Mir-615-5p inhibits cervical cancer progression by targeting TMIGD2

Hereditas, Год журнала: 2025, Номер 162(1)

Опубликована: Янв. 9, 2025

Abstract Background Cervical cancer (CC) is a prevalent gynecological malignancy, contributing to substantial number of fatalities among women. MicroRNAs (miRNAs) have emerged as promising biomarkers with significant potential for the early detection and prognosis CC. Objective This study aimed explore clinical significance biological role miR-615-5p in CC, goal identifying novel this disease. Materials methods The levels TMIGD2 mRNA tissue samples cells were quantified through quantitative reverse transcription real-time PCR, followed by statistical analyses investigate correlation between data. effects on proliferation metastasis CC evaluated using Cell Counting Kit-8 Transwell assays. mechanism was elucidated bioinformatics Dual-luciferase reporter assay. Western blotting employed measure protein TMIGD2. Results In downregulation related poor an independent prognostic factor. reduced cells. overexpression restrained Furthermore, identified target gene regulated miR-615-5p, its expression notably elevated influence behaviors mediated modulation Conclusions Downregulation indicator exerted tumor-suppressive inhibiting cell growth regulation

Язык: Английский

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Bidirectionally Favorable Platform: A Dual-Targeting Probe-Encoded Maple Leaf-Type Fluorescent Lateral Flow Immunoassay for Multiple Biomarker Detection

Analytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

In the traditional multiplexed lateral flow immunoassay (LFIA), different detection probes against targets are necessary. However, relative complexity and high cost of probe preparation, as well insufficient user-friendliness, limit application LFIA in disease diagnosis. Here, we reported a bidirectionally favorable (BDF-LFIA) platform to maximize convenience for both manufacturers users. Red-emitting time-resolved fluorescent nanoparticles were coated with antibodies recognize multiple simultaneously, which greatly simplified preparation by manufacturers. Ultrabright green-emitting gold nanoclusters pre-embedded on test line reference signal achieve target concentration-dependent maple leaf-type hue readout from green yellow red, was quite user-friendly. Taking cancer biomarkers alpha-fetoprotein carcinoembryonic antigen examples, this assay achieved visual 2 ng/mL. Compared conventional LFIA, BDF-LFIA could generate more discernible around threshold concentration targets. Moreover, successfully diagnosed 54 clinical samples. Overall, showed bidirectional benefits users provided new concept detection.

Язык: Английский

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Combining immune checkpoints with TNFSF agonists: a new horizon for cancer and autoimmune therapies

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 17, 2025

The immune response is orchestrated by a complex network of cytokines, which play fundamental role in both autoimmune diseases and cancer therapy. Immune checkpoint inhibitors (ICIs), target key inhibitory pathways such as PD-1/PD-L1 CTLA-4, have revolutionized immunotherapy reinstating T-cell activity overcoming evasion mechanisms [1]. Despite their success cancers like melanoma lung cancer, substantial number patients fail to respond ICIs. This resistance often due the lack pre-existing immunity, emergence mechanisms, or an immunosuppressive tumor microenvironment (TME), highlighting need for more targeted therapeutic strategies [2]. In this context, cytokines receptor networks, particularly those within necrosis factor superfamily (TNFSF) its receptors (TNFRSF), emerged pivotal players regulating responses.Figure 1 illustrates TNFSF signaling pathway. It shows structure unbound state interaction with receptor. Upon binding, forms receptor-ligand complex, depicted middle portion. lower part highlights downstream events following clustering. clustering activates TRAF2 plays critical modulating responses. These interactions are regulation enhance potential targeting [3]. Cytokines OX40, 4-1BB, CD40 promote activation, survival, proliferation, contributing anti-tumor immunity homeostasis However, constrained exhaustion effects TME, can limit efficacy, similarly ICIs [4]. (left), followed binding (green, blue, pink) (middle). right panel (orange) bound receptor, initiating formation complex. how ligandreceptor triggers leading essential responses.To overcome these limitations, combining agonists presents synergistic strategy. While unmask suppression restore responses, agonists, OX40 activation providing robust [5]. Furthermore, TNFR2 could modulate regulation, influencing regulatory activity, offering benefits 带格式的: 缩进: 首行缩进: 0 字符 diseases.However, integration also faces challenges, immunerelated adverse (irAEs), optimal dosing strategies, identifying who would benefit most from therapies. [6]. Precision medicine, guided biomarkers advanced diagnostic techniques, will be hurdles. Opinion Article explores offer novel approach cytokine networks advancing treatment outcomes cancer.ICIs therapy PD-1, PD-L1, restoring enhancing elimination. low infiltration emphasizing complementary [7].TNFSF CD40, provide complement amplifying proliferation through co-stimulatory signals [8]. CD4+ CD8+ while 4-1BB cytotoxicity natural killer (NK) cell activity. Similarly, stimulate antigen-presenting cells (APCs), fostering adaptive immunity. reduce counteract influences T (Tregs) myeloid-derived suppressor (MDSCs) TME. Table summarizes clinical development, including Urelumab Selicrelumab ABBV-927 diseases. agents highlight diverse applications combination potent immunotherapies raises concerns about immune-related release syndrome autoimmunity.Careful patient selection, biomarker-driven stratification, optimized mitigate risks.The synergy between arises mechanisms. it promotes tumor-free survival. some trials, therapies ipilimumab (a CTLA-4 inhibitor) BMS-986178 did not improve rate compared monotherapy. safety profiles combinations varied, common side lymphopenia, rash, pyrexia, fatigue.Further research needed optimize better [21].Clinical trials started explore various cancers, melanoma, non-small colorectal cancer. Early-phase PD-1 shown promising results, improved objective rates progressionfree survival [22][23][24]. blockade CD8 + T-cell-dependent manner murine gliomas. reduces TIL improves functionality. Efficacy correlates expression on TILs, location histology, license models where levels were previously [25]. being investigated ICIs, preliminary data suggesting enhanced regression durable responses [26][27][28]. when paired demonstrated ability convert immunologically cold tumors into hot ones, rendering them susceptible attack [29,30]. ongoing Phase I/II study, intratumoral sotigalimab (CD40 agonist) systemic pembrolizumab (anti-PD-1) was evaluated treatment-naïve, unresectable stage III/IV metastatic patients. As December 2021, 30 participants enrolled, well-tolerated no treatment-related discontinuations deaths. injection-site reactions, 6 experiencing grade-3 events. overall (ORR) 50% (5 complete 10 partial responses), disease control 67%. Notably, observed PD-L1 negative elevated LDH. Immunologic analyses showed increased higher clonality gene related antigen presentation, correlating efficacy warranting further investigation [31].Despite encouraging progress, significant challenges remain realizing full ICI agonist combinations. One primary risk irAEs. Both independently induce activation-related toxicities, (CRS), autoimmunity, inflammation. When combined, may exacerbate effects, necessitating careful dose optimization monitoring [32].Another challenge lies specificity. expressed multiple types, Tregs activated cells, off-target effects. For instance, Treg function settings, TME context-dependent, potentially favoring either activation. inadvertently activate pathogenic subsets, complicating outcomes. Patient stratification biomarker identification pose heterogeneity across different populations requires precision medicine identify likely Biomarkers expression, infiltration, guide but predictive value needs validation [33].Finally, logistical trial design execution must addressed [34]. CombiningICIs consideration schedules, administration sequences, partners maximize minimizing toxicity. Developing standardized protocols establishing endpoints accelerating translation practice.The offers opportunities diseases, addressing delicate balance suppression.ICIs, inhibitors, contexts, broad leads exacerbating autoimmunity [35,36]. contrast, approach, leveraging properties fine-tune [37].For example, candidates promoting expansion, maintaining tolerance mitigating hyperactive [38]. mechanism relevant rheumatoid arthritis, inflammation driven effector myeloid predominant. Studies that only enhances inflammatory macrophages dendritic cells. Additionally, DR3agonists selectively subsets without overactivating entire system. specificity especially valuable chronic conditions lupus sclerosis, system persistently hyperactive. By homeostasis, flares global immunosuppression [38,39]. erythematosus (SLE), Anifrolumab has positive results II III trials. August drug approved FDA moderate severe active SLE.Clinical improving organspecific markers, interferon-I [40,41].The create unique synergies.ICIs reactivate suppressed functionality reverse underlying viral infections, tolerogenic capacity existing treatments biologics small-molecule opens new avenues Targeted use achieve remission traditionally refractory single-agent therapies, representing advancement field therapeutics [42].The represents rapidly evolving area vast unmet fully realize potential, several areas demand focused innovation.While first-generation promise, types poses Next-generation should focus achieving controllable [43]. recent study development bispecific OX40-PD-L1 antibody, targets [9,44,45]. Advances antibody engineering, antibodies conditional allow precise delivery specific (TME) sites pathology. designing presence high other markers characteristic associated toxicities.One combinatory agonists. Biomarker paramount [46]. A Zhang et al. (2022) highlighted predict [35]. (e.g., cells), TNFRSF density selection high-throughput sequencing, single-cell analysis, artificial intelligence our prognostic biomarkers, paving way truly personalized immunotherapy.While benefits, amplified combined modalities [47]. Such Traditional Therapies:Combining chemotherapy radiotherapy Combining creating immunogenic [48].While current predominantly therapy, [36].Robust preclinical accurately recapitulate human predicting toxicity [49]. organoid systems, humanized mouse models, computational simulations findings success. Recent regimens, significantly [19]. On front, designs incorporating real-time accelerate effective therapies.The complexity necessitates collaboration disciplines [50]. Immunologists, oncologists, biologists, pharmaceutical scientists work together integrate insights basic research, practice, technological innovation. Partnerships academia, industry, agencies crucial streamlining pathway discovery implementation. Successful examples cross-disciplinary include progressed stages [22].The provides lifting suppression, allowing reactivation amplify effectively transforming "cold" "hot" ones bolstering diseases.Despite immense remain, regard irAEs, specificity, optimizing selection. diagnostics, nextgeneration safety. integrating interdisciplinary collaboration, strategy holds promise hope

Язык: Английский

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Adverse drug reaction assessment of pembrolizumab in cervical cancer treatment: a real-world pharmacovigilance study using the FAERS database

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 8, 2025

Objective Advanced cervical cancer remains associated with high mortality rates. While pembrolizumab has improved clinical outcomes in cancer, the therapeutic efficacy advanced stages is often compromised by immune-related adverse events (irAEs). This study aimed to systematically analyze pembrolizumab-associated (AEs) using FDA Adverse Event Reporting System (FAERS) database, providing new insights for optimizing practice. Methods AE reports related were extracted from FAERS database (Q1 2016 Q4 2024). Disproportionality analyses performed multiple algorithms, including reporting odds ratio (ROR), proportional (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). AEs classified system organ class (SOC) preferred term (PT) based on Medical Dictionary Regulatory Activities (MedDRA), then ranked frequency signal strength. Results A total of 646 pembrolizumab-related identified. Age distribution peaked at 45–65 years cohort (32.75%), followed 18–44 (12.85%), 66–75 (11.76%), >75 (4.64%). Among 270 documented onset timelines, predominantly occurred 3–6 months after initiation (n=114, 41.36%). Clinical categorized as other (52.80%), hospitalization (27.00%), death (10.25%), unknown (6.06%), life-threatening (2.77%), disability (1.12%). Predominant involved hematologic, endocrine, dermatologic, neurologic, gastrointestinal, urinary, reproductive systems. Conclusion real-world pharmacovigilance characterizes identifying high-signal such hematologic disorders, endocrine dysfunction, dermatologic toxicities. These findings provide critical evidence risk stratification safety monitoring practice, emphasizing need organ-specific vigilance during treatment window.

Язык: Английский

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Phototheranostics: An Advanced Approach for Precise Diagnosis and Treatment of Gynecological Inflammation and Tumors

Biomaterials, Год журнала: 2024, Номер 316, С. 123012 - 123012

Опубликована: Дек. 15, 2024

Язык: Английский

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Editorial: Novel immune markers and predictive models for immunotherapy and prognosis in breast and gynecological cancers

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 29, 2024

Editorial: Novel immune markers and predictive models for immunotherapy prognosis in breast gynecological cancers

Язык: Английский

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Electrochemical detection of cervical cancer biomarkers

Clinica Chimica Acta, Год журнала: 2024, Номер 567, С. 120103 - 120103

Опубликована: Дек. 18, 2024

Язык: Английский

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