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Cancer Treatments: from Research to Application
Salinomycin: One of the best
Summary
Salinomycin is as an antimicrobial and anticoccidial antibiotic. In 2009, a groundbreaking result was published in the scientific journal Cell (Ref), showing that Salinomycin can be effective in killing the cancer stem cells (CSC), the cancer cell population that is responsible for chemo resistance and metastasis. Although the study was focused on breast cancer, Salinomycin will do the same in most epithelial cancers.
In my opinion, this is one of the most effective anti cancer substance I am aware of, that can trigger an intensive anticancer response. However, somehow, the intensive response doesn’t happen always and it is not clear why. It seems that Sal works best in epithelial cancers. Example of epithelial cancers are cancers of endocrine glands (e.g. adrenal, thyroid, pituitary), breast, ovarian, lung, etc. Cancers that develop in epithelial cells are called carcinomas (Carcinoma is the term used for a malignant epithelial tumor). About 80-90% of cancers are this type. (Ref.)
Besides is wide effectiveness in various types of cancers, another strong point of Salinomycin is that even if it will not kill the cancer cells, it is a potent inhibitor of the ABC transporter P-glycoprotein/MDR1 in different cancer cells. Ref1 Ref2 This means that Sal will turn cancers that are or have become insensitive to chemo therapies, into cancers that will be again sensitive to chemo.
Soon after its discovery, in 2009, it has been patented by a company founded by the scientists who discovered the anti cancer effects of Sal. The company is also supported by Harvard University and MTI. Its name is Verastem. In their product portfolio, Salinomycin goes under VS-507 name while being promoted as an Wnt Inhibitor.
Update 27.02.2016: My understanding of Salinomycin today, based on personal view and that of others:
1. Salinomycin seems to be most effective in epithelial cancers
2. Salinomycin seems to work well when combined with Chemo (such as Cisplatin, Gemcitabine, Erlotinib and at least a few others) and/or 3BP
3. The Chemo and or 3BP has to be applied first and than Salinomycin after
4. Following the above, Salinomycin may lead to response that will decay in the following days of application if there is no other Chemo applied –> the effect fades away (I would not call this resistance)
5. If Chemo or 3BP is applied again than there is response again
6. Salinomycin must be applied at a delay of several days from Chemo and or 3Bp for the most intense response. That means that if Salinomycin is applied just after (e.g. during the same day) there may be no or little response to that
7. Following the Salinomycin effectiveness, cancer cells will die via necrosis – so there may be a strong immune reaction during the following days – blood measurements will show strong increase in LDH and others (e.g. potassium) for a few days suggesting tumor lysis (TLS). TLS can be dangerous if too much cancer is killed at once so it needs to be manged carefully.
Note that the above are extremely valuable conclusions following my intensive search for answers on this topic and identifying patterns.
Strangely enough, it seems that Salinomycin is not anymore on the pipeline of Verastem???
Case reports
Salinomycin as a drug for targeting human cancer stem cells.
“Salinomycin was therapeutically applicated €œfirst-in-man€ in 2010, in the context of a pilote clinical trial with a small cohort of patients with metastatic breast, ovarian, and head and neck cancers. Intravenous administration of 0.20-0.25 mg/kg salinomycin every second day for three weeks resulted in partial regression of tumor metastasis and showed only minor acute and long-term side effects, but no severe acute and long-term side effects observed with conventional chemotherapeutic drugs.”
“As shown in Figure 3, systemic salinomycin therapy induced a marked regression of the subcutaneous thoracal metastases. A biopsy of the regressive subcutaneous thoracal metastases was obtained after 12 cycles of salinomycin therapy, and the specimen was investigated by molecular histopathology. As determined by TdT-mediated dUTP nick end labeling (TUNEL) histopathology, ~85% of the cells had undergone apoptosis. Moreover, the serum levels of the tumormarkers Ca 15-3 (cut off <31€‰U/mL) and CEA (cut off <3.4€‰ng/mL) declined from 14.3 U/mL and 50.8€‰ng/mL before salinomycin therapy to 7.2 U/mL and 15.5€‰ng/mL after salinomycin therapy, respectively. Intravenous salinomycin therapy resulted in minor acute side effects, including tachycardia and mild tremor for 30€“60€‰min. after administration but lacked severe and long-term side effects observed with conventional chemotherapeutic drugs, such as myelodepression, neutropenia, alopecia, nausea and vomiting, or gastrointestinal, thromboembolic, and neurological side effects. Similar results of salinomycin-induced partial tumor and metastasis regression were obtained in three other patients with metastatic breast cancer, one patient with metastatic ovarian cancer, and one patient with metastatic head and neck squamous cell carcinoma.” Ref.
Anecdotal reports/stories
Case 1: SCLC: Cancer Treatment Institute of Colombia Demonstrates Unprecedented Results Using Unique Cancer Drug Combination of 3-Bromopyruvate and Salinomycin for Treatment of Multiple Types of Cancer
With masses in both lungs and a depressed platelet count, the prognosis for the patient was poor; he had previously undergone standard chemoradiotherapy, but the cancer returned within three months. His attending physician recommended against additional treatments. At Cancer Treatment Institute of Colombia, the patient received 21 total rounds of salinomycin and 3-BrPA, delivered on alternating days. Chest CT scans four weeks later confirmed the total disappearance of SCLC. Just as encouraging was that the patient experienced no significant adverse reactions during his treatment.
Case 2: Adrenal cancer – to be added
I am sure there will be many to come.
Mechanism
Potassium ionophore, specifically targeting the cancer stem cells (CSC). As a result, it will induce an efflux of K+ from mitochondria and cytoplasm. While the CSC killing mechanism is not that clear to the scientists, here you can read a bit more about the possible mechanism.
One potential mechanism: Salinomycin treatment led to increased cytosolic Na+concentration, which consequently resulted in elevated cytosolic Ca2+ by means of Na(+)/Ca(2+) exchangers (NCXs) in the plasma membrane as well as the mitochondria. Elevated Ca(2+) then leads to calpain activation, which triggers caspase-dependent apoptosis involving caspases 12, 9 and 3. In addition, cytochrome c released from depolarized mitochondria directly activates caspase 9. (Combined inhibition of calpain and the mitochondrial NCXs resulted in significantly decreased cytotoxicity and was comparable to caspase 3 inhibition.) Ref.
Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells. Ref
Salinomycin, a polyether ionophore antibiotic isolated from Streptomyces albus, has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways. Ref
Salinomycin to selectively target €œCD133+€ cell subpopulations: http://link.springer.com/article/10.1245%2Fs10434-011-1561-2
Has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways http://www.ncbi.nlm.nih.gov/pubmed/23251084
The in vitro IC50 of salinomycin varies, depending on the source, cell type used and treatment period (Ref.).
Here is a new (2017) paper discussing various anti cancer mechanism of Salynomicin: http://journals.sagepub.com/doi/full/10.1177/1010428317695035 and below is a figure from the article, indicating the various mechanisms:
Update Sept 2017: A recent Nature Chemistry papers proposing a new mechanism related to Salinomycin’s anti cancer action: https://www.nature.com/nchem/journal/vaop/ncurrent/full/nchem.2778.html
This mechanism could sit at the basis of all the other mechanisms that have been previously identified.
In this paper it is suggested that Salinomycin is accumulating and sequestering iron in lysosomes. When the cells are left without Iron in cytosol, they will trigger the degradation of ferritin in lysosomes, leading to further iron loading in the lysosomes. Iron-mediated production of reactive oxygen species promoted lysosomal membrane permeabilization, activating a cell death pathway consistent with ferroptosis.
Here is a nice recent paper on Lysosomes as Oxidative Targets for Cancer Therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516749/
To understand what Ferropoptosis is, you can read this paper: https://www.nature.com/cdd/journal/v23/n3/full/cdd2015158a.html
If indeed, this is the main mechanism responsible for Sal anti cancer mechanism, Iron Chelation prior to Sal treatments should be avoided. Indeed this paper suggest that Iron chelators can stop ferroptosis (Ref.). Opposite to that, Iron ionophores such as Disulfiram may help Salinomycin enhance this anti-cancer mechanism.
Interestingly, Chloroquine was suggested to work well with Salinomycin (Ref.) but due to a different reason. Based on the above, I can imagine Chloroquine can support the ferroptosis induced by Salinomycin due to a possibly similar action on Iron in the lysosames (Ref.)
Safety/Toxicity
This substance can be lethal if administrated at higher doses than it should. If on the other hand the administration dose is correct, as demonstrated by the articles above, there is a dose window where cancer cells are killed while the normal cells are not affected.
A case of accidental inhalation and swallowing of about 1mg/kg by a 35 years/old man leading to sever acute toxicity with acute nausea, photophobia, leg weekness, blod preasure elevation, chronic creatinine kinase elevation and muscle pain http://www.ncbi.nlm.nih.gov/pubmed/15107902
Note that this is about 4x higher dose than that used for cancer treatment.
Short term side effects have been reported and to my knowledge those may be: 30-60 min tremor after the administration, short term impact on peripheral view, fever after the administration, pain in the tumor area.
Inhibition of Na(+)/Ca(2+) exchangers (NCX) prevents salinomycin-induced neuropathy. Blocking mitochondrial Na(+)/Ca(2+) exchangers does not impair antineoplastic efficacy. Ref
Existing ion channel blockers, such as amiodarone, dronedarone, bepridil, aprindine, and cibenzoline, have been found to have an NCX inhibitory action. (Ref.)
Administration (Intra Venous – IV)
So far I am aware of two other administration protocols:
Note that there is another version of Salinomycin i.e. Sodium Salt >90% which may be 10x cheaper. However its effectiveness in humans is unknown.
Also note that on the web we will find easy to buy 24% purity (which typically is Sodium Salt version). This is used for treatment of animals.
So, the best seems to be Salinomycin base version (CAS Number 53003-10-4) as it seems that this was used before in the published cases, but Salinomycin Sodium Salt (CAS Number 55721-31-8) may also be relevant.
Tumor acidosis enhances cytotoxic effects and autophagy inhibition by salinomycin on cancer cell lines and cancer stem cells. http://europepmc.org/abstract/med/27248168
Improving Sal effectiveness:
While there is a lot of research indicating that Salinomycin can overcome multi drug resistance, there is also research indicating that Salinomycin is a substrate of P-glycoprotein and P-glycoprotein over expression may also limit Salinomycin brain penetration as well as oral bio-availability (Ref.). Here is another example of research indicating that MDR1 overexpression leads to resistance to Salinomycin https://www.researchgate.net/publication/279529617_Drug_Transporter-Mediated_Protection_of_Cancer_Stem_Cells_From_Ionophore_Antibiotics
However, I do know based on genetic profiling of my wife’s tumor (but also specific literature) that she had a high MDR1 over expression level. And we did saw strong response to Salinomycin. So our results may also be related with some of the drugs and supplements she was taking, with MDR1 inhibition capabilities. Those are e.g. sometimes Verapamil, sometimes Ketokonazole. As a result, when there is no response to Salinomycin treatment, P-glycoprotein inhibitors such as Verapamil, Ketoconazole, or Tetrandrine should be administrated prior and/or during the Sal treatment.
Since MDR1 pump is ATP driven, lowering ATP prior to Sal treatment should also improve effectiveness. Using Metformin and/or Doxicycline would then help. Same applies for Phlorizin and 2DG. Note: we always used Metformin and sometimes Doxicycline. These will slow down mitochondria.
Preparation method:
I will share my research on this asap.
Source & Cost
Chemical suppliers such as Sigma. Salinomycin base version (CAS Number 53003-10-4). Material cost is a few thousands euro/dollars for one cycle (12 IVs) depending on your weight.
Synergies & Antagonsists
Synergies:
2-DG, 3BP, other glycolisis inhibitors: http://www.ncbi.nlm.nih.gov/pubmed/25912307
HDAC inhibitors (e.g. Valproic acid): http://www.ncbi.nlm.nih.gov/pubmed/24351423
Autophagy Inhibitors (e.g. Chloroquine): http://www.ncbi.nlm.nih.gov/pubmed/23670030
Doxorubicin: http://www.ncbi.nlm.nih.gov/pubmed/25892525
Metformin: http://www.ncbi.nlm.nih.gov/pubmed/25375092
5-fluorouracil: http://www.ncbi.nlm.nih.gov/pubmed/24816638
Nelfinavir https://orca-mwe.cf.ac.uk/98987/1/Dunlop-Tee2017Oncotarget.pdf
Patents
Therapeutic compositions and related methods of use
Based on this the formulation was found to remain stable in normal saline up to 24 hours at room temperature.
Relevant Literature
Salinomycin suppresses TGF-β1-induced epithelial-to-mesenchymal transition in MCF-7 human breast cancer cells.
Acidosis enhances the ability of salinomycin to kill cancer cells and cancer stem cells
Preclinical drug metabolism and pharmacokinetics of Salinomycin, a potential candidate for targeting human cancer stem cells
Concomitant administration of Ketoconazole (KTC) on SAL pharmacokinetics: KTC, being a selective CYP3A4 inhibitor increased the systemic exposure of SAL significantly to 7-fold in AUC0-α and 3-fold increase in Cmax of SAL in rats with concomitant KTC administration.
Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death
Our in vitro studies further demonstrate that the combined use of 2-Fluoro 2-deoxy D-glucose, or 2-deoxy D-glucose with Salinomycin is lethal in cancer cells
HDAC inhibitors enhance the lethality of low dose salinomycin in parental and stem-like GBM cells.
Collectively our data demonstrate that the lethality of low nanomolar concentrations of salinomycin are enhanced by HDAC inhibitors in GBM cells and that increased death receptor signaling together with reduced mitochondrial function are causal in the combinatorial drug necro-apoptotic killing effect.
Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells. In conclusion, these findings provide evidence that combination treatment with salinomycin and pharmacological autophagy inhibitors will be an effective therapeutic strategy for eliminating cancer cells as well as cancer stem cells.
Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin.
Salinomycin decreases doxorubicin resistance in hepatocellular carcinoma cells by inhibiting the β-catenin/TCF complex association via FOXO3a activation.
Salinomycin inhibits growth of pancreatic cancer and cancer cell migration by disruption of actin stress fiber integrity.
Salinomycin inhibits the tumor growth of glioma stem cells by selectively suppressing glioma-initiating cells.
Metformin and salinomycin as the best combination for the eradication of NSCLC monolayer cells and their alveospheres (cancer stem cells) irrespective of EGFR, KRAS, EML4/ALK and LKB1 status. In conclusion, METF in combination with SAL could be a promising treatment option for patients with advanced NSCLC irrespective of their EGFR, KRAS, EML4/ALK and LKB1 status.
Inhibition of autophagic flux by salinomycin results in anti-cancer effect in hepatocellular carcinoma cells.
Specific targeting of neurotoxic side effects and pharmacological profile of the novel cancer stem cell drug salinomycin in mice. Inhibition of the mitochondrial Na(+)/Ca(2+) exchanger partially prevented the development ofsalinomycin-induced neuropathy in vivo, an approach which did not reduce salinomycin‘s antineoplastic efficacy in vitro.
Salinomycin treatment reduces metastatic tumor burden by hampering cancer cell migration. Our findings clearly show that salinomycin can strongly inhibit cancer cell migration independent of the induction of cell death. We furthermore demonstrate for the first time that salinomycin treatment reduces metastasis formation in vivo, strengthening its role as promising anti-cancer therapeutic.
Salinomycin increases chemosensitivity to the effects of doxorubicin in soft tissue sarcomas.
The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Treatment of the MDR cell lines with salinomycin restored a normal drug sensitivity of these cells.
Combining targeted drugs to overcome and prevent resistance of solid cancers with some stem-like cell features
Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity http://aac.asm.org/content/59/9/5135.full
Dual targeting of androgen receptor and mTORC1 by salinomycin in prostate cancer. http://www.ncbi.nlm.nih.gov/pubmed/27557496
Androgen receptor (AR) and PI3K/AKT/mTORC1 are major survival signals that drive prostate cancer to a lethal disease. Reciprocal activation of these oncogenic pathways from negative cross talks contributes to low/limited success of pathway-selective inhibitors in curbing prostate cancer progression. We report that the antibiotic salinomycin, a cancer stem cell blocker, is a dual-acting AR and mTORC1 inhibitor, inhibiting PTEN-deficient castration-sensitive and castration-resistant prostate cancer in culture and xenograft tumors. AR expression, its transcriptional activity, and androgen biosynthesis regulating enzymes CYP17A1, HSD3β1 were reduced by sub-micro molar salinomycin. Estrogen receptor-α expression was unchanged. Loss of phosphorylated AR at serine-81, which is an index for nuclear AR activity, preceded total AR reduction. Rapamycin enhanced the AR protein level without altering phosphoAR-Ser81 and CYP17A1. Inactivation of mTORC1, evident from reduced phosphorylation of mTOR and downstream effectors, as well as AMPK activation led to robust autophagy induction. Apoptosis increased modestly, albeit significantly, by sub-micro molar salinomycin. Enhanced stimulatory TSC2 phosphorylation at Ser-1387 by AMPK, and reduced inhibitory TSC2 phosphorylation at Ser-939/Thr-1462 catalyzed by AKT augmented TSC2/TSC1 activity, which led to mTORC1 inhibition. AMPK-mediated raptor phosphorylation further reduced mTOR’s kinase function and mTORC1 activity. Our novel finding on dual inhibition of AR and mTORC1 suggests that salinomycin is potentially active as monotherapy against advanced prostate cancer.
Salinomycin: A new paradigm in cancer therapy http://journals.sagepub.com/doi/full/10.1177/1010428317695035
The primary hurdle in the treatment of cancer is acquisition of resistance by the tumor cells toward multiple drugs and selectively targeting the cancer stem cells. This problem was overcome by the chemotherapeutic property of recently discovered drug salinomycin. Exact mechanism of action of salinomycin is not yet known, but there are multiple pathways by which salinomycin inhibits tumor growth. Salinomycin decreases the expression of adenosine triphosphate–binding cassette transporter in multidrug resistance cells and interferes with Akt signaling pathway, Wnt/β-catenin, Hedgehog, and Notch pathways of cancer progression. Salinomycin selectively targets cancer stem cells. The potential of salinomycin to eliminate both cancer stem cells and therapy-resistant cancer cells may characterize the compound as a novel and an efficient chemotherapeutic drug.
Clinics Treating Patients with Salinomycin
Columbia: Advanced Medical Therapeutics
My review: Unknown
US: Advanced Rejuvenation Institute
My review: Unknown
Disclaimer:
This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learn on this road.
Salinomycin is as an antimicrobial and anticoccidial antibiotic. In 2009, a groundbreaking result was published in the scientific journal Cell (Ref), showing that Salinomycin can be effective in killing the cancer stem cells (CSC), the cancer cell population that is responsible for chemo resistance and metastasis. Although the study was focused on breast cancer, Salinomycin will do the same in most epithelial cancers.
In my opinion, this is one of the most effective anti cancer substance I am aware of, that can trigger an intensive anticancer response. However, somehow, the intensive response doesn’t happen always and it is not clear why. It seems that Sal works best in epithelial cancers. Example of epithelial cancers are cancers of endocrine glands (e.g. adrenal, thyroid, pituitary), breast, ovarian, lung, etc. Cancers that develop in epithelial cells are called carcinomas (Carcinoma is the term used for a malignant epithelial tumor). About 80-90% of cancers are this type. (Ref.)
Besides is wide effectiveness in various types of cancers, another strong point of Salinomycin is that even if it will not kill the cancer cells, it is a potent inhibitor of the ABC transporter P-glycoprotein/MDR1 in different cancer cells. Ref1 Ref2 This means that Sal will turn cancers that are or have become insensitive to chemo therapies, into cancers that will be again sensitive to chemo.
Soon after its discovery, in 2009, it has been patented by a company founded by the scientists who discovered the anti cancer effects of Sal. The company is also supported by Harvard University and MTI. Its name is Verastem. In their product portfolio, Salinomycin goes under VS-507 name while being promoted as an Wnt Inhibitor.
Update 27.02.2016: My understanding of Salinomycin today, based on personal view and that of others:
1. Salinomycin seems to be most effective in epithelial cancers
2. Salinomycin seems to work well when combined with Chemo (such as Cisplatin, Gemcitabine, Erlotinib and at least a few others) and/or 3BP
3. The Chemo and or 3BP has to be applied first and than Salinomycin after
4. Following the above, Salinomycin may lead to response that will decay in the following days of application if there is no other Chemo applied –> the effect fades away (I would not call this resistance)
5. If Chemo or 3BP is applied again than there is response again
6. Salinomycin must be applied at a delay of several days from Chemo and or 3Bp for the most intense response. That means that if Salinomycin is applied just after (e.g. during the same day) there may be no or little response to that
7. Following the Salinomycin effectiveness, cancer cells will die via necrosis – so there may be a strong immune reaction during the following days – blood measurements will show strong increase in LDH and others (e.g. potassium) for a few days suggesting tumor lysis (TLS). TLS can be dangerous if too much cancer is killed at once so it needs to be manged carefully.
Note that the above are extremely valuable conclusions following my intensive search for answers on this topic and identifying patterns.
Strangely enough, it seems that Salinomycin is not anymore on the pipeline of Verastem???
Case reports
Salinomycin as a drug for targeting human cancer stem cells.
“Salinomycin was therapeutically applicated €œfirst-in-man€ in 2010, in the context of a pilote clinical trial with a small cohort of patients with metastatic breast, ovarian, and head and neck cancers. Intravenous administration of 0.20-0.25 mg/kg salinomycin every second day for three weeks resulted in partial regression of tumor metastasis and showed only minor acute and long-term side effects, but no severe acute and long-term side effects observed with conventional chemotherapeutic drugs.”
“As shown in Figure 3, systemic salinomycin therapy induced a marked regression of the subcutaneous thoracal metastases. A biopsy of the regressive subcutaneous thoracal metastases was obtained after 12 cycles of salinomycin therapy, and the specimen was investigated by molecular histopathology. As determined by TdT-mediated dUTP nick end labeling (TUNEL) histopathology, ~85% of the cells had undergone apoptosis. Moreover, the serum levels of the tumormarkers Ca 15-3 (cut off <31€‰U/mL) and CEA (cut off <3.4€‰ng/mL) declined from 14.3 U/mL and 50.8€‰ng/mL before salinomycin therapy to 7.2 U/mL and 15.5€‰ng/mL after salinomycin therapy, respectively. Intravenous salinomycin therapy resulted in minor acute side effects, including tachycardia and mild tremor for 30€“60€‰min. after administration but lacked severe and long-term side effects observed with conventional chemotherapeutic drugs, such as myelodepression, neutropenia, alopecia, nausea and vomiting, or gastrointestinal, thromboembolic, and neurological side effects. Similar results of salinomycin-induced partial tumor and metastasis regression were obtained in three other patients with metastatic breast cancer, one patient with metastatic ovarian cancer, and one patient with metastatic head and neck squamous cell carcinoma.” Ref.
Anecdotal reports/stories
Case 1: SCLC: Cancer Treatment Institute of Colombia Demonstrates Unprecedented Results Using Unique Cancer Drug Combination of 3-Bromopyruvate and Salinomycin for Treatment of Multiple Types of Cancer
With masses in both lungs and a depressed platelet count, the prognosis for the patient was poor; he had previously undergone standard chemoradiotherapy, but the cancer returned within three months. His attending physician recommended against additional treatments. At Cancer Treatment Institute of Colombia, the patient received 21 total rounds of salinomycin and 3-BrPA, delivered on alternating days. Chest CT scans four weeks later confirmed the total disappearance of SCLC. Just as encouraging was that the patient experienced no significant adverse reactions during his treatment.
Case 2: Adrenal cancer – to be added
I am sure there will be many to come.
Mechanism
Potassium ionophore, specifically targeting the cancer stem cells (CSC). As a result, it will induce an efflux of K+ from mitochondria and cytoplasm. While the CSC killing mechanism is not that clear to the scientists, here you can read a bit more about the possible mechanism.
One potential mechanism: Salinomycin treatment led to increased cytosolic Na+concentration, which consequently resulted in elevated cytosolic Ca2+ by means of Na(+)/Ca(2+) exchangers (NCXs) in the plasma membrane as well as the mitochondria. Elevated Ca(2+) then leads to calpain activation, which triggers caspase-dependent apoptosis involving caspases 12, 9 and 3. In addition, cytochrome c released from depolarized mitochondria directly activates caspase 9. (Combined inhibition of calpain and the mitochondrial NCXs resulted in significantly decreased cytotoxicity and was comparable to caspase 3 inhibition.) Ref.
Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells. Ref
Salinomycin, a polyether ionophore antibiotic isolated from Streptomyces albus, has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways. Ref
Salinomycin to selectively target €œCD133+€ cell subpopulations: http://link.springer.com/article/10.1245%2Fs10434-011-1561-2
Has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways http://www.ncbi.nlm.nih.gov/pubmed/23251084
The in vitro IC50 of salinomycin varies, depending on the source, cell type used and treatment period (Ref.).
Here is a new (2017) paper discussing various anti cancer mechanism of Salynomicin: http://journals.sagepub.com/doi/full/10.1177/1010428317695035 and below is a figure from the article, indicating the various mechanisms:
Update Sept 2017: A recent Nature Chemistry papers proposing a new mechanism related to Salinomycin’s anti cancer action: https://www.nature.com/nchem/journal/vaop/ncurrent/full/nchem.2778.html
This mechanism could sit at the basis of all the other mechanisms that have been previously identified.
In this paper it is suggested that Salinomycin is accumulating and sequestering iron in lysosomes. When the cells are left without Iron in cytosol, they will trigger the degradation of ferritin in lysosomes, leading to further iron loading in the lysosomes. Iron-mediated production of reactive oxygen species promoted lysosomal membrane permeabilization, activating a cell death pathway consistent with ferroptosis.
Here is a nice recent paper on Lysosomes as Oxidative Targets for Cancer Therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516749/
To understand what Ferropoptosis is, you can read this paper: https://www.nature.com/cdd/journal/v23/n3/full/cdd2015158a.html
If indeed, this is the main mechanism responsible for Sal anti cancer mechanism, Iron Chelation prior to Sal treatments should be avoided. Indeed this paper suggest that Iron chelators can stop ferroptosis (Ref.). Opposite to that, Iron ionophores such as Disulfiram may help Salinomycin enhance this anti-cancer mechanism.
Interestingly, Chloroquine was suggested to work well with Salinomycin (Ref.) but due to a different reason. Based on the above, I can imagine Chloroquine can support the ferroptosis induced by Salinomycin due to a possibly similar action on Iron in the lysosames (Ref.)
Safety/Toxicity
This substance can be lethal if administrated at higher doses than it should. If on the other hand the administration dose is correct, as demonstrated by the articles above, there is a dose window where cancer cells are killed while the normal cells are not affected.
A case of accidental inhalation and swallowing of about 1mg/kg by a 35 years/old man leading to sever acute toxicity with acute nausea, photophobia, leg weekness, blod preasure elevation, chronic creatinine kinase elevation and muscle pain http://www.ncbi.nlm.nih.gov/pubmed/15107902
Note that this is about 4x higher dose than that used for cancer treatment.
Short term side effects have been reported and to my knowledge those may be: 30-60 min tremor after the administration, short term impact on peripheral view, fever after the administration, pain in the tumor area.
Inhibition of Na(+)/Ca(2+) exchangers (NCX) prevents salinomycin-induced neuropathy. Blocking mitochondrial Na(+)/Ca(2+) exchangers does not impair antineoplastic efficacy. Ref
Existing ion channel blockers, such as amiodarone, dronedarone, bepridil, aprindine, and cibenzoline, have been found to have an NCX inhibitory action. (Ref.)
Administration (Intra Venous – IV)
So far I am aware of two other administration protocols:
- Protocol as published in 2012 by the scientists from Heidelberg, Germany. This protocol has been administrated to multiple patients (4 cases published in one paper) with good results in all cases. The protocol used was suggesting the following:
– one cycle is defined by 12 intravenous administrations, in alternative days (i.e. a total of 24 days)
– each IV would consist of 0.200mg/kg to 0.250mg/kg Salinomycin (i.e. 10mg Salinomicyn in and IV for a person of 50kg receiving a 0.200mg/kg dose)
– the cycles may be repeated after a few months - A more intensive protocol I heard of being used:
– one cycle is defined as 4 weeks treatment, 5 days/week (Monday to Friday)
– each IV would consist of 0.250mg/kg to 0.300mg/kg Salinomycin
– the cycle should be repeated 4x with one month break between each - However, in other cases 0.180mg/kg to 0.200mg/kg is enough to trigger an immune response during the following 3-4 days, that includes episodes of fever and pain at the tumor site.
Note that there is another version of Salinomycin i.e. Sodium Salt >90% which may be 10x cheaper. However its effectiveness in humans is unknown.
Also note that on the web we will find easy to buy 24% purity (which typically is Sodium Salt version). This is used for treatment of animals.
So, the best seems to be Salinomycin base version (CAS Number 53003-10-4) as it seems that this was used before in the published cases, but Salinomycin Sodium Salt (CAS Number 55721-31-8) may also be relevant.
Tumor acidosis enhances cytotoxic effects and autophagy inhibition by salinomycin on cancer cell lines and cancer stem cells. http://europepmc.org/abstract/med/27248168
Improving Sal effectiveness:
While there is a lot of research indicating that Salinomycin can overcome multi drug resistance, there is also research indicating that Salinomycin is a substrate of P-glycoprotein and P-glycoprotein over expression may also limit Salinomycin brain penetration as well as oral bio-availability (Ref.). Here is another example of research indicating that MDR1 overexpression leads to resistance to Salinomycin https://www.researchgate.net/publication/279529617_Drug_Transporter-Mediated_Protection_of_Cancer_Stem_Cells_From_Ionophore_Antibiotics
However, I do know based on genetic profiling of my wife’s tumor (but also specific literature) that she had a high MDR1 over expression level. And we did saw strong response to Salinomycin. So our results may also be related with some of the drugs and supplements she was taking, with MDR1 inhibition capabilities. Those are e.g. sometimes Verapamil, sometimes Ketokonazole. As a result, when there is no response to Salinomycin treatment, P-glycoprotein inhibitors such as Verapamil, Ketoconazole, or Tetrandrine should be administrated prior and/or during the Sal treatment.
Since MDR1 pump is ATP driven, lowering ATP prior to Sal treatment should also improve effectiveness. Using Metformin and/or Doxicycline would then help. Same applies for Phlorizin and 2DG. Note: we always used Metformin and sometimes Doxicycline. These will slow down mitochondria.
Preparation method:
I will share my research on this asap.
Source & Cost
Chemical suppliers such as Sigma. Salinomycin base version (CAS Number 53003-10-4). Material cost is a few thousands euro/dollars for one cycle (12 IVs) depending on your weight.
Synergies & Antagonsists
Synergies:
2-DG, 3BP, other glycolisis inhibitors: http://www.ncbi.nlm.nih.gov/pubmed/25912307
HDAC inhibitors (e.g. Valproic acid): http://www.ncbi.nlm.nih.gov/pubmed/24351423
Autophagy Inhibitors (e.g. Chloroquine): http://www.ncbi.nlm.nih.gov/pubmed/23670030
Doxorubicin: http://www.ncbi.nlm.nih.gov/pubmed/25892525
Metformin: http://www.ncbi.nlm.nih.gov/pubmed/25375092
5-fluorouracil: http://www.ncbi.nlm.nih.gov/pubmed/24816638
Nelfinavir https://orca-mwe.cf.ac.uk/98987/1/Dunlop-Tee2017Oncotarget.pdf
Patents
Therapeutic compositions and related methods of use
Based on this the formulation was found to remain stable in normal saline up to 24 hours at room temperature.
Relevant Literature
Salinomycin suppresses TGF-β1-induced epithelial-to-mesenchymal transition in MCF-7 human breast cancer cells.
Acidosis enhances the ability of salinomycin to kill cancer cells and cancer stem cells
Preclinical drug metabolism and pharmacokinetics of Salinomycin, a potential candidate for targeting human cancer stem cells
Concomitant administration of Ketoconazole (KTC) on SAL pharmacokinetics: KTC, being a selective CYP3A4 inhibitor increased the systemic exposure of SAL significantly to 7-fold in AUC0-α and 3-fold increase in Cmax of SAL in rats with concomitant KTC administration.
Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death
Our in vitro studies further demonstrate that the combined use of 2-Fluoro 2-deoxy D-glucose, or 2-deoxy D-glucose with Salinomycin is lethal in cancer cells
HDAC inhibitors enhance the lethality of low dose salinomycin in parental and stem-like GBM cells.
Collectively our data demonstrate that the lethality of low nanomolar concentrations of salinomycin are enhanced by HDAC inhibitors in GBM cells and that increased death receptor signaling together with reduced mitochondrial function are causal in the combinatorial drug necro-apoptotic killing effect.
Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells. In conclusion, these findings provide evidence that combination treatment with salinomycin and pharmacological autophagy inhibitors will be an effective therapeutic strategy for eliminating cancer cells as well as cancer stem cells.
Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin.
Salinomycin decreases doxorubicin resistance in hepatocellular carcinoma cells by inhibiting the β-catenin/TCF complex association via FOXO3a activation.
Salinomycin inhibits growth of pancreatic cancer and cancer cell migration by disruption of actin stress fiber integrity.
Salinomycin inhibits the tumor growth of glioma stem cells by selectively suppressing glioma-initiating cells.
Metformin and salinomycin as the best combination for the eradication of NSCLC monolayer cells and their alveospheres (cancer stem cells) irrespective of EGFR, KRAS, EML4/ALK and LKB1 status. In conclusion, METF in combination with SAL could be a promising treatment option for patients with advanced NSCLC irrespective of their EGFR, KRAS, EML4/ALK and LKB1 status.
Inhibition of autophagic flux by salinomycin results in anti-cancer effect in hepatocellular carcinoma cells.
Specific targeting of neurotoxic side effects and pharmacological profile of the novel cancer stem cell drug salinomycin in mice. Inhibition of the mitochondrial Na(+)/Ca(2+) exchanger partially prevented the development ofsalinomycin-induced neuropathy in vivo, an approach which did not reduce salinomycin‘s antineoplastic efficacy in vitro.
Salinomycin treatment reduces metastatic tumor burden by hampering cancer cell migration. Our findings clearly show that salinomycin can strongly inhibit cancer cell migration independent of the induction of cell death. We furthermore demonstrate for the first time that salinomycin treatment reduces metastasis formation in vivo, strengthening its role as promising anti-cancer therapeutic.
Salinomycin increases chemosensitivity to the effects of doxorubicin in soft tissue sarcomas.
The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Treatment of the MDR cell lines with salinomycin restored a normal drug sensitivity of these cells.
Combining targeted drugs to overcome and prevent resistance of solid cancers with some stem-like cell features
Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity http://aac.asm.org/content/59/9/5135.full
Dual targeting of androgen receptor and mTORC1 by salinomycin in prostate cancer. http://www.ncbi.nlm.nih.gov/pubmed/27557496
Androgen receptor (AR) and PI3K/AKT/mTORC1 are major survival signals that drive prostate cancer to a lethal disease. Reciprocal activation of these oncogenic pathways from negative cross talks contributes to low/limited success of pathway-selective inhibitors in curbing prostate cancer progression. We report that the antibiotic salinomycin, a cancer stem cell blocker, is a dual-acting AR and mTORC1 inhibitor, inhibiting PTEN-deficient castration-sensitive and castration-resistant prostate cancer in culture and xenograft tumors. AR expression, its transcriptional activity, and androgen biosynthesis regulating enzymes CYP17A1, HSD3β1 were reduced by sub-micro molar salinomycin. Estrogen receptor-α expression was unchanged. Loss of phosphorylated AR at serine-81, which is an index for nuclear AR activity, preceded total AR reduction. Rapamycin enhanced the AR protein level without altering phosphoAR-Ser81 and CYP17A1. Inactivation of mTORC1, evident from reduced phosphorylation of mTOR and downstream effectors, as well as AMPK activation led to robust autophagy induction. Apoptosis increased modestly, albeit significantly, by sub-micro molar salinomycin. Enhanced stimulatory TSC2 phosphorylation at Ser-1387 by AMPK, and reduced inhibitory TSC2 phosphorylation at Ser-939/Thr-1462 catalyzed by AKT augmented TSC2/TSC1 activity, which led to mTORC1 inhibition. AMPK-mediated raptor phosphorylation further reduced mTOR’s kinase function and mTORC1 activity. Our novel finding on dual inhibition of AR and mTORC1 suggests that salinomycin is potentially active as monotherapy against advanced prostate cancer.
Salinomycin: A new paradigm in cancer therapy http://journals.sagepub.com/doi/full/10.1177/1010428317695035
The primary hurdle in the treatment of cancer is acquisition of resistance by the tumor cells toward multiple drugs and selectively targeting the cancer stem cells. This problem was overcome by the chemotherapeutic property of recently discovered drug salinomycin. Exact mechanism of action of salinomycin is not yet known, but there are multiple pathways by which salinomycin inhibits tumor growth. Salinomycin decreases the expression of adenosine triphosphate–binding cassette transporter in multidrug resistance cells and interferes with Akt signaling pathway, Wnt/β-catenin, Hedgehog, and Notch pathways of cancer progression. Salinomycin selectively targets cancer stem cells. The potential of salinomycin to eliminate both cancer stem cells and therapy-resistant cancer cells may characterize the compound as a novel and an efficient chemotherapeutic drug.
Clinics Treating Patients with Salinomycin
Columbia: Advanced Medical Therapeutics
My review: Unknown
US: Advanced Rejuvenation Institute
My review: Unknown
Disclaimer:
This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learn on this road.
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I would like to ask should be there one month break after salinomycin cycle.
I combine salinomycin with Paw paw for treating my mother with metastasis. She has already the last phase of cancer and I am afraid to stop using salinomycin for one month because of cancer progress.
Please let me know soon,
Best Regards
Pavel
Could you please share with us here (or in private with me) how you administrate Sal, what is the source, tumor location, how your mother is feeling, side effects, observed treatments results, etc? That would be very helpful.
where can I get Salinomycin Sodium Salt >90% ???
I cannot find it
and the other thing , is it okay for salinomycin to stay in warm condition for about 2 weeks ?
when I order anything from the internet it usually take about 2 weeks to arrive
is there any clinic giving it orally or any success reports about that ?
the same dose 0.2mg/kg orally , I’m wondering if the bioavailability is good or low ?
but also I will give it to my mother at the same dose as IV , 0.2mg/kg , and the purity is >90%
for me it’s better than nothing , I will try to get Salinomycin soon
Thank you so much 🙂
just a heads up Salinomycin taken orally is highly toxic and can have life threatening effects.
Source: http://www.krebs-kompass.de/showthread.php?t=51961
When given IV it implies that those administrating it have experience with chemicals, drugs, etc. and think carefully about what they are doing given that the substance goes directly to the blood. So they are clearly aware about the max safe dose to be administrate.
On the other hand, given that oral administration can be accessible to ANYONE, statistically there is a much much higher chance that someone with less experience will make a mistake. The chance for mistakes is even higher given that: 1. the max safe dose is very very small (i.e. 300ug/kg/day) – someone may easily make the mistake and assume mg instead of ug; 2. Salinomyin that is accessible to anyone is the one used for animals which is typically low purity, i.e. 12% to 24% in purity – sometime the purity may not be clear and we could easily double the dose simply because the purity would not be clear.
In conclusion, to administrate orally I would need to know:
1. what is the max safe dose and what is the working latitude: based on the above references the max safe dose is 0.3mg/kg/day and the working latitude in which we may expect anti cancer effectiveness is 0.2mg to 0.3mg/kg/day
2. what is the purity of the Salinomycin I have: the most accessible one is in the range of 12% to 14%
3. I would need to know my weight and to do a bit of math but CAREFULLY
So assuming I have Salinomycin 24%, I have 50kg and I would like to administrate 0.2mg/kg/day this is the math that I have to do: (0.2*50)/0.24=42. This means that I would have to take 42mg of the LOW purity (24%) Salinomycin mix each day to reach a daily dose that may be effective. However, if I would have the highest Salinomycin purity of nearly 100%, I would only have to take 10mg in a day.
Here is a nice an clever man making mistakes, i.e. using Salinomycin orally at 330mg/day!!! https://www.cancercompass.com/message-board/message/all,65701,25.htm I do not know his weight and purity of the Sal he used but that is TOO high to start with! And indeed, based on his later reports, he ended up not well using this dose.
Lets do the match and some guessing: Lets assume he used the lowest purity available 12% and the max safe dose of 0.3mg/kg/day. If this is the case he would have to have 132kg which is not typical for a cancer patient. If the purity of his Salinomycin was 24% than he would have to have 262kg in order to take that dose …. and note that I used 0.3mg/kg/day which is the max safe dose, i.e. at the edge with being unsafe …
In conclusion, I think administrating Salinomicyn orally is very risky if we do not pay very serious attention, and even knowledgeable people may make mistakes!
Note: regardless if IV or oral, I would always start with half of the minimum of effective dose (as already used on humans) and increase step by step to the effective range.
In any-case, your point is very good in that it will probably be beneficial to also add an anti Candida treatment next to Salinomycin.
Therefore, if you can share your Candida fighting view here would be great (with scientific references please, because otherwise we find many non scientific views on the web which most of the time have no value and are misleading). Thank you.
I will never use Sal Orally , but still concerned about the sodium salt version , it’s a lot cheaper but I will use it with my mother soon .
today I finally get the official email address of Tripoli university , it should be easy now to get anything I wan’t from the western chemical suppliers
I will get both Salinomycin versions , I will try the base version first , then I will try the other …
hope things work good 🙂
due to many problems with airports here in Libya , they can’t ship in less than 5 days
it may took from 5 to 10 days , and they told us if the shipping time of Salinomycin took about 2 weeks , it may not arrive in a good shape
but they will try to ship in less than 1 week
however , we gonna use it anyway
and of course this means we cannot order 3-BP since it’s stability is very low , unless if my father travels to Germany the next month
———–
the other thing about Sal
isn’t there any information yet about the effectiveness of the Sodium Salt version ?
the chemical companies are talking about it’s effectiveness against cancer the same way they talk about the base version
but still I’m not feeling comfortable to use it , I wish I can know more about it
the base version is very expensive , we could only buy 2 IVs for my mother monthly , but also combined with MG
that’s what we have for now , and thank you so much 🙂
Side effects of SAL maybe are manageable http://www.nature.com/cddis/journal/v2/n6/full/cddis201146a.html by inhibition of mitochondrial NCXs.Here is one such an inhibitor http://www.rxlist.com/vascor-drug.htm
I find this very interesting since initially I expected that intracellular Ca accumulation is the origin of the antineoplatsic effects. The fact that after applying NCX inhibitors he anticancer effect is still there is may mean that the antineoplastic effects are related to intracellular acidifying effect of Sal.
she is feeling like tired, increased heart rate, blurred vision , fatigue , tired
little tremor , but also she is feeling tired and fatigued , a little bit of pain in her arms
this is nearly half the dose , 0.1 to 0.12 mg/kg
hope it will continue like that 🙂
maybe I want to share some details about what happened
before 4 weeks , the tumor marker was 517, but because of low blood counts , the oncologist didn’t administrate chemo until 8 days later
in these 8 days , I give to my mother DCA only , but also because of delaying chemo , the markers may have been climbed a little bit
but I’m not sure about that , anyway
after that my mother received chemo and like always (combining chemo + DCA)
the last week I administrated Salinomycin to my mother (at night) , about half the normal dose (0.1 to 0.12 mg/kg)
and paclitaxel was enough to completely solubilize it !
immediately after administrating Sal , my mother felt like things are getting darker , and the heart rate increased (like she was running then became tired) , mild tremor , mild fever , some pain in her arms , felt weak a little bit
but also non of those side effects was annoying to her , she felt like things are going good , almost all the side effects disappeared after about 1 hour
some side effects didn’t disappear until about 6 hours , but the day after that she felt completely normal
yesterday (after about 4 days from administrating Sal) the tumor marker result was 408
it was a very good result , but I don’t know if I didn’t administrate Sal , what could the result be ?
I’m feeling like the cancer are trying hard to resist both DCA and chemo , I should use more than that to be in the safe side
but after all, I made it to this level , and I’m very happy about that 🙂
I have some questions related to Sal
what is the best time to use it ? the last day before administrating chemo ? or before that ?
I have only 15mg left (about 0.2mg/kg) so I need to use it carefully in the right time
also I will buy Salinomycin Sodium salt version , I need to try it and know more about it 🙂
sorry for my long comment and poor English language , and thank you so much Daniel for all your shared information
and from the bottom of my heart I wish the very best for both you and your wife
Sal is good both before and after Chemo but if I would have only one dose and need to chose, I would give it several days after chemo.
The very best for your mother and you Emad!
Was it through IV? How did you handle the preparation then?
Also, is it possible for an individual to buy products from a chemicals company? It seems it would require being a company or laboratory. How did you do it?
Thank you very much
first , thanks to Daniel for sharing all this information , I have just followed his words step by step
I’m not sure if I did it in a good way , but I will answer you about what I did
I give Sal to my mother through IV , I have a very clean glass vial , and put about 8mg of Sal powder in it (about 0.1mg/kg)
after that I added 0.5ml paclitaxel solution to the 8mg Sal powder , and without mixing it , just kept it 24 hours in the freezer , this was enough to solubilize Salinomycin
then I pull out the Salinomycin solution (Sal + paclitaxel) from the vial with a syringe
then put the sterile filter on the syringe to sterilize the solution , through the filter I pushed the solution into a 500ml NaCl , administrated during about 2 hours
and like I said I’m not sure if I done it in the right way but every thing went so good 🙂
————
regarding your last question , I got Sal from Santa Cruz , my father is a professor in the University of Tripoli (Libya) he have an official email address from the University
it doesn’t matter if you are a student or doctor or not in a university at all , all you need is an official email address from any university , if you don’t have it , look for your friends , its not hard to have one
and that is enough to let a chemical supplier sell there products to you 🙂
Kind regards
thank you so much for this info. You seem to have some experience in those things as it looks fairly difficult. Anyway, I’ll look into it. My wife has GBM and I’m trying to find additional treatments on top of chemo as chemo-resistance occurs in most cases.
Thanks again.
there is one thing that you don’t know about it but its fairly easy to know about it , which is inserting the IV with cannula , and you can solve this problem by asking a friend or a nurse that can do this for you or help you learn about it
also it will be easier if you have a medical port , but don’t worry if you don’t know about it
if its not hard for you to insert IVs , then everything is solved !
anything else is easy to do , I can share much more details on how to prepare DCA and Sal , just make sure to know how to insert IVs with normal saline bags
the hardest thing you can face is the financial problems , which is the hardest problem for us now , we can’t make more than 500 euros per month
but in your case , having some help or experience isn’t hard at all
I will love to hear more from you , and will be happy to answer any questions here
my best wishes for you and your wife
regards,
Pouya.
OK its a good idea , its not an odd request
I will do it , I’m not sure if it will be in a good quality but I will show everything I can in it
but just you have to wait until Friday or Saturday
I will prepare DCA IV on Friday , and for Salinomycin I can’t prepare it until the next week
I will put it in my mind so its just a matter of time 🙂
I wish for you the best ,
Kind Regards
thanks a lot for your wishes. I was not aware of DCA and I find it interesting. You seem to administer through IV although I’ve read that it can be taken orally. Why IV? For Sal IV, it requires materials and tools first. I guess I need to ask a nurse about the whole process. It’s still something I’d rather let the doctors do, but unfortunately they would not want to hear about alternative approaches that are not fully validated. Too risky, maybe, but what is the risk of doing nothing but a standard protocol that is known to work very poorly in most cases?
Anyway, I’m looking forward to further news from you if you can give some, as your situation evolves.
Best wishes to you and your mother.
sorry for my late response
I was too busy and the internet connection is so bad these days here in Libya
I want to know how to share the video with you
and also with Daniel’s permission
I hope you all doing good
this is my email address, hyp3rbor3an@gmail.com , also if you have either Whatsapp, Telegram, Viber, etc, let me know. it might be easier to send videos through them.
things didn’t go well recently
the chemo cycle has been delayed for 2 weeks because of low blood counts
then my grandfather (from my mother) passed away
and also the hospital just run out of most of the chemotherapy drugs
so after all they just give my mother Carboplatin , with no Gemzar (it used to be given in a combination)
and also , I have no Salinomycin left , just DCA with Carboplatin
today the results come out , the tumor marker climbed from 317 to 381
but thank god it didn’t climb more just like what happened several months ago
my next strategy now is to use Salinomycin monosodium Salt
https://www.scbt.com/scbt/product/salinomycin-monosodium-salt-55721-31-8
I contacted scbt.com , and they said that its purity is 90%
and still I don’t want to use MG , I want to keep it as my last option
again , thank you so much for your question , my best wishes to you all
I am just wondering if you know if there are any clinical trials currently going on and testing salinomycin on cancer patients? I have not managed to find any…
Also, I am wondering if you have heard of Prof. Cord Naujokat and his work with salinomycin? He is apparently treating cancer patients with salinomycin, combined with immunotherapy or chemotherapy. We are considering it as a treatment, but it is impossible to find any results from these treatments. Apperently there are several doctors in Germany using Salinomycin, but I can´t find anything on how treated patients are now doing/what the success has been…. If you have any information on this could you please share it with us.
Kind regards,
Marina
Strangely enough Sal was on the pipeline of a pharma company and fro inside sources I new it was showing good results but somehow Sal went out of their pipeline without any communication.
At this pint I am not aware of any trial on Sal. Indeed Naujokat seems to use it in combi with chemo. If you want to access that, you will need to contact him personalty. His e-mail address can be found on the web or in the scientific articles he published.
I do not expect you will find statistics related to the success of Sal.
Personally, I strongly believe in Sal as I have seen it working.
Kind regards,
Daniel
thank you very much for your reply. I have some few more questions, and I have sent you an e-mail. Hope to hear from you.
Kind regards, Marina
I am very sorry about your wife Daniel.But we are very lucky that she has a brilliant husband like you.You made a valuable work for
all people.
I have been entering your website everyday and reading everything.I think there are hundreds of patients,sons,daughters
like me reading but not writing.I am researching for my lovely mother who has diagnosed with Ovarian ca spread to peritonium.
A very late stage as you know.I hope i am going to help people and we can make research alltogether.Now ca125 is 35.
We have used iv curcumin,iv vitaminC,hyperthermia and HBOT.We refused the surgery because she is 70 years old.And now we have to deal with cancer stem cells which is not gone by chemo.I can share my experiences if you need.
I have to say that EMAD is my idol.Extremely he makes a good care of his mother.
Tumor markers are going up and he makes them going down,amazing.I wonder the latest results of salinomycin treatment Emad.
Kind Regards,Ergin
I hope from the bottom of my heart to see you win your own battle and save your mother , and hope the best for all the patients around the world , God bless them
I am too so sorry for what happened recently with Daniel , he was and still my hero
but for us, what we have to do is just keep fighting and do our best , we have nothing else to do
and to share about our recent results
the tumor marker declined from 408 to 317
what we did is like always : Chemo + DCA , (and also added one shot Salinomycin)
last week , I administrated Sal to my mother at night , about 0.2mg/kg
and after the administration she had a very strong tremor that last’s for over an hour , very strong tremor from her lips to her feet
I scarred a little bit, but it was only less than 2 hours , then everything became normal again
and there was other side effects like these which are mentioned in this post
and I should notice something , the strong effect added by Salinomycin are not showing on tumor marker ca 15-3
its only telling us that there is a good result , but how good is it are something I can’t know from this result
what I know is the side effects are telling me that there is a lot of cells died suddenly
if it was a normal cells then how could my mother feel completely normal after just a bit of hours !?
if its not an effect made by dying cancer cells then what is the origin of this strong tremor !?
I can’t track the complete effect , we can’t have a CT Scan right now , the tumor marker ca 15-3 are telling us whether there is a good result or bad , but usually we can’t know about how much cancer shrinked or progressed until we do CT Scan
until now , things are going good , but I can’t be happy until we can completely relay on treatments other than chemo , which is not easy for us with our financial problems , chemo are always doing damage to the immune system , and sometimes we are doing blood transfusion because of low blood counts
that’s all I have for now
my best wishes to you Ergin and for all the brave cancer fighters around the world
I cannot write anything.It says spam.I need your email adress.I may help you finding Salinomycin.
Ergin
If you make an account as a new user, I will only have to approve your post first time – after that you will be able to post without the need of my approval.
I would appreciate if you will share here what is your way of finding Salinomycin, expected cost and quality. In this way you will contribute to growing the information here, that may help others. Thank you in advance.
Kind regards,
Daniel
Although i am not a millionare,It is honour for me to help Emad if he accepts ofcourse.As we know that he has financial problems.I am going to buy Salinomycin from a seller which Emad choose.
I am always thinking like you.If the things goes upsidedown,what will i do ?ofcourse nobody wants to give advices in this website.
BUT Emad has a great story and i feel myself to help him.I hope his valuable work gives a positive feedback at the end.
Emad deserves some help.Am i wrong?
Kind Regards
Ergin
Thank you for your response.
Now, people can advise each other here as the Disclaimer of this website covers that, clarifying that non of that represents medical advice.
Off course Emad deserves all the help and it would be great if you can support him financially to continue the treatments for his dear mother. It is a honor to see that happening here and I thank you in advance for supporting Emad!
Kind regards,
Daniel
to me , this is enough to not forget your willing for help for my entire life
and i will always hope the best for your mother just as i hope the best for my mother
if you choose to help me , then i will choose the way that can help not only me , but also other people who are fighting cancer
I’m focusing on Salinomycin monosodium salt , its very cheep and if i succeed to have a good results with it
then other people will also use it easily as it will not cost thousands just like the base version
so at this point , i need to prove that the cheep version is working , it may save a lot of lives if it shows a successful results
https://www.scbt.com/scbt/product/salinomycin-monosodium-salt-55721-31-8
here you can find it , it only costs 146 dollars , that’s enough to help me and also enough to let all the people know whether its effective and probably safe or not
and again , thank you so much Ergin 🙂
At Ergins’s request I sent to you his e-mail address.
Salinomycin Sodium Salt has been used by some clinics I know – but I am not sure what was the result – I will check that.
If I would be you I would make sure from now on I will not be left without the most relevant treatments as I know sometime ago you were left without DCA that helps your mother and now Salinomycin … you always need to have a buffer.
All the best to you and your mom and hope to hear good news soon.
I have been searching for silver and salinomycin.And found this intresting article.
What do you think about silver nano particles.?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977082/
Kind Regards
Ergin
Thank you for your comment and sorry for the delay of my response.
In general, I am positive regarding the use of silver nano particles.
This is one of the subjects on my list to address when I find the time.
Kind regards,
Daniel
Could you please send your email adress.
I think Daniel has mine and can share with you.
Kind regards
Ergin
I am so sorry about your grandfather.
The dates and the messages are mixed so i didnt see that very bad happening.
For your mother,it seems dca doesnt work too much without chemo.But works a little bit as you said,the markers didnt get too much higher.
As i dont know if you use dca or not in 2 weeks.
I wonder your mothers blood counts aswell.
For my mother,the tumor markers begin to rise,but she was flu.I hope thats because of it.
This week we have pet scan.I want to write our story and treatments which we took;,after the pet scan results.
Kind regards
Ergin
I’m not happy to hear about the tumor markers are rising with your mother , but there is always some ups and downs with these markers , its not something we should afraid of , its always a matter of time to find the best thing that can work
as I said in the comment below , we all wish to hear a good news from you today Ergin
regarding your question , I was using DCA continuously and didn’t stop
You are all my hero, not only Daniel.
MEECH,PAUL,EMAD,ANN ETC..
You are all brave fighters,that who are genious and believe to science.
I have been going to all famous doctors in my country since 2015.But they have no knowlodge to answer my questions indeed.
They all said that my family is out of science because we refuse surgery.
Here i have found lots of answers to my questions.But also not enough.I think people have different psychology.This may be cause of the bad situation of the terminal cases.People choose alternative ways when they are in terminal case.(Although I dont want to say it is alternative,these are science)).
I also think twice when writing to this site.May be people think that this is a cure for themselves.But it is not.
I sent my mothers blood to USA for gene sequencing.There are lots of mutations there which does not belongs to ovarian ca.
I dont want to mix peoples thoughts,but they mixed mine by saying that chemo is poison.But i see that chemo works with those alternatives when you have to deal with cancer stem cells.
I have read 4000 academic papers in 12 months.And yes i found the answer.There is a cure for cancer.
It is HEAT with cytotoxic drugs and nano particles..But a huge conversation.We can not find brave enough people to search and done themselves.
I am an electronical engineer.We have been producing ecg monitors and electrosurgical devices since 1975.We have great technology both software and hardware..We produced mild hyperthermia devices for only muscles and physical therapies.But due to low demand we had to close the department.But now there is a big interest in magnetic nano particles thermal therapy.They cure mices %100 by salinomycin,silver,chemo,doxorubicin lipid,(cytotoxic drug) etc binding with magnetic nano particles,with chitosan etc and targeting them to tumors by antibodies or overexpression(Most famous CD44 or folate receptor) with HEAT.Also spinning particles cause necrosis without heat and a great responce of whole body immune responce by chitosan .Really interesing technology.My aim is first to try this tech on animals,especially dogs suffering from cancer.Later a clinical trial on human.
If we can see more people here we can really help others.
I never like to talk bigger than me.Tomorrow we have the results of pet scan.I hope it will be good.
I will write you our protocol if it will be good or not.
Kind Regards
Ergin
thank you so much for your great words , I am sure your readings and searching will definitely give us the very good progress towards the cure for cancer
and we all are here to make this science reality
I hope to hear a good news from you today , god save your mother and all our lovers
Sincerely , Emad
Thank you for answering.I feel very lonely these days.It is very hard to find someone to help me and to help my projects.
Today i got the PET results.Totally dissapointing for me.There is no responce to treatment.All of the tumors are alive.
I think they became resistant.
But interestingly a little bit progress.3 months before and after no change as we got 9 chemos.I feel so tired tonight.
Tomorrow i will write our protocol.May be it helps someone who knows.
Emad please write me an email,where will i send the salinomycin?
Kind Regards
Ergin
the same feeling I had some months ago , when you thought you will see a good results then you see the opposite
but don’t let this feeling control you , there is a lot of alternatives that we never tried yet
did you try other strong alternatives like Sal , 3-BP , MG ???
if you didn’t try them , maybe its time to use them
what I mean is just focus on the next step , and I’m sure there would be treatments that will work for sure
please stay strong , I will send you my email
Kind Regards, Emad
I am very sorry to hear that the response to the current treatment is not there. I thought about your points and I would like to offer you the following:
1. if you like, you can write an overview of the medical history including the tumor evolution (primary location and mets if they are), treatments (alternative and conventional in the past, present and planned; any form of treatments you used or are using). you send me this overview and I will make a post out of it. In this way others can both learn from you and give feedback to you.
2. if you like, you can write the details of your project and I can write a post out of that if it makes sense – in this way maybe you can find someone here to support you with it
Any of the above can be sent by e-mail to me.
All the best,
Daniel
Thank you very much for your kind words and want to help me Emad,Daniel.
You gave me a breath.Here is our treatment after diagnosis of ovarian ca,primary peritonium.
There was lots of metastasis on periton and there was an omental cake(the final word of cancer doctor said).
But only on periton and around the bowel neighbour to periton.
CA125 was 400 ,11 months ago.
1.)Three courses(3 months,9 chemo)taxane+carboplatin+nerium oleander injections.
CA125 was declined to only 5.WBC never went below 5.
2.)And we stopped chemo and refuse surgery.Only nerium oleander injecitons.
After 2 months past without chemo,CA125 begin to rise upto 95.
3.)We began chemo + iv vitamin C + iv Curcumin + local hyperthermia on abdomen for 2 courses(6 chemo)+metformin.
CA125 declined to 35.
4.)We had to change our doctor because he said we Must do surgery.
We began insulin potentiation therapy for 3 courses(9 chemo) with different doctor.
On chemo days iv mannose + iv sulphur + iv iron + iv vitc + iv vit b complex + hyperthermia + HBOT.
On normal days only pills(2DG + curcumin + melatonin + metformin + artemisinin + beta glucan)
There is no responce after changing the doctor.From first day to last CA125 rised to 57.
Still lots of tumors on peritonon PET last week.I am always thinking about iv curcumin.Is it our drug which works best?I began to use iv curcumin again.
2 weeks past now.WBC were always 2-2,5 range before iv curcumin.Now it is 3,6.
I wonder the results on tuesday(chemo day),especially CA125.
I talked with Dr,he said very surprising! and not good pet result.Now we have to make more agressive therapy.
He is going to use DCA on tuesday.He has Salinomycin and 3bp in his clinic but didnt try yet.
I really dont know what to do.The clinic is 450km far away from us.Everyweek we have to go by car.
There is stg wrong with his protocol i think.They all became resistant.He said he gives low dose chemo but wbc became very low
after courses.Ipt potantiates chemo.Last week her blood sugar downs to 30 during ipt.I was really afraid.
Normal blood sugar level is around 100 after we began to use 2DG and metformin.
Before it was around 175.
Daniel and friends.What do you think about our protocol?What is wrong with it?
Is it iron,sulphur,2DG etc.
Do you think that should we give chance to iv curcumin for one or two weeks before DCA?
Sorry for the quantities of the medicines.I will write them when i learnd the exact weights
Kind Regards
Ergin
today I tried Salinomycin monosodium salt today , about 0.12mg/kg
I didn’t notice any difference between the side effects of the base version or sodium salt version , its almost the same side effects
it was a low dose , my mother felt little tremor and increased heart rate , hotness , its almost the same side effects she felt when I give her low dose from the base version
that’s what I have until now
Ergin , thank you so much for everything , all my family thanks you so much for your great help , we will not forget it , and we always wish the best for your dear mother
also we cannot forget to thank you Daniel for sharing all this great information
I will continue to share everything in time
Kind Regards
I am happy that it arrived.Please be careful.
I hope it helps to your mother.Believe me i am living in internet and in Daniels website.
I always see you like my brother.We are a huge family here.I hope one day we meet eachother with our hero Daniel.
We began chemo today.Bevacizumab,gemzar,iv curcumin,iv vit c.
Tomorrow carboplatin.I hope it works.
After 2 days we interrupted DCA,collodial silver LDH COME TO 230! FROM 100.
Dr said stop DCA!!!
I asked for tinzaparin.He began laughing to me.He gave the lecture about tinzaparin today in class.
It makes nothing on tumor progress he said.On human,not lab.
I asked what about the resistivity releasing for platinium?
He laughed again.
I asked salinomycin.He never heard.
And so on.
I’m managing to administrate them together , hope there is no interactions between them
————
like Ergin said , I really wish to meet you all 🙂
Let’s make a goal out of that. Once we put it in our mind, it will happen and we will meet each other 🙂
Thank you for your help
I administrated Sal monosodium salt again to my mother tonight , about 0.2mg/kg
the very same side effects she felt when I gave her Sal base version
tremor , increased heart rate , little fatigue and disturbance vision (she see everything became darker then brighter , some time unclear)
Daniel do you think this side effect on the eyes are related to Sal it self , or its related to the treatment response ?
its the first side effect my mother is feeling all the time , also its the first one to go , it lasts about an hour just like the other side effects
————–
sure I made the goal to meet each other , and I believe it will happen 🙂
she is feeling little pain over her body but not sure if tumor are there or not , almost all the mets are small , most of them are less than 1cm
I give Sal 2 times recently , the first was January-25th , the second was yesterday January-29
also I gave her Sal 2 times 3 months ago , she felt the same , always the first side effect is seeing stars ! brightness , darkness , and so on ….
is it good to give multiple lower doses ? maybe better than giving one strong dose ?
——————-
also today the tumor marker results show a little decline , from 353 to 334
its not that good , but I think the main reason it didn’t decline is because I didn’t give enough DCA before administrating chemo
to my knowledge , when there is low or no DCA given before 2 days of chemo , there wouldn’t be any effect from chemo , probably the tumor marker will rise ! , that’s what happened before
the problem now we are facing is low Hemoglobin level , my mother will need blood transfusion again , after that we can continue , using chemo + Sal + DCA all together (not at the same time of course) , I wish the next result will be good
I don’t know if there is a combination existed in this world stronger than this one !?
For us, 2h was better. Great to hear that tumors are <1mm! I remember I cam across an article suggesting lower dose should be fine as well. However, what has been used so far across the world was based on the Hidelberg model of 0.2 to 0.3 mg/kg. For us, when given faster, even 0.12mg/kg led to effectiveness. I am sorry to hear about the hemoglobin. Is that due to chemo? Pau d'arco in higher doses may help improve hemoglobin.
There are always ways to improve the treatment, e.g. I would clearly consider this option: http://www.cancertreatmentsresearch.com/?p=736 specifically for those using chemo.
When I can I will write more on new treatment options.
Btw, if you read my post on DCA you will see that procaine administrated prior to DCA may increase its effectiveness.
Kind regards,
Daniel
that's for most of them but there is some mets with nearly 2cm
the hemoglobin not usually decreasing but it suddenly decreased from 10 to 7.5 in 3 weeks !
but also my mother injured her arm 2 weeks ago and it was bleeding (not very much) also when the dentist used to work on her teeth she bleeds (good amount of bleeding)
do you think that this helped decrease hemoglobin ?
I will try to get Pau d'arco , thank you so much for that , also will try procaine and do the best to make DCA work well
—————
another thing , I administrated Sal again today at night , I tried to administrate it slowly , the side effects on the vision was very little , but also generally the side effects was less , there was a tremor for about an hour , she didn't feel tired and the heart rate didn't increase that much
I'm not sure if its due to the dose , I'm sure that its maximum 0.2mg / kg , but could be a little bit lower than that
or could it be the response is decreasing ? is there any side effects when there is no response ?
I hope its suitable now for chemo to work better when response to Salinomycin became lower
I would not expect that the decrease of hemolobin to be related to the events you mentioned above.
Check the potential side effects of the chemos you are curently using.
Or maybe you are using Vit C and Artesunate IV? This may also lead to the same impact on Hb.
With the exception of tremor, most of the Sal-related side effects you are mentioning above are just a direct result of Sal on normal cells and not tumor lysis related results. To my knowledge, these are sensations experienced when Sal acts against the tumors:
– If the tumors are large enough, the patient will feel pain at the tumor location.
– Regardless of the tumor size, if Sal kills cancer cells and the immune system is in a good shape to “learn and act”, there may be immune reactions leading to lysis that can be experienced as tremor. The tremor events can be short events coming and going, even days after the administration of Sal.
In my experience, slower administration of Sal will lead to decrease of side effects but I fell that also leads to a reduction of the anti cancer effects. It’s a trade off.
I wonder which Chemotherapy is your mother taking?
how are you ? I sent an email days ago , hope you and your mother are fine
my mother is taking a combination of Carboplatin and Gemzar
what about your mother ?
Thanks alot,she has bowel problems.Very big pains sometimes.There are tumors there,i hope they are not getting bigger,i hope chemo will work.On saturday we will see ca125.(it was 93 last count)
She takes chemo exactly same with your mother.But he add avastin and it makes her stomach painful.
Previous week we afraid of stomach or bowel bleeding.
I hope salinomycin will reduce the resistivity for your mother.Does it take weeks to show its efficacy?
I wonder if you try citric acid or not?and your opinions about it?It also helps to reduce resistivity.
I asked you chemo because i read that DCA doesnt help to all chemos on resistant cells.
Especially doesnt help cispilatin.Or modest.And DCA works best when given before chemo.
How many days before chemo do you give DCA?And do you give DCA in same day with salinomycin?
sorry for being with that kind of a doctors , hope he just can give benefits with working strategies not just laughing
until now I didn’t share anything about these treatments to any doctor , they just can’t thing out of the box
but after you return to chemo again I think you will see better results in coming days
I really wish the best for you brother
if we administrated Sal before 1 day from chemo or at the same day , would it boost the chemo effect ?
like inhibiting the ABC transporter ? if there is a high chance that it will boost the chemo effectiveness then we should consider it with chemo or before it, not just after it
May be your Dr has to change chemo.There should be another option.
Our dr changed carboplatin to oxaliplatin.And gemzar as you know.
But we met neuropathy for the first time.On hands and feet.
Avastin 1xmonth.
Are you using any antiangioegenesis inhibitor?
but for me I prefer to continue with (Gemzar + Carboplatin combination) there side effects are not so bad
my mother is always dealing with neuropathy , she is always taking B vitamins to help reduce the side effect
the tumor marker results today shows a very little decline from 334 to 322 !
like always , we used Chemo (Carboplatin and Gemzar) and DCA , also I have administrated Sal 3 times before chemo , and one other time after 1 week of chemo
and in all the times there was a marked tremor
the problem here is that blood counts are going down all the time , and with all this there is only little decline !?
I don’t know what to do ?
are there any mistake using DCA and Sal ? or maybe Salinomycin monosodium salt is not effective like the base version ?
or should I start using MG ? or should try Sal in the same day of chemo ?
I really don’t know what to do , very strange things are happening
So you are in the stable disease situation. Off course you want to be more effective than that, but that is not so bad in the end.
However, we can all think and generate ideas on what could be the way towards improving the results.
But in order to have good ideas, i suggest that you explain in a clear manner (which I know you can) where are the tumors located currently, tumor type, and the exact treatments you were doing during the past few months. Everything should be simple but aligned on a time line so that is clear, and connected to the markers.
You send me this overview, I make a post out of it, and we think together.
Just one point I wish to add now: according to the article I wrote recently, it makes sense to always add a little procaine IV just before DCA to increase DCA effectiveness. Actually only recently I found the reference indicating that but in 2014 when some large tumor has been melted away from my wife we were using DCA IV and Procaine IV just before that (in a German clinic). Only now I realized how good it was.
Kind regards,
Daniel
Perhaps Emad would have some idea?
Thanks
why don’t you buy it ?
is it financial problems ? or not able to have an email address of a university ? or you can’t administrate something like it ?
its not like I’m convincing you to give it , no , I can’t say to anyone to use it , its your responsibility , and when I use it , I took the responsibility by my self
but it feels comfortable to have some of these in your home , even just watching it without using it can make you feel better and more capable to stop the cancer
its just my thoughts
THanks
its frustrating indeed , but I’m mostly concerned about the financial problems
for me , 500 dollars monthly should be enough to access both 3-BP and Sal , and maybe you can even add what you used to add with your mother
the other 2 problems are used to be the biggest problems , but what I see is that they are so easy to solve , just having a plan to solve them will sure do the job
Second, i am not sure what other requirements are needed to be met to have the “pleasure” to pay that money for the treatments.
As for adminstering the treatments, i would get someone to do it, with a little help from you, thanks to your invaluable experience.
In the end we all want our mothers back in good health with a smile on their face. 🙂 So we best help each other as best we can.
Let us not forget the power of the mind.
https://www.youtube.com/watch?v=ztHa5h12ZsU
PS, if Morgan Freeman says it, it’s FACT! True Story Bro!
Now the fun side, https://www.youtube.com/watch?v=Maa0K4ycASo
Many Thanks,
Alex
did you talk to him ? or you can ask him to give you my email so I can answer in details
regarding administration , I think the better thing is to ask Daniel about it , I’m sure he will help
and btw , I loved the both videos , especially the second one I watched it more than once 😀
wish you the best
Only the issue is an email ending with edu in Romania as you know.
The others is easy ,we talked with Alex.
we should talk it private.
Kind Regards
Ergin
Many thanks for your monumental initiative.
This is a message regarding my mother’s breast cancer. She was diagnosed with ER-ve, PR-ve, Her2+ve breast cancer a year ago.During Feb-March this year she had integrative therapy in a Bangkok clinic which included various infusions, IPT and Hyperthermia, after which her tumor mass had reduced by around 70%. She was on supplements and vitamin c infusions during April and June. Since the markers were steadily moving, she tried Chlorine dioxide (MMS therapy) during the last three weeks after which the markers got elevated further. Together with ultrasound imaging, we are convinced that there is a progression of the disease again. We have not tried further chemo or Herceptin as yet since April 2017.
She is keen on trying Salinomycin (CAS Number 53003-10-4 ). We are hoping to get access although the dealer indicates that it is for research use only. If you think it is suitable, could you please let me know the dosage (she weighs 53 kgs) and procedure of making an IV out of it. Besides this, there is a rather ill-equippeed clinic which claims to sell 3BP in Bangalore. We are concerned about a lack of safe administration.
We have also thought of methylglyoxal (through Dr Manju Ray), but have deferred it fearing that she may not be able to use Metformin.
Her energy levels are not bad and she has been able to carry on with daily routine activities although her current appetite is around 70% of her usual intake. Her medical records can be accessed from the links in the PS below.
Any other advice would be also valuable. I would be happy to share any other information that you may require.
We had deferred Herceptin fearing its toxicity, but we are in a reconciliatory mood now.
Thanks,
Manju
I am glad to hear about the 70% tumor reduction. What were the IVs used during that time next to IPT and Hyperthermia? Also, please let us know the name of the clinic since others would like to know that too.
Regarding Salinomycin, I can share what I did in terms of formulation and administration. However, note that Sal can be dangerous if not used properly. Do you have a doctor that can support you with giving it?
Kind regards,
Daniel
Many thanks for your response. There are at least two integrative cancer clinics in Bangkok which are pretty similar. One is Absolute Health and the other is Verita Life. Mom was at Verita Life. Infusion list comprises Vitamin C, B17, Sodium Selenite, Artesunate, DCA, Curcumin, ALA, L-Carnitine besides with Ozone therapy.
We know a doctor (not an oncologist) who does vitamin C and B17 infusions locally. So am sure, that Sal would be used professionally, and hence please educate on the Sal IV preparation. Also, since the CEA marker which was showing a downward trend has reversed direction and risen from 11 to 45 in the last six weeks. Hence she has started on a low dose Capecitabine (Xeloda) since a week. From what I understand from the readings on this site, Sal has no issues with low dose chemo, but would it be wise to use Metformin and Methylglyoxal in addition? In particular, if there is an unfavorable interaction between Metformin and Methylglyoxal, which one would be a stronger one given that she has tried Metformin for 5 months now? I await your kind response. Thanks again.
Kind Regards,
Manju
Further to my previous message, is capecitabine (500 mg twice a day) a strong enough chemo to go along with Sal? Thanks again!
Was this the Brio clinic in Bangkok?
I noticed on their webpage that they offer 3-BP treatment.
If you went to the Brio clinic, was this treatment offered?
I have suggested this formulation of MG to others. If you might have the ability to synthesize it, then it might
be of help.
Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect
https://science.institut-curie.org/cancer-stem-cells-iron-translocation-and-new-therapeutic-strategy/
i have some questions,i ve read you were delaying the chemo/3bp/saly etc whenever your mom red blood were down.
1/the whit blood cells were at the maximum at that time right?
if the wbc are high that s mean there is immune activity (wich is probably cleaning and killing cancer cells)
2/what did you do to increase the red blood?
3/what are the risks if you do the perfusion when the rbc are down?
thanks in advance for your reply
1- no not at the maximum , but they were better than HB and Platelets , I am not sure why they are better but I didn’t notice anything special
2- at first we did give my mother a lot of supplements , natural and pharmaceutical , but at certain point the HB continues to drop after every chemo cycle , and then we decided to do blood transfusion which I believe it made cancer somehow more aggressive ! , DCA and chemo combination used to shrink the tumor , after doing blood transfusion it barely make it stable !!!
I’m not sure if its really because of blood transfusion but the real thing is that the resistance and aggressiveness started at the same time with doing transfusions
3- if you have a cancer patient that will do blood transfusion then maybe its better to do the transfusion at the end of the cycle , and do chemo after 2 days at least from the transfusion , also don’t do any transfusion after chemo at the beginning of the cycle , it may interrupt the chemo and make it weak , I remember when my mother did transfusion after 2 days of chemo , there was no effect at all , and the tumor markers jumped like a rocket from 322 to 650 in 1 month !
also if its possible to give anti-angiogenesis when doing transfusion it may help to not make cancer aggressive , in anyway the aggressiveness should happen temporarily , thanks to Ovidiu (our friend in this blog) he did talk about this thing
also to note , there are some chemo drugs like Gemzar and Carboplatin that cause the HB , RBCs and platelets to drop , but there are others which are more tolerable and will not cause the same problem
tell me if you have any other question , wish you the best
thank you for your detailed reply
i have few more questions for you and members:
1/can we make a solution of sal with dmso? as i know it s not possible with sterile water or nacl
2/do you think it can be better if we inject it directly to the tumours (or nearby)
3/does you mother have swelling of the abdomen after the sal or the 3bp?
thanks in advance
1- I didn’t try dmso but it may dissolve it at the beginning but then it will precipitate , I asked the same question to Daniel before
2- I really don’t have any idea about this one , but also Daniel may have
3- no, there is no observed side effects when using 3-BP , with Salinomycin the side effects are mainly tremor , and sometimes feeling things around becoming darker or brighter , increased heart rate and a little bit of tiredness (all are gone in less than 2 hours)
any other question please ask , i will be happy if my answers are helping
i have sent you the email on your website email address.
let me know
thanks
I haven’t received the e-mail. Probably you sent that to the other e-mail. Can you please send the e-mail again to the Gmail address listed on the Contact page? Thank you.
Kind regards,
Daniel
forwarded to the gmail adress
thanks
I found an article about comparison study of the cytotoxicity of salinomycin and salinomycin sodium toward human breast cancer stem cells as well as breast cancer cells.But i couldnt send the message,i think it is went to trash.
In summary, there is no difference on efficiency with x10 cheaper salt version.
Kind Regards
Ergin
http://en.cnki.com.cn/Article_en/CJFDTOTAL-XYGZ201104010.htm
Sal is working on ROS generation,3BP is working on OXPHOS inhibition partly if it is true ofcourse.
Sometimes ago i gave a link here,it says in glycolitic enviorement ROS works better.
When i find it i will give the link again.
And here is an example of a paper indicating the pro oxidant nature of 3BP https://www.nature.com/cgt/journal/v19/n1/full/cgt201159a.html you can read the discussions section on potential mechanisms that lead to generatio of hydrogen perox.
There is no doubt 3BP acts in a prooxidant manner in cancers, also based on personal experience.
I dont understand from several days that why we inhibit both oxphos and glucose in lots of article.And Is there a limit of ROS?.For example modest levels feed cancer or not?
ROSelevating and ROS-depleting.
Glycolitic inhibitor is must but what about ROS?
And there is a relationship with antioxidant,oxidant and different in cell types.
Highly confused:)
There is much more then that but in simple words:
– mitochondrial respiration (OXPHOS) leads to energy production but also increased ROS production
– increased ROS would lead to cancer cell death
– so the cell needs to increase antioxidant production to fight ROS
– and does that by e.g. upregulating glycolisis which in turn helps not only to generate energy for the cell but also generate NADPH which is a critical cofactor for the maintenance of glutathione (GSH)
here is more about that: https://www.ncbi.nlm.nih.gov/books/NBK22389/
– this means that when you block glucose entering the cell, there will be less capability to produce antioxidants
– if the cell is still eating, it has to do that via mitochondria (OXPHOS or respiration) which is an oxidative process and so will produce ROS
– since it needs more energy then the normal cell, it will produce more ROS
– but if no glucose, then also less antioxidant production and so this will put an oxidative pressure on the cell
– if now you further add treatments that are oxidative, like chemo or 3BP you will add extra oxidative pressure
In summary, this is about the balance of oxidant vs anti oxidant process in the cell in simple terms: the point is that cancer cells, because they need to divide fast they need to produce more energy but the side effect of that is that they also produce ROS which they need to cancel – this is why they will be more sensitive to the pro oxidant therapies compared to normal cells.
Therefore, anti oxidant therapies will be more preventive therapies focused on supporting normal cell function. While when you treat existing tumors, pro oxidant therapies are the way to go. I think.
Again this speaking from oxidant/antioxidant perspective.
Because we can also speak from the energy blocking perspective. Or from cholesterol blocking perspective. Or from pH perspective. And so on …. since cancer cells are sensitive to many other aspects, more then the normal cells.
Some application of the points from above on what we already know:
In the context of the picture above, you can imagine that DCA, which will start up mitochondria (if that not working properly) will lead to ROS production. But also more energy production.
On the other hand, Metformin which slows down mitocondria while reduce the ROS but will also stop energy production in the cell.
When stopping glycolisis, we will stop energy production on this path, but not necessarily Glutathion production support, since that is dependede on one of the first Glycolisis steps. And various inhibitors of glyco can stop glyco at various steps. But when we stop Glucose entering the cell like with Phlorezin (and less with ketogenic diet), we really stop both energy production via Glyco but also Gluthathion support. That will support 2x Chemo because you stop two important mechanism that are used to fight Chemo.
Using glyco and mito inhibitors is an energy strategy. Eg. 3BP+Metformin and others.
Using proxidant activators is an oxidant strategy. Eg. 3BP+DCA+Chemo+Paracetamol and others.
I was writing fast, so I hope is clear enough and helps to clarify a bit.
Kind regards,
Daniel
I am also wondering after phlorizination how can we give premedication before chemo?Does it contains glucose?
Why my mothers blood glucose goes high after administration?
Do you have an idea?
Daniel thanks again
Kind Regards
Ergin
Can you please reformulate your question? Is not clear for me what you mean. Are you using Phlorezin already with your doctor?
Kind regards,
Daniel
I think a very important problem that we have to solve.
https://www.cancertreatmentsresearch.com/phlorizinphloretin-a-strong-glucose-transport-inhibitor/#comment-5803
Kind Regards
Ergin