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Множественная миелома высокого риска: от молекулярной классификации к новаторскому лечению с помощью Моноклональных антител и режиссёрской терапии Т-Келл.

Большие генетические миеломы по-прежнему являются серьезной терапевтической проблемой, поскольку пациенты, имеющие неблагоприятные генетические аномалии, такие, как дель(17p), TP53 мутации и biallelic del(1p32), по-прежнему сталкиваются с плохими результатами, несмотря на недавние терапевтические достижения. В рамках этого обзора изучаются меняющиеся определения и молекулярные характеристики HRMM с уделением особого внимания последним обновленным данным о стратегиях стратификации и лечения рисков. Новая генетическая классификация, предложенная на 2025 Совещание ЕММА обеспечивает более высокую

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… All these alterations are linked to tumor invasion, metastasis, higher ability to resist starvation and stress, and increased genomic and chromosomal instability [ 37 ]. 4.2. …

Targeting the gut microbiota to enhance the antitumor efficacy and attenuate the toxicity of CAR-T cell therapy: a new hope?

Chimeric antigen receptor (CAR) -T cell therapy has achieved tremendous efficacy in the treatment of hematologic malignancies and represents a promising treatment regimen for cancer. Despite the striking response in patients with hematologic malignancies, most patients with solid tumors treated with CAR-T cells have a low response rate and experience major adverse effects, which indicates the need for biomarkers that can predict and improve clinical outcomes with future CAR-T cell treatments. Recently, the role of the gut microbiota in cancer therapy has been established, and growing evidence

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… In recent decades, several different dietary strategies, including long-term caloric restriction, intermittent fasting, short-term starvation, high-fiber diets, ketogenic diets and fermented food, have been widely studied in the context of cancer and have been demonstrated to improve the antitumor efficacy …

SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone.

Post-translational modifications comprise series of enzymatically-driven chemical modifications, virtually involving the entire cell proteome, that affect the fate of a target protein and, in turn, cell activity. Different classes of modifications can be established ranging from phosphorylation, glycosylation, ubiquitination, acetylation, methylation, lipidation and their inverse reactions. Among these, SUMOylation and NEDDylation are ubiquitin-like multi-enzymatic processes that determine the bound of SUMOs and NEDD8 labels, respectively, on defined amino acidic residues of a specific protein

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… MKK7 NEDDylation is affected by different environmental factors; indeed, MKK7 NEDDylation is induced in response to stressful stimuli (nutrient starvation, free fatty acids, and sorbitol osmotic stimulation). …

Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change.

The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids. To date, several molec

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… It has been found that inhibition of serine metabolism, by serine starvation or RNAi knockdown of SHMT2, caused accumulation of precursors and inhibition of cancer cell proliferation, by depleting 1C carbon units for purine biosynthesis [ 65 , 66 , 67 ]. …

Late Breaking Orals.

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Polyphyllin I Inhibits the Metastasis of Cervical Cancer Through the Regulation of the β-Catenin Signaling Pathway.

Cervical cancer ranks as the fourth most prevalent cancer and cause of cancer-related mortality among women globally. It exhibits a recurrence/metastasis rate of approximately 30% and a dismal 5-year survival of only 17% in metastatic cases. Despite significant advancements in surgical techniques, chemoradiotherapy, and targeted therapies, effective treatment options for metastatic cervical cancer remain limited. This study explored Polyphyllin I (PPI), which is a monomeric compound derived from the Rhizoma of Paris Polyphyllin, as a potential inhibitor of cervical cancer metastasis. Mechanist

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… The treatment of wild-type MMH hepatocytes with TGFB1 leads to the suppression of autophagy, while starvation-induced autophagy inhibits TGFB1-mediated EMT. …

Olive Leaf Extract (OLE) Anti-Tumor Activities Against Hematologic Tumors: Potential Therapeutic Implications for Pediatric Patients with B-Acute Lymphoblastic Leukemia.

Background/Objectives: Several studies reported that olive leaf extract (OLE) may exert potent anti-cancer activities against human solid and hematological tumors. Such effects are mostly related to the polyphenol oleuropein and its derivatives, which are highly concentrated in OLE. Here, we investigated the anti-tumor effects of OLE in vitro against human acute leukemia and lymphoma cells. Methods: Cell proliferation and apoptosis have been evaluated by flow cytometry (using CFSE and Annexin-V/7AAD, respectively) in the presence or absence of OLE at different concentrations and in combination

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… SOD2 is a regulator of proteasomal degradation promoting an adaptive cellular starvation response Cell Rep. 2025 44 115434 10.1016/j.celrep.2025.115434 40131931 PMC12094083 72. Rath-Deschner B. Nogueira A.V.B. Memmert S. Nokhbehsaim M. Augusto Cirelli J. Eick S. Miosge N. Kirschneck C. Kesting M. …

Functions and Therapeutic Potentials of Long Noncoding RNA in Skeletal Muscle Atrophy and Dystrophy.

Skeletal muscle is the most abundant tissue in the human body and is responsible for movement, metabolism, energy production and longevity. Muscle atrophy is a frequent complication of several diseases and occurs when protein degradation exceeds protein synthesis. Genetics, ageing, nerve injury, weightlessness, cancer, chronic diseases, the accumulation of metabolic byproducts and other stimuli can lead to muscle atrophy. Muscular dystrophy is a neuromuscular disorder, part of which is caused by the deficiency of dystrophin protein and is mostly related to genetics. Muscle atrophy and muscular

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… During muscle atrophy induced by starvation, immobilization or ageing, the expression of activating transcription factor 4 (ATF4) increases [ 37 ]. ATF4 binds to C/EBPβ to promote the expression of growth arrest and DNA damage inducible α ( Gadd45α ) [ 38 ]. …

Effects of Obesity and Calorie Restriction on Cancer Development.

The risk of malignant tumor development is increasing in the world. Obesity is an established risk factor for various malignancies. There are many metabolic alterations associated with obesity which promote cancerogenesis. Excessive body weight leads to increased levels of estrogens, chronic inflammation and hypoxia, which can play an important role in the development of malignancies. It is proved that calorie restriction can improve the state of patients with various diseases. Decreased calorie uptake influences lipid, carbohydrate and protein metabolism, hormone levels and cell processes. Ma

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… On the other hand, starvation can increase mTORC1 signaling activity via deregulation of MiT/TFE-RagD-mTORC1-MiT/TFE feedback circuit [ 127 ]. Functional caloric restriction in T-cells triggered by elevated potassium ion levels lead to T cell disfunction and stemness [ 128 ]. 6. …

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill.

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-

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… Autophagy maintains the functions of various organelles, inhibits the toxic effects of waste products, and supplies substrates to maintain metabolic pathways during starvation. To some extent, autophagy could suppress carcinogenesis ( White, 2015 ). …

Metabolic features of myeloma cells in the context of bone microenvironment: Implication for the pathophysiology and clinic of myeloma bone disease.

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of malignant plasma cells (PCs) into the bone marrow (BM). The complex interaction between the BM microenvironment and MM PCs can lead to severe impairment of bone remodeling. Indeed, the BM microenvironment exerts a critical role in the survival of malignant PCs. Growing evidence indicates that MM cells have several metabolic features including enhanced glycolysis and an increase in lactate production through the upregulation of glucose transporters and enzymes. More recently, it has been reported that MM ce

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… MM cell lines resistant to GLS1 inhibitors were very sensitive to Gln starvation ( 6 ). …

Tumor microenvironment signaling and therapeutics in cancer progression.

Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss t

Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.

Cancer is more than just a collection of tumor cells. The complex tumor system, including the tumor immune microenvironment (TIME), is continually changing. Tumor cells are in constant communication with all stromal elements (e.g., fibroblasts, endothelial cells, and extracellular matrix) and immune effector cells (e.g., T cells, B cells, natural killer cells, dendritic cells, macrophages, and myeloid-derived suppressor cells). Together, these intricate interactions among cell and molecular signaling pathways collectively drive tumor growth, tumor invasion, and metastasis and significantly aff

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… Under conditions of nutrient starvation, for example, glucose or glutamine starvation, cancer cells upregulate de novo serine synthesis by controlling the transcription of master metabolism enzymes in the serine synthesis pathway, such as PHGDH, PSAT1, and PSPH. …

Микроаэробный маленький белок от теплового шока способствует ризобию лимуминозараму/Писуму симбиозу и взаимодействует с широким диапазоном бактерироидных белков.

Во время создания симбиоза с бобовыми растениями ризобия подвергается воздействию враждебной физической и химической микроокружающей среды, к которой требуется адаптация. Протеины реакции на стресс, включая небольшие белки от теплового удара (SHSP), ранее, как было установлено, дифференцировались в бактерироидах, индуцируемых ризобием лимуминозарум бv. viciae UPM791 в различных хост-узлах. В ходе этой работы мы провели функциональный анализ зависящих от принимающей стороны SHSP RLV_1399. Рlv_1399- Исключенный штамм мутантов был нарушен в симбиотических свойствах гороха, но не чечевиц. Выражени

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… Our analysis also identified one component of the Suf machinery that mediates the iron-sulfur cluster assembly in proteins involved in a number of biological processes, such as electron transfer, redox sensing, and catalysis, playing an important role under oxidative stress and iron starvation limitation …

Synthetic Flozins in Cancer Prevention and Combination Strategies: Structural Insights and Therapeutic Potential.

The growing number of cancer cases highlights the urgent need to develop new therapies based on effective molecules. Although anticancer activity remains a key element of oncological pharmacology, the importance of agents that support physiological functions and improve the quality of life of cancer patients is also recognised. Compounds that combine these two functions could represent a significant trend in oncology. Moreover, repurposing approved drugs for conditions beyond their original indications could be a promising strategy. An interesting example of this is synthetic flozins (SGLT2 in

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… Canagliflozin reduces chemoresistance in hepatocellular carcinoma through PKM2–c-Myc complex-mediated glutamine starvation Free Radic. Biol. Med. 2023 208 571 586 10.1016/j.freeradbiomed.2023.09.006 37696420 126. Zhou J. Feng J. Wu Y. Dai H.Q. Zhu G.Z. Chen P.H. Wang L.M. Lu G. Liao X.W. Lu P.Z. …

Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia.

While the understanding of the genomic aberrations that underpin chronic and acute myeloid leukaemia (CML and AML) has allowed the development of therapies for these diseases, limitations remain. These become apparent when looking at the frequency of treatment resistance leading to disease relapse in leukaemia patients. Key questions regarding the fundamental biology of the leukaemic cells, such as their metabolic dependencies, are still unresolved. Even though a majority of leukaemic cells are killed during initial treatment, persistent leukaemic stem cells (LSCs) and therapy-resistant cells

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… Of note, culture of primary AML cells with FLT3 ligand protects them from serum starvation-induced apoptosis, by preventing BAX upregulation [ 127 ]. This could be due to increased BH3 sequestration by BCL-2, preventing BAX activation. …

Frailty in Aging and the Search for the Optimal Biomarker: A Review.

In the context of accelerated aging of the population worldwide, frailty has emerged as one of the main risk factors that can lead to loss of self-sufficiency in older people. This syndrome is defined as a reduced state of physiological reserve and functional capacity. The main diagnostic tools for frailty are based on scales that show deficits compared to their clinical application, such as the Fried frailty phenotype, among others. In this context, it is important to have one or more biomarkers with clinical applicability that can objectively and precisely determine the degree or risk of fra

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… Plasma Nτ-Methylhistidine Concentration Is a Sensitive Index of Myofibrillar Protein Degradation during Starvation in Rats Biosci. Biotechnol. Biochem. 1996 60 501 502 10.1271/bbb.60.501 8901113 139. Bui D. Ravasz D. Chinopoulos C. …

Cancer and Exercise: Warburg Hypothesis, Tumour Metabolism and High-Intensity Anaerobic Exercise.

There is ample evidence that regular moderate to vigorous aerobic physical activity is related to a reduced risk for various forms of cancer to suggest a causal relationship. Exercise is associated with positive changes in fitness, body composition, and physical functioning as well as in patient-reported outcomes such as fatigue, sleep quality, or health-related quality of life. Emerging evidence indicates that exercise may also be directly linked to the control of tumour biology through direct effects on tumour-intrinsic factors. Beside a multitude of effects of exercise on the human body, on

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… These authors concluded that total body acidification was promising in antagonizing tumour growth, and its effects were independent of starvation-ketosis. Acidosis was not suggested to favour solid tumour growth, and it was shown to have the potential to delay it, at least in some cases. …

The metabolic syndrome-cancer axis: global research trends and clinical landscapes.

BackgroundThe link between metabolic syndrome (MetS) and cancer has been widely studied, but overall research patterns, shared mechanisms, and applications remain unclear. A bibliometric and bioinformatics analysis is needed to identify trends and clarify the molecular pathways connecting MetS to cancer.MethodsA bibliometric analysis using Web of Science and PubMed assessed publication trends, collaboration, key authors/journals, and research topics from 2000 to 2024. Visualization and analysis used VOSviewer, CiteSpace, and Bibliometrix. Also included bioinformatics for protein interaction ne

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… Unlike simple starvation, cachexia is caused by malignant inflammation, which describes the complex interplay between tumor-derived factors such as ZAG, PTHrP and host cytokines such as TNF-α, IL-6. …

The skeleton: an overlooked regulator of systemic glucose metabolism in cancer?

Recent discoveries demonstrated the skeleton's role as an endocrine organ regulating whole-body glucose homeostasis. Glucose metabolism is critical for rapid cell proliferation and tumour growth through increasing glucose uptake and fermentation of glucose to lactate despite being in an aerobic environment. This hypothesis paper discusses emerging evidence on how bones can regulate whole-body glucose homeostasis with potential to impact on tumour growth and proliferation. Moreover, it proposes a clinical link between bone glucose metabolism and prognosis of cancer based on recent clinical tria

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… Notwithstanding, an in vivo study conducted in mice highlighted that short-term starvation, therefore glucose restriction, enhances chemotherapy drugs efficacy, promotes tumour deceleration and increases cancer-free survival in melanoma, glioma and breast cancer. …