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Journal of Nanobiotechnology Sep 2023Targeting EBV-proteins with mRNA vaccines is a promising way to treat EBV-related tumors like nasopharyngeal carcinoma (NPC). We assume that it may sensitize tumors to...
BACKGROUND
Targeting EBV-proteins with mRNA vaccines is a promising way to treat EBV-related tumors like nasopharyngeal carcinoma (NPC). We assume that it may sensitize tumors to immune checkpoint inhibitors.
RESULTS
We developed an LMP2-mRNA lipid nanoparticle (C2@mLMP2) that can be delivered to tumor-draining lymph nodes. C2@mLMP2 exhibited high transfection efficiency and lysosomal escape ability and induced an increased proportion of CD8 + central memory T cells and CD8 + effective memory T cells in the spleen of the mice model. A strong synergistic anti-tumor effect of C2@mLMP2 in combination with αPD-1 was observed in tumor-bearing mice. The mechanism was identified to be associated with a reverse of CD8 + T cell exhaustion in the tumor microenvironment. The pathological analysis further proved the safety of the vaccine and the combined therapy.
CONCLUSIONS
This is the first study proving the synergistic effect of the EBV-mRNA vaccine and PD-1 inhibitors for EBV-related tumors. This study provides theoretical evidence for further clinical trials that may expand the application scenario and efficacy of immunotherapy in NPC.
Topics: Animals; Mice; Herpesvirus 4, Human; T-Cell Exhaustion; Immune Checkpoint Inhibitors; Nasopharyngeal Carcinoma; RNA, Messenger; Nasopharyngeal Neoplasms; Tumor Microenvironment
PubMed: 37679769
DOI: 10.1186/s12951-023-02069-w -
European Journal of Nuclear Medicine... Nov 2023Prognostic prediction is crucial to guide individual treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients. Recently, multi-task deep learning...
PURPOSE
Prognostic prediction is crucial to guide individual treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients. Recently, multi-task deep learning was explored for joint prognostic prediction and tumor segmentation in various cancers, resulting in promising performance. This study aims to evaluate the clinical value of multi-task deep learning for prognostic prediction in LA-NPC patients.
METHODS
A total of 886 LA-NPC patients acquired from two medical centers were enrolled including clinical data, [F]FDG PET/CT images, and follow-up of progression-free survival (PFS). We adopted a deep multi-task survival model (DeepMTS) to jointly perform prognostic prediction (DeepMTS-Score) and tumor segmentation from FDG-PET/CT images. The DeepMTS-derived segmentation masks were leveraged to extract handcrafted radiomics features, which were also used for prognostic prediction (AutoRadio-Score). Finally, we developed a multi-task deep learning-based radiomic (MTDLR) nomogram by integrating DeepMTS-Score, AutoRadio-Score, and clinical data. Harrell's concordance indices (C-index) and time-independent receiver operating characteristic (ROC) analysis were used to evaluate the discriminative ability of the proposed MTDLR nomogram. For patient stratification, the PFS rates of high- and low-risk patients were calculated using Kaplan-Meier method and compared with the observed PFS probability.
RESULTS
Our MTDLR nomogram achieved C-index of 0.818 (95% confidence interval (CI): 0.785-0.851), 0.752 (95% CI: 0.638-0.865), and 0.717 (95% CI: 0.641-0.793) and area under curve (AUC) of 0.859 (95% CI: 0.822-0.895), 0.769 (95% CI: 0.642-0.896), and 0.730 (95% CI: 0.634-0.826) in the training, internal validation, and external validation cohorts, which showed a statistically significant improvement over conventional radiomic nomograms. Our nomogram also divided patients into significantly different high- and low-risk groups.
CONCLUSION
Our study demonstrated that MTDLR nomogram can perform reliable and accurate prognostic prediction in LA-NPC patients, and also enabled better patient stratification, which could facilitate personalized treatment planning.
Topics: Humans; Prognosis; Nomograms; Nasopharyngeal Carcinoma; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Deep Learning; Nasopharyngeal Neoplasms; Retrospective Studies
PubMed: 37596343
DOI: 10.1007/s00259-023-06399-7 -
Cancer Journal (Sudbury, Mass.)The global incidence of human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has surged in recent decades, with HPV+ HNSCC accounting for... (Review)
Review
The global incidence of human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has surged in recent decades, with HPV+ HNSCC accounting for >70% of oropharynx cancers in the United States. Its incidence in men has surpassed that of HPV+ cervical cancer in women, and reliable assays are needed for early detection and to monitor response to therapy. Human papillomavirus-positive OPSCC has a more favorable response to therapy and prognosis than HPV-negative (HPV-) HNSCC, motivating regimens to deintensify curative surgery or chemoradiotherapy protocols. A barrier to deintensifying and personalizing therapy is lack of reliable predictive biomarkers. Furthermore, HPV- HNSCC survival rates are static without reliable surveillance biomarkers available. The emergence of circulating plasma-based biomarkers reflecting the tumor-immune microenvironment heralds a new era in HNSCC diagnosis and therapy. We review evidence on tumor-derived extracellular vesicles (exosomes) as biomarkers for diagnosis, prognostication, and treatment in HPV+ and HPV- HNSCC.
Topics: Male; Female; Humans; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Human Papillomavirus Viruses; Carcinoma, Squamous Cell; Papillomavirus Infections; Exosomes; Oropharyngeal Neoplasms; Biomarkers; Liquid Biopsy; Tumor Microenvironment
PubMed: 37471614
DOI: 10.1097/PPO.0000000000000671 -
Journal of Clinical Microbiology Aug 2023Twelve high-risk alpha human papillomavirus (HPV) genotypes cause approximately 690,000 cancer cases annually, with cervical and oropharyngeal cancer being the two most... (Review)
Review
Twelve high-risk alpha human papillomavirus (HPV) genotypes cause approximately 690,000 cancer cases annually, with cervical and oropharyngeal cancer being the two most prominent types. HPV testing is performed in laboratory settings for various applications of a clinical, epidemiological, and research nature using a range of clinical specimens collected by clinicians or by individuals (self-collected specimens). Here, we reflect on the importance and justification of using the right test for the right application and provide practical updates for laboratories either participating in or anticipating involvement in HPV testing in three specimen types, namely, urine, blood, and oral specimens, which are considered "alternative" specimens by many. In addition to clinician-collected cervical samples and self-collected cervicovaginal samples, first-void urine is emerging as a credible specimen for HPV-based cervical cancer screening, triage of HPV screen-positive women, monitoring HPV vaccine impact, and HPV testing in groups for which a less invasive sample is preferred. Detection of cell-free DNA (including HPV DNA) in blood has great promise for the early detection of HPV-attributable oropharyngeal cancer (HPV-AOC) and potentially other HPV-driven cancers and as an adjunct prognostic marker in long-term tumor surveillance, including treatment response. The moderate sensitivity of HPV testing in oral rinses or swabs at HPV-AOC diagnosis prevents its use in HPV-AOC secondary prevention but represents a promising prognostic tool in HPV-AOC tertiary prevention, where the HPV persistence in oral rinses throughout treatment may predict early HPV-AOC recurrences and/or the development of secondary HPV-AOC. The increasing sophistication of specific collection devices designed for alternative samples and the enhanced precision of novel molecular technologies are likely to support the evolution of this field and catalyze potential translation into routine practice.
Topics: Humans; Female; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Uterine Cervical Dysplasia; Papillomavirus Infections; Early Detection of Cancer; Laboratories; Papillomaviridae; Oropharyngeal Neoplasms; DNA, Viral; Sensitivity and Specificity; Vaginal Smears
PubMed: 37439692
DOI: 10.1128/jcm.01403-22 -
Medical Science Monitor : International... Sep 2023Cinobufagin (CBF) is a bufadienolide, which is a major active ingredient of toad venom. In recent years, CBF has attracted increasing attention due to its highly potent...
Cinobufagin (CBF) is a bufadienolide, which is a major active ingredient of toad venom. In recent years, CBF has attracted increasing attention due to its highly potent and multiple pharmacological activities. To better understand the status of research on CBF, we collated recent studies on CBF to provide a valuable reference for clinical researchers and practitioners. According to reports, CBF exhibits extensive pharmacological properties, including antitumor, analgesic, cardioprotection, immunomodulatory, antifibrotic, antiviral, and antiprotozoal effects. Studies on the pharmacological activity of CBF have mainly focused on its anticancer activity. It has been demonstrated that CBF has a therapeutic effect on liver cancer, osteosarcoma, melanoma, colorectal cancer, acute promyelocytic leukemia, nasopharyngeal carcinoma, multiple myeloma, gastric cancer, and breast cancer. However, the direct molecular targets of CBF are currently unknown. In addition, there are few reports on toxicological and pharmacokinetic of CBF. Subsequent studies focusing on these aspects will help promote the development and application of CBF in clinical practice.
Topics: Humans; Amphibian Venoms; Bufanolides; Bone Neoplasms; Nasopharyngeal Neoplasms
PubMed: 37743616
DOI: 10.12659/MSM.940889 -
Frontiers in Bioscience (Landmark... May 2024Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the... (Review)
Review
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA), and circular RNA can modulate PTEN through various pathways, thereby impacting the biological behavior of NPC. In addition, PTEN is involved in regulating the tumor microenvironment of NPC, and its interaction with the Epstein-Barr virus has also recently become a focus of research. A comprehensive understanding of the PTEN regulatory network provides a foundation for future personalized and targeted therapeutic strategies. This study expands our understanding of the pathogenesis of NPC and suggests new directions in the field of tumor biology and NPC treatment.
Topics: Humans; PTEN Phosphohydrolase; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; MicroRNAs; Tumor Microenvironment; Cell Proliferation; Apoptosis; Gene Expression Regulation, Neoplastic; RNA, Long Noncoding; Autophagy; Cell Movement; RNA, Circular; Herpesvirus 4, Human; Signal Transduction
PubMed: 38812313
DOI: 10.31083/j.fbl2905179 -
Annals of Medicine Dec 2023To investigate the treatment of intractable epistaxis after radiotherapy for nasopharyngeal carcinoma (NPC). This review focuses on the anatomy and pathophysiology,... (Review)
Review
To investigate the treatment of intractable epistaxis after radiotherapy for nasopharyngeal carcinoma (NPC). This review focuses on the anatomy and pathophysiology, mechanism, and clinical treatments of epistaxis after NPC radiotherapy. For treating NPC, radiation therapy is the primary therapeutic modality. However, radiotherapy can lead to varied degrees of harm to the neighboring tissues and is correlated with numerous complications. Among these complications, epistaxis is a common occurrence after NPC radiotherapy, owing to damage to the surrounding tissues caused by radiotherapy. Unfortunately, epistaxis, particularly carotid blowout, can have a dangerous course and a high mortality rate. Accurate understanding of epistaxis following radiotherapy, prompt bleeding cessation, and reduction of bleeding volume are key considerations. Nasal tamponade is a crucial rescue treatment, while tracheotomy is an active and effective method. Intravascular balloon embolization is a reliable and effective treatment method for ICA hemorrhage, and vascular embolization is the primary approach for treating external carotid artery maxillary bleeding. Implantation of a covered stent can achieve hemostasis without altering hemodynamics. A comprehensive approach utilizing these methods can improve the success rate of treating nosebleeds following NPC radiotherapy.HighlightsThe mortality rate for carotid blowout following radiotherapy for NPC is high.Radiation therapy and tumor condition are correlated with epistaxis in NPC.Treatment methods for NPC-related epistaxis include posterior nostril tamponade, endoscopic hemostasis, DSA, selective vascular embolization, and stent implantation.The use of a covered stent for NPC-related carotid blowout achieves hemostasis without altering blood perfusion.Effective and timely application of various hemostasis methods is key to improving the success rate of rescue, considering the characteristics of NPC-related epistaxis.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Epistaxis; Carotid Arteries; Embolization, Therapeutic
PubMed: 37074291
DOI: 10.1080/07853890.2023.2200257 -
American Journal of Human Genetics Jul 2023Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain...
Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Follow-Up Studies; Genetic Predisposition to Disease; Genetic Association Studies; Polymorphism, Single Nucleotide; Homeodomain Proteins
PubMed: 37352861
DOI: 10.1016/j.ajhg.2023.06.003 -
International Journal of Environmental... Nov 2023While abundant evidence exists linking alcohol, tobacco, and HPV infection to a carcinogenic impact on the oropharynx, the contribution of inhalational workplace hazards... (Review)
Review
While abundant evidence exists linking alcohol, tobacco, and HPV infection to a carcinogenic impact on the oropharynx, the contribution of inhalational workplace hazards remains ill-defined. We aim to determine whether the literature reveals occupational environments at a higher-than-average risk of developing oropharyngeal cancer (OPC) and summarize the available data. To identify studies assessing the relationship between occupational exposure and risk of OPC, a search of the literature through the PubMed-NCBI database was carried out and, ultimately, 15 original articles meeting eligibility criteria were selected. Only original articles in English focusing on the association between occupational exposure and risk or death of specifically OPC were included. The available data are supportive of a potentially increased risk of OPC in waiters, cooks and stewards, artistic workers, poultry and meat workers, mechanics, and World Trade Center responders exposed to dust. However, the available literature on occupation-related OPC is limited. To identify occupational categories at risk, large cohorts with long follow-ups are needed. Identification of causal associations with occupation-related factors would require dose-response analyses adequately adjusted for confounders.
Topics: Humans; Oropharyngeal Neoplasms; Causality; Occupational Exposure; Occupations; Carcinogens; Papillomavirus Infections
PubMed: 37947576
DOI: 10.3390/ijerph20217020 -
Brazilian Journal of Otorhinolaryngology 2024
Topics: Humans; Lipoma; Laryngeal Neoplasms; Pharyngeal Neoplasms; Tomography, X-Ray Computed; Male; Female; Middle Aged
PubMed: 38442639
DOI: 10.1016/j.bjorl.2024.101407