Результаты поиска

Collateral Victim or Rescue Worker?-The Role of Histone Methyltransferases in DNA Damage Repair and Their Targeting for Therapeutic Opportunities in Cancer.

Disrupted DNA damage signaling greatly threatens cell integrity and plays significant roles in cancer. With recent advances in understanding the human genome and gene regulation in the context of DNA damage, chromatin biology, specifically biology of histone post-translational modifications (PTMs), has emerged as a popular field of study with great promise for cancer therapeutics. Here, we discuss how key histone methylation pathways contribute to DNA damage repair and impact tumorigenesis within this context, as well as the potential for their targeting as part of therapeutic strategies in ca

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention.

The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstre

The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.

Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, characterized by rapid progression, treatment resistance, and poor prognosis, with a survival rate of less than five years despite advances in medical interventions. A hallmark of GBM is metabolic reprogramming, which supports tumor growth and progression. Mitochondrial dysfunction plays a critical role in this metabolic shift by altering energy production and disrupting key cellular pathways. However, the precise molecular mecha-nisms underlying these alterations remain inadequately understood. This review highlights th

Glioma drug development benefits from emerging phase 0 and window-of-opportunity trial paradigm.

Clinical drug development is fundamentally difficult for rare and difficult-to-treat solid tumors, for example, glioma. Glioblastoma (GBM), an invariably fatal primary brain tumor, poses a significant challenge in the realm of effective treatments, necessitating an accelerated approach to innovative drug discovery. Investigators keep requiring a process toward obtaining more reliable early-stage signals related to drug activity and a process toward translating those signals into clinical benefits efficiently in late-stage drug development. Besides, these processes could increase the likelihood

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the

Достижения в области циркуляции биомаркеров нейродегенеративных заболеваний, травматологических травм мозга и опухолей центральной нервной системы.

Неврологические расстройства, включая нейродегенеративные заболевания, травматические травмы мозга (ТБИ) и опухоли центральной нервной системы (ЦНС), являются сложными условиями, которые оказывают значительное воздействие на пациентов во всем мире. Своевременная диагностика и мониторинг имеют решающее значение для улучшения результатов, что обусловливает потребность в надежных биомаркерах. В частности, биомаркеры, обнаруживаемые в цереброспиновой жидкости (CSF) и крови, позволяют получить важные данные о наличии и прогрессировании заболеваний. В рамках этого обзора изучается эволюция циркулиру

Keyword Index for Volume 111

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Immune landscape-based machine-learning-assisted subclassification, prognosis, and immunotherapy prediction for glioblastoma.

IntroductionAs a malignant brain tumor, glioblastoma (GBM) is characterized by intratumor heterogeneity, a worse prognosis, and highly invasive, lethal, and refractory natures. Immunotherapy has been becoming a promising strategy to treat diverse cancers. It has been known that there are highly heterogeneous immunosuppressive microenvironments among different GBM molecular subtypes that mainly include classical (CL), mesenchymal (MES), and proneural (PN), respectively. Therefore, an in-depth understanding of immune landscapes among them is essential for identifying novel immune markers of GBM.

MicroRNA in cancer therapy: breakthroughs and challenges in early clinical applications.

MicroRNAs (miRNAs) have emerged as pivotal regulators in cancer biology, influencing tumorigenesis, progression, and resistance to therapy. Their ability to modulate multiple oncogenic and tumor-suppressive pathways positions them as promising therapeutic tools or targets. This review examines the dual role of miRNAs in solid and hematological malignancies, starting from their dysregulation in various cancer types. Therapeutic approaches, including miRNA replacement and inhibition strategies, are discussed alongside innovative delivery systems such as lipid nanoparticles and exosomes. Despite

NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.

Metabolic alterations are a common survival mechanism for prostate cancer progression and therapy resistance. Oxidative stress in the cellular and tumor microenvironment dictates metabolic switching in the cancer cells to adopt, prosper and escape therapeutic stress. Therefore, regulation of oxidative stress in tumor cells and in the tumor-microenvironment may enhance the action of conventional anticancer therapies. NRF2 is the master regulator for oxidative stress management. However, the overall oxidative stress varies with PCa clinical stage, metabolic state and therapy used for the cancer.

A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.

Emerging evidence in cancer neuroscience has established a reciprocal bidirectional loop between neural signaling and tumor metabolism as a central driver of malignant progression. This review critically evaluates bidirectional neuro-metabolic symbiosis and its profound implications for overcoming treatment refractoriness. We first analyzed the anterograde mechanism, in which peripheral nerve terminals and systemic endocrine factors impose distinct metabolic dependencies on malignant and stromal cell populations. By forcing alterations in nutrient utilization pathways, these neural cues create

Совпадение в полном тексте источника
… In T-cell acute lymphoblastic leukemia, resistance stems from the RNA methylation dynamics. Gong et al. [ 155 ] revealed that the m6A demethylase ALKBH5 removes m6A modifications from ubiquitin-specific peptidase 1 (USP1). …

A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer.

Cancer is the second leading cause of death in the United States and is a major public health concern worldwide. Basic, clinical and epidemiological research is leading to improved cancer detection, prevention, and outcomes. Recent technological advances have allowed unbiased and comprehensive screening of genome-wide gene expression. Small non-coding RNAs (sncRNAs) have been shown to play an important role in biological processes and could serve as a diagnostic, prognostic and therapeutic biomarker for specific diseases. Recent findings have begun to reveal and enhance our understanding of th

Abstracts from the 53rd European Society of Human Genetics (ESHG) Conference: e-Posters.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Комплексный номер копий с высоким разрешением и гистомолекулярный анализ диффузной глиомы в масштабах полушария, H3 G34-mutant обнаруживает общие аномалии TP53.

Диффузная глиома в масштабах полушария, Н3 G34-mutant (В тыс.DHG-H3 G34 характеризуется главным образом молекулярным профилированием метилирования и исследованиями последовательности. Мы описываем комплексную гистомолекулярную оценку, включая профили копий с высоким разрешением серии 60 DHG-H3 G34 для дальнейшего понимания спектра генетических изменений, связанных с этим типом опухолей. Случаи были подвергнуты клиническому тестированию с использованием: 187-gene мутация и синтез были нацелены на нейроонтологию следующего поколения (n = 60) и онкосканского хромосомного микроаррара (n = 26) одно

Identification and Verification of SLC27A1, PTBP1 and EIF5A With Significantly Altered Expression in Aggressive Pituitary Adenomas.

BackgroundAggressive pituitary adenoma encircling the internal carotid artery has a poor clinical prognosis because of a high surgical risk and a high recurrence rate. This seriously affects patients' quality of life and yet there is no effective medical treatment. The European Diagnostic Guidelines have recommended the use of temozolomide (TMZ) for these aggressive pituitary adenomas, but the treatment remission rate has been less than 50%.MethodsIn this study, transcriptome sequencing of pituitary tumour tissues and TMZ-treated pituitary tumour cell lines were employed to explore the signifi

The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors.

Histone acetyltransferases p300 (E1A-associated protein p300) and CBP (CREB binding protein), collectively known as p300/CBP due to shared sequence and functional synergy, catalyze histone H3K27 acetylation and consequently induce gene transcription. p300/CBP over-expression or over-activity activates the transcription of oncogenes, leading to cancer cell growth, resistance to apoptosis, tumor initiation and development. The discovery of small molecule inhibitors targeting p300/CBP histone acetyltransferase activity, bromodomains, dual inhibitors of p300/CBP and BRD4 bromodomains, as well as p

The Multifaceted Roles of Myrrha in the Treatment of Breast Cancer: Potential Therapeutic Targets and Promises.

BackgroundBreast cancer is a critical threat to human health, and effective targeted agents showing lower systemic toxicity are still lacking. Therefore, exploring new potent therapeutic candidates with a broader safety margin is warranted. Alternative medicine, which has historically been used in traditional Chinese medicine, has played an increasingly prominent role in this area of research. This study introduces Commiphora myrrha (or myrrh) as a potential therapeutic candidate for treating breast cancer patients. Myrrh bioactive extracts have been used traditionally for decades to treat num

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-5.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...].

Fanconi anemia pathway as a prospective target for cancer intervention.

Fanconi anemia (FA) is a recessive genetic disorder caused by biallelic mutations in at least one of 22 FA genes. Beyond its pathological presentation of bone marrow failure and congenital abnormalities, FA is associated with chromosomal abnormality and genomic instability, and thus represents a genetic vulnerability for cancer predisposition. The cancer relevance of the FA pathway is further established with the pervasive occurrence of FA gene alterations in somatic cancers and observations of FA pathway activation-associated chemotherapy resistance. In this article we describe the role of th