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Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic dat

Mechanisms Behind the Pharmacological Application of Biochanin-A: A review.

This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when a

Network Pharmacology Identifies Therapeutic Targets and the Mechanisms of Glutathione Action in Ferroptosis Occurring in Oral Cancer.

Oral cancer (OC) is one of the most pernicious cancers with increasing incidence and mortality worldwide. Surgery is the primary approach for the treatment of early-stage OC, which reduces the quality of life of the patients. Therefore, there is an urgent need to discover novel treatments for OC. Targeting ferroptosis to induce cell death through the modulation of lipid oxidation has been used as a new approach to treat many cancers. Glutathione (GSH) is a coenzyme factor of GSH peroxidase 4, and it carries potential applicability in treating OC. By using network pharmacology and molecular doc

Blocking the IL‑6 pathway to treat immune checkpoint inhibitor‑induced inflammatory arthritis (Review).

The incorporation of immune checkpoint inhibitors (ICIs) into cancer treatment has revolutionized oncology, providing marked advantages in managing various types of cancer. Nevertheless, the increasing use of ICIs has led to the emergence of immune‑related side effects, including autoimmune diseases such as inflammatory arthritis. IL‑6 signaling is crucial in the development of inflammatory arthritis and is linked to both the benefits and adverse effects of ICIs. The present review summarizes the latest progress in the IL‑6 pathway in inflammatory arthritis and discusses the therapeutic potent

Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.

Nucleocytoplasmic transport (NCT) regulates the spatial distribution of proteins and RNA between the nucleus and cytoplasm. NCT dysregulation can mislocalize tumor suppressors, DNA-repair factors, transcription factors, and drug targets in cancer. In this review, we conceptualize NCT-dependent protein mislocalization as a spatial regulatory framework for anticancer drug resistance, rather than as a catalogue of transport components. We systematically discuss how nuclear pore complex (NPC) remodeling, transport-receptor imbalance, post-translational modification (PTM)-regulated cargo routing, s

RNA modifications in cancer.

RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), are implicated in various cellular processes. These modifications are regulated by proteins that write, erase, and read RNA and modulate RNA stability, splicing, translation, and degradation. Recent studies have highlighted their roles in metabolic reprogramming, signaling pathways, and cell cycle control, which are essential for tumor proliferation and survival. Despite these scientific advances, the precise

PRMT5: An Emerging Target for Pancreatic Adenocarcinoma.

The overall survival of pancreatic ductal adenocarcinoma (PDAC) remains poor and its incidence is rising. Targetable mutations in PDAC are rare, thus novel therapeutic approaches are needed. Protein arginine methyltransferase 5 (PRMT5) overexpression is associated with worse survival and inhibition of PRMT5 results in decreased cancer growth across multiple cancers, including PDAC. Emerging evidence also suggests that altered RNA processing is a driver in PDAC tumorigenesis and creates a partial dependency on this process. PRMT5 inhibition induces altered splicing and this vulnerability can be

State of the Art of Pharmacological Activators of p53 in Ocular Malignancies.

The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival

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… Cyclin D-Cdk4,6 Drives Cell-Cycle Progression via the Retinoblastoma Protein’s C-Terminal Helix Mol. Cell 2019 74 758 770.e4 10.1016/j.molcel.2019.03.020 30982746 PMC6800134 71. Engeland K. …

Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells.

: Lesions with driver mutations, including atypical nevi and seborrheic keratoses, are very common in dermatology, and are prone to senescence. The molecular events that prevent senescent lesions from becoming malignant are not well understood. We have developed a model of vascular proliferation using a temperaturesensitive, large T antigen and oncogenic HRas. By elevating the temperature to 39 °C, we can turn off large T antigen and study the molecular events in cells with the Ras driver mutation. To assess the signaling events associated with the switch from a proliferative to a nonprolifera

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

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… Inhibition of PC cell-derived growth factor (PCDGF)/granulin-epithelin precursor (GEP) decreased cell proliferation and invasion through downregulation of cyclin D and CDK 4 and inactivation of MMP-2. BMC Cancer. 2007;7:22. doi: 10.1186/1471-2407-7-22. 90. Viallard C., Larrivée B. …

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

Targeting nuclear import and export in hematological malignancies.

The transport of proteins across the nuclear membrane is a highly regulated process, essential for the cell function. This transport is actively mediated by members of the karyopherin family, termed importins, or exportins, depending on the direction of transport. These proteins play an active part in tumorigenesis, through aberrant localization of their cargoes, which include oncogenes, tumor-suppressor genes and mediators of key signal transduction pathways. Overexpression of importins and exportins is reported in many malignancies, with implications in cell growth and viability, differentia

Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy.

Histone deacetylases (HDACs) are pivotal epigenetic regulators that control gene expression, cell proliferation, and differentiation, and their dysregulation is closely associated with the onset and progression of multiple cancers. The therapeutic importance of these enzymes is reflected by FDA approval of HDAC inhibitors for oncology indications. Despite this clinical success, most FDA-approved agents employ conventional zinc-binding groups (ZBGs) such as hydroxamic acid and 2-aminoanilide, which are frequently linked to metabolic instability, genotoxicity, and poor pharmacokinetic behavior.

Three- размерная структура комплекса Palbociclib-HIV TAR.

Мы представляем структуру HIV-1 элемент реакции на трансактивацию (TAR), связанный с киназным ингибитором palbociclib, однозначным лигандом nM и ингибитором с низким значением nM комплекса супер удлинения. Маленькая молекула перестраивает РНК, чтобы создать глубокий связующий карман в новой структуре ТАР. Он заменяет A22 на "интермолекулярную пару" с U40, создавая постоянно сложенную пару. 11 спираль, которая включает в себя three :: новые три базы, включая саму A22 и нуклеотиды UCU. Мутация нуклеотидов в связующем кармане или небольшие модификации малой молекулы, отменяющей связующую способно

Targeting the AMP-Activated Protein Kinase for Cancer Prevention and Therapy.

Despite the advances in biomedical research and clinical applications, cancer remains a leading cause of death worldwide. Given the limitations of conventional chemotherapeutics, including serious toxicities and reduced quality of life for patients, the development of safe and efficacious alternatives with known mechanism of action is much needed. Prevention of cancer through dietary intervention may hold promise and has been investigated extensively in the recent years. AMP-activated protein kinase (AMPK) is an energy sensor that plays a key role in the regulation of protein and lipid metabol

The role and mechanisms of action of microRNAs in cancer drug resistance.

MicroRNAs (miRNAs) are small non-coding RNAs with a length of about 19-25 nt, which can regulate various target genes and are thus involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. Drug resistance in cancer chemotherapy is one of the main obstacles to curing this malignant disease. Statistical data indicate that over 90% of the mortality of patients with cancer is related to drug resistance. Drug resistance of cancer chemotherapy can be caused by many mechanisms, such as decreased antitumor drug uptake, modified

Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications.

Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evid

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… In transformed follicular lymphoma, chidamide impacts on the PI3K-AKT pathway ( Zhong et al., 2021 ) and in lymphoma it causes G0/G1 arrest, declining the cyclin D and c-myc expression, and increasing p53 and p21. Additionally, chidamide induces caspase-dependent apoptosis ( Yuan et al., 2019 ). …

Reactive Oxygen Species Bridge the Gap between Chronic Inflammation and Tumor Development.

According to numerous animal studies, adverse environmental stimuli, including physical, chemical, and biological factors, can cause low-grade chronic inflammation and subsequent tumor development. Human epidemiological evidence has confirmed the close relationship between chronic inflammation and tumorigenesis. However, the mechanisms driving the development of persistent inflammation toward tumorigenesis remain unclear. In this study, we assess the potential role of reactive oxygen species (ROS) and associated mechanisms in modulating inflammation-induced tumorigenesis. Recent reports have e

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… Inhibition of ROS blocks serum-induced G0/G1 to S phase transition by reducing the activities of cyclin E-CDK2 and cyclin D-CDK4 complexes [ 183 , 189 , 190 ]. …

Proteomic and transcriptomic analyses to explain the pleiotropic effects of Ankaferd blood stopper.

Ankaferd blood stopper is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica and has been used as a topical hemostatic agent and with its clinical application established in randomized controlled trials and case reports. Ankaferd has been successfully used in gastrointestinal endobronchial mucosal and cutaneous bleedings and also in abdominal, thoracic, dental and oropharyngeal, and pelvic surgeries. Ankaferd's hemostatic action is thought to form a protein complex with coagulation factors that facilitate adhesion of

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation.

Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basi

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… Bromelain diminished the expression of the cell cycle regulatory proteins cyclin A, cyclin B, and cyclin D, resulting in G1 arrest [ 352 ]. …