Laurent Schwartz

Assistance Publique – Hôpitaux de Paris | AP-HP · la liberté a un prix et il est élevé

We previously demonstrated that most diseases display a form of anabolism due to mitochondrial impairment: in cancer, a daughter cell is formed; in Alzheimer's disease, amyloid plaques; in inflammation cytokines and lymphokines. The infection by Covid-19 follows a similar pattern. Long-term effects include redox shift and cellular anabolism as a re...

Chlorine dioxide is a potent oxidant with in vitro anticancer activity. Its precise mechanism of action has not been thoroughly explored, but it is proposed that it acts through the redox imbalance of cancer cells. Three patients were treated for metastatic cancer (kidney, prostate, lymphoma, uterus and melanoma), on a compassionate basis. We repor...

Immunotherapy has recently yielded tremendous progress in the fight against malignancies. Its precise mechanism of action remains controversial. Activated leukocytes release reactive oxygen species which kill cancer cells. In the body, chlorine dioxide, orally ingested degrades into free radicals such as found in neutrophils. Chlorine dioxide is a...

The present paper deals with the development of a new and original hexadecyltrimethylammonium bromide (CTAB)-modified carbon paste electrode (CPE) dedicated for the direct analysis of nitrites in aquaculture and rat blood. The surface morphologies and contact angles of unmodified and modified CPEs were performed using Scanning Electron Microscopy (...

In this study, the neuroprotective potential of either Pergularia tomentosa leaf methanolic extract (PtE) alone or in combination with selenium nanoparticles (SeNPs-PtE) was investigated against lead acetate (PbAc)-induced neurotoxicity. Experimental rats were pretreated with PtE (100 mg/kg) or SeNPs-PtE (0.5 mg/kg) and injected intraperitoneally w...

This is a manifesto written by physicians and scientists for the drama of cancer to end

Specialization characterizes pharmacology, with the consequence of classifying the various treatments into unrelated categories. Treating a specific disease usually requires the design of a specific drug. The second law of thermodynamics is the driving force both for chemical reactions and for life. It applies to diseases and treatment. In most com...

Singlet dioxygen 1O2 is one excited state among the three other possible spectroscopic states of molecular oxygen. Here, we first describe the use of published spectroscopic data and thermodynamic modeling based on irreversible entropy production. Such concepts are further applied to the synthesis of singlet dioxygen and its reactions with crucial...

Cellular bioenergetics requires an intense ATP turnover that is increased further by hypermetabolic states caused by cancer growth or inflammation. Both are associated with metabolic alterations and, notably, enhancement of the Warburg effect (also known as aerobic glycolysis) of poor efficiency with regard to glucose consumption when compared to m...

We propose a simple mechanism for the self-replication of protocells. Our main hypothesis is that the amphiphilic molecules composing the membrane bilayer are synthesized inside the protocell through exothermic chemical reactions. The slow increase of the inner temperature forces the hottest molecules to move from the inner leaflet to the outer lea...

COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work o...

Tumor cells are known to favor a glycolytic metabolism over oxidative phosphorylation (OxPhos), which takes place in mitochondria, to produce the energy and building blocks essential for cell maintenance and cell growth. This phenotypic property of tumor cells gives them several advantages over normal cells and is known as the Warburg effect. Tumor...

COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a...

A hyper-specialization characterizes modern medicine with the consequence of classifying the various diseases of the body into unrelated categories. Such a broad diversification of medicine goes in the opposite direction of physics, which eagerly looks for unification. We argue that unification should also apply to medicine. In accordance with the...

Yarrowia lipolytica is a non-conventional yeast with promising industrial potentials for lipids and citrate production. It is also widely used for studying mitochondrial respiration due to a respiratory chain like those of mammalian cells. In this study we used a genome-scale model (GEM) of Y. lipolytica metabolism and performed a dynamic Flux Bala...

Alzheimer’s disease (AD) and cancer have much in common than previously recognized. These pathologies share common risk factors (inflammation and aging), with similar epidemiological and biochemical features such as impaired mitochondria. Metabolic reprogramming occurs during aging and inflammation. We assume that inflammation is directly responsib...

In nature, every physical process involving matter is ruled by the second law of thermodynamics (the total entropy of an isolated system can never decrease over time, and is constant if and only if all processes are reversible). The living cell being a material system should comply by releasing entropy either into the body or into the outside envir...

The occurrence of mitochondrial respiration has allowed evolution toward more complex and advanced life forms. However, its dysfunction is now also seen as the most probable cause of one of the biggest scourges in human health, cancer. Conventional cancer treatments such as chemotherapy, which mainly focus on disrupting the cell division process, h...

The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the “Warburg Effect”. However, cytoplasmic glucose utilization can also occu...

The Warburg effect, a hallmark of cancer, has recently been identified as a metabolic limitation of Chinese Hamster Ovary (CHO) cells, the primary platform for the production of monoclonal antibodies (mAb). Metabolic engineering approaches, including genetic modifications and feeding strategies, have been attempted to impose the metabolic prevalenc...

We report the case of a cohort of 2500 French patients treated among others with methylene blue for cancer care. During the COVID-19 epidemics none of them developed influenza-like illness. Albeit this lack of infection might be by chance alone, it is possible that methylene blue might have a preventive effect for COVID-19 infection. This is in lin...

Abstract Mitotic tumor cells have to synthetize fatty acids and lipid membranes; fatty acid synthesis forms a malonylCoA intermediate, which inhibits the mitochondrial fatty acid carnityl transporter and closes automatically their degradation and beta-oxidation into acetylCoA. Since the glycolytic supply of acetylCoA is OFF as well, (a persistent p...

In tumor cells, ketolysis becomes the unique source of mitochondrial acetyl CoA. Indeed, the glycolytic acetyl CoA production is blocked (pyruvate kinase and pyruvate dehydrogenase are inhibited by phosphorylation). Whereas, the fatty acid degradation into acetyl CoA is also turned off by malonyl CoA, the product of acetyl CoA carboxylase, which fo...

Citation: Maurice Israël and Laurent Schwartz (2020) The metabolic rewiring observed in cancer renders tumor cells dependent of ketone bodies and vulnerable to SCOT inhibition. Endocrinol Diabetes Metab J Volume 4(1): 1-13 (2020). Abstract The finding that autoantibodies against glutamic acid decarboxylase that synthesizes GABA, provoke Diabetes ty...

Citation: Maurice Israël and Laurent Schwartz (2020) The metabolic rewiring observed in cancer renders tumor cells dependent of ketone bodies and vulnerable to SCOT. Endocrinol Diabetes Metab J Volume 4(1): 1-13 (2020). Abstract The finding that autoantibodies against glutamic acid decarboxylase that synthesizes GABA, provoke Diabetes type I, draws...

Hyperosmotic conditions are associated to several pathological states. In this article, we evaluate the consequence of hyperosmotic medium on cellular energy metabolism. We demonstrate that exposure of cells to hyperosmotic conditions immediately reduces the mitochondrial oxidative phosphorylation rate. This causes an increase in glycolysis, which...

In the recent years, cancer research succeeded with sensitive detection methods, targeted drug delivery systems, and the identification of a large set of genes differently expressed. However, although most therapies are still based on antimitotic agents, which are causing wide secondary effects, there is an increasing interest for metabolic therapi...

Background: Diseases and health conditions have been classified according to anatomical site, etiological, and clinical criteria. Physico-chemical mechanisms underlying the biology of diseases, such as the flow of energy through cells and tissues, have been often overlooked in classification systems. Objective: We propose a conceptual framework tow...

Introduction: Exposure to traumatic brain injury is a core risk factor that predisposes an individual to sporadic neurodegenerative diseases. We provide evidence that mechanical stress increases brain levels of hallmark proteins associated with neurodegeneration. Methods: Wild-type mice were exposed to multiple regimens of repetitive mild trauma...

Currently, the predominant hypothesis explains cellular differentiation and behaviour as an essentially genetically driven intracellular process, suggesting a gene-centrism paradigm. However, although many living species genetic has now been described, there is still a large gap between the genetic information interpretation and cell behaviour pred...

As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase cataboli...

In this paper, we derive an electrostatic-electrodynamic model of the exchanges of ions between a cell and its exterior during its growth, as well as a model of exchange of ions within the cell. Observations show that, in the phase G1, the growth of the volume explains the variation of density of ions (by dilution), hence explains the change of ele...

It is a longstanding debate whether cancer is one disease or a set of very diverse diseases. The goal of this paper is to suggest strongly that most (if not all) the hallmarks of cancer could be the consequence of the Warburg‘s effect. As a result of the metabolic impairment of the oxidative phosphorylation, there is a decrease in ATP concentration...

We study, in this paper, a model for the core of the system of the Glycerophospholipid metabolism in the murine cells. It comprises the simple and enzymatic reactions of PhosphatidylEthanolamine and the PhosphatidylCholine . The model’s general structure is taken from a number of books and articles. We translate this model into a set of ordinary di...

To better understand the energetic status of proliferating cells, we have measured the intracellular pH (pHi) and concentrations of key metabolites, such as adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP) in normal and cancer cells, extracted from fresh human colon tissue...

Introduction Des nombreuses evidences epidemiologiques et anatomopathologiques suggerent que l’exposition au traumatisme crânien (TC) predispose l’individu a un risque supplementaire de developper une maladie neurodegenerative sporadique. Objectifs Demontrer que l’exposition au stress mecanique cerebral peut declencher ou/et accelerer les cascades...

Introduction L’influence de l’energie mecanique dans le developpement de la maladie d’Alzheimer (MA) est incertaine. Objectifs Estimer que l’atrophie cerebrale dans la maladie d’Alzheimer (MA) est reliee a une surpression au sein du parenchyme cerebral. Patients et methodes Des donnees de volumetrie et d’elasticite cerebrale (module de Young) ont e...

Introduction: Extracellular accumulation of amyloid-β protein and intracellular accumulation of tau in brain tissues have been described in animal models of Alzheimer's disease (AD) and mechanical stress-based diseases of different mechanisms, such as traumatic brain injury (TBI), arterial hypertension (HTN), and normal pressure hydrocephalus (NPH...

The pathogenesis of common diseases such as Alzheimer’s disease (AD) and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation...

Les tumeurs cancéreuses se comportent comme des parasites métaboliques qui puisent dans les réserves de l’hôte pour alimenter leurs biosynthèses, tandis qu’elles sécrètent des déchets (NO, polyamines, ammoniac, lactate…) qui favorisent la croissance tumorale et un microenvironnement acide aidant à l’envahissement et à la prolifération. Dans le méta...

The effects related to endogenous mechanical energy in Alzheimer's disease (AD) pathology have been widely overlooked. With the support of available data from literature and mathematical arguments, we hypothesize that brain atrophy in AD could be co-driven by the cumulative impact of the pressure within brain tissues. Brain volumetric and physical...

Ovarian carcinoma is the leading cause of death from gynecological cancer because there is risk of chemoresistance. As previously demonstrated in our laboratory, Alpha-lipoic acid (LA), a co-factor for metabolic enzymes, suppresses the tumor growth. In this study, we have researched the mechanisms that are responsible for the activity of LA. We hav...

The different phases of the eukaryotic cell cycle are exceptionally well-preserved phenomena. DNA decompaction, RNA and protein synthesis (in late G1 phase) followed by DNA replication (in S phase) and lipid synthesis (in G2 phase) occur after resting cells (in G0) are committed to proliferate. The G1 phase of the cell cycle is characterized by an...

Background: The combination of hydroxycitrate and lipoic acid has been demonstrated to be effective in reducing murine cancer growth. Early reports suggest a major efficacy in advanced human cancer.Patients and Methods: Three patients with advanced, chemoresistant cancer were treated by a combination of lipoic acid and hydroxicitrate (MetablocTM) f...

Cancer cells cooperate with stromal cells and use their environment to promote tumor growth. Energy production depends on nutrient availability and O2 concentration. Well-oxygenated cells are highly proliferative and reorient the glucose metabolism towards biosynthesis, whereas glutamine oxidation replenishes the TCA cycle coupled with OXPHOS-ATP p...

Background: The combination of hydroxycitrate and lipoic acid has been demonstrated by several series of experiments in several laboratories to be effective in reducing murine cancer growth. Patients and Methods: Forty patients with advanced incurable cancers were treated by metabolic treatment. All had been given a dismal prognosis with a life exp...

The combination of hydroxycitrate and lipoic acid has been demonstrated by several laboratories to be effective in reducing murine cancer growth. All patients had failed standard chemotherapy and were offered only palliative care by their referring oncologist. Karnofsky status was between 50 and 80. Life expectancy was estimated to be between 2 and...

Background: Inflammation has been noted to occur due to increased interstitial pressure. This same interstitial pressure in the liver is likely the cause of tumors receiving their blood supply primarily from the hepatic artery.

Radiotherapy has a relevant action on the tumor environment and its distant component. Abscopal effect is the bystander effect of radiotherapy observed at a site distant to the irradiated one within the same patient. Abscopal effect even though described, is not a common clinical event. We are reporting a documented observation of an abscopal effec...

Hyperthermia has long been known to interfere with the tumor metabolism. The goal of this paper is to review the potential of metabolic therapy and to suggest that its combination with hyperthermia may be of interest.

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Hypoxia is common in solid tumors and in many other disease states such as myocardial infarction, stroke, bone fracture, and pneumonitis. Once hypoxia has developed, the undernourished and hypoxic cells trigger signals in order to obtain new blood vessels to satisfy their increasing demands and to resolve hypoxia. The principal signal activated is...

Three physico-chemical cell parameters have been shown by the biologists to be of importance for understanding the cell behavior: the transmembrane potential (TMP) which modifies substantially the cell functional activity, the intracellular pHi whose dynamics influences a number of other ionic fluxes and, to a lesser extent, the cell volume. In thi...

Describing detailed statistical results for each experiment.

Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell...

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Introduction: our previous publications demonstrate that lipoic acid (ALA) and hydroxycitrate (HCA) combination decreases the tumor growth in mice with either lung cancer, bladder cancer or melanoma. ALA is a well known treatment of the diabetic neuropathy but its intere...

Recent epidemiological studies have suggested a link between cancer and pathophysiological conditions associated with hyperinsulinemia. In this report, we address the possible role of insulin exposure in melanocyte transformation. To this aim, normal melanocytes were exposed to chronic insulin and glucose supplementation (twice the standard medium...

Tumor interstitial fluid (TIF) is a watery phase that accumulates inside the tumor interstitium. Its genesis and fate depend on various factors, namely tumor type, metabolic state of the tumor, expression of vascular endothelial growth factor, and absence of lymphatic system. For almost 30 years TIF remained a neglected entity until it was demonstr...

The metabolism of tumor cells plays an important role in cancer development. Although aerobic glycolysis is inefficient from the standpoint of ATP production, it provides cancer cells with biomolecules implicated in the synthesis of lipids and nucleotides required for cellu-lar proliferation. Thus, targeting aerobic glycolysis has clearly been reco...

Previous studies have suggested a link between cancer types and pathophysiological conditions associated to hyperinsulinemia such as type 2 diabetes, metabolic syndrome, obesity and chronic inflammation. In this report we investigated the link between hyperinsulinemia and cancer. As end points of transformation, the following criteria were used, in...

We present a model of 3-D vascular formation which is able to explain how the capillary system matures into two 3-D arborescent vasculatures which interdigitate in the distal parts, without forming direct shunts.

We have investigated the effect of loss of cell polarity at the individual cell level on the global pattern formation of squamous cell carcinoma. Simple models of cancer growth are able to reproduce qualitatively the sequence of observed abnormalities of metaplasia, dysplasia and carcinoma in situ and invasive carcinoma. The models are based on los...