Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Page 2 of 2 Previous  1, 2

Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Sat Mar 31, 2018 1:29 am

Mitochondrial Uncoupling and the Warburg Effect: Molecular Basis for the Reprogramming of Cancer Cell Metabolism
Ismael Samudio, Michael Fiegl and Michael Andreeff
DOI: 10.1158/0008-5472.CAN-08-3722 Published March 2009

Abstract

The precise mitochondrial alterations that underlie the increased dependence of cancer cells on aerobic glycolysis for energy generation have remained a mystery. Recent evidence suggests that mitochondrial uncoupling—the abrogation of ATP synthesis in response to mitochondrial membrane potential—promotes the Warburg effect in leukemia cells, and may contribute to chemoresistance. Intriguingly, leukemia cells cultured on bone marrow–derived stromal feeder layers are more resistant to chemotherapy, increase the expression of uncoupling protein 2, and decrease the entry of pyruvate into the Krebs cycle—without compromising the consumption of oxygen, suggesting a shift to the oxidation of nonglucose carbon sources to maintain mitochondrial integrity and function. Because fatty acid oxidation has been linked to chemoresistance and mitochondrial uncoupling, it is tempting to speculate that Warburg's observations may indeed be the result of the preferential oxidation of fatty acids by cancer cell mitochondria. Therefore, targeting fatty acid oxidation or anaplerotic pathways that support fatty acid oxidation may provide additional therapeutic tools for the treatment of hematopoietic malignancies. [Cancer Res 2009;69(6)–6]

The Warburg Effect and Mitochondrial Uncoupling

More than half a century ago, Otto Warburg ( 1) proposed that cancer cells originated from non-neoplastic cells acquired a permanent respiratory defect that bypassed the Pasteur effect, i.e., the inhibition of fermentation by oxygen. This hypothesis was based on results of extensive characterization of the fermentation and oxygen consumption capacity of normal and malignant tissues—including mouse ascites and Earle's cells of different malignancies but same genetic origin—that conclusively showed a higher ratio of fermentation to respiration in the neoplastic cells. Moreover, the data indicated that the more malignant Earle's cancer cells displayed a higher ratio of fermentation to respiration than their less malignant counterparts, suggesting to Warburg and his colleagues that a gradual and cumulative decrease in mitochondrial activity was associated with malignant transformation. Interestingly, the precise nature of these gradual and cumulative changes has eluded investigators for nearly 80 years, albeit Warburg's observations of an increased rate of aerobic glycolysis in cancer cells have been reproduced countless times—not to mention the wealth of positron emission tomography images that support an increased uptake of radiolabeled glucose in tumor tissues.

It is noteworthy that although Warburg's hypothesis remains a topic of discussion among cancer biologists, Otto Warburg himself had alluded to an alternative hypothesis put forth by Feodor Lynen—one which did not necessitate permanent or transmissible alterations to the oxidative capacity of mitochondria—that suggested the possibility that the increased dependence of cancer cells on glycolysis stemmed not from their inability to reduce oxygen, but rather from their inability to synthesize ATP in response to the mitochondrial proton gradient (ΔΨM; ref. 1). Lynen's hypothesis was partly based on his work ( 2) and the previous work of Ronzoni and Ehrenfest ( 3) using the prototypical protonophore 2,4-dinitrophenol, which causes a “short circuit” in the electrochemical gradient that abolishes the mitochondrial synthesis of ATP, and decreases the entry of pyruvate into the Krebs cycle. Subsequent work showed that mitochondrial uncoupling (i.e., the abrogation of ATP synthesis in response to ΔΨM) results in a metabolic shift to the use of nonglucose carbon sources to maintain mitochondrial function ( 4, 5). Given the elusiveness of permanent transmissible alterations to the oxidative capacity of cancer cells that could broadly support Warburg's hypothesis, could Lynen's hypothesis better explain the dependence of cancer cells on glycolysis for ATP generation?

Over the past several decades, it has become increasingly clear that mitochondrial uncoupling occurs under physiologic conditions, such as during cold acclimation in mammals, and is mediated, at least in part, by uncoupling proteins (UCP; ref. 6, 7). UCP1 was the first UCP identified, and was shown to play a role in energy dissipation as heat in mammalian brown fat ( 6). During cold acclimation, UCP1 accumulates in the inner mitochondrial membrane and short circuits ΔΨM (created by the mitochondrial respiratory chain) by sustaining an inducible proton conductance ( 7). Other UCPs have been identified in humans (UCP2-4), although their functions may be unrelated to the maintenance of core body temperature, and instead involved in the reprogramming of metabolic pathways. For instance, recent work shows that UCP2 is necessary for efficient oxidation of glutamine ( Cool, and may promote the metabolic shift from glucose oxidation to fatty acid oxidation ( 4). Likewise, UCP3 has also been shown to promote fatty acid oxidation in muscle tissue via, in part, an increased flux of fatty acid anions ( 9); however, such as for UCP2, the nature of its proton conductance remains controversial (reviewed in ref. 10). More interesting, perhaps, are recent observations that UCP2 is overexpressed in various chemoresistant cancer cell lines and primary human colon cancer, and that overexpression of this UCP leads to an increased apoptotic threshold ( 11), suggesting that in addition to metabolic reprogramming, UCPs may ipso facto provide a prosurvival advantage to malignant cells.

It is important to point out that physiologic fatty acid oxidation has been shown to be associated with an uncoupling and/or thermogenic phenotype in various cell types (reviewed in ref. 12). In addition, it is also significant that glycolysis-derived pyruvate, as well as α-ketoglutarate derived from glutaminolysis, may be necessary to provide anaplerotic substrates (i.e., those that replenish intermediates in metabolic cycles) for efficient Krebs cycle use of fatty acid-derived acetyl CoA ( 13), suggesting the possibility that in certain cell types, high rates of aerobic glycolysis may be necessary for efficient mitochondrial oxidation of fatty acids (“fats burn in the fire of carbohydrates”). The above support the concept—and indirectly, Lynen's hypothesis—that the Warburg effect may, in fact, be the result of fatty acid and/or glutamine oxidation in favor of pyruvate use.

Mitochondrial Uncoupling in Leukemia Cells


We have recently reported that leukemia cells cultured on bone marrow–derived mesenchymal stromal cells (MSC) show increased aerobic glycolysis and reduced ΔΨM ( 14). A priori we hypothesized that MSC decreased mitochondrial function in leukemia cells; however, our experiments revealed that the oxygen consumption capacity of leukemia cells was not affected and, in fact, displayed a transient (∼6–8 h) increase after exposure to MSC. In addition, leukemia cells cultured on MSC were less sensitive to the ΔΨM-dissipating effects of oligomycin and, as previously reported ( 15, 16), more resistant to apoptosis induced by a variety of chemotherapeutic agents, suggesting that leukemia cells cultured on MSC feeder layers were displaying a prosurvival mitochondrial metabolic shift, rather than a compromised mitochondrial function. Additionally, it was observed that in contrast to hypoxia (∼6% oxygen), which markedly increased the uptake of glucose, and a fluorescent glucose derivative from the medium, MSC feeder layers did not increase the uptake of glucose in leukemia cells, further supporting the notion that the increased accumulation of lactate in the medium of MSC-leukemia cocultures is indicative of reduced entry of pyruvate into the Krebs cycle of leukemia cells.

Because the above observations supported the possibility that MSC may induce mitochondrial uncoupling in leukemia cells, we investigated whether MSC feeder layers were modulating the expression of UCPs (UCP1–4). We observed that leukemia cells only expressed UCP2 and that MSC induced pronounced accumulation of this UCP. Surprisingly, siRNA silencing of UCP2 expression did not completely overcome the dissipation of ΔΨM induced by MSC, albeit decreased expression of this protein markedly decreased the accumulation of lactate in the medium of MSC-leukemia cocultures. Moreover, although leukemia cells rapidly lost ΔΨM when exposed to MSC feeder layers (∼30 minutes), maximal expression of UCP2 did not occur until 24 to 48 hours after coculture, and conversely, the rapid dissipation of ΔΨM was insensitive to inhibition of protein synthesis with cycloheximide. Taken together, the above results suggest that although UCP2 expression may contribute to the observed loss of ΔΨM, it is likely that other factor(s) may initiate the dissipation of the electrochemical gradient; however, the data reported support the notion that UCP2 is indeed involved in metabolic reprogramming away from the oxidation of pyruvate, a phenomenon that may, in turn, facilitate the maintenance of a reduced ΔΨM.

Our data using the protonophore CCCP also supported the notion that, at least in leukemia cells, dissipation of the proton gradient per se opposed the onset of apoptosis. Likewise, MSC feeder layers protected OCI-AML3 cells from apoptosis, but not the growth inhibitory effects of mitoxanthrone, AraC, and vincristine. It is noteworthy that leukemia cells that did not increase the expression of UCP2 when cultured with MSC feeder layers did not increase lactate generation, did not dissipate ΔΨM, and were not protected from the cytotoxic effects of chemotherapy when cultured with MSC, suggesting that the observed metabolic reprogramming in OCI-AML3 cells is associated with chemoresistance. It is thus provoking to speculate that targeting UCP2, as well as the metabolic reprogramming involved in initiating and maintaining the dissipation of ΔΨM (increased glutamine and/or fatty acid metabolism, etc.), could be exploited therapeutically to overcome microenvironment-induced chemoresistance.

Implications of Mitochondrial Uncoupling


The metabolic shift from the oxidation pyruvate to the uncoupled oxidation of glutamine or fatty acids highlights two critical concepts. First, glycolysis remains the critical pathway by which cancer cells meet their energy demands, not because of permanent transmissible alterations to the oxidative capacity of cells, but rather because of the inability of uncoupled mitochondria to generate ATP. Second, the continued reduction of oxygen, in the absence of pyruvate oxidation, suggests that anaplerotic reactions from nonglucose carbon skeletons must be replenishing critical intermediates from the Krebs cycle—reactions that may be amenable to therapeutic intervention, and that may critically depend on highly conserved UCPs—to in turn support the oxidation of fatty acids or glutamine ( Fig. 1 ). Curiously, anaplerotic reactions have recently been reported to support the activity of the Krebs cycle in glioma cells ( 17), which use most of their glutamine carbon skeletons to regenerate α-ketoglutarate, while at the same time using glucose carbon skeletons to synthesize fatty acids. Moreover, the required NADPH (the biosynthetic reducing equivalent) for fatty acid synthesis was provided by conversion of glutamate-derived malate to pyruvate and, to a lesser extent, from the activity of the pentose phosphate shunt, further highlighting the importance of glutamine metabolism via the Krebs cycle ( 17). In the above study, it was evident that the metabolism of glucose was largely anaerobic, although the cells maintained the ability to consume oxygen, as well as an active Krebs cycle, suggesting the possibility that mitochondrial uncoupling and UCPs may promote the observed metabolic pattern.

Figure 1.Figure 1.

   Download figureOpen in new tabDownload powerpoint

Figure 1.

Mitochondrial uncoupling mediates the metabolic shift to aerobic glycolysis in cancer cells. A, coupled mitochondria (blue) oxidize pyruvate through the Krebs cycle. B, uncoupled mitochondria (orange) display a metabolic shift to the oxidation of other carbon sources, supported in part by fatty acid and glutamine metabolism that may depend on UCP2 expression. C, uncoupled mitochondria are more resistant to cytotoxic insults and oppose the activation of the intrinsic apoptotic pathway.

Notably, a recent report showed that the entry of pyruvate into the Krebs cycle, via pyruvate dehydrogenase, is supressed in cancer cells, and that the reactivation of pyruvate dehydrogenase activity by dichloroacetate induced cell death in several solid tumor cell lines and xenografts ( 18), supporting the notion that mitochondrial glucose oxidation may be incompatible with cancer cell survival. Likewise, it is interesting that pharmacologic inhibition of fatty acid oxidation has been shown to potentiate apoptosis induced by a variety of chemotherapeutics in cancer cell lines ( 19), as well as palmitate-induced apoptosis in hematopoietic cells ( 20), suggesting a priori that the metabolism of fatty acids in the mitochondria may be linked to cell survival. In light of the above, it is intriguing to propose that targeting the mitochondrial metabolism of fatty acids and/or glutamine may hold therapeutic promise for the treatment of human malignancies. Conversely, given the important role of UCPs in the metabolic shift associated with increased fatty acid and glutamine metabolism in favor of glucose oxidation, it would be of great interest to develop therapeutic strategies that targeted these proteins.

http://cancerres.aacrjournals.org/content/69/6/2163.long


Also:

https://themedicalbiochemistrypage.org/glycolysis.php

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Sat Mar 31, 2018 10:34 pm

Apparent mouse cure for Lymphoma:
-----
A Cancer 'Vaccine' Cured 97% of Tumors in Mice. What's That Mean for People?
By Rachael Rettner, Senior Writer | March 29, 2018 07:13am ET

https://www.livescience.com/62161-cancer-vaccine-trial.html (more at link...)


A Cancer 'Vaccine' Cured 97% of Tumors in Mice. What's That Mean for People?

Credit: Shutterstock

A promising new cancer "vaccine" that cured up to 97 percent of tumors in mice will soon be tested in humans for the first time — but experts say that we're still a long way off from this type of drug being prescribed to cancer patients.

Researchers from Stanford University will test the therapy in about 35 people with lymphoma by the end of the year, according to SFGate, a local news outlet in San Francisco. The treatment stimulates the body's immune system to attack cancer cells. In studies in mice with various cancers — including lymphoma, breast cancer and colon cancer — the treatment eliminated cancer tumors in 87 out of 90 mice, even when the tumors had spread to other parts of the body, the researchers said.

Dr. Alice Police, the regional director of breast surgery at Northwell Health Cancer Institute in Westchester, New York, who was not involved in the study, said that the news of a human trial to test this treatment is "exciting." However, she cautioned that results in animal studies don't always translate to people.

"We've been able to cure a lot of cancers in mice for a long time," Police told Live Science. What's more, the current human trials are for patients with lymphoma, and so it could be many years before doctors know if this treatment works for other cancers, such as breast and colon cancer, Police said. [10 Do's and Don'ts to Reduce Your Risk of Cancer]

A cancer vaccine?

The new treatment is not technically a vaccine, a term used for substances that provide long-lasting immunity against disease. But the treatment does involve a vaccine-like injection, SFGate reported. (According to the American Society of Clinical Oncology, a "cancer vaccine" can refer to a treatment that's used to prevent cancer from coming back and destroys cancer cells that are still in the body.)

Instead, the treatment is a type of immunotherapy. It contains a combination of two agents that stimulate T cells, a type of immune cell, to attack cancer. Normally, the body's T cells recognize cancer cells as abnormal and will infiltrate and attack them. But as a tumor grows, it suppresses the activity of the T cells so that these cells can no longer keep the cancer at bay.

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Sun Apr 01, 2018 11:39 pm

Makes me wonder how Ayahuasca and Syrian Rue work in the brain?  Perhaps they suppress this generation of the MIF in the pituitary gland?
---------
QJM. 2010 Nov; 103(11): 831–836.
Published online 2010 Aug 30. doi:  10.1093/qjmed/hcq148
PMCID: PMC2955282
PMID: 20805118

Inflammation and cancer: macrophage migration inhibitory factor (MIF)—the potential missing link
H. Conroy, L. Mawhinney, and S. C. Donnelly

Author information ► Copyright and License information ► Disclaimer
This article has been cited by other articles in PMC.

Abstract


Macrophage migration inhibitory factor (MIF) was the original cytokine, described almost 50 years ago and has since been revealed to be an important player in pro-inflammatory diseases. Recent work using MIF mouse models has revealed new roles for MIF. In this review, we present an increasing body of evidence implicating the key pro-inflammatory cytokine MIF in specific biological activities related directly to cancer growth or contributing towards a microenvironment favouring cancer progression.
...
The discovery that MIF was secreted from corticotrophic pituitary cells led to its classification as a hormone as well as a cytokine. Its release coincides with, and is induced by adrenocorticotrophic hormone and its ability to override the anti-inflammatory effects of this hormone suggested an inbuilt regulatory mechanism.9 This ability to promote inflammation while hindering the anti-inflammatory effects of glucocorticoids was implicated in the pathogenesis of acute respiratory distress syndrome (ARDS).12 Direct association between MIF expression levels and degrees of disease pathogenesis in a number of inflammatory diseases was revealed through analysis of genetic variation within the MIF gene.13–15 Allelic variation within a repeat region found upstream of the MIF promoter, determines efficiency of expression of the protein. Individuals carrying five copies of the CATT repeat element were found to display lower MIF levels, with those possessing increasing numbers of repeats (6, 7 or 8 ) having a corresponding increase in expression. In cystic fibrosis patients, this increase in MIF production associated with carrying the 6 and 7 repeat variants was associated with enhanced end-organ injury. Rheumatoid arthritis patients carrying the 6 and 7 repeat variants had both higher basal levels of MIF and higher levels following stimulation with forskolin or serum. The higher levels of MIF associated with this particular variant also correlated with progressive disease.16 In relation to malignant diseases, individuals carrying the seven-repeat allele were also found to have an increased incidence of prostate cancer.17 MIF biological activity has also been implicated in the pathogenesis of atherosclerosis and abdominal aortic aneurysm.18 In the context of atherosclerosis, MIF has also been identified as a non-cognate receptor of CXCR2 and CXCR4 and has functional chemokine activity in evolving atherosclerosis mediating monocyte arrest and the formation of plaques.19 Additionally, as part of this disease process MIF can induce the CXCR ligand, Interleukin (IL)-8 and regulators of macrophage infiltration ICAM-1 and CD44, confirming its relevance in this disease.20

Mounting evidence suggests that inflammation is closely associated with many types of cancer. 21 Inflammatory pathways designed to defend against infection and injury can promote an environment which favours tumour growth and metastasis. Chronic inflammatory conditions and infections have been directly linked to specific cancers, see Table 1. Supporting this observation, treatment with non-steroidal anti-inflammatory drugs has been shown to reduce the risk of developing colon cancer.22 Consequently, there is heightened interest both within academia and industry, to define key regulatory events within the inflammatory process which predispose individuals to enhanced cancer risk. This would provide the rational for significant investment in these high-value therapeutic targets for drug development.
MIF and cancer

MIF’s unique biological activities have the potential to contribute to an in vivo microenvironment favouring tumour growth and invasiveness. These functional activities include: tumour suppressor downregulation, COX-2 and PGE2 upregulation, potent induction of angiogenesis and enhanced tumour growth, proliferation and invasiveness (summarized in Table 2).

Table 2

MIF biological activities which favour tumour pathogenesis
MIF functional activities Role in tumourigenesis
P53 inhibition Accumulation of mutation
Inhibition of apoptosis
Proliferation of cells
Sustained ERK activation Promotes invasion
Inhibits cell death
COX-2/PGE-2 induction Tumour Growth
Viability
Metastasis
Endothelial cell proliferation and differentiation Promotes angiogenesis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955282/

.......

Hypoxia stimulates the expression of macrophage migration inhibitory factor in human vascular smooth muscle cells via HIF-1α dependent pathway


   Hua Fu1, 2, Fengming Luo2, 3, Li Yang4, Wenchao Wu2 and Xiaojing Liu2Email author
BMC Cell Biology201011:66
https://doi.org/10.1186/1471-2121-11-66

©️  Fu et al; licensee BioMed Central Ltd. 2010
Received: 21 April 2010
Accepted: 20 August 2010
Published: 20 August 2010

Abstract

Background

Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells (VSMC) functions. Macrophage migration inhibitory factor (MIF) is a well known proinflammatory factor, and recent evidence suggests an important role of MIF in the progression of atherosclerosis and restenosis. However, the potential link between hypoxia and MIF in VSMC has not been investigated. The current study was designed to test whether hypoxia could regulate MIF expression in human VSMC. The effect of modulating MIF expression on hypoxia-induced VSMC proliferation and migration was also investigated at the same time.

Results

Expression of MIF mRNA and protein was up-regulated as early as 2 hours in cultured human VSMCs after exposed to moderate hypoxia condition (3% O2). The up-regulation of MIF expression appears to be dependent on hypoxia-inducible transcription factor-1α(HIF-1α) since knockdown of HIF-1α inhibits the hypoxia induction of MIF gene and protein expression. The hypoxia induced expression of MIF was attenuated by antioxidant treatment as well as by inhibition of extracellular signal-regulated kinase (ERK). Under moderate hypoxia conditions (3% O2), both cell proliferation and cell migration were increased in VSMC cells. Blocking the MIF by specific small interference RNA to MIF (MIF-shRNA) resulted in the suppression of proliferation and migration of VSMCs.

https://bmccellbiol.biomedcentral.com/articles/10.1186/1471-2121-11-66

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Tue Apr 03, 2018 1:53 am


Uncoupling protein-2 modulates the lipid metabolic response
www.jimmunol.org/content/183/10/6313.full.pdf
http://www.physiology.org/doi/full/10.1152/ajpgi.00016.2008
....
UCP2 Regulates the Glucagon Response to Fasting and Starvation

Emma M. Allister1, Christine A. Robson-Doucette1, Kacey J. Prentice1, Alexandre B. Hardy1, Sobia Sultan1, Herbert Y. Gaisano1, Dong Kong2, Patrick Gilon3, Pedro L. Herrera4, Bradford B. Lowell2 and Michael B. Wheeler1⇑

Corresponding author: Michael B. Wheeler, michael.wheeler{at}utoronto.ca.

Diabetes 2013 May; 62(5): 1623-1633. https://doi.org/10.2337/db12-0981


Abstract

Glucagon is important for maintaining euglycemia during fasting/starvation, and abnormal glucagon secretion is associated with type 1 and type 2 diabetes; however, the mechanisms of hypoglycemia-induced glucagon secretion are poorly understood. We previously demonstrated that global deletion of mitochondrial uncoupling protein 2 (UCP2−/−) in mice impaired glucagon secretion from isolated islets. Therefore, UCP2 may contribute to the regulation of hypoglycemia-induced glucagon secretion, which is supported by our current finding that UCP2 expression is increased in nutrient-deprived murine and human islets. Further to this, we created α-cell–specific UCP2 knockout (UCP2AKO) mice, which we used to demonstrate that blood glucose recovery in response to hypoglycemia is impaired owing to attenuated glucagon secretion. UCP2-deleted α-cells have higher levels of intracellular reactive oxygen species (ROS) due to enhanced mitochondrial coupling, which translated into defective stimulus/secretion coupling. The effects of UCP2 deletion were mimicked by the UCP2 inhibitor genipin on both murine and human islets and also by application of exogenous ROS, confirming that changes in oxidative status and electrical activity directly reduce glucagon secretion. Therefore, α-cell UCP2 deletion perturbs the fasting/hypoglycemic glucagon response and shows that UCP2 is necessary for normal α-cell glucose sensing and the maintenance of euglycemia.

Elevated basal glucagon levels and reduced hypoglycemia-induced glucagon secretion are underappreciated and poorly understood aspects of type 1 and type 2 diabetes (1–3). Although high plasma glucose normally inhibits glucagon secretion, it remains unclear whether this in vivo response is mediated by glucose sensing, neuronal modulation, paracrine/endocrine control, or a combination thereof (4–10). Uncoupling protein 2 (UCP2), an inner mitochondrial membrane protein, is expressed in pancreatic α-cells (11), and its expression can be induced in adipose tissue by a ketogenic diet (12), suggesting a role in the fasting response. While the precise physiological function of UCP2 in islet cells is still debated, it can mildly dissipate the proton motive force generated during mitochondrial electron transport and limit ATP synthesis under certain conditions (13–15). Additionally, UCP2 can limit mitochondrial reactive oxygen species (ROS) production, which can alter associated signaling pathways and/or protect against oxidative stress (16–18). In β-cells, UCP2 deletion elicits only small changes in mitochondrial membrane potential (ΔΨm) with limited effect on ATP (18,19) but rather increases ROS production, which amplifies insulin secretion (18,20). α-Cells, like β-cells, have glucose-sensing machinery that center on KATP channel activity, cellular depolarization, and calcium influx, triggering exocytosis; however, unlike β-cells, they are electrically active and secretory at low glucose concentrations (5,21–24). UCP2 in α-cells could therefore be an important regulator of glucagon secretion via regulation of ATP production, plasma membrane potential, and ROS levels.

Previously, we showed that islets from mice globally lacking UCP2 (UCP2−/−) displayed higher basal glucagon secretion and impaired low glucose–mediated glucagon secretion (11). Due to UCP2’s wide expression profile in glucose-sensitive tissues, these changes in α-cell function in UCP2−/− mice could be the result of β-cell and/or extra-pancreatic deletion. To decipher the role of UCP2 in α-cells and in the response to fasting, we created an α-cell–specific UCP2 knockout (UCP2AKO) deletion mouse model. These mice displayed reduced fasting plasma glucagon levels and impaired glucagon secretion, due in part to elevated ROS, enhanced glucose-induced hyperpolarization of the ΔΨm, and depolarization of plasma membrane potential. Therefore, we conclude that α-cell UCP2 plays a key role in the hypoglycemic response.

(more at link...)

http://diabetes.diabetesjournals.org/content/62/5/1623

......


UCP2 is highly expressed in pancreatic α-cells and influences secretion and survival

Jingyu Diao, Emma M. Allister, Vasilij Koshkin, Simon C. Lee, Alpana Bhattacharjee, Christine Tang, Adria Giacca, Catherine B. Chan and Michael B. Wheeler
PNAS August 19, 2008. 105 (33) 12057-12062; https://doi.org/10.1073/pnas.0710434105

Edited by Donald F. Steiner, University of Chicago, Chicago, IL, and approved May 21, 2008

↵*J.D. and E.M.A. contributed equally to this work. (received for review November 6, 2007)

Abstract

In pancreatic β-cells, uncoupling protein 2 (UCP2) influences mitochondrial oxidative phosphorylation and insulin secretion. Here, we show that α-cells express significantly higher levels of UCP2 than do β-cells. Greater mitochondrial UCP2-related uncoupling was observed in α-cells compared with β-cells and was accompanied by a lower oxidative phosphorylation efficiency (ATP/O). Conversely, reducing UCP2 activity in α-cells was associated with higher mitochondrial membrane potential generated by glucose oxidation and with increased ATP synthesis, indicating more efficient metabolic coupling. In vitro, the suppression of UCP2 activity led to reduced glucagon secretion in response to low glucose; however, in vivo, fasting glucagon levels were normal in UCP2−/− mice. In addition to its effects on secretion, UCP2 played a cytoprotective role in islets, with UCP2−/− α-cells being more sensitive to specific death stimuli. In summary, we demonstrate a direct role for UCP2 in maintaining α-cell function at the level of glucose metabolism, glucagon secretion, and cytoprotection.

ATP glucagon islet mitochondria diabetes

Blood-glucose levels are tightly regulated by the islet hormones insulin and glucagon. Insulin is secreted from β-cells when glucose levels are high to increase glucose utilization, whereas glucagon is secreted from α-cells when glucose levels are low to elevate blood glucose. It is well established that β-cell dysfunction, resulting in a lack of insulin secretion, is a key event in the development of hyperglycemia that is associated with both type 1 and 2 diabetes (1, 2). In type 2 diabetes, β-cell dysfunction can in part be explained by the loss of proper glucose sensing, leading to abnormal insulin secretion. However, in both forms of diabetes, glucagon secretion can be dysregulated during hyper- and hypoglycemia (3, 4), suggesting that glucose sensing by the α-cell is also impaired. For this reason, it is important to understand mechanistically how glucagon is regulated by glucose in normal and diseased states.

High plasma levels of glucose inhibit glucagon secretion; however, it is still unclear whether this in vivo response is mediated directly via glucose sensing or indirectly by neuronal modulation and/or paracrine/endocrine effects (5–Cool. Pancreatic α-cells, like β-cells, possess ATP-dependent K+ (KATP) channels; however, the metabolism/oxidation of glucose resulting in closure of the KATP channels causes inhibition of glucagon secretion (9, 10). It is suggested that N-type Ca2+ channels modulate this alternate excitability downstream of KATP-channel closure (10). Glucose metabolism in α-cells generates a proton-motive force (pmf) in the inner mitochondria that drives the synthesis of ATP via ATP synthase. Uncoupling proteins (UCPs) are mitochondrial carrier proteins that can dissipate the proton gradient to prevent the pmf from becoming excessive when there is nutrient overload, which can reduce reactive oxygen species (ROS) produced by electron transport (11). There are five mitochondrial UCP homologues in mammals (12). The closely related UCPs are UCP1–3. UCP1 is mainly expressed in brown adipose tissue and UCP3 in muscle and adipose tissue, whereas UCP2 has been found in liver, brain, pancreas, and adipose tissue and immune cells (13, 14). Specifically, UCP2 is expressed in pancreatic islets where its β-cell overexpression increases mitochondrial uncoupling, decreases mitochondrial membrane potential (ΔΨm), reduces mitochondrial ROS production and cytoplasmic ATP content, and therefore attenuates glucose stimulated insulin secretion (GSIS) by antagonizing the KATP-channel pathway (15–17). Uncoupling processes have not been studied in α-cells where they could regulate ATP production and glucagon secretion. UCP2 may be cytoprotective in some cell types, such as macrophages, cardiomyocytes, and neurons (18, 19), and thus expression of UCP2 in α-cells may modulate susceptibility to stress stimuli and influence cell survival (20). This study aims to identify whether UCP2 is expressed in α-cells, and if so, to characterize the role it plays in regulating glucagon secretion and cell survival.

(more at link...)

http://www.pnas.org/content/105/33/12057.long

...

Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization

Claire Pecqueur
, Thi Bui
, Chantal Gelly
, Julie Hauchard
, Céline Barbot
, Frederic Bouillaud
, Daniel Ricquier
, Bruno Miroux
, and Craig B. Thompson

Published Online:13 Sep 2007https://doi.org/10.1096/fj.07-8945com
Abstract

Uncoupling protein-2 (UCP2) belongs to the mitochondrial carrier family and has been thought to be involved in suppressing mitochondrial ROS production through uncoupling mitochondrial respiration from ATP synthesis. However, we show here that loss of function of UCP2 does not result in a significant increase in ROS production or an increased propensity for cells to undergo senescence in culture. Instead, Ucp2−/− cells display enhanced proliferation associated with a metabolic switch from fatty acid oxidation to glucose metabolism. This metabolic switch requires the unrestricted availability of glucose, and Ucp2−/− cells more readily activate autophagy than wild-type cells when deprived of glucose. Altogether, these results suggest that UCP2 promotes mitochondrial fatty acid oxidation while limiting mitochondrial catabolism of pyruvate. The persistence of fatty acid catabolism in Ucp2+/+ cells during a proliferative response correlates with reduced cell proliferation and enhances resistance to glucose starvation-induced autophagy.—Pecqueur, C., Bui, T., Gelly, C., Hauchard, J., Barbot, C., Bouillaud, F., Ricquier, D., Miroux, B., Thompson, C. B. Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization.

http://www.fasebj.org/doi/abs/10.1096/fj.07-8945com?journalCode=fasebj

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Tue Apr 03, 2018 1:57 am

Keep in mind that a lot of type-1 diabetics become alcoholic/heavy-drinkers over the years.
.....
Uncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold

Balazs Horvath, Claudia Spies, Gyongyi Horvath, Wolfgang J. Kox, Suzanne Miyamoto, Sean Barry, Craig H. Warden, Ingo Bechmann, Sabrina Diano, Jill Heemskerk, Tamas L. Horvath

   Hematology and OncologyGeneral Pediatrics

Research output: Contribution to journal › Article

   27 Citations

Abstract

Abuse of ethanol is a major risk factor in medicine, in part because of its widespread effect on the activity of the central nervous system, including behavior, pain, and temperature sensation. Uncoupling protein 2 (UCP2) is a mitochondrial protonophore that regulates cellular energy homeostasis. Its expression in mitochondria of axons and axon terminals of basal forebrain areas suggests that UCP2 may be involved in the regulation of complex neuronal responses to ethanol. We employed a paradigm in which acute exposure to ethanol induces tolerance and altered pain and temperature sensation. In UCP2 overexpressing mice, sensitivity to ethanol was decreased compared to that of wild-type animals, while UCP2 knockouts had increased ethanol sensitivity. In addition, UCP2 expression was inversely correlated with the impairment of pain and temperature sensation induced by ethanol. Taken together, these results indicate that UCP2, a mitochondrial uncoupling protein previously associated with peripheral energy expenditure, is involved in the mediation of acute ethanol exposure on the central nervous system. Enhancement of UCP2 activation after acute alcohol consumption might decrease the time of recovery from intoxication, whereas UCP2 inhibition might decrease the tolerance to ethanol.


https://ucdavis.pure.elsevier.com/en/publications/uncoupling-protein-2-ucp2-lowers-alcohol-sensitivity-and-pain-thr

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Sun Apr 15, 2018 4:37 am

Focuses on Iron. Like Malaria...Absinthe tends to affect parasitical/fermentation cell action towards Iron as a source of novel energy (ATP/Charge flows). Iron in a women's breast can be prone to cancer in certain situations:

https://www.ncbi.nlm.nih.gov/pubmed/22311047

Mol Biol Rep. 2012 Jul;39(7):7373-9. doi: 10.1007/s11033-012-1569-0. Epub 2012 Feb 5.
Artemisia absinthium (AA): a novel potential complementary and alternative medicine for breast cancer.
Shafi G1, Hasan TN, Syed NA, Al-Hazzani AA, Alshatwi AA, Jyothi A, Munshi A.
Author information
Abstract

Natural products have become increasingly important in pharmaceutical discoveries, and traditional herbalism has been a pioneering specialty in biomedical science. The search for effective plant-derived anticancer agents has continued to gain momentum in recent years. The present study aimed to investigate the role of crude extracts of the aerial parts of Artemisia absinthium (AA) extract in modulating intracellular signaling mechanisms, in particular its ability to inhibit cell proliferation and promote apoptosis in a human breast carcinoma estrogenic-unresponsive cell line, MDA-MB-231, and an estrogenic-responsive cell line, MCF-7. Cells were incubated with various concentrations of AA, and anti-proliferative activity was assessed by MTT assays, fluorescence microscopy after propidium iodide staining, western blotting and cell cycle analysis. Cell survival assays indicated that AA was cytotoxic to both MDA-MB-231 and MCF-7 cells. The morphological features typical of nucleic staining and the accumulation of sub-G1 peak revealed that the extract triggered apoptosis. Treatment with 25 μg/mL AA resulted in activation of caspase-7 and upregulation of Bad in MCF-7 cells, while exposure to 20 μg/mL AA induced upregulation of Bcl-2 protein in a time-dependent response in MDA-MB-231 cells. Both MEK1/2 and ERK1/2 was inactivated in both cell lines after AA treatment in a time-dependent manner. These results suggest that AA-induced anti-proliferative effects on human breast cancer cells could possibly trigger apoptosis in both cell lines through the modulation of Bcl-2 family proteins and the MEK/ERK pathway. This might lead to its possible development as a therapeutic agent for breast cancer following further investigations.

PMID:
   22311047
DOI:
   10.1007/s11033-012-1569-0

(related)

https://en.wikipedia.org/wiki/Oligonol (lychee fruit with other additives)
....

Eur J Cancer Prev. 2007 Aug;16(4):342-7.
Induction of apoptosis in MCF-7 and MDA-MB-231 breast cancer cells by Oligonol is mediated by Bcl-2 family regulation and MEK/ERK signaling.
Jo EH1, Lee SJ, Ahn NS, Park JS, Hwang JW, Kim SH, Aruoma OI, Lee YS, Kang KS.
Author information

Abstract

Oligonol is a novel catechin-rich biotechnology product. The role of oligonol in modulating intracellular signaling mechanisms was investigated with the view of demonstrating its potential chemopreventive effect and the ability to inhibit cell proliferation using the estrogen-responsive MCF-7 and the estrogen-unresponsive MDA-MB-231 human breast cancer cell lines. Cell survival assay indicated that Oligonol was cytotoxic to both cells. Oligonol triggered apoptosis as revealed by the morphological features typical of nucleus staining and the accumulation of sub-G1 peak. Treatment with 25 microg/ml Oligonol resulted in an activation of caspase-7 and up-regulation of Bad on MCF-7 cells, while the Oligonol (20 microg/ml) induced up-regulation of Bcl-2 protein in a time-response manner on MDA-MB-231 cells. ERK1/2 in both cells were inactivated after Oligonol treatment in a time-dependent manner, and also inactivated upstream MEK1/2. Oligonol triggers apoptosis in MCF-7 and MDA-MB-231 cells through the modulation of pro-apoptotic Bcl-2 family proteins and MEK/ERK signaling pathway.

PMID:
   17554207
DOI:
   10.1097/01.cej.0000236247.86360.db
....


The effect of Oligonol intake on cortisol and related cytokines in healthy young men

Jeong-Beom Lee, Young-Oh Shin,corresponding author Young-Ki Min, and Hun-Mo Yang
Author information ► Article notes ► Copyright and License information ► Disclaimer
This article has been cited by other articles in PMC.
Go to:

Abstract

This study investigated the effects of Oligonol intake on cortisol, interleukin (IL)-1β, and IL-6 concentrations in the serum at rest and after physical exercise loading. Nineteen healthy sedentary male volunteers participated in this study. The physical characteristics of the subjects were: a mean height of 174.2 ± 2.7 cm, a mean weight of 74.8 ± 3.6 kg and a mean age of 22.8 ± 1.3 years. Each subject received 0.5 L water with Oligonol (100 mg/day) (n = 10) or a placebo (n = 9) daily for four weeks. The body composition, the white blood cell (WBC) and differential counts as well as the serum cortisol, IL-1β, and IL-6 concentrations were measured before and after Oligonol intake. The cortisol concentration and serum levels of IL-1β and IL-6 after Oligonol intake were significantly decreased compared to before treatment (P < 0.01, respectively). In addition, the rate of increase of these factors after exercise was decreased compared to the placebo group. There was no change in the WBC and differential cell counts. These results suggest that oral Oligonol intake for four weeks had a significant effect on inhibition of inflammatory markers in healthy young men.

Keywords: Oligonol, cortisol, interleukin-1β, interleukin-6
Go to:

Introduction

The plants, vegetables, herbs and spices used in traditional medicine have been widely studied for their prophylactic and chemopreventive effects on human disease; in addition, they have been used for drug discovery and development [1-2]. Oligonol is a novel compound produced from the oligomerization of polyphenol. It is an optimized phenolic product containing catechin-type monomers and oligomers (dimer, trimer, and tetramer) of proanthocyanidin that are easily absorbed [3]. Oligonol is composed of 50% oligomers whereas a typical polyphenol polymer contains less than 10%. Thus, polyphenol polymers are not as efficiently bioactive or easily absorbed as Oligonol because of their high molecular weight.

Extracts or other purified preparations of phenolic rich foods have antioxidant, antibacterial, anti-inflammatory, antiallergic, hepatoprotective, antithrombotic, antiviral, anticarcinogenic, vasodilatory, and neuroprotective properties [4-7]. Nagakawa et al. [8] examined the effects of proanthocyanidin-rich extracts in rats subjected to renal ischemia-reperfusion. Their results suggested that Oligonol might play a role in modulating the cerebral and renal ischemia associated with oxidative stress. It has been shown that Oligonol exhibits significant protection against b-amyloid- and high glucose-induced cytotoxicity in rat pheochromocytoma PC12 cells and in the porcine proximal tubule cell line LLC-PK1, respectively [9,10].

In spite of the findings of recent studies on Oligonol, except for the study reported by Fujii and colleagues [11], there has been no study demonstrating the anti-inflammatory and anti-oxidative effects of Oligonol in humans. Thus, the purpose of the present study was to examine the effects of Oligonol intake for four weeks on cortisol and related cytokines, such as interleukin (IL)-6 and IL-1β, in healthy male subjects.

Exercise-induced stress was evaluated in this study. Exercise has acute and chronic effects on the systemic immunity and inflammatory response. It causes changes in stress hormones and cytokine concentrations. Following prolonged running at high intensity, the concentration of serum cortisol has been shown to be significantly elevated above control levels for several hours; this has been related to many of the cell trafficking changes that occur during recovery. Exercise that causes muscle cell injury can result in sequential release of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 [12,13]. The inflammatory cytokines help regulate the rapid migration of neutrophils, and then later monocytes, into the areas of injured muscle cells and other metabolically active tissues to initiate repair [14].

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Sun Apr 15, 2018 4:57 am

BMC Complement Altern Med. 2014 Jul 18;14:252. doi: 10.1186/1472-6882-14-252.
Synergistic anticancer effects of a bioactive subfraction of Strobilanthes crispus and tamoxifen on MCF-7 and MDA-MB-231 human breast cancer cell lines.
Yaacob NS1, Kamal NN, Norazmi MN.

Author information
Abstract

BACKGROUND:

Development of tumour resistance to chemotherapeutic drugs and concerns over their toxic effects has led to the increased use of medicinal herbs or natural products by cancer patients. Strobilanthes crispus is a traditional remedy for many ailments including cancer. Its purported anticancer effects have led to the commercialization of the plant leaves as medicinal herbal tea, although the scientific basis for its use has not been established. We previously reported that a bioactive subfraction of Strobilanthes crispus leaves (SCS) exhibit potent cytotoxic activity against human breast cancer cell lines. The current study investigates the effect of this subfraction on cell death activities induced by the antiestrogen drug, tamoxifen, in estrogen receptor-responsive and nonresponsive breast cancer cells.

METHODS:

Cytotoxic activity of SCS and tamoxifen in MCF-7 and MDA-MB-231 human breast cancer cells was determined using lactate dehydrogenase release assay and synergism was evaluated using the CalcuSyn software. Apoptosis was quantified by flow cytometry following Annexin V and propidium iodide staining. Cells were also stained with JC-1 dye to determine changes in the mitochondrial membrane potential. Fluorescence imaging using FAM-FLICA assay detects caspase-8 and caspase-9 activities. DNA damage in the non-malignant breast epithelial cell line, MCF-10A, was evaluated using Comet assay.

RESULTS:

The combined SCS and tamoxifen treatment displayed strong synergistic inhibition of MCF-7 and MDA-MB-231 cell growth at low doses of the antiestrogen. SCS further promoted the tamoxifen-induced apoptosis that was associated with modulation of mitochondrial membrane potential and activation of caspase-8 and caspase-9, suggesting the involvement of intrinsic and extrinsic signaling pathways. Interestingly, the non-malignant MCF-10A cells displayed no cytotoxicity or DNA damage when treated with either SCS or SCS-tamoxifen combination.

CONCLUSIONS:

The combined use of SCS and lower tamoxifen dose could potentially reduce the side effects/toxicity of the drug. However, further studies are needed to determine the effectiveness and safety of the combination treatment in vivo.

https://www.ncbi.nlm.nih.gov/pubmed/25034326
.....
Artemisia Cancer Cure?
Posted on February 24, 2011 | 39 Comments

I had recently come across a testimony from a Doctor who treated a boy with cancer with artemisia, among other things, and he stated that it produced a prompt remission. So I looked into Artemisia.

Artemisia cure for cancer?

In an archeological dig in China in the 1970’s, many ancient herbal remedies were uncovered. Among them was one for malaria using Artemisia. As a result, this herb began to be used widely for malaria treatment. Of note, this is Artemisia Annua, also known as Sweet Annie or Qing Hao in Chinese, not Artemisia Absinthe, which is known as Wormwood and is commonly used in anti-parasite cures.

But what’s more, in 1995, bioengineering professors Henry Lai and Nahendra Singh from the University of Washington began studying its potential as an anti-cancer drug and found it killed cancer cells in vitro in a matter of hours, and was even able to cure a dog from bone cancer withing 5 days.
After pumping the cancer cells with maximum amounts of iron using something called holotransferrin, Lai and Singh introduced artemisinin to selectively kill the cancer cells.
http://www.utne.com/2002_si/CouldWormwoodbetheCureforCancer.aspx

If you go to Prof Lai’s page at the U of W, you will see that his research is focused on
biological effects of electromagnetic fields and cancer treatment using Artemisinin and synthetic compounds. He has an entire page dedicated to Artemisinin information.
http://depts.washington.edu/bioe/research/research_artemisinin.html

Of course, it comes with a warning that the FDA has not approved Artemisia for use in the treatment of cancer, that more research is needed and that you should consult with your doctor (who will, in accordance with the FDA, recommend that you be poisoned and irradiated).

But below that, you will find a list of 206 studies going back as far as 1996, showing that artemisinin induces apoptosis, aka cell death, in cancer tumors and basically cures cancer.
http://depts.washington.edu/bioe/people/core/lai.html

You would think that after over 15 years of such promising research in vitro and in animals, someone would have done a human study by now- but no. I guess it would be considered unethical to deprive someone of ‘standard of care’, but you would think that surely they could find someone to volunteer to delay his murderous standard treatment by a couple of weeks to see if Artemisia would work as well for him as it does for the mice. I’m sure this could be done, but who will fund it? The problem is always funding because it all comes down to money. Investment vs return. If you use cheap herbs to actually restore people’s health, you lose out on some big bucks. That’s the bottom line for Big Pharma.

Instead of funding studies with natural herbs, research has taken the direction of studying a synthetic, patentable version of artemisinin as well as nanotechnology that could be used to deliver it. Is this really necessary? The plain of herbs worked for the dog, who I hear was still alive two years after the study, and that’s about 14 dog-years. Pretty good long-term survival, I would say.

We are told that cancer is some mysterious, horrible, incurable condition that can only be addressed with toxic, expensive pharma treatments. I used to work as a transcriptionist in an Oncology dept and I had full confidence in standard treatment. Day after day, I typed out reports of people improving, going into remission, being declared cancer-free. It never occurred to me that I never got to type reports about patients dying because once they died, their files were handled by the morgue. We are told that ‘cancer’ is this incurable mystery, but if you look into it a little more, you will find that cancer is no mystery and it is certainly curable, or at least manageable in other cases. Doctors who use alternative treatments to cure people from cancer are often persecuted, even run out of the country.

The fact is, there is a cure for cancer. Not one cure, actually, but many. ‘Cancer’ is nothing but an umbrella term used to describe about 100 conditions that involve abnormal cell proliferation and tumors, which can have many causes and to which there are many remedies. I would recommend “Knockout” by Suzanne Somers as a primer in alternative cancer treatments. Yes, Chrissie from Three’s Company. No, she’s not playing doctor, she’s interviewing doctors. You can get more info at http://suzannesommers.com

Preventing people’s access to natural cancer treatments is done under the pretense of ethics, but nothing could be more unethical than forcing people to undergo horrendous toxic treatments which have a very low success rate. But the word is getting out and people are saying Enough is Enough! We have been lied to! We demand real medicine! We demand health freedom! We will not allow you to profit off our sickness and death!

Note: Dr Lai’s experiments involved artemisinin and holotransferrin. This should not be interpreted to mean you can cure yourself of cancer at home using Artemisia Annua.

https://thetruthergirls.wordpress.com/2011/02/24/artemisia-cancer-cure/

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Sun Apr 15, 2018 5:09 am

Basically to activities to help cure cancer:

1. Go on a fasts (water only) so that the body uses Ketones for fuel
2. Drink Absinthe (Mephisto from Austria with full Grande Sage wormwood)
3. Filter soaked/boiled Methanol extracts of powdered Syrian Rue seeds with White Vinegar/Alcohol -- (use Mephisto)
4. DCA - DichloroAcetate (mentioned earlier)
5. Eliminate all forms of Fructose/Corn Syrup from the diet. Fructose feeds cancer directly.
6. Use cordecyps mushroom as an oxidation action.
7. Curcumin with Manuka Honey (attacks the fermentation cycle)
8. Cell mitochondria enhancers (NAD+, NMN, Oaxacletate, ATP pills, Oligonol (Korean lychee drink),  etc...)
9. Get Metformin



Results

We show that metformin decreases mitochondrial respiration, causing an increase in the fraction of mitochondrial respiration devoted to uncoupling reactions. Thus, cells treated with metformin become energetically inefficient, and display increased aerobic glycolysis and reduced glucose metabolism through the citric acid cycle. Conflicting prior studies proposed mitochondrial complex I or various cytosolic targets for metformin action, but we show that the compound limits respiration and citric acid cycle activity in isolated mitochondria, indicating that at least for these effects, the mitochondrion is the primary target. Finally, we demonstrate that cancer cells exposed to metformin display a greater compensatory increase in aerobic glycolysis than nontransformed cells, highlighting their metabolic vulnerability. Prevention of this compensatory metabolic event in cancer cells significantly impairs survival.
Conclusions

Together, these results demonstrate that metformin directly acts on mitochondria to limit respiration and that the sensitivity of cells to metformin is dependent on their ability to cope with energetic stress.
https://cancerandmetabolism.biomedcentral.com/articles/10.1186/2049-3002-2-12



Last edited by Cr6 on Fri May 04, 2018 1:02 am; edited 2 times in total

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Fri May 04, 2018 12:56 am

Background on how TB rewires ATP usage like Cancer does. Syrian Rue reportedly is effective against TB in manner that it is said to be effective against many cancers -- ATP generation in the UV range is increased with Harmine.

Harmine (banisterine). C13H12ON2 - It is present in P. harmala and in some species of Banisteia, viz., B. caapi, Spruce., B. lutea and B. metallicolor. The alkaloid is optically inactive and forms colorless rhombic prisms from methanol. It is slightly soluble in water, alcohol or ether. Solutions of its salts show a deep blue fluorescence. The hydrochloride has been found to be highly active against Mycobacterium tuberculosis [7].

-------
An adenosine triphosphate-independent proteasome activator contributes to the virulence of Mycobacterium tuberculosis

Mycobacterium tuberculosis encodes a proteasome that is highly similar to eukaryotic proteasomes and is required to cause lethal infections in animals. The only pathway known to target proteins for proteasomal degradation in bacteria is pupylation, which is functionally analogous to eukaryotic ubiquitylation. However, evidence suggests that the M. tuberculosis proteasome contributes to pupylation-independent pathways as well. To identify new proteasome cofactors that might contribute to such pathways, we isolated proteins that bound to proteasomes overproduced in M. tuberculosis and found a previously uncharacterized protein, Rv3780, which formed rings and capped M. tuberculosis proteasome core particles. Rv3780 enhanced peptide and protein degradation by proteasomes in an adenosine triphosphate (ATP)-independent manner. We identified putative Rv3780-dependent proteasome substrates and found that Rv3780 promoted robust degradation of the heat shock protein repressor, HspR. Importantly, an M. tuberculosis Rv3780 mutant had a general growth defect, was sensitive to heat stress, and was attenuated for growth in mice. Collectively, these data demonstrate that ATP-independent proteasome activators are not confined to eukaryotes and can contribute to the virulence of one the world’s most devastating pathogens.

Authors:
   Jastrab, Jordan B. [1] ; Wang, Tong [2] ; Murphy, J. Patrick [3] ; Bai, Lin [2] ; Hu, Kuan [4] ; Merkx, Remco [5] ; Huang, Jessica [6] ; Chatterjee, Champak [6] ; Ovaa, Huib [5] ; Gygi, Steven P. [3] ; Li, Huilin [4] ; Darwin, K. Heran [1]
   + Show Author Affiliations

Publication Date:
   2015-03-23

https://www.osti.gov/pages/biblio/1215607-adenosine-triphosphate-independent-proteasome-activator-contributes-virulence-mycobacterium-tuberculosis


.........
Extracellular Adenosine Triphosphate Affects the Response of Human Macrophages Infected With Mycobacterium tuberculosis

Abstract

Granulomas are the hallmark of Mycobacterium tuberculosis infection. As the host fails to control the bacteria, the center of the granuloma exhibits necrosis resulting from the dying of infected macrophages. The release of the intracellular pool of nucleotides into the surrounding medium may modulate the response of newly infected macrophages, although this has never been investigated. Here, we show that extracellular adenosine triphosphate (ATP) indirectly modulates the expression of 272 genes in human macrophages infected with M. tuberculosis and that it induces their alternative activation. ATP is rapidly hydrolyzed by the ecto-ATPase CD39 into adenosine monophosphate (AMP), and it is AMP that regulates the macrophage response through the adenosine A2A receptor. Our findings reveal a previously unrecognized role for the purinergic pathway in the host response to M. tuberculosis. Dampening inflammation through signaling via the adenosine A2A receptor may limit tissue damage but may also favor bacterial immune escape.

All living cells sense and respond to changes in their external environment. This is particularly true of cells of the immune system. These cells express receptors that recognize both conserved structural motifs on microbes, known as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), resulting from tissue damage [1, 2]. In studies on infectious diseases, much attention has been paid to the role of PAMPs and the responses they induce. However, the DAMPs released by necrotic cells are also very likely to affect the host immune response. These molecules, which include high-mobility group box 1 protein, uric acid, heat shock proteins, and nucleotides, have been described to promote and to exacerbate inflammation by activating the NF-κB pathway [1]. A high concentration of extracellular adenosine triphosphate (eATP) serves as a danger signal to alert the immune system to tissue damage [3]; it promotes adhesion of neutrophils to the vascular endothelium, increases secretion of inflammatory cytokines by monocytes or macrophages, induces maturation of dendritic cells, and stimulates effector T-cell function [3].

Tuberculosis research is not an exception to this rule; it has been mainly focused on the role of PRRs and mycobacterial PAMPs at the expense of the role of DAMPs. Mycobacterium tuberculosis, the etiologic agent of this disease has been described to interact with a multitude of PRRs, including Toll-like receptor 2 (TLR2), TLR4, TLR9, NOD-like receptor 2, and some C-type lectins (mannose receptor, DC-SIGN, dectin-1, and Mincle) [4]. Upon ligation of these receptors, macrophages secrete cytokines and chemokines that orchestrate the formation of granulomas. Tuberculosis is characterized by a caseous necrosis in tissues, and, interestingly, M. tuberculosis favors necrosis over apoptosis in infected macrophages [5]. Infected phagocytes are thus exposed to molecules usually present in the cytosol or in the nucleus of the cell. Surprisingly, little is known about how these DAMPs modulate antimycobacterial responses. It has been shown that eATP induces apoptosis of M. tuberculosis–infected phagocytes and mycobacterial killing via phagosome-lysosome fusion and autophagy induction in a P2X7-dependent manner [6–9]. However, the consequences of an eATP-rich microenvironment for mycobacterial killing remain controversial [10]. The concentration of ATP required to limit bacterial growth in macrophages is very high (3 mM) [6–9, 11], well above physiological concentrations. Indeed, in the extracellular space, the steady state concentration of ATP is between 1 and 10 nM [12], although in various pathological situations, such as inflammation, the concentration of eATP may be in the 100-μmol/L range [3].

Here, we report an investigation of whether eATP, at concentrations likely to be present at the site of infection, influences the response of human monocyte-derived macrophages upon M. tuberculosis infection. We found that stimulation of M. tuberculosis–infected macrophages with ATP is accompanied by changes in expression of genes associated mainly with the immune response. In particular, ATP strongly decreased the secretion of inflammatory mediators such as tumor necrosis factor α (TNF-α) and chemokines responsible for the recruitment of innate effector cells, and it increases the expression of tissue-repair-associated genes like VEGF and transforming growth factor α (TGF-α). Alternative activation of macrophages by eATP required its degradation by the ectonucleotidase CD39, and we provide strong evidence that the resulting adenosine monophosphate (AMP) mediated the observed effect through the stimulation of the adenosine A2A receptor. These various findings show that an extracellular AMP-rich microenvironment, similar to that probably prevailing in granulomas, modulates the macrophage response to M. tuberculosis infection and may favor bacterial persistence by dampening the host immune response.
https://academic.oup.com/jid/article/210/5/824/2908522

...
Structure of the mycobacterial ATP synthase Fo rotor ring in complex with the anti-TB drug bedaquiline

INTRODUCTION

Tuberculosis (TB) killed more than 1.3 million people in 2012 (1). The
sharply increasing infection rates documented in the latest World
Health Organization Global Tuberculosis Report (2) pose a threat to
global TB eradication programs (3), making the development of new
and alternative antibiotics, particularly against multidrug-resistant (MDR)
Mycobacterium tuberculosis, an urgent priority. Bedaquiline (BDQ; marketed
as Sirturo) is a novel antitubercular compound that belongs to
the chemical class of diarylquinolines. It was shown to equally inhibit the
growth of drug-sensitive and drug-resistant M. tuberculosis in active TB
infections (4). In vitro–generated BDQ-resistant mutants suggested the
rotor ring of the organism’s F1Fo-ATP synthase as the drug target (4).
The F1Fo-ATP synthase is a macromolecular, membrane-embedded protein
complex that uses the transmembrane electrochemical ion (H+ or
Na+) gradient to convert adenosine diphosphate (ADP) and inorganic
phosphate (Pi) into adenosine triphosphate (ATP) by a rotary mechanism
(5–Cool. The membrane-embedded Fo domain of the complex
harbors the rotor ring of the F-type ATP synthase; usually in bacteria,
it consists of identical copies of c-subunits, forming an hourglass-shaped
cylinder with a central pore (the c-ring) (9). It shuttles ions across the
membrane and thereby powers the synthesis of ATP within the three
catalytically active sites of the F1 headpiece.

http://advances.sciencemag.org/content/advances/1/4/e1500106.full.pdf

https://www.researchgate.net/publication/51332213_Bioluminescence_assay_of_adenosine_triphosphate_in_drug_susceptibility_testing_of_Mycobacterium_tuberculosis

Second link:
https://research.pasteur.fr/en/publication/extracellular-adenosine-triphosphate-affects-the-response-of-human-macrophages-infected-with-mycobacterium-tuberculosis/
https://en.wikipedia.org/wiki/ATP_phosphoribosyltransferase

.....


Involvement of tryptophan(s) at the active site of polyphosphate/ATP glucokinase from Mycobacterium tuberculosis


Pei Chung Hsieh, Bhami C. Shenoy, F. Carl Haase, Joyce E. Jentoft, Nelson F B Phillips

Abstract

The glucokinase (EC 2.7.1.63) from Mycobacterium tuberculosis catalyzes the phosphorylation of glucose using inorganic polyphosphate (poly(P)) or ATP as the phosphoryl donor. The nature of the poly(P) and ATP sites was investigated by using N-bromosuccinimide (NBS) as a probe for the involvement of tryptophan in substrate binding and/or catalysis. NBS oxidation of the tryptophan(s) resulted in fluorescence quenching with concomitant loss of both the poly(P)- and ATP-dependent glucokinase activities. The inactivation by NBS was not due to extensive structural changes, as evidenced by similar circular dichroism spectra and fluorescence emission maxima for the native and NBS-inactivated enzyme. Both phosphoryl donor substrates in the presence of xylose afforded ∼65% protection against inactivation by NBS. The Km values of poly(P) and ATP were not altered due to the modification by NBS, while the catalytic efficiency of the enzyme was decreased, suggesting that the essential tryptophan(s) are involved in the catalysis of the substrates. Acrylamide quenching studies indicated that the tryptophan residue(s) were partially shielded by the substrates against quenching. The Stern-Volmer quenching constant (Ksv) of the tryptophans in unliganded glucokinase was 3.55 M-1, while Ksv values of 2.48 and 2.57 M-1 were obtained in the presence of xylose+poly(P)5 and xylose+ATP, respectively. When the tryptophan-containing peptides were analyzed by peptide mapping, the same peptide was found to be protected by xylose+poly(P)5 and xylose+ATP against oxidation by NBS. The two protected peptides were determined to be identical by N-terminal sequence analysis and amino acid composition. It is proposed from these results that one or both of the tryptophans present in the protected peptide may be located at a common catalytic center and that this peptide may constitute part of the poly(P) and ATP binding regions.

https://cwru.pure.elsevier.com/en/publications/involvement-of-tryptophans-at-the-active-site-of-polyphosphateatp-2

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Wed May 09, 2018 2:42 am

Came across this quote on Garcinia Cambogia. Interesting that (ATP) adenosine triphosphate-citrate-lyase was mentioned as a factor in cancer growth in another article mentioned earlier:
----
1. Weight Loss

The key active ingredient found in the rind of garcinia cambogia is hydroxycitric acid (HCA), which some research suggests can help certain people lose weight. (1)

Some studies have found that garcinia cambogia might, in fact, be able to help with low amounts of fat loss, plus some of the other health concerns mentioned above, although its effectiveness is rarely strong or consistent. For example, research suggests that HCA works by blocking a certain enzyme called adenosine triphosphate-citrate-lyase, which contributes to the formation of fat cells. But studies comparing GC’s effects to controls have found that it might only increase weight loss by a mere one to two pounds on average.
https://draxe.com/garcinia-cambogia/
....
Abstract

1-Oncogenes express proteins of "Tyrosine kinase receptor pathways", a receptor family including insulin or IGF-Growth Hormone receptors. Other oncogenes alter the PP2A phosphatase brake over these kinases.
2-Experiments on pancreatectomized animals; treated with pure insulin or total pancreatic extracts, showed that choline in the extract, preserved them from hepatomas.
Since choline is a methyle donor, and since methylation regulates PP2A, the choline protection may result from PP2A methylation, which then attenuates kinases.
3-Moreover, kinases activated by the boosted signaling pathway inactivate pyruvate kinase and pyruvate dehydrogenase. In addition, demethylated PP2A would no longer dephosphorylate these enzymes. A "bottleneck" between glycolysis and the oxidative-citrate cycle interrupts the glycolytic pyruvate supply now provided via proteolysis and alanine transamination. This pyruvate forms lactate (Warburg effect) and NAD+ for glycolysis. Lipolysis and fatty acids provide acetyl CoA; the citrate condensation increases, unusual oxaloacetate sources are available. ATP citrate lyase follows, supporting aberrant transaminations with glutaminolysis and tumor lipogenesis. Truncated urea cycles, increased polyamine synthesis, consume the methyl donor SAM favoring carcinogenesis.
4-The decrease of butyrate, a histone deacetylase inhibitor, elicits epigenic changes (PETEN, P53, IGFBP decrease; hexokinase, fetal-genes-M2, increase)
5-IGFBP stops binding the IGF - IGFR complex, it is perhaps no longer inherited by a single mitotic daughter cell; leading to two daughter cells with a mitotic capability.
6-An excess of IGF induces a decrease of the major histocompatibility complex MHC1, Natural killer lymphocytes should eliminate such cells that start the tumor, unless the fever prostaglandin PGE2 or inflammation, inhibit them...

https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-10-70

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

BioCancer: R library for DNA influences

Post by Cr6 on Sun May 20, 2018 2:26 am

An interesting R library from BioConductor:

https://kmezhoud.github.io/bioCancer/


bioCancer - Interactive Multi-OMICS Cancers Data Visualization and Analysis

Travis-CI Build Status releaseVersion develVersion Bioc total

bioCancer is a browser-based interface for Cancer Genomics Data analysis and visualization developped by R, and based on the Shiny package.

Interactivities

bioCancer is listening user setting. Results are updated immediately when inputs are changed (i.e., no separate dialog boxes).
Context

bioCancer focuses on Cancer Genomics data visualisation and Genes Classifications.

Circomics: Pull User genetic profiles with existing Cancer studies



Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Cr6 on Mon May 21, 2018 1:58 am

Article by Sam Apple (journalist who helped popularize the Warburg Effect again):
-----------

It's getting clearer — the diet-cancer connection points to sugar and carbs
By Sam Apple
Oct 27, 2017 | 4:00 AM

In August of 2016, the New England Journal of Medicine published a striking report on cancer and body fat: Thirteen separate cancers can now be linked to being overweight or obese, among them a number of the most common and deadly cancers of all — colon, thyroid, ovarian, uterine, pancreatic and (in postmenopausal women) breast cancer.

Earlier this month, a report from the Centers for Disease Control and Prevention added more detail: Approximately 631,000 Americans were diagnosed with a body fat-related cancer in 2014, accounting for 40% of all cancers diagnosed that year.

Increasingly, it seems not only that we are losing the war on cancer, but that we are losing it to what we eat and drink.

These new findings, while important, only tell us so much. The studies reflect whether someone is overweight upon being diagnosed with cancer, but they don't show that the excess weight is responsible for the cancer. They are best understood as a warning sign that something about what or how much we eat is intimately linked to cancer. But what?

When insulin rises to abnormally high levels and remains elevated, it can promote the growth of tumors directly and indirectly.
Share quote & link

The possibility that much of our cancer burden can be traced to diet isn't a new idea. In 1937, Frederick Hoffman, an actuary for the Prudential Life Insurance Co., devoted more than 700 pages to a review of all the medical thinking on the topic at the time. But with little in the way of evidence, Hoffman could only guess at which of the many theories might be correct. If we've made little progress since then in pinpointing specific foods that cause cancer, it's in large part because nutrition studies aren't well-suited to cracking the problem.

A cancer typically arises over years, or decades, making the type of study that might definitively establish cause and effect — an experiment in which people are randomly assigned to different diets — nearly impossible to carry out. The next-best option — observational studies that track what a specific group of individuals eats and which members of the group are later diagnosed with cancer — tends to generate as much confusion as knowledge. One day we read that a study has linked eating meat to cancer; a month later, a new headline declares the exact opposite.

And yet researchers have made progress in understanding the diet-cancer connection. The advances have emerged in the somewhat esoteric field of cancer metabolism, which investigates how cancer cells turn the nutrients we consume into fuel and building blocks for new cancer cells.

Largely ignored in the last decades of the 20th century, cancer metabolism has undergone a revival as researchers have come to appreciate that some of the most well-known cancer-causing genes, long feared for their role in allowing cancer cells to proliferate without restraint, have another, arguably even more fundamental role: allowing cancer cells to "eat" without restraint. This research may yield a blockbuster cancer treatment, but in the meantime it can provide us with something just as crucial — knowledge about how to prevent the disease in the first place.

Lewis Cantley, the director of the cancer center at Weill Cornell Medicine, has been at the forefront of the cancer metabolism revival. Cantley's best explanation for the obesity-cancer connection is that both conditions are also linked to elevated levels of the hormone insulin. His research has revealed how insulin drives cells to grow and take up glucose (blood sugar) by activating a series of genes, a pathway that has been implicated in most human cancers.

The problem isn't the presence of insulin in our blood. We all need insulin to live. But when insulin rises to abnormally high levels and remains elevated (a condition known as insulin resistance, common in obesity), it can promote the growth of tumors directly and indirectly. Too much insulin and many of our tissues are bombarded with more growth signals and more fuel than they would ever see under normal metabolic conditions. And because elevated insulin directs our bodies to store fat, it can also be linked to the various ways the fat tissue itself is thought to contribute to cancer.


(more at link..... http://www.latimes.com/opinion/op-ed/la-oe-apple-cancer-and-diet-20171027-story.html )
------
An Old Idea, Revived: Starve Cancer to Death

In the early 20th century, the German biochemist Otto Warburg believed that tumors could be treated by disrupting their source of energy. His idea was dismissed for decades — until now.

SAM APPLE
MAY 12, 2016
Continue reading the main story
The story of modern cancer research begins, somewhat improbably, with the sea urchin. In the first decade of the 20th century, the German biologist Theodor Boveri discovered that if he fertilized sea-urchin eggs with two sperm rather than one, some of the cells would end up with the wrong number of chromosomes and fail to develop properly. It was the era before modern genetics, but Boveri was aware that cancer cells, like the deformed sea urchin cells, had abnormal chromosomes; whatever caused cancer, he surmised, had something to do with chromosomes.

Today Boveri is celebrated for discovering the origins of cancer, but another German scientist, Otto Warburg, was studying sea-urchin eggs around the same time as Boveri. His research, too, was hailed as a major breakthrough in our understanding of cancer. But in the following decades, Warburg’s discovery would largely disappear from the cancer narrative, his contributions considered so negligible that they were left out of textbooks altogether.

Unlike Boveri, Warburg wasn’t interested in the chromosomes of sea-urchin eggs. Rather, Warburg was focused on energy, specifically on how the eggs fueled their growth. By the time Warburg turned his attention from sea-urchin cells to the cells of a rat tumor, in 1923, he knew that sea-urchin eggs increased their oxygen consumption significantly as they grew, so he expected to see a similar need for extra oxygen in the rat tumor. Instead, the cancer cells fueled their growth by swallowing up enormous amounts of glucose (blood sugar) and breaking it down without oxygen. The result made no sense. Oxygen-fueled reactions are a much more efficient way of turning food into energy, and there was plenty of oxygen available for the cancer cells to use. But when Warburg tested additional tumors, including ones from humans, he saw the same effect every time. The cancer cells were ravenous for glucose.

Warburg’s discovery, later named the Warburg effect, is estimated to occur in up to 80 percent of cancers. It is so fundamental to most cancers that a positron emission tomography (PET) scan, which has emerged as an important tool in the staging and diagnosis of cancer, works simply by revealing the places in the body where cells are consuming extra glucose. In many cases, the more glucose a tumor consumes, the worse a patient’s prognosis.

In the years following his breakthrough, Warburg became convinced that the Warburg effect occurs because cells are unable to use oxygen properly and that this damaged respiration is, in effect, the starting point of cancer. Well into the 1950s, this theory — which Warburg believed in until his death in 1970 but never proved — remained an important subject of debate within the field. And then, more quickly than anyone could have anticipated, the debate ended. In 1953, James Watson and Francis Crick pieced together the structure of the DNA molecule and set the stage for the triumph of molecular biology’s gene-centered approach to cancer. In the following decades, scientists came to regard cancer as a disease governed by mutated genes, which drive cells into a state of relentless division and proliferation. The metabolic catalysts that Warburg spent his career analyzing began to be referred to as “housekeeping enzymes” — necessary to keep a cell going but largely irrelevant to the deeper story of cancer.

“It was a stampede,” says Thomas Seyfried, a biologist at Boston College, of the move to molecular biology. “Warburg was dropped like a hot potato.” There was every reason to think that Warburg would remain at best a footnote in the history of cancer research. (As Dominic D’Agostino, an associate professor at the University of South Florida Morsani College of Medicine, told me, “The book that my students have to use for their cancer biology course has no mention of cancer metabolism.”) But over the past decade, and the past five years in particular, something unexpected happened: Those housekeeping enzymes have again become one of the most promising areas of cancer research. Scientists now wonder if metabolism could prove to be the long-sought “Achilles’ heel” of cancer, a common weak point in a disease that manifests itself in so many different forms.

There are typically many mutations in a single cancer. But there are a limited number of ways that the body can produce energy and support rapid growth. Cancer cells rely on these fuels in a way that healthy cells don’t. The hope of scientists at the forefront of the Warburg revival is that they will be able to slow — or even stop — tumors by disrupting one or more of the many chemical reactions a cell uses to proliferate, and, in the process, starve cancer cells of the nutrients they desperately need to grow.

Even James Watson, one of the fathers of molecular biology, is convinced that targeting metabolism is a more promising avenue in current cancer research than gene-centered approaches. At his office at the Cold Spring Harbor Laboratory in Long Island, Watson, 88, sat beneath one of the original sketches of the DNA molecule and told me that locating the genes that cause cancer has been “remarkably unhelpful” — the belief that sequencing your DNA is going to extend your life “a cruel illusion.” If he were going into cancer research today, Watson said, he would study biochemistry rather than molecular biology.

“I never thought, until about two months ago, I’d ever have to learn the Krebs cycle,” he said, referring to the reactions, familiar to most high-school biology students, by which a cell powers itself. “Now I realize I have to.”
(more at link.....
https://www.nytimes.com/2016/05/15/magazine/warburg-effect-an-old-idea-revived-starve-cancer-to-death.html
)

Cr6
Admin

Posts : 911
Join date : 2014-08-09

View user profile http://milesmathis.forumotion.com

Back to top Go down

Re: Cancer and ATP: The Photon Energy Pathway (DCA as anti-tumor)

Post by Sponsored content


Sponsored content


Back to top Go down

Page 2 of 2 Previous  1, 2

Back to top


 
Permissions in this forum:
You cannot reply to topics in this forum