In vivo (Athens, Greece) · 2009
Breast-like vulvar lesion with concurrent breast cancer: a case report and critical literature review.
Клинический случайСтатьяОбзорНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Perrone Giuseppe, Altomare Vittorio, Zagami Mariagiovanna, Vulcano Ettore, Muzii Ludovico, Battista Cleonice, Rabitti Carla, Muda Andrea Onetti
Аннотация
BACKGROUND/AIM: Cancer metabolism is often viewed as a cooperative reliance on glucose and glutamine; however, whether these nutrients can enforce discrete, non-overlapping metabolic states remains unclear. This study aimed to isolate nutrient-specific regulatory programs.
MATERIALS AND METHODS: MDA-MB-231 human breast cancer cells were cultured under four distinct metabolic environments: glucose/glutamine nutrient-repleted (fed), dual glucose/glutamine deficiency, and isolated repletion of either glucose or glutamine. Groups were evaluated for integrated transcriptomic, metabolomic, and lipidomic profiles to identify only the non-redundant, nutrient-enforced architectures.
RESULTS: The data show a mutually restrictive mechanistic state. Glutamine functions as a metabolic architect, restoring glycolytic enzyme transcripts (without lactate production), while inducing PDK1/3 which would decouple glycolysis from the TCA cycle. These changes are concomitant with a glutamine flux toward reductive TCA-driven lipogenesis, citric acid overflow, sterol synthesis (SREBF1/2), structural membrane expansion (phospholipids/sphingolipids) and the unique production of alanine as a nitrogen pool, independent of glycolytic flux. Conversely, glucose alone acts as the executor, licensing chromatin engagement, DNA replication, and mitotic progression. Glucose alone resolved ER stress, restored hexose-phosphate-derived glycosylation (mannose-6-phosphate), enabled lactic acid production, and diverted excess carbon into a triglyceride storage pool (>40% of lipids). Notably, each nutrient suppressed core elements of the other's program, revealing a reciprocal activation-braking system. Interestingly, ATP yield from glucose or glutamine alone were comparable, but not arbitrary; instead, aligned with the functional state of the cell. Glucose alone supported glycolytic phosphorylation and proliferative execution, as marked by lactate accumulation, whereas glutamine alone supported Krebs cycle-related phosphorylation, characterized by citrate accumulation and the maintenance of cellular structure and membrane infrastructure.
CONCLUSION: Glucose and glutamine enforce a balance of two independent, reciprocally regulated metabolic states. This data provides a systems-level explanation for metabolic resilience in cancer and may lead to the identification of nutrient-specific targets for combination therapy.
MATERIALS AND METHODS: MDA-MB-231 human breast cancer cells were cultured under four distinct metabolic environments: glucose/glutamine nutrient-repleted (fed), dual glucose/glutamine deficiency, and isolated repletion of either glucose or glutamine. Groups were evaluated for integrated transcriptomic, metabolomic, and lipidomic profiles to identify only the non-redundant, nutrient-enforced architectures.
RESULTS: The data show a mutually restrictive mechanistic state. Glutamine functions as a metabolic architect, restoring glycolytic enzyme transcripts (without lactate production), while inducing PDK1/3 which would decouple glycolysis from the TCA cycle. These changes are concomitant with a glutamine flux toward reductive TCA-driven lipogenesis, citric acid overflow, sterol synthesis (SREBF1/2), structural membrane expansion (phospholipids/sphingolipids) and the unique production of alanine as a nitrogen pool, independent of glycolytic flux. Conversely, glucose alone acts as the executor, licensing chromatin engagement, DNA replication, and mitotic progression. Glucose alone resolved ER stress, restored hexose-phosphate-derived glycosylation (mannose-6-phosphate), enabled lactic acid production, and diverted excess carbon into a triglyceride storage pool (>40% of lipids). Notably, each nutrient suppressed core elements of the other's program, revealing a reciprocal activation-braking system. Interestingly, ATP yield from glucose or glutamine alone were comparable, but not arbitrary; instead, aligned with the functional state of the cell. Glucose alone supported glycolytic phosphorylation and proliferative execution, as marked by lactate accumulation, whereas glutamine alone supported Krebs cycle-related phosphorylation, characterized by citrate accumulation and the maintenance of cellular structure and membrane infrastructure.
CONCLUSION: Glucose and glutamine enforce a balance of two independent, reciprocally regulated metabolic states. This data provides a systems-level explanation for metabolic resilience in cancer and may lead to the identification of nutrient-specific targets for combination therapy.