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- Almangush, A, et al.
(författare)
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Improving Risk Stratification of Early Oral Tongue Cancer with TNM-Immune (TNM-I) Staging System
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:13
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Tidskriftsartikel (refereegranskat)abstract
- Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.
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- Almangush, A, et al.
(författare)
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Stromal categorization in early oral tongue cancer
- 2021
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 478:5, s. 925-932
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Tidskriftsartikel (refereegranskat)abstract
- Stromal categorization has been used to classify many epithelial cancer types. We assessed the desmoplastic reaction and compared its significance with other stromal characteristics in early (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC). In this multi-institutional study, we included 308 cases treated for early OTSCC at five Finnish university hospitals or at the A.C. Camargo Cancer Center in São Paulo, Brazil. The desmoplastic reaction was classified as immature, intermediate, or mature based on the amount of hyalinized keloid-like collagen and myxoid stroma. We compared the prognostic value of the desmoplastic reaction with a stromal grading system based on tumor-stroma ratio and stromal tumor-infiltrating lymphocytes. We found that a high amount of stroma with a weak infiltration of lymphocytes was associated statistically significantly with a worse disease-free survival with a hazard ratio (HR) of 2.68 (95% CI 1.26–5.69), worse overall survival (HR 2.95, 95% CI 1.69–5.15), and poor disease-specific survival (HR 2.66, 95% CI 1.11–6.33). Tumors having a high amount of stroma with a weak infiltration of lymphocytes were also significantly associated with a high rate of local recurrence (HR 4.13, 95% CI 1.67–10.24), but no significant association was found with lymph node metastasis (HR 1.27, 95% CI 0.37–4.35). Categorization of the stroma based on desmoplastic reaction (immature, intermediate, mature) showed a low prognostic value for early OTSCC in all survival analyses (P > 0.05). In conclusion, categorization of the stroma based on the amount of stroma and its infiltrating lymphocytes shows clinical relevance in early OTSCC superior to categorization based on the maturity of stroma.
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- Kallionpaa, R. A., et al.
(författare)
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Mast Cells in Human Cutaneous Neurofibromas: Density, Subtypes, and Association with Clinical Features in Neurofibromatosis 1
- 2022
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Ingår i: Dermatology. - : S. Karger AG. - 1018-8665 .- 1421-9832. ; 238:2, s. 329-339
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cutaneous neurofibromas (cNFs) are hallmarks of neurofibromatosis 1 (NF1) and cause the main disease burden in adults with NF1. Mast cells are a known component of cNFs. However, no comprehensive characterization of mast cells in cNFs is available, and their contributions to cNF growth and symptoms such as itch are not known. Methods: We collected 60 cNFs from ten individuals with NF1, studied their mast cell proteinase content, and compared the mast cell numbers to selected clinical features of the tumors and patients. The tumors were immunolabeled for the mast cell markers CD117, tryptase, and chymase, and the percentage of immunopositive cells was determined using computer-assisted methods. Results: The median proportions of positive cells were 5.5% (range 0.1-14.4) for CD117, 4.0% (1.2-7.0) for tryptase, and 5.0% (1.1-15.9) for chymase. The median densities of cells immunopositive for CD117, tryptase, and chymase were 280, 243, and 250 cells/mm(2), respectively. Small tumors, growing tumors, and tumors from patients below the median age of 33 years displayed a high proportion of mast cells. Cells expressing both tryptase and chymase were the predominant mast cell type in cNFs, followed by cells expressing chymase only. Conclusion: The results highlight the abundance of mast cells in cNFs and that their number and subtypes clearly differ from those previously reported in unaffected skin.
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- Naakka, E, et al.
(författare)
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miR-22 and miR-205 Drive Tumor Aggressiveness of Mucoepidermoid Carcinomas of Salivary Glands
- 2022
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 11, s. 786150-
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Tidskriftsartikel (refereegranskat)abstract
- To integrate mRNA and miRNA expression profiles of mucoepidermoid carcinomas (MECs) and normal salivary gland (NSGs) tissue samples and identify potential drivers.Material and MethodsGene and miRNA expression arrays were performed in 35 MECs and six NSGs.ResultsWe found 46 differentially expressed (DE) miRNAs and 3,162 DE mRNAs. Supervised hierarchical clustering analysis of the DE transcripts revealed two clusters in both miRNA and mRNA profiles, which distinguished MEC from NSG samples. The integrative miRNA-mRNA analysis revealed a network comprising 696 negatively correlated interactions (44 miRNAs and 444 mRNAs) involving cell signaling, cell cycle, and cancer-related pathways. Increased expression levels of miR-205-5p and miR-224-5p and decreased expression levels of miR-139-3p, miR-145-3p, miR-148a-3p, miR-186-5p, miR-338-3p, miR-363-3p, and miR-4324 were significantly related to worse overall survival in MEC patients. Two overexpressed miRNAs in MEC (miR-22 and miR-205) were selected for inhibition by the CRISPR-Cas9 method. Cell viability, migration, and invasion assays were performed using an intermediate grade MEC cell line. Knockout of miR-205 reduced cell viability and enhanced ZEB2 expression, while miR-22 knockout reduced cell migration and invasion and enhanced ESR1 expression. Our results indicate a distinct transcriptomic profile of MEC compared to NSG, and the integrative analysis highlighted miRNA-mRNA interactions involving cancer-related pathways, including PTEN and PI3K/AKT.ConclusionThe in vitro functional studies revealed that miR-22 and miR-205 deficiencies reduced the viability, migration, and invasion of the MEC cells suggesting they are potential oncogenic drivers in MEC.
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- Alabi, RO, et al.
(författare)
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Measuring the Usability and Quality of Explanations of a Machine Learning Web-Based Tool for Oral Tongue Cancer Prognostication
- 2022
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 19:14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Machine learning models have been reported to assist in the proper management of cancer through accurate prognostication. Integrating such models as a web-based prognostic tool or calculator may help to improve cancer care and assist clinicians in making oral cancer management-related decisions. However, none of these models have been recommended in daily practices of oral cancer due to concerns related to machine learning methodologies and clinical implementation challenges. An instance of the concerns inherent to the science of machine learning is explainability. Objectives: This study measures the usability and explainability of a machine learning-based web prognostic tool that was designed for prediction of oral tongue cancer. We used the System Usability Scale (SUS) and System Causability Scale (SCS) to evaluate the explainability of the prognostic tool. In addition, we propose a framework for the evaluation of post hoc explainability of web-based prognostic tools. Methods: A SUS- and SCS-based questionnaire was administered amongst pathologists, radiologists, cancer and machine learning researchers and surgeons (n = 11) to evaluate the quality of explanations offered by the machine learning-based web prognostic tool to address the concern of explainability and usability of these models for cancer management. The examined web-based tool was developed by our group and is freely available online. Results: In terms of the usability of the web-based tool using the SUS, 81.9% (45.5% strongly agreed; 36.4% agreed) agreed that neither the support of a technical assistant nor a need to learn many things were required to use the web-based tool. Furthermore, 81.8% agreed that the evaluated web-based tool was not cumbersome to use (usability). The average score for the SCS (explainability) was 0.74. A total of 91.0% of the participants strongly agreed that the web-based tool can assist in clinical decision-making. These scores indicated that the examined web-based tool offers a significant level of usability and explanations about the outcome of interest. Conclusions: Integrating the trained and internally and externally validated model as a web-based tool or calculator is poised to offer an effective and easy approach towards the usage and acceptance of these models in the future daily practice. This approach has received significant attention in recent years. Thus, it is important that the usability and explainability of these models are measured to achieve such touted benefits. A usable and well-explained web-based tool further brings the use of these web-based tools closer to everyday clinical practices. Thus, the concept of more personalized and precision oncology can be achieved.
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- Almangush, A, et al.
(författare)
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Biomarkers for Immunotherapy of Oral Squamous Cell Carcinoma: Current Status and Challenges
- 2021
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 11, s. 616629-
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Tidskriftsartikel (refereegranskat)abstract
- Oral squamous cell carcinoma (OSCC) forms a major health problem in many countries. For several decades the management of OSCC consisted of surgery with or without radiotherapy or chemoradiotherapy. Aiming to increase survival rate, recent research has underlined the significance of harnessing the immune response in treatment of many cancers. The promising finding of checkpoint inhibitors as a weapon for targeting metastatic melanoma was a key event in the development of immunotherapy. Furthermore, clinical trials have recently proven inhibitor of PD-1 for treatment of recurrent/metastatic head and neck cancer. However, some challenges (including patient selection) are presented in the era of immunotherapy. In this mini-review we discuss the emergence of immunotherapy for OSCC and the recently introduced biomarkers of this therapeutic strategy. Immune biomarkers and their prognostic perspectives for selecting patients who may benefit from immunotherapy are addressed. In addition, possible use of such biomarkers to assess the response to this new treatment modality of OSCC will also be discussed.
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- Almangush, A, et al.
(författare)
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Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: Ready for Prime Time?
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- The evaluation of tumor-infiltrating lymphocytes (TILs) has received global attention as a promising prognostic cancer biomarker that can aid in clinical decision making. Proof of their significance was first shown in breast cancer, where TILs are now recommended in the classification of breast tumors. Emerging evidence indicates that the significance of TILs extends to other cancer types, including head and neck cancer. In the era of immunotherapy as a treatment choice for head and neck cancer, assessment of TILs and immune checkpoints is of high clinical relevance. The availability of the standardized method from the International Immuno-oncology Biomarker Working Group (IIBWG) is an important cornerstone toward standardized assessment. The aim of the current article is to summarize the accumulated evidence and to establish a clear premise for future research toward the implementation of TILs in the personalized management of head and neck squamous cell carcinoma patients.
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