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Histone modifications across cancers: mechanisms, therapy and clinical translation.

Cancer continues to be a major cause of death across the globe, and epigenetic dysregulation, including histone modifications, has been recognized as a major hallmark of cancer development, heterogeneity, and drug resistance. This review seeks to offer an overview of histone modifications in cancer, including the more studied histone modifications such as acetylation and methylation, as well as the less explored histone modifications such as phosphorylation, ubiquitination, and glycosylation. It also examines the role of histone modifications in the dysregulation of the three categories of enz

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… For example, vorinostat with carboplatin/paclitaxel for ovarian cancer, panobinostat with decitabine/temozolomide for melanoma, and valproic acid with different chemotherapy regimens for different types of cancer. … The advancement of epigenetic biomarkers, such as distinct DNA methylation patterns (e.g., MGMT promoter methylation correlating with temozolomide response in glioblastoma) or histone modification signatures, shows potential for patient stratification [ 166 ]. …

Advancing CAR T-Cell Therapy in Solid Tumors: Current Landscape and Future Directions.

BackgroundChimeric Antigen Receptor (CAR) T-cell therapy has transformed the treatment of hematological malignancies, yet its application in solid tumors remains constrained by unique biological and logistical barriers.ObjectiveThis review critically examines the evolving landscape of CAR T-cell therapy in solid malignancies, with a focus on antigen heterogeneity, the immunosuppressive tumor microenvironment, and risks of on-target, off-tumor toxicity.MethodsWe outline recent advances in CAR engineering, including co-stimulatory optimization, dual- and multi-antigen targeting, armored CARs, an

Curcumin as a promising therapeutic agent for diabetic neuropathy: from molecular mechanisms to functional recovery.

Diabetes mellitus is an endocrine disorder characterized by prolonged hyperglycemia. It results from either insulin deficiency (type 1 diabetes mellitus, T1DM) or insulin resistance (type 2 diabetes mellitus, T2DM). This condition has emerged as a significant health concern in recent years. Hyperglycemia induces the overproduction of reactive oxygen species (ROS), which can modulate multiple pathways, including AGEs-RAGE, PKC stimulation, NF-κB and PI3K/AKT. These pathways contribute to diabetes-related complications such as inflammation, oxidative stress, insulin resistance, and reduced gluco

Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects.

Metabolic reprogramming is a fundamental hallmark and a key driver of malignant tumors. By reshaping glucose, lipid, and amino acid metabolism, as well as mitochondrial function, it sustains the abnormal proliferation and survival of tumor cells, making it a crucial target for anti-tumor therapy. Curcumin, a natural multi-target compound, exhibits unique advantages in intervening in tumor metabolic reprogramming due to its low toxicity and broad-spectrum regulatory properties. In various tumor models, it can directly modulate the activity of key glycolytic enzymes, such as hexokinase 2, lactat

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… This mechanism not only induces ferroptosis in tumor cells but also enhances resistance to temozolomide [ 121 ]. In melanoma cells, the analog MitoCur-1 inhibits cystine uptake by targeting SLC7A11 and suppresses the deubiquitinating enzyme USP14. …

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies.

Among women, breast cancer ranks as the most prevalent form of cancer, and the presence of metastases significantly reduces prognosis and diminishes overall survival rates. Gaining insights into the biological mechanisms governing the conversion of cancer cells, their subsequent spread to other areas of the body, and the immune system's monitoring of tumor growth will contribute to the advancement of more efficient and targeted therapies. MicroRNAs (miRNAs) play a critical role in the interaction between tumor cells and immune cells, facilitating tumor cells' evasion of the immune system and p

γδ T Cells: Game Changers in Immune Cell Therapy for Cancer.

Gamma delta (γδ) T cells are a unique subset of T lymphocytes with distinctive features that make them highly promising candidates for cancer therapy. Their MHC-independent recognition of tumor antigens, ability to mediate direct cytotoxicity, and role in modulating the tumor microenvironment position them as versatile agents in cancer immunotherapy. This review integrates and synthesizes the existing data on γδ T cells, with an emphasis on the development and optimization of in vitro expansion protocols. Critical aspects are detailed such as activation strategies, co-culture systems, cytokine

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… Lamb L., Lobbous M., Goswami T., Rochlin K., Shepard J., Weekley B.B., Lucas C., Langford C., Youngblood S., Haak M.T., et al. 637 INB-200: Phase I Study of Gene Modified Autologous Gamma-Delta (Γδ) T Cells in Newly Diagnosed Glioblastoma (GBM) Patients Receiving Maintenance Temozolomide (TMZ): Immunobiologic …

Circadian clocks and adaptive immune function: from mechanisms to therapeutic applications.

The circadian clock exerts profound regulatory control over adaptive immunity, particularly affecting T and B lymphocyte development, trafficking, activation, and effector function. These immune cells possess autonomous molecular clocks governed by core genes such as Bmal1, Clock, Per1/2, and Cry1/2, which influence transcriptional programs related to receptor expression, cytokine signaling, and metabolism. Circadian regulation shapes the daily oscillation of lymphocyte recirculation through lymphoid organs, modulates antigen responsiveness, and fine-tunes subset differentiation-most notably s

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… . | Lung cancer survivors | Morning bright light therapy vs dim light | 2016-10 | 2018-01 | Interventiomal NCT02781792 | Temozolomide Chronotherapy for High Grade Glioma | 2 | High grade glioma (II-IV) | TMZ morning vs evening administration | 2016-08-11 | 2024-07-18 | Interventional NCT03955510 | Abnormal …

Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies.

The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem-aging, which diminishes the overall quality of human life. The aging process of the body begins with the activation of effector signaling pathways of aging in cells, resulting in the loss of their normal functions and deleterious effects on the microenvironment. This, in turn, leads to chronic inflammation and similar transformations in neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of

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… BH3 mimetic drugs cooperate with Temozolomide, JQ1 and inducers of ferroptosis in killing glioblastoma multiforme cells Cell Death Differ. 2022 29 1335 1348 10.1038/s41418-022-00977-2 35332309 PMC9287558 70. Triana-Martinez F. Picallos-Rabina P. Da Silva-Alvarez S. Pietrocola F. Llanos S. …

Систематический обзор потенциального ускорения нееврокогнитивного старения пожилых лиц, переживших рак.

По мере роста показателей выживаемости больше внимания стало уделяться возможным когнитивным сиквелам у пожилых больных раком, что можно объяснить ускоренным старением мозга. В этом обзоре мы представляем полный обзор исследований, посвященных нейроимации, нейрокогнитивным и нейродегенеративным расстройствам у пожилых выживших жертв рака (см.>65 лет), на основе three базы данных (Pubmed, Web of Science and Medline). Ninety-six В него были включены исследования. Были обнаружены данные о функциональных и структурных изменениях в мозге (фронтальные области, базальная ганглиа, серые и белые вещест

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… Quality of Life Perception, Cognitive Function, and Psychological Status in a Real-World Population of Glioblastoma Patients Treated with Radiotherapy and Temozolomide: A Single-Center Prospective Study. Am. J. Clin. Oncol. 2018;41:1263–1271. doi: 10.1097/COC.0000000000000459. 29. …

Current Status of 68Ga-Pentixafor in Solid Tumours.

Chemokine receptor CXCR4 is overexpressed in neoplasms and its expression is related to tumour invasion, metastasis and aggressiveness. 68Ga-Pentixafor is used to non-invasively image the expression of CXCR4 in tumours and has been widely used in haematological malignancies. Recent evidence shows that therapies targeting CXCR4 can increase the chemosensitivity of the tumour as well as inhibit tumour metastasis and aggressiveness. 68Ga-Pentixafor has shown promise as an elegant radiotracer to aid in the selection of patients whose tumours demonstrate CXCR4 overexpression and who therefore may b

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… The management of GBM consists of a combination of rescue surgery and temozolomide-based chemoradiation therapy [ 36 ]. Delineation of the tumour extent and subsequent treatment planning remains a challenge due to the limited accuracy of MRI. …

Poster Presentation

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… Material and Method: 15 newly diagnosed post operative Grade III & IV gliomas prospectively enrolled & received adjuvant RT (60Gy/30 fractions) using IMRT with concurrent Temozolomide (TMZ) 75mg/m2 over 6 weeks followed by adjuvant TMZ 150-200 mg/m2. …

Polypharmacy and medication use in patients with chronic kidney disease with and without kidney replacement therapy compared to matched controls.

BackgroundThis study aims to examine polypharmacy (PP) prevalence in patients with chronic kidney disease (CKD) Stage G4/G5 and patients with kidney replacement therapy (KRT) compared with matched controls from the general population. Furthermore, we examine risk factors for PP and describe the most commonly dispensed medications.MethodsDutch health claims data were used to identify three patient groups: CKD Stage G4/G5, dialysis and kidney transplant patients. Each patient was matched to two controls based on age, sex and socio-economic status (SES) score. We differentiated between 'all medic

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… ATC code | Name L01AA01 | Cyclofosfamide L01AA02 | Chloorambucil L01AA03 | Melfalan L01AA09 | Bendamustine L01AB01 | Busulfan L01AC01 | Thiotepa L01AD02 | Lomustine L01AX03 | Temozolomide L01BA04 | Pemetrexed L01BB03 | Tioguanine L01BB05 | Fludarabine L01BB06 | Clofarabine L01BB07 | Nelarabine L01BC01 …

miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy.

In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system's multiple signalling pathways by binding to the

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… Additionally, the use of miR-17-92 clusters in combination with chimeric antigen cells and in combination with temozolomide has increased the therapeutic efficacy and survival rate among patients of glioblastoma [ 192 ]. 8. …

Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives.

The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a

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… Galectin-1 knockdown increases sensitivity to temozolomide in a B16F10 mouse metastatic melanoma model. J. Invest. Dermatol. 2007;127:2399–2410. doi: 10.1038/sj.jid.5700869. 66. …

CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.

Several landmark studies over the past decade have uncovered a critical role of the CRL3KBTBD4 ubiquitin ligase complex in regulating stability of corepressor of repressor element 1 silencing transcription factor (CoREST) complex proteins and normal hematopoietic stem cell self-renewal. There is now mounting evidence that the CoREST complex plays oncogenic roles, although the contributions of its catalytic versus noncatalytic functions remain unclear. Here, we summarize and discuss mechanisms whereby the CoREST complex coopts tissue-specific transcription factors to elicit pathogenic activity

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… LSD1 knockdown or inhibition in GBM stem cells was also reported to diminish their capacity to undergo homologous recombination and nonhomologous end-joining DNA repair thereby enhancing efficacy of temozolomide, an adjuvant chemotherapeutic agent ( 151 ). …

Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.

This comprehensive review investigates the complex interactions between oncogenesis and stem cells, underscoring the crucial importance of cancer stem cells (CSCs) in the mechanisms of tumorigenesis, metastatic dissemination, and resistance to therapeutic interventions. CSCs constitute a distinct subset within neoplasms, defined by unique characteristics such as the ability to self-renew, the potential to differentiate into various cellular phenotypes, and an inherent resistance to conventional treatment strategies. It is hypothesized that these properties are regulated by a multitude of signa

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to ac

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… For glioma, the most common tumor type in the head and neck, surgical resection combined with temozolomide adjuvant chemotherapy is often used ( 9 , 10 ); nonetheless, patients with glioma are prone to develop chemotherapy resistance ( 11 , 12 ). … In addition to the construction of a nano-miRNA system, exosomes are often used to deliver chemotherapy drugs (e.g., doxorubicin, paclitaxel, curcumin, temozolomide, 5-fluorouracil [5-FU]) ( 198 ). …

Radiometals in Imaging and Therapy: Highlighting Two Decades of Research.

The present article highlights the important progress made in the last two decades in the fields of molecular imaging and radionuclide therapy. Advancements in radiometal-based positron emission tomography, single photon emission computerized tomography, and radionuclide therapy are illustrated in terms of their production routes and ease of radiolabeling. Applications in clinical diagnostic and radionuclide therapy are considered, including human studies under clinical trials; their current stages of clinical translations and findings are summarized. Because the metalloid astatine is used for

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… [ 279 ] 223 Ra + [ 177 Lu]Lu-PSMA- I & T | PSMA | NCT05383079 (phase II; recruiting) | Metastatic castration-resistant prostate cancer [ 280 ] Cabozantinib in Combination With [ 177 Lu]Lu- DOTATATE (LuTATE) | SSTR2 | NCT05249114 (Phase Ib; ongoing) | Neuroendocrine tumors [ 281 ] capecitabine (CAP)/temozolomide …

Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives.

Aberrant glycosylation is a hallmark of cancer and can lead to changes that influence tumor behavior. Glycans can serve as a source of novel clinical biomarker developments, providing a set of specific targets for therapeutic intervention. Different mechanisms of aberrant glycosylation lead to the formation of tumor-associated carbohydrate antigens (TACAs) suitable for selective cancer-targeting therapy. The best characterized TACAs are truncated O-glycans (Tn, TF, and sialyl-Tn antigens), gangliosides (GD2, GD3, GM2, GM3, fucosyl-GM1), globo-serie glycans (Globo-H, SSEA-3, SSEA-4), Lewis anti

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… Recently, another clinical trial ( NCT04560166 ) began evaluating Naxitamab and GM-CSF in combination with irinotecan and temozolomide for patients with primary refractory high-risk NB or in their first relapse. Table 2 shows selected clinical trials of antibodies targeting TACAs. … October 2010–September 2021 | NCT00026312 [ 36 ] hu3F8 (Naxitamab) + GM-CSF | II | High risk Neuroblastoma | Recruiting 4/2018–11/2027 | NCT03363373 hu3F8 + GM-CSF | I/II | High risk Neuroblastoma | Active, not recruiting 12/2012–12/2023 | NCT01757626 [ 43 , 44 ] Naxitamab hu3F8 + GM-CSF + irinotecan and temozolomide …

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio.

To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatme

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… Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. New Engl J Med (2005) 352(10):987–96. 10.1056/NEJMoa043330 13. Katanyoo K, Tangjitgamol S, Chongthanakorn M, Tantivatana T, Manusirivithaya S, Rongsriyam K, et al. …