Variable Expression of Oncogene-Induced Senescence/SASP Surrogates in HPV-Associated Precancerous Cervical Tissue DOI Creative Commons
Tareq Saleh, Nisreen Himsawi,

Amani Al Rousan

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(12), P. 13696 - 13712

Published: Dec. 2, 2024

Oncogene-induced senescence (OIS) is a form of cellular triggered by oncogenic signaling and, potentially, infection with viruses. The role senescence, along its associated secretory phenotype, in the development cervical cancer remains unclear. Additionally, expression senescence-associated phenotype (SASP) has not yet been explored premalignant lesions infected Human Papilloma Virus (HPV). This study aimed to investigate OIS and SASP markers HPV-infected precancerous lesions. We used set patient-derived (n = 32) noncancerous (chronic cervicitis; n 10) tissue samples gene several (LMNB1, CDKN2A, CDKN2B, CDKN1A), (IL1A, CCL2, TGFB1, CXCL8, MMP9) biomarkers using qRT-PCR. status was confirmed based on Lamin B1 downregulation immunohistochemical staining. HPV for all tested. Most showed high expression, however, exhibited significant (p < 0.001). Fifty-five percent were positive infection, HPV-16 as dominant genotype. coincided E6 expression. CDKN2A CDKN2B higher compared tissue, while LMNB1 downregulated. profile included elevated CXCL8 TGFB1 reduced IL1A, MMP9. this work shall provide an opportunity further examine process malignant transformation.

Language: Английский

Resolution of oncogene-induced senescence markers in HPV-infected cervical cancer tissue DOI Creative Commons
Ashraf I. Khasawneh, Sofian Al Shboul, Nisreen Himsawi

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 21, 2025

Language: Английский

Citations

1
Targeting therapy-induced senescence as a novel strategy to combat chemotherapy-induced peripheral neuropathy DOI
Mohammad Alsalem,

Amr Ellaithy,

Sarah Bloukh

et al.

Supportive Care in Cancer, Journal Year: 2024, Volume and Issue: 32(1)

Published: Jan. 1, 2024

Language: Английский

Citations

5
Therapy‐induced senescent cancer cells exhibit complement activation and increased complement regulatory protein expression DOI
Anas H. A. Abu-Humaidan, Mohammad A. Ismail, Fatima Ahmad

et al.

Immunology and Cell Biology, Journal Year: 2024, Volume and Issue: 102(4), P. 240 - 255

Published: Jan. 24, 2024

Abstract Therapy‐induced senescence (TIS) is a primary response to chemotherapy, contributing untoward treatment outcomes such as evasion of immunosurveillance. Despite the established role complement system in immune cancer, mediating against senescent tumor cells remains poorly understood. To explore this relationship, we exposed lung adenocarcinoma (A549), breast (MCF7) and pancreatic carcinoma (Panc‐1) cell lines sublethal doses either etoposide or doxorubicin trigger TIS. Identification TIS was based on morphological changes, upregulation senescence‐associated β‐galactosidase, p21 Cip1 induction lamin B1 downregulation. Using immunofluorescence microscopy, quantitative PCR, ELISA conditioned media silico analysis, investigated activation, protein expression, C3 levels secreted proteins part secretory phenotype (SASP), respectively. In undergoing TIS, complement‐related changes included (i) activation terminal pathway, evidenced by deposition C5b‐9 cells; (ii) an increase expression CD59 factor H (iii) A549 cells, elevation with its secretion into medium. addition, increased observed cancer samples expressing hallmarks following exposure neoadjuvant chemotherapy. conclusion, led complement, regulatory expression. Complement appears play shaping microenvironment upon induction.

Language: Английский

Citations

5
Cisplatin Provokes Peripheral Nociception and Neuronal Features of Therapy-Induced Senescence and Calcium Dysregulation in Rats DOI
Tareq Saleh, Randa Naffa, Noor A. Barakat

et al.

Neurotoxicity Research, Journal Year: 2024, Volume and Issue: 42(1)

Published: Jan. 31, 2024

Language: Английский

Citations

4
O-GlcNAcylation inhibition redirects the response of colon cancer cells to chemotherapy from senescence to apoptosis DOI Creative Commons

Ingrid Loison,

Adrien Pioger,

Sonia Paget

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(10)

Published: Oct. 19, 2024

Abstract The potential use of pro-senescence therapies, known as TIS (Therapy-Induced Senescence), for the treatment colorectal cancer (CRC) generated significant interest since they require lower doses compared to those required inducing apoptosis. However, senescent cell cycle-arrested cells are long-lived, and studies have revealed escape mechanisms contributing tumor recurrence. To deepen our understanding survival pathways used by cells, we delved into involvement hexosamine biosynthetic pathway (HBP). HBP provides UDP-GlcNAc, substrate O -GlcNAc transferase (OGT), which catalyzes -GlcNAcylation, a post-translational modification implicated in regulating numerous cellular functions aberrantly elevated CRC. In this study, demonstrated, p53-proficient colon lines HCT116 LS174T, that induced low-dose SN38 or etoposide was accompanied with decrease GFAT (the rate limiting enzyme HBP), OGT -GlcNAcase (OGA) expression correlated slight reduction -GlcNAcylation levels. Further decreasing level knocking-down redirected response subtoxic chemotherapy from senescence apoptosis, correlation an enhancement DNA damages. Pharmacological inhibition OSMI-4 LS174T patient-derived tumoroid model supported these findings. Taken together, results suggest combing inhibitors low conventional chemotherapeutic drugs could potentially reduce side effects while preserving efficacy. Furthermore, approach may increase specificity, CRC exhibit higher levels normal tissues.

Language: Английский

Citations

4
Comparative analysis of senescence induction by different chemotherapeutic agents in HCT116 colon cancer cells DOI

Adrien Pioger,

Ingrid Loison,

Inès Metatla

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 752, P. 151482 - 151482

Published: Feb. 11, 2025

Language: Английский

Citations

0
Classification of lung adenocarcinoma based on senescence-related genes identifies a cluster with immunotherapy resistance and poor prognosis DOI Creative Commons

Xinrui Gao,

Xiang Shen,

Shasha Huang

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 20, 2025

Lung adenocarcinoma is one of the major contributors to cancer-related mortality, with immunotherapy emerging as a key treatment. However, many patients exhibit resistance immune checkpoint inhibitors. Cellular senescence has been linked tumor progression and drug resistance, influencing microenvironment. This study applied consensus clustering classify lung into two clusters based on senescence-related gene expression, revealing differing characteristics. One identified exhibited immunosuppressive characteristics showed immunotherapy. A risk score was developed using machine learning predict response prognosis. High correlated poorer survival increased across multiple cancer types. The model robust predictive ability in both training validation cohorts. These findings suggest link between further investigation their relationship could reveal new perspectives for

Language: Английский

Citations

0
Role of Senescence-Associated Biomarkers and Immune Dynamics in Predicting Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer DOI Creative Commons
Yandong Liu,

Chenchen Wu,

Xiao Lu

et al.

International Journal of General Medicine, Journal Year: 2025, Volume and Issue: Volume 18, P. 1957 - 1967

Published: April 1, 2025

Neoadjuvant chemoradiotherapy (nCRT) is one of the standard treatments for locally advanced rectal cancer (LARC). However, therapeutic responses to this form treatment greatly vary from patient another. In work, we focused on changes serum senescence-associated secretory phenotype (SASP) factors and immune cell infiltration post-nCRT in a search possible predictors response nCRT. Twenty patients treated with nCRT were included underwent assessments before (pre-) after (post-) treatment. Inflammatory cytokines such as IL-1α, IL-6, IL-8; chemokines CCL5, CXCL1, CCL2 serum; infiltrations including CD8+, CD4+, CD206+ macrophages assessed by ELISA IHC, respectively. Tumor regressions evaluated MSK three-tier TRG grading system. Significant upregulation IL-8, CRP, CXCL1 was found, together increased CD8+ T tumor regression responders. IL-1α pre-nCRT levels promised predictive biomarkers, given that higher pretreatment associated lower regression. Increased cytotoxic improved outcome, whereas CD4+ cells M2 did not reach statistical significance. CCL2, cells, identified candidate markers might monitor effectiveness patients. These findings reinforce insights into microenvironment modulated SASP components imply need larger studies validate associations.

Language: Английский

Citations

0
Dissociation between the expression of cGAS/STING and a senescence-associated signature in colon cancer DOI Creative Commons
Sofian Al Shboul, Ola Abu Al Karsaneh,

Moath M. Alrjoub

et al.

International Journal of Immunopathology and Pharmacology, Journal Year: 2025, Volume and Issue: 39

Published: Jan. 1, 2025

Objective: The effect of the cGAS/STING pathway on antitumor immunity and its connection to senescence in vivo necessitates further investigation. Introduction: Cellular secretory phenotype (the SASP) are implicated modulating immune microenvironment cancer possibly through pathway. Methods: Gene expression data from paired colon adjacent non-malignant mucosa (98 patients, n = 196 samples; 65 130 samples) were analyzed for a signature. Immunohistochemistry assessed protein 124 colorectal samples. Results: Approximately one-quarter patients displayed profiles both gene sets, yet without significantly correlating with expression. Notably, cGAS was higher than STING tumor tissue compared colonic mucosa. Protein analysis showed 83% positive 39% expression, discrepancies patterns. Additionally, 15% samples lacked markers, while 35% exhibited staining both. No significant correlations found between status stage, patient age, lymphovascular invasion, or lymph node involvement. Conclusions: Our findings demonstrate marker but no correlation cGAS/STING.

Language: Английский

Citations

0
A Conversation with ChatGPT on Contentious Issues in Senescence and Cancer Research DOI Open Access
Ahmed M. Elshazly,

Uruk Shahin,

Sofian Al Shboul

et al.

Molecular Pharmacology, Journal Year: 2024, Volume and Issue: 105(5), P. 313 - 327

Published: March 8, 2024

Artificial intelligence (AI) platforms, such as Generative Pretrained Transformer (ChatGPT), have achieved a high degree of popularity within the scientific community due to their utility in providing evidence-based reviews literature. However, accuracy and reliability information output ability provide critical analysis literature, especially with respect highly controversial issues, has generally not been evaluated. In this work, we arranged question/answer session ChatGPT regarding several unresolved questions field cancer research relating therapy-induced senescence (TIS), including topics reversibility, its connection tumor dormancy, pharmacology newly emerging drug class senolytics. provided responses consistent available although occasionally overlooking essential components current understanding role TIS biology treatment. Although ChatGPT, similar AI an accurate review outputs should still be considered carefully, issues biology.

SIGNIFICANCE STATEMENT

Intelligence platforms great for researchers investigate biomedical literature prompt manner. arise when it comes certain biological questions, field. This work discussion some yet-to-be-fully-elucidated conundrums treatment highlights strengths weaknesses utilizing analyzing on topic.

Language: Английский

Citations

2