Abstract：
:We have previously presented a new Systemic Evolutionary Theory of Cancer (SETOC) based on the failure of proper endosymbiosis in eukaryotic cells. Here, we propose that the progressive uncoupling of two endosymbiotic subsystems (information and energy) inside the cell, as a consequence of long-term injuries, gives rise to alterations (i) in tissue interactions and (ii) in cell organization. In the first case, we argue that the impairment of both the coherent state and the synergy between intercellular communications underpins the onset of tissue dysplasia, that usually evolves towards cancer development. In the second case, we suggest that the rupture of endosymbiosis drives a sort of cell regression towards a protist-like entity represented by the concept of "de-emergence" postulated in our systemic evolutionary approach to carcinogenesis. This conceptual association of the cancer cell with a protist-like organism could support the development of novel cancer therapeutic approaches. To this end, we propose a paradigm shift in cancer pharmacology since: i) our knowledge of cancer pathophysiology as a complex system is insufficient, despite a vast knowledge of molecular mechanisms underlying cancer; ii) current cancer pharmacology deals only with microvariables (e.g. gene or protein targets), which do not account for the integrated pathophysiology of cancer, rather than with macrovariables (e.g. pH, membrane potential, electromagnetic fields, cell communications and so on) and mesovariables (between micro and macro), such as the interaction between various cellular components including cellular organelles. This paradigm shift should allow cancer pharmacology to move forward from molecular treatments (focusing on single targets) to modular treatments that consider cancer-related processes (i.e. inflammation, coagulation, etc.) or even to a sort of ecosystemic treatment addressing the whole functioning of the "cancer ecosystem". Examples of ecosystems treatment may be natural plant derivatives that act synergistically or pulsed electromagnetic fields which can act on particular biological processes in cancer cells. In addition, we need different working theoretical models on which to base new anticancer pharmacological approaches. Finally, we examine what value our systemic evolutionary approach could add to cancer treatments, in particular in liver cancer as a paradigm for developing potential applications.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Mazzocca A,Ferraro G,Misciagna G,Fais Sdoi
10.1016/j.mehy.2018.09.033subject
Has Abstractpub_date
2018-12-01 00:00:00pages
80-87eissn
0306-9877issn
1532-2777pii
S0306-9877(18)30667-4journal_volume
121pub_type
杂志文章abstract：:Patients with chronic kidney disease (CKD) experience co-morbid illnesses, including cardiovascular disease and retinopathy. Sevelamer hydrochloride (Renagel®); a non-calcium phosphate binder reduces coronary artery and aortic calcification as compared to calcium containing phosphate binders and additionally effects i...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.12.035
更新日期：2013-04-01 00:00:00
abstract：:For diagnosis of Human Immunodeficiency Virus (HIV) infection by the recently developed Polymerase Chain Reaction (PCR), the two commonly used clinical samples are either the peripheral blood monocytes (PBMC) or the plasma of the infected individuals. In the former instance, DNA is extracted from PBMC. The integrated ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(93)90188-v
更新日期：1993-01-01 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：:Despite all improvements in transplant medicine, renal transplant recipients have a high risk for cardiovascular mortality. A high prevalence of cardiovascular complications in renal transplant recipients (RTR) is explained by cardiovascular risk factors present before transplantation, in addition to the development o...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2013.10.030
更新日期：2014-01-01 00:00:00
abstract：:Chronic Interstitial Nephritis in Agricultural Communities (CINAC) continues to attract controversy in the scientific community. It was previously known as Chronic Kidney Disease of Unknown Etiology (CKDu) and is not associated with the common aetiological factors such as diabetes. There is general acceptance that it ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.110414
更新日期：2021-01-01 00:00:00
abstract：:The authors sought to establish whether maternal dietary methanol during pregnancy was a factor in the etiology of autism spectrum disorders. A seven item questionnaire was given to women who had given birth to at least one child after 1984. The subjects were solicited from a large primary care practice and several in...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2015.06.025
更新日期：2015-10-01 00:00:00
abstract：:The classical form of Barlow's disease or infantile scurvy, with bruises, broken bones and sores that will not heal, is rarely seen today, but it seems to be reappearing under a different guise, when infants with borderline vitamin C depletion are assaulted with too many inoculations at one time.Moreover, it is now so...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(02)00114-7
更新日期：2002-07-01 00:00:00
abstract：:Nasopharyngeal angiofibroma is a histologically benign tumor composed of stroma and vessels. The vascular component of the lesion is prone to bleeding and responsible for its clinical "malignancy". Some nasopharyngeal angiofibromas are resistant to surgical therapy because of extensive growth and occasionally bone des...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2007.06.011
更新日期：2008-01-01 00:00:00
abstract：:Intrauterine growth retardation (IUGR) is associated with insulin resistance, non-insulin-dependent diabetes mellitus (NIDDM) and cardiovascular diseases in adulthood. Postnatal tissues contain stem cells that though quiescent, retain their capacity to self-renew and regenerate tissues to fulfil organ demands. I propo...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(03)00182-8
更新日期：2003-09-01 00:00:00
abstract：:Although the classical ideal is that scientific theories are evaluated by a careful teasing-out of their internal logic and external implications, and checking whether these deductions and predictions are in-line-with old and new observations; the fact that so many vague, dumb or incoherent scientific theories are app...
journal_title：Medical hypotheses
pub_type： 社论
doi：10.1016/j.mehy.2008.05.018
更新日期：2008-09-01 00:00:00
abstract：:An expansion of the 'stable' gene hypothesis proposed previously is the hypothesis that there is a range of genes, some proto-oncogenes and some not, varying from those with multiple copies in the genome, wide distribution among species, and limited mutability because of a specific protective stabilizing mechanism of ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(95)90078-0
更新日期：1995-02-01 00:00:00
abstract：:Vitamin A is a fat-soluble vitamin required for many physiological functions. The intracellular transport of vitamin A is assisted by proteins called cellular retinol-binding proteins (CRBP I/II). The absorption, storage and usage of vitamin A are regulated by a protein called lecithin:retinol acyltransferase (LRAT), ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2016.01.013
更新日期：2016-03-01 00:00:00
abstract：:Dupuytren's disease is a pathological condition of the palmar fascia characterized by the formation of contractile disease cords that result in permanent finger contracture. This condition is believed to progress from a myofibroblast-rich nodule in the early clinical stages of the disease to a contractile disease cord...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.10.009
更新日期：2010-03-01 00:00:00
abstract：:Clinical studies have shown that ionic zinc (Zn2+) dissolved in the mouth shortened manifestations of the common cold significantly, by an unknown mechanism. The observed immediate effect on symptoms is consonant with osmotic transport of Zn2+, placing a temporary chemical clamp on critical nerves. It is proposed that...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(96)90259-5
更新日期：1996-03-01 00:00:00
abstract：:The paper proposes a mechanism for regulating nucleo-cytoplasmic exchanges of macromolecules via NPC in vertebrates. Bending of NE toward the transport vector significantly contributes to the dynamics. ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1998.0813
更新日期：2000-01-01 00:00:00
abstract：:Several earlier observations by us and other investigators led us to propose a thesis that B lymphocytes, when activated by a virus, allo-antigen or bacterial protein would enter into effector arm of the immune response and cause allograft and tumor rejection or GVH-type of lesion in immunosuppressed animals. These ef...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(90)90071-l
更新日期：1990-05-01 00:00:00
abstract：:Burnout is a state of physical or mental collapse caused by overwork or stress. Burnout during residency training has gained significant attention secondary to concerns regarding job performance and patient care. The new COVID-19 pandemic has raised public health problems around the world and required a reorganization...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.109972
更新日期：2020-11-01 00:00:00
abstract：:Homeostasis, or the maintenance of constant internal environment in the organism, is disrupted by injury. In this case, pathological defence reactions such as inflammation and healing take place in order to restore it. They succeed if etiological harmful factors are eliminated. In the opposite case, constant injury le...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(91)90247-v
更新日期：1991-10-01 00:00:00
abstract：:Hypertensive left ventricular hypertrophy (LVH) is a maladaptive response to chronic pressure overload and a strong independent risk factor for cardiovascular disease. Regression of LVH is associated with improved prognosis. Regression of LVH with antihypertensive therapy (angiotensin-converting enzyme inhibitors, ang...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2015.12.016
更新日期：2016-02-01 00:00:00
abstract：:Human papillomavirus (HPV) type 16 is causally associated with a subset of oral cancers, predominantly those cancers arising in the oropharynx (OP). Increased HPV16 E6 and E7 oncogene expressions are responsible for the malignant transmission in these cancers. ErbB-2 is the family member most closely implicated in hum...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2004.03.013
更新日期：2004-01-01 00:00:00
abstract：:Long pentraxin 3 (PTX3) is a recently discovered multimeric inflammatory mediator that is structurally linked to short pentraxins, such as C-reactive protein (CRP) and serum amyloid P component. PTX3 is produced by a variety of tissues and cells, including vascular endothelial cells and macrophages. Because of its ext...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.05.011
更新日期：2012-09-01 00:00:00
abstract：:Intractable epilepsy has always posed a challenge to management; conventional, surgical and alternative techniques available so far (e.g., vagal nerve stimulation, i.e. VNS). The author has attempted to search for a novel alternative (drug-regime) approach to its management to minimise any invasive technique or surger...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(03)00150-6
更新日期：2003-08-01 00:00:00
abstract：:Anorexia nervosa was explored as the possible expression of an aberration of the processing of information which ordinarily has value in life protection or extension. Each of 6 areas was briefly reviewed, and noted to have the potential for failure to balance 2 or more factors. Anorexia nervosa may prove to be a psych...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(90)90079-t
更新日期：1990-09-01 00:00:00
abstract：:The hypothesis of the evolutionary origin of bipolar disorder (EOBD) synthesized ideas about the biological clock and seasonal shifts in mood (Rosenthal, Wehr) with theorizing that bipolar disorder descends from a pyknic (compact, cold-adapted) group (Kretchmer). The hypothesis suggested that bipolar behaviors evolved...
journal_title：Medical hypotheses
pub_type： 历史文章,杂志文章
doi：10.1016/j.mehy.2011.10.005
更新日期：2012-01-01 00:00:00
abstract：:The morphological changes used to confirm a diagnosis of coeliac disease (CD) are precisely those predicted if the surface energy of the interface between duodenal epithelium and the luminal contents were raised to levels comparable to those demonstrated by the hydrophobic nature of the stomach wall. This hypothesis p...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(90)90126-y
更新日期：1990-07-01 00:00:00
abstract：:Personality trait research has shown associations with many genes, prominently those of the catecholamine metabolism such as dopamine beta hydroxylase (DBH), catechol-O-methyltransferase (COMT), and monoamine oxidase A (MAOA). Because DBH gene is in linkage disequilibrium with ABO gene, there is reason to think that o...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.04.039
更新日期：2011-08-01 00:00:00
abstract：:The CoV-19 infection appears to be unusual among patients with type 1 Diabetes Mellitus, although they are considered a fragile population. We think that this in part due to the peculiar immune condition that leads to the destruction of the Beta cells. ...
journal_title：Medical hypotheses
pub_type： 信件
doi：10.1016/j.mehy.2020.109795
更新日期：2020-09-01 00:00:00
abstract：:The etiology of focal distribution of atherosclerotic lesions has received much attention for many years. Current theories focus on mechanical factors such as low endothelial shear stress as an initiating factor for atherosclerosis formation. However, some evidences revealed that it could not be initiator of endotheli...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2008.11.049
更新日期：2009-12-01 00:00:00
abstract：:Several attempts to control the dreadfulness of SARS-CoV-2 are still underway. Based on the literature evidences we have speculated a prospective contemporary remedy, which was categorized into Specificity, Remedy, and a Conveyor. In which, pros and cons were discussed and inferred the possible alternatives. (a) Speci...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.109976
更新日期：2020-11-01 00:00:00
abstract：:It is suggested that apart from aflatoxins, plant medicinal preparations containing active compounds imperatorin, dictamine, marmesin and heraclenin may be responsible for some human cancers in Nigeria and perhaps other parts of Africa. Therefore, in this paper, a hypothesis is put forward that these compounds or thei...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(83)90096-8
更新日期：1983-07-01 00:00:00
