Browse
Submit Data
Databases
API
Help

Dataset Information

38 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Despite recent advances in therapeutic modalities such as radiochemotherapy, the long-term prognosis for patients with advanced head and neck squamous cell carcinoma (HNSCC), especially nonviral HNSCC, remains very poor, while survival of patients with human papillomavirus (HPV)-associated HNSCC is greatly improved after radiotherapy. The goal of this study is to develop a mechanism-based treatment protocol for high-risk patients with HPV-negative HNSCC. To achieve our goal, we have investigated molecular mechanisms underlying differential radiation sensitivity between HPV-positive and -negative HNSCC cells. Here, we found that autophagy is associated with radioresistance in HPV-negative HNSCC, whereas apoptosis is associated with radiation sensitive HPV-positive HNSCC. Interestingly, we found that photodynamic therapy (PDT) directed at the endoplasmic reticulum (ER)/mitochondria initially induces paraptosis followed by apoptosis. This led to a substantial increase in radiation responsiveness in HPV-negative HNSCC, while the same PDT treatment had a minimal effect on HPV-positive cells. Here, we provide evidence that the autophagic adaptor p62 mediates signal relay for the induction of apoptosis, promoting ionizing radiation (XRT)-induced cell death in HPV-negative HNSCC. This work proposes that ER/mitochondria-targeted PDT can serve as a radiosensitizer in intrinsically radioresistant HNSCC that exhibits an increased autophagic flux.

SUBMITTER: Cho WJ

PROVIDER: S-EPMC7998908 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

C6-pyridinium ceramide sensitizes SCC17B human head and neck squamous cell carcinoma cells to photodynamic therapy.

Project description:Combining photodynamic therapy (PDT) with another anticancer treatment modality is an important strategy for improved efficacy. PDT with Pc4, a silicon phthalocyanine photosensitizer, was combined with C6-pyridinium ceramide (LCL29) to determine their potential to promote death of SCC17B human head and neck squamous cell carcinoma cells. PDT+LCL29-induced enhanced cell death was inhibited by zVAD-fmk, a pan-caspase inhibitor, and fumonisin B1 (FB), a ceramide synthase inhibitor. Quantitative confocal microscopy showed that combining PDT with LCL29 enhanced FB-sensitive ceramide accumulation in the mitochondria. Furthermore, PDT+LCL29 induced enhanced FB-sensitive redistribution of cytochrome c and caspase-3 activation. Overall, the data indicate that PDT+LCL29 enhanced cell death via FB-sensitive, mitochondrial ceramide accumulation and apoptosis.

| S-EPMC4662378 | biostudies-literature

Head and neck squamous cell carcinoma

Project description:Quantitative (iTRAQ 4-plex) proteomic analysis of progressive head and neck cancers

2022-03-01 | PXD001438 | Pride

Resistance to anti-EGFR targeted therapy in head and neck squamous cell carcinoma

Project description:Total proteins were extracted in triplicate from cetuximab-sensitive and -resistant SC263 and SCC22b HNSCC cells. The LC system was coupled to a Q-Exactive Plus Orbitrap mass spectrometer (Thermo Fisher Scientific) programmed to acquire in data-dependent mode. A target of 1.7 x103 ions and a maximum injection time of 80 ms were used for MS/MS. The method was set to analyze the top 20 most intense ions from the survey scan and dynamic exclusion was enabled for 20 s. Tandem mass spectra were processed using MaxQuant software version 1.6.7.0. Proteins were identified using the Andromeda search engine and using the Homo sapiens proteome reference database (UniProt, release 20200130, 20366 entries). The parameters chosen for the identification include: digestion enzyme used was trypsin, maximum number of allowed missed cleavages was two. Oxidation of methionine, N-terminal acetylation, and phosphorylation of serine, threonine and tyrosine were set as variable modifications, while carbamidomethylation of cysteine was set as a fixed modification. A maximum number of 5 modifications per peptide was set. The precursor mass tolerance was set to 4.5 ppm and the fragmentation mass tolerance to 20 ppm. The peptide-to-spectrum match (PSM) and protein false discovery rates (FDR) were set at 1%. The match-between-runs and the label-free quantification (LFQ) methods were enabled using default parameters. After data treatment using MaxQuant, statistical analysis was done using Perseus software (version 1.6.7.0). The data matrix was filtered by removing the potential contaminants and decoy reverse sequences. The LFQ intensities were then log2-transformed and missing values were replaced by imputation based on the normal distribution. This resulted in the quantification of the expression of 2,741 unique proteins.

2024-12-13 | MSV000096655 | MassIVE

PD1/PD-L1 inhibition as a potential radiosensitizer in head and neck squamous cell carcinoma: a case report.

Project description:BACKGROUND:Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION:We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy. CONCLUSION:T cell activation induced by checkpoint inhibition may dramatically improve tumor response to radiation. More data are needed to identify the toxicity and efficacy of sequential or concurrent checkpoint inhibitors and radiotherapy.

| S-EPMC5109767 | biostudies-literature

Head and neck squamous cell carcinoma.

Project description:Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour-node-metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies.

| S-EPMC7944998 | biostudies-literature

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma.

Project description:EGFR is an established therapeutic target in head and neck squamous cell carcinoma (HNSCC). The EGFR-targeting monoclonal antibody cetuximab (Erbitux, Imclone Systems, Inc., Branchburg, USA) was FDA-approved for use in HNSCC in 2006. The molecular basis for the efficacy of an antibody approach compared with inhibition of EGFR tyrosine kinase function using small-molecule inhibitors, or downregulation of protein expression via antisense strategies, remains incompletely understood.A literature search was performed to identify studies elucidating mechanisms of action of several approaches to targeting EGFR in HNSCC (monoclonal antibodies, tyrosine kinase inhibitors, antisense approaches, and ligand-toxin conjugates).Monoclonal antibodies decrease tumor growth via receptor endocytosis and recruitment of host immune defenses. Tyrosine kinase inhibitors bind to the ATP binding pocket of the tyrosine kinase domain, inhibiting signaling. Antisense approaches decrease EGFR expression with high specificity, though drug delivery remains problematic. Ligand-toxin conjugates facilitate the entry of toxin and the ADP-ribosylation of the ribosome, thereby inhibiting translation.Elucidation mechanisms by which these different strategies inhibit EGFR function may enhance the development of more effective treatments for HNSCC and enable prospective identification of individuals who will benefit from EGFR inhibition.

| S-EPMC2947445 | biostudies-literature

Induction Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

Project description:The optimal approach to locally advanced head and neck squamous cell carcinoma (LAHNSCC) treatment remains controversial. For non-resectable LAHNSCC, the clinical interest of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) or radiotherapy has been questioned. With the approval of immunotherapy and targeted therapy for this disease, treatment options have become more complex. Although new trial data have appeared every year, the results are still inconclusive. In this review, we provide readers with information on new strategies for LAHNSCC induction therapy, which will facilitate evidence-based decision making in LAHNSCC treatment.

| S-EPMC10260727 | biostudies-literature

Advances in CAR-T Cell Therapy in Head and Neck Squamous Cell Carcinoma.

Project description:Surgery with the assistance of conventional radiotherapy, chemotherapy and immunotherapy is the basis for head and neck squamous cell carcinoma (HNSCC) treatment. However, with these treatment modalities, the recurrence and metastasis of tumors remain at a high level. Increasingly, the evidence indicates an excellent anti-tumor effect of chimeric antigen receptor T (CAR-T) cells in hematological malignancy treatment, and this novel immunotherapy has attracted researchers' attention in HNSCC treatment. Although several clinical trials have been conducted, the weak anti-tumor effect and the side effects of CAR-T cell therapy against HNSCC are barriers to clinical translation. The limited choices of targeting proteins, the barriers of CAR-T cell infiltration into targeted tumors and short survival time in vivo should be solved. In this review, we introduce barriers of CAR-T cell therapy in HNSCC. The limitations and current promising strategies to overcome barriers in solid tumors, as well as the applications for HNSCC treatment, are covered. The perspectives of CAR-T cell therapy in future HNSCC treatment are also discussed.

| S-EPMC10052000 | biostudies-literature

Immunotherapy for Head and Neck Squamous Cell Carcinoma.

Project description:PURPOSE OF REVIEW:Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents. RECENT FINDINGS:Agents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (ICR). The anti PD1 agent, nivolumab, was recently approved by the FDA as a standard of care regimen for patients with platinum refractory recurrent/metastatic (R/M) HNSCC. Molecular pathways leading to resistance are starting to be identified, and work is underway to understand the most optimal treatment regimen with incorporation of immunotherapy. ICR has renewed interest in the immunology of cancer, but resistance is not uncommon, and thus understanding of these mechanisms will allow the clinician to appropriately select patients that will benefit from this therapy.

| S-EPMC5835060 | biostudies-literature

Exosomes in Head and Neck Squamous Cell Carcinoma.

Project description:Exosomes are small membranous vesicles that contain proteins, lipids, genetic material, and metabolites with abundant information from parental cells. Exosomes carry and deliver bioactive contents that can reprogram the functions of recipient cells and modulate the tumor microenvironment to induce pathological events through cell-to-cell communication and signal transduction. Tumor-derived exosomes (TDEs) in head and neck squamous cell carcinoma (HNSCC) are involved in most aspects of cancer initiation, invasion, progression, immunoregulation, therapeutic applications, and treatment resistance. In addition, HNSCC-derived exosomes can be used to obtain information on diagnostic and therapeutic biomarkers in circulating blood and saliva. Currently, the biology, mechanisms, and applications of TDEs in HNSCC are still unclear, and further research is required. In this review, we discuss various aspects of exosome biology, including exosomal components, exosomal biomarkers, and molecular mechanisms involved in immunoregulation, cancer metastasis, and therapy resistance. We also describe recent applications to update our understanding of exosomes in HNSCC.

| S-EPMC6759986 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data