Результаты поиска

FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy.

BackgroundFifty percent of patients with muscle-invasive bladder cancer (MI-BC) die from their disease and current chemotherapy treatment only marginally increases survival. Novel therapies targeting receptor tyrosine kinases or activated oncogenes may improve outcome. Hence, it is necessary to stratify patients based on mutations in relevant oncogenes. Patients with non-muscle-invasive bladder cancer (NMI-BC) have excellent survival, however two-thirds develop recurrences. Tumor specific mutations can be used to detect recurrences in urine assays, presenting a more patient-friendly diagnostic

Checking NEKs: Overcoming a Bottleneck in Human Diseases.

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as th

Совпадение в полном тексте источника
… NEK2 is regulated by the cell cycle, and high levels of NEK2 were found in the S and G2 phases, and low levels were found in the M and G1 phases [ 9 ]. Furthermore, the NEK2 protein is essential for centrosome integrity and plays a role in the regulation of centrosome separation [ 20 ]. …

DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.

Resistance to chemo- and radiotherapy is a common event among cancer patients and a reason why new cancer therapies and therapeutic strategies need to be in continuous investigation and development. DNA damage response (DDR) comprises several pathways that eliminate DNA damage to maintain genomic stability and integrity, but different types of cancers are associated with DDR machinery defects. Many improvements have been made in recent years, providing several drugs and therapeutic strategies for cancer patients, including those targeting the DDR pathways. Currently, poly (ADP-ribose) polymera

Совпадение в полном тексте источника
… There are two major classes of G1 cyclins that regulate cell cycle progression during the G1 phase: cyclin D, which cooperates with either CDK4 or CDK6, and cyclin E, which binds CDK2. During cell cycle progression in the early G1 phase, cyclin D–CDK4/6 complexes phosphorylate the Rb protein. … Complete phosphorylation of the Rb protein is achieved at the end of the G1 phase by the CDK2/cyclin E complex. Fully phosphorylated Rb protein is inactive and releases the E2F factor, allowing the expression of S phase genes, leading the cells through the G1/S checkpoint. …

Мужской пол и возраст являются независимыми факторами риска для стадии саркопении у пациентов с хронической почечной недостаточностью, не находящихся на гемодиализе.

ОБЪЕКТ: Риск развития саркопении у пожилых людей с хронической почечной недостаточностью (ХПН), не находящихся на диализе, остается спорным. Целью данного исследования было изучить связь между саркопенией, диабетом и ХПН до начала диализа, а также оценить влияние пола и возраста на риск развития саркопении у пожилых пациентов с ХПН до начала диализа. МЕТОДЫ: Участники старше 60 лет были отобраны из сообщества Новой Тайpei, Тайвань. Измеряли силу хватания, массу скелетной мышцы конечностей и время прохождения 6-метровой дистанции. Диагноз саркопении был установлен согласно консенсусу Азиатской

Oxidative Stress in Multiple Myeloma: Pathogenic Mechanisms, Biomarkers, and Redox-Targeted Therapeutic Strategies.

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by high metabolic activity, chronic endoplasmic reticulum stress, and persistent redox imbalance. Excessive immunoglobulin synthesis and adaptation to the hypoxic bone marrow microenvironment lead to sustained production of reactive oxygen species (ROS). Their excessive accumulation promotes genomic instability, disease progression, osteolytic bone disease, and resistance to therapy. Paradoxically, MM cells adapt to oxidative stress by activating antioxidant and metabolic defense mechanisms, including Nuclear factor ery

Analysis of differential gene immune infiltration and clinical characteristics of skin cutaneous melanoma based on systems biology and drug repositioning methods to identify drug candidates for skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) has a low early detection rate and a high mortality rate. There are many problems such as side effects and drug resistance in existing therapeutic drugs. Current studies have confirmed that SKCM pathogenesis-related genes promote the invasion and metastasis of cutaneous melanoma, but their roles in the tumor microenvironment (TME) remain unclear. Network pharmacology provides new opportunities for drug repurposing and repositioning, and is a fast, safe, and inexpensive drug discovery method to find new drugs for the treatment of SKCM. In this study, based on 3 da

The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

Most antiviral agents are designed to target virus-specific proteins and mechanisms rather than the host cell proteins that are critically dysregulated following virus-mediated reprogramming of the host cell transcriptional state. To overcome these limitations, we propose that elucidation and pharmacologic targeting of host cell Master Regulator proteins—whose aberrant activities govern the reprogramed state of infected-coronavirus cells—presents unique opportunities to develop novel mechanism-based therapeutic approaches to antiviral therapy, either as monotherapy or as a complement to establ

The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer.

One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, and the outlook is still dreadfully dire. The pursuit of a paradigm change in treatment approaches is, therefore, imperative. Tyrosine kinases (TKs), a subclass of protein kinases, regulate vital cellular function by phosphorylating tyrosine residues in proteins. Mutations, overexpression, and autocrine parac

Совпадение в полном тексте источника
… In human malignant glioma (U251MG) cells, it was found to inhibit cell growth, induce the arrest of the cell cycle at the G0/G1 phase, and suppress the expression of key cell cycle regulatory proteins, thereby hindering tumor proliferation [ 92 ]. … Fsetin’s antiproliferative effect, which entails causing a modest G2/M arrest and stopping the cell cycle in the G1 phase, is ascribed to its inhibition of VEGF production [ 165 ]. …

SAE1 May Play a Pro-Carcinogenic Role in Pancreatic Adenocarcinoma: A Comprehensive Study Integrating Multiple Pieces of Evidence.

SAE1, a key factor in tumour development, has not been thoroughly examined in pancreatic adenocarcinoma (PAAD), a cancer with high incidence and poor prognosis. We conducted a comprehensive study, integrating mRNA data, immunohistochemistry, CRISPR-modified cell line analysis and single-cell RNA sequencing to assess SAE1's role in PAAD. We also used ChIP-Seq to explore SAE1's transcriptional regulation and analysed clinical data, drug sensitivity and molecular docking models. SAE1 mRNA was significantly overexpressed in PAAD, with a substantial impact on cell proliferation and migration. Funct

Совпадение в полном тексте источника
… Fludarabine can disrupt the cell cycle process of lymphoma cells by blocking the G0/G1 phase and promoting cell apoptosis [ 78 ]. …

FDA-Approved Small Molecule Compounds as Drugs for Solid Cancers from Early 2011 to the End of 2021.

Solid cancers are the most common types of cancers diagnosed globally and comprise a large number of deaths each year. The main challenge currently in drug development for tumors raised from solid organs is to find more selective compounds, which exploit specific molecular targets. In this work, the small molecule drugs registered by the Food and Drug Administration (FDA) for solid cancers treatment between 2011 and 2022 were identified and analyzed by investigating a type of therapy they are used for, as well as their structures and mechanisms of action. On average, 4 new small molecule agent

Совпадение в полном тексте источника
… Hence, this drug inhibits the cell cycle in the G1 phase and the proliferation of ALK-dependent cancer cells. Among the existing therapies targeting EGFR-mutated NSCLC, there have been two FDA-approved medicaments during the last eleven years, i.e., osimertinib and mobocertinib . … They inhibit Rb protein phosphorylation in the early G1 phase, thereby blocking cell-cycle transition from G1 to S phase and reducing cancer cell growth ( Figure 2 ) [ 61 , 62 , 63 , 64 ]. …

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

Совпадение в полном тексте источника
… While it accumulates in the cytoplasm during the G1 phase of cell cycle, p53 enters the nucleus during the G1/S phase transition [ 27 ]. Nuclear exclusion of p53 is observed in many tumors and is mediated by XPO1 [ 28 ]. …

Recent Trends in anti-tumor mechanisms and molecular targets of celastrol.

Celastrol, a compound derived from traditional Chinese medicine, has therapeutic effects and has been used to treat inflammation-related diseases, cancer, cardiovascular diseases, and neurodegenerative diseases. However, current reviews lack a comprehensive and systematic summary of the anti-tumor mechanisms and molecular targets of celastrol. For this reason, this paper reviews the anticancer properties of celastrol and the molecular mechanisms underlying its anticancer effects. This paper primarily focuses on the mechanism of action of celastrol in terms of inhibition of cell proliferation a

Совпадение в полном тексте источника
… Celastrol also enhances p21 and p27 expression while decreasing Cyclin D1 and Cyclin E levels, inhibiting cell proliferation and leading to G1 phase arrest in multiple myeloma cells 20 . … Additionally, celastrol increases the expression of TNF receptor superfamily members (TNRSF) 1A and 10B, and TNFRSF1A is associated with the death domain, Fas, and Fas-associated via the death domain, leading to cell cycle arrest in the G1 phase and G2/M phase, and inducing apoptosis 34 . …

Casein Kinase 2 Inhibitor, CX-4945, Induces Apoptosis and Restores Blood-Brain Barrier Homeostasis in In Vitro and In Vivo Models of Glioblastoma.

Background: In oncology, casein kinase 2 (CK2), a serine/threonine kinase, has a dual action, regulating cellular processes and acting as an oncogenic promoter. Methods: This study examined the effect of CX-4945, a selective CK2 inhibitor, in a human U-87 glioblastoma (GBM) cell line, treated with CX-4945 (5, 10, and 15 μM) for 24 h. Similarly, the hCMEC/D3 cell line was used to mimic the blood-brain barrier (BBB), examining the ability of CX-4945 to restore BBB homeostasis, after stimulation with lipopolysaccharide (LPS) and then treated with CX-4945 (5, 10, and 15 μM). Results: We reported t

Synthetic lethality and DNA damage response targeting in cancer stem cells: a comprehensive review.

This comprehensive review explores the critical intersection of Synthetic Lethality (SL) and DNA Damage Response (DDR) targeting within Cancer Stem Cells (CSCs), a subpopulation central to tumor initiation, metastasis, and therapeutic resistance. CSCs exhibit unique biological properties, including enhanced DNA repair mechanisms and metabolic plasticity, rendering them intrinsically resistant to conventional therapies. The fundamental mechanisms of DDR pathways and their dysregulation in cancer are delineated, highlighting how these vulnerabilities can be exploited through SL. The review synth

TACC3, correlated with immune cell infiltrates, is a novel prognostic biomarker in BRCA.

Transforming acidic coiled-coil-containing protein 3 (TACC3) plays a crucial oncogenic role in various carcinomas and may act as a novel prognostic factor. However, its prognostic significance and underlying mechanisms in breast cancer (BRCA) remain unclear and require further investigation. This research included 181 breast cancer tissues, and the expression levels of TACC3 were analyzed by immunohistochemistry staining and grading. The mRNA expression of TACC3 in pan-cancer was analyzed with The Cancer Genome Atlas data platform. Receiver operating characteristic curve analysis assessed TACC

The Clinical Impact of Death Domain-Associated Protein and Holliday Junction Recognition Protein Expression in Cancer: Unmasking the Driving Forces of Neoplasia.

Death domain-associated protein (DAXX) and Holliday junction recognition protein (HJURP) act as chaperones of H3 histone variants H3.3 and centromere protein A (CENPA), respectively, and are implicated in many physiological processes, including aging and epigenetic regulation, by controlling various genes' transcription and subsequently protein expression. Research has highlighted both these biomolecules as participants in key procedures of tumorigenesis, including cell proliferation, chromosome instability, and oncogene expression. As cancer continues to exert a heavy impact on patients' well

Совпадение в полном тексте источника
… HJURP acts as a centromere protein A (CENPA) histone chaperone, aiding its deposition during the late mitosis/early G1 phase of the cell cycle [ 7 ]. HJURP plays a vital role in safeguarding chromosome stability. …

" Nucleolus in Human Beasons: Ribosome Biogenesis " , " Nucleolar Survey " и " Terrapeutic Opportunities " .

Nucleolus превратился в динамичную и многофункциональную субядерную органилию, интегрирующую рибосомный биогенез с клеточным ростом и сигнализацией стресса. Регулирование нуклеолярной функции все чаще признается в качестве главного движителя человеческих заболеваний, связывающего изменённое рибосомное производство и нуклеолярное наблюдение с раком, рибосомопатиями, синдромами преждевременного старения, нейродегенерацией и иммунными расстройствами. В этом обзоре мы интегрируем структурные, молекулярные и болезнетворные перспективы нуклеолярной биологии для определения того, как рипосомный биоге

Clinical Experience with Targeted Alpha-Emitter Peptide Receptor Radionuclide Therapy (α-PRRT) for Somatostatin Receptor-Positive Neuroendocrine Tumors.

Background: α-emitting Peptide Receptor Radionuclide Therapy (α-PRRT) is emerging as a promising new generation of PRRT for neuroendocrine tumors (NETs), providing enhanced tumor cell cytotoxicity and reduced irradiation of adjacent healthy tissues due to its high linear energy transfer (LET) and short particle range. This review summarizes available clinical evidence on α-PRRT using different α-emitting isotopes, including actinium-225, lead-212, and bismuth-213, in somatostatin receptor (SSTR)-positive NETs. Methods: A comprehensive literature search was conducted across PubMed, Embase, Coch

The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications.

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (N

New approaches for cancer treatment: antitumor drugs based on gene-targeted nucleic acids.

Currently, the main way to fight cancer is still chemotherapy. This method of treatment is at the height of its capacity, so, setting aside the need for further improvements in traditional treatments for neoplasia, it is vital to develop now approaches toward treating malignant tumors. This paper reviews innovational experimental approaches to treating malignant malformations based on the use of gene-targeted drugs, such as antisense oligonucleotides (asON), small interfering RNA (siRNA), ribozymes, and DNAzymes, which can all inhibit oncogene expression. The target genes for these drugs are t