ok I took 500 grams of what I have and waiting to see what it was about it that bugged me so far I noticed a decline in thinking... how to make a tea became an issue but it could just be me.
and I read something else I likely have not business reading but I do that all the time... methylation is impaired by EBV and my understanding is this is protective ? maybe not sure to stomach cancers...
I am going to put it here for the person who had cancer already... in case it is of use to them and when I can think better I will weigh fixing methyl... if it seems wise... depending on what I sort out from my methyl genetics have not done that yet... been working on it a long time...
https://infectagentscancer.biomedcentral.com/articles/10.1186/1750-9378-5-27
here is a teaser
"
Prior studies have shown loss of three critical tumor suppressor gene products, CDH1 (E-cadherin), p73, and CDKN2A (p16), in EBV-infected gastric cancers [
9,
10,
11,
12,
13,
14,
15,
16,
17,
18]. Virus-associated methylation of these genes, along with evidence of global DNA methylation in EBV-positive cancers, suggests that EBV-related gastric cancers are a subset of CpG island methylator phenotype (CIMP) cancers [
4,
11,
19,
20,
21,
22,
23,
24,
25,
26]. A potential mediator is DNA methyltransferase 1 (
DNMT1) that is upregulated in naturally infected gastric cancers and could help establish methylation patterns propagated to daughter cells upon cell division [
21,
27,
28,
29]. Ongoing studies are aimed at understanding the role of EBV and Helicobacter pylori infection in causing inflammation and associated global hypermethylation during gastric cancer development [
22].
In cell line models, DNMT1 overexpression is mediated by EBV LMP1 and LMP2 [
21,
28,
29,
30,
31]. EBV seems to employ epigenetic mechanisms to control the host transcriptome and also to control expression of its own virally encoded genes [
11,
12,
14,
15,
19,
21,
24,
29,
32,
33]. Upon initial infection of a cell, the unmethylated viral genome can undergo viral replication with new virion production, while a subset of infected cells acquire a highly methylated viral genome that squelches expression of foreign proteins and mediates long-term viral persistence by way of latent infection [
23,
34]. Infected tumors tend to have highly methylated EBV DNA, and methylation-related silencing of viral genes helps explain how infected tumors evade immune destruction.
While methylation of gene promoters is typically associated with transcriptional
downregulation via selective binding of repressor proteins, the first protein ever shown to bind and
activate a methylated promoter was EBV BZLF1, the key factor controlling the switch from latent to replicative forms of viral infection [
35]. It appears that the virus has cleverly evolved a means of overcoming promoter methylation to its advantage [
34,
35]. Antiviral strategies are being explored for their antineoplastic potential. Interestingly, the most commonly used antiviral agents, acyclovir and ganciclovir, are effective at shutting down viral replication but they do not eliminate expression of latent and early lytic viral genes such as LMP1, LMP2 and BZLF1.
The clinical implications of EBV-related methylation of the gastric cancer genome are immense. First, emerging evidence shows the potential for improved diagnosis of gastric cancer by testing gastric washes for cancer-specific methylation patterns, perhaps in concert with tests for EBV to identify the virus-infected subset of cancers [
36,
37,
38,
39,
40]. Differing patterns of promoter methylation in virus-positive compared to virus-negative cells [
11,
21,
24] emphasize the need to characterize methylation patterns in a manner that that maximizes assay sensitivity for cancer detection. Both infection and altered DNA methylation appear to be early events in carcinogenesis [
2,
41], potentially facilitating detection of precancerous lesions in stomach juice.
A second clinical implication is the potential for improved treatment of gastric cancer using drugs that reverse the effect of promoter hypermethylation [
42,
43]. In particular, demethylating agents that inhibit DNA methyltransferase and reverse tumor suppressor gene silencing or oncogene activation are potential antineoplastic strategies [
43]. Consideration must be given to possible differences in the effect of demethylating agents in virus-positive
versus virus-negative tumors [
43,
44,
45]. We and others have shown that naturally infected gastric cancers have lower CDKN2A (p16) expression [
14,
15]. In a clinical trial of fluorouracil (5FU) for gastric cancer,
CDKN2A promoter methylation status was an independent predictor of survival [
46]. The rationale for using demethylating agents like 5-aza-2'-deoxycytidine in clinical trials rests on scientific evidence that demethylating therapy modifies the tumorigenic properties of cancer cells.
Several investigators have successfully infected epithelial cell lines with EBV
in vitro[
47,
48]. In the current study, EBV-positive and EBV-negative AGS gastric cancer cells were examined for differences in gene expression patterns using low-density microarray analysis and reverse transcription polymerase chain reaction (rtPCR). AGS is a cell line that was originally grown from gastric adenocarcinoma tissue and now is widely used as a model of gastric cancer. The role of DNA methylation in mediating selected effects was examined by bisulfite DNA sequencing and by testing the ability of a demethylating agent to reverse the effect of EBV on gene silencing. Results revealed extensive gene dysregulation upon EBV infection in AGS cells with evidence that promoter methylation is responsible, at least in part. Reversal of virus-associated transcriptional effects suggests that demethylating agents should be explored for their potential to control growth of EBV-related malignancies.
Conclusions
EBV infection had a profound effect on expression of
IGFBP3. Unlike
IGFBP3 transcripts which were upregulated, most of the tested gene were
downregulated by EBV infection. Methylation may be a common mechanism for diverse effects of viral infection. To the extent that viral infection is associated with methylation
in vivo, demethylating agents could provide a unified therapeutic approach to overcoming viral effects.
Demethylating agents are already used clinically for managing certain neoplasms [
98], and their efficacy in EBV-related gastric cancer should be considered. Our pilot data shows frequent and substantial restoration of multiple transcripts in 5aza-treated, infected cells. Pilot sequencing data identify selective effects of virus infection and 5aza treatment on promoter methylation, providing an impetus for further work to characterize viral-mediated effects and to understand how treatments might be devised to overcome viral effects in tumor cells.
This may be the wrong place of this if so move it to where you think it is ok