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Mukaigawa T, Asakura K, Tsuzuki A, Urikura A, Yoshida T, Goto S, Okada S, Hiiragi Y, Sato F. Subtraction CT Improves Detectability of Mandibular Bone Invasion in Oral Squamous Cell Carcinoma. Laryngoscope 2025; 135:1706-1714. [PMID: 39651678 DOI: 10.1002/lary.31946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 11/17/2024] [Accepted: 11/22/2024] [Indexed: 12/11/2024]
Abstract
OBJECTIVE Pretreatment evaluation of bone invasion in head and neck cancer is critical for treatment strategies. We investigated the usefulness of subtraction CT (SCT) in evaluating mandibular bone invasion in oral squamous cell carcinoma (OSCC). METHODS This retrospective investigation included patients with OSCC who underwent surgery at the Shizuoka Cancer Center Hospital between 2018 and 2022. We evaluated tumor invasion of the mandibular bone by interpreting conventional computed tomography (CT), SCT, and magnetic resonance imaging (MRI) and comparing the findings with the pathological examination. Sensitivity and specificity were compared using the McNemar test, whereas Spearman's correlation and Bland-Altman methods were utilized to assess mandibular bone invasion depth. RESULTS A total of 71 patients were enrolled. SCT showed significantly higher sensitivity than conventional CT for evaluating mandibular marrow invasion (97.2% vs. 80.6%, p = 0.031). In the evaluation of mandibular canal involvement, SCT showed significantly higher specificity than MRI (95.9% vs. 81.6%, p = 0.016). Furthermore, SCT demonstrated the highest correlation with pathological bone invasion depth (correlation coefficients: CT = 0.933, SCT = 0.950, MRI = 0.908; all p < 0.05). CONCLUSION These results suggest that SCT is more effective than conventional imaging for diagnosing mandibular bone invasion and may be a useful modality for the pretreatment diagnosis of head and neck cancer. LEVEL OF EVIDENCE 3 Laryngoscope, 135:1706-1714, 2025.
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Affiliation(s)
- Takashi Mukaigawa
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Koiku Asakura
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Ayaka Tsuzuki
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Atsushi Urikura
- Department of Radiological Technology, National Cancer Center Hospital, Tokyo, Japan
| | - Tsukasa Yoshida
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Seiya Goto
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Shinichi Okada
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yohei Hiiragi
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Fuyuki Sato
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
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Salama V, Humbert-Vidan L, Godinich B, Wahid KA, ElHabashy DM, Naser MA, He R, Mohamed ASR, Sahli AJ, Hutcheson KA, Gunn GB, Rosenthal DI, Fuller CD, Moreno AC. Machine learning predicting acute pain and opioid dose in radiation treated oropharyngeal cancer patients. FRONTIERS IN PAIN RESEARCH 2025; 6:1567632. [PMID: 40256643 PMCID: PMC12006146 DOI: 10.3389/fpain.2025.1567632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 03/20/2025] [Indexed: 04/22/2025] Open
Abstract
Introduction Acute pain is common among oral cavity/oropharyngeal cancer (OCC/OPC) patients undergoing radiation therapy (RT). This study aimed to predict acute pain severity and opioid doses during RT using machine learning (ML), facilitating risk-stratification models for clinical trials. Methods A retrospective study examined 900 OCC/OPC patients treated with RT during 2017-2023. Pain intensity was assessed using NRS (0-none, 10-worst) and total opioid doses were calculated using morphine equivalent daily dose (MEDD) conversion factors. Analgesics efficacy was assessed using combined pain intensity and total MEDD. ML predictive models were developed and validated, including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), and Gradient Boosting Machine (GBM). Model performance was evaluated using discrimination and calibration metrics, while feature importance was investigated using bootstrapping. Results For predicting pain intensity, the GBM demonstrated superior discrimination performance (AUROC 0.71, recall 0.39, and F1 score 0.48). For predicting the total MEDD, LR model outperformed other models (AUROC 0.67). For predicting analgesics efficacy, the SVM achieved the highest specificity (0.97), while the RF and GBM models achieved the highest AUROC (0.68). RF model emerged as the best calibrated model with an ECE of 0.02 and 0.05 for pain intensity and MEDD prediction, respectively. Baseline pain scores and vital signs demonstrated the most contributing features. Conclusion ML models showed promise in predicting end-of-treatment pain intensity, opioid requirements and analgesics efficacy in OCC/OPC patients. Baseline pain score and vital signs are crucial predictors. Their implementation in clinical practice could facilitate early risk stratification and personalized pain management.
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Affiliation(s)
- Vivian Salama
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Department of Medical Oncology and Radiation Oncology, West Virginia University Cancer Institute, Morgantown, WV, United States
| | - Laia Humbert-Vidan
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Brandon Godinich
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech Health Sciences Center, El Paso, TX, United States
| | - Kareem A. Wahid
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Dina M. ElHabashy
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Mohamed A. Naser
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Renjie He
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Abdallah S. R. Mohamed
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Ariana J. Sahli
- Department of Head and Neck Surgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States
| | - Katherine A. Hutcheson
- Department of Head and Neck Surgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States
| | - Gary Brandon Gunn
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - David I. Rosenthal
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Clifton D. Fuller
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Amy C. Moreno
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Zhang Y, Wang Y, Peng J, Zhao K, Li L, Zhang Y, Zhai Z, Yuan S, Li S, Ye F, Wang L. Expression and prognostic significance of the m6A RNA methylation regulator HNRNPC in HNSCC. Front Oncol 2025; 15:1516867. [PMID: 39990687 PMCID: PMC11842334 DOI: 10.3389/fonc.2025.1516867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/17/2025] [Indexed: 02/25/2025] Open
Abstract
Background N6-methyladenosine (m6A) RNA modification is crucial for tumor development and progression; however, which m6A regulators play a pivotal role in head and neck squamous cell carcinoma (HNSCC) remains ambiguous. Methods Utilizing the Cancer Genome Atlas (TCGA) database, the expression levels of m6A regulators in HNSCC were examined, which led to the identification of heterogeneous nuclear ribonucleoprotein C (HNRNPC) as a key gene. Further experiments were performed in patient samples, stable cell lines, and a murine xenograft tumor model. Results A reliable survival risk model of m6A was constructed based on the TCGA database. Gene Expression Omnibus (GEO), normal and tumor tissue microarrays (TMA), and tumor tissue samples from patients with HNSCC were observed that a high level of HNRNPC expression was closely linked to a poor prognosis among patients. Knockdown of HNRNPC in the HNSCC cell lines HSC-3 and CAL-27 resulted in a significant decrease in proliferation, invasion, and malignant transformation abilities. RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation and sequencing (MeRIP-seq) data revealed that HNRNPC is involved in cell differentiation, cell migration and apoptosis. The mouse xenograft model elucidated that HNRNPC can promote tumorigenesis and progression of HNSCC. Conclusions HNRNPC can serve as a valuable predictor of tumor progression and prognosis in patients with HNSCC.
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Affiliation(s)
- Yulin Zhang
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yixu Wang
- Department of Otolaryngology, Head and Neck Surgery, People’s Hospital, Peking University, Beijing, China
| | - Jilin Peng
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Kun Zhao
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ling Li
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuan Zhang
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ziyu Zhai
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Sijie Yuan
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shichao Li
- Department of Otolaryngology Head and Neck Surgery, Henan Provincial People’s Hospital, Zhengzhou, Henan, China
- Department of Otolaryngology Head and Neck Surgery, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Department of Otolaryngology Head and Neck Surgery, People’s Hospital of Henan University, Zhengzhou, Henan, China
| | - Fanglei Ye
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Le Wang
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Shekhawat JK, Sharma J, Choudhury B, Chugh A, Purohit P, Sharma P, Banerjee M. Aberrant DNA methylation of EDNRB, MGMT and TIMP3 gene promoters in saliva of head and neck carcinoma patients as a diagnostic tool. Mol Biol Rep 2025; 52:152. [PMID: 39847241 DOI: 10.1007/s11033-025-10250-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 01/10/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND Differential DNA methylation in the promoter region of tumour suppressor genes leads to gene function silencing. MATERIALS AND METHODS In this study, we aimed to evaluate the salivary promoter methylation of EDNRB, MGMT and TIMP3 genes in H&NC patients (n = 100), premalignant lesions patients (n = 25) and healthy controls (n = 50). Blood and saliva samples were collected from all three groups and 20 concomitant tumour tissues were collected from the H&NC patients. Probe-based Methylation-specific PCR (MSP) was performed to assess the relative quantification of methylation. RESULTS Significant promoter hypermethylation was detected in all three genes between H&NC patients vs. healthy controls and premalignant lesion patients vs. healthy controls. Spearman correlation analysis showed, no significant association between methylation levels and clinicopathological characteristics of HNC patients while tobacco smoking was significantly related to EDNRB methylation in premalignant lesions. The receiver operating curve (ROC) generated for EDNRB, MGMT and TIMP3 genes from saliva samples was able to differentiate between cancer vs. healthy controls and premalignant vs. healthy controls. The combined diagnostic efficiency of the panel was higher than the genes singly. The combined sensitivity of EDNRB and TIMP3 increased to 92%. CONCLUSION This indicates that EDNRB and TIMP3 have potential value in clinical practice as effective diagnostic markers for H&NC using saliva samples.
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Affiliation(s)
- Jyoti Kanwar Shekhawat
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Jyoti Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Bikram Choudhury
- Department of Otorhinolaryngology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Ankita Chugh
- Department of Dentistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Purvi Purohit
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Praveen Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Mithu Banerjee
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India.
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Demir B, Abuzaid G. Association Between Mean Platelet Volume, Platelet Count, and Distribution Width With Depth of Invasion in Oral Cancers. EAR, NOSE & THROAT JOURNAL 2025; 104:NP40-NP45. [PMID: 35411813 DOI: 10.1177/01455613211032532] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION To examine the potential predictive roles of the preoperative mean platelet volume (MPV), platelet count (PC), and platelet distribution width (PDW) in patients with oral cancer and their association with the depth of invasion (DOI). METHODS This retrospective study included 122 patients (66 males, 56 females) diagnosed with oral cancer between January 2009 and January 2015 by our Otolaryngology Department. At diagnosis, the mean age was 64.6 ± 13.9 years. The average follow-up period was 39.2 ± 23.9 months. RESULTS We found significant differences in all parameters (PDW, MPV, PC) based on the positivity of the lymph node and the tumor stage. The mean PDW, MPV, and PC were significantly higher in the exitus group than in the survivor group (P = .010, .036, and .047, respectively). In patients with high PDW, we observed a lower progression-free survival. We observed that PDW had a significant impact on the recurrence of the disease. Platelet distribution width, MPV, and PC were significant prognostic factors. A high PDW increased fatality 4.1 times, and a high MPV increased fatality 4.7 times (P = .040 and .032, respectively). We found in a univariate analysis that tumor grade, PDW, MPV, and PC were predictive factors for fatality. On multivariate analysis, we found that MPV, PC, and predictors were independent of tumor grade. We observed an association between MPV and DOI. CONCLUSION High PC, MPV, and PDW could be meaningful prognostic predictors for low survival rates. Mean platelet volume appears to be a more effective marker because it is associated with the DOI and prognosis. However, further research is required to confirm our findings.
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Affiliation(s)
- Berat Demir
- Department of Otorhinolaryngology-Head and Neck Surgery, Marmara University Medical Faculty, Pendik Training and Research Hospital, Istanbul, Turkey
| | - Ghazi Abuzaid
- Department of Otorhinolaryngology-Head and Neck Surgery, Marmara University Medical Faculty, Pendik Training and Research Hospital, Istanbul, Turkey
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Sharma A, Quereshy H, Cabrera CI, Fowler N, Li S, Dorth J, Thuener JE, Rezaee RP, Tamaki A. Role of 18F-FDG PET/CT in the management of head and neck cancer patients with persistent cervical lymphadenopathy following chemoradiation. Head Neck 2024; 46:3013-3021. [PMID: 39011903 DOI: 10.1002/hed.27872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 06/10/2024] [Accepted: 07/05/2024] [Indexed: 07/17/2024] Open
Abstract
BACKGROUND We aim to describe the management and outcomes of patients with persistent lymphadenopathy (LAD) after primary chemoradiation for head and neck squamous cell carcinoma (HNSCC) based on post-treatment PET/CT results. METHODS Retrospective chart review was conducted of all patients who underwent primary concurrent chemoradiation for HNSCC at a tertiary care center from 2010 to 2022 and had persistent post-treatment LAD. RESULTS Nearly 62% of patients were managed conservatively, and 27.0% underwent neck dissection. PET-positive patients were more likely to undergo neck dissection than PET-negative patients (p = 0.042). Positive predictive value (PPV) and negative predictive values (NPV) of PET/CT in detecting residual disease in the neck were 48.0% and 73.7%, respectively. CONCLUSIONS PPV and NPV of PET/CT for detecting residual neck disease in patients with post-treatment LAD was lower than those of HNSCC patients with and without persistent LAD reported in other studies.
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Affiliation(s)
- Anu Sharma
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Humzah Quereshy
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Ear, Nose, and Throat Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Claudia I Cabrera
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Ear, Nose, and Throat Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Nicole Fowler
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Ear, Nose, and Throat Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Shawn Li
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Ear, Nose, and Throat Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Jennifer Dorth
- Department of Radiation Oncology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Jason E Thuener
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Ear, Nose, and Throat Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Rod P Rezaee
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Ear, Nose, and Throat Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Akina Tamaki
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Ear, Nose, and Throat Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
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Beiboer C, Andela R, Schwandt LQ, van der Cingel MCJM. Nurses' experiences of palliative end-of-life care in patients at risk of a carotid blowout syndrome: A qualitative exploration. Eur J Oncol Nurs 2024; 73:102694. [PMID: 39406176 DOI: 10.1016/j.ejon.2024.102694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 08/26/2024] [Accepted: 09/22/2024] [Indexed: 11/26/2024]
Abstract
PURPOSE Hospital nurses play an important role in providing palliative end-of-life care, for example for patients with carotid blowout. In such cases, dying is a severe event in which exsanguination occurs. Little is known about nurses' experiences regarding care to patients at risk of a carotid blowout. This study aims to explore thoughts, experiences, and opinions of nurses about what they consider to be quality end-of-life nursing care for patients and their relatives, specifically those at risk of carotid blowout syndrome and the impact of providing such care on their professional and emotional well-being. METHODS This study employed a qualitative design using audio-recorded, semi-structured focus group interviews. Three focus groups were conducted, comprising 11 nurses who worked on a head and neck unit. Interview transcripts were analyzed using thematic analysis. RESULTS Participants reported nursing priorities in end-of-life carotid blowout care, comprising patients' wishes, emotional support, preparing patients and dying care. Participants mentioned that a carotid blowout event was rare and impactful. A comprehensive protocol and scenario-based training facilitated the provision of end-of-life care. This study identified areas for improvement, such as the opportunity for moral support and debriefing after a blowout event for involved nurses. CONCLUSION Remarkable knowledge emerged about nurses' experiences regarding end-of-life care and frequently used nursing interventions. Being prepared and having a workable protocol to deliver end-of-life care emerge as key. This exploratory study facilitates discussion of areas important to nurses providing end-of-life care in rare and impactful conditions.
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Affiliation(s)
- Christien Beiboer
- Research Group Nursing Research, Medical Center Leeuwarden, Henry Dunantweg 2, 8934 AD, Leeuwarden, the Netherlands.
| | - Richtsje Andela
- Research Group Nursing Research, Medical Center Leeuwarden, Henry Dunantweg 2, 8934 AD, Leeuwarden, the Netherlands.
| | - Leonora Q Schwandt
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical Centre Leeuwarden, Henry Dunantweg 2, 8934 AD, Leeuwarden, the Netherlands.
| | - Margreet C J M van der Cingel
- Department of Nursing Leadership and Research, Research Group Care & Wellbeing NHL Stenden University of Applied Sciences / Medical Centre Leeuwarden, Rengerslaan 8-10, 8917 DD, Leeuwarden, the Netherlands.
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Kim GJ, Bang J, Lee OH, Kim SY, Sun DI. Impact of contralateral occult neck metastasis in HPV-associated tonsil cancer: Is elective contralateral neck dissection required? JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2024; 126:102140. [PMID: 39521177 DOI: 10.1016/j.jormas.2024.102140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 10/19/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Contralateral elective neck dissection in human papillomavirus (HPV)- associated tonsil cancer is a matter of debate. OBJECTIVES The aim of this study was to analyze rates of contralateral lymph node (LN) metastasis and their prognostic effects on HPV-associated tonsil cancer. We also assessed the necessity of elective contralateral neck dissection. METHODS To investigate the pathologic incidence of and risk factors for contralateral nodal disease in HPV-associated tonsil cancer treated with upfront primary surgery and bilateral neck dissection, the records of 68 patients were reviewed. RESULTS Six (8.8%) patients displayed pathologic contralateral nodal disease; four of the patients had LN metastasis confirmed in contralateral level II, one patient had LN metastasis in level III, and one patient had multi-level metastasis in contralateral levels II and III. Contralateral LN metastasis showed a significant association with greater depth of invasion (DOI) in primary tumor (p = 0.032), count of positive LN (p = 0.008), and positive LN ratio of the ipsilateral neck (p = 0.01). Patients with contralateral LN metastasis showed a significantly worse five-year overall survival but no significant difference in disease-free survival. CONCLUSION HPV-associated tonsil cancer has exceedingly low rates of occult contralateral LN metastasis. However, in cases of ipsilateral multiple node metastases and higher DOI, it may be worth considering elective contralateral neck dissection based on the risk of occult metastasis.
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Affiliation(s)
- Geun-Jeon Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jooin Bang
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Oh-Hyeong Lee
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Sang-Yeon Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Dong-Il Sun
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
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Acharya SK, Shai S, Choon YF, Gunardi I, Hartanto FK, Kadir K, Roychoudhury A, Amtha R, Vincent-Chong VK. Cancer Stem Cells in Oral Squamous Cell Carcinoma: A Narrative Review on Experimental Characteristics and Methodological Challenges. Biomedicines 2024; 12:2111. [PMID: 39335624 PMCID: PMC11429394 DOI: 10.3390/biomedicines12092111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 09/11/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024] Open
Abstract
Cancer stem cells (CSCs) represent a subpopulation of cancer cells that are believed to initiate and drive cancer progression. In animal models, xenotransplanted CSCs have demonstrated the ability to produce tumors. Since their initial isolation in blood cancers, CSCs have been identified in various solid human cancers, including oral squamous cell carcinoma (OSCC). In addition to their tumorigenic properties, dysregulated stem-cell-related signaling pathways-Wnt family member (Wnt), neurogenic locus notch homolog protein (Notch), and hedgehog-have been shown to endow CSCs with characteristics like self-renewal, phenotypic plasticity, and chemoresistance, contributing to recurrence and treatment failure. Consequently, CSCs have become targets for new therapeutic agents, with some currently in different phases of clinical trials. Notably, small molecule inhibitors of the hedgehog signaling pathway, such as vismodegib and glasdegib, have been approved for the treatment of basal cell carcinoma and acute myeloid leukemia, respectively. Other strategies for eradicating CSCs include natural compounds, nano-drug delivery systems, targeting mitochondria and the CSC microenvironment, autophagy, hyperthermia, and immunotherapy. Despite the extensive documentation of CSCs in OSCC since its first demonstration in head and neck (HN) SCC in 2007, none of these novel pharmacological approaches have yet entered clinical trials for OSCC patients. This narrative review summarizes the in vivo and in vitro evidence of CSCs and CSC-related signaling pathways in OSCC, highlighting their role in promoting chemoresistance and immunotherapy resistance. Additionally, it addresses methodological challenges and discusses future research directions to improve experimental systems and advance CSC studies.
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Affiliation(s)
- Surendra Kumar Acharya
- Department of Oral Medicine, Radiology and Surgery, Faculty of Dentistry, Lincoln University College, Petaling Jaya 47301, Selangor, Malaysia
| | - Saptarsi Shai
- Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX 77030, USA;
| | - Yee Fan Choon
- Department of Oral and Maxillofacial Surgical Sciences, Faculty of Dentistry, MAHSA University, Jenjarom 42610, Selangor, Malaysia;
| | - Indrayadi Gunardi
- Oral Medicine Department, Faculty of Dentistry, Universitas Trisakti, Jakarta 11440, Indonesia; (I.G.); (F.K.H.)
| | - Firstine Kelsi Hartanto
- Oral Medicine Department, Faculty of Dentistry, Universitas Trisakti, Jakarta 11440, Indonesia; (I.G.); (F.K.H.)
| | - Kathreena Kadir
- Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia;
| | - Ajoy Roychoudhury
- Department of Oral and Maxillofacial Surgery, All India Institute of Medical Sciences, New Delhi 110029, India;
| | - Rahmi Amtha
- Oral Medicine Department, Faculty of Dentistry, Universitas Trisakti, Jakarta 11440, Indonesia; (I.G.); (F.K.H.)
| | - Vui King Vincent-Chong
- Department of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
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Villa A, William WN, Hanna GJ. Cancer Precursor Syndromes and Their Detection in the Head and Neck. Hematol Oncol Clin North Am 2024; 38:813-830. [PMID: 38705773 DOI: 10.1016/j.hoc.2024.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2024]
Abstract
This article explores the multifaceted landscape of oral cancer precursor syndromes. Hereditary disorders like dyskeratosis congenita and Fanconi anemia increase the risk of malignancy. Oral potentially malignant disorders, notably leukoplakia, are discussed as precursors influenced by genetic and immunologic facets. Molecular insights delve into genetic mutations, allelic imbalances, and immune modulation as key players in precancerous progression, suggesting potential therapeutic targets. The article navigates the controversial terrain of management strategies of leukoplakia, encompassing surgical resection, chemoprevention, and immune modulation, while emphasizing the ongoing challenges in developing effective, evidence-based preventive approaches.
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Affiliation(s)
- Alessandro Villa
- Oral Medicine, Oral Oncology and Dentistry, Miami Cancer Institute, Baptist Health South Florida, 8900 N. Kendall Drive. Miami, FL 33176, USA; Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - William N William
- Thoracic Oncology Program, Grupo Oncoclínicas Grupo Oncoclínicas, Av. Pres. Juscelino Kubitschek, 510, 2º andar, São Paulo, São Paulo 04543-906, Brazil
| | - Glenn J Hanna
- Department of Medical Oncology, Center for Head & Neck Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Dana Building, Room 2-140. Boston, MA 02215, USA.
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11
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Masago K, Kuroda H, Sasaki E, Fujita Y, Fujita S, Horio Y, Endo M, Ishihara H, Hanai N, Matsushita H. Novel gene fusions in human oropharyngeal carcinoma. Cancer Genet 2024; 286-287:29-34. [PMID: 38971117 DOI: 10.1016/j.cancergen.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 05/13/2024] [Accepted: 06/30/2024] [Indexed: 07/08/2024]
Abstract
Few reports have analyzed the fusion genes involved in carcinogenesis in the oropharynx, where the incidence of human papillomavirus-associated tumors is relatively low. The aim of this study was to identify novel driver fusion genes in patients with oropharyngeal cancer. The study enrolled fifty-seven patients who were diagnosed with oropharyngeal carcinoma. RNA sequencing data from fresh-frozen specimens were used to identify candidate fusion genes via the JAFFA, arriba, and STAR-Fusion pipelines. Candidate fusion genes were confirmed by direct sequencing. The expression level of a candidate fusion gene was compared to that of tumors without fusion genes. Finally, filtering was performed for driver genes using the annoFuse pipeline. In addition, the VIRTUS pipeline was used to analyze the presence of human papillomavirus in the tumors. We identified 5 (8.8 %) novel potential driver in-frame fusion genes, MKNK2::MOB3A, ICMT::RPS6KA3, ATP1B3::GRK7, CSNK2A1::KIF16B, and FGFR3::MAEA, and 1 (1.8 %) known in-frame fusion gene, FGFR3::TACC3, in 57 patients with pharyngeal carcinoma. Our results suggest that sporadic fusion genes may contribute to tumorigenesis in oropharyngeal carcinomas.
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Affiliation(s)
- Katsuhiro Masago
- Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan; Division of Translational Oncoimmunology, Aichi Cancer Research Institute, Nagoya, Japan.
| | - Hiroaki Kuroda
- Department of Respiratory Surgery, Aichi Cancer Center Hospital, Nagoya, Japan; Division of Translational Oncoimmunology, Aichi Cancer Research Institute, Nagoya, Japan; Department of Thoracic Surgery, Teikyo University Mizonokuchi Hospital, Kawasaki, Japan
| | - Eiichi Sasaki
- Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan
| | - Yasuko Fujita
- Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan
| | - Shiro Fujita
- Department of Respiratory Medicine, Kobe Central Hospital, Kobe, Japan
| | - Yoshitsugu Horio
- Department of Respiratory Medicine, Aichi Cancer Center Hospital, Nagoya, Japan; Division of Translational Oncoimmunology, Aichi Cancer Research Institute, Nagoya, Japan
| | - Motoyoshi Endo
- Department of Molecular Biology, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Hiromasa Ishihara
- Division of Translational Oncoimmunology, Aichi Cancer Research Institute, Nagoya, Japan
| | - Nobuhiro Hanai
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hirokazu Matsushita
- Division of Translational Oncoimmunology, Aichi Cancer Research Institute, Nagoya, Japan
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12
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Hirai R, Kinugasa H, Yamamoto S, Ako S, Tsutsumi K, Abe M, Miyahara K, Nakagawa M, Otsuka M. Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer. Br J Cancer 2024; 130:1725-1731. [PMID: 38538728 PMCID: PMC11091138 DOI: 10.1038/s41416-024-02654-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 03/01/2024] [Accepted: 03/05/2024] [Indexed: 05/15/2024] Open
Abstract
BACKGROUND Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients. METHODS Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of DCC, PTGDR1, EDNRB, and ECAD, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR. RESULTS Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of DCC (p = 0.003), EDNRB (p = 0.001), and ECAD (p = 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples, DCC showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864-0.970), compared with those for EDNRB (0.680) and ECAD (0.639). When the cutoff for the methylation values of DCC was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%. CONCLUSIONS DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.
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Affiliation(s)
- Ryosuke Hirai
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata, Kitaku, Okayama, Okayama, 700-8558, Japan
| | - Hideaki Kinugasa
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata, Kitaku, Okayama, Okayama, 700-8558, Japan.
| | - Shumpei Yamamoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata, Kitaku, Okayama, Okayama, 700-8558, Japan
| | - Soichiro Ako
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata, Kitaku, Okayama, Okayama, 700-8558, Japan
| | - Koichiro Tsutsumi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata, Kitaku, Okayama, Okayama, 700-8558, Japan
| | - Makoto Abe
- Department of Internal Medicine, Hiroshima City Hospital, 7-33, Motomachi, Nakaku, Hiroshima, Hiroshima, 730-8518, Japan
| | - Koji Miyahara
- Department of Internal Medicine, Hiroshima City Hospital, 7-33, Motomachi, Nakaku, Hiroshima, Hiroshima, 730-8518, Japan
| | - Masahiro Nakagawa
- Department of Internal Medicine, Hiroshima City Hospital, 7-33, Motomachi, Nakaku, Hiroshima, Hiroshima, 730-8518, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata, Kitaku, Okayama, Okayama, 700-8558, Japan
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13
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Moratin J, Horn D, Oehme M, Semmelmayer K, Flechtenmacher C, Ristow O, Held T, Engel M, Hoffmann J, Freudlsperger C. Variation of resection margins in oral cancer in dependence of tumor stage and subsite - a retrospective cohort study. Clin Oral Investig 2024; 28:327. [PMID: 38764079 PMCID: PMC11102874 DOI: 10.1007/s00784-024-05711-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 05/07/2024] [Indexed: 05/21/2024]
Abstract
OBJECTIVES Surgical resection is a key component of the treatment of head and neck cancer and the achievement of free surgical margins are essential for the patients' outcome in terms of survival. While there is a general recommendation for a free resection range of 5 mm, up to date, there is a lack of investigations on the quality of tumor resection in dependence of affected subsite and tumor stage. In the presented study, predictors for the achieved resection margins in surgically treated oral squamous cell carcinomas were analyzed. MATERIALS AND METHODS A cohort of 567 patients was included in a retrospective analysis and resection status with exact margin ranges were analysed. Tumor stage, affected subsite and the results of the intraoperative frozen section analysis were assessed. Primary endpoint was the achieved resection margin in mm, secondary endpoints were overall and progression-free survival. RESULTS The observed mean values of minimal resection margins differed significantly between the investigated subsites (p = 0.042),pathological tumor stages (p < 0.001) and in tumors which demonstrated perineural infiltration (Pn1, p = 0.002). Furthermore, there was a significant impact of the results of the intraoperative frozen section analysis on progression-free and overall survival (p < 0.001). CONCLUSIONS Our data clearly indicate that resection status differs between tumors of different subsites and tumor stages. CLINICAL RELEVANCE Clinical procedures should be adapted in order to achieve similar certainty in all resections, and, thus to improve patients' outcome.
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Affiliation(s)
- Julius Moratin
- Department of Oral and Cranio-Maxillofacial Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
| | - Dominik Horn
- Department of Oral and Maxillofacial Surgery, Saarland University Hospital, Kirrberger Straße, 66424, Homburg, Germany
| | - Marcel Oehme
- Department of Oral and Cranio-Maxillofacial Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
| | - Karl Semmelmayer
- Department of Oral and Cranio-Maxillofacial Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
| | - Christa Flechtenmacher
- Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
| | - Oliver Ristow
- Department of Oral and Cranio-Maxillofacial Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
| | - Thomas Held
- Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
| | - Michael Engel
- Department of Oral and Cranio-Maxillofacial Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
| | - Jürgen Hoffmann
- Department of Oral and Cranio-Maxillofacial Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
| | - Christian Freudlsperger
- Department of Oral and Cranio-Maxillofacial Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
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14
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Sarubo M, Mouri Y, Moromizato A, Yamada A, Jin S, Shao W, Hagita H, Miyoshi K, Kudo Y. Involvement of TGFBI-TAGLN axis in cancer stem cell property of head and neck squamous cell carcinoma. Sci Rep 2024; 14:6767. [PMID: 38514830 PMCID: PMC10957997 DOI: 10.1038/s41598-024-57478-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 03/17/2024] [Indexed: 03/23/2024] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a significant healthcare burden globally. Previous research using single-cell transcriptome analysis identified TGFBI as a crucial marker for the partial-epithelial-mesenchymal transition (partial-EMT) program. However, the precise role of TGFBI in HNSCC progression remains unclear. Therefore, our study aimed to clarify the impact of TGFBI on the malignant behavior of HNSCC cells. Through RNA-sequencing data from the TCGA database, we validated that increased TGFBI expression correlates with a higher occurrence of lymph node metastasis and unfavorable prognosis in HNSCC cases. Functional experiments demonstrated that TGFBI overexpression enhances the ability of sphere formation, indicating stem-cell-like properties. Conversely, TGFBI depletion reduces sphere formation and suppresses the expression of cancer stem cell (CSC) markers. RNA-sequencing analysis of TGFBI-overexpressing and control HNSCC cells revealed TAGLN as a downstream effector mediating TGFBI-induced sphere formation. Remarkably, TAGLN depletion abolished TGFBI-induced sphere formation, while its overexpression rescued the suppressed sphere formation caused by TGFBI depletion. Moreover, elevated TAGLN expression showed correlations with the expression of TGFBI and partial-EMT-related genes in HNSCC cases. In conclusion, our findings suggest that TGFBI may promote CSC properties through the upregulation of TAGLN. These novel insights shed light on the involvement of the TGFBI-TAGLN axis in HNSCC progression and hold implications for the development of targeted therapies.
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Affiliation(s)
- Motoharu Sarubo
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Yasuhiro Mouri
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Akira Moromizato
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Azusa Yamada
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Shengjan Jin
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Wenhua Shao
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Hiroko Hagita
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Keiko Miyoshi
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Yasusei Kudo
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
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15
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Ganesh A, Ashikha Shirin Usman P, K.P. A, Thomas P, Ganapathy DM, Sekar D. Expression analysis of transforming growth factor beta (TGF-β) in oral squamous cell carcinoma. ORAL ONCOLOGY REPORTS 2024; 9:100195. [DOI: 10.1016/j.oor.2024.100195] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2025]
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16
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Chen KM, Sun YW, Hu J, Balogh K, Gowda K, Aliaga C, Sun D, Christensen N, Amin S, El-Bayoumy K. Gender Difference in DNA Damage Induced by the Environmental Carcinogen Dibenzo[ def,p]chrysene Individually and in Combination with Mouse Papillomavirus Infection in the Mouse Oral Cavity. ACS OMEGA 2024; 9:8434-8438. [PMID: 38405470 PMCID: PMC10882652 DOI: 10.1021/acsomega.3c09611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/23/2024] [Accepted: 01/26/2024] [Indexed: 02/27/2024]
Abstract
Tobacco smoking and human papillomavirus infection are established etiological agents in the development of head and neck squamous cell carcinoma (HNSCC). The incidence and mortality of HNSCC are higher in men than women. To provide biochemical basis for sex differences, we tested the hypothesis that carcinogen treatment using dibenzo[def,p]chrysene, which is an environmental pollutant and tobacco smoke constituent, in the absence or presence of the mouse papillomavirus infection results in significantly higher levels of DNA damage in the oral cavity in male than in female mice. However, the results of the present investigation do not support our hypothesis since we found that females were more susceptible to carcinogen-induced covalent DNA damage than males independent of the viral infection. Since DNA damage represents only a single-step in the carcinogenesis process, additional factors may contribute to sex differences in humans.
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Affiliation(s)
- Kun-Ming Chen
- Department
of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United States
| | - Yuan-Wan Sun
- Department
of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United States
| | - Jiafen Hu
- The
Jake Gittlen Laboratories for Cancer Research, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United States
- Department
of Pathology, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United
States
| | - Karla Balogh
- The
Jake Gittlen Laboratories for Cancer Research, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United States
| | - Krishne Gowda
- Department
of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United
States
| | - Cesar Aliaga
- Department
of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United States
| | - Dongxiao Sun
- Department
of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United
States
| | - Neil Christensen
- The
Jake Gittlen Laboratories for Cancer Research, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United States
- Department
of Pathology, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United
States
| | - Shantu Amin
- Department
of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United
States
| | - Karam El-Bayoumy
- Department
of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033-2360, United States
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17
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Salama V, Humbert-Vidan L, Godinich B, Wahid KA, ElHabashy DM, Naser MA, He R, Mohamed ASR, Sahli AJ, Hutcheson KA, Gunn GB, Rosenthal DI, Fuller CD, Moreno AC. Comparison of Machine Leaning Models for Prediction of Acute Pain Severity and On-Treatment Opioid Utilization in Oral Cavity and Oropharyngeal Cancer Patients Receiving Radiation Therapy: Exploratory Analysis from a Large-Scale Retrospective Cohort. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.02.06.24302341. [PMID: 38370746 PMCID: PMC10871386 DOI: 10.1101/2024.02.06.24302341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/20/2024]
Abstract
Background Acute pain is a common and debilitating symptom experienced by oral cavity and oropharyngeal cancer (OC/OPC) patients undergoing radiation therapy (RT). Uncontrolled pain can result in opioid overuse and increased risks of long-term opioid dependence. The specific aim of this exploratory analysis was the prediction of severe acute pain and opioid use in the acute on-treatment setting, to develop risk-stratification models for pragmatic clinical trials. Materials and Methods A retrospective study was conducted on 900 OC/OPC patients treated with RT during 2017 to 2023. Clinical data including demographics, tumor data, pain scores and medication data were extracted from patient records. On-treatment pain intensity scores were assessed using a numeric rating scale (0-none, 10-worst) and total opioid doses were calculated using morphine equivalent daily dose (MEDD) conversion factors. Analgesics efficacy was assessed based on the combined pain intensity and the total required MEDD. ML models, including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), and Gradient Boosting Model (GBM) were developed and validated using ten-fold cross-validation. Performance of models were evaluated using discrimination and calibration metrics. Feature importance was investigated using bootstrap and permutation techniques. Results For predicting acute pain intensity, the GBM demonstrated superior area under the receiver operating curve (AUC) (0.71), recall (0.39), and F1 score (0.48). For predicting the total MEDD, LR outperformed other models in the AUC (0.67). For predicting the analgesics efficacy, SVM achieved the highest specificity (0.97), and best calibration (ECE of 0.06), while RF and GBM achieved the same highest AUC, 0.68. RF model emerged as the best calibrated model with ECE of 0.02 for pain intensity prediction and 0.05 for MEDD prediction. Baseline pain scores and vital signs demonstrated the most contributed features for the different predictive models. Conclusion These ML models are promising in predicting end-of-treatment acute pain and opioid requirements and analgesics efficacy in OC/OPC patients undergoing RT. Baseline pain score, vital sign changes were identified as crucial predictors. Implementation of these models in clinical practice could facilitate early risk stratification and personalized pain management. Prospective multicentric studies and external validation are essential for further refinement and generalizability.
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18
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Sharma S, Rai S, Misra D, Misra A, Sharma S, Sharma A, Prayasi MS. Human Urinary Metabolomics as Biomarkers in Tobacco Users: A Systematic Review. Contemp Clin Dent 2024; 15:3-9. [PMID: 38707674 PMCID: PMC11068250 DOI: 10.4103/ccd.ccd_23_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 05/27/2021] [Accepted: 12/07/2023] [Indexed: 05/07/2024] Open
Abstract
Aim Urine as a biofluid has been rarely used as a diagnostic fluid in oral diseases. The article aims to systematically review the utility of human urinary carcinogen metabolites as an approach for obtaining important information about tobacco and cancer. Materials and Methods The following article reviews the use of urine and its metabolites as biomarkers in various lesions of the oral cavity including oral squamous cell carcinoma and as a screening method in evaluating tobacco and its components. A bibliographic comprehensive search was carried out in the main databases: PUBMED, SciELO, Google Scholar, VHL, and LILACS for articles that were published from 1985 to 2020. The inclusion criteria were "urinary metabolites," "oral cancer/HNSCC," "body fluids," "tobacco," and "metabolomics." A total of 55 articles were collected which included laboratory studies, systematic reviews, and literature of urinary metabolites in tobacco users. Results Most of the studies carried out show accurate results with high sensitivity of urinary metabolite biomarkers in individuals with tobacco-based habits and lesions caused by them. Conclusion The review indicates that urinary metabolite analysis demonstrates its applicability for the diagnosis and prognosis of disease. Urine is a remarkable and useful biofluid for routine testing and provides an excellent resource for the discovery of novel biomarkers, with an advantage over tissue biopsy samples due to the ease and less invasive nature of collection.
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Affiliation(s)
- Somya Sharma
- Department of Oral Pathology, Institute of Dental Studies and Technologies, Modinagar, Uttar Pradesh, India
| | - Shalu Rai
- Department of Oral Medicine and Radiology, Institute of Dental Studies and Technologies, Modinagar, Uttar Pradesh, India
| | - Deepankar Misra
- Department of Oral Medicine and Radiology, Institute of Dental Studies and Technologies, Modinagar, Uttar Pradesh, India
| | - Akansha Misra
- Department of Oral Pathology, Institute of Dental Studies and Technologies, Modinagar, Uttar Pradesh, India
| | - Shalini Sharma
- Department of Oral Medicine and Radiology, Institute of Dental Studies and Technologies, Modinagar, Uttar Pradesh, India
| | - Anusuya Sharma
- Department of Pathology, University of Health Sciences, Rohtak, Haryana, India
| | - Manish Singh Prayasi
- Department of Oral Medicine and Radiology, Institute of Dental Studies and Technologies, Modinagar, Uttar Pradesh, India
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19
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Matsui H, Mukaigawa T, Goto S, Okada S, Hiiragi Y, Wada K. Risk factors for late postoperative bleeding after partial glossectomy for tongue cancer. Acta Otolaryngol 2024; 144:76-81. [PMID: 38343347 DOI: 10.1080/00016489.2024.2310695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 01/18/2024] [Indexed: 03/16/2024]
Abstract
BACKGROUND Partial glossectomy is the most common procedure for early-stage tongue cancer. Although late postoperative bleeding occasionally occurs, the associated risk factors have not been adequately identified. AIMS/OBJECTIVES We aimed to investigate the rate and risk factors for late postoperative bleeding after transoral partial glossectomy with or without neck dissection for tongue cancer at our institution. MATERIAL AND METHODS We analysed 211 patients who had undergone transoral partial glossectomy between January 2016 and January 2023. The potential risk factors associated with late postoperative bleeding were investigated using univariate and multivariate logistic regression analyses. RESULTS Of the 211 patients, 40 (19%) showed late postoperative bleeding, with 19 (9%) classified as grade IIIa (Clavien-Dindo classification). Regarding all grades, late postoperative bleeding was significantly higher in patients aged <70 years and in those with polyglycolic acid (PGA) sheets (p = .046 and .030, respectively). For grade ≥ IIIa, late postoperative bleeding was significantly higher in patients with a history of anticoagulant/platelet administration, a mucosal defect covered with fibrin glue and a PGA sheet (p = .045 and .026, respectively). CONCLUSIONS AND SIGNIFICANCE The findings of this study suggest that primary closure decreases the frequency of late postoperative bleeding.
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Affiliation(s)
- Hidehito Matsui
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
- Department of Otolaryngology, Toho University Omori Medical Center, Tokyo, Japan
| | - Takashi Mukaigawa
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Seiya Goto
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Shinichi Okada
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yohei Hiiragi
- Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kota Wada
- Department of Otolaryngology, Toho University Omori Medical Center, Tokyo, Japan
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20
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Steen S, Semmelmayer K, Flechtenmacher C, Hoffmann J, Freier K, Horn D, Hess J, Freudlsperger C, Moratin J. Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma. Int J Mol Sci 2023; 24:16386. [PMID: 38003576 PMCID: PMC10671831 DOI: 10.3390/ijms242216386] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 11/12/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors.
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Affiliation(s)
- Sonja Steen
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
| | - Karl Semmelmayer
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
| | - Christa Flechtenmacher
- Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany;
- Tissue Bank of the National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
| | - Jürgen Hoffmann
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
| | - Kolja Freier
- Department of Oral and Maxillofacial Surgery, Saarland University Hospital, 66421 Homburg, Germany; (K.F.)
| | - Dominik Horn
- Department of Oral and Maxillofacial Surgery, Saarland University Hospital, 66421 Homburg, Germany; (K.F.)
| | - Jochen Hess
- Department of Otorhinolaryngology, Head and Neck Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany;
- Research Group Molecular Mechanisms of Head and Neck Tumors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Christian Freudlsperger
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
| | - Julius Moratin
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
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21
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Stöth M, Meyer T, Gehrke T, Hagen R, Scheich M, Hackenberg S, Scherzad A. Discontinuation of anti‑programmed cell death protein 1 immune checkpoint inhibition after complete remission in head and neck squamous cell carcinoma: A case report and literature review. Oncol Lett 2023; 26:489. [PMID: 37818135 PMCID: PMC10561138 DOI: 10.3892/ol.2023.14076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 07/07/2023] [Indexed: 10/12/2023] Open
Abstract
Programmed cell death protein 1 (PD-1) inhibition plays a central role in the current treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Some patients achieve a durable response, and even complete remission (CR) is possible, though it occurs rarely. In cases of durable CR, there are no guidelines regarding a possible discontinuation of immunotherapy. Since clinical experience on this issue is limited, the present study reported on a case of a durable CR following discontinuation of PD-1 inhibition in R/M-HNSCC and additionally presented an overview on the current literature. The present study reported on a case of CR of recurrent oropharyngeal cancer after four cycles of PD-1 monotherapy with Nivolumab. The therapy was discontinued after overall 46 cycles. Even after 3 more years of follow-up, there was no sign of tumor recurrence. Overall, according to reports from the literature, CR seems to be an indicator for durable disease control after therapy discontinuation. Since data on therapy termination is rare, decisions about when to stop successful immunotherapy in R/M-HNSCC have to be made individually for each patient.
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Affiliation(s)
- Manuel Stöth
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, D-97080 Würzburg, Germany
| | - Till Meyer
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, D-97080 Würzburg, Germany
| | - Thomas Gehrke
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, D-97080 Würzburg, Germany
| | - Rudolf Hagen
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, D-97080 Würzburg, Germany
| | - Matthias Scheich
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, D-97080 Würzburg, Germany
| | - Stephan Hackenberg
- Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital, Rhine-Westphalia Technical University of Aachen, D-52074 Aachen, Germany
| | - Agmal Scherzad
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, D-97080 Würzburg, Germany
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22
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Sykes EA, Weisbrod N, Rival E, Haque A, Fu R, Eskander A. Methods, Detection Rates, and Survival Outcomes of Screening for Head and Neck Cancers: A Systematic Review. JAMA Otolaryngol Head Neck Surg 2023; 149:1047-1056. [PMID: 37796524 DOI: 10.1001/jamaoto.2023.3010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/06/2023]
Abstract
Importance Head and neck cancers (HNCs) are often diagnosed at advanced clinical stages during their symptomatic phase, leading to a reduced treatment window and poor survival. Screening programs have been suggested as a mitigation strategy. Objective To examine the effectiveness of current HNC screening programs in improving diagnosis and survival in adults. Evidence Review This Preferred Reporting Items for Systematic Reviews and Meta-analyses-guided systematic review involved use of peer-reviewed, English-language journal articles identified from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials between January 1, 2001, and July 15, 2022. Snowballing was applied to retrieve more studies. Eligible articles were original clinical trials and observational studies presenting a universal or risk-targeted screening program of primary HNC in the adult population. Reporting quality was assessed using the JBI's critical appraisal tools. Findings Database searches yielded 3646 unique citations with an additional 8 studies found via snowballing. Five reviewers assessed the full text of 106 studies. Sixteen articles were ultimately included in the review, involving 4.7 million adults (34.1%-100% male; median age, 30-59 years). Fifteen studies were based in Asia and 1 in Europe (Portugal). Five reported data from randomized clinical trials. An oral inspection conducted once or once every 2 to 3 years was described in 11 studies for screening oral cancer, while multistep screening involving Epstein-Barr virus serologic testing for nasopharyngeal carcinoma delivered every 1 to 4 years was presented in 5. In 4 trials and 6 observational studies, screening significantly increased the detection of localized (stage I/II) tumor or was associated with an increased proportion of diagnoses, respectively, regardless of the population and cancer subsites. Universal screening of asymptomatic adults improved 3- to 5-year overall survival but did not increase cancer-specific survival in 4 trials. Targeted screening improved overall and cancer-specific survival or was associated with improved survival outcomes in 2 trials and 2 observational studies, respectively. Studies had low to medium risks of bias. Conclusions and Relevance Evidence from the existing literature suggests that a risk-targeted screening program for oral and nasopharyngeal cancers could improve diagnosis and patient survival. Screening adherence, societal cost-effectiveness, and optimal risk stratification of such a program warrant future research, especially in low-incidence settings outside Asia.
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Affiliation(s)
- Edward A Sykes
- Odette Cancer Centre-Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Department of Otolaryngology-Head and Neck Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Natalie Weisbrod
- Odette Cancer Centre-Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Queen's University, Kingston, Ontario, Canada
| | - Ella Rival
- Odette Cancer Centre-Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- McMaster University, Hamilton, Ontario, Canada
| | - Aminul Haque
- Department of Dental & Faciomaxillary Surgical Oncology, National Institute of Cancer Research and Hospital, Dhaka, Bangladesh
| | - Rui Fu
- Department of Otolaryngology-Head and Neck Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Antoine Eskander
- Odette Cancer Centre-Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Department of Otolaryngology-Head and Neck Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
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23
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Na'ara S, Subramaniam N, Deganello A, Shinnawi S, Billan S, Mattavelli D, Ferrari M, Balasubramanian D, Thankappan K, Iyer S, Gil Z. Primary Tumor Staging for Oral Cancer and a Proposed Modification Incorporating Perineural Invasion: An International Multicenter Study. Adv Biol (Weinh) 2023; 7:e2300162. [PMID: 37415540 DOI: 10.1002/adbi.202300162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/02/2023] [Indexed: 07/08/2023]
Abstract
The objective of this study is to determine if the incorporation of perineural invasion (PNI) into the T-classification would improve the prognostic performance of TNM-8. An international, multicenter study of 1049 patients with oral cavity squamous cell carcinoma that were treated from 1994 to 2018 is performed. Various classification models are developed within each T-category and evaluated using the Harrel-concordance index (C-index), Akaike-information criterion (AIC), and visual inspection. Stratification into distinct prognostic categories, with internal validation, is performed using bootstrapping analysis (SPSS and R-software). Through multivariate analysis, PNI is significantly associated with disease-specific survival (p < 0.001). PNI integration into the staging system results in a significantly improved model compared with the current T category alone (lower AIC, p < 0.001). The PNI-integrated model is superior in predicting differential outcomes between T3 and T4 patients. A new model for T-classification of oral cavity squamous cell carcinoma is proposed, which is based on incorporating PNI into the staging system. These data can be used for future evaluations of the TNM staging system.
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Affiliation(s)
- Shorook Na'ara
- Department of Otolaryngology-Head and Neck Surgery, University of California-San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA
- Department of Otolaryngology Head and Neck Surgery, The Head and Neck Center, Rambam Healthcare Campus, Rappaport School of Medicine, Technion - Israel Institute of Technology, Haifa, 3109601, Israel
| | - Narayana Subramaniam
- Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Alberto Deganello
- Otolaryngology Head and Neck Surgery, Department of IRCCS National Cancer Institute (INT), Milan, 20133, Italy
- Department of Oncology and Hematology-Oncology, University of Milan, Milan, Italy
| | - Shadi Shinnawi
- Department of Otolaryngology Head and Neck Surgery, The Head and Neck Center, Rambam Healthcare Campus, Rappaport School of Medicine, Technion - Israel Institute of Technology, Haifa, 3109601, Israel
| | - Salem Billan
- Oncology Department, The Head and Neck Center, Rambam Healthcare Campus, Haifa, 3109601, Israel
| | - Davide Mattavelli
- Unit of Otorhinolaryngology-Head and Neck Surgery, Department of Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, 25123, Italy
| | - Marco Ferrari
- Unit of Otorhinolaryngology-Head and Neck Surgery, Department of Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, 25123, Italy
| | - Deepak Balasubramanian
- Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Krishnakumar Thankappan
- Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Subramania Iyer
- Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Ziv Gil
- Head and Neck Center, Holy Family Hospital, Nazareth, 1641100, Israel
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24
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Kumar K, Hallikeri K, Oli A, Goni M, Jain A, Poyya J, Shilpasree AS, Javaregowda PK. Quantitative analysis of lncRNA in formalin-fixed paraffin-embedded tissues of oral squamous cell carcinoma. Biotechniques 2023; 75:133-142. [PMID: 37589188 DOI: 10.2144/btn-2023-0033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023] Open
Abstract
The study evaluated expression profiles of few regulatory lncRNAs in oral squamous cell carcinoma and normal mucosa adjacent to oral cancer using paired fresh frozen and formalin-fixed paraffin-embedded (FFPE) tissues stored at a different duration of time (1-5 years) using real-time quantitative PCR. The quantity and quality of total RNA isolated from FFPE tissues was less compared with that of fresh frozen tissues, which resulted in a noncorrelation of quantification cycle values. Following normalization, the expression of lncRNAs in the paired tissues did not differ significantly. The differential expression of the lncRNAs in the study was consistent with The Cancer Genome Atlas head and neck squamous cell carcinoma database. The study findings demonstrate the possibility of performing accurate quantitative analysis of lncRNAs using short amplicons and standardized real-time quantitative PCR assays in oral squamous cell carcinoma FFPE samples.
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Affiliation(s)
- Kiran Kumar
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, SDM College of Dental Sciences and Hospital (a constituent unit of Shri Dharmasthala Manjunatheshwara University), Dharwad, Karnataka State, 580009, India
| | - Kaveri Hallikeri
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, SDM College of Dental Sciences and Hospital (a constituent unit of Shri Dharmasthala Manjunatheshwara University), Dharwad, Karnataka State, 580009, India
| | - Ajaykumar Oli
- Department of Biomedical Science, SDM Research Institute for Biomedical Sciences (a constituent unit of Shri Dharmasthala Manjunatheshwara University), Dharwad, Karnataka State, 580009, India
| | - Mallikarjun Goni
- Department of Biomedical Science, SDM Research Institute for Biomedical Sciences (a constituent unit of Shri Dharmasthala Manjunatheshwara University), Dharwad, Karnataka State, 580009, India
| | - Apoorva Jain
- Department of Biomedical Science, SDM Research Institute for Biomedical Sciences (a constituent unit of Shri Dharmasthala Manjunatheshwara University), Dharwad, Karnataka State, 580009, India
| | - Jagadeesha Poyya
- Department of Biomedical Science, SDM Research Institute for Biomedical Sciences (a constituent unit of Shri Dharmasthala Manjunatheshwara University), Dharwad, Karnataka State, 580009, India
| | - Alagilavada S Shilpasree
- Department of Biochemistry, SDM College of Medical Sciences and Hospital (a constituent unit of Shri Dharmasthala Manjunatheshwara University), Dharwad, Karnataka State, 580009, India
| | - Palaksha Kanive Javaregowda
- Department of Biomedical Science, SDM Research Institute for Biomedical Sciences (a constituent unit of Shri Dharmasthala Manjunatheshwara University), Dharwad, Karnataka State, 580009, India
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25
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Sireci F, Lorusso F, Dispenza F, Immordino A, Gallina S, Salvago P, Martines F, Bonaventura G, Uzzo ML, Spatola GF. A Prospective Observational Study on the Role of Immunohistochemical Expression of Orphanin in Laryngeal Squamous Cell Carcinoma Recurrence. J Pers Med 2023; 13:1211. [PMID: 37623462 PMCID: PMC10455511 DOI: 10.3390/jpm13081211] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 07/21/2023] [Accepted: 07/29/2023] [Indexed: 08/26/2023] Open
Abstract
To date, histological biomarkers expressed by laryngeal cancer are poorly known. The identification of biomarkers associated with laryngeal squamous cell carcinoma (SCC), would help explain the tumorogenesis and prevent the possible recurrence of the lesion after treatment. For this reason, the aim of this study is to investigate, for the first time, the Orphanin expression in 48 human specimens of laryngeal SCC and evaluate its possible correlation with patients prognosis. We analyzed pathological specimens from 48 patients with laryngeal SCC to detect the presence of Orphanin by using an immunohistochemistry test. We compared the findings with healthy tissue acquired from patients who underwent surgery for mesenchymal benign tumours of the larynx. The specimens were stained with anti-Orphanin monoclonal antibodies. Results were processed through a computerised image analysis system to determine a scale of staining intensity. All the tumoural specimens examined showed a significant immunoreaction for Orphanin when compared with healthy tissues (p < 0.05) but with a different immune reactivity related to clinical-pathological features. A high Orphanin expression was not significantly related to Histological Grading (HG), TNM, and stage (p > 0.05). In the multivariate analysis, the Orphanin expression was significantly related only to the malignant recurrence (p < 0.05). Our study suggests that Orphanin could have a role in tumorigenesis by increasing the recurrence of cancer; therefore, it should be further explored as a possible biomarker for laryngeal cancer.
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Affiliation(s)
- Federico Sireci
- Otorhinolaryngology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (F.S.); (F.L.); (F.D.); (S.G.)
| | - Francesco Lorusso
- Otorhinolaryngology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (F.S.); (F.L.); (F.D.); (S.G.)
| | - Francesco Dispenza
- Otorhinolaryngology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (F.S.); (F.L.); (F.D.); (S.G.)
| | - Angelo Immordino
- Otorhinolaryngology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (F.S.); (F.L.); (F.D.); (S.G.)
| | - Salvatore Gallina
- Otorhinolaryngology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (F.S.); (F.L.); (F.D.); (S.G.)
| | - Pietro Salvago
- Audiology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (P.S.); (F.M.)
| | - Francesco Martines
- Audiology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (P.S.); (F.M.)
| | - Giuseppe Bonaventura
- Histology and Embriology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (G.B.); (M.L.U.); (G.F.S.)
| | - Maria Laura Uzzo
- Histology and Embriology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (G.B.); (M.L.U.); (G.F.S.)
| | - Giovanni Francesco Spatola
- Histology and Embriology Section, Biomedicine, Neuroscience and Advanced Diagnosics Department, University of Palermo, Via del Vespro 129, 133, 90127 Palermo, Italy; (G.B.); (M.L.U.); (G.F.S.)
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26
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Shao B, Ye Z, Sun B, Xiao Z. Molecular Evolutionary Landscape of the Immune Microenvironment of Head and Neck Cancer. Biomolecules 2023; 13:1120. [PMID: 37509156 PMCID: PMC10377423 DOI: 10.3390/biom13071120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/23/2023] [Accepted: 06/28/2023] [Indexed: 07/30/2023] Open
Abstract
Head and neck cancer is a highly heterogeneous malignant tumor. Numerous studies have shown that the immune microenvironment of head and neck cancer has a significant impact on its occurrence and development, as well as its prognosis. However, there have been fewer studies related to the accurate immunophenotyping of head and neck cancer. In this study, we used gene expression profile information and clinical information from the TCGA-HNSC cohort (502 samples) and the GSE655858 cohort (270 samples) to identify and independently validate three immune subtypes (Cluster1-Cluster3) with different immune-related molecular profiles and clinical outcomes. Cluster2, which is mainly dominated by B-lymphocyte infiltration, was found to have the best prognosis. In addition, a support vector machine (SVM)-based classifier was constructed, which could accurately classify HNSC based on 19 genes. Furthermore, the results of the prognostic analysis showed activation of antibody-secreting B-lymphocyte function, which showed a good prognostic effect in all three immune subtypes of HNSC. Finally, the immune evolutionary landscape of HNSC was constructed in an attempt to explain the evolutionary pattern of the immune subtypes of HNSC. In summary, we provide a conceptual framework for understanding the tumor immune microenvironment in HNSC and demonstrate the importance of immune infiltration of B lymphocytes in HNSC. Further research is needed to assess the importance of these immunophenotypes in combination drug therapy and to provide a basis for screening appropriate patients for immunotherapy.
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Affiliation(s)
- Baoyi Shao
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Zheng Ye
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Bo Sun
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Zhongdang Xiao
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
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27
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Ma W, Liu R, Zhao K, Zhong J. Vital role of SHMT2 in diverse disease. Biochem Biophys Res Commun 2023; 671:160-165. [PMID: 37302290 DOI: 10.1016/j.bbrc.2023.05.108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 05/25/2023] [Indexed: 06/13/2023]
Abstract
One-carbon metabolism is essential for our human cells to carry out nucleotide synthesis, methylation, and reductive metabolism through one-carbon units, and these pathways ensure the high proliferation rate of cancer cells. Serine hydroxymethyltransferase 2 (SHMT2) is a key enzyme in one-carbon metabolism. This enzyme can convert serine into a one-carbon unit bound to tetrahydrofolate and glycine, ultimately supporting the synthesis of thymidine and purines and promoting the growth of cancer cells. Due to SHMT2's crucial role in the one-carbon cycle, it is ubiquitous in human cells and even in all organisms and highly conserved. Here, we summarize the impact of SHMT2 on the progression of various cancers to highlight its potential use in the development of cancer treatments.
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Affiliation(s)
- Wenqi Ma
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250013, China
| | - Ronghan Liu
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250013, China
| | - Kai Zhao
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250013, China
| | - Jiangbo Zhong
- Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250013, China.
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28
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Abstract
Head and neck cancers are a heterogeneous group of highly aggressive tumors and collectively represent the sixth most common cancer worldwide. Most head and neck cancers are squamous cell carcinomas (HNSCCs). Current multimodal treatment concepts combine surgery, chemotherapy, irradiation, immunotherapy, and targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of HNSCC and revealed novel therapeutic targets and prognostic/predictive biomarkers. Notably, HNSCC is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). The TME consists of different subsets of immune cells that infiltrate the tumors and interact with the tumor cells or with each other. Understanding multiple pivotal factors in HNSCC tumorigenesis and tumor progression may help define novel targets and develop more effective therapies for patients. This review provides a comprehensive overview of the latest advances in the molecular biology of HNSCC and their effects on clinical oncology; it is meant for a broad readership in the head and neck cancers field.
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Affiliation(s)
- Subramanya Pandruvada
- Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, United States.
| | - Remi Kessler
- Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Ann Thai
- Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC, United States
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29
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Osanai M, Takasawa A, Takasawa K, Kyuno D, Ono Y, Magara K. Retinoic acid metabolism in cancer: potential feasibility of retinoic acid metabolism blocking therapy. Med Mol Morphol 2023; 56:1-10. [PMID: 36592231 DOI: 10.1007/s00795-022-00345-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 12/26/2022] [Indexed: 01/03/2023]
Abstract
Retinoic acid (RA) is an active metabolite of vitamin A, which is an essential signaling molecule involved in cell fate decisions, such as differentiation, proliferation, and apoptosis, in a wide variety of cell types. Accumulated data have demonstrated that expression of RA-metabolizing enzymes, CYP26A1, B1, and C1 (cytochrome P450, family 26A1, B1, and C1, respectively), protects cells and tissues from exposure to RA through restriction of RA access to transcriptional machinery by converting RA to rapidly excreted derivatives. CYP26 enzymes play similar but separate roles in limiting the consequences of fluctuations in nutritional vitamin A. Recently, we found that RA depletion caused by expression of CYP26A1 promotes malignant behaviors of tumor cells derived from various tissues, implicating CYP26A1 as a candidate oncogene. We also showed that the expression levels of CYP26 enzymes are elevated in various types of cancer. We have provided evidence for oncogenic and cell survival properties of CYP26 enzymes, indicating that these molecules are possible therapeutic targets for CYP26-expressing malignancies.
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Affiliation(s)
- Makoto Osanai
- Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
| | - Akira Takasawa
- Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-Ku, Sapporo, 060-8556, Japan
| | - Kumi Takasawa
- Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-Ku, Sapporo, 060-8556, Japan
| | - Daisuke Kyuno
- Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-Ku, Sapporo, 060-8556, Japan
| | - Yusuke Ono
- Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-Ku, Sapporo, 060-8556, Japan
| | - Kazufumi Magara
- Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-Ku, Sapporo, 060-8556, Japan
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30
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Patel R, Didzbalis CJ, Tseng CC, Talmor G, Park RCW. Facility volume and survival: Human papilloma virus positive oropharyngeal squamous cell carcinoma. Am J Otolaryngol 2023; 44:103762. [PMID: 36628908 DOI: 10.1016/j.amjoto.2022.103762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 12/18/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND To analyze the impact of facility volume on survival for human papilloma virus positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) patients. METHODS Patients treated for HPV+ OPSCC from 2010 to 2017 were queried from the National Cancer Database. Facilities of average annual case volume <50th percentile were categorized as low-volume (LV) and >95th percentile as high-volume (HV). RESULTS 11,546 were included, with 10,305 patients (89.3 %) treated at LV and 1241 (10.7 %) at HV facilities. A greater proportion of cases involving resection of base of tongue and lingual tonsil were treated at HV (30.3 %) compared to LV (22.3 %) facilities (p < 0.001). Patients treated at a HV facility had greater percentage of clinical T4 (11.2 % vs. 8.6 %, p = 0.001) and N+ disease (90.5 % vs. 85.7 %, p < 0.001) patients. Survival analysis showed no statistically significant difference between five-year overall survival rates by facility volume (p = 0.388) for all patients. On multivariable analysis, facility volume was not associated with survival (HR: 0.968 [0.758-1.235], p = 0.791). These trends were found for both patients undergoing primary surgery or chemoradiotherapy. CONCLUSION Our data indicates that patients with HPV+ OPSCC do not experience a survival benefit with treatment at HV facility, suggesting these patients may be adequately treated at LV centers.
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Affiliation(s)
- Rushi Patel
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Christopher J Didzbalis
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Christopher C Tseng
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Guy Talmor
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Richard Chan Woo Park
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA.
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Wenhua S, Tsunematsu T, Umeda M, Tawara H, Fujiwara N, Mouri Y, Arakaki R, Ishimaru N, Kudo Y. Cancer cell-derived novel periostin isoform promotes invasion in head and neck squamous cell carcinoma. Cancer Med 2023; 12:8510-8525. [PMID: 36691359 PMCID: PMC10134278 DOI: 10.1002/cam4.5601] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 12/20/2022] [Accepted: 12/21/2022] [Indexed: 01/25/2023] Open
Abstract
It recently has been reported that partial-epithelial-mesenchymal transition (p-EMT) program is associated with metastasis in head and neck squamous cell carcinoma (HNSCC). We previously have identified POSTN (which encodes periostin) as an invasion-promoting molecule in HNSCC. Interestingly, POSTN expression is frequently observed in cancer cells with higher p-EMT score by using a previous single-cell transcriptomic data of HNSCC cases. Although it is known that POSTN has 11 splicing variants, the role of them has not been determined in HNSCC. Here, we found that HNSCC cells with EMT features expressed POSTN isoforms, Iso3 (lacking exon 17 and 21) and Iso5 (lacking exon 17), whereas fibroblast expressed Iso3 and Iso4 (lacking exon 17, 18, and 21). The expression of POSTN Iso3 and Iso4 are known to be widely observed in various cell types including stromal cells. Therefore, we focused on the role of novel cancer cell-derived POSTN isoform, Iso5, in HNSCC. Single overexpression of POSTN Iso5 as well as Iso3 promoted invasion. Surprisingly, Iso5 synergistically promoted invasion together with Iso3. Notably, Iso5 as well as Iso3 upregulated p-EMT-related genes. We suggest that a novel cancer-specific POSTN isoform lacking exon 17 (Iso5) can be a useful marker for detecting cancer cells undergoing p-EMT. Moreover, a POSTN Iso5 can be a novel target for diagnosis and therapy in HNSCC.
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Affiliation(s)
- Shao Wenhua
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Takaaki Tsunematsu
- Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Masaaki Umeda
- Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Hiroaki Tawara
- Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Natsumi Fujiwara
- Department of Oral Healthcare Promotion, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Yasuhiro Mouri
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Rieko Arakaki
- Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Naozumi Ishimaru
- Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Yasusei Kudo
- Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
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32
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Budi HS, Younus LA, Lafta MH, Parveen S, Mohammad HJ, Al-qaim ZH, Jawad MA, Parra RMR, Mustafa YF, Alhachami FR, Karampoor S, Mirzaei R. The role of miR-128 in cancer development, prevention, drug resistance, and immunotherapy. Front Oncol 2023; 12:1067974. [PMID: 36793341 PMCID: PMC9923359 DOI: 10.3389/fonc.2022.1067974] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 12/30/2022] [Indexed: 02/03/2023] Open
Abstract
A growing body of evidence has revealed that microRNA (miRNA) expression is dysregulated in cancer, and they can act as either oncogenes or suppressors under certain conditions. Furthermore, some studies have discovered that miRNAs play a role in cancer cell drug resistance by targeting drug-resistance-related genes or influencing genes involved in cell proliferation, cell cycle, and apoptosis. In this regard, the abnormal expression of miRNA-128 (miR-128) has been found in various human malignancies, and its verified target genes are essential in cancer-related processes, including apoptosis, cell propagation, and differentiation. This review will discuss the functions and processes of miR-128 in multiple cancer types. Furthermore, the possible involvement of miR-128 in cancer drug resistance and tumor immunotherapeutic will be addressed.
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Affiliation(s)
- Hendrik Setia Budi
- Department of Oral Biology, Dental Pharmacology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Laith A. Younus
- Department of Clinical Laboratory Sciences, Faculty of Pharmacy, Jabir Ibn, Hayyan Medical University, Al Najaf Al Ashraf, Iraq
| | | | - Sameena Parveen
- Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan, Saudi Arabia
| | | | | | | | | | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, Iraq
| | - Firas Rahi Alhachami
- Radiology Department, College of Health and Medical Technology, Al-Ayen University, Thi-Qar, Nasiriyah, Iraq
| | - Sajad Karampoor
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Rasoul Mirzaei
- Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
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Colevas SM, Merfeld EC, Pflum ZE, Gessert TG, Wieland AM, Glazer TA, Burr AR, Harari PM, Hartig GK. Functional Outcomes After Transoral Plus Lateral Pharyngotomy Approach for Advanced Oral and Oropharyngeal Tumors. OTO Open 2023; 7:e35. [PMID: 36998565 PMCID: PMC10046711 DOI: 10.1002/oto2.35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 01/05/2023] [Accepted: 02/01/2023] [Indexed: 02/25/2023] Open
Abstract
Objective The aim of this study was to evaluate our institutional experience with the combined transoral plus lateral pharyngotomy (TO+LP) approach in a subset of patients with advanced or recurrent oral and oropharyngeal malignancy. Study Design A retrospective study of procedures utilizing TO+LP for cancer resection between January 2007 and July 2019. Setting Tertiary academic medical center. Methods Thirty-one patients underwent a TO+LP approach for the resection of oral and oropharyngeal tumors. Functional and oncologic outcomes were analyzed. Results Eighteen (58.1%) patients were treated with TO+LP for recurrent disease. Twenty-nine required free tissue transfer and 2 (6.5%) had positive margins. The median time to decannulation was 22 days (range 6-100 days). Thirteen (41.9%) patients still required enteral feeding at their most recent follow-up. Patients without a history of prior radiation were decannulated sooner (p = .009) and were less likely to require enteral feeding at the first postoperative follow-up (p = .034) than those who had prior head and neck radiotherapy. Conclusion A TO+LP approach can be used to achieve good functional and oncologic results for selected patients with advanced or recurrent oral and oropharyngeal cancer when minimally invasive options such as transoral robotic surgery, transoral laser microsurgery, or radiotherapy are not possible.
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Affiliation(s)
- Sophia M. Colevas
- Department of Surgery, Division of Otolaryngology–Head and Neck Surgery University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
| | - Emily C. Merfeld
- Department of Human Oncology University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
| | - Zachary E. Pflum
- Department of Surgery, Division of Otolaryngology–Head and Neck Surgery University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
| | - Thomas G. Gessert
- Department of Surgery, Division of Otolaryngology–Head and Neck Surgery University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
| | - Aaron M. Wieland
- Department of Surgery, Division of Otolaryngology–Head and Neck Surgery University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
| | - Tiffany A. Glazer
- Department of Surgery, Division of Otolaryngology–Head and Neck Surgery University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
| | - Adam R. Burr
- Department of Human Oncology University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
| | - Paul M. Harari
- Department of Human Oncology University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
| | - Gregory K. Hartig
- Department of Human Oncology University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA
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Sachdeva A, Dhawan D, Jain GK, Yerer MB, Collignon TE, Tewari D, Bishayee A. Novel Strategies for the Bioavailability Augmentation and Efficacy Improvement of Natural Products in Oral Cancer. Cancers (Basel) 2022; 15:cancers15010268. [PMID: 36612264 PMCID: PMC9818473 DOI: 10.3390/cancers15010268] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
Oral cancer is emerging as a major cause of mortality globally. Oral cancer occupies a significant proportion of the head and neck, including the cheeks, tongue, and oral cavity. Conventional methods in the treatment of cancer involve surgery, radiotherapy, and immunotherapy, and these have not proven to completely eradicate cancerous cells, may lead to the reoccurrence of oral cancer, and possess numerous adverse side effects. Advancements in novel drug delivery approaches have gained popularity in cancer management with an increase in the number of cases associated with oral cancer. Natural products are potent sources for drug discovery, especially for anticancer drugs. Natural product delivery has major challenges due to its low solubility, poor absorption, inappropriate size, instability, poor permeation, and first-pass metabolism. Therefore, it is of prime importance to investigate novel treatment approaches for the delivery of bioactive natural products. Nanotechnology is an advanced method of delivering cancer therapy with minimal damage to normal cells while targeting cancer cells. Therefore, the present review elaborates on the advancements in novel strategies for natural product delivery that lead to the significant enhancement of bioavailability, in vivo activity, and fewer adverse events for the prevention and treatment of oral cancer. Various approaches to accomplish the desired results involve size reduction, surface property modification, and polymer attachment, which collectively result in the higher stability of the formulation.
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Affiliation(s)
- Alisha Sachdeva
- Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, Delhi Pharmaceutical Sciences and Research University, New Delhi 110 017, India
| | - Dimple Dhawan
- Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, Delhi Pharmaceutical Sciences and Research University, New Delhi 110 017, India
| | - Gaurav K. Jain
- Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, Delhi Pharmaceutical Sciences and Research University, New Delhi 110 017, India
- Center for Advanced Formulation Development, Delhi Pharmaceutical Sciences and Research University, New Delhi 110 017, India
| | - Mükerrem Betül Yerer
- Department of Pharmacology, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey
| | - Taylor E. Collignon
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Devesh Tewari
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi 110 017, India
- Correspondence: or (D.T.); or (A.B.)
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
- Correspondence: or (D.T.); or (A.B.)
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35
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GATA6 regulates expression of annexin A10 (ANXA10) associated with epithelial–mesenchymal transition of oral squamous cell carcinoma. Arch Oral Biol 2022; 144:105569. [DOI: 10.1016/j.archoralbio.2022.105569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/03/2022] [Accepted: 10/07/2022] [Indexed: 11/16/2022]
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36
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Farris JC, Steber CR, Black PJ, Chan MD, Ververs JD, Cramer CK, Browne JD, Waltonen JD, Sullivan CA, Patwa HS, Laxton AW, Tatter SB, Frizzell BA, Porosnicu M, Lycan TW, Greven KM, Hughes RT. Intensity-modulated radiotherapy with planned Gamma Knife radiosurgery boost for head and neck cancer with extensive disease in proximity to critical structures. Head Neck 2022; 44:2571-2578. [PMID: 36047613 PMCID: PMC9813854 DOI: 10.1002/hed.27176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 07/14/2022] [Accepted: 08/16/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND To describe intensity-modulated radiotherapy (IMRT) with Gamma Knife Radiosurgery (GKRS) boost for locally advanced head and neck cancer (HNC) with disease near dose-limiting structures. METHODS Patients with HNC treated with IMRT/GKRS as part of a combined modality approach between 2011 and 2021 were reviewed. Local control, overall survival and disease-specific survival were estimated using the Kaplan Meier method. RESULTS Twenty patients were included. Nineteen patients had T3-4 tumors. Median follow-up was 26.3 months. GKRS site control was 95%. Two patients progressed at the treated primary site, one patient failed at the edge of the GKRS treatment volume, with no perineural or intracranial failure. 2-year OS was 94.7% (95% CI: 85.2%-100%). Concurrent chemotherapy was given in nine patients (45%). One patient (5%) received induction/concurrent chemotherapy. Brain radionecrosis occurred in three patients, one of which was biopsy-proven. CONCLUSIONS IMRT plus GKRS boost results in excellent disease control near critical structures with minimal toxicity.
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Affiliation(s)
- Joshua C. Farris
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Cole R. Steber
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Paul J. Black
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Michael D. Chan
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - James D. Ververs
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Christina K. Cramer
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - James D. Browne
- Department OtolaryngologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Joshua D. Waltonen
- Department OtolaryngologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | | | - Hafiz S. Patwa
- Department OtolaryngologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Adrian W. Laxton
- Department of NeurosurgeryWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Stephen B. Tatter
- Department of NeurosurgeryWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Bart A. Frizzell
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Mercedes Porosnicu
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA,Department of Internal Medicine, Section of Hematology and OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Thomas W. Lycan
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA,Department of Internal Medicine, Section of Hematology and OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Kathryn M. Greven
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
| | - Ryan T. Hughes
- Department of Radiation OncologyWake Forest School of MedicineWinston SalemNorth CarolinaUSA
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Jin Y, Jung SN, Lim MA, Oh C, Piao Y, Kim HJ, Nguyena Q, Kang YE, Chang JW, Won HR, Koo BS. SHMT2 Induces Stemness and Progression of Head and Neck Cancer. Int J Mol Sci 2022; 23:ijms23179714. [PMID: 36077112 PMCID: PMC9456418 DOI: 10.3390/ijms23179714] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/20/2022] [Accepted: 08/24/2022] [Indexed: 11/16/2022] Open
Abstract
Various enzymes in the one-carbon metabolic pathway are closely related to the development of tumors, and they can all be potential targets for cancer therapy. Serine hydroxymethyltransferase2 (SHMT2), a key metabolic enzyme, is very important for the proliferation and growth of cancer cells. However, the function and mechanism of SHMT2 in head and neck cancer (HNC) are not clear. An analysis of The Cancer Genome Atlas (TCGA) data showed that the expression of SHMT2 was higher in tumor tissue than in normal tissue, and its expression was significantly associated with male sex, aggressive histological grade, lymph node metastasis, distant metastasis, advanced TNM stage, and lymphovascular invasion in HNC. SHMT2 knockdown in FADU and SNU1041 cell lines significantly inhibited cell proliferation, colony formation, migration, and invasion. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using TCGA data revealed that SHMT2 was closely related to cancer stem cell regulation and maintenance. Furthermore, we found that silencing SHMT2 inhibited the expression of stemness markers and tumor spheroid formation compared with a control group. On the contrary, stemness markers were significantly increased after SHMT2 overexpression in HEP-2 cells. Interestingly, we found that knocking down SHMT2 reduced the expression of genes related to the Notch and Wnt pathways. Finally, silencing SHMT2 significantly reduced tumor growth and decreased stemness markers in a xenograft model. Taken together, our study suggests that targeting SHMT2 may play an important role in inhibiting HNC progression.
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Affiliation(s)
- Yanli Jin
- Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - Seung-Nam Jung
- Department of Otolaryngology—Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - Mi Ae Lim
- Department of Otolaryngology—Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - Chan Oh
- Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - Yudan Piao
- Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - Hae Jong Kim
- Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - QuocKhanh Nguyena
- Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - Yea Eun Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - Jae Won Chang
- Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea
- Department of Otolaryngology—Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - Ho-Ryun Won
- Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea
- Department of Otolaryngology—Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon 35015, Korea
| | - Bon Seok Koo
- Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea
- Department of Otolaryngology—Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon 35015, Korea
- Correspondence: ; Tel.: +82-42-280-7690
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Callahan SC, Kochat V, Liu Z, Raman AT, Divenko M, Schulz J, Terranova CJ, Ghosh AK, Tang M, Johnson FM, Wang J, Skinner HD, Pickering CR, Myers JN, Rai K. High enhancer activity is an epigenetic feature of HPV negative atypical head and neck squamous cell carcinoma. Front Cell Dev Biol 2022; 10:936168. [PMID: 35927986 PMCID: PMC9343809 DOI: 10.3389/fcell.2022.936168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 06/27/2022] [Indexed: 11/13/2022] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with significant mortality and frequent recurrence. Prior efforts to transcriptionally classify HNSCC into groups of varying prognoses have identified four accepted molecular subtypes of the disease: Atypical (AT), Basal (BA), Classical (CL), and Mesenchymal (MS). Here, we investigate the active enhancer landscapes of these subtypes using representative HNSCC cell lines and identify samples belonging to the AT subtype as having increased enhancer activity compared to the other 3 HNSCC subtypes. Cell lines belonging to the AT subtype are more resistant to enhancer-blocking bromodomain inhibitors (BETi). Examination of nascent transcripts reveals that both AT TCGA tumors and cell lines express higher levels of enhancer RNA (eRNA) transcripts for enhancers controlling BETi resistance pathways, such as lipid metabolism and MAPK signaling. Additionally, investigation of higher-order chromatin structure suggests more enhancer-promoter (E-P) contacts in the AT subtype, including on genes identified in the eRNA analysis. Consistently, known BETi resistance pathways are upregulated upon exposure to these inhibitors. Together, our results identify that the AT subtype of HNSCC is associated with higher enhancer activity, resistance to enhancer blockade, and increased signaling through pathways that could serve as future targets for sensitizing HNSCC to BET inhibition.
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Affiliation(s)
- S. Carson Callahan
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Veena Kochat
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Zhiyi Liu
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Ayush T. Raman
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Graduate Program in Quantitative Sciences, Baylor College of Medicine, Houston, TX, United States
- Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, MA, United States
| | - Margarita Divenko
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jonathan Schulz
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Christopher J. Terranova
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Archit K. Ghosh
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Ming Tang
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, United States
| | - Faye M. Johnson
- The University of Texas Graduate School of Biomedical Sciences, Houston, TX, United States
- Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jing Wang
- The University of Texas Graduate School of Biomedical Sciences, Houston, TX, United States
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Heath D Skinner
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Department of Radiation Oncology, University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, PA, United States
| | - Curtis R. Pickering
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- The University of Texas Graduate School of Biomedical Sciences, Houston, TX, United States
| | - Jeffrey N. Myers
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- The University of Texas Graduate School of Biomedical Sciences, Houston, TX, United States
| | - Kunal Rai
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States
- The University of Texas Graduate School of Biomedical Sciences, Houston, TX, United States
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Vieira GV, Somera dos Santos F, Lepique AP, da Fonseca CK, Innocentini LMAR, Braz-Silva PH, Quintana SM, Sales KU. Proteases and HPV-Induced Carcinogenesis. Cancers (Basel) 2022; 14:cancers14133038. [PMID: 35804810 PMCID: PMC9264903 DOI: 10.3390/cancers14133038] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/01/2022] [Accepted: 06/15/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary Human papillomavirus (HPV) infection is a sexually transmitted disease with high prevalence worldwide. Although most HPV infections do not lead to cancer, some HPV types are correlated with the majority of cervical cancers, and with some anogenital and oropharyngeal cancers. Moreover, enzymes known as proteases play an essential role in the pathogenic process in HPV-induced carcinogenesis. This review highlights the role of proteases and recent epidemiological data regarding HPV-dependent carcinogenesis. Abstract Persistent infection with Human papillomavirus (HPV) is the main etiologic factor for pre-malignant and malignant cervical lesions. Moreover, HPV is also associated with oropharynx and other anogenital carcinomas. Cancer-causing HPV viruses classified as group 1 carcinogens include 12 HPV types, with HPV 16 and 18 being the most prevalent. High-risk HPVs express two oncoproteins, E6 and E7, the products of which are responsible for the inhibition of p53 and pRB proteins, respectively, in human keratinocytes and cellular immortalization. p53 and pRB are pleiotropic proteins that regulate the activity of several signaling pathways and gene expression. Among the important factors that are augmented in HPV-mediated carcinogenesis, proteases not only control processes involved in cellular carcinogenesis but also control the microenvironment. For instance, genetic polymorphisms of matrix metalloproteinase 1 (MMP-1) are associated with carcinoma invasiveness. Similarly, the serine protease inhibitors hepatocyte growth factor activator inhibitor-1 (HAI-1) and -2 (HAI-2) have been identified as prognostic markers for HPV-dependent cervical carcinomas. This review highlights the most crucial mechanisms involved in HPV-dependent carcinogenesis, and includes a section on the proteolytic cascades that are important for the progression of this disease and their impact on patient health, treatment, and survival.
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Affiliation(s)
- Gabriel Viliod Vieira
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (G.V.V.); (C.K.d.F.); (L.M.A.R.I.)
| | - Fernanda Somera dos Santos
- Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (F.S.d.S.); (S.M.Q.)
| | - Ana Paula Lepique
- Department of Immunology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil;
| | - Carol Kobori da Fonseca
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (G.V.V.); (C.K.d.F.); (L.M.A.R.I.)
| | - Lara Maria Alencar Ramos Innocentini
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (G.V.V.); (C.K.d.F.); (L.M.A.R.I.)
- Clinical Hospital of Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto 14049-900, SP, Brazil
| | - Paulo Henrique Braz-Silva
- Department of Stomatology, School of Dentistry, University of Sao Paulo, São Paulo 05508-000, SP, Brazil;
- Laboratory of Virology, Institute of Tropical Medicine of Sao Paulo, School of Medicine, University of Sao Paulo, Sao Paulo 05403-000, SP, Brazil
| | - Silvana Maria Quintana
- Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (F.S.d.S.); (S.M.Q.)
| | - Katiuchia Uzzun Sales
- Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, SP, Brazil; (G.V.V.); (C.K.d.F.); (L.M.A.R.I.)
- Correspondence: ; Tel.: +55-16-3315-9113
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Getz KR, Bellile E, Zarins KR, Chinn SB, Taylor JMG, Rozek LS, Wolf GT, Mondul AM. The association between inflammatory biomarkers and statin use among patients with head and neck squamous cell carcinoma. Head Neck 2022; 44:1393-1403. [PMID: 35338544 PMCID: PMC9088158 DOI: 10.1002/hed.27040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 02/08/2022] [Accepted: 03/09/2022] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Tumor-infiltrating lymphocytes (TILs) and cytokines are associated with prognosis among patients with head and neck squamous cell carcinoma (HNSCC). Statins (cholesterol-lowering drugs) may improve HNSCC prognosis, particularly in human papillomavirus (HPV)-positive cases, but the mechanism remains unclear. METHODS Statin use was collected from medical records for HNSCC cases (2008-2014). TILs were counted in tumor tissue, and a total weighted score (TILws) was created. Cytokines were measured in blood. The associations between statins and biomarkers were estimated using logistic (biomarker categories: <median, ≥median) and linear regression models (log-transformed continuous biomarkers) adjusted for age, smoking, and comorbidities. RESULTS We observed a positive association between statins and TILs among HPV-positive patients (TILws odds ratio [OR] = 2.80; 95% CI = 1.03-7.61), but no association among HPV-negative patients. We observed no association between statins and cytokines. CONCLUSIONS Statins may influence TILs in HPV-positive patients. This may be the mechanism through which they improve prognosis in HPV-positive HNSCC patients.
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Affiliation(s)
- Kayla R Getz
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Emily Bellile
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Katie R Zarins
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Steven B Chinn
- Department of Otolaryngology, University of Michigan, Ann Arbor, Michigan, USA
| | - Jeremy M G Taylor
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Laura S Rozek
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.,Department of Otolaryngology, University of Michigan, Ann Arbor, Michigan, USA
| | - Gregory T Wolf
- Department of Otolaryngology, University of Michigan, Ann Arbor, Michigan, USA
| | - Alison M Mondul
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
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Adam DP, Grudzinski J, Bormett I, Cox BL, Marsh IR, Bradshaw TJ, Harari PM, Bednarz B. Validation of Monte Carlo 131 I radiopharmaceutical dosimetry workflow using a 3D printed anthropomorphic head and neck phantom. Med Phys 2022; 49:5491-5503. [PMID: 35607296 PMCID: PMC9388595 DOI: 10.1002/mp.15699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 04/11/2022] [Accepted: 04/14/2022] [Indexed: 11/11/2022] Open
Abstract
Purpose Approximately 50% of head and neck cancer (HNC) patients will experience loco‐regional disease recurrence following initial courses of therapy. Retreatment with external beam radiotherapy (EBRT) is technically challenging and may be associated with a significant risk of irreversible damage to normal tissues. Radiopharmaceutical therapy (RPT) is a potential method to treat recurrent HNC in conjunction with EBRT. Phantoms are used to calibrate and add quantification to nuclear medicine images, and anthropomorphic phantoms can account for both the geometrical and material composition of the head and neck. In this study, we present the creation of an anthropomorphic, head and neck, nuclear medicine phantom, and its characterization for the validation of a Monte Carlo, SPECT image‐based, 131I RPT dosimetry workflow. Methods 3D‐printing techniques were used to create the anthropomorphic phantom from a patient CT dataset. Three 131I SPECT/CT imaging studies were performed using a homogeneous, Jaszczak, and an anthropomorphic phantom to quantify the SPECT images using a GE Optima NM/CT 640 with a high energy general purpose collimator. The impact of collimator detector response (CDR) modeling and volume‐based partial volume corrections (PVCs) upon the absorbed dose was calculated using an image‐based, Geant4 Monte Carlo RPT dosimetry workflow and compared against a ground truth scenario. Finally, uncertainties were quantified in accordance with recent EANM guidelines. Results The 3D‐printed anthropomorphic phantom was an accurate re‐creation of patient anatomy including bone. The extrapolated Jaszczak recovery coefficients were greater than that of the 3D‐printed insert (∼22.8 ml) for both the CDR and non‐CDR cases (with CDR: 0.536 vs. 0.493, non‐CDR: 0.445 vs. 0.426, respectively). Utilizing Jaszczak phantom PVCs, the absorbed dose was underpredicted by 0.7% and 4.9% without and with CDR, respectively. Utilizing anthropomorphic phantom recovery coefficient overpredicted the absorbed dose by 3% both with and without CDR. All dosimetry scenarios that incorporated PVC were within the calculated uncertainty of the activity. The uncertainties in the cumulative activity ranged from 23.6% to 106.4% for Jaszczak spheres ranging in volume from 0.5 to 16 ml. Conclusion The accuracy of Monte Carlo‐based dosimetry for 131I RPT in HNC was validated with an anthropomorphic phantom. In this study, it was found that Jaszczak‐based PVCs were sufficient. Future applications of the phantom could involve 3D printing and characterizing patient‐specific volumes for more personalized RPT dosimetry estimates.
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Affiliation(s)
- David P Adam
- Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, 53705
| | - Joseph Grudzinski
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, 53705
| | - Ian Bormett
- Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, 53705
| | - Benjamin L Cox
- Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, 53705
| | - Ian R Marsh
- Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, 53705
| | - Tyler J Bradshaw
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, 53705
| | - Paul M Harari
- Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, 53705
| | - Bryan Bednarz
- Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, 53705
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Brunese L, Mercaldo F, Reginelli A, Santone A. A novel methodology for head and neck carcinoma treatment stage detection by means of model checking. Artif Intell Med 2022; 127:102263. [DOI: 10.1016/j.artmed.2022.102263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 02/18/2022] [Accepted: 02/23/2022] [Indexed: 11/02/2022]
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Xi S, Yang YG, Suo J, Sun T. Research Progress on Gene Editing Based on Nano-Drug Delivery Vectors for Tumor Therapy. Front Bioeng Biotechnol 2022; 10:873369. [PMID: 35419357 PMCID: PMC8996155 DOI: 10.3389/fbioe.2022.873369] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 03/11/2022] [Indexed: 12/25/2022] Open
Abstract
Malignant tumors pose a serious threat to human health and have high fatality rates. Conventional clinical anti-tumor treatment is mainly based on traditional surgery, chemotherapy, radiotherapy, and interventional therapy, and even though these treatment methods are constantly updated, a satisfactory efficacy is yet to be obtained. Therefore, research on novel cancer treatments is being actively pursued. We review the classification of gene therapies of malignant tumors and their advantages, as well as the development of gene editing techniques. We further reveal the nano-drug delivery carrier effect in improving the efficiency of gene editing. Finally, we summarize the progress in recent years of gene editing techniques based on nano-drug delivery carriers in the treatment of various malignant tumors, and analyze the prospects of the technique and its restricting factors.
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Affiliation(s)
- Shiwen Xi
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, China
- Gastrointestinal Surgical Department, The First Hospital, Jilin University, Changchun, China
| | - Yong-Guang Yang
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, China
- National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China
- International Center of Future Science, Jilin University, Changchun, China
| | - Jian Suo
- Gastrointestinal Surgical Department, The First Hospital, Jilin University, Changchun, China
| | - Tianmeng Sun
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, China
- National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China
- International Center of Future Science, Jilin University, Changchun, China
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Habib I, Anjum F, Mohammad T, Sulaimani MN, Shafie A, Almehmadi M, Yadav DK, Sohal SS, Hassan MI. Differential gene expression and network analysis in head and neck squamous cell carcinoma. Mol Cell Biochem 2022; 477:1361-1370. [PMID: 35142951 DOI: 10.1007/s11010-022-04379-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 01/27/2022] [Indexed: 10/19/2022]
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with a poor prognosis, whose biomarkers have not been studied in great detail. We have collected genomic data of HNSCC patients from The Cancer Genome Atlas (TCGA) and analyzed them to get deeper insights into the gene expression pattern. Initially, 793 differentially expressed genes (DEGs) were categorized, and their enrichment analysis was performed. Later, a protein-protein interaction network for the DEGs was constructed using the STRING plugin in Cytoscape to study their interactions. A set of 10 hub genes was selected based on Maximal Clique Centrality score, and later their survival analysis was studied. The elucidated set of 10 genes, i.e., PRAME, MAGEC2, MAGEA12, LHX1, MAGEA3, CSAG1, MAGEA6, LCE6A, LCE2D, LCE2C, referred to as potential candidates to be explored as HNSCC biomarkers. The Kaplan-Meier overall survival of the selected genes suggested that the alterations in the candidate genes were linked to the decreased survival of the HNSCC patients. Altogether, the results of this study signify that the genomic alterations and differential expression of the selected genes can be explored in therapeutic interpolations of HNSCC, exploiting early diagnosis and target-propelled therapy.
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Affiliation(s)
- Insan Habib
- Department of Computer Science, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India
| | - Farah Anjum
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia
| | - Taj Mohammad
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India
| | - Md Nayab Sulaimani
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India
| | - Alaa Shafie
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia
| | - Mazen Almehmadi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia
| | - Dharmendra Kumar Yadav
- College of Pharmacy, Gachon University of Medicine and Science, Hambakmoeiro, Yeonsu-gu, Incheon City, 21924, South Korea.
| | - Sukhwinder Singh Sohal
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Australia
| | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
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Early Response Prediction of Multiparametric Functional MRI and 18F-FDG-PET in Patients with Head and Neck Squamous Cell Carcinoma Treated with (Chemo)Radiation. Cancers (Basel) 2022; 14:cancers14010216. [PMID: 35008380 PMCID: PMC8750157 DOI: 10.3390/cancers14010216] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 12/20/2021] [Accepted: 12/23/2021] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Patients with locally-advanced head and neck squamous cell carcinoma (HNSCC) have variable responses to (chemo)radiotherapy. A reliable early prediction of outcomes allows for enhancing treatment efficacy and follow-up monitoring. Early tumoral changes can be captured by functional imaging (DWI/IVIM/DCE/18F-FDG-PET-CT) parameters, which allow for the construction of accurate patient-specific prognostic models for locoregional recurrence-free survival, distant metastasis-free survival and overall survival. We also present clinical applicable risk stratification in high/medium/low risks for these patient outcomes. This can enable personalized treatment (adaptation) management early on during treatment, improve counseling and enhance patient-specific post-therapy monitoring. Abstract Background: Patients with locally-advanced head and neck squamous cell carcinoma (HNSCC) have variable responses to (chemo)radiotherapy. A reliable prediction of outcomes allows for enhancing treatment efficacy and follow-up monitoring. Methods: Fifty-seven histopathologically-proven HNSCC patients with curative (chemo)radiotherapy were prospectively included. All patients had an MRI (DW,-IVIM, DCE-MRI) and 18F-FDG-PET/CT before and 10 days after start-treatment (intratreatment). Primary tumor functional imaging parameters were extracted. Univariate and multivariate analysis were performed to construct prognostic models and risk stratification for 2 year locoregional recurrence-free survival (LRFFS), distant metastasis-free survival (DMFS) and overall survival (OS). Model performance was measured by the cross-validated area under the receiver operating characteristic curve (AUC). Results: The best LRFFS model contained the pretreatment imaging parameters ADC_kurtosis, Kep and SUV_peak, and intratreatment imaging parameters change (Δ) Δ-ADC_skewness, Δ-f, Δ-SUV_peak and Δ-total lesion glycolysis (TLG) (AUC = 0.81). Clinical parameters did not enhance LRFFS prediction. The best DMFS model contained pretreatment ADC_kurtosis and SUV_peak (AUC = 0.88). The best OS model contained gender, HPV-status, N-stage, pretreatment ADC_skewness, D, f, metabolic-active tumor volume (MATV), SUV_mean and SUV_peak (AUC = 0.82). Risk stratification in high/medium/low risk was significantly prognostic for LRFFS (p = 0.002), DMFS (p < 0.001) and OS (p = 0.003). Conclusions: Intratreatment functional imaging parameters capture early tumoral changes that only provide prognostic information regarding LRFFS. The best LRFFS model consisted of pretreatment, intratreatment and Δ functional imaging parameters; the DMFS model consisted of only pretreatment functional imaging parameters, and the OS model consisted ofHPV-status, gender and only pretreatment functional imaging parameters. Accurate clinically applicable risk stratification calculators can enable personalized treatment (adaptation) management, early on during treatment, improve counseling and enhance patient-specific post-therapy monitoring.
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Semkin VA, Vozgoment OV, Nadtochiy AG, Ivanova AA. [Lymphotropic therapy in the treatment of patients with postoperative secondary lymphedema of the maxillofacial region]. STOMATOLOGIIA 2022; 101:47-52. [PMID: 35943500 DOI: 10.17116/stomat202210104147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
OBJECTIVE The aim of study was to improve the effectiveness of treatment of patients with secondary postoperative lymphedema of the maxillofacial region using lymphotropic therapy. MATERIAL AND METHODS During 2020-2021 8 patients aged 40 to 70 years with secondary postoperative lymphedema of the maxillofacial region were treated in the Central Research Institute of Dentistry and Maxillofacial Surgery. The article presents the clinical and ultrasound results of a study of the effectiveness of the lymphotropic therapy in the treatment of patients with secondary lymphedema of the maxillofacial region. RESULTS Six patients with an early stage of lymphedema had a complete regression of edema and normalization of the ultrasound picture of the soft tissues of the maxillofacial region. In 2 patients with late-stage lymphedema there was a regression of edema, but the preservation of residual swelling of soft tissues and signs of fibro-fatty transformation of soft tissues were revealed on ultrasound examination. CONCLUSION Lymphotropic therapy with antifibrotic and anti-inflammatory drugs is one of the effective methods of treating postoperative secondary lymphedema of the maxillofacial region at the early stages of the disease.
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Affiliation(s)
- V A Semkin
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia
| | - O V Vozgoment
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia
- Russian Medical Academy of Continuous Professional Education, Moscow, Russia
| | - A G Nadtochiy
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia
| | - A A Ivanova
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia
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Jo S, Yeo MS, Shin YK, Shin KH, Kim SH, Kim HR, Kim SJ, Cho SR. Therapeutic Singing as a Swallowing Intervention in Head and Neck Cancer Patients With Dysphagia. Integr Cancer Ther 2021; 20:15347354211065040. [PMID: 34903088 PMCID: PMC8679067 DOI: 10.1177/15347354211065040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: Head and neck cancer patients often suffer from dysphagia after surgery and
radiotherapy. A singing-enhanced swallowing protocol was established to
improve their swallowing function. This study aimed to evaluate the
beneficial effects of therapeutic singing on dysphagia in head and neck
cancer (HNC) patients. Methods: Patients who participated in this study were allocated to the intervention
group (15 patients) and the control group (13 patients). Patients assigned
to the intervention group received therapeutic singing 3 times per week for
4 weeks. Each group was divided into 2 subgroups, including the oral cavity
cancer group and the pharyngeal cancer group. The patients’ vocal functions
were evaluated in maximum phonation time, pitch, intensity, jitter, shimmer,
harmonics to noise ratio, and laryngeal diadochokinesis (L-DDK). To evaluate
swallowing function, videofluoroscopic swallowing study was done, and the
results were analyzed by videofluoroscopic dysphagia scale (VDS) and dynamic
imaging grade of swallowing toxicity (DIGEST). Results: Among the voice parameters, L-DDK of the intervention group significantly
increased compared to that of the control group. Swallowing functions of the
intervention group were significantly improved in VDS and DIGEST after the
intervention. Detailed items of VDS and DIGEST showed improvements
especially in the pharyngeal phase score of VDS, such as laryngeal
elevation, pharyngeal transit time, and aspiration. In addition, the
pharyngeal cancer group showed significant improvements in VDS and DIGEST
scores after the intervention. Conclusions: Our outcomes highlight the beneficial effects of singing for HNC patients
with dysphagia. The notable improvements in the pharyngeal phase suggest
that therapeutic singing would be more appropriate for HNC patients who need
to improve their intrinsic muscle movements of vocal fold and laryngeal
elevation.
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Affiliation(s)
- Seongmoon Jo
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea.,Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Myung Sun Yeo
- Department of Music Therapy, Graduate School, Ewha Womans University, Seoul, Korea.,Music Therapy Education, Graduate School of Education, Ewha Womans University, Seoul, Korea
| | - Yoon-Kyum Shin
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea.,Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Ki Hun Shin
- Yonsei University College of Medicine, Seoul, Korea
| | - Se-Heon Kim
- Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Ryun Kim
- Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Soo Ji Kim
- Department of Music Therapy, Graduate School, Ewha Womans University, Seoul, Korea.,Music Therapy Education, Graduate School of Education, Ewha Womans University, Seoul, Korea
| | - Sung-Rae Cho
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea.,Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.,Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Korea
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Li W, Wang T, Zhang X, Zhu J, Li XY, Peng F, Dai J, Wang J, Zhang L, Wang Y, Chen X, Xue T, Ding C, Wang C, Jiao L. Distinct lipid profiles of radiation-induced carotid plaques from atherosclerotic carotid plaques revealed by UPLC-QTOF-MS and DESI-MSI. Radiother Oncol 2021; 167:25-33. [PMID: 34902371 DOI: 10.1016/j.radonc.2021.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 11/29/2021] [Accepted: 12/03/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND PURPOSE Radiotherapy is a standard treatment for head and neck tumors that significantly increases patients' long-term survival rates. However, late cerebrovascular complications, especially carotid artery stenosis (CAS), have gained increasing attention. Investigation of biomarkers of radiation-induced CAS may help to elucidate the mechanism by which radiation induces damage to blood vessels and identify possible preventive measures against such damage. MATERIALS AND METHODS In this study, we used lipidomics strategy to characterize the lipids present in 8 radiation-induced carotid plaques (RICPs) and 12 atherosclerotic carotid plaques (ASCPs). We also used desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to map the spatial distribution of the screened lipids from 2 RICPs samples and 2 ASCPs samples. RESULTS The results showed that 31 metabolites in RICPs were significantly higher than that in ASCPs, 24 of which were triglycerides (TGs). We used four machine learning models to select potential indicators from the 31 metabolites. Six TGs [TG(17:2/17:2/18:0), TG(17:1/17:2/18:0), TG(17:0/17:2/18:0), TG(17:2/17:2/20:0), TG(17:1/17:2/20:0), TG(15:0/22:0/22:2)] were found to be the potential markers for distinguishing RICPs and ASCPs (AUC = 0.83). The DESI-MSI results suggested that the 6 TGs were localized in the collagen fiber regions and confirmed the differences of these TGs between the two kinds of plaques. CONCLUSIONS The 6 TGs primarily localized in the collagen fiber regions of plaques are likely to be potential indicators for the differentiation of RICPs from ASCPs which may have implications in the mechanisms and possible preventive measures against RICPs.
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Affiliation(s)
- Wei Li
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Liaocheng Brain Hospital, China; Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Tao Wang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xiao Zhang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Junge Zhu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xu-Ying Li
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Fangda Peng
- National Center for Occupational Safety and Health, NHC (National Center for Occupational Medicine of Coal Industry, NHC), Beijing, China
| | - Jing Dai
- National Center for Occupational Safety and Health, NHC (National Center for Occupational Medicine of Coal Industry, NHC), Beijing, China
| | - Jiyue Wang
- Department of Neurosurgery, Liaocheng Brain Hospital, China
| | - Liyong Zhang
- Department of Neurosurgery, Liaocheng Brain Hospital, China
| | - Yabing Wang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xianyang Chen
- Zhongguancun Biological and Medical Big Data Center, Beijing, China; Bao Feng Key Laboratory of Genetics and Metabolism, Beijing, China
| | - Teng Xue
- Zhongguancun Biological and Medical Big Data Center, Beijing, China; Zhongyuanborui Key Laborotory of Genetics and Metabolism, Guangdong-Macao In-depth Cooperation Zone in Hengqin, China
| | - Chunguang Ding
- National Center for Occupational Safety and Health, NHC (National Center for Occupational Medicine of Coal Industry, NHC), Beijing, China.
| | - Chaodong Wang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Diseases, Beijing, China.
| | - Liqun Jiao
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, Beijing, China; China International Neuroscience Institute (China-INI), Beijing, China.
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Adeola HA, Sabiu S, Aruleba RT, Adekiya TA, Adefuye AO, Adefuye OJ, Oyinloye BE. Phytodentistry in Africa: prospects for head and neck cancers. CLINICAL PHYTOSCIENCE 2021. [DOI: 10.1186/s40816-021-00254-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Orthodox dentistry has undergone significant changes in recent times with the introduction of various omics and molecular targeted therapies both at the experimental/trial and clinical implementation level. Although, significant milestones have been achieved in the molecular dentistry field in the past decade, there remains a dearth of application of phytopharmacological innovation in personalized and targeted therapies for dental diseases.
Main body
From time immemorial, plant products have long been an integral aspect of dental practice ranging from chewing sticks/herbal kinds of toothpaste to dental/impression materials. The current era of precision medicine seeks to apply a multipronged molecular and bio-computational approaches to solve fundamental medical problems that have hitherto remained difficult. Remarkable changes in the molecular/omics era, have transformed empirical therapies into personalized/individualized ones. Furthermore, the combinatorial application and the widespread introduction of high-throughput molecular tools such as pharmacogenomics, phytopharmacology, metabolomics, mathematical modelling, and genetic engineering inter alia, has tremendously improved the diagnostic and therapeutic landscape of medicine. Additionally, the variable molecular epidemiology of diseases among different population and emerging molecular evidence warrants the use of customized novel theranostic techniques. Unfortunately, the footprint of such emerging application is sparse in dental diseases such as maxillofacial cancers.
Conclusion
Hence, this review seeks to evaluate the potential application of phytopharmacological approaches to head and neck cancers in a resource-limited environment, such as Africa.
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Lee JW, Lee HY. Targeting Cancer Stem Cell Markers or Pathways: A Potential Therapeutic Strategy for Oral Cancer Treatment. Int J Stem Cells 2021; 14:386-399. [PMID: 34711702 PMCID: PMC8611309 DOI: 10.15283/ijsc21084] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/14/2021] [Accepted: 06/05/2021] [Indexed: 12/16/2022] Open
Abstract
Cancer stem cells (CSCs) are a small subset of cancer cells with stem cell-like properties, self-renewal potential, and differentiation capacity into multiple cell types. Critical genetic alterations or aberrantly activated signaling pathways associated with drug resistance and recurrence have been observed in multiple types of CSCs. In this context, CSCs are considered to be responsible for tumor initiation, growth, progression, therapeutic resistance, and metastasis. Therefore, to effectively eradicate CSCs, tremendous efforts have been devoted to identify specific target molecules that play a critical role in regulating their distinct functions and to develop novel therapeutics, such as proteins, monoclonal antibodies, selective small molecule inhibitors, and small antisense RNA (asRNA) drugs. Similar to other CSC types, oral CSCs can be characterized by certain pluripotency-associated markers, and oral CSCs can also survive and form 3D tumor spheres in suspension culture conditions. These oral CSC-targeting therapeutics selectively suppress specific surface markers or key signaling components and subsequently inhibit the stem-like properties of oral CSCs. A large number of new therapeutic candidates have been tested, and some products are currently in the pre-clinical or clinical development phase. In the present study, we review new oral CSC-targeted therapeutic strategies and discuss the various specific CSC surface markers and key signaling components involved in the stem-like properties, growth, drug resistance, and tumorigenicity of oral CSCs.
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Affiliation(s)
- Jin Woo Lee
- Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, Korea.,Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, Korea
| | - Hwa-Yong Lee
- Department of Biomedical Science, Jungwon University, Goesan, Korea.,Division of Science Education, Kangwon National University, Chuncheon, Korea
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