Observations of unprecedented remissions following novel treatment for acute leukemia in children in 1948

Spain, Peter D; Kadan‐Lottick, Nina S.

doi:10.1258/jrsm.2012.12k013

Cited by 9 publications

(5 citation statements)

References 35 publications

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“…Altered metabolism is a hallmark of cancers, dating back to the Warburg Effect, first observed in 1930 [ 54 ], and includes other pathways like shifted oxidative phosphorylation and glutaminolysis, as a means of increasing biomass production and diverting carbon sources into biosynthetic pathways that promote sustained tumor proliferation [ 55 ]. Therefore, metabolic inhibitors represent promising anti-cancer drugs, and their use has dated back to the 1940s for treating acute leukemia in children [ 56 ]. These drugs have been shown to result in high levels of toxicity, partially given that many other cell types heavily rely on the same metabolic pathways.…”

Section: Discussionmentioning

confidence: 99%

Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment

et al. 2022

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Contrary to the “obesity paradox,” which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developing lung cancer or those already with early-stage disease are either overweight or obese. Findings from resected patient tumors and mouse lung tumor models show obesity dampens immune activity in the tumor microenvironment (TME) encouraging disease progression. In line with this, we have observed a marked, obesity-specific enhancement in the presence and phenotype of immunosuppressive regulatory T (Treg) cells in murine tumors as well as the airways of both humans and mice. Leveraging direct metabolomic measurements and robust inferred analyses from RNA-sequencing data, we here demonstrate for the first time that visceral adiposity alters the lung microenvironment via dysregulated acetyl-CoA metabolism in a direction that facilitates immune suppression and lung carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment

et al. 2022

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“…Disease-modifying anti-rheumatic drugs (DMARDs), used for decades in the treatment of other types of inflammatory arthritides, have been studied to varying degrees with mixed results in chronic CPP arthritis. Methotrexate (MTX) is a structural analog of folate that inhibits DNA synthesis and hence cellular replication and is one of the oldest DMARDs, in use since the 1950s [ 46 ]. Its use in the management of CPP arthritis remains unclear as studies have shown contrasting views [ 33 , 47 , 48 ].…”

Section: Reviewmentioning

confidence: 99%

A Narrative Review of Chondrocalcinosis: Clinical Presentation, Diagnosis, and Therapies

Kim,

Afroz,

Gillespie

et al. 2024

Cureus

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Calcium pyrophosphate deposition disease is categorized into radiographic chondrocalcinosis, acute calcium pyrophosphate arthritis, chronic calcium pyrophosphate arthritis, and osteoarthritis with calcium pyrophosphate deposition. These entities collectively are characterized by the deposition of calcium into joints, which then may cause localized and systemic inflammation, resulting in pain and swelling in the affected joints. Patients with the ANKH gene are more susceptible to the development of CPP arthritis as are those with primary hyperparathyroidism, hypomagnesemia, and hemochromatosis. Radiographic chondrocalcinosis is asymptomatic. Acute calcium pyrophosphate arthritis results in self-limited periods of joint pain and swelling in the affected joint. Along with localized inflammation, there may also be systemic inflammation characterized by fever and elevated inflammatory markers. Chronic calcium pyrophosphate arthritis results in periods of quiescence interrupted by flares that are identical to acute periods of disease. Osteoarthritis associated calcium pyrophosphate arthritis presents with chronic pain well described in osteoarthritis with periods of acute flares. In 2023, a joint effort by the American College of Rheumatology and the European League Against Rheumatism developed guidelines meant to aid in the recognition of calcium pyrophosphate deposition diseases. The diagnosis is made if there is proof of either crowned dens syndrome or synovial fluid analysis demonstrating calcium pyrophosphate crystals or when more than 56 points are summed utilizing the criteria described in the guidelines. Radiographic chondrocalcinosis requires no therapy. Acute calcium pyrophosphate arthritis is treated with the goal of aborting the flare. Treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, oral corticosteroids, parenteral corticosteroids, intraarticular corticosteroids, IL-1 inhibitors, or parenteral adrenocorticotropic hormone (ACTH). The goal in treatment for chronic calcium pyrophosphate arthritis is the suppression of acute flares. The drugs used for acute flare treatment may be given as maintenance therapy with the additional options of methotrexate and hydroxychloroquine.

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“…Egy amerikai patológus, Sidney Farber a folsav tumorregressziót előidéző hatását bizonyító állatkísérletekre támaszkodva előrehaladott rákos betegeknél kezdte alkalmazni a folsavterápiát [52,53]. A várakozásokkal ellentétben azonban azt tapasztalta, hogy leukaemiások esetében jelentősen felerősödött a daganatos folyamat, így felállította a "gyorsító jelenség" elméletét.…”

Section: A Folátmetabolizmus Gyógyszeres Befolyásolásaunclassified

“…[54]. A DHFR enzim gátlása révén egyaránt megakadályozta a DNS-szintézis és a DNSmetiláció megfelelő módon történő lejátszódását [54], így a csontvelő egészséges működésének visszaállításával az addig kezelhetetlennek hitt gyermekkori acut lymphoblastos leukaemia első hatékony terápiás lehetőségévé vált [53].…”

Section: A Folátmetabolizmus Gyógyszeres Befolyásolásaunclassified

A B₉-vitamin élettani és kórélettani jelentősége. Összegzés a folsav táplálékkiegészítőként történő alkalmazásának 30. évfordulójára

et al. 2019

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Vitamin B9, also known as folate, can be found in natural and synthetic forms, mostly in vegetables or folic acid containing food supplements. By participating in the proper cell development and division, its presence is indispensable for certain basic metabolic processes. The decreased folate level of the body, mainly caused by environmental and hereditary factors as well as aging, can lead to genetic, epigenetic and metabolic changes. It can be related to the development of megaloblastic anemia, various cardiovascular diseases (such as atherosclerosis, stroke) obstetrical complications (such as abruption of the placentae, spontaneous abortion, preterm delivery, neural tube defect), neuropsychiatric diseases (such as Alzheimer’s disease, Parkinson’s disease, depression) and tumors. The vitamin has a preventive effect in all the above-mentioned diseases, however, in the case of tumor existence, its therapeutic use requires great care, as it may promote the progression of certain precancerous lesions. Food fortification with folic acid is currently being carried out in more than 60 countries in order to ensure a minimum vitamin B9 requirement for the population and therefore to prevent the development of the diseases that are connected to folic acid deficiency. Due to its assumable role in carcinogenesis, an initial concern had taken place when fortification was implemented (1998), however, the present statistical data do not confirm such adverse health effects. On the other hand, several beneficial properties can be connected to the vitamin, that can be the reason why more and more countries are considering to join this program. Besides the fact that folic acid is a widely used food supplement, it is also applied in oncological medicine (leucovorin) to increase the effectiveness of certain chemotherapeutical drugs (e.g. methotrexate, 5-fluorouracil). Orv Hetil. 2019; 160(28): 1087–1096.

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Observations of unprecedented remissions following novel treatment for acute leukemia in children in 1948

Cited by 9 publications

References 35 publications

Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment

Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment

A Narrative Review of Chondrocalcinosis: Clinical Presentation, Diagnosis, and Therapies

A B₉-vitamin élettani és kórélettani jelentősége. Összegzés a folsav táplálékkiegészítőként történő alkalmazásának 30. évfordulójára

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Observations of unprecedented remissions following novel treatment for acute leukemia in children in 1948

Cited by 9 publications

References 35 publications

Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment

Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment

A Narrative Review of Chondrocalcinosis: Clinical Presentation, Diagnosis, and Therapies

A B9-vitamin élettani és kórélettani jelentősége. Összegzés a folsav táplálékkiegészítőként történő alkalmazásának 30. évfordulójára

Contact Info

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About

A B₉-vitamin élettani és kórélettani jelentősége. Összegzés a folsav táplálékkiegészítőként történő alkalmazásának 30. évfordulójára