T3 may promote cancer cell proliferation says study. Triiodothyronine was found to enhance the MCF-7 and T47-D breast cancer cell lines. The conclusion of the abstract discusses a role of T3 in breast cancer development and progression. This likely has more to do with progression than development through increased metabolism of the cell lines.
Testosterone plays an important role in glucose and lipid metabolism. Thus, low Testosterone, will result in increased disruption in the homeostasis of glucose and lipids resulting in increased weight, insulin resistance, diabetes, metabolic syndrome...
Low SHBG was also shown to be associated with MetS
Total Testosterone in men decreased by 30% over the lifetime of men in this study compared to 64% decrease in bioavailable Testosterone in men. Decreased BMD was associated with this loss. Similar findings for Estrogen was also noted in men.
Testosterone levels vary amongst men by geography. Testosterone levels are higher, 20% higher, in Asian men living in Hong Kong and Japan versus those that live in the US. This is very similar to some of the date around breast cancer in Asian women. Both suggesting diet and environment as the variable.
The typical onset of TS occurs at 6–7 years of age and is characterized by the appearance of simple, recurrent motor tics, followed by the manifestation of phonic tics after several months [12]. In most children, TS symptoms undergo a progressive exacerbation, which reaches its zenith at the beginning of puberty (11–12 years of age), and is then followed by a gradual remission in the majority of patients
30–40% of TS-affected children retain their symptoms in adulthood
Multiple neurotransmitters have been implicated in TS, including dopamine (DA), serotonin, norepinephrine, acetylcholine, glutamate and γ-amino-butyric acid (GABA)
ample evidence supports the involvement of DAergic dysfunctions in TS
male gender is a major risk factor for TS (with a male:female prevalence ratio estimated at ~4:1)
the typical age of onset coincides with adrenarche (6–7 years old); symptoms increase in severity until the beginning of puberty (12 years old) and then undergo a spontaneous amelioration, which becomes apparent with the end of puberty (at 18–19 years of age)
TS is diagnosed later in females than males
female gender may predict greater tic severity in adulthood
a number of clinical observations showed that tics in TS patients could be exacerbated by anabolic androgens
steroidogenic enzymes and androgen receptors may serve as putative therapeutic targets for this disorder
Unlike males, tic severity is typically increased after puberty in females
26% of females were found to experience exacerbation of tics in the estrogenic phase of the menstrual cycle, and this phenomenon was found to be correlated with increased tic severity at menarche
biochemical hallmark of adrenarche is the acquisition of 17,20 lyase activity by cytochrome P450 C17 (CYP17A1)
increased synthesis of dehydroepiandrosterone (DHEA) and androstenedione, which leads to the growth of axillary and pubic hair as well as enhancement in the oiliness of the skin
interesting read on hormones and tourette's.. Proposed that 5 alpha reductase activity is involved in worsening of tics. This makes sense as Testosterone in men with low T is known to increase dopamine and dopaminergic dysfunction is known to play a role in tourette's; the clinical presentation of girls vs boys is very different. The authors of this article propose that 5 alpha reductase activity controls a back door method where by progesterone is converted to androgens.
administered zoledronic acid (4 mg). Prednisolone (1 mg/kg/day) was started and simultaneously, she was administered first cycle of ABVD (Adriamycin: 25 mg/m2, Bleomycin: 10 U/m2, Vinblastine: 6 mg/m2 and Dacarbazine: 375 mg/m2), which led to normalisation of serum calcium levels over 4 days and improvement in her hemoglobin levels
Etiology of anemia in Hodgkin’s lymphoma is multifactorial. Anemia of chronic disease, decreased red cell survival, infiltration of bone marrow by tumor and marrow suppression by chemotherapy/radiotherapy are the common mechanisms
Our case had only a transient response to steroids and chemotherapy. Therefore, she was treated with Rituximab which brought hemolysis under control
Hypercalcemia in HL is rare and its incidence has been reported as 0.9, 1.6 and 5.4 % in different series
Hypercalcemia of malignancy involves three mechanisms: 1. Humoral hypercalcemia mediated by PTHrP—seen in solid tumors like breast cancer and adult T cell leukemia/lymphoma (ATLL), 2. Direct osteoclast mediated bone resorption due to bony metastasis—seen in solid tumors and multiple myeloma, 3. Calcitriol mediated hypercalcemia—seen in Hodgkin’s and non-Hodgkin’s lymphoma as well as granulomatous disorders like tuberculosis, sarcoidosis, leprosy and disseminated Candidiasis
Mechanism of hypercalcemia in HL has long been suggested to involve extra-renal activation of 1α-hydroxylase leading to production of 1, 25(OD)2 Vitamin D3 or Calcitriol, an active metabolite of Vitamin D, which leads to increased re-absorption of calcium and phosphate from intestine, increased osteoclast activation and bone resorption as well as increased phosphate re-absorption in renal tubules
The source of 1α-hydroxylase in HL has been postulated as monocytes and macrophages infiltrating the tumor akin to tuberculosis or sarcoidosis and is stimulated by IFN-γ secreted by T-lymphocytes
Like sarcoidosis, patients with HL exhibit increased sensitivity to Vitamin D supplements and sunlight, which have been found to precipitate hypercalcemia in these patients
Classical biochemical profile in Calcitriol mediated hypercalcemia include: an elevated calcium, normal/slightly elevated phosphate, normal 25(OH) Vitamin D, suppressed PTHrP and PTH, elevated Calcitriol and a normal/increased tubular reabsorption of phosphate
not been associated with a poorer prognosis and tends to subside after treatment of the underlying disease
Female aging is characterized by menopausal change in sex steroid hormones concomitant to increase in aging-related decrements in skeletal muscle performance that can be attenuated by HRT use
The major canonical pathways found to be differentially regulated included mitochondrial dysfunction, oxidative phosphorylation, glycolysis, and TCA-cycle, strong indicators for affected energy metabolism
E2 to exert anti-apoptotic effects in muscle progenitor cells by improving mitochondrial function
E2 is a major regulator of human skeletal muscle signaling in women
After menopause, when ovarian E2 production is ceased, the prevalence of cardio-metabolic diseases increases. Our result that different trajectories of the energy pathways in the skeletal muscle may be regulated by E2 provides candidate molecules as key targets for future interventions to prevent or treat postmenopausal metabolic dysregulation
Study finds Estradiol regulates human skeletal muscle cell signaling (mitochondrial function, oxidative phosphorylation, glycolysis, and TCA cycle) in study of pre/post menopause women through proteome analysis. This study would have been complete if they had carried to search beyond that of protein to epigenetics.
Stretch marks are formed deep within the dermis layer and happen due to rapid stretching, this causes damage to the skin's connecting tissues. To get rid of these stretch marks we are introducing to you our latest laser treatment i.e. PIXIGENUS. It is a unique technology to eliminate stretchmarks from various parts of the body. Watch the full video to know more.
Stretch marks are caused because of rapid stretching of the skin that results into scars and discoloration of the skin. There are many reasons which can lead to stretch marks such as rapid weight reduction, quick weight gain, excessive exercise, steroids, pregnancy, hormonal changes, puberty etc.
Millions of women have stretch marks, but this fact does little to lessen the embarrassment that most women feel at the appearance of these unattractive striations on their skin. Stretch marks, also known as striae, are a form of scarring on the skin with an off-color hue. Over time they may reduce, but will not disappear completely. Tearing of the dermis results into stretch marks.
In early PET literature focusing on analysis of solitary pulmonary nodules, some researchers defined malignancy based on a SUVmax threshold of greater than 2.5
We contend that SUV analysis has virtually no role in this setting.
tumours grow as spheres, whereas inflammatory processes are typically linear
Far more important than the SUVmax is the pattern rather than intensity of metabolic abnormality and the correlative CT findings
Descriptively, we define SUV < 5 as “low intensity”, 5–10 as “moderate”, 10–15 as “intense” and >15 as “very intense”
Evolving literature suggests that intensity of uptake is an independent prognostic factor and in some tumour subtypes superior to histopathologic characterisation.
aerobic glycolysis
Our practice of thresholding the grey and colour scale to liver as detailed above results in similar image intensity to a fixed upper SUV threshold of 8 to 10
The advantage of using the liver as a reference tissue is also aided by this organ having rather low variability in metabolic activity
When the liver is abnormal and cannot be used as a reference organ, we use the default SUV setting of an upper SUV threshold of 8
One of the most challenging aspects of oncologic FDG PET/CT review, however, is to recognise all the patterns of metabolic activity that are not malignant and which consequently confound interpretation
Many benign and inflammatory processes are also associated with high glycolytic activity
Future articles in the “How I Read” series will address the specific details of reading PET/CT in various cancers
The intensity of uptake in metastases usually parallels that in the primary site of disease
For example, discordant low-grade activity in an enlarged lymph node in the setting of intense uptake in the primary tumour suggests it is unlikely malignant and more likely inflammatory or reactive
By CT criteria the enlarged node is ‘pathologic’ but the discordantly low metabolic signature further characterises this is as non-malignant since such a node is not subject to partial volume effects and therefore the intensity of uptake should be similar to the primary site
The exception is when the lymph node is centrally necrotic as a small rim of viable tumour is subject to partial volume effects with expectant lower intensity of uptake; integrating the CT morphology is therefore critical to reaching an accurate interpretation
Small nodes that are visualised on PET are conversely much more likely to be metastatic as such nodes are subject to partial volume effects.
The exception to this rule is tumours with a propensity for tumour heterogeneity at different sites
The combination of FDG and a more specific tracer, which visualises the well-differentiated disease can be very useful to characterise this phenomenon
“metabolic signature”
For the majority of malignant processes, the intensity of metabolic abnormality correlates with degree of aggressiveness or proliferative rate.
a negative PET/CT study in a patient with biopsy proven malignancy would be considered false-negative
Warburg effect
There, however, are a significant minority of tumours that utilise substrates other glucose such as glutamine or fatty acids as a source of the carbon atoms required for growth and proliferation
This includes a subset of diffuse gastric adenocarcinomas, signet cell colonic adenocarcinomas and some sarcomas, particularly liposarcoma
There may be a role for other radiotracers such as fluorothymidine (FLT) or amino acid substrates in this setting.
Some tumours harbour mutations that result in defective aerobic mitochondrial energy metabolism, effectively simulating the Warburg effect
patients with hereditary paraganglioma and pheochromocytoma highlight this phenomenon
These have intense uptake on FDG PET/CT despite often having low proliferative rate.
Uterine fibroids, hepatic adenomas, fibroadenomas of the breast and desmoid tumours are benign or relatively benign lesions that can have quite high FDG-avidity.
Metabolic activity switches off rapidly following initiation of therapy
Common examples where patients have commenced active therapy but the referrer is requesting “staging” includes hormonal therapy (eg. tamoxifen) in breast cancer, oral capecitabine in colorectal cancer or high dose steroids in Hodgkin’s lymphoma
It is therefore critical to perform PET staging before commencement of anti-tumour therapy
The potential advantage of routine diagnostic CT is improved anatomic localisation and definition
Without intravenous contrast, additional identification of typical oncologic complications such as pulmonary embolism or venous thrombosis cannot be identified
If the study is performed as an “interim” restaging study after commencement of therapy but before completion, in order to reach a valid or clinically useful conclusion findings must be interpreted in the context of known changes that occur at a specific timing and type of therapy
The most well studied use of interim PET is in Hodgkin’s lymphoma where repeat PET after two cycles of ABVD-chemotherapy provides powerful prognostic information and may improve outcomes by enabling early change of management
good read on the PET/CT scan reading. They mention that tumors are spheres and inflammation is linear, yet inflammation coexists with cancer; hard to simply delineate these on simple terms. I do agree aon the metabolic signature of the PET/CT scan
Data from the American Cancer Society show that the rate of increase in cancer deaths/year (3.4%) was two-fold greater than the rate of increase in new cases/year (1.7%) from 2013 to 2017
cancer is predicted to overtake heart disease as the leading cause of death in Western societies
cancer can also be recognized as a metabolic disease.
glucose is first split into two molecules of pyruvate through the Embden–Meyerhof–Parnas glycolytic pathway in the cytosol
Aerobic fermentation, on the other hand, involves the production of lactic acid under normoxic conditions
persistent lactic acid production in the presence of adequate oxygen is indicative of abnormal respiration
Otto Warburg first proposed that all cancers arise from damage to cellular respiration
The Crabtree effect is an artifact of the in vitro environment and involves the glucose-induced suppression of respiration with a corresponding elevation of lactic acid production even under hyperoxic (pO2 = 120–160 mmHg) conditions associated with cell culture
the Warburg theory of insufficient aerobic respiration remains as the most credible explanation for the origin of tumor cells [2, 37, 51, 52, 53, 54, 55, 56, 57].
The main points of Warburg’s theory are; 1) insufficient respiration is the predisposing initiator of tumorigenesis and ultimately cancer, 2) energy through glycolysis gradually compensates for insufficient energy through respiration, 3) cancer cells continue to produce lactic acid in the presence of oxygen, and 4) respiratory insufficiency eventually becomes irreversible
Efraim Racker coined the term “Warburg effect”, which refers to the aerobic glycolysis that occurs in cancer cells
Warburg clearly demonstrated that aerobic fermentation (aerobic glycolysis) is an effect, and not the cause, of insufficient respiration
all tumor cells that have been examined to date contain abnormalities in the content or composition of cardiolipin
The evidence supporting Warburg’s original theory comes from a broad range of cancers and is now overwhelming
respiratory insufficiency, arising from any number mitochondrial defects, can contribute to the fermentation metabolism seen in tumor cells.
data from the nuclear and mitochondrial transfer experiments suggest that oncogene changes are effects, rather than causes, of tumorigenesis
Normal mitochondria can suppress tumorigenesis, whereas abnormal mitochondria can enhance tumorigenesis
In addition to glucose, cancer cells also rely heavily on glutamine for growth and survival
Glutamine is anapleurotic and can be rapidly metabolized to glutamate and then to α-ketoglutarate for entry into the TCA cycle
Glucose and glutamine act synergistically for driving rapid tumor cell growth
Glutamine metabolism can produce ATP from the TCA cycle under aerobic conditions
Amino acid fermentation can generate energy through TCA cycle substrate level phosphorylation under hypoxic conditions
targeting glucose and glutamine will deprive the microenvironment of fermentable fuels
Although Warburg’s hypothesis on the origin of cancer has created confusion and controversy [37, 38, 39, 40], his hypothesis has never been disproved
Warburg referred to the phenomenon of enhanced glycolysis in cancer cells as “aerobic fermentation” to highlight the abnormal production of lactic acid in the presence of oxygen
Emerging evidence indicates that macrophages, or their fusion hybridization with neoplastic stem cells, are the origin of metastatic cancer cells
Radiation therapy can enhance fusion hybridization that could increase risk for invasive and metastatic tumor cells
Kamphorst et al. in showing that pancreatic ductal adenocarcinoma cells could obtain glutamine under nutrient poor conditions through lysosomal digestion of extracellular proteins
It will therefore become necessary to also target lysosomal digestion, under reduced glucose and glutamine conditions, to effectively manage those invasive and metastatic cancers that express cannibalism and phagocytosis.
Previous studies in yeast and mammalian cells show that disruption of aerobic respiration can cause mutations (loss of heterozygosity, chromosome instability, and epigenetic modifications etc.) in the nuclear genome
The somatic mutations and genomic instability seen in tumor cells thus arise from a protracted reliance on fermentation energy metabolism and a disruption of redox balance through excess oxidative stress.
According to the mitochondrial metabolic theory of cancer, the large genomic heterogeneity seen in tumor cells arises as a consequence, rather than as a cause, of mitochondrial dysfunction
A therapeutic strategy targeting the metabolic abnormality common to most tumor cells should therefore be more effective in managing cancer than would a strategy targeting genetic mutations that vary widely between tumors of the same histological grade and even within the same tumor
Tumor cells are more fit than normal cells to survive in the hypoxic niche of the tumor microenvironment
Hypoxic adaptation of tumor cells allows for them to avoid apoptosis due to their metabolic reprograming following a gradual loss of respiratory function
The high rates of tumor cell glycolysis and glutaminolysis will also make them resistant to apoptosis, ROS, and chemotherapy drugs
Despite having high levels of ROS, glutamate-derived from glutamine contributes to glutathione production that can protect tumor cells from ROS
reason to eliminate glutamine in cancer patients and even GSH with cancer patients
It is clear that adaptability to environmental stress is greater in normal cells than in tumor cells, as normal cells can transition from the metabolism of glucose to the metabolism of ketone bodies when glucose becomes limiting
Mitochondrial respiratory chain defects will prevent tumor cells from using ketone bodies for energy
glycolysis-dependent tumor cells are less adaptable to metabolic stress than are the normal cells. This vulnerability can be exploited for targeting tumor cell energy metabolism
In contrast to dietary energy reduction, radiation and toxic drugs can damage the microenvironment and transform normal cells into tumor cells while also creating tumor cells that become highly resistant to drugs and radiation
Drug-resistant tumor cells arise in large part from the damage to respiration in bystander pre-cancerous cells
Because energy generated through substrate level phosphorylation is greater in tumor cells than in normal cells, tumor cells are more dependent than normal cells on the availability of fermentable fuels (glucose and glutamine)
Ketone bodies and fats are non-fermentable fuels
Although some tumor cells might appear to oxidize ketone bodies by the presence of ketolytic enzymes [181], it is not clear if ketone bodies and fats can provide sufficient energy for cell viability in the absence of glucose and glutamine
Apoptosis under energy stress is greater in tumor cells than in normal cells
A calorie restricted ketogenic diet or dietary energy reduction creates chronic metabolic stress in the body
. This energy stress acts as a press disturbance
Drugs that target availability of glucose and glutamine would act as pulse disturbances
Hyperbaric oxygen therapy can also be considered another pulse disturbance
The KD can more effectively reduce glucose and elevate blood ketone bodies than can CR alone making the KD potentially more therapeutic against tumors than CR
Campbell showed that tumor growth in rats is greater under high protein (>20%) than under low protein content (<10%) in the diet
Protein amino acids can be metabolized to glucose through the Cori cycle
The fats in KDs used clinically also contain more medium chain triglycerides
Calorie restriction, fasting, and restricted KDs are anti-angiogenic, anti-inflammatory, and pro-apoptotic and thus can target and eliminate tumor cells through multiple mechanisms
Ketogenic diets can also spare muscle protein, enhance immunity, and delay cancer cachexia, which is a major problem in managing metastatic cancer
GKI values of 1.0 or below are considered therapeutic
The GKI can therefore serve as a biomarker to assess the therapeutic efficacy of various diets in a broad range of cancers.
It is important to remember that insulin drives glycolysis through stimulation of the pyruvate dehydrogenase complex
The water-soluble ketone bodies (D-β-hydroxybutyrate and acetoacetate) are produced largely in the liver from adipocyte-derived fatty acids and ketogenic dietary fat. Ketone bodies bypass glycolysis and directly enter the mitochondria for metabolism to acetyl-CoA
Due to mitochondrial defects, tumor cells cannot exploit the therapeutic benefits of burning ketone bodies as normal cells would
Therapeutic ketosis with racemic ketone esters can also make it feasible to safely sustain hypoglycemia for inducing metabolic stress on cancer cells
Ketones are much more than energy adaptabilit, but actually are therapeutic.
ketone bodies can inhibit histone deacetylases (HDAC) [229]. HDAC inhibitors play a role in targeting the cancer epigenome
Therapeutic ketosis reduces circulating inflammatory markers, and ketones directly inhibit the NLRP3 inflammasome, an important pro-inflammatory pathway linked to carcinogenesis and an important target for cancer treatment response
Chronic psychological stress is known to promote tumorigenesis through elevations of blood glucose, glucocorticoids, catecholamines, and insulin-like growth factor (IGF-1)
In addition to calorie-restricted ketogenic diets, psychological stress management involving exercise, yoga, music etc. also act as press disturbances that can help reduce fatigue, depression, and anxiety in cancer patients and in animal models
Ketone supplementation has also been shown to reduce anxiety behavior in animal models
This physiological state also enhances the efficacy of chemotherapy and radiation therapy, while reducing the side effects
lower dosages of chemotherapeutic drugs can be used when administered together with calorie restriction or restricted ketogenic diets (KD-R)
Besides 2-DG, a range of other glycolysis inhibitors might also produce similar therapeutic effects when combined with the KD-R including 3-bromopyruvate, oxaloacetate, and lonidamine
oxaloacetate is a glycolytic inhibitor, as is doxycycline, and IVC.
A synergistic interaction of the KD diet plus radiation was seen
It is important to recognize, however, that the radiotherapy used in glioma patients can damage the respiration of normal cells and increase availability of glutamine in the microenvironment, which can increase risk of tumor recurrence especially when used together with the steroid drug dexamethasone
Poff and colleagues demonstrated that hyperbaric oxygen therapy (HBOT) enhanced the ability of the KD to reduce tumor growth and metastasis
HBOT also increases oxidative stress and membrane lipid peroxidation of GBM cells in vitro
The effects of the KD and HBOT can be enhanced with administration of exogenous ketones, which further suppressed tumor growth and metastasis
Besides HBOT, intravenous vitamin C and dichloroacetate (DCA) can also be used with the KD to selectively increase oxidative stress in tumor cells
Recent evidence also shows that ketone supplementation may enhance or preserve overall physical and mental health
Some tumors use glucose as a prime fuel for growth, whereas other tumors use glutamine as a prime fuel [102, 186, 262, 263, 264]. Glutamine-dependent tumors are generally less detectable than glucose-dependent under FDG-PET imaging, but could be detected under glutamine-based PET imaging
GBM and use glutamine as a major fuel
Many of the current treatments used for cancer management are based on the view that cancer is a genetic disease
Emerging evidence indicates that cancer is a mitochondrial metabolic disease that depends on availability of fermentable fuels for tumor cell growth and survival
Glucose and glutamine are the most abundant fermentable fuels present in the circulation and in the tumor microenvironment
Low-carbohydrate, high fat-ketogenic diets coupled with glycolysis inhibitors will reduce metabolic flux through the glycolytic and pentose phosphate pathways needed for synthesis of ATP, lipids, glutathione, and nucleotides
The SOC for GBM was modified in this patient to initiate KMT prior to surgical resection, to eliminate steroid medication, and to include HBOT as part of the therapy
the greatest therapeutic benefit for patients (near 1.0)
The observed reduction in blood glucose in our patient would reduce lactic acid fermentation in the tumor cells, while the elevation of ketone bodies would fuel normal cells thus protecting them from hypoglycemia and oxidative stress
Previous studies showed that GBM survival and tumor growth was correlated with blood glucose levels
Evidence indicates that glioma cells cannot effectively use ketone bodies for energy due to defects in the number, structure, and function of their mitochondria
The accuracy of the GKI as a predictor for therapeutic efficacy, however, is better when ketone bodies are measured from the blood than when measured from the urine
A reduction of glucose-driven lactic acid fermentation would not only increase tumor cell apoptosis, but would also reduce inflammation and edema in the tumor microenvironment thus reducing tumor cell angiogenesis and invasion
Besides serving as a metabolic fuel for GBM, glutamine is also an essential metabolite for normal immune cells
therapies that inhibit glutamine availability and utilization must be strategically employed to avoid inadvertent impairment of immune cell functions
we used the non-toxic green tea extract, EGCG, and chloroquine in an attempt to limit glutamine availability to the tumor cells
EGCG is thought to target the glutamate dehydrogenase activity that facilitates glutamine metabolism in GBM cells
Chloroquine, on the other hand, will inhibit lysosomal digestion thus restricting fermentable amino acids and carbohydrates from phagocytosed materials in the tumor microenvironment
HBOT to increase oxidative stress in the tumor cells
As glucose and glutamine fermentation protect tumor cells from oxidative stress, reduced availability of these metabolites under ketosis could enhance the therapeutic action of HBOT, as we recently described
Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast
Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day
KD (increased to 1,500 kcal/day at day 22
the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA)
Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D
This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies
Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers
less than 20% of younger adults generally survive beyond 24 months
glucose and glutamine are the primary fuels that drive the rapid growth of most tumors including GBM
Glucose drives tumor growth through aerobic fermentation (Warburg effect), while glutamine drives tumor growth through glutaminolysis
The fermentation waste products of these molecules, i.e., lactic acid and succinic acid, respectively, acidify the tumor microenvironment thus contributing further to tumor progression
Glucose and glutamine metabolism is also responsible for the high antioxidant capacity of the tumor cells thus making them resistant to chemo- and radiotherapies
The reliance on glucose and glutamine for tumor cell malignancy comes largely from the documented defects in the number, structure, and function of mitochondria and mitochondrial-associated membranes
These abnormalities cause the neoplastic GBM cells to rely more heavily on substrate level phosphorylation than on oxidative phosphorylation for energy
dexamethasone not only increases blood glucose levels but also increases glutamine levels through its induction of glutamine synthetase activity
Calorie restriction and restricted KD are anti-angiogenic, anti-inflammatory, anti-invasive, and also kill tumor cells through a proapoptotic mechanism
Evidence also shows that therapeutic ketosis can act synergistically with several drugs and procedures to enhance cancer management improving both progression free and overall survival
hyperbaric oxygen therapy (HBOT) increases oxidative stress on tumor cells especially when used alongside therapies that reduce blood glucose and raise blood ketones
The glutamine dehydrogenase inhibitor, epigallocatechin gallate (EGCG) is also proposed to target glutamine metabolism