Requesting Assistance - Diagnosed with Vestibular Schwannoma

[Peater Piper]

Hi Everyone,

I had an MRI of the brain on March 15, 2023, due to increased tinnitus in the right ear along with numbness on the right side of the face. The symptoms had actually started 3-4 months ago, but I didn't recognize them until the entire right side of my face started to get a pins and needles feeling in early February after (what seemed to be) a minor bout of COVID-19. I figured it would improve, but it seemed to get worse, hence the MRI. They found a 3 cm vestibular schwannoma (aka acoustic neurinoma) that's pressing against the trigeminal nerve. For those who aren't aware, it's a benign tumor growing from the schwann cells that encase the auditory nerves. Typical growth rate is considered 1-2 mm per year, so I may have had this for 15-30 years, but growth of a centimeter in a year seems possible. Due to it's size, a craniotomy is considered the only option. The surgery is likely to cause total hearing loss in the affected ear, along with possible facial paralysis and other problems. It's not a pretty procedure, and many patients end up very depressed afterward. I'm researching the best neurosurgeons because it will probably come down to surgery, and soon. Trigeminal nerve compression is not a good sign.

I find it very hard to believe there's no other interventions besides surgery for such a slow growing tumor. I may have 1-2 months to see if I can start shrinking this sucker before I need to schedule surgery. I also have a history of Lyme Disease, for which I've been treated twice (w/ Doxycycline) but never felt it was eradicated. I have a suspicion the bacteria may be involved somehow, possibly aggravating the tumor and accelerating its growth. I'm using Buhner Herbals that I already had on hand (Cat's Claw and Japanese Knotweed - I know, the resveratrol, but the evidence is convincing it's effective against the bacteria, can cross the BBB, and has anti-tumor properties), and have done some other research on supplements with efficacy against schwannomas. Unfortunately almost everything is in vitro, the science seems comfortable declaring surgery is the only intervention at the moment. There is evidence that 4% of people have spontaneous shrinkage for unknown reasons, so it's not impossible.

So I'm here to see if anyone has ideas and/or experience with other brain tumors. I was already eating a high carb and protein diet, drinking plenty of coffee, and taking aspirin, so I think it's safe to say these aren't doing the trick. I already have Sulforaphane and Curcumin on hand, and I'm expecting Artemisia Tincture and Artemisinin capsules in the next few days. Lycopodium appears to have completely eradicated the tumor in one person, but I don't know if it was a fluke, misdiagnosis, or a lie. Below are some studies I've found. I appreciate any advice or information that can be provided.

Artesunate
Artesunate induces necrotic cell death in schwannoma cells - Cell Death & Disease

Established as a potent anti-malaria medicine, artemisinin-based drugs have been suggested to have anti-tumour activity in some cancers. Although the mechanism is poorly understood, it has been suggested that artemisinin induces apoptotic cell death. Here, we show that the artemisinin analogue artesunate (ART) effectively induces cell death in RT4 schwannoma cells and human primary schwannoma cells. Interestingly, our data indicate for first time that the cell death induced by ART is largely dependent on necroptosis. ART appears to inhibit autophagy, which may also contribute to the cell death. Our data in human schwannoma cells show that ART can be combined with the autophagy inhibitor chloroquine (CQ) to potentiate the cell death. Thus, this study suggests that artemisinin-based drugs may be used in certain tumours where cells are necroptosis competent, and the drugs may act in synergy with apoptosis inducers or autophagy inhibitors to enhance their anti-tumour activity.

Our data show that ART effectively killed RT4 schwannoma cells at 25 μM, and the cells were almost 100% killed at the concentration of 50 μM in 24 h

Ailanthone
Ailanthone Promotes Human Vestibular Schwannoma Cell Apoptosis and Autophagy by Downregulation of miR-21 - PubMed

Ailanthone (AIL) is a quassinoid isolated from the traditional Chinese medicinal herb Ailanthus altissima. The antitumor activities of AIL have been reported in several cancers. The purpose of the present study was to explore the effect of AIL on vestibular schwannomas (VSs). Various concentrations of AIL (0-1 μM) were used to treat human primary VS cells, and then cell viability, proliferation, apoptosis, and autophagy were assessed. Expression of miR-21 in VS cells was altered by miRNA transfection. The functional actions of AIL on miR-21 dysregulated cells were also assessed. AIL significantly reduced the viability of VS cells, and the IC50 value was 0.48 ± 0.023 μM. In response to 0.6 μM AIL, BrdU+ cell rate and cyclin D1 expression were reduced, apoptotic cell rate was increased, caspase 3 and caspase 9 were cleaved, Beclin-1 and LC3-II were accumulated, and p62 was downregulated. miR-21 was lowly expressed in AIL-treated cells, and AIL-induced apoptosis and autophagy were attenuated by miR-21 overexpression. In addition, AIL downregulated Ras and Raf and deactivated MEK, ERK, mTOR, and p70S6K, while the downregulation and deactivation induced by AIL were reversed by miR-21 overexpression. To conclude, AIL inhibited VS cell proliferation and induced apoptosis and autophagy. The antitumor activities of AIL in VS cells were realized possibly via downregulation of miR-21 and blocking the Ras/Raf/MEK/ERK and mTOR pathways.

Curcumin
Upregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cells - Cancer Cell International

In this study, curcumin exerted cellular cytotoxicity against RT4 schwannoma cells, with an increase in TUNEL-positive cells. Curcumin also activated the expression of apoptotic proteins, such as polyADP ribose polymerase, caspase-3, and caspase-9. The miRNA array revealed that seven miRNAs (miRNA 350, miRNA 17-2-3p, let 7e-3p, miRNA1224, miRNA 466b-1-3p, miRNA 18a-5p, and miRNA 322-5p) were downregulated following treatment with both 10 and 20 μM curcumin in RT4 cells, while four miRNAs (miRNA122-5p, miRNA 3473, miRNA182, and miRNA344a-3p) were upregulated. Interestingly, transfection with a miRNA 344a-3p mimic downregulated the mRNA expression of Bcl2 and upregulated that of Bax, Curcumin treatment in RT 4 cells also reduced the mRNA expression of Bcl2 and enhanced expression of Bax, Overexpression of miRNA344a-3p mimic combined with curcumin treatment activated the expression of apoptotic proteins, including procaspase-9 and cleaved caspase-3 while inhibition of miRNA 344a-3p using miR344a-3p inhibitor repressed cleaved caspase-3 and -9 in curcumin treated RT-4 cells compared to control.

Preclinical validation of anti‐nuclear factor‐kappa B therapy to inhibit human vestibular schwannoma growth

Vestibular schwannomas (VSs), the most common tumors of the cerebellopontine angle, arise from Schwann cells lining the vestibular nerve. Pharmacotherapies against VS are almost non‐existent. Although the therapeutic inhibition of inflammatory modulators has been established for other neoplasms, it has not been explored in VS. A bioinformatic network analysis of all genes reported to be differentially expressed in human VS revealed a pro‐inflammatory transcription factor nuclear factor‐kappa B (NF‐κB) as a central molecule in VS pathobiology. Assessed at the transcriptional and translational level, canonical NF‐κB complex was aberrantly activated in human VS and derived VS cultures in comparison to control nerves and Schwann cells, respectively. Cultured primary VS cells and VS‐derived human cell line HEI‐193 were treated with specific NF‐κB siRNAs, experimental NF‐κB inhibitor BAY11‐7082 (BAY11) and clinically relevant NF‐κB inhibitor curcumin. Healthy human control Schwann cells from the great auricular nerve were also treated with BAY11 and curcumin to assess toxicity. All three treatments significantly reduced proliferation in primary VS cultures and HEI‐193 cells, with siRNA, 5 μM BAY11 and 50 μM curcumin reducing average proliferation (±standard error of mean) to 62.33% ± 10.59%, 14.3 ± 9.7%, and 23.0 ± 20.9% of control primary VS cells, respectively. These treatments also induced substantial cell death. Curcumin, unlike BAY11, also affected primary Schwann cells. This work highlights NF‐κB as a key modulator in VS cell proliferation and survival and demonstrates therapeutic efficacy of directly targeting NF‐κB in VS.

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Sulforaphane
Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo - Scientific Reports

Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli, with potent chemoprotective effects in several cell types. Our objective was to determine whether SFN is effective against VS in vitro and in vivo. Human primary VS cells, HEI-193 schwannoma cells, and SC4 Nf2−/− Schwann cells were used to investigate the inhibitory effects of SFN in vitro. Cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and cell viability and metabolic activity was calculated by MTT assay. Apoptosis was measured by flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and Western blot for cleaved caspases. A mouse model with a murine schwannoma allograft was also used to examine the antitumor activity of SFN. SFN exhibited significant antiproliferative activity in schwannoma cells in vitro, via the inhibition of HDAC activity and the activation of ERK. SFN treatment induced apoptosis and cell cycle arrest at the G2/M phase. SFN also significantly inhibited schwannoma growth in vivo. Our preclinical studies motivate a future prospective clinical study of SFN for the treatment of VS.

Lycopodium

https://ijrh.researchcommons.org/cgi/viewcontent.cgi?article=1646&context=journal

Case study of patient who presented with a 2.5 cm vestibular schwannoma based on a CT scan, which completely disappeared from future CT scans after one year taking Lycopodium as well as symptom management with Chininum sulph.

Honokiol
The inhibitory effect of honokiol, a natural plant product, on vestibular schwannoma cells - PubMed

Honokiol exhibited significant antiproliferative activity in a dose-dependent manner on HEI 193 cells. Significant apoptosis was detected on schwannoma cells with 7 mg/mL(IC50) honokiol. Western blot analysis showed significant inhibition of ERK phosphorylation. Honokiol, a low molecular weight natural product, inhibits cell proliferation and promotes apoptosis in schwannoma cells by targeting the ERK pathway. Our data suggest that honokiol can be evaluated as a chemotherapeutic agent for VS.

 

[Vileplume]

Do you track your body temperature?

I have no particular knowledge on tumors, but I think increasing the metabolic rate is always a helpful approach to a chronic issue.

 

[Peater Piper]

My body temperature is usually in the upper 98's, sometimes over 99 degrees.

 

[area51puy]

are taking any supplements or medicines currently?

 

[Peater Piper]

are taking any supplements or medicines currently?

I'd actually stopped everything for a few weeks before the MRI because of the odd sensations, I wasn't sure what was going on. Currently I'm on Cat's Claw, Japanese Knotweed, Sulforaphane, and Curcumin. Artemisia tincture will be arriving today, and Artemisinin tomorrow. I also received a call from a neurosurgeon today and they're already looking to get another MRI with contrast (first MRI didn't use contrast) and prep for surgery, so I need to either commit to treating for a few months, or stop everything and strengthen myself for the surgery. Just about everything is contraindicated with surgery due to blood thinning properties and kidney stress.

 

[Peatress]

I'd actually stopped everything for a few weeks before the MRI because of the odd sensations, I wasn't sure what was going on. Currently I'm on Cat's Claw, Japanese Knotweed, Sulforaphane, and Curcumin. Artemisia tincture will be arriving today, and Artemisinin tomorrow. I also received a call from a neurosurgeon today and they're already looking to get another MRI with contrast (first MRI didn't use contrast) and prep for surgery, so I need to either commit to treating for a few months, or stop everything and strengthen myself for the surgery. Just about everything is contraindicated with surgery due to blood thinning properties and kidney stress.

Please ask your doctors to reconsider using contrast dye. It’s toxic to the brain. Some years ago a friend was diagnosed with a brain tumour. Researching the topic at the time B3 came up a lot – this won’t thin the blood. The other useful substances were vitamin D and progesterone. Supplementing D does thin the blood but it’s dose dependent. Progesterone won’t if it’s not in vitamin E (please check first)

FDA issues tougher warning on MRI dye tied to brain effects

(HealthDay)—The U.S. Food and Drug Administration on Tuesday called for tougher warnings and "additional research" into a dye commonly used with standard MRIs.

medicalxpress.com

Some MRI Contrast Agents Containing Gadolinium Can Cause Problems Ranging From "Brain Fog" To Permanent Disability

Gadolinium Deposition Disease Symptoms Typically Begin Couple Of Months After Use And Can Continue For Many Years Without Any Diagnosis (Posted by Tom Lamb at DrugInjuryWatch.com) During MRI and MRA procedures patients often receive injections of gadolinium-based contrast agents (GBCAs). Some of...

www.drug-injury.com

Contrast Dye and the Kidneys

Diagnostic tests such as MRIs, CT scans and angiograms are routinely used because they provide important information about many diseases or injuries and can help in diagnosis and treatment. In many cases, the use of a contrast dye is necessary to enhance these tests, but sometimes these dyes can...

www.kidney.org

Despite what we are being told all contrast dyes are unsafe.

 

[Peater Piper]

Please ask your doctors to reconsider using contrast dye.

Thanks, it's something I'd like to avoid. I'll mention it to the surgeon, but I don't know how understanding he's going to be. I assume he'll say something like he needs the best view possible since he'll be cutting into my brain. Even the MRI without contrast gave me problems. My hearing was almost gone in the affected ear the following day, but it bounced back to about 50-60%.

 

[Peatress]

Thanks, it's something I'd like to avoid. I'll mention it to the surgeon, but I don't know how understanding he's going to be. I assume he'll say something like he needs the best view possible since he'll be cutting into my brain. Even the MRI without contrast gave me problems. My hearing was almost gone in the affected ear the following day, but it bounced back to about 50-60%.

MRIs are not without problems. I felt very weird after the last one I had.

When I had the contrast dye a few years ago I said no but the radiologist talked me into it. I regret it till today. You have a lot on your plate already so I hope you find a sympathetic doctor.

 

[Funnywhensunny]

My Avant Laser has sertings for Tumor, vertigo,…

 

[Herbie]

Cyproheptadine, progesterone, t3, t4. Aspirin, lisuride.

 

[LucyL]

Given it's benign, and given you may have had it a long time, if it were me I would certainly postpone such major surgery for a few months, do some more research, try a few things and shop around to different surgeons, if you are able.

 

[jameske]

You could try reducing your electromagnetic exposure. Replace wifi with wired. Keep cell phones well away from you as much as you can manage. Sleep underneath some sort of EM shielding net. Switch off appliances and plugs etc when not in use.

 

[Peater Piper]

So I'm trying to put together what the information below means. Would methylene blue plus pyrucet force the tumor back into oxidative phosphorylation and avoid the excess peroxynitrite, thus restoring Complex IV? I recall travis previously mentioning that methylene blue may INCREASE peroxynitrite. I'm already using aspirin, B3, and ubiquinone. It sounds like urate may be beneficial as well. That or go full keto and avoid providing glucose as a fuel source. @haidut et al

Peroxynitrite supports a metabolic reprogramming in merlin-deficient Schwann cells and promotes cell survival

Neurofibromatosis type 2 (NF2) is an autosomal-dominant disorder characterized by the development of bilateral vestibular schwannomas. The NF2 gene encodes the tumor suppressor merlin, and loss of merlin activity promotes tumorigenesis and causes NF2. ...

www.ncbi.nlm.nih.gov

Here we show that peroxynitrite is necessary for NF2 schwannoma cell survival. Prevention of tyrosine nitration decreased cell survival of mouse and human merlin-deficient (MD) but not wildtype (WT) Schwann cells. Furthermore, we show for the first time that peroxynitrite controls energy metabolism of human MD-Schwann cells through the down-regulation of mitochondrial activity and increasing glycolysis and glutamine dependence, a metabolic phenotype shared by other tumor cell types. We observed a significant decrease in the levels and activity of the mitochondrial oxidative phosphorylation complexes in the absence of merlin expression, leading to a decrease in mitochondrial oxygen consumption rate (OCR). Scavenging peroxynitrite-derived radicals with urate reverted the metabolic phenotype of human MD-Schwann cells back to that of isogenic WT-Schwann cells at least in part by increasing the levels and activity of the cytochrome c oxidase (complex IV). Together these observations reveal that peroxynitrite plays an important role in the regulation of the metabolic phenotype of NF2 schwannoma cells. Proteins oxidized by peroxynitrite could be exceptional targets for the development of tumor-directed therapies for the treatment of NF2 and possibly for treatment of other solid tumors.

Surprisingly, there was a significant decrease in the levels of subunits of complex I (NADH:ubiquinone oxidoreductase, NDUFA9 subunit), complex II (succinate:ubiquinone oxidoreductase, SDHA subunit), and complex IV (cytochrome c oxidase, COX IV subunit) in human MD, compared with WT-Schwann cells (Fig. 4C). The decrease in oxidative phosphorylation complex levels correlated with a significant decrease in complex I, II + III, and IV activity in human MD-Schwann cells (Fig. 4D), without changes in either mitochondrial count or total mitochondrial area per cell (Fig. 4E). Together these results imply that upon loss of merlin function, there is a reprogramming of energy metabolism in human MD-Schwann cells through a decrease in mitochondrial respiratory chain levels and activity.

In tumor cells, decreased mitochondrial activity correlates with increased aerobic glycolysis and/or glutaminolysis to produce ATP and the biosynthetic intermediates needed for cell proliferation (45, 46). We assessed the glycolytic rate of human WT- and MD-Schwann cells by extracellular flux analysis after incubation of the cells in the presence and absence of urate for 48 h. After addition of glucose to the culture media, human MD-Schwann cells showed increased glycolysis and increased glycolytic capacity, measured as the glycolytic rate in the presence of 1 μm oligomycin, compared with human WT-Schwann cells; both parameters were partially reversed after scavenging of peroxynitrite-derived radicals (Fig. 7A). In agreement with the increased reserved respiratory capacity observed in human WT-Schwann cells after urate treatment (Fig. 3E), there was a corresponding decrease in the glycolytic reserve of these cells (Fig. 7A), supporting a possible role for low levels of peroxynitrite formation in the regulation of energy metabolism in human WT-Schwann cells only under stress conditions. Notably, there was a significantly increased acidification of the culture medium by human MD-Schwann cells in the presence of glutamine as the sole fuel source (nonglycolytic acidification) that was completely reversed after incubation with urate. This suggests that peroxynitrite may favor a shift toward glutaminolysis in human MD-Schwann cells. Supporting these observations, human MD-Schwann cells showed increased glutamine dependence, measured as the capacity of the mitochondria to utilize alternative fuel sources (glucose and fatty acids) in the presence of BPTES, an inhibitor of glutaminase, the enzyme that converts glutamine to glutamate (Fig. 7B). Together, these results suggest that peroxynitrite supports a metabolic shift from mitochondrial oxidative phosphorylation toward glycolysis and glutaminolysis in human MD-Schwann cells (Fig. 8).

Inactivation of complex IV has the potential to induce tumor progression. Silencing of the complex induces a metabolic shift and a transcriptional reprogramming that leads to invasive behavior in nontumorigenic skeletal myoblasts, and increased invasiveness in breast and esophageal cancer cell lines (61). Furthermore, we and others have shown that even small changes in mitochondrial activity can have a great impact in cell metabolism (29, 62, 63). Scavenging of peroxynitrite-derived radicals in human MD-deficient Schwann cells reprogrammed their mitochondrial metabolism to that of isogenic WT-Schwann cells. Incubation of human MD-Schwann cells with urate not only significantly increased the levels of complex IV, but also increased its activity and the mitochondrial oxygen consumption rate to WT levels. Although scavenging of peroxynitrite-derived radicals restored the levels of complex I and II, there were no associated changes in activity, suggesting that the activity of these complexes may be regulated by other mechanisms, for example, at the level of complex assembly. Nevertheless, the complete restoration of human MD-Schwann cell oxygen consumption rate to that of WT-Schwann cells after urate treatment suggests that complex IV is the critical regulatory step.