Daniel Orrego
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hippocratesresearchfoundation.org
Daniel Orrego
@hippocratesresearchfoundation.org
Studying the intersection of metabolism and disease.
How can we know that Hyperbaric Oxygen Therapy induces cell membrane damage to tumor cells? Because, the effects of oxidative stress from hyperoxia on cell morphology has been demonstrated using atomic force microscopy, in context to metabolic isolation, via lowering of glucose.
February 12, 2024 at 3:57 PM
While most efforts to understand cancer immune resistance largely focus on somatic alterations of cancer cells, comparatively less information is available about environmental factors affecting the delicate balance between metabolism, microbiota, immunity, and oncogenesis.
January 26, 2024 at 12:30 PM
Glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a calorie and macronutrient controlled nutritional regimen.
January 24, 2024 at 12:35 PM
Direct calorimetry as applied to the measurement of the heat production rate in tumour cells, demonstrates that tumor metabolism is accompanied
by either production or adsorption of heat, whereby the measurement of heat production provides a means for monitoring overall survivorship.
January 15, 2024 at 12:44 PM
Given that tumor microenvironments are lacking in key nutrients and oxygen, cancer becomes resistant to chemo and radiation. Conventional anticancer drugs, such as 5-FU
and cisplatin, exert cytotoxic effects in
normal medium but only have a minimal effect in
nutrient-deprived, hypoxic conditions.
January 12, 2024 at 12:50 PM
One of the key hallmarks recognized 100 years ago, is cancer cells’ remarkable tendency to reprogram their metabolic capability. Inhibition of oxidative phosphorylation (OXPHOS) leads to elevated glycolytic metabolism.
January 11, 2024 at 12:44 PM
Lonidamine inhibits glycolysis
through its inhibitory effect on mitochondrial-bound Hexokinase II. The inhibition of HK-II by lonidamine leads to decreased glucose phosphorylation.
January 3, 2024 at 12:26 PM
Notably, the dismal record of the Standard of Care persists, insofar that even presumably compelling new drug development, often times only contributes 2.4 months to median Overall Survivorship, across any number of tumor models.
January 2, 2024 at 12:41 PM
Despite advances in the number and specificity of targeted chemotherapeutics, radiation, surgical techniques, immunotherapy and hormone ablatement therapy, more people die from cancer, year over year, every year.
January 1, 2024 at 3:10 PM
As with glucose, the consumption of glutamine via the TCA cycle produces high-energy electrons that are processed through the electron transport chain for the production of ATP. Thus, glutamine is also a major cancer cell energy and anabolic substrate.
December 29, 2023 at 12:11 PM
Tumor cells exhibit a high rate of glutamine consumption that cannot be explained by the nitrogen demand imposed by nucleotide synthesis or maintenance of amino acid pools. Glutamine facilitates the cell's ability to use glucose-derived carbon and TCA cycle intermediates as biosynthetic precursors.
December 28, 2023 at 11:51 AM
Although impaired respiration can render tumor cells dependent on glycolysis for energy in the presence of oxygen (Warburg effect), it has now been demonstrated that glutamine alone can provide enough energy through substrate level phosphorylation in the TCA cycle to maintain tumor cell viability.
December 27, 2023 at 12:52 PM
Notably, in tumor cells, the initial step of glutamine fermentation is driven by glutaminase, which is mitochondrial. Subsequent steps, are catalyzed by transaminases or glutamate dehydrogenase; isocitrate dehydrogenase; aconitase, as performed by either cytosolic or mitochondrial isoforms.
December 26, 2023 at 12:18 PM
"Although in the tumor every oxygen molecule breathed is just as effective as in muscle- the Meyerhof quotient is equal in the two cases- yet the respiration does not cause the glycolysis to disappear. The respiration of the carcinoma tissue is too small in comparison to its glycolytic power."
December 22, 2023 at 12:51 PM
Over a million FDG-PET studies have unequivocally identified increased glucose uptake as a hallmark of metastatic cancer in humans. These observations, combined with new molecular insights with HIF-1α and c-myc, have rekindled an interest in this important phenotype.
December 21, 2023 at 12:47 PM
Warburg proposed that cancer cells cause an injury
to respiration as they progress from a differentiated cellular state to a proliferative state.
The majority of cancer cells use substrate level fermentation to drive increased flux
through the tricarboxylic acid cycle, which promotes tumor growth.
December 20, 2023 at 12:47 PM
The six classical hallmarks of cancer (i.e., limitless replication, self-provision of proliferative stimuli, insensitivity to antiproliferative signals, disabled apoptosis, sustained angiogenesis, invasiveness/metastatic potential), may directly or indirectly implicate dysregulated mitochondria.
December 19, 2023 at 12:41 PM
Study design and methodology are instrumental in demonstrating the level of confidence one can have in the outcomes of any given scientific inquiry. Crucially, in cancer research, the tumor model used in pre-clinical studies is immensely instructive as regards response to interventions.
December 18, 2023 at 1:08 PM
News reports about cancer frequently discuss aggressive treatment and survival but rarely discuss treatment failure, adverse events, end-of-life care, or death. These portrayals of cancer care in media may give patients an inappropriately optimistic view of cancer treatment, outcomes, and prognosis.
December 15, 2023 at 12:45 PM
Caloric and macronutrient control demonstrably inhibit angiogenesis and upregulate apoptosis. Vascular Endothelial Growth Factor and Insulin Like Growth Factor 1, both key catalysts of cellular proliferation, are downregulated when overall caloric density is consistently controlled.
December 14, 2023 at 1:01 PM
The life expectancy following diagnosis with Grade IV Glioblastoma is 2–4 months without treatment. Survival at 5 years for patients with Glioblastoma who receive treatment with concurrent chemoradiotherapy followed by maintenance temozolomide is around 8–14%. This is a near uniformly fatal disease.
December 13, 2023 at 12:46 PM
Since President Nixon, in 1971, declared a 'War on Cancer', the annual death toll in raw numbers has continued to rise uniformly, year after year, with comparatively modest improvements in Overall Survivorship. Hence, will science and medicine be able to reverse this trend over the next 40 years?
December 12, 2023 at 12:50 PM
What does therapeutic ketosis (Glucose 55-65mg/dL, Ketones (2.0-7.0mM/L) actually look like? By what specific interventions is it achieved? What measurable clinical outcomes can it predictably and repeatably produce? Here is where the case documentary record provides insight and instruction.
December 11, 2023 at 12:45 PM
While sustained caloric and macronutrient control sufficient to induce therapeutic ketosis has been demonstrated to downregulate the threshold availability of glucose for substrate level fermentation by disease, even less rigorous forms of dietary control can have profound near term effects.
December 8, 2023 at 12:59 PM
While comparatively speaking, the Standard of Care is generally successful in addressing pediatric cancers, with mortality attributable to recurrence or progression of primary disease decreasing, increases in rates of mortality attributable to subsequent neoplasms are increasing, longitudinally.
December 7, 2023 at 12:53 PM