Sensitization of cancer (stem) cells by Doxycycline to Vitamin C, Berberine, Chloroquine and others

Dear all,


I recently came across the below study, which I thought was rather interesting:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620172/

The authors used incrementally higher dosages of Doxycycline (12.5 uM, 25 u.M, 50 uM) in vitro on cancer cells in an effort to create metabolically inflexible cells and to test whether these would be then be more sensitive to metabolic inhibitors, including natural agents (Vitamin C and Berberine) and various meds (Atovaquone, Irinotecan, Sorafenib, Niclosamide, Chloroquine, and Stiripentol).

The cancer cells in the study ended up being highly sensitized to some of these agents, for example Vitamin C (4-10 x more sensitive), Berberine and Chloroquine. It's noteworthy that, following Docycycline treatment, cells became sensitive to Vitamin C at a dosage level which is reachable orally (IC-50 = within the range of 100uM - 250 uM). My understanding is that newer Vitamin C formulations using oral Liposomal delivery (e.g.: https://www.livonlabs.com/cgi-bin/start.cgi/liposome-encapsulated/lypo-spheric-vitamin-c.html) can reach concentrations of up to 400 uM in the blood, a level at which cell elimination in vitro was in excess of 90%).

I'm curious if these results could be replicated at least directionally in a human setting, as it would be a rather cost effective and non-toxic approach. Any thoughts?

A few questions I'd have for example are:

1. Is this Doxycycline cell sensitization replicable in a human setting? If so, at what dosage?
2. Is there any chance an oral Vitamin C formulation (e.g. Liposomal) could replicate the effect seen in vitro? Alternatively, I presume IV infusions would do the job?
3. Which of the other agents would be the most feasible otherwise?

Best regards,
John

Cocktail Interactions with Chemo and Radiation

Stephen, I can’t remember what RX/supplements to hold or continue during radiation and/or TMZ?
Can you help?

*Oct 2013 husband diagnosed GBM#4, left frontal lobe, total resection, no seizures. 
*Total 6 wks SOC, TMZ & Radiation. Drug cocktails below. 
*Dec 2013- Oct 2015 Optune Trial/TMZ. Stopped Optune due to skin issues.
*Jan 2015, NO thought recurrence so changed him to CCNU cuz TMZ “failed him”. The CCNU was brutal on him so he stopped it July 2015.
*I did not agree it was recurrence as looked like necrosis to me. I was upset off TMZ since Methylated. June 2015 took him to UCSF/Berger. He agreed didn’t think recurrence either so we decided to ”watch and wait". Since “supposed” recurrence never materialized, he stopped all treatments July 2015 except Drug Cocktails. 

*Jan 2018, GBM recurrence a little forward of original tumor (not area they watched b4). Full resection. Since still methylated and was treatment free since July 2015, decided to try TMZ for 12 mos and Cyberknife radiation for 5 days. 

Tumor is: IDH-1 R132H wildtype. ATRX retained, Mib 10%, MGMT Methylated 
Will have the gene testing results soon.

Hubby is 76.5 yrs old, has some cognitive/motivation issues from 2013 treatment but physically adept. 
Due to his age, I am light on the cocktails:
A) Chemo: TMZ, 300mg 5/23
1) Divalproex Sodium (Valproex Acid) 250 mg DR x 2 daily 
2) Sulfamethox-TMP DS 800 – 160 MG TAB 3 days a wk 
3) Celecoxib 200 mg x 2 
4) Cimetidine, 200 mg x 2 
5) Maitake D fraction Pro 4x, 100 mg x 6 
6) Coriolus – PSP, 400 mg x 6 
7) LEF European Milk Thistle: 240 Silymarin, 90mg Silybin, 24 mg Isosilybin A & B, phospholipids x 2 
8) D3-5,000 IU 1 pill x 1 
9) BroccoMax Broccoli seed extract (sulforaphane Glucosinolate), 30 mg x 1 
10) pTeroPure (Pterostilbene) 50 mg x 1 
11) Mega Lycopene, 15 mg x 1 
12) Melatonin, 20 mg x 1 
13) Longvida curcumin, 1000 mg x 1 
14) Multi-vitamin (not sure if I should give him??) 
15) Pro Omega, 1175 mg x 1 
16) Berberine, 500 mg x 1 
17) Probiotic x 1 
18) Decaf Mega Green Tea Extract, 725 mg x 2 
19) LEF Ultra Soy Extract, genistein not taking right now 
20) Boswellia, not taking currently

Thank you and Blessings to you all!
Candy

Vitamin c

There is very little here about vitamin c. Our naturopath recommends high dose vitamin c. What are your thoughts?

Keppra and Temozolomide

Hi Everyone!

I'm new to this blog. I've read many posts and this is a great help to me, as I'm a beginner in the drug coctail treatment.

Our story briefly:
1) My father, 55, was diagnosed with an unknown brain tumor in October 2015 (the biggest dimension 43 mm). Craniotomy was carried out 3 days after the diagnosis. Preliminary histopathology - astrocytoma III, final result - glioblastoma IV.
2) First MRI after the surgery in December, right before chemoradiation, showed still a big tumour. According to the oncologist - radical recurrence. According to another neurosurgeon (we consulted the MR image in another hospital) - first craniotomy improperly done (!!). I'm not sure who's right... the other neurosurgeon, specialized in gliomas, was very convincing.
3) We decided for another surgery (by another surgeon). The resection must have been deeper as afterwards my dad's sight is worse (he sees everything darker, has problems with reading, seeing details etc., however he's getting better, it's been 6.5 weeks since the surgery).
4) Now chemoradiation. First cycle of Temodal during radiation for 42 days on a daily basis.
5) Tumour unmethylated, IDH1 negative. Other genetical tests of a frozen sample in progress.

We are at the very beginning of the drug&supplements treatment. It's very difficult to collect all the prescribed drugs. We're located in Poland. Started like that:
Temodal (150 mg/day);
Depakine (valproic acid) 2x500mg/day- prescribed by the neurosurgeon to prevent seizures;
Keppra (will start tomorrow, 2x500 mg/day)- added in order to sensitize the tumour for TMZ (prescribed by our GP on request, she agreed);
Dexamethasone (2 mg/day);
Proton pump inhibitor (1x/day) - drug called IPP20 in Poland;
"Pheonix tears" with high THC and CBD (rectal application) - 2 ml/day
Curcumin (up to 3000mg/day)
Quercetin
Vitamin C (1000 mg/day)
Sugar-free diet and radical reduction of meat. Working on reduction of gluten.


I have one question and would be grateful if anyone could advise sth:
What would be the best scheme of taking Keppra to sensitize the tumour for TMZ. Does it matter, if the first doze (500mg) is taken with Temodal on an empty stomach or he can take it later, after his daily radiation (with a meal afterwards)?
Should we add Prozac and Disulfiram, apart from Keppra, for a better chance of TMZ working?


Cheers!
Piotr