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Появляющаяся роль BTK Inhibitors в многоразовом склерозе: от иммунобиологии к клиническому переводу.

Множественный склероз (MS), аутоиммунное заболевание, предполагает периферическую иммунную активацию, за которой следует воспаление CNS в разрозненной форме. Несмотря на то, что высокоэффективные методы коррекции заболеваний (HO-DMT) оказались эффективными в борьбе с рецидивами у пациентов с синдромом MS, они не позволяют эффективно ориентироваться на хроническую микрогильевую активацию и удушающие повреждения у пациентов с синдромом MS. Тейросиновые ингибиторы киназы Брютона (BTKis), которые являются перорально активными и способными пересечь мозговой барьер, были признаны эффективными для мо

Риск заражения иммунной контрольной точкой: систематический обзор и метаанализ.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Относительный риск (RR) инфекции для пациентов, прошедших курс лечения с ингибиторами для иммунных контрольно-пропускных пунктов (ИПК), неизвестен. ЦЕЛИ: В этом исследовании была проведена оценка риска инфицирования пациентов с твердыми опухолями, проходящих курс лечения в рамках ИКИ, на основе систематического обзора и метаанализа. ПАТИЕНТЫ И МЕТОДЫ: Были проведены обыски баз данных библиотеки Кокрана, ЭМБАСЕ и Пубмеда 1 декабрь 2020. Включены случайные испытания, сравнивающие любой ICI в одиночку с химиотерапией (CT) или с другими агентами против плацебо, КТ или других

Role of Cyclin-Dependent Kinase Inhibitors in Endometrial Cancer.

Endometrial Cancer (EC) is an important cause of death in women worldwide. Despite early diagnosis and optimal treatment of localized disease, relapsed patients have few therapeutic options because after first line therapy, currently no standard of care exists. On the basis of endocrine positivity of most endometrioid ECs, Endocrine Therapy (ET) is a reasonable and widely accepted option. Better knowledge of molecular mechanisms involved in cancer highlighted the deregulated activity of Cyclin-Dependent Kinases (CDKs) in the cell cycle as a hallmark of carcinogenesis supporting the development

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… In response to mitogenic and growth signals, during G1 phase, CDK4/6 and cyclin D form a complex that phosphorylates retinoblastoma susceptible protein (Rb) causing the dissociation of E2F factor from Rb [ 38 ]. … Indeed, preclinical studies suggest that Estradiol and Progesterone have opposite activity in terms of nuclear levels of p27, an inhibitor of CDK2-cyclin E and CDK4-cyclin D and consequently on cell cycle arrest in G1 phase. …

PD 0332991, a selective cyclin D kinase 4/6 inhibitor, sensitizes lung cancer cells to treatment with epidermal growth factor receptor tyrosine kinase inhibitors.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major challenge to targeted therapy for non-small cell lung cancer (NSCLC). We investigated whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse EGFR-TKI resistance in human lung cancer cells and explored the underlying mechanisms. We found that PD 0332991 potentiated gefitinib-induced growth inhibition in both EGFR-TKI-sensitive (PC-9) and EGFR-TKI-resistant (PC-9/AB2) cells by down-regulating proliferation and inducing apoptosis and G0/G1 cell cycle arrest. Tumor xenogra

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… PD 0332991 enhanced the gefitinib-induced inhibition of cell proliferation, apoptosis, and G0/G1 phase arrest in lung adenocarcinoma cell lines EdU staining was used to determine the effect of PD 0332991 on NSCLC cell proliferation. … Figure 2 PD 0332991 enhances gefitinib-induced anti-proliferation, apoptosis and G1 phase arrest in gefitinib sensitive and resistant cells A. …

Candesartan cilexetil as a repurposed therapeutic candidate for nasopharyngeal carcinoma: Integrated in vitro and in silico analyses.

Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia and is often diagnosed at advanced stages, where current treatment options are limited and associated with high relapse rates and toxicity. Repurposing clinically approved drugs provides a rapid, cost-effective strategy to identify new therapeutic interventions. Here, we investigated candesartan cilexetil (CC), an angiotensin II type 1 receptor (AT1R) blocker widely used for hypertension (13), for its potential anti-cancer effects in NPC. In vitro assays were performed to assess cell viability, proliferation, clonogenic sur

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… Flow cytometric analysis demonstrated that CC treatment (12.5 - 25.0 μM for 48 h) induced a clear accumulation of TW01 cells in the G0/G1 phase (Figure 5 (Fig. 5) ). … CC induces accumulation in the G0/G1 phase. (B) The percentage of cells in each phase of the cell cycle (G0/G1, S, and G2/M) was quantified, showing significant differences between the treatment conditions and the control. The experiment was performed in biological triplicate. …

Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats.

Background and objectivesA drug repurposing strategy is an approach for identifying new therapeutic uses for approved or investigational drugs. Thanks to the moderate cost of repurposing a drug compared to bringing new chemical entity to the market, drug repurposing is rapidly gaining ground. The aim of this work is to study the anti-obesity effect of disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor approved by the Food and Drug Administration (FDA) to treat chronic alcoholism since 1951.MethodsThirty male Albino rats were randomly assigned to six groups. G1, the control grou

метрики соотношений на основе пропорциональности при подсчете данных о составе.

Составные данные включают векторы, описывающие составные части целого. Данные, полученные с помощью различных -омикических платформ, таких, как 16S и RNA, носят составный характер. В таких данных корреляции между характеристиками первичных счетов не имеют сколько-нибудь значимого толкования. Для решения этой проблемы были сформулированы критерии пропорциональности. Однако имманентная погрешность возникает тогда, когда эти метрики рассчитываются эмпирически на основе показателей, основанных на подсчете, из-за изменчивости глубин считываемого материала. Мы подсчитали погрешность, введенная путем

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… In the G1 phase, there were 56 gene pairs in common, in G2M phase, there were 38 gene pairs in common, and in S phase, there were 40 gene pairs in common ( Supplementary Fig. S6 ). Relatedly, the empirical and model-based estimates are compared in Fig. 4 . … Silencing KFI20B has also been shown to increase cell arrest in G1 phase[ 30 ]. Table 1. …

Реальные результаты лечения от рака яичников в мире после " Мирветуксимаб соравтансин " : результаты работы в университете.

Foreign Mirvetuximab Soravtansine (MIRV) — антитело-наркомания, ориентированная на фолатовый рецептор альфа (FRα), выраженная в большинстве раковых заболеваний яичников. В ходе испытаний были получены положительные результаты, однако были использованы жесткие критерии отбора, а эффективность и токсичность в реальном мире по-прежнему являются неполными. Мы провели оценку общего выживаемости (ОС), без прогрессии выживаемости (ПФС) и токсичности среди общего гинекологического онкологического населения, лечившегося с помощью MIRV, в отношении повторяющегося рака яичников. 2022 и апрель 2025. Демог

Improved oncolytic and immunostimulatory activity of the spontaneous jin-3 reovirus mutant in preclinical bladder cancer models.

Immunotherapy has emerged as a promising strategy for treatment of urothelial carcinoma of the bladder (UCB) but not all patients show clinically desirable responses upon treatment with immune-checkpoint inhibition. Oncolytic viruses may unleash the full potential of immunotherapy. Besides tumor-lysing properties, oncolytic viruses can induce durable and systemic anti-viral and anti-tumor immune responses. Here, we evaluated and compared oncolytic and immunostimulatory properties of wild-type reovirus (R124) and the junction-adhesion molecule-independent mutant reovirus (jin-3) in preclinical

Screening the Active Phytochemicals From Eclipta prostrata and Unraveling Their Molecular Insight Into Human Malignancies.

Current drugs against multiple human malignancies are limited, and developing new treatment strategies is improbable within a short time. So, considering the current situation, phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies. Therefore, we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually. We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search, and these compounds have chemoth

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… Park and colleagues demonstrated that alpha‐amyrin (15.45 ± 6.82 μM) induced apoptosis in A549 lung tumor cells and triggered G1 phase halt in cell‐division cycle progression through enhanced Bax protein expression, inhibition of Bcl‐2, and initiation of caspase‐3 cleavage [ 91 ]. … Furthermore, LUT, in conjunction with asiatic acid (AsA) induced apoptosis and caused sub‐G1‐phase arrest in cervical carcinoma cells (CaSki and HeLa) by regulating various signaling pathways, such as PI3K/AKT, JNK/p38 MAPK, and FAK, while upregulating ERK signaling [ 213 ]. …

Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing.

Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial sm

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… Together with its binding partners cyclin-dependent kinase (CDK) 4 and CDK6, cyclin D1 forms active complexes that promote the phosphorylation of retinoblastoma protein (RB) and activation of E2F-responsive gene with roles in DNA synthesis, and in turn promote progression through the G1 phase of the …

Gambogenic acid synergistically potentiates bortezomib-induced apoptosis in multiple myeloma.

Background: Although the introduction of protease inhibitor bortezomib (BTZ) and immunomodulatory agent lenalidomide has led to improved outcomes in patients with multiple myeloma (MM), the disease remains incurable. Gambogenic acid (GNA), a polyprenylated xanthone isolated from the traditional Chinese medicine gamboge, has been reported to have potent antitumor activity and can effectively inhibit the survival and proliferation of cancer. In this study, we hypothesized that GNA could synergistically potentiate BTZ-induced apoptosis of MM cells and that combining BTZ and GNA may provide a more

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… The percentage of MM.1S in sub G1 phase after 48h 0.90μM GNA treatment was 30.23±0.66% and the percentage in sub G1 phase after 4.0nM BTZ plus 0.9μM GNA treatment was 34.93±3.09%. …

Всеобъемлющий анализ SOX7 дает новое представление о его роли опухоля и его целевых генах с терапевтическими последствиями в множестве миеломы.

Множественная миелома (ММ) — неизлечимая гематология. SOX7, расположенное в области 8p23.1 в MM, предлагается действовать в качестве ограничителя опухоли. Мы описали SOX7 с помощью генетического, эпигенетического и функционального анализа в линиях клеток MM. SOX7 часто замолчали из-за исключения и/или содействия гиперметилированию. Эктомическое выражение SOX7 в KMS-18 и MM.1S привело к постепенному снижению числа камер, передаваемых SOX7, и вызвало арест и/или апоптоз в клеточном цикле G1. Хотя повторное выражение SOX7 не повысило бортезомибную эффективность, лечение панхистоном деацетилазным

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… Ectopic SOX7 Expression Causes G1 Phase Cell Cycle Arrest in MM Cell Lines In order to investigate the mechanisms underlying the tumor suppressor effect observed in the GFP competition assay, we examined whether the re-expression of SOX7 induces cell cycle arrest. … Compared with the DMSO-treated control, panobinostat treatment increased the proportion of cells in the G1 phase, with a concomitant decrease in the S and G2/M phases at all tested concentrations ( Figure S6D ). We next examined the effect of panobinostat on cell survival ( Figure S7A–C ). …

Iron deprivation in cancer--potential therapeutic implications.

Iron is essential for normal cellular function. It participates in a wide variety of cellular processes, including cellular respiration, DNA synthesis, and macromolecule biosynthesis. Iron is required for cell growth and proliferation, and changes in intracellular iron availability can have significant effects on cell cycle regulation, cellular metabolism, and cell division. Perhaps not surprisingly then, neoplastic cells have been found to have higher iron requirements than normal, non-malignant cells. Iron depletion through chelation has been explored as a possible therapeutic intervention i

A Super-Enhancer-Driven Transcriptional Regulatory Circuit Underlying Abiraterone Resistance in Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) remains the leading cause of mortality among prostate cancer patients. While second-generation androgen receptor (AR) pathway-targeted therapies, such as Abiraterone, have significantly improved survival outcomes, resistance to these treatments ultimately emerges, posing a critical challenge. Understanding the mechanisms underlying Abiraterone resistance is essential for developing strategies to enhance patient outcomes. In this study, a super-enhancer (SE)-driven transcriptional regulatory circuit is identified involving BCL6, NFIB, and SMAD3 that f

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… Therefore, we hypothesize that silencing the loop may reduce the expression of CCND3 and CDK2 by regulating their transcription, resulting in the G0/G1 phase arrest in C42B‐ABi cells. Figure 6 The super‐enhancer‐driven transcription factor loop mediates cell cycle arrest in the G0/G1 phase. … We speculate that cholesterol synthesis inhibition may lead to cell cycle arrest at the G0/G1 phase in C42B‐ABi cells. Therefore, we used siRNA and statins to respectively inhibit SREBF2 and HMGCR, and found the cell cycle was indeed arrested at the G0/G1 phase (Figure 6H,I ). …

Effective Targeting of Melanoma Cells by Combination of Mcl-1 and Bcl-2/Bcl-xL/Bcl-w Inhibitors.

Recent advances in melanoma therapy have significantly improved the prognosis of metastasized melanoma. However, large therapeutic gaps remain that need to be closed by new strategies. Antiapoptotic Bcl-2 proteins critically contribute to apoptosis deficiency and therapy resistance. They can be targeted by BH3 mimetics, small molecule antagonists that mimic the Bcl-2 homology domain 3 (BH3) of proapoptotic BH3-only proteins. By applying in vitro experiments, we aimed to obtain an overview of the possible suitability of BH3 mimetics for future melanoma therapy. Thus, we investigated the effects

Targeting HDACs with dacinostat amplifies radiation-induced DNA damage via sustained phosphorylated p53 and repair inhibition in aggressive meningioma.

The lack of standard systemic treatments in meningioma presents a therapeutic challenge, making radiotherapy a crucial intervention for recurrent, high-grade, or inoperable tumours. Nonetheless, the efficacy of radiotherapy is constrained by the inherent radioresistance of meningiomas, attributed to their proficient DNA damage repair and robust cell cycle checkpoint regulation. These biological barriers, along with anatomical constraints of avoiding damage to adjacent neural tissues, restrict dose escalation and therapeutic gains. Histone deacetylases (HDACs) are mediators of radioresistance i

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… Proteins associated with SUMOylation, RNA polymerase I transcription inhibition, mitotic G1 phase and G1/S transition, and RHO GTPase signalling formed distinct functional clusters (Supplementary Fig. S6c ). … Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase. Cell Cycle. 2013;12:1424–32. 24. Amano T, Nakamizo A, Mishra SK, Gumin J, Shinojima N, Sawaya R, et al. …

Healthcare workload associated with transition onto kidney replacement therapy: a retrospective cohort study.

BACKGROUND AND HYPOTHESIS: Transition onto kidney replacement therapy (KRT) is a complex, intensive phase for patients with advanced chronic kidney disease (CKD), characterised by high healthcare utilisation. Frequent outpatient visits, surgical and radiological procedures, hospitalisations and haemodialysis (HD) sessions impose a significant time burden on patients. The concept of time toxicity is widely described in oncology, and captures the disruption to patients' lives due to treatment-related demands. We aimed to quantify time- based healthcare workload during the transition onto KRT and

Influence of Metamizole on Antitumour Activity of Risedronate Sodium in In Vitro Studies on Canine (D-17) and Human (U-2 OS) Osteosarcoma Cell Lines.

The availability of metamizole varies greatly around the world. There are countries such as the USA, UK, or Australia where the use of metamizole is completely forbidden, and there are also countries where this drug is available only on prescription (e.g., Greece, Italy, Spain, etc.) and those in which it is sold OTC-over the counter (e.g., most Asian and South American countries). Metamizole, as a drug with a strong analgesic effect, is used as an alternative to other non-steroidal anti-inflammatory drugs, alone or in combination with opioid drugs. Risedronate sodium is a third-generation bis

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… The combination of 100 µg/mL of risedronate sodium and 50 µg/mL of metamizole reduced the number of cells in the G0/G1 phase, causing cell cycle arrest in the G2/M phase. … This study proved that risedronate sodium slightly increases the number of the cells in the G0/G1 phase due to cell arrest, and causes a significant decrease in cell percentage in the S phase. …

Natural anti-cancer products: insights from herbal medicine.

Herbal medicine exhibits a broad spectrum of potent anti-cancer properties, including the enhancement of tumor immune responses, reversal of multidrug resistance, regulation of autophagy and ferroptosis, as well as anti-proliferative, pro-apoptotic, and anti-metastatic effects. This review systematically explores recent advances (primarily documented since 2019) in research on key anti-cancer compounds derived from herbal medicine, such as apigenin, artemisinin, berberine, curcumin, emodin, epigallocatechin gallate (EGCG), ginsenosides, icariin, resveratrol, silibinin, triptolide, and ursolic

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… For instance, artesunate inhibits colon cancer cell proliferation by inducing cell cycle arrest at G0/G1 phase and subsequent cell senescence [ 138 ]. … Berberine can arrest the cell cycle of lymphocytic Jurkat cells at G0/G1 phase, suggesting that it may play a positive role in the treatment of leukemia [ 235 ]. …