAL/RAS promoter
RAF/RAS
inhibitor
Growth and Synthesis
TGF-beta cell growth, cell proliferation, cell differentiation and apoptosis.
RAS GENES cell signaling pathways that control cell growth and cell death
p53 protein (like Rb) is a target for the oncogeneproteinsof SV40, adenoviruses, and human papillomaviruses and measles virus and is frequently inactivated in a variety of human cancers, incl: leukemias, lymphomas, sarcomas, brain tumors, carcinomas of many tissues, incl: breast, colon, and lung. In total, mutations of p53 may play a role in up to 50% of all cancers. Mutant APC incr polyposis, mut BRCA1,2 incr BC …muts linked to each cancer
REGULATORY APPROVALS: These Coding and Non-Coding Genes have been Silenced Epigenetically in Cancer and should be tested for Response by every chemical residue produced. Ref: Open Biol v.7(9); 2017 Sep. PMC5627056. Pere Llinas-Arias and Manuel Esteller.
Initial genetic changes start in an early adenoma and accumulate as it transforms to carcinoma.
1. Chromosomal instability.
2. Microsatellite instability. 3. CpG island methylator phenotype pathways responsible for genetic instability in CR.
4. Chromosomal instability pathway consist of activation of proto-oncogenes (KRAS)
5. 6. 7. Inactivation of at least three tumor suppression genes, namely loss of APC, p53 and loss of heterozogosity (LOH) of long arm of chromosome 18.
8. 9. Mutations of TGFBR and PIK3CA genes have also been recently described.
Colorectal cancer is a disease that directly results from the serial accumulation of genetic alterations (for example, mutations in genes such as APC, KRAS and TP53) and epigenetic alterations (for example, aberrant methylation of MLH1 and CDKN2A, etc.) in an evolving clone of colon epithelial cells, which in aggregate leads to the initiation and progression of neoplasms along a polyp to cancer progression sequence.6Gut. 2007 Mar; 56(3): 318–320. W.M. Grady and C. M. Ulrich
Question. What step and how many steps does the pathogen carry out and is it different for every pathogen/cancer? P Yes. Its complex.
U.S. scientists Andrew Fire and Craig Mello were awarded the Nobel Prize in Physiology or Medicine in 2006 for discovery of RNA interference.
The RNA-interference mechanism consists of cleaving a double-stranded RNA present in a cell, which often represents a foreign genome of RNA viruses, into short fragments with Dicer enzyme. One of the two strands of an RNA fragment is integrated into the RISC protein complex (RNA-induced silencing complex) and interacts with a complementary viral mRNA, which then is cleaved with the RISC complex. This stops the synthesis of the protein encoded by this mRNA . Along with response to foreign RNA, cells synthesize their own short interfering RNAs (siRNA) from the so-called microRNA (miRNA). MicroRNA processing is similar to processing of double-stranded viral RNAs. MicroRNAs inhibit cell protein synthesis through degrading mRNAs or building on mRNAs barriers for protein-synthesizing molecular machine (ribosomes). Thus, microRNAs are part of the system for regulating gene expression in a cell. [Also makes them a target for pharmacology]
Mutual regulation of miRNAs and DNA methylation Both miRNAs and DNA methylation play important roles in cancer initiation, progression, and metastasis. Wang and Wu.
Down-regulated microRNA in Breast Cancer
MicroRNAs may fine-tune the expression of as much as 30% of all mammalian protein-encoding genes. ABSTRACT. microRNAs (miRNAs) and DNA methylation are the 2 epigenetic modifications that have emerged in recent years as the most critical players in the regulation of gene expression. Compelling evidence has indicated the roles of miRNAs and DNA methylation in modulating cellular transformation and tumorigenesis. Wang & Wu Epigenetics 2017.
microRNA-409-3 BC cell invasion & metastasis in BC
microRNA-340 migration, invasion metastasis in BC
microR-21 promotion and invasion in BC. both hyper- and hypo-methylation of miRNAs occur frequently in human cancers.
Gastric Adenocarcinoma MicroRNA Profiles in Fixed Tissue and in Plasma Reveal Cancer-Associated and Epstein-Barr Virus-Related Expression Patterns
STAT3 It regulates genes that are involved in cell growth and division, cell movement, and the self-destruction of cells (apoptosis).
E.f produces hydroxyl radicals in epithelia causing DNA damage
E.C colibactin DS DNA breaks, mutations, chromosomal aberrations
BTF is genotoxic enterotoxin -> proliferation and broken intestinal barrier, persistent inflammation, pro-proliferative and antiapoptotic properties
Two pathways to Colorectal Cancer identified.
TGF-beta cell growth,
cell proliferation,
cell differentiation
apoptosis.
CIN ie loss or gain of whole chromosomes reduces mitotic fidelity ie errors in copy w poor prognosis. Proteins associated w CIN may have depletions, over expression, knockout…ex downregulation of Sgo1 in CC leads to progression.
Breast Cancer Carcinogenesis
Epigenetics Primer
Methylation happens on CpG islands
The transcriptional potentials can form cancer profiles
active
Usually inactive
Effects of HPV E6 and E7 Oncogenes’ attack on Methylation represses tumor suppressor genes. DNMT transfers methyl groups to DNA. Too many blocks TSG’s.
Inactivation of tumor suppressor genes gives cancer a shoe into the cell cycle and stop normal cell death ie apoptosis.
Epigenetic Carcinogenesis. Overexpression of DNMT1 results in hypermethylation of tumor-suppressor gene promoters, which leads to cellular transformation and tumorigenesis in HPV carcinogenesis.
Human papilloma virus, DNA methylation and microRNA expression in cervical cancer (Review)
Authors:
Hilda Jiménez-Wences Oscar Peralta-Zaragoza Gloria Fernández-Tilapa
Non-sequence dependent inheritance; some changes in expression are in fact heritable
DNA methylation in cancer Alters expression profile to cancer profile
Transposons and imprinted gene promoters become hypomethylated resulting in their aberrant activation (indicated by the green arrow)
During tumorigenesis, tumor suppressor gene promoters with CpG islands become methylated, resulting in the formation of silent chromatin structure and aberrant silencing
U.S. scientists Andrew Fire and Craig Mello were awarded the Nobel Prize in Physiology or Medicine in 2006 for discovery of RNA interference.
The RNA-interference mechanism consists of cleaving a double-stranded RNA present in a cell, which often represents a foreign genome of RNA viruses, into short fragments with Dicer enzyme. One of the two strands of an RNA fragment is integrated into the RISC protein complex (RNA-induced silencing complex) and interacts with a complementary viral mRNA, which then is cleaved with the RISC complex. This stops the synthesis of the protein encoded by this mRNA . Along with response to foreign RNA, cells synthesize their own short interfering RNAs (siRNA) from the so-called microRNA (miRNA). MicroRNA processing is similar to processing of double-stranded viral RNAs. MicroRNAs inhibit cell protein synthesis through degrading mRNAs or building on mRNAs barriers for protein-synthesizing molecular machine (ribosomes). Thus, microRNAs are part of the system for regulating gene expression in a cell. [Also makes them a target for pharmacology]
Dicer fragment cuts the two-strand RNA, resulting in a siRNA. These processed RNAs combine with catalytically active proteins (nucleases, RISC). A combination of RISC and siRNA specifically decomposes mRNA and prevents translation.
Incorporated Viral RNA
Blocked
Translation
Inflammation C link big
Recurrent antibiotic exposure may promote cancer formation – another step in understanding the role of the human microbiota? Ben Boursi, M.D.,1,2,3,* Ronac Mamtani, M.D. M.S.C.E., Eur J Cancer 2015 Nov 5 51(17)
125,441 cases and 490,510 matched controls were analyzed. For gastro- intestinal malignancies, the use of penicillin was associated with an elevated risk of esophageal, gastric, and pancreatic cancers.
The association increased with the number of antibiotic courses and reached 1.4 for gastric cancers associated with >5 courses of penicillin (95%CI 1.2–1.8).
Lung cancer risk increased with the use of penicillin, cephalosporines, or macrolides (AOR for >5 courses of penicillin: 1.4 95%CI 1.3–1.6).
The risk of prostate cancer increased modestly with the use of penicillin, quinolones, sulphonamides and tetracyclines.
The risk for breast cancer was modestly associated with exposure to sulphonamides. There was no association between use of anti-virals and anti-fungals and cancer risk.
Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells; CATCH 22 ~Kill infection cause cancer. What about dietary residuesSameer Kalghatgi1,*, Catherine S. Spina1,2,3,*
Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy
It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria.
We show that clinically relevant doses of bactericidal antibiotics—quinolones, aminoglycosides, and β-lactams—cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic–induced effects lead to oxidative damage to DNA, proteins, and membrane lipids.
Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects.
Deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l-cysteine or prevented by preferential use of bacteriostatic antibiotics.
Antibiotics can cause oxidative tissue damage in mammals
Environ Health Perspect. 1995 Nov; 103(Suppl 8): 263–268. PMCID: PMC1518971 Research Article Bacterial infection as a cause of cancer. J Parsonnet
1. induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Helicobacter pylori infection. H. pylori has been epidemiologically linked to adenocarcinoma of the distal stomach by its propensity to cause lifelong inflammation.
2. Bile salt metabolites increase colonic cell proliferation. Exogenous compounds such as rutin may be metabolized into mutagens by resident colonic flora
3. Bacteroides species can produce fecapentaenes, potent in vitro mutagens, in relatively high concentrations
Canadians infected by HCV in blood products over a period of four or five years.
You get hepatitis C by coming into contact with blood infected with the hepatitis C virus or through infected bodily fluids, such as semen and vaginal fluid.
HBV, HCV Progression to Liver Carcinoma
IGF insulin like growth factors, PDGF platelet derived growth factors, TGF-beta transcription factors , ET-1 regulates gene expression, modulate mitogenesis, apoptosis, angiogenesis, tumour invasion and development of metastases.
P53 Jekyll and Hyde. WTP53 protein known as PUMA (acronym for “p53 upregulated modulator of apoptosis”). Jinchul Kim, Lili Yu, Xuemei Fu, Yang Xu UC LA March 2019 ScienceDaily
[HCV, HBV] MicroRNA gene expression profile of hepatitis C virus–associated hepatocellular carcinoma†‡ H. Varnholt et al. 2007
In order to obtain a comprehensive microRNA gene expression profile, 80 microRNAs were examined in a subset of tumors, which yielded 10 up-regulated and 19 down-regulated microRNAs compared to normal liver.
Subsequently, five microRNAs (miR-122, miR-100, miR-10a, miR-198, and miR-145) were selected on the basis of the initial results and further examined in an extended tumor sample set of 43 hepatocellular carcinomas and 9 dysplastic nodules.
miR-122, miR-100, and miR-10a were overexpressed whereas miR-198 and miR-145 were up to 5-fold down-regulated in hepatic tumors compared to normal liver parenchyma.
Conclusion: A subset of microRNAs are aberrantly expressed in primary liver tumors (suggests epigenetics role-my comment)
Hep B Virus-hepatocellular carcinoma. reverseDNA
Hepatitis B is highly contagious. It spreads through contact with infected blood and certain other bodily fluids. Although the virus can be found in saliva, it’s not spread through sharing utensils or kissing. It also doesn’t spread through sneezing, coughing, or breastfeeding. Mar 29, 2017
Avoid contact with blood, body fluids
Latex gloves
HBV CDC Recommendation 2018
Hepatitis B Timing for Newborns
This year’s schedule also adds information on the change made last year to administer the first of three doses of the hepatitis B vaccine within the first 24 hours after birth to every nonpremature newborn (birthweight of at least 2000 g).
Dr Meissner, a member of the AAP Committee on Infectious Disease, explained that the CDC estimates there are approximately 1000 potentially preventable hepatitis B cases among infants born in the United States each year. Those cases may result from misinterpretation of the mother’s screening or miscommunication when a mother tests positive, but that information isn’t properly recorded or never makes it to the pediatrician.
When information is misinterpreted or miscommunicated, some pediatricians may not administer the vaccine appropriately.
Human Papilloma Viruses HPV
HPV cancers increasing dsDNA
Natural history and epidemiology of HPV infection and cervical cancer. Xavier Castellsague’
Cervical cancer is the most common cancer affecting women in developing countries. It has been estimated to have been responsible for almost 260 000 deaths annually, of which about 80% occurred in developing countries.
Persistent infection by certain oncogenic HPV types is firmly established as the necessary cause of most premalignant and malignant epithelial lesions of the cervix and of a variable fraction of neoplastic lesions of the vulva, vagina, anus, penis, and oropharynx.
There are more than 100 known HPV genotypes, at least 15 of which can cause cancer of the cervix and other sites. HPV 16 and 18, the two most common oncogenic types, cause approximately 70% of all cervical cancers worldwide. HPV, especially genotypes 6 and 11, can also cause genital warts.
HPV is highly transmissible and it is now considered the most common sexually transmitted infection STD in most populations.
Although most women infected with the virus become negative within 2 years, women with persistent high-risk HPV infections are at greatest risk for developing cervical cancer.
Two Big Guns E6 and E7 HPV Carcinogenesis via viral oncogenes E6 and E7 down regulating cell cyclins, pRB and p53 tumor suppressor genes
CIN= chromosome instability
Cancers HPV’s are implicated in.
Anal cancer
Breast cancer
Cervical cancer
Colorectal cancer
Lung cancer
Oropharyngeal cancer
Skin neoplasm
Squamous cell carcinoma
Residue Reviews; Divergence; Quickies 4 Secs
Allan Astrup Jensen (1983) did a comprehensive review of this issue and published it in Residue Reviews, which is no longer in print. His study was titled “Chemical Contaminants in Human Milk”
I examined his findings and looked up the carcinogenicity of the chemicals in Irving Saks (1981) “Cancer Causing Chemicals”
Antibiotics create ROS in mitochondria and poison those organelles. Turning my attention to pesticide/chemical residues for a bit because they do most of the mutations that complete the cancers.
DIET
H2O
Lotions, creams, cosmetics
Methylation-Alkylation; DNA methyltransferase damage
Antibiotics
Pesticides
RNS and ROS (endogenous and exogenous) radicals can produce DNA damage; linked to colorectal, prostate, breast, lung, bladder cancers
Types of Damage to DNA
Carcinogenesis via Carcinogen exposure
Benzene Leukemia modus operandi
Chemical Carcinogenesis; chemicals can induce specific cancers
Red meat/Processed meat Carcinogenesis; Problem, antibiotics used to fight carcinogenic pathogen infection can produce lipid peroxides increasing risk of mutations leading to cancer. Catch 22!
Lipid peroxides produced in mitochondria by antibiotics.
Problem for Clinicians. Effect of drugs on Chromosome Structure Am J Clin Nutr 1975
Aneuploidy an early biomarker of cancer (pubmed 27729050)
Clastogens include; antibiotics, drugs, viruses, X Rays, oral contraceptives etc.
Clastogens decrease cell division rate, break chromosomes, chromosome deficiency, deletions, rearrangements, changes I chromosome number
Chromosome aberrations (CAs), sister chromosome exchanges (SCEs) and micronuclei (MN) predict cancer risk
CA’s in periferal blood lymphocytes a good marker for cancer risk.
Previous slide, recall lipid peroxide induced cancer mutations
Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules. Mutations in the GSS gene prevent cells from making adequate levels of glutathione, leading to the signs and symptoms of glutathione synthetase deficiency.
ROS can lead to premature aging and cancer.
Lipid peroxidation of cell membrane leads to cell death.
Antibiotics=BO, need to test them all.
Research
Glutathione
Disease.
Taking a Hint from the Red meat carcinogenesis Story and from Sameer Calghatgi’s find of Lipid Peroxidase and ROS Spiking in Antibiotic Exposure of Mitochondria Led me to this Hypothesis for Antibiotic Carcinogenesis
Alcohol Carcinogenesis may operate synergistically with pathogens. ROS increased by stress on mitochondria via antibiotics from dietary sources or prescriptions. Catch 22 again.
Genotoxic Carcinogenesis
DNA Adducts are carcinogens attached to a section of DNA.
DNA adducts like dimethylbenzanthracene DMBA indicate exposure to carcinogen, not necessarily active cancer. Useful markers of exposure to carcinogens.
Adducts can result in various changes to DNA.
DNA damaging agents plus epigenetic alteration
DNA/Epig
Messing Up the DNA Repair Crew
Effects of Commonly Used Pesticides in China on the Mitochondria and Ubiquitin-Proteasome System in Parkinson’s Disease. Int J Mol Sci. 2017 Dec; 18(12): 2507. Published online 2017 Nov 23. doi: 10.3390/ijms18122507
The story on antibiotic impacts on mitochondria is getting very interesting from being associated with increased cancer risk to being used in the fight against cancer. Clearly the research folks are on that story. I would like to see a detailed inventory for all antibiotics on their impacts on mitochondria and the UPS. The Eureka story I want to bring to your attention is pesticide residues, mitochondria and the integrity of the UPS system. Previous studies have linked individual pesticides to mitochondrial dysfunction [20,21,22,23,24] or UPS dysfunction [25,26,27,28,29] and this has serious and major systemic harm potential. So where are we on this aspect?
My cancer findings~1/2 ED’s~Bcanc Cancer Causing Pesticides in Mothers Milk. JJ1990 Pesticide finding
DDT -endocrine disrupting chemical, meaning it mimics human hormones (ed)
Oral-mouse-conclusive carcinogen
(OMC) for short
Subcutaneous-mouse-conclusive (SMC)
Suspected animal carcinogen (SAC) IARC
Pesticide Finding
PCB (ed)
DDE (ed) Strong BC links
Hexachlorobenzene (ed)
Conclusive human and mouse liver carcinogen
Oral-mouse conclusive carcinogen
Oral hamster conclusive,
Pesticide Finding
Hexachlorocyclohexane (HCH) (ed)
Dieldrin (ed)
Heptachlor epoxide (ed)
Oral mouse conclusive, animal positive (IARC)
oral rat suggestive, oral mouse conclusive, animal positive (IARC)
Oral rat conclusive, oral mouse conclusive, IARC positive
Pesticide Findings
1,2-dichloroethane
Nicotine
Mouse conclusive, rat conclusive, bioassay positive
Oral rat suggestive, ipr mouse suggestive, scu hamster suggestive, ipr mouse conclusive, Human suspected
Conclusion
The number of potentially cancer causing c pesticides found in mothers milk is of great concern even though the levels might be very small, because they are widespread, and individual susceptibility to cancer varies for many reasons including genetic and where immune systems are weakened
Volatile Chemicals in Mothers Milk in the United States: Pellizzeri et. Al. (1982) found:
Many VOC’s are carcinogens, mutagens, teratogenic, embroyotoxic, immunotoxic, behavioral impacts, developmental and neurological
This group contains some very nasty chemicals including narcotics, irritants, carcinogens, substances capable of clonic convulsions, coma and death and probably much more
They tell us that the chemical industry and regulators are not doing their job, to protect us from these nasty chemicals
The Sources
The Canadian Diet
The Canadian Diet (McLeod et al. (1980)
The average daily dietary intake (ADI) in micrograms per kilogram during the period 1976-1978
There were 24 different residues at that time including organochlorines, organophosphates, sulfur compounds, nitroaniline, pthalonitrile, and carbamate pesticides
The Canadian Diet (McLeod et al. (1980)
Reported for the first time were chlordane, methidathion, phosalone, toxaphene, chlorothalonil, dichloran, quintozene, sulfur, chlorpropham, and PCB’s. However, had he used a higher level of analysis, he might have picked up still more ingredients.
The Canadian Diet (McLeod et al. (1980) Chemical Carcinogenicity
Daily dietary intake of pesticides, industrial chemicals and the elements
Rather than breaking these down I will simply list the lot since we already have experience with many of them from Canada and mothers milk and wildlife studies
USA Dietary Contaminants; discovery of synergisms; (we know these from drug interactions)
diazinon, dichloran, dicofol, dieldrin, dimethoate, endosulfan I, endosulfan II, endosulfan sulfate, endrin, ethion, 2-ethylhexyl diphenyl phosphate, fenitrothion (reacts with DDT and viruses to make them more dangerous ie lethal in ducks) fenthion, fonofos, heptachlor epoxide, hexachlorobenzene, leptophos, linuron, malathion, methidathion, methoxychlor,
I leave the US Dietary endocrine disruptivity and carcinogenicity to the young ecologists
All were in the WHO and FAO (food and agri org) acceptable levels for ADI! Are they truly safe?
Int J Mol Sci. 2017 Nov 23;18(12). pii: E2507. doi: 10.3390/ijms18122507. Effects of Commonly Used Pesticides in China on the Mitochondria and Ubiquitin-Proteasome System in Parkinson’s Disease. Chen T1, Tan J2, Wan Z3, Zou Y4, Afewerky HK5,6,7, Zhang Z8, Zhang T9,10,11.
Abstract
Evidence continues to accumulate that pesticides are the leading candidates of environmental toxins that may contribute to the pathogenesis of Parkinson’s disease. The mechanisms, however, remain largely unclear. According to epidemiological studies, we selected nine representative pesticides (paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate, tebufenpyrad, trichlorphon and carbaryl) which are commonly used in China and detected the effects of the pesticides on mitochondria and ubiquitin-proteasome system (UPS) function. Our results reveal that all the nine studied pesticides induce morphological changes of mitochondria at low concentrations. Paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate and tebufenpyrad induced mitochondria fragmentation.
RESIDUES IN BOTTLED WATER
Water Treatment Generated Carcinogens. J Jyrkkanen, 2002
dichloromethane (side issue; solvent residue of decaffienated coffee)
chloroform(trichloromethane) CHCl3
bromoform CHBr3
bromodichloromethane CHCl2Br
dibromochloromethane CHClBr2
Group B carcinogens, shown to cause cancer in animals.
THM’s (known animal carcinogens)
They are Cancer Group B carcinogens ([my comment..we are animals, mammals to be precise]). Trichloromethane (chloroform) is by far the most common in most water systems. Dibromochloromethane is the most serious cancer risk, (0.6 ug/l to cause a 10-6 cancer risk increase) followed in order by Bromoform (4 ug/l), and Chloroform (6 ug/l). Current regulations limit the concentration of these 4 chemicals added together (total trihalomethane or TTHM levels) to 100 ug/l.
Kenneth P. Cantor et.al. Dec 1987 JNCI [ found that people who drank 8 cups of chlorinated tap water for 40-59 years had a 40% greater risk of bladder cancer than those who drank less tap water or unchlorinated water. People who drank 8 cups of chlorinated tap water for 60 or more years had an 80% greater risk of bladder cancer]
Haloacetic Acids HAA, CBP’s
monobromoacetic acid
dibromoacetic acid
monochloroacetic acid
dichloroacetic acid ***
trichloroacetic acid
A statistically significant increase of carcinogenicity (hepatocellular carcinoma) was noted at 1.6g/1 DCA. Exposure to 0.5g/1 DCA increased hepatocellular neoplasia, (carcinoma and adenoma) at 100 weeks. These data demonstrate that DCA is an hepatocarcinogen to the male F344 rat. A. B deAnglo.
Ozonation, is expensive and in salty water can produce other carcinogens, bromates. Treatment with ozone causes few DBPs but does result in the production of bromate when used in water with high bromine concentrations. Bromate has been shown in studies by the EPA to cause mesotheliomas in rats and kidney tumors in both rats and mice. In addition, oral exposures to potassium bromate have been shown to cause renal cancer in rats.
Chloramination; and DBP’s
The Chloramines are:
monochloramine (NH2Cl)
dichloramine (NHCl2)
trichloramine, nitrogen trichloride (NCl3).
Chloramination DBP’s Summary; definitely some toxins, carcinogens
Conclusion : organic byproducts of chlorination are the chemicals of greatest concern in assessment of the carcinogenic potential of chlorinated drinking water. [J Natl Cancer Inst 85:817–822, 1993]
Chloramine Toxicology
Chloramines are composed of three chemicals formed when chlorine and ammonia-nitrogen are combined in water. In high doses chloramines cause blood and liver damage in laboratory animals. Monochloramine is preferred because of its biocidal properties and minimal taste and odor. Monochloramine is created by controlling the chlorine-to-ammonia ratio to a value generally less than 5:1 by weight or 1:1 on a molar basis.
Impending Regulations
The EPA is considering extensive revisions to the regulations covering disinfection by-products (DBP’s).
The limit for TTHM’s would be lowered to 80 ug/l, and three additional categories of DBP’s . This standard will replace the current standard of a maximum allowable annual average level of 100 parts per billion in December 2001 for large surface water public water systems. [Canada uses 100 ppb]. The standard will become effective for the first time in December 2003 for small surface water and all ground water systems.
An MCL for total haloacetic acids of 60 ug/l is expected. Potential nervous system and liver effects.
Chlorite is to be regulated with an MCL set at 1 mg/l (1 ppm). Excessive levels linked to hemolytic anemia.
Bromate, the other newly regulated DBP , is a concern only for systems using ozone. An MCL of 10 ug/l is expected. Excessive levels causes gastrointestinal, kidney, and hearing effects.
Data Gaps
Reproductive toxicity. Robert Chapin, a reproductive toxicologist in the Laboratory of Toxicology, is responsible for studies on 10 compounds identified as high priorities by the EPA: the THMs bromodichloromethane and chlorodibromomethane; the HAAs bromochloroacetic acid, dibromochloroacetic acid, and tribromoacetic acid; the haloacetonitriles bromoacetonitrile and dibromoacetonitrile; hexachloropropanone (a member of a lesser class of DBPs called the haloketones); sodium bromate; and a mixture of mono-, di-, and trichloroacetic acids, mono- and dibromoacetic acids, and bromochloroacetic acid (all HAAs). Long-term rodent carcinogenicity studies are being developed for six compounds under Boorman and one compound (MX)
Nitrification
Blue-green algal blooms, if water temps high
Chloramines also have been found to produce total trihalomethanes (TTHMs)
bromodichloromethane
chlorodibromomethane
bromoform
dihaloacetic acids poorly controlled under some conditions (HAAs).
dichloroacetic acid causes cancer in rodents
dissolved organic halogen poorly controlled under some conditions
Research results imply that many unreported DBPs are created by chloramines.
two-step microbial process, ammonia is converted to nitrite and then to nitrate. The intermediate stage-nitrite–depletes the chloramine residual and increases heterotrophic bacteria.
nitrite
nitrate (two-headed fish in hatcheries)
haloacetonitriles
mutagen X, (MX)
Canadian Guidelines for Nitrite and Nitrates in Drinking Water
I am leaning towards reverse osmosis or activated charcoal or untreated pure water from a known tested healthy source like rain or a mountain spring. These may not be fool-proof either. One has to know their water.
Some countries fluoridate their water purportedly to provide drinkers with better teeth. I would expect fluoride to behave like these other halogens, chlorine and bromine, and generate a similar class of carcinogens and related byproducts. The reader should search the literature if they are curious about this. I have heard that fluoridation in the USA causes 10,000 additional cancer deaths per year. I do not recall the reference. Over-dosing is very likely for diebetics who drink large volumes of water and they are at special risk if it is added to the water. Fluoride is present in a balanced diet so one has to wonder why the health authorities wouldn’t rather simply promote a balanced diet rather than fluoridate the water.
To sort through the health effects puzzle mozaic as it develops, keep abreast of research at Entrez PubMed or Medline etc. online journals, and compare original research results with what EPA and NIH are saying and how they translate this into policy recommendations. Another journal with some interesting relavence is Ecotoxicology and Environmental Safety
One of the biggest concerns I have is that to escape the known toxics DBP’s from chlorination, many communities are getting on the chloramine bandwagon despite the fact that the health effects and toxics BP’s are poorly known.
Water policy should evolve towards removing undesirable substances rather than replacing them with toxics and perhaps we should regard water in a more sacred light like our distant ancestors did rather than regarding it as a good hiding place for our excrement and toxic wastes and pesticide residues. Sacred springs were places of worship to the ancient Celts and Norse. What was so wrong with Grannies old Rain Barrel anyway?
How exactly did we, and the millions of other species, survive hundreds of millions of years of evolution without chlorinating our drinking water?One of my greatest joys is hiking in the mountains is stooping to drink from a spring gushing forth from the base of a scree slope. To know how terrible city water is, one only has to do this once. There is no greater gift that nature has to offer than clean water. It is the stuff of life itself. You see, our bodies are filters of all that passes through. We best be careful not to clog those pores with the crud of human neglect. Know your water, care for it and respect it, and don’t forget the other creatures’ needs as well.
Fine particulate and sulfur oxide–related pollution were associated with all-cause, lung cancer, and cardiopulmonary mortality. Each 10-µg/m3 elevation in fine particulate air pollution was associated with approximately a 4%, 6%, and 8% increased risk of all-cause, cardiopulmonary, and lung cancer mortality, respectively. Measures of coarse particle fraction and total suspended particles were not consistently associated with mortality.
Int J Mol Sci. 2017 Nov 23;18(12). pii: E2507. doi: 10.3390/ijms18122507. Effects of Commonly Used Pesticides in China on the Mitochondria and Ubiquitin-Proteasome System in Parkinson’s Disease. Chen T1, Tan J2, Wan Z3, Zou Y4, Afewerky HK5,6,7, Zhang Z8, Zhang T9,10,11.
9 common pesticides (paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate, tebufenpyrad, trichlorphon and carbaryl) and the effects on mitochondria and ubiquitin-proteasome system (UPS) function.
Our results reveal that all the nine studied pesticides induce morphological changes of mitochondria at low concentrations. Paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate and tebufenpyrad induced mitochondria fragmentation
Etiology of human breast cancer is unknown, whereas the Mouse Mammary Tumor Virus (MMTV) is recognized as the etiologic agent of mouse mammary carcinoma.
Several data strongly suggest a causative role of MMTV in humans, such as the presence of viral sequences in a high percentage of infiltrating breast carcinoma and in its preinvasive lesions, the production of viral particles in primary cultures of breast cancer, the ability of the virus to infect cells in culture.
This paper demonstrates that MMTV is present in human saliva and salivary glands. MMTV presence was investigated by fluorescent PCR, RT-PCR, FISH, immunohistochemistry, and whole transcriptome analysis. Saliva was obtained from newborns, children, adults, and breast cancer patients. The saliva of newborns is MMTV-free, whereas MMTV is present in saliva of children (26.66%), healthy adults (10.60%), and breast cancer patients (57.14% as DNA and 33.9% as RNA). MMTV is also present in 8.10% of salivary glands. RNA-seq analysis performed on saliva of a breast cancer patient demonstrates a high expression of MMTV RNA in comparison to negative controls. The possibility of a contamination by murine DNA was excluded by murine mtDNA and IAP LTR PCR.
These findings confirm the presence of MMTV in humans, strongly suggest saliva as route in inter-human infection, and support the hypothesis of a (MMTV) viral origin for human breast carcinoma.
2018 CDC HPV Recommendation
HPV Vaccination Rates Low
One trend Dr Meissner finds particularly troubling is continued low uptake of HPV vaccine — about 50% for males and just more than 60% in females, he noted.
“We would sure like to see them a lot higher because there are about 31,000 cases of HPV-induced cancers each year in the US — mainly cervical cancer for women and oral/pharyngeal cancer for men. The vast majority of these cancers could be prevented by administering the HPV vaccine.”
Now, only two doses are necessary before a child’s 15th birthday. After that birthday, people need three doses, the schedule states.
“At least 80% of the population is going to be infected by at least one strain of HPV in their life, so if you could prevent your son or daughter from getting cancer, it’s hard to understand why a parent wouldn’t jump at that,” Dr Meissner said.
MMTV and HIV Transmission via milk. P kill MMTV w Flash Heating Also
“These findings confirm the presence of MMTV in humans, strongly suggest saliva as route in inter-human infection, and support the hypothesis of a viral origin for human breast carcinoma.”
HPV 16 dsDNA V
Oncotarget. 2017 Sep 30;8(49):86710-86717. doi: 10.18632/oncotarget.21414. eCollection 2017 Oct 17.
MDM4 genetic variants predict HPV16-positive tumors of patients with squamous cell carcinoma of the oropharynx.
November 30, 2017 Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) Summary: UV radiation has been known for a long time to be a risk factor for the development of skin cancer.
Simultaneous infection with human papillomaviruses (HPV) has also been suspected to promote skin cancer, particularly in organ transplant recipients. Scientists have now been able to show for the first time in a natural system
that papillomaviruses associated with UV light promote the development of non-melanoma skin cancer.
DDE/DDT a probable factor in Breast cancer and possible cofactor with oncogenic viruses. OC’s a risk factor World-wide. A strong probability of their contribution to cancer progression. 4-5000 metric tons used worldwide today. India biggest user. BKME mills also put it out in effluent.
Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system (CNS)
caused by the polyoma virus JC virus (JCV) and characterized by focal demyelination. The virus has worldwide distribution, with a seroprevalence of 39% to 69% among adults.Jul 6, 2017
Special risk of causing demyelination and potentially fatal (PML) inflammation of the white matter (leuko-) of the brain.
Polyomavirus simian vacuolating virus 40 (SV40) is a known oncogenic DNA virus which induces primary brain and bone cancers, malignant mesothelioma, and lymphomas in laboratory animals. From African monkeys.
A meta-analysis of molecular, pathological, and clinical data from 1,793 cancer patients indicates that there is a significant excess risk of SV40 associated with human primary brain cancers, primary bone cancers, malignant mesothelioma, and non-Hodgkin’s lymphoma.
Experimental data suggest that SV40 may be functionally important in the development of some of those human malignancies.” Possible human carcinogen. Class 2b.
SV40, simian v 40, a highly cancerous polyoma v
Originated from African Monkeys brought to the US and spread through Polio vaccine.
Adrenal tumor
Brain tumor, glioblastoma multiforme
Mesothelioma
NHL non-Hodgkins lymphoma
Thyroid cancer
SV40 is believed to suppress the transcriptional properties of the tumor-suppressing p53 in humans through the SV40 large T-antigen and SV40 small T-antigen
SV40 may spread through a respiratory or fomite, i.e., hand-to-mouth, route. From this initial portal of entry, the virus must have access to the circulatory and/or lymphatic system in order to reach its presumed site of persistence, the kidney, or the tissues and organs that give rise to the tumors associated with the virus. J of Virology. This Article
doi: 10.1128/JVI.77.9.5039-5045.2003 J. Virol. May 2, 2003
Herpes Viruses this is the most comprehensive study demonstrating that EBV is present and transcriptionally active in the brain of most cases of MS and supports a role for the virus in MS pathogenesis. Hassani
Ex: EBV or Herpes-4; cancer plus MS 2018
Epstein-Barr virus is present in the brain of most cases of multiple sclerosis and may engage more than just B cells. Hassani A et al 2 Feb 2018
Epstein-Barr virus (EBV) HHV-4…dsDNA Mono-kissing disease Present in 90% of People
Breast cancer, Gall bladder, Nasopharyngeal cancers
Detection of Epstein-Barr Virus in Invasive Breast Cancers
Mathilde Bonnet Jean-Marc Guinebretiere Elisabeth Kremmer Virginie Grunewald Ellen Benhamou Genevieve Contesso Irene Joab
“our results show the presence of EBV genome in a large subset of breast cancers. Because it is more frequently associated with the most aggressive tumors, EBV may play a role in their development”
Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. The epidemiology of EBV and its association with malignant disease Henrik Hjalgrim, Jeppe Friborg, and Mads Melbye. Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S. Denmark
Epstein-Barr virus (EBV) is an ancient virus, and has probably coevolved with its different hosts over the last 90–100 million years (McGeoch et al., 1995).
Ability to establish lifelong latency and intermittent reactivation after primary infection
Limited clinical symptoms in the majority of infected individuals, EBV has become ubiquitous in all human populations
EBV Ubiquitous
EBV mono
The salient features of EBV-latent antigens in B-cell lymphomas.
Abhik Saha, and Erle S. Robertson Clin Cancer Res 2011;17:3056-3063
Epstein-Barr virus (EBV) is associated with a wide variety of B-cell-derived lymphoid neoplasms, including Burkitt lymphoma, lymphomas arising in immunocompromised patients (post-transplant and HIV-associated lymphomas), and Hodgkin lymphoma.
EBV has been linked to some T-cell lymphomas (angioimmunoblastic T-cell lymphoma, extranodal nasal-type natural killer/T-cell lymphoma, and other rare histotypes), nasopharyngeal cancer, and a subset of gastric cancers.
Advances in our understanding of the pathobiology of EBV oncogenesis, including the transforming and immunogenic properties of the virus and the role of immune dysregulation, have provided the rationale for new treatment strategies.
Epstein–Barr virus (EBV) was the first virus shown to cause cancer in humans and is associated with a wide range of human cancers originating from epithelial cells, lymphocytes and mesenchymal cells.
EBV-associated neoplasms affect both immune-competent hosts and immune-compromized patients who have received an organ transplant or who exhibit iatrogenic immune suppression.
The development of an EBV-associated neoplasm is largely dependent on environmental factors and genetic susceptibility to viral infection that is associated with genetically prone immune deregulation.1
EBV leads to the extensive methylation of both the host and viral genome. Epigenetic tagging??
Prevention. CMV is most commonly contracted through contact with the bodily fluids of a person carrying an active CMV infection. For pregnant women, women who might become pregnant, or women who work with young children, it is imperative to practice CMV precautions in order to avoid exposure to CMV.
BK Virus (BKV) polyoma V…dsDNA ~CRC cofactor, ~prostate C
Brain tumor, Glioblastoma; Prostate cancer
BK Virus
BK Risk factors
BK transmission
Kaposi’s sarcoma, KSHV & HHV8…dsDNA
Kaposi sarcoma (KS) is a cancer that causes patches of abnormal tissue to grow under the skin, in the lining of the mouth, nose, and throat, in lymph nodes, or in other organs. These patches, or lesions, are usually red or purple. They are made of cancer cells, blood vessels, and blood cells.
Received:04 December 1995Accepted:29 January 1996Published online:01 March 1996
EV…RNA Viruses on upswing!
Enterovirus Prevention
Carcinoid tumors. CDC
Many people who are infected with non-polio enteroviruses do not have symptoms but can still spread the virus to other people. This makes it is difficult to prevent them from spreading. But the best way to help protect yourself and others from non-polio enterovirus infections is to—
wash your hands often with soap and water, especially after using the toilet and changing diapers
avoid close contact, such as touching and shaking hands, with people who are sick
clean and disinfecting frequently touched surfaces
There is no vaccine to protect you from non-polio enterovirus infection.
Retroviruses +ssRNA
A retrovirus is a single-stranded positive-sense RNA virus with a DNA intermediate and, as an obligate parasite, targets a host cell.
Retroviridae includes such important human pathogens as human immunodeficiency virus (HIV) and human T-lymphotropic virus (HTLV), the causes of AIDS and adult T-cell leukemia respectively.
There are 1. exogenous retroviruses 2. endogenous retroviruses that we have inherited from when we lived 90 million years as a fish to the present.
Retroviruses; Endogenous ERVs are fossil viruses, Exogenous ie HIV, HTLV-1 similar components, ie; reverse transcriptase; transmitted parent to offspring in genome. Form 8% of nucleotides.
HIV AIDS most recent acquisition from African monkeys brought to USA to make polio vaccine by Dr. Maurice Hilleman.
Integration of retroviral DNA into a germ cell can result in a provirus that is transmitted vertically to the host’s offspring. In humans, such endogenous retroviruses (HERVs) comprise >8% of the genome.
The HERV-K(HML-2) proviruses consist of ~90 elements related to mouse mammary tumor virus, which causes breast cancer in mice. A subset of HERV-K(HML-2) proviruses has some or all genes intact, and even encodes functional proteins, though a replication competent copy has yet to be observed.
More than 10% of HML-2 proviruses are human-specific, having integrated subsequent to the Homo-Pan divergence, and, of these, 11 are currently known to be polymorphic in integration site with variable frequencies among individuals.
Increased expression of the most recent HML-2 proviruses has been observed in tissues and cell lines from several types of cancer, including breast cancer, for which expression may provide a meaningful marker of the disease.
HTLV-1…ssRNA-RT, Leukemia, adult T cell leukemia. Serious related disease not curable yet.
Summary: Human T-cell leukemia virus type 1 (HTLV–1), the first human retrovirus to be discovered, is present in diverse regions of the world, where its infection is usually neglected in health care settings and by public health authorities.
Usually asymptomatic in the beginning of the infection and disease typically .
HTLV-1 Transmission
Transmission found to be from mother to child and predominantly through breastfeeding
Sexual intercourse, and blood contact, including the transfusion of infected cellular products or sharing of needles and syringes.
Flash heating milk may render virus inactive but birthing exposes infant to maternal blood
A Diversion on AIDS; ssRNA-RT AIDS HIV-1,2,3,4
MH Imported HIV in African Green monkeys for Polio vaccine. HK used Congo chimps for same.
Dr. Hilary Koprowski injected HIV1 infected Chimp polio serum into 244,596 Congolese starting the African AIDS epidemic.
Mona monkey, Red capped mangabay->Chimp->SIVcpz->Human HIVcpz= HIVm+n
AIDS 39,000,000 killed by 2016; 40% increase in cancer risk
WWII Killed Soviet Union 27,000,000
(+/-)RNA
Nomenclature of retroviruses
Leukemia and AIDS viruses
Projections
Early link to Sex Transmission
4 Types
WHO Dunnit?
After Sex
By products of infection widespread
Cancer
SSHV-8
From Chimp/Green monkey to 39,000,000 deaths in 60 years Drug found that blocks sexual transmission. ***
RNA V paramyxoviruses. JCCI: Measles Virus (MV): Association with Cancer Samuel Ariad1*, Irena Lazarev1 and Daniel Benharroch2 1Department of Oncology, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel 2Department of Pathology, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Corresponding Author : Samuel Ariad Department of Oncology, Soroka Medical Center Beer Sheva, P.O.Box 151, Israel 84101
MV has been detected in several malignancies, including lung, breast, and endometrial cancers, as well as Hodgkin’s lymphoma. The presence of MV in these tumors was associated with distinct clinico-pathological characteristics: in lung cancer, older ages of patients and over expression of Pirh2, and in breast cancer, age less than 50 years, lower histological grade, and over expression of p53. Nectin-4 is the MV receptor in epithelial cells and is highly expressed in certain epithelial tumors. MV-associated tumorigenesis may be linked to the effect of MV-phosphoprotein on Pirh2, an E3 ubiquitin ligase of p53. By way of MV interaction with Nectin-4 and Pirh2,
persistent MV infection may co-act with other factors in transforming cells to become malignant.
Bacterial Cancers; Ex: Helicobacter pylori Stomach and colon cancer (CRC)
Houghton and Wang; Identifying the Cancer Stem Cell
We reasoned that BMDC are the ultimate uncommitted stem cell and represent the ideal candidate for transformation in an inflammatory environment.
BMDC have the capacity for self-renewal, are long-lived and chemoresistant, and may be inherently mutagenic.63
In support of our theory that bone marrow is the source of the cancer stem cell, there is accumulating data that demonstrate a surprising degree of plasticity of adult bone marrow stem cells.
Dis Esophagus. 2014 Sep-Oct;27(7):645-53. doi: 10.1111/dote.12194. Epub 2014 Mar 17. Association of Helicobacter pylori infection with esophageal adenocarcinoma ESCC and squamous cell carcinoma: a meta-analysis. Nie S1, Chen T, Yang X, Huai P, Lu M.
CagA-positive strains {H.pylori} might have a positive association with ESCC in non-Asian population and an inverse association in Asian population.
H Pylori Prevention/Treatment
CDC What can people do to prevent H. pylori infection?
Since the source of H. pylori is not yet known, recommendations for avoiding infection have not been made. wash hands thoroughly, to eat food that has been properly prepared, and to drink water from a safe, clean source.
2014 – Aug 14, 2014 – Washing hands thoroughly, eating food that is properly prepared and drinking water from a safe, clean source are important steps for preventing H. pylori infection in children.
PANCREATIC CANCER. 2015 Nov;44(8):1340-4. doi: 10.1097/MPA.0000000000000414. Cytotoxin-Associated Gene A-Negative Strains of Helicobacter pylori as a Potential Risk Factor of Pancreatic Cancer: A Meta-Analysis Based on Nested Case-Control Studies. Chen XZ1, Wang R, Chen HN, Hu JK.
Population-based nested case-control studies comparing the serological prevalence of Helicobacter pylori between pancreatic cancer cases and cancer-free controls were eligible.
Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer risk between Helicobacter pylori infected and noninfected persons were estimated.
CagA-negative nonvirulent strains of Helicobacter pylori had a significant increased risk for pancreatic cancer (OR, 1.47; 95% CI, 1.11-1.96; P = 0.008).
The CagA-negative non-virulent strains of Helicobacter pylori may be a potential risk factor of pancreatic cancer. High-quality prospective large-scaled studies are required for more conclusive results.
Jan 20, 2011 – Streptococcus bovis (S. bovis) bacteria are associated with colorectal cancer and adenoma. S. bovis is currently named S. gallolyticus. 25 to 80% of patients with S. bovis/gallolyticus bacteremia have concomitant colorectal tumors. Colonic neoplasia may arise years after the presentation of bacteremia
Diagn Microbiol Infect Dis. 2016 Jun;85(2):239-42. doi: 10.1016/j.diagmicrobio.2016.02.019. Epub 2016 Feb 26. Bacteremia with the bovis group streptococci: species identification and association with infective endocarditis and with gastrointestinal disease. Marmolin ES1 and others.
The association of S. gallolyticus subsp. gallolyticus with colorectal neoplasia and with infective endocarditis and the association between S. gallolyticus subsp. pasteurianus and pancreatic cancer were found to be clinically important.
Also, a very high 1-year mortality rate with S. lutetiensis (66.7%) and S. gallolyticus subsp. pasteurianus (58.7%) bacteremia calls for intensive investigation for underlying disease focusing on the pancreas and the hepatobiliary system.
S. g, S. p and S. l, CRC and Pancreatic Cancer (2a in my opinion)
Lab Characteristics
CRC: Fusobacterium nucleatum Promotes Colorectal Carcinogenesis by Modulating E-Cadherin/β-Catenin Signaling via its FadA Adhesin . Mara Roxanna Rubenstein et al Cell Host and Microbe. 2013
An estimated 15% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host sequence subtraction and found marked over-representation of Fusobacterium nucleatum sequences in tumors ..
Fusobacterium-plaque-colon C
Schematic of the proposed mechanism of Fusobacterium nucleatum-induced impairment of autophagic flux enhancing the expression of proinflammatory cytokines via ROS in Caco-2 Cells (see text for details).
INTERLEUKINS
Brush twice daily
Brushing your teeth regularly could help to prevent bowel cancer, a study suggests.
This is because the mouth bacteria that cause bleeding gums can travel via the blood to the bowel where they could trigger cancer or worsen existing tumours.
The bug fusobacterium has been found to be hundreds of times more common in cancerous tumours than in normal cells.
Now researchers have found that the microbes can make pre-cancerous growths in the bowel turn cancerous. They can also make any existing tumours in the bowel grow larger.
Wash your hands. Frequent hand-washing in hot, soapy water is the best way to control infection. …
Avoid drinking untreated water. …
Avoid raw fruits and vegetables. … Choose hot foods.
Salmonella typhi-gall bladder cancer
Salmonella Prevention
Quick Tips for Preventing Salmonella. Cook poultry, ground beef, and eggs thoroughly. Do not eat or drink foods containing raw eggs, or raw (unpasteurized) milk. If you are served undercooked meat, poultry or eggs in a restaurant, don’t hesitate to send it back to the kitchen for further cooking.Mar 9, 2015
Cooked meat, eggs, poultry, pasteurized milk. Zero raw
Schistosomiasis Life Cycle
Schistosoma helminths
Bladder cancer
Colorectal cancer
Liver cancer
Japonicum
Schistosoma nasale blood fluke
B
In the short term, enhanced knowledge of pathogenesis, particularly inflammation and its associated DNA damage—both nitrative and oxidative—may assist in disease control, provided the at-risk populations can be educated of the elevated risk of CCA from repeated infections.
Also, dietary changes that include natural products rich in anti-oxidants may provide enhanced protection against CCA.
In the longer term, it should be feasible to develop specific and sensitive techniques for detection of oxidative damage markers in serum, urine, or faeces for early cancer screening of the at-risk populations. We and others are now actively engaged in this endeavour.
BILE DUCT CARCINOMA Opisthorchis viverrini, O. felineus, and Clonorchis sinensis
Liver Flukes linked to Cholangiocarcinomas
Figure 2. Life Cycles of O. viverrini and C. sinensis
Figure 2. Life Cycles of O. viverrini and C. sinensis
Sripa B, Kaewkes S, Sithithaworn P, Mairiang E, Laha T, et al. (2007) Liver Fluke Induces Cholangiocarcinoma. PLOS Medicine 4(7): e201. https://doi.org/10.1371/journal.pmed.0040201
Genome Biol. 2001; 2(6): reviews1017.1–reviews1017.5. Published online 2001 Jun 5. Endogenous retroviruses in the human genome sequence David J Griffiths1
Like other transposable elements, HERVs are thought to have played an important role in the evolution of mammalian genomes
This paper presents a new, recently formulated theory, which concerns the etiopathological process of autoimmune diseases. This theory takes into account the existence in the human genome, since approximately 40 million years, of so-called human endogenous retroviruses (HERVs), which are transmitted to descendants “vertically” by the germ cells. It was recently established that these generally silent sequences perform some physiological roles, but occasionally become active and influence the development of some chronic diseases like diabetes, some neoplasms, chronic diseases of the nervous system (eg, sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short synopsis of immunological processes involved in the pathogenesis of autoimmune diseases, such as molecular mimicry, epitope spreading and activation of the superantigen. We then focus on experimental findings related to systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome and some diseases of hepar and otorhinal tissues. We conclude the outline of this new model of the development of chronic diseases and indicate the conclusions important for the teaching of the basis of pathology.
Eight per cent of the human genome is derived from the integration of retroviral sequences that were incorporated in our DNA more than 25 million years ago. Although some of these elements show mutations and deletions, some HERVs are transcriptionally active and produce functional proteins…..epigenetic changes observed in pathological conditions such as systemic lupus erythematosus (SLE) or cancer could be translated into an effect on the activation of some of the retroelements present in our genome which ultimately could have a direct or indirect role on the initiation and clinical evolution of certain chronic diseases.
Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes.
Aberrant expression of coding genes or long non-coding RNAs (lncRNAs) with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression.
Dispersed across the human genome, endogenous retroviruses (ERVs) provide autonomous gene regulatory modules
Growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation. EX: ADENOCARINOMA & HL
Human Genome + Mitochondrial genome 3200000000 nucleotides + 16569 nucleotides 25,601,325 (8%) x total nucleotides are HERV’s and they come in 3 flavors, good, neutral and bad.
Most DNA involved in maintenance of ribosomes and respiration.
Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules. Mutations in the GSS gene prevent cells from making adequate levels of glutathione, leading to the signs and symptoms of glutathione synthetase deficiency.
ROS can lead to premature aging and cancer.
Lipid peroxidation of cell membrane leads to cell death.
Antibiotics=BO, need to test them all.
Research
Glutathione
Disease.
Looming Catch 22 Mitochondria Antibiotic Crisis
As microbes acquire increasing resistance to existing antibiotics we will require new stronger antibiotics.
The mitochondria is vulnerable to antibiotics and pesticides and its destruction will lead to shorter lives, loss of the p53 gene, more cancers and damage to the heart and brain. Result mitochondrial knockdown.
deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l-cysteine or prevented by preferential use of bacteriostatic antibiotics.
REQUIREMENT. Create mitochondria friendly antibiotics, pesticides that are also neutral in carcinogenicity.
P53 Master Guardian of our Genes Polio Vaccine, Asbestos
Polio vaccination used Rhesus monkey kidney based serum carrying SV40 virus.
SV40 caused kidney disease, sarcoma and other cancers in animals tested, SV40 now probably being passed around by human progeny having become a HERV-SV40
98 million Americas got vaccinated and SV40 targets p53 gene, causing cells to lose control of normal death, DNA repair and healthy wild type p53 production
10-30 million of those exposed to SV40. Only discovered 1961 SV40 caused cancers in lab rats. Gov downplayed
Asbestos mutates p53 genes. Canada Mining and exporting presently. Mesothelioma
In cells w DNA tumor virus, ex SV40, p53 binds to its antigens (Tag). P53-Tag complex promotes cancer by activating Insulin growth factor IGF-I. Maurizzio Boccetta. [Cancer Res 2008;68(4):1022–9], 2008. Mutated p53 also inhibits healthy Wild type p53
Targeting DNA hypermethylation, using nucleoside analogs, is an efficient approach to reprogram cancer cell epigenome leading to reduced proliferation, increased differentiation, recognition by the immune system, and ultimately cancer cell death.
DNA methyltransferase inhibitors have been approved for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myelogenous leukemia.
To improve clinical efficacy and overcome mechanisms of drug resistance, a second generation of DNA methyltransferase inhibitors has been designed and is currently in clinical trials.
Although efficient in monotherapy against hematologic malignancies, the potential of DNA methyltransferase inhibitors to synergize with small molecules targeting chromatin or immunotherapy will provide additional opportunities for their future clinical application against leukemia and solid tumors.
The prevention of infection-associated cancers Silvio De Flora Paolo Bonanni Carcinogenesis, Volume 32, Issue 6, 1 June 2011, Pages 787–795, https://doi.org/10.1093/carcin/bgr054 Published: 24 March 2011
In principle, the fact that certain chronic infections lie at the root of 20% of human cancers is expected to render their primary prevention more practicable. In fact,
removal of the etiological agent will result in the control not only of the specific infectious disease but also in the prevention of the associated cancer.
In certain prevention programs, vaccination of the population, cancer prevention has been a ‘side effect’ of an intervention that originally had mainly been addressed to the prevention of a fearful infectious disease.
In other cases, such as the anti-HPV vaccination, the intervention program has been launched with the specific objective of preventing the associated cancer rather than the infectious disease, which has poor clinical relevance.
Indeed, this is an outstanding breakthrough in cancer prevention strategies.
From: The prevention of infection-associated cancers
This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable.
Only 5–10% of all cancer cases can be attributed to genetic defects remaining 90–95% have their roots in the environment and lifestyle.
Lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity.
almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc.
Regulatory Failure
If you received a blood transfusion or blood products in Canada between January 1, 1986 and July 1, 1990, you may have received the hepatitis C virus HCV. The Canadian government never required testing of Blood or Blood products for HCV between 1 Jan 1986 and 1 July 1990 and those people might now be dealing with HCV cancers. Regulatory oversights require people to be vigilant of government because they may be remiss in the tasks needed to do a thorough job of protecting our health. Jake Epp PC and Perrin Beatty PC, Mulroney at the time. Don’t let smiles and promises fool you.
Oral Polio Vaccine Was Contaminated with SV40 Monkey Viruses
by Barbara Loe Fisher
Published October 15, 2016 | Vaccination, History
Millions of people exposed to SV40 which has now become endemic to humans and is spread by carriers. It was obtained from Rhesus monkey kidney serum in the 1950’s. Louis St. Laurent LIB and John Diefenbaker PC were in power at that time.
1,4-Dioxane is primarily used as a solvent in the manufacture of pharmaceuticals, veterinary drugs and natural health products, for research and development and as an analytical reagent for laboratory use.
It may also be found as an impurity in ethoxylated substances which are used in numerous industries (manufacturing of personal care products, detergents, pesticides, food packaging and additives, etc.).
1,4-Dioxane is manufactured in and imported into Canada.
Why did the Government of Canada assess it?
Prior to the assessment, 1,4-dioxane was identified as a potential concern for human health based on its classification by international organizations as a substance which may cause cancer in laboratory animals, and based on a high potential for exposure (not including workplace exposures) to the general population of Canada.
How are Canadians exposed to it?
The general population of Canada may be exposed to 1,4-dioxane from environmental media (ambient air, indoor air and drinking water), from various foods, from pharmaceuticals and natural health products, and during the use of consumer products such as personal care and household products containing this substance.
Pesticide Registry in Canada 1500 listed; 2,4-D example???
So Whats
Missing??
-inerts used
-formulation
-contaminants
-epigenetic
profile
-synonyms
-market name
-CAS#
Pesticide Registration in Canada. Contaminants of 2,4-D
Need a full list name(s) of product, inerts, surfactants, contaminants, CAS No.
In 2008 I reported the following contaminants of 2,4-D. Amongst the dioxins there are the following found by Federal Researchers in Canada: 2,7-dichlorodibenzodioxin, 1,3,7-trichlorodibenzodioxin, 1,3,6,8-tetrachlorodibenzodioxin, 1,3,7,9-tetrachlorodibenzodioxin (Cochran, et. al. 1981, Agriculture Canada). Other contaminants revealed by the USA Government House Senate Oversight Committee to the International Agent Orange Committee of which I was a member are: octachlorobisfirone, xanthen-9-ones (Coddling Moth Ovicide), mono, di, tri, and tetradioxins (repeat of above), n-nitrosomethylamines, n-nitrosodiethylamines, ortho and para monochlorophenol isomers, (2,6-Di, 2,4,6 tri-) chloromethoxy phenol isomers, n-nitrosodiethanolamine, 3 chlorophenoxymethanes. These were kindly provided to me by my deceased friend, Joe Cole, Chairman of the IAOC. RIP Old buddy and thanks for your service to humanity. http://pr-rp.hc-sc.gc.ca/pi-ip/result-eng.php…
Above Not listed in Canada in the registry.
Epigenetic potentials of all chemicals critical/omitted.
Aloe barbadensis Miller (Aloe vera) is an herbal remedy promoted to treat a variety of illnesses; however, only limited data are available on the safety of this dietary supplement. Drinking water exposure of F344/N rats and B6C3F1 mice to an Aloe vera whole-leaf extract (1, 2, and 3%) for 13 weeks resulted in goblet cell hyperplasia of the large intestine in both species.
These results indicate that Aloe vera whole-leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice and a carcinogen of the large intestine in F344/N rats.
Hand Wash soap being sold in Canada w whole leaf extract of Aloe barbadensis.
The Deadly Paradox of the Fix. We kill our mitochondria when we kill the pathogen.
Sci Transl Med. Author manuscript; available in PMC 2013 Sep 3.
Major IARC Reference. A Need to fund these wonderful folks and spread their wisdom.
There is a need to keep these people well funded and also hold their feet to the fire. They buried the SV40, EBOLA, HIV origin stories. Prevention and serum safety are the crux.
Int J Mol Sci. 2017 Nov 23;18(12). pii: E2507. doi: 10.3390/ijms18122507. Effects of Commonly Used Pesticides in China on the Mitochondria and Ubiquitin-Proteasome System in Parkinson’s Disease. Chen T1, Tan J2, Wan Z3, Zou Y4, Afewerky HK5,6,7, Zhang Z8, Zhang T9,10,11.
Evidence continues to accumulate that pesticides are the leading candidates of environmental toxins that may contribute to the pathogenesis of Parkinson’s disease.
We selected nine representative pesticides (paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate, tebufenpyrad, trichlorphon and carbaryl) commonly used in China and detected the effects of the pesticides on mitochondria and ubiquitin-proteasome system (UPS) function.
Our results reveal that all the nine studied pesticides induce morphological changes of mitochondria at low concentrations. Paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate and tebufenpyrad induced mitochondria fragmentation.
LAME, NEEDS REPLACEMENT: Cambridge Working Group Recommendations Working with Hazardous Pandemic Organisms July 14 2014 http://www.cambridgeworkinggroup.org
Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks. An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control
Experiments involving the creation of potential pandemic pathogens should be curtailed until there has been a quantitative, objective and credible assessment of the risks, potential benefits, and opportunities for risk mitigation, as well as comparison against safer experimental approaches.
A modern version of the Asilomar process, which engaged scientists in proposing rules to manage research on recombinant DNA, could be a starting point to identify the best approaches to achieve the global public health goals of defeating pandemic disease and assuring the highest level of safety.
REPLACE with World Wide Ban on Weaponization [make more lethal, contagious, useful for military assassinations] of organisms. Its time has come. CRISPR and Epigenetic Manipulation has made it too dangerous. Too easy to create cut and paste pandemic lethals. LGT also means creations have lateral transfer potential.
Proposed Regulatory Reform Addenda
Stop revolving door of corporate executives in government regulatory jobs.
Prohibit lobbying for laws to suit chemical companies and pharmaceuticals.
Clearly list active ingredients, surfactants, additives, contaminants on MSDS sheets.
To existing regulatory approval requirements Add assays of pesticides, biologicals, drugs especially antibiotics, phthalates, flame retardants, to DNA, RNA(s) including microRNA’s to epigenetic impact challenge testing for both methylating and alkylating in local and global genomes. Possibly add phosphorylating at a later date for Rb gene.
Examine heritability of epigenetic results found for at least 3 generations.
Examine lateral gene transfer potential of introduced modified genes in the microbiome and in human cells.
Product or substance [ex:a ntibiotic or pesticide] effects on mitochondria lipid peroxidase, ROS, glutathione, effects on tumor suppressor genes, DNA repair genes, microRNA up or down regulation, genes found silenced in cancer or deleterious genes activated, impacts on the ubiquitin-proteasome system(UPS).
Report endocrine disrupting results in murine testing.
Global UN Convention ban on weaponizing disease genes with mutations, chimeraic hybrid creations, epigenetic modifications.
7 March 2019. UN War Crime Proposal. There needs to be a UN Approved War Crime and Criminal law created governing the creation, possession, weaponization, military use, sale and marketing of the substances capable of silencing these genes which effectively restricts only open scientific research as a reason for working with such materials. They need to be added to California Proposition 65 and WHO’s IARCS list of human carcinogens and registered in law at the ICC in the Hague. This needs to be covered by a global convention at the UN.
Magic Code Found in miRNA siRNA in every cell and Pr Coding RNA that causes cancer cells to commit suicide. Marcus E. Peter — the Tomas D. Spies Professor of Cancer Metabolism at Northwestern University Feinberg School of Medicine in Chicago, IL — revealed not only that certain RNA molecules can kill cancer cells, but that they can also simultaneously prevent them from becoming resistant to treatment.
University of California San Diego School of Medicine researchers have identified the molecular mechanism activated by the presence of tetrahydrocannabinol (THC) — the ingredient that causes people to feel the euphoria or “high” associated with cannabis — in the bloodstream that accelerates cancer growth in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma.
“HPV-related head and neck cancer is one of the fastest growing cancers in the United States. While at the same time, exposure to marijuana is accelerating. This is a huge public health problem,” said Joseph A. Califano III, MD, senior author and professor and vice chief of the Division of Otolaryngology in the Department of Surgery at UC San Diego School of Medicine.
Head and neck squamous cell carcinoma is the sixth most common cancer worldwide. These cancers begin in the cells that line the mucous membranes inside the mouth, nose and throat. Approximately 30 percent of cases of this disease are related to HPV infection, and it is these cases, in particular that are on the rise. Califano suggested increased marijuana use may be a driving factor.
Previous studies have linked daily marijuana exposure to an increased prevalence of HPV-related throat cancer. However, a mechanism linking cannabis exposure to increased growth of the cancer was unknown.
Reporting in the January 13, 2020 online edition of Clinical Cancer Research, a journal of the American Association for Cancer Research, researchers outline how the presence of THC in the bloodstream activates the p38 MAPK pathway, which controls programmed cell death called apoptosis. When activated, p38 MAPK prevents apoptosis from occurring, thus allowing cancer cells to grow uncontrollably.
Working with Chao Liu, MD, visiting scientist at UC San Diego and a physician at China’s Central South University, and other colleagues, Califano and team used animal and human cell lines to show that THC turns p38 MAPK on and were able to stop the growth of HPV-positive head and neck cancer by turning off the pathway.
The team then analyzed blood samples from patients with HPV-related throat cancer who had their genomes comprehensively mapped to define activated gene pathways. Similar to the cell lines, the blood samples showed p38 MAPK activation and loss of apoptosis in tumors from patients with THC in their blood.
In another study Hart S, Fischer et al. found that concentrations of THC comparable with those detected in the serum of patients after THC administration accelerate proliferation of cancer cells instead of apoptosis and thereby contribute to cancer progression in patients.
This has major ramifications for treatment of HPV cancers which are so prevalent at this time.
The smoke from marijuana must also be suspect in cancer based solely on our experience with cigarettes and cancer which has enormous documentation.
Bibliography
Yadira Galindo. How Marijuana Accelerates Growth of HPV-related Head and Neck Cancer Identified. January 13, 2020 |
Hart S, Fischer OM, Ullrich A. Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res. 2004 Mar 15;64(6):1943-50. doi: 10.1158/0008-5472.can-03-3720. PMID: 15026328.
Environment Gene Interactions 