Immunogenic cell death signatures derived from on-treatment tumor specimens for predicting immune checkpoint blockade therapy response and prognosis in metastatic melanoma DOI Creative Commons
Huancheng Zeng,

Qiongzhi Jiang,

Rendong Zhang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 17, 2024

Abstract Melanoma is a highly malignant form of skin cancer that typically originates from abnormal melanocytes. Despite significant advances in treating metastatic melanoma with immune checkpoint blockade (ICB) therapy, substantial number patients do not respond to this treatment and face risks recurrence metastasis. This study collected data multiple datasets, including cohorts Riaz et al., Gide MGH, Abril-Rodriguez focusing on on-treatment samples during ICB therapy. We used the single-sample gene set enrichment analysis (ssGSEA) method calculate immunogenic cell death scores (ICDS) employed an elastic network algorithm construct model predicting efficacy. By analyzing 18 ICD signatures, we identified 9 key signatures effectively predict response for specimens. Results showed high had significantly higher rates therapy compared those low scores. ROC demonstrated AUC values both training validation sets were around 0.8, indicating good predictive performance. Additionally, survival revealed longer progression-free (PFS) overall (OS). identify related melanoma. These features can only efficacy but also provide references clinical decision-making. The results indicate plays important role immunotherapy expressing more accurately prognosis specimens, thus providing basis personalized treatment.

Language: Английский

Targeting breast cancer cells with 2-Indolyl-1,3,4-oxadiazole compounds by inducing apoptosis, paraptosis and autophagy DOI

Pradeep M. Uppar,

Na Young Kim,

Keshav Kumar Harish

et al.

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111528 - 111528

Published: April 1, 2025

Language: Английский

Citations

0
A Nanorobotics-Based Approach of Breast Cancer in the Nanotechnology Era DOI Open Access

Anca-Narcisa Neagu,

Taniya Jayaweera,

Krishan Weraduwage

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4981 - 4981

Published: May 2, 2024

We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating nanorobots, have demonstrated ingenious applications biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance to classic onco-therapies real-time monitoring tumors, nanorobots designed perform multiple tasks at a small scale, even organelles molecular level. Over last few years, most been bioengineered as biomimetic biocompatible nano(bio)structures, resembling different organisms cells, such urchin, spider, octopus, fish, spermatozoon, flagellar bacterium helicoidal cyanobacterium. In this review, readers will be able deepen their knowledge structure, behavior role several types among other theranostics. summarized here characteristics many functionalized nanodevices counteract main neoplastic hallmark features BC, from sustaining proliferation evading anti-growth signaling resisting programmed cell death inducing angiogenesis, activating invasion metastasis, preventing genomic instability, avoiding immune destruction deregulating autophagy. Most these function targeted self-propelled smart nano-carriers nano-drug delivery systems (nano-DDSs), enhancing efficiency safety chemo-, radio- photodynamic therapy, current imagistic techniques used diagnosis. tested vitro, using various lines, well vivo, mainly based on mice models. still waiting for that low-cost, wider transition favorable effects laboratory clinical practice.

Language: Английский

Citations

2
Zinc–Nickel Bimetallic Hydroxide Nanosheets Activate the Paraptosis–Pyroptosis Positive Feedback Cycle for Enhanced Tumor Immunotherapy DOI
Youdong Chen, Yujie Lu,

Huali Lei

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(43), P. 29913 - 29929

Published: Oct. 15, 2024

Immunotherapy holds significant promise for cancer treatment. However, the highly immunosuppressive nature of solid tumors limits its effectiveness. Herein, we developed bioactive zinc–nickel hydroxide (ZnNi(OH)4) nanosheets (NSs) that can effectively initiate paraptosis–pyroptosis positive feedback cycle through synergistic ionic effect, thereby mitigating immunosuppression and enhancing efficacy immunotherapy. The acid-sensitive ZnNi(OH)4 NSs releases Ni2+ Zn2+ in weakly acidic tumor microenvironment. released alleviated pyroptosis inhibition by inducing paraptosis inhibiting autophagic flux. Concurrently, triggered release endogenous within cell a coordination competition mechanism, further amplifying zinc overload-mediated pyroptosis. Interestingly, pyroptosis-associated oxidative stress endoplasmic reticulum promote Ni2+-mediated paraptosis, forming loop between paraptosis. This process not only kills cells but also stimulates strong inflammatory response, antitumor immune response immunotherapy efficacy. Overall, this study proposes an effective induction strategy based on metal ions demonstrates effectiveness potentiating

Language: Английский

Citations

2
Exploring paraptosis as a therapeutic approach in cancer treatment DOI Creative Commons
Ling‐Chu Chang,

Shih-Kai Chiang,

Shuen‐Ei Chen

et al.

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Nov. 4, 2024

Abstract A variety of cell death pathways play critical roles in the onset and progression multiple diseases. Paraptosis, a unique form programmed death, has gained significant attention recent years. Unlike apoptosis necrosis, paraptosis is characterized by cytoplasmic vacuolization, swelling endoplasmic reticulum mitochondria, absence caspase activation. Numerous natural products, synthetic compounds, newly launched nanomedicines have been demonstrated to prime through paraptotic program may offer novel therapeutic strategies for cancer treatment. This review summarizes findings, delineates intricate network signaling underlying paraptosis, discusses potential implications targeting The aim this expand our understanding process explore

Language: Английский

Citations

2
Blood-brain barrier-penetrative fluorescent anticancer agents triggering paraptosis and ferroptosis for glioblastoma therapy DOI Creative Commons
Jiefei Wang,

Mingyue Cao,

Lulu Han

et al.

Published: March 8, 2024

Currently used drugs for glioblastoma (GBM) treatments are ineffective, primarily due to the significant challenges posed by strong drug resistance, poor blood-brain barrier (BBB) permeability, and lack of tumor specificity. Here, we report two cationic fluorescent anticancer agents (TriPEX-ClO4 TriPEX-PF6) capable BBB penetration efficient GBM therapy via paraptosis ferroptosis induction. These aggregation-induced emission (AIE)-active specifically target mitochondria, effectively triggering ATF4/JNK/Alix-regulated GPX4-mediated ferroptosis. Specifically, they rapidly induce substantial cytoplasmic vacuolation, accompanied reactive oxygen species generation intracellular Ca2+ overload, thereby disrupting metabolisms inducing non-apoptotic cell death. In vivo imaging revealed that TriPEX-ClO4 TriPEX-PF6 successfully traversed orthotopic glioma initiated effective synergistic post-intravenous injection. Our AIE emerged as pioneering inducers against drug-resistant GBM, significantly extending survival up 40 days compared temozolomide (20 days) in GBM-bearing mice. compelling results open new venues development innovative brain diseases.

Language: Английский

Citations

2
Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer DOI Creative Commons

Yiting Geng,

Wei Xia, Xiao Zheng

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(11-12), P. 1959 - 1977

Published: July 3, 2024

Cetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, non-classical programmed cell death, has garnered increased attention for its potential application value antitumor treatments. We aimed identify essential pathways and signaling molecules involved paraptosis inhibition select them as therapeutic targets cetuximab resistance. Additionally, engineered exosome technology drug delivery system with both targeted effector properties.

Language: Английский

Citations

2
Prognostic and immunological implications of heterogeneous cell death patterns in prostate cancer DOI Creative Commons

Ming Wang,

Bangshun Dai, Qiushi Liu

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Aug. 24, 2024

Prostate cancer is one of the most common cancers in men with a significant proportion patients developing biochemical recurrence (BCR) after treatment. Programmed cell death (PCD) mechanisms are known to play critical roles tumor progression and can potentially serve as prognostic therapeutic biomarkers PCa. This study aimed develop signature for BCR PCa using PCD-related genes. We conducted an analysis 19 different modes PCD comprehensive model. Bulk transcriptomic, single-cell genomic, clinical data were collected from multiple cohorts, including TCGA-PRAD, GSE58812, METABRIC, GSE21653, GSE193337. analyzed expression mutations constructed, evaluated, validated Ten found be associated PCa, specific patterns exhibited by various components within microenvironment. Through Lasso Cox regression analysis, we established Cell Death Index (PCDI) utilizing 11-gene signature. High PCDI values five independent datasets increased risk patients. Notably, older age advanced T N staging higher values. By combining staging, constructed nomogram enhanced predictive performance. Additionally, high significantly correlated decreased drug sensitivity, drugs such Docetaxel Methotrexate. Patients lower demonstrated immunophenoscores (IPS), suggesting response rate immune therapy. Furthermore, was checkpoint genes key microenvironment, macrophages, cells, NK cells. Finally, specimens differential PCDI-related PCDRGs at both gene protein levels. In conclusion, developed novel PCD-based feature that successfully predicted provided insights into sensitivity potential These findings have implications treatment

Language: Английский

Citations

2
Roles of Sirtuins in Hearing Protection DOI Creative Commons
Chail Koo, Claus‐Peter Richter, Xiaodong Tan

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(8), P. 998 - 998

Published: July 28, 2024

Hearing loss is a health crisis that affects more than 60 million Americans. Currently, sodium thiosulfate the only drug approved by Food and Drug Administration (FDA) to counter hearing loss. Sirtuins were proposed as therapeutic targets in search for new compounds or drugs prevent cure age-, noise-, drug-induced are proteins involved metabolic regulation with potential ameliorate sensorineural The mammalian sirtuin family includes seven members, SIRT1-7. This paper literature review on sirtuins their protective roles Literature NCBI PubMed database NUsearch included keywords 'sirtuin' 'hearing'. Studies without relevance studies excluded. Only primary research articles data expression physiologic auditory tests considered. identified 183 records hearing. After removing duplicates, eighty-one remained. screening eligibility criteria, there forty-eight statistically significant relevant Overall, SIRT1 (

Language: Английский

Citations

1
Endoplasmic reticulum stress response pathway-mediated cell death in ovarian cancer DOI Creative Commons

Qiaochu Chen,

Chan Li,

Wei Wei

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Sept. 10, 2024

The endoplasmic reticulum (ER) is one of the largest organelles, and Endoplasmic Reticulum Stress Response Pathway a series responses triggered by homeostatic imbalance ER state in which unfolded or misfolded proteins accumulate ER, can trigger cell death. Cell death plays crucial role development diseases such as gynecological oncology. Herein, we review current research on response ovarian cancer, discussing key sensors (IRE1, PERK, ATF6), conditions under it occurs (Ca

Language: Английский

Citations

1
Natural products‐induced cancer cell paraptosis DOI Creative Commons
Haitham Al‐Madhagi

Food Science & Nutrition, Journal Year: 2024, Volume and Issue: 12(11), P. 9866 - 9871

Published: Sept. 12, 2024

Cancer cell can be killed in a programmed way by natural products process known as paraptosis.

Language: Английский

Citations

1