Is the Hoffman Effect for Methionine Overuse Analogous to the Warburg Effect for Glucose Overuse in Cancer?

Hoffman, Robert M.

doi:10.1007/978-1-4939-8796-2_21

Cited by 6 publications

(4 citation statements)

References 31 publications

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“…Methionine addiction is due to cancer cells having an increased overall rate of transmethylation compared to normal cells that leads to methionine overuse, thereby depleting cellular pools of S-adenosylmethionine (7,8). Overuse of methionine by cancer cells is called the "Hoffman effect" (9), a possibly stronger effect than the Warburg effect of overuse of glucose by cancer cells (10). DNA hypomethylation in human cancer, discovered in our laboratory (11)(12)(13), is probably the result of elevated (7) and altered transmethylation occurring in cancer cells (14).…”

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confidence: 99%

Oral dosing of Recombinant Methioninase Is Associated With a 70% Drop in PSA in a Patient With Bone-metastatic Prostate Cancer and 50% Reduction in Circulating Methionine in a High-stage Ovarian Cancer Patient

2020

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Background/Aim: Methionine addiction is a general and fundamental hallmark of cancer. Methionine addiction can be targeted by methionine restriction (MR). Our laboratory has studied methionine addiction in cancer and MR for almost 50 years. The present study describes oral recombinant methioninase (o-rMETase), as a supplement, to induce MR in cancer patients. Patients and Methods: One patient, a 67-year-old female with high-stage ovarian cancer took o-rMETase twice a day at 250 units per dose for approximately one month. A second patient, a 76-year-old male with bone-metastatic prostate cancer, took o-rMETase twice a day at 250 units per dose during three months. Results: The first patient's circulating methionine levels decreased 50% within 4 hours of taking 250 units of o-rMETase. The second patient's PSA dropped approximately 70% over 3 months. During this time the patient's hemoglobin increased. Conclusion: o-rMETase has no side effects and is potentially efficacious. Future studies involving larger cohorts of patients with high-stage cancer are required to determine if o-rMETase, as a supplement, can increase survival and improve the quality of life.

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Oral dosing of Recombinant Methioninase Is Associated With a 70% Drop in PSA in a Patient With Bone-metastatic Prostate Cancer and 50% Reduction in Circulating Methionine in a High-stage Ovarian Cancer Patient

2020

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“…Methionine is an essential amino acid and, like folate, must be obtained from the diet. Numerous tumors are dependent on methionine metabolism for growth and survival, a phenomenon termed the Hoffman effect, and the activity of methionine metabolism can provide both diagnostic and prognostic information in cancer [48][49][50][51][52][53]. For example, 11 C-methionine is used for positron emission tomography to differentiate recurrent brain tumors from necrotic tissue [53].…”

Section: Interactions Between Radiation and The Methionine Cyclementioning

confidence: 99%

Interactions between Radiation and One-Carbon Metabolism

Korimerla

Wahl

2022

IJMS

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Metabolic reprogramming is a hallmark of cancer. Cancer cells rewire one-carbon metabolism, a central metabolic pathway, to turn nutritional inputs into essential biomolecules required for cancer cell growth and maintenance. Radiation therapy, a common cancer therapy, also interacts and alters one-carbon metabolism. This review discusses the interactions between radiation therapy, one-carbon metabolism and its component metabolic pathways.

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“…Эта зависимость связана с повышенной чувствительностью указанных новообразований к дефициту метионина. Это явление характеризуется неспособностью клеток ряда опухолей пролиферировать в присутствии его метаболического предшественника -гомоцистеина, в то время как на пролиферацию неопухолевых клеток эти условия не влияют [37,38]. In vitro получены прямые доказательства того, что ограничение содержания метионина в рационе питания закономерно приводит к избирательной гибели клеток новообразования по сравнению с нормальными, что в комбинации с определенными химиопрепаратами рассматривается как многообещающая противоопухолевая стратегия [39,40].…”

Section: аминокислотаunclassified

Changes in free amino acid contentrations in blood serum of children with acute lymphoblastic leukemia and lymphomas after chemotherapy

Жуковская¹,

Коробейникова²,

Карелин³

et al. 2022

Zhurnal «Patologicheskaia Fiziologiia I Eksperimental`naia Terapiia»

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Введение. Гемобластозы составляют треть всех видов опухолей у детей. В патогенезе многих злокачественных новообразований все чаще выявляется существенная роль изменений аминокислотного профиля у пациентов. Цель работы - изучение содержания свободных аминокислот в сыворотке крови у детей после курса химиотерапии острого лимфобластного лейкоза и лимфом агрессивного течения. Методика. В исследование включено 155 детей и подростков - 59 девочек и 96 мальчиков в возрасте от 4 до 17 лет. Все пациенты находились в состоянии стойкой ремиссии острого лимфобластного лейкоза и лимфом (коды заболеваний по МКБ-10: С 91, С 81-84, соответственно). В сыворотке крови определяли концентрацию 25 свободных аминокислот методом ВЭЖХ. Результаты. Установлено статистически значимое снижение в сыворотке крови уровня цитруллина (у 23% пациентов) и метионина (у 42 %). Избыток содержания аспарагиновой кислоты в сыворотке крови отмечен у 69% детей. У 42% был повышен уровень глутаминовой кислоты. Содержание серина значительно превышало норму у 96% пациентов; пролина и тирозина у 31 и 81%, соответственно. Заключение. Существенное повышение в сыворотке крови уровней аспарагиновой и глутаминовой кислот, серина, пролина и тирозина свидетельствует о дисбалансе соотношения аминокислот у пациентов с гемобластозами и лимфомами в анамнезе. В связи с этим, требуется дальнейшая оптимизации стратегии антибластомной терапии, в том числе направленной на нормализацию содержания в крови указанных аминокислот. Снижение концентрации аминокислоты цитруллина, вырабатываемой энтероцитами тонкой кишки, связано, как правило, с токсическим поражением слизистой оболочки желудочно-кишечного тракта в результате химиотерапии. Hemoblastosis comprises a third of all tumors in children. Changes in the amino acid profile play a huge role in the pathogenesis of various malignant neoplasms, as recent research has demonstrated. Aim: To study free amino acid concentrations in blood serum of children with acute lymphoblastic leukemia and lymphomas after chemotherapy. Methods. 155 children and teenagers, 59 females and 96 males, 4 to 17 years old, were included in the study. All patients were in sustained remission of acute lymphoblastic leukemia and lymphoma (ICD-10 disease codes: C 01, C 81-84. The serum concentration of 25 free amino acids was analyzed with HPLC. Results. There was a significant decrease in some free amino acid concentrations in serum compared to reference values, specifically citrulline (23% of cases) and methionine (42% of cases). Excess serum aspartic acid was observed in 69% of patients, and 42% had elevated glutamic acid. Serum serine exceeded its normal values in 96% of patients, and proline and tyrosine exceeded normal values in 31% and 81% of patients, respectively. Conclusion. The increases in serum concentrations of aspartic and glutamic acids, serine, proline, and tyrosine indicate disbalance of the amino acid profile of patients with hemoblastosis. Further research on chemotherapy effectiveness is required with the exclusion of these amino acids from the diet. A decrease in the concentration of citrulline, an amino acid produced by enterocytes of small intestine, is more likely related to toxic damage of the gastrointestinal tract mucosa after chemotherapy.

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Is the Hoffman Effect for Methionine Overuse Analogous to the Warburg Effect for Glucose Overuse in Cancer?

Cited by 6 publications

References 31 publications

Oral dosing of Recombinant Methioninase Is Associated With a 70% Drop in PSA in a Patient With Bone-metastatic Prostate Cancer and 50% Reduction in Circulating Methionine in a High-stage Ovarian Cancer Patient

Oral dosing of Recombinant Methioninase Is Associated With a 70% Drop in PSA in a Patient With Bone-metastatic Prostate Cancer and 50% Reduction in Circulating Methionine in a High-stage Ovarian Cancer Patient

Interactions between Radiation and One-Carbon Metabolism

Changes in free amino acid contentrations in blood serum of children with acute lymphoblastic leukemia and lymphomas after chemotherapy

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