Radiation Therapy in the Treatment of Head and Neck Rhabdomyosarcoma

Frankart, A.J.; Breneman, John C.; Pater, Luke

doi:10.3390/cancers13143567

Cited by 11 publications

(13 citation statements)

References 71 publications

(108 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RMS represents a heterogeneous type of sarcomas associated with poor prognosis. Nearly two thirds of patients present RMS before 10 years old with a peak incidence at ages 3 to 5 [27]. RMS could manifest throughout the body with skeletal muscles including head and neck in 40% of patients [28].…”

Section: Discussionmentioning

confidence: 99%

Arsenic Sulfide EnhancesRadiosensitization in Rhabdomyosarcoma via Activating NFATc3-RAG1 Mediated DNA Double Strand Break (DSB)

Cai

Zhu

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Due to the high level of recurrence and metastasis, rhabdomyosarcoma (RMS) represents one of the most lethal soft-tissue sarcomas in children. It is thus imperative to explore a novel radiosensitizer to enhance the curative of radiotherapy in RMS patients. The trace element arsenic has been reported to function as a radiosensitizer in sarcomas. To determine whether arsenic sulfide (As4S4) potentiates radiation sensitization in RMS, we carried out this study to investigate the mechanism of As4S4 in radiotherapy. Methods: RMS cell line (A-673) was treated with As4S4 and radiotherapy. Cell viability and drug-induced apoptosis were detected by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Western blot and real-time qPCR were carried out to detect the nuclear factor of activated T-cells 3 (NFATc3) and recombination activating 1 (RAG1). DNA damage-associated proteins were also determined. For in vivo experiments, the therapeutic efficacy of As4S4-induced radiosensitization was evaluated via xenograft tumors in mice. To identify NFATc3 and RAG1, which were mostly involved in the mechanism of radiosensitization, we established a clinical cohort of 59 RMS patients. Immunohistochemistry (IHC) staining was applied to detect the expression of NFATc3 and RAG1 in RMS tissues in order to analyze the relationship with prognosis. We further developed a prediction model using stepwise logistic regression. Results: As4S4 combined with radiotherapy exhibited predominant inhibition in RMS cells through CCK-8 and flow cytometry. We revealed that As4S4 as well as the knockdown of NFATc3 resulted in DSB in RMS cells by the increased expression of RAG1. Our in vivo experiment confirmed that co-treatment exerted efficient inhibition of RMS growth. In a clinical cohort of 59 RMS patients, survival analysis showed that NFATc3 and RAG1 were related to overall survival (OS). Cox regression analysis further indicated that NFATc3, RAG1, and Risk level could be regarded as independent prognostic factors for RMS patients. Conclusions: In summary, As4S4 enhances radiosensitization in RMS via activating NFATc3-RAG1 mediated DNA DSB. NFATc3 and RAG1 are potential therapeutic targets in treating RMS. Our findings led us to conclude that As4S4 could be considered a radio-sensitizing agent for treating RMS.

show abstract

Section: Discussionmentioning

confidence: 99%

Arsenic Sulfide EnhancesRadiosensitization in Rhabdomyosarcoma via Activating NFATc3-RAG1 Mediated DNA Double Strand Break (DSB)

Cai

Zhu

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Head and neck squamous cell carcinomas (HNSCCs) are one of the most common malignant cancers ( 1 , 34 , 35 ). The mainstay treatments for HNSCC at the early stage are surgery and/or radiation, which benefit most patients with a good prognosis ( 4 , 36 , 37 ). For HNSCC patients at the advanced or late stages, systematic therapies are recommended, including chemotherapy, targeted therapy, and immunotherapy ( 12 , 38 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

“…For HNSCC patients at the advanced or late stages, systematic therapies are recommended, including chemotherapy, targeted therapy, and immunotherapy ( 12 , 38 , 39 ). Although many HNSCC patients at the advanced/late stages initially respond well to these treatments, most of them will eventually fail and progress to recurrent and/or metastatic diseases ( 2 , 4 , 40 ). For example, a randomized phase III clinical trial to compare the efficacy between different strategies of chemotherapy in advanced HNSCC showed that patients treated by cisplatin and fluorouracil (CF) had a median survival of 8.7 months, as compared to patients administered by cisplatin and paclitaxel (CP) with a median survival of 8.1 months ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…HNSCC possesses a high incidence of cervical lymph node metastases, increased capacities of invasive and recurrence, and contributes to the poor prognosis ( 2 , 3 ). The main treatment options for HNSCC include surgery, chemotherapy, radiotherapy, molecular targeted therapy, and multimethod in conjunction with surgical excision of tumor tissue, but the effectiveness of these approaches is limited due to tumor heterogeneity ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel neutrophil extracellular trap signature to predict prognosis and immunotherapy response in head and neck squamous cell carcinoma

Chen

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers, and patients with HNSCC possess early metastases and poor prognosis. Systematic therapies (including chemotherapy, targeted therapy, and immunotherapy) are generally applied in the advanced/late stages of HNSCC, but primary and acquired resistance eventually occurs. At present, reliable biomarkers to predict the prognosis of HNSCC have not been completely identified. Recent studies have shown that neutrophil extracellular traps (NETs) are implicated in cancer progression, metastasis and cancer immune response, and NET-related gene signatures are associated with the prognosis of patients with several human cancers. To explore whether NET-related genes play crucial roles in HNSCC, we have performed systematic analysis and reported several findings in the current study. Firstly, we identified seven novel NET-related genes and developed a NET-score signature, which was highly associated with the clinicopathological and immune traits of the HNSCC patients. Then, we, for the first time, found that NIFK was significantly upregulated in HNSCC patient samples, and its levels were significantly linked to tumor malignancy and immune status. Moreover, functional experiments confirmed that NIFK was required for HNSCC cell proliferation and metastasis. Altogether, this study has identified a novel NET-score signature based on seven novel NET-related genes to predict the prognosis of HNSCC and NIFK has also explored a new method for personalized chemo-/immuno-therapy of HNSCC.

show abstract

“…The diversity of clinical manifestations, the multiplicity of pathological changes, and the different sites of onset make RMS one of the most complex pediatric tumors ( Ramadan et al, 2020 ; Zoroddu et al, 2021 ). Surgical resection, chemotherapy, and radiotherapy are the main treatments for RMS ( van Erp et al, 2018 ; Frankart et al, 2021 ). With the continuous improvement of chemotherapy regimens, the survival rate of RMS patients has increased to 70–80% ( Pappo and Dirksen, 2018 ; Mohammad et al, 2020 ).…”

Section: Roles and Significance Of Circrnas In Pediatric Malignant Solid Tumorsmentioning

confidence: 99%

Emerging Role and Mechanism of circRNAs in Pediatric Malignant Solid Tumors

Shen

Liu

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Circular RNAs (circRNAs) are non-coding RNAs with covalent closed-loop structures and are widely distributed in eukaryotes, conserved and stable as well as tissue-specific. Malignant solid tumors pose a serious health risk to children and are one of the leading causes of pediatric mortality. Studies have shown that circRNAs play an important regulatory role in the development of childhood malignant solid tumors, hence are potential biomarkers and therapeutic targets for tumors. This paper reviews the biological characteristics and functions of circRNAs as well as the research progress related to childhood malignant solid tumors.

show abstract

Radiation Therapy in the Treatment of Head and Neck Rhabdomyosarcoma

Cited by 11 publications

References 71 publications

Arsenic Sulfide EnhancesRadiosensitization in Rhabdomyosarcoma via Activating NFATc3-RAG1 Mediated DNA Double Strand Break (DSB)

Arsenic Sulfide EnhancesRadiosensitization in Rhabdomyosarcoma via Activating NFATc3-RAG1 Mediated DNA Double Strand Break (DSB)

A novel neutrophil extracellular trap signature to predict prognosis and immunotherapy response in head and neck squamous cell carcinoma

Emerging Role and Mechanism of circRNAs in Pediatric Malignant Solid Tumors

Contact Info

Product

Resources

About