CACA guidelines for ultrasound hyperthermia for oral and maxillofacial head and neck squamous cell carcinoma

Most of the patients with oral and maxillofacial malignancy are in the middle and advanced stages at diagnosis and the incidence rate is increasing in recent years.Chemotherapy alone is difficult to benefit the survival of patients with advanced oral and maxillofacial malignancy.Ultrasound hyperthermia is a new and effective treatment for malignant tumor,which is developing rapidly in addition to conventional treatment.However,at present,ultrasound hyperthermia has not been widely used in the treatment of oral and maxillofacial malignancy.Therefore,formation of a guideline on ultrasound hyperthermia for oral and maxillofacial malignancy is mandatory,in order to promote and standardize the clinical practice of ultrasound hyperthermia in this field,and improve the long-term survival rate and quality of life of patients.

A novel intronic circular RNA,circGNG7,inhibits head and neck squamous cell carcinoma progression by blocking the phosphorylation of heat shock protein 27 at Ser78 and Ser82

Background:There is increasing evidence that circular RNAs(circRNAs)play a significant role in pathological processes including tumorigenesis.In contrast to exonic circRNAs,which are the most frequently reported circRNAs in cancer so far,the studies of intronic circRNAs have been greatly lagged behind.Here,we aimed to investigate the regulatory role of intronic circRNAs in head and neck squamous cell carcinoma(HNSCC).Methods:We conducted whole-transcriptome sequencing with four pairs of primary tumor tissues and adjacent normal tissues from HNSCC patients.Then,we characterized circGNG7 expression in HNSCC tissues and cell lines and explored its association with the prognosis of HNSCC patients.We also identified interactions between circGNG7 and functional proteins,which alter downstream signaling that regulate HNSCC progression.Results:In this study,we identified a new intronic circRNA,circGNG7,and validated its functional roles in HNSCC progression.CircGNG7 was predominately localized to the cytoplasm,and its expression was downregulated in both HNSCC tissues andCAL27,CAL33,SCC4,SCC9,HN6,and HN30 cells.Low expression of circGNG7 was significantly correlated with poor prognosis in HNSCC patients.Consistent with this finding,overexpression of circGNG7 strongly inhibited tumor cell proliferation,colony formation,in vitro migration,and in vivo tumor growth.Mechanistically,the expression of circGNG7 in HNSCC cells was regulated by the transcription factor SMAD family member 4(SMAD4).Importantly,we discovered that circGNG7 could bind to serine residues 78 and 82 of the functional heat shock protein 27(HSP27),occupying its phosphorylation sites and hindering its phosphorylation,which reduced HSP27-JNK/P38 mitogen-activated protein kinase(MAPK)oncogenic signaling.Downregulation of circGNG7 expression in HNSCC increased HSP27-JNK/P38 MAPK signaling and promoted tumor progression.Conclusions:Our results revealed that a new intronic circRNA,circGNG7,functions as a strong tumor suppressor and that circGNG7/HSP27-JNK/P38 MAPK signaling is a novel mechanism by which HNSCC progression can be controlled.

Candidate therapeutic agents in a newly established triple wild-typemucosalmelanoma cell line

Background:Mucosalmelanoma has characteristically distinct genetic features and typically poor prognosis.The lack of representativemucosal melanoma models,especially cell lines,has hindered translational research on this melanoma subtype.In this study,we aimed to establish and provide the biological properties,genomic features and the pharmacological profiles of a mucosal melanoma cell line that would contribute to the understanding and treatment optimization of molecularly-defined mucosal melanoma subtype.Methods:The sample was collected from a 67-year-old mucosal melanoma patient and processed into pieces for the establishment of cell line and patientderived xenograft(PDX)model.The proliferation and tumorigenic property of cancer cells from different passageswere evaluated,andwhole-genome sequencing(WGS)was performed on the original tumor,PDX,established cell line,and the matched blood to confirm the establishment and define the genomic features of this cell line.AmpliconArchitect was conducted to depict the architecture of amplified regions detected by WGS.High-throughput drug screening(HTDS)assay including a total of 103 therapeutic agents was implemented on the established cell line,and selected candidate agents were validated in the corresponding PDX model.Results:A mucosal melanoma cell line,MM9H-1,was established which exhibited robust proliferation and tumorigenicity after more than 100 serial passages.Genomic analysis of MM9H-1,corresponding PDX,and the original tumor showed genetic fidelity across genomes,and MM9H-1 was defined as a triple wild-type(TWT)melanoma subtype lacking well-characterized“driver mutations”.Instead,the amplification of several oncogenes,telomerase reverse transcriptase(TERT),v-Rafmurine sarcoma viral oncogene homolog B1(BRAF),melanocyte Inducing transcription factor(MITF)and INO80 complex ATPase subunit(INO80),via large-scale genomic rearrangement potentially contributed to oncogenesis of MM9H-1.Moreover,HTDS identified proteasome inhibitors,especially bortezomib,as promising therapeutic candidates for MM9H-1,which was verified in the corresponding PDX model in vivo.Conclusions:We established and characterized a new mucosal melanoma cell line,MM9H-1,and defined this cell line as a TWT melanoma subtype lacking well-characterized“driver mutations”.The MM9H-1 cell line could be adopted as a unique model for the preclinical investigation of mucosal melanoma.