Abstract:
:Cancer cells have a greater need for energy and a ready supply of the building blocks necessary for the synthesis of macromolecules (nucleotides, protein, lipids) in order to duplicate genome and biomass. The hypothesis can be postulated that those precursors for synthetic processes, which can only be furnished by glycolysis, cannot be sufficiently recruited from external sources (the blood stream) and that glycolysis is necessarily markedly activated. It can also be hypothesized that the Krebs cycle, which also furnishes precursors for macromolecule synthesis to meet the requirements of proliferating cells, is depleted of intermediates. In view of its cyclic nature requiring not only pyruvate but also oxalacetate as the "last" metabolite of the reaction sequence for its sustenance, the Krebs cycle may be partially inactivated. While anaplerotic reactions and other sources (amino acids and fatty acids) could supply the cycle with intermediates, those pathways constitute futile cycles for amino and fatty acids as they would be partially degraded in the cycle and the intermediates thus obtained would be exported into the cytoplasm for synthetic processes with no advantage for the cell. It is also hypothesized that glutamine, an important fuel for cancer cells and playing a critical role in anaplerosis, may not contribute to reinforce the cycle; malate and α-ketoglutarate, two products of glutamine metabolism, might be exported from the mitochondria as precursors of biosynthetic pathways. It is possible then that malate, used for NADPH production required in the biosynthetic pathways, and glycerol-phosphate, too used for biosynthetic purposes (lipid biosynthesis), are unable to sustain the mitochondrial redox shuttles reducing the respiratory capacity of the mitochondria. Low shuttle capacity implies that NADH generated by glycolysis needs to be continuously re-oxidized in the cytoplasm via lactate dehydrogenase to maintain glycolysis fully activated, causing the abnormal lactate production observed in cancer. The paper goes onto discuss the essential role of glucose in cancer cell proliferation also in inducing the Crabtree effect. It is finally hypothesized that respiration inhibition after cancer cells have been supplied with glucose is due to reactivation in a suited medium of biosynthetic pathways with the consequences described above.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Dell' Antone Pdoi
10.1016/j.mehy.2012.06.002subject
Has Abstractpub_date
2012-09-01 00:00:00pages
388-92issue
3eissn
0306-9877issn
1532-2777pii
S0306-9877(12)00267-8journal_volume
79pub_type
杂志文章abstract::Howard Gardner identified five different kinds of creative activity among eminent creators, namely, solving a well-defined problem, putting forth a general conceptual scheme, creating a product that embodies ideas, stylized innovation of an art form, and a 'high-stakes' performance in the socio-political arena. In thi...
journal_title:Medical hypotheses
pub_type: 传,历史文章,杂志文章
doi:10.1054/mehy.1998.0777
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND:Somatization is a multisomatoform disorder characterized by medically unexplained, functional or psychosomatic symptoms. Similar somatic symptoms are key components of depression and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). METHODS:This paper reviews the evidence that such symptoms are o...
journal_title:Medical hypotheses
pub_type: 杂志文章,评审
doi:10.1016/j.mehy.2012.02.023
更新日期:2012-06-01 00:00:00
abstract::Review of 18th and 19th century psychiatric therapies raises the possibility that several may have altered the activity of vasopressin or Na-K-ATPase. Bleeding, whirling, nausea created by medicines, and vagus nerve stimulation by application of electricity through the skin all perturb the hypothalamic hormone, argini...
journal_title:Medical hypotheses
pub_type: 历史文章,杂志文章
doi:10.1016/j.mehy.2003.10.007
更新日期:2004-01-01 00:00:00
abstract::"Consciousness" "mood," "identity" and "personality" are all emergent properties from whole-brain organizations; these are typically disturbed in psychiatric disorders. This work proposes that the underlying etiopathology of mental disorders originates from disturbances to global brain dynamics, or "Globalopathies" th...
journal_title:Medical hypotheses
pub_type: 杂志文章,评审
doi:10.1016/j.mehy.2013.09.032
更新日期:2013-12-01 00:00:00
abstract::The initial treatment for hypotension due to blood loss is intravenous fluids. Occasionally there is need for additional medication, as well as stopping the source of the bleeding. The literature in the main discusses the use of dopamine. Ephedrine has not been reviewed as useful in such situations. This article discu...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(91)90242-q
更新日期:1991-07-01 00:00:00
abstract::It is a known fact that individuals who engaged in delinquent behavior in childhood are more probable to carry on similar behavior in adulthood. If the factors that lead children to involve in delinquency are defined, the risk of dragging children into crime can be detected before they are involved in crime and delinq...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2020.110118
更新日期:2020-10-01 00:00:00
abstract::The present study developed a feature selection (FS)-based decision support system using the electroencephalography (EEG) signals recorded from neonates with and without seizures. The study employed 10 different FS algorithms to reduce the classification cost by using fewer features and to improve the classification p...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2019.109464
更新日期:2020-02-01 00:00:00
abstract::We describe a six-month-old girl with microcephaly, developmental delay, truncal hypotonia, left pyramidal signs, partial seizures and myoclonic spasms, born to a feverish mother. MRI showed bilateral vascular lesions in the territory of the middle cerebral arteries, prevalent in the right hemisphere, together with hy...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2011.04.023
更新日期:2011-08-01 00:00:00
abstract::Bone and cartilage are major weight-bearing connective tissues in human and possesses utmost vulnerability for degeneration. The potential causes are mechanical trauma, cancer and disease condition like osteoarthritis and osteoporosis, etc. The regeneration/repair is a challenging, since their complex structures and a...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2017.07.021
更新日期:2017-10-01 00:00:00
abstract::Why is modern science less efficient than it used to be, why has revolutionary science declined, and why has science become so dishonest? One plausible explanation behind these observations comes from an essay First and second things published by CS Lewis. First Things are the goals that are given priority as the prim...
journal_title:Medical hypotheses
pub_type: 社论
doi:10.1016/j.mehy.2009.08.017
更新日期:2010-01-01 00:00:00
abstract::Articles dealing with the epidemiological aspects of asthma were carefully reviewed in order to support or reject our clinical impression of increased rate of asthma among immigrants. Particular emphasis was put on data on very high or very low rates of asthma. The proposed theories to explain these differences were c...
journal_title:Medical hypotheses
pub_type: 杂志文章,meta分析
doi:10.1016/s0306-9877(98)90047-0
更新日期:1998-10-01 00:00:00
abstract::The paradigm of an immune system presumes that a system arose specifically to combat infection -- hence its name. This paradigm gained credibility with the discovery of antibodies and anamnestic immunity, even though these are relatively late arrivals in evolution. Another presumption has been that thymus-dependent T ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1054/mehy.1997.0645
更新日期:1999-03-01 00:00:00
abstract::The rise of anatomical realism in sculpture with the Classical Greeks puzzles art historians. Recently, it has been discovered that the motor cortex perceives motor actions. I argue that Classical artists discovered a new aesthetic based on using art to stimulate not just, as previously, the visual cortex, but also th...
journal_title:Medical hypotheses
pub_type: 历史文章,杂志文章
doi:10.1016/s0306-9877(98)90257-2
更新日期:1998-07-01 00:00:00
abstract::Chronic stresses can induce physiological and psychological changes and result in stress-related neuropsychiatry, sometimes they may also contribute to hypersensitivity to pain known as stress-induced hyperalgesia (SIH). Recently it was found that GABAergic disinhibition is closely related to morphine and chronic infl...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2014.10.008
更新日期:2014-12-01 00:00:00
abstract::It is proposed that, in addition to genetic factors involved in immune attack on myelin, higher concentrations of nerve growth factor in certain tissues during development determine susceptibility to multiple sclerosis. High early nerve growth factor in some vasculature of spontaneously hypertensive rats increases sym...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/s0306-9877(98)90071-8
更新日期:1998-12-01 00:00:00
abstract:UNLABELLED:Physiological acts present the puzzle that we are unable to explain how we performed them, how we solved the technical difficulties involved in their execution. For instance, when we sing, we produce various musical notes by changing the shape of the larynx. The normal person does not even know what the lary...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/s0306-9877(02)00156-1
更新日期:2002-12-01 00:00:00
abstract::Since forced unilateral nostril breathing activates the contralateral brain hemisphere, an animal analogue of this technique could be provided by methylmethacrylate gluing large plastic pellets in either the right or left nostrils in a group of rats. A large number of physiological, pharmacological, and immunological ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(89)90047-9
更新日期:1989-03-01 00:00:00
abstract::Jet lag is a travel-induced circadian rhythm phenomenon that afflicts healthy individuals following long- distance flights through several time zones. The typical jet-lag manifestations - insomnia during local sleep time, day fatigue, reduced concentration, irritability, and exhaustion with mild depression - are attri...
journal_title:Medical hypotheses
pub_type: 杂志文章,评审
doi:10.1054/mehy.2000.1094
更新日期:2001-01-01 00:00:00
abstract::A wealth of research data points to increased oxidative stress as a key driver of the cardiac remodeling triggered by chronic pressure overload, loss of functional myocardial tissue, or atrial fibrillation. Oxidative stress is a mediator of the cardiomyocyte hypertrophy and apoptosis, the cardiac fibrosis, and the def...
journal_title:Medical hypotheses
pub_type: 杂志文章,评审
doi:10.1016/j.mehy.2009.12.025
更新日期:2010-08-01 00:00:00
abstract::Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2008.07.044
更新日期:2009-02-01 00:00:00
abstract::S-allylgutimine has immunostimulant and tumor cell inhibitory activities. This complex action may be a result of the stimulation of IL-2 production. The effectiveness of immunotherapy depends on the uncoupling of IL-2 downregulation. This principle can be widely used with those immunological diseases where IL-2 level ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(93)90214-b
更新日期:1993-06-01 00:00:00
abstract::Pre-implantation genetic diagnosis (PGD) is a powerful clinical tool to identify embryos with or at risk of specific genetic diseases before implantation in utero after in vitro fertilization (IVF). PGD is performed on embryo biopsies that are obtained by aspiration of one or two cells from pre-implantation embryos at...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2014.08.019
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:There is widespread loss of acetylcholine and other neurotransmitters in Alzheimer's disease and vascular dementia. It has generally been assumed that death of neurons causes neurotransmitter loss, but alternatively neurotransmitter depletion itself may at least contribute to neurodegeneration. PRESENTATION...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2006.02.043
更新日期:2006-01-01 00:00:00
abstract::Colic is generally defined as excessive crying in early infancy and can have negative consequences on the infant as well as on the infant's family life. Excessive crying can result in escalating parental stress levels, abusive caregiver response, increased risk of shaken baby syndrome and parental postpartum depressio...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2014.05.018
更新日期:2014-09-01 00:00:00
abstract::We would like to put forward the hypothesis that cancer patients may produce autoantibodies that promote uncontrolled cell growth and thereby function as oncogenes. Dying cells release proteins that stimulate the production of autoantibodies, an event also known to occur during the earliest stages of tumor growth. If ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2006.03.006
更新日期:2006-01-01 00:00:00
abstract::Lack of vascularization results in increased demand for oxygen and creates a defined feature of the tumor microenvironment known as tumor hypoxia. It is well established that in response to hypoxia, hypoxia-inducible factor-1 α (HIF-1α) is induced which is an important factor in angiogenesis, invasion and metastasis. ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2020.110357
更新日期:2021-01-01 00:00:00
abstract::Synthetic ligands of the retinoid X receptor (RXR) have shown antidiabetic activity in mice, apparently owing to the fact that they stimulate the transcriptional activity of PPAR-gamma/RXR heterodimers, much like thiazolidinedione drugs. The chlorophyll metabolite phytanic acid has been shown to be a natural ligand fo...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1054/mehy.2000.1153
更新日期:2001-02-01 00:00:00
abstract::Both human cell lines HL-60 and AML-193 exhibit a myeloblastic and promyelocytic morphology, respectively, but may be regarded as bipotent leukemic precursors. They can be triggered to differentiate to either granulocytes or monocytes upon retinoic acid (RA) or 1,25-dihydroxyvitamin D (D3) addition, respectively. We h...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/s0306-9877(98)90025-1
更新日期:1998-03-01 00:00:00
abstract::In a recent paper it was argued that all stem cells are small motile cells, the haemopoietic stem cell being no exception. Although haemopoietic stem cells arise and mature in an extravascular milieu, they are present in small numbers in the peripheral circulation, where they have a lymphocyte-like appearance, and in ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(94)90144-9
更新日期:1994-09-01 00:00:00
abstract::A comparison of more important physical, chemical and biological properties of the nitric oxide (NO) and free stable nitroxyl radicals (nitroxides) on the base of their structural similarity is made in the article. The active moiety in the nitroxide molecule represents a sterically hindered nitric oxide. The mechanism...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1054/mehy.2001.1284
更新日期:2001-09-01 00:00:00