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Frontiers in Oncology 2024Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity and is associated with high morbidity due to local invasion and lymph node...
Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity and is associated with high morbidity due to local invasion and lymph node metastasis. Tumor infiltrating lymphocytes (TILs) are associated with good prognosis in oral cancer patients and dictate response to treatment. Ectopic sites for immune activation in tumors, known as tertiary lymphoid structures (TLS), and tumor-associated high-endothelial venules (TA-HEVs), which are specialized lymphocyte recruiting vessels, are associated with a favorable prognosis in OSCC. Why only some tumors support the development of TLS and HEVs is poorly understood. In the current study we explored the infiltration of lymphocyte subsets and the development of TLS and HEVs in oral epithelial lesions using the 4-nitroquinoline 1-oxide (4NQO)-induced mouse model of oral carcinogenesis. We found that the immune response to 4NQO-induced oral epithelial lesions was dominated by T cell subsets. The number of T cells (CD4+, FoxP3+, and CD8+), B cells (B220+) and PNAd+ HEVs increased from the earliest to the latest endpoints. All the immune markers increased with the severity of the dysplasia, while the number of HEVs and B cells further increased in SCCs. HEVs were present already in early-stage lesions, while TLS did not develop at any timepoint. This suggests that the 4NQO model is applicable to study the dynamics of the tumor immune microenvironment at early phases of oral cancer development, including the regulation of TA-HEVs in OTSCC.
PubMed: 38812785
DOI: 10.3389/fonc.2024.1343839 -
Asian Pacific Journal of Cancer... May 2024To systematically review the existing scientific literature in providing a comprehensive, quantitative analysis on the prognostic ability of Cancer Associated... (Meta-Analysis)
Meta-Analysis
AIM
To systematically review the existing scientific literature in providing a comprehensive, quantitative analysis on the prognostic ability of Cancer Associated Fibroblasts (CAFs) in Oral Squamous Cell Carcinoma (OSCC) a novel meta-analysis.
METHODS
Review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and registered in PROSPERO - CRD CRD42023467899. Electronic databases were searched for studies having data on effect of CAFs on overall survival rate and disease prognosis in patients with OSCC, oral epithelial dysplasia (OED) compared to normal healthy controls. Quality assessment of included was evaluated through Newcastle Ottawa scale (NOS) for included studies through its domains. The hazard ratio (HR) and risk ratio (RR) was used as summary statistic measure with random effect model and p value <0.05 as statistically significant.
RESULTS
Twenty studies fulfilled the eligibility criteria and were included in qualitative synthesis and eighteen studies for meta -analysis. Included studies had moderate to low risk of bias. It was observed through the pooled estimate that overall survival rate - (HR) =2.30 (1.71 - 3.10) was lesser in group with high CAFs compared to low CAFs while pooled estimate through RR =1.53 (0.73 - 3.19) and RR = 5.72 (2.40 - 13.59) signified that overall survival rate was lower n OSCC patients with high CAF compared to patients with OED and healthy controls. Publication bias through the funnel plot showed asymmetric distribution with presence of systematic heterogeneity indicating presence of publication bias.
CONCLUSION
Abundance of CAFs in tumor stroma of OSCC patients is associated with overall poor survival rate and poor disease prognosis. CAFs acts as a good prognostic and therapeutic marker in disease progression and advancements and should be assessed early to reduce patient's mortality and morbidity.
Topics: Humans; Mouth Neoplasms; Prognosis; Myofibroblasts; Carcinoma, Squamous Cell; Survival Rate; Biomarkers, Tumor
PubMed: 38809619
DOI: 10.31557/APJCP.2024.25.5.1477 -
Pathology Oncology Research : POR 2024Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental...
Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%-70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology. A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget's disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the gene in the index patient's DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother). Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients' chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs.
Topics: Humans; Gardner Syndrome; Female; Adolescent; Genetic Testing; Tooth Abnormalities; Early Diagnosis; Pedigree
PubMed: 38807857
DOI: 10.3389/pore.2024.1611768 -
JPMA. the Journal of the Pakistan... May 2024To determine the expression of podoplanin, and to correlate it with histopathological grades in oral epithelial dysplasia and oral squamous cell carcinoma cases.
OBJECTIVE
To determine the expression of podoplanin, and to correlate it with histopathological grades in oral epithelial dysplasia and oral squamous cell carcinoma cases.
METHODS
The retrospective, analytical, cross-sectional study was conducted at the City Laboratory, Peshawar, Pakistan, and comprised specimen block data of histologically diagnosed cases of oral benign lesions, dysplastic lesions and oral squamous cell carcinoma from January 2017 to August 2021. Two sections (4um) were cut from each specimen block for Haematoxylin and Eosin staining and immunohistochemistry. The slides were re-evaluated by two pathologists for confirmation of the diagnosis, and podoplanin marker was applied to cases selected using immunohistochemistry. Data was analysed using SPSS 22.
RESULTS
Of the 80 cases identified, 68(85%) were analysed. There were 20(29.4%) benign cases; 11(55%) females and 9(45%) males with mean age 39.90±16.23 years, 20(29.4%) oral dysplastic cases; 14(70%) males and 6(30%) females with mean age 57.75±12.02 years, and 28(41.2%) oral squamous cell carcinoma cases; 17(61%) males and 11(39%) females with mean age 50.55±14.80 years. Podoplanin expression in oral epithelial dysplasia cases was significant (p=0.028), while it was not significant in the other 2 groups (p>0.05).
CONCLUSIONS
Podoplanin when used along with histopathological evaluation could aid as an adjuvant technique in the diagnosis and grading of oral epithelial dysplasia.
Topics: Humans; Female; Male; Membrane Glycoproteins; Mouth Neoplasms; Middle Aged; Adult; Cross-Sectional Studies; Retrospective Studies; Aged; Carcinoma, Squamous Cell; Precancerous Conditions; Pakistan; Young Adult; Mouth Mucosa; Neoplasm Grading; Biomarkers, Tumor; Immunohistochemistry
PubMed: 38783429
DOI: 10.47391/JPMA.8277 -
BMC Oral Health May 2024Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disorder. Besides skeletal abnormalities, CCD is often associated with dental complications, such as...
BACKGROUND
Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disorder. Besides skeletal abnormalities, CCD is often associated with dental complications, such as multiple supernumerary teeth and permanent teeth impaction or delayed eruption.
METHODS
Supernumerary teeth of axial, sagittal and coronal CBCT view was characterized in detail and 3D image reconstruction was performed. Number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth, direction of supernumerary teeth in CCD patients were analyzed.
RESULTS
The mean age of the 3 CCD patients in this study was 16.7 years. Among 36 supernumerary teeth, the majority of them were identified as apical side located and lingual side located. Normal orientation was the most common type in this study, followed by sagittal orientation, and horizontal orientation. Horizontal orientation teeth were all distributed in the mandible. Supernumerary teeth exhibited significantly shorter crown and dental-root lengths, as well as smaller crown mesiodistal and buccolingual diameters (P < 0.01). There was no difference in the number of supernumerary teeth between the maxilla and mandible, and the premolars region had the largest number of supernumerary teeth and the incisor region had the smallest number.
CONCLUSIONS
This study compares number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth and direction of supernumerary teeth, this study also provides a reference for the comprehensive evaluation of CCD patients before surgery.
Topics: Humans; Cleidocranial Dysplasia; Tooth, Supernumerary; Imaging, Three-Dimensional; Cone-Beam Computed Tomography; Adolescent; Male; Female; Tooth Crown; Tooth Root; Odontometry; Young Adult; Mandible; Bicuspid; Maxilla; Image Processing, Computer-Assisted
PubMed: 38760743
DOI: 10.1186/s12903-024-04353-z -
Iranian Journal of Medical Sciences May 2024
Topics: Humans; Papillomavirus Infections; Mouth Neoplasms; Papillomaviridae; Human Papillomavirus Viruses
PubMed: 38751875
DOI: 10.30476/IJMS.2024.101269.3394 -
Frontiers in Molecular Neuroscience 2024Inner ear malformations are predominantly attributed to developmental arrest during the embryonic stage of membranous labyrinth development. Due to the inherent... (Review)
Review
Inner ear malformations are predominantly attributed to developmental arrest during the embryonic stage of membranous labyrinth development. Due to the inherent difficulty in clinically assessing the status of the membranous labyrinth, these malformations are diagnosed with radiographic imaging, based on the morphological characteristics of the bony labyrinth. While extensive research has elucidated the intricacies of membranous labyrinth development in mouse models, comprehensive investigations into the developmental trajectory of the bony labyrinth, especially about its calcification process, have been notably lacking. One of the most prominent types of inner ear malformations is known as incomplete partition (IP), characterized by nearly normal external cochlear appearance but pronounced irregularities in the morphology of the modiolus and inter-scalar septa. IP type II (IP-II), also known as Mondini dysplasia, is generally accompanied by an enlargement of the vestibular aqueduct and is primarily attributed to mutations in the gene. In the case of IP-II, the modiolus and inter-scalar septa of the cochlear apex are underdeveloped or missing, resulting in the manifestation of a cystic structure on radiographic imaging. In this overview, we not only explore the normal development of the bony labyrinth in mice but also present our observations on otolith mineralization. Furthermore, we investigated the specifics of bony labyrinth and otolith mineralization in -deficient mice, which served as an animal model for IP-II. We ensured that these findings promise to provide valuable insights for the establishment of therapeutic interventions, optimal timing, targeted sites, and preventive measures when considering the management of this condition.
PubMed: 38742227
DOI: 10.3389/fnmol.2024.1384764 -
Journal of Clinical Medicine Apr 2024This retrospective cross-sectional study investigated the cutoff values (COVs) for developmental dysplasia of the hip (DDH) using a three-dimensional (3D) pelvic model...
This retrospective cross-sectional study investigated the cutoff values (COVs) for developmental dysplasia of the hip (DDH) using a three-dimensional (3D) pelvic model reconstructed using computed tomography (CT). We included 107 healthy Japanese participants and 73 patients who had undergone curved periacetabular osteotomy (CPO) for DDH between 2012 and 2017. The hip CT images were adjusted to the anterior pelvic plane (APP), functional pelvic plane (FPP), sagittal anterior center-edge angle (ACEA), and sagittal posterior center-edge angle (PCEA). The lateral center-edge angle (LCEA), acetabular roof obliquity (ARO), anterior acetabular sector angle (AASA), and posterior acetabular sector angle (PASA) were measured. Receiver operating characteristic (ROC) curves were used to calculate the COVs, and the association between the parameters was analyzed using multiple logistic regression. The ARO (≥10.2°) and LCEA (≤22.2°) were independent influencing factors for the APP, whereas the AASA (≤53.1°) and LCEA (≤24.5°) were independent influencing factors for the FPP. The 3D criteria for the diagnosis of DDH in Japanese individuals can identify DDH with insufficient anterior coverage, which anteroposterior plain radiographs cannot visualize, and can help determine indications for acetabular osteotomy.
PubMed: 38731066
DOI: 10.3390/jcm13092536 -
Cells Apr 2024Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of encoding for Gα and leading to excessive cyclic adenosine monophosphate...
Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of encoding for Gα and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gα activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gα activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gα activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.
Topics: Humans; Animals; Mesenchymal Stem Cells; Transcriptome; Mice; Fibrous Dysplasia of Bone; Male; Female; Cytokines; GTP-Binding Protein alpha Subunits, Gs; Adult; Middle Aged
PubMed: 38727310
DOI: 10.3390/cells13090774 -
Cureus Apr 2024The assessment of sagittal skeletal dysplasia is crucial for accurate diagnosis and treatment planning, thus necessitating a thorough evaluation. A novel cephalometric...
INTRODUCTION
The assessment of sagittal skeletal dysplasia is crucial for accurate diagnosis and treatment planning, thus necessitating a thorough evaluation. A novel cephalometric parameter, known as the Zeta angle, was proposed in this study for the evaluation of the maxillomandibular relationship in the sagittal plane.
MATERIALS AND METHODS
This observational study was carried out using 291 pre-treatment lateral cephalograms of participants aged between 15 and 25 years, categorized into skeletal class I, II, and III relationships based on Wits appraisal, ANB angle, and Beta angle. The individuals reported to the Department of Orthodontics from January 2021 to October 2023, Manav Rachna Dental College, Manav Rachna International Institute of Research and Studies, Faridabad. The Zeta angle was constructed using three skeletal reference points as point Pt (pterygoid), point M (center of premaxilla), and point Pm (suprapogonion) and was measured perpendicular to point M on the Pt-Pm line and the M-Pm line to determine the severity and type of maxillomandibular discrepancy in the sagittal plane. Statistical tests were used to obtain the mean values for the Zeta angle. Analysis of variance (ANOVA), followed by the Bonferroni post-hoc test, was used to assess skeletal differences between the groups. Receiver operating characteristic (ROC) curves were used to evaluate the sensitivity and specificity of this angle.
RESULTS
The results indicated that a Zeta angle between 57° and 64° had a class I skeletal jaw pattern, a Zeta angle less than 57° indicated a class II skeletal jaw pattern, and a Zeta angle greater than 64° indicated a class III skeletal jaw pattern. ROC curves showed that a Zeta angle less than 57.5° had 80% sensitivity and 82.5% specificity in distinguishing class II from the class I subset. A Zeta angle greater than 64.5° has a sensitivity and specificity of 92.5% in distinguishing class III from the class I subset.
CONCLUSION
The Zeta angle may serve as an additional diagnostic tool for the reliable determination of sagittal jaw relationships due to its establishment based on stable anatomical points, thus remaining unaffected by jaw rotations and orthodontic treatments.
PubMed: 38721219
DOI: 10.7759/cureus.57788