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1.
J Craniofac Surg ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38861333

ABSTRACT

PURPOSE: Studies regarding oral injuries from playground equipment in children remain limited. This study aimed to clarify the characteristics of oral injury caused by playground equipment and identify associations with concomitant head injury. METHODS: Children treated between 2011 and 2021 at an oral surgery clinic for oral injuries from playground equipment were retrospectively investigated. The following factors were analyzed: demographic characteristics, mechanism of injury, type of equipment causing the injury, classification of oral injury, and whether the Department of Emergency and Critical Care Medicine was consulted regarding the head injury. The data collected were statistically analyzed using the Fisher-Freeman-Halton test with significance adopted at the 5% level. RESULTS: This study analyzed data from 82 children. Injuries were concentrated in age groups of 2 to 3 years (32.9%), 4 to 5 years (28.0%), and 6 to 7 years (25.6%). Regarding the mechanism of injury, falls were more common (89.0%) than impact/striking (11.0%). The type of equipment most frequently causing injury was slides (29.3%), followed by swings (23.2%) and iron bars (18.3%). Injuries were classified as soft tissue injury alone (56.1%) or tooth injury and/or jaw fracture (43.9%). Consultation with the Department of Emergency and Critical Care Medicine for head injury was uncommon (13.4%), and all consultations for brain injury diagnosed minor injuries. CONCLUSION: Oral injuries caused by playground equipment were frequent between 2 and 7 years old. The most common cause was falls, with most injuries caused by slides, swings, or iron bars. Approximately half of the oral injuries were soft tissue injuries only, while the other half were associated with tooth and/or jaw injuries. Department of Emergency and Critical Care Medicine consultations for head trauma were uncommon and consistently confirmed minor injuries.

2.
Clin Case Rep ; 12(3): e8611, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38449892

ABSTRACT

Key Clinical Message: Foreign bodies penetrating from the oral cavity can damage surrounding tissues. This case is considered an extremely rare and fortunate instance in which a maxillary denture appeared to weaken the external force and change the direction of the scissors, preventing damage to vital organs. Abstract: The patient was a 73-year-old man. While on a ladder pruning a plant, he accidentally fell. The gardening scissors passed through the maxillary sinus from the maxillary alveolus and penetrated below the zygomatic arch. At the time of injury, the patient was wearing a metal-frame denture on the maxilla, and contact between the cutting edge and the denture was speculated to have weakened the piercing force of the blade and changed the direction of the cutting edge. This extremely rare case demonstrates how a maxillary denture could reduce the severity of a penetrating injury caused by scissors.

3.
Clin Case Rep ; 11(9): e7822, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37636885

ABSTRACT

If a foreign body is seen on chest or abdominal radiographs, accidental aspiration or ingestion of a dental-related foreign body may be suspected. This report describes a case in which vascular embolization coils seen on radiography were suspected to represent a swallowed dental prosthesis. A 72-year-old man with a history of endovascular embolization of portosystemic shunt was admitted for mandibular fracture. On hospital day 2, a foreign body was noted on chest radiographs taken to confirm pleural effusion. No foreign body had been evident on radiographs of the same area the previous day. The foreign body was suspected to be a dental prosthesis, but intraoral examination ruled out this possibility, and the foreign body turned out to be metal coils used to embolize the shunt. Dentists and oral surgeons should be aware that medical devices such as vascular embolization coils can produce images similar to a dental-related foreign body on chest or abdominal radiographs, and dental-related foreign body ingestion or aspiration should be considered in the differential diagnosis.

4.
Sci Rep ; 13(1): 13631, 2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37604970

ABSTRACT

B1-type MX ceramics are composed of transition metals (M) and C, N, and/or O (X) occupying the M and X sites, respectively, and having M-X nearest neighbor (NN) bonds and M-M and X-X next nearest neighbor (NNN) bonds. Substitution of the elements and the formation of structural vacancies in B1-type ceramics change the numbers and strengths of the bonds, leading to novel properties. The change in elastic modulus of off-stoichiometric TiC in equilibrium with a Ti-Mo solid solution phase was experimentally investigated based on the rule of mixtures from the Voigt model. The experimentally obtained values agreed well with the results of density functional theory calculations. The bulk modulus (K) of TiC increased from 205.6 to 239.2 GPa as the fraction of Ti sites occupied by Mo increased from 0.11 to 0.33, whereas the Young's modulus (E) and the shear modulus (G) remained nearly constant. On the other hand, all three elastic moduli decreased with increasing vacancy fraction at the C sites. These results suggest that the M-X bond strength should be the dominant factor in these moduli and the effect of M-M bond on K is greater than that of G and E.

5.
JMA J ; 6(3): 358-359, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37560361
6.
Gerontol Geriatr Med ; 9: 23337214231191295, 2023.
Article in English | MEDLINE | ID: mdl-37565024

ABSTRACT

Introduction: Various diseases cause pigmentation of the oral mucosa. Among them, however, Laugier-Hunziker syndrome is not well known to dentists. Laugier-Hunziker syndrome is a benign pigmentary disorder characterized by the unique expression of pigmentation of the mucosa, nails and skin. In this report, we present a rare case of Laugier-Hunziker syndrome that occurred in an elderly person. Case Presentation: The patient was an 84-year-old female resident of an elderly care facility. The institutional dental hygienist reported that she was concerned about the discoloration of the oral mucosa. On examination, she had pigmentation of her oral mucosa and nails. She had no history of any disease or medication that would cause pigmentation. Although this condition was initially unknown to us, a diagnosis of Laugier-Hunziker syndrome was made. Conclusion: We report a case of Laugier-Hunziker syndrome in an elderly woman, which is not a well-known condition among dental professionals. More knowledge about diseases that cause pigmentation of the oral mucosa would be helpful in dental practice, especially at external facilities.

7.
JHEP Rep ; 5(7): 100741, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37274775

ABSTRACT

Background & Aims: HIV-seropositivity shortens survival in patients with hepatocellular carcinoma (HCC). Although risk factors for HCC including HCV infection can influence T cell phenotype, it is unknown whether HIV can influence functional characteristics of the T cell infiltrate. Methods: From the Liver Cancer in HIV biorepository, we derived 129 samples of transplanted (76%) or resected (20%) HCC in eight European and North American centres. We profiled intra- and peritumoural tissue to evaluate regulatory CD4+/FOXP3+ and immune-exhausted CD8+/PD1+ T cells in HIV+ (n = 66) and HIV- (n = 63) samples. We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples evaluated in relationship with HIV status. We correlated immunopathologic features with patients' characteristics including markers of HIV infection. Results: Of the 66 HIV+ patients, 83% were HCV coinfected with an undetectable HIV viral load (51%) and a median blood CD4+ cell count of 430 cells/mm3 (range 15-908). Patients who were HIV+ were compared with HIV- controls with similar staging characteristics including Barcelona Clinic Liver Cancer (BCLC) stage A-B (86% vs. 83%, p = 0.16), <3 nodules (90% vs. 83%, p = 0.3) and median alpha-foetoprotein values (10.9 vs. 12.8 ng/ml, p = 0.72). HIV+ samples had higher PD-L1 expression rates in tumour tissue (51% vs. 8% p <0.0001) and displayed denser intratumoural CD4+/FOXP3+ (p <0.0001), CD8+/PD1+ (p <0.0001), with lower total peritumoural CD4+ (p <0.0001) and higher peritumoural CD8+/PD1+ (p <0.0001). Gene set analysis revealed HIV+ cases to have evidence of dysregulated adaptive and innate immunity. Tumour-infiltrating lymphocyte clonality was not influenced by HIV status. Conclusions: HIV-associated HCC harbours a profoundly immune-exhausted tumour microenvironment, warranting prospective testing of immunotherapy in this treatment-deprived patient population. Impact and Implications: Hepatocellular carcinoma is a non-AIDS defining malignancy characterised by poor survival. The programmed cell death (PD-1) pathway governs antiviral and anticancer immune exhaustion and is a therapeutic target in HCC. This study highlights how HIV infection is associated with significantly higher PD-L1 expression in HCC cells and in the surrounding microenvironment, leading to changes in cytotoxic and regulatory T cell function and dysregulation of proinflammatory pathways. Taken together, our results suggest dysfunctional T cell immunity as a mechanism of worse outcome in these patients and suggest clinical testing of checkpoint inhibitors in HIV-associated HCC.

8.
In Vivo ; 37(4): 1880-1885, 2023.
Article in English | MEDLINE | ID: mdl-37369479

ABSTRACT

BACKGROUND/AIM: Oral adverse events caused by anticancer drugs are diverse, but few reports have examined pigmentation of the oral mucosa. The aim of this study was to clarify the prevalence of oral mucosal pigmentation caused by anticancer drugs. PATIENTS AND METHODS: This single-centre retrospective study investigated patients who underwent oral examination in our hospital during cancer chemotherapy for 3 years from April 1, 2019 to March 31, 2021. Inclusion criteria were patients who could be followed-up for ≥3 months after completing chemotherapy with drugs that caused pigmentation. The primary predictive variable was the cancer chemotherapeutic agent used. The primary outcome variable was pigmentation of the oral mucosa. Collected data were statistically analysed using the χ2 test or Fisher's exact test, with the level of significance set at p<0.05. RESULTS: A total of 388 patients were enrolled in the study. Eleven patients (2.8%) showed oral mucosal pigmentation. Drugs causing pigmentation [deposition rate (number of patients with deposits/users)] were TS-1 (combination of tegafur, gimeracil, and oteracil potassium) [12.2% (5/41)], paclitaxel [4.0% (2/50)], gemcitabine [5.0% (1/20)], cyclophosphamide [2.3% (1/42)], carboplatin [1.6% (1/64)], fluorouracil [2.3% (1/43)], and capecitabine [3.4% (1/29)]. CONCLUSION: Oral pigmentation due to cancer chemotherapy was found in 2.8% of patients. TS-1, carboplatin, cyclophosphamide, capecitabine, fluorouracil, gemcitabine, and paclitaxel caused pigmentation of the oral mucosa. Among these, TS-1 was the most likely to cause pigmentation, affecting 12.2% of users.


Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Capecitabine , Carboplatin , Mouth Mucosa , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Agents/adverse effects , Fluorouracil/adverse effects , Paclitaxel/adverse effects , Gemcitabine , Pigmentation , Neoplasms/drug therapy , Neoplasms/chemically induced , Cyclophosphamide
9.
J Clin Exp Hematop ; 63(2): 90-98, 2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37245972

ABSTRACT

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly recognized disease entity characterized by EBV-positive atypical B-cell proliferation. EBVMCU is a localized self-limited disease that affects mucosa and skin, especially the oral cavity. EBVMCU develops in immunosuppressive patients, such as those with methotrexate (MTX)-administrated rheumatoid arthritis (RA). Here we clinicopathologically analyzed 12 EBVMCU patients in a single institution. All cases were administrated MTX for RA, and five cases occurred in the oral cavity. All cases except one had demonstrated spontaneous regression after withdrawal of the immunosuppressive agent. We found 4 of 5 cases in the oral cavity had preceding traumatic events in the same site within a week before the onset of EBVMCU. Although there is no detailed and large study that has analyzed the trigger of EBVMCU, a traumatic event would indeed be a significant trigger for EBVMCU in the oral cavity. The cases were histologically classified; six cases were diffuse large B-cell lymphoma-type, five were polymorphous-type, and one was Hodgkin-like lesion type due to morphological appearance and immunophenotype. The PD-L1 expression was also examined by two antibodies for PD-L1 (E1J2J and SP142). Both antibodies revealed identical results for PD-L1 expression, and three cases were positive for PD-L1. The application of SP142 for evaluating the immune status of lymphomagenesis has also been proposed. Nine of 12 cases were negative for PD-L1, which implies that most EBVMCU cases may be caused by an immunodeficiency, rather than an immune-evasion, mechanism. However, as three cases were positive for PD-L1, immune escape may underly the pathogenesis in a subset of EBVMCU cases.


Subject(s)
Arthritis, Rheumatoid , Epstein-Barr Virus Infections , Humans , Methotrexate/adverse effects , Epstein-Barr Virus Infections/chemically induced , Epstein-Barr Virus Infections/complications , Ulcer , Herpesvirus 4, Human/metabolism , B7-H1 Antigen , Immunosuppressive Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/complications
11.
Gerontol Geriatr Med ; 9: 23337214231162750, 2023.
Article in English | MEDLINE | ID: mdl-36968121

ABSTRACT

Purpose: Clasp-penetrating oral injury caused by removable partial dentures is basically a minor injury but can also cause complications such as continuous bleeding. No systematic investigations of clasp injury have been undertaken. The aims of this study were to reveal the characteristics of clasp injury and estimate variables associated with clasp injury of the oral mucosa. Methods: This retrospective study used clasp injury as the outcome variable, with primary predictor variables of demographic characteristics, medical history, local characteristics, and denture design, including the site of the affected clasp. Denture type was examined according to the classification of Kennedy. Collected data were statistically analyzed using the χ2 test or Fisher's exact test and the level of significance adopted was 5%. Results: This report consists of 73 cases (36 men and 37 women), of which 31 cases had precise denture information. Among them, clasp injuries were more common with Class I (51.6%) and Class II (32.3%) dentures (p < .001). Premolar (64.5%) and canine clasps (32.3%) were significantly more frequently involved (p < .001). Conclusion: Clasp injury of the oral mucosa was significantly more common on the tongue, and mandibular free-end saddle dentures with premolar or canine clasps were the most notable risk factor for clasp-penetrating injury of the oral mucosa.

12.
Photosynth Res ; 155(1): 77-92, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36306003

ABSTRACT

Modern models for estimating canopy photosynthetic rates (Ac) can be broadly classified into two categories, namely, process-based mechanistic models and artificial intelligence (AI) models, each category having unique strengths (i.e., process-based models have generalizability to a wide range of situations, and AI models can reproduce a complex process using data without prior knowledge about the underlying mechanism). To exploit the strengths of both categories of models, a novel "hybrid" canopy photosynthesis model that combines process-based models with an AI model was proposed. In the proposed hybrid model, process-based models for single-leaf photosynthesis and image analysis first transform raw inputs (environmental data and canopy images) into the single-leaf photosynthetic rate (AL) and effective leaf area index (Lc)), after which AL and Lc are fed into an artificial neural network (ANN) model to predict Ac. The hybrid model successfully predicted the diurnal cycles of Ac of an eggplant canopy even with a small training dataset and successfully reproduced a typical Ac response to changes in the CO2 concentration outside the range of the training data. The proposed hybrid AI model can provide an effective means to estimate Ac in actual crop fields, where obtaining a large amount of training data is difficult.


Subject(s)
Solanum melongena , Artificial Intelligence , Photosynthesis/physiology , Plant Leaves/physiology
13.
Medicines (Basel) ; 9(11)2022 Oct 26.
Article in English | MEDLINE | ID: mdl-36355058

ABSTRACT

Purpose: Denture loss is still being reported as a problem in geriatric facilities, although losses seem less frequent than in the last decade. However, there have been no reports that have examined recent losses of dentures in detail. The aim of this study was to clarify the actual situation of recent denture loss, together with the denture loss rate in Japan. Materials and methods: This retrospective study investigated the number of cases of denture loss, the denture loss rate for denture wearers, and the details of losses in geriatric facilities during the 1-year period from 1 April 2020 to 31 March 2021. Results: Eleven special elderly nursing homes and four group homes participated in this research. The number of residents from each was 315 and 40 and the number of denture wearers was 165 and 33, respectively (p < 0.001). The loss of dentures was found in one case from a special elderly nursing home and in one case from a group home. The loss rate for denture wearers was 1.01% in total, with 0.61% for special elderly nursing homes and 3.03% for group homes, with no significant differences between the two types of facilities. Conclusion: In geriatric facilities in Japan, the current 1-year denture loss rate for denture wearers was 1.01%. This seems to represent a considerable decrease when compared with the previous report. Further, proper denture management and staff efforts appear to have contributed to a reduction in denture loss against a background of promoting oral healthcare.

14.
Case Rep Dent ; 2022: 9592077, 2022.
Article in English | MEDLINE | ID: mdl-36046849

ABSTRACT

Hematopoietic stem cell transplantation (HSCT) is a common method for patients such as hematologic malignancies. However, HSCT generally has a higher risk of secondary solid cancer development. The aim of this study was to emphasize the need for lifelong follow-up of oral secondary solid cancer. The patient was a male who underwent HSCT for chronic myelogenous leukaemia at the age of 31 years. He underwent ten onsets on oral secondary solid cancers during his subsequent follow-up of more than 20 years. In conclusion, patients after HSCT require lifelong observation of oral secondary solid cancer, which may be accompanied by repeated new and recurrent occurrences.

15.
Fitoterapia ; 162: 105284, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36007806

ABSTRACT

The nitrogen-fixing actinomycete Frankia coexists with actinorhizal plants via nodules and supplies nitrogen compounds to the plants. Although communication has been suggested to exist through chemical substances in this nodule symbiosis, the details underlying this mechanism remain elusive. The biphenyl-type diarylheptanoids (BP-CDHs), alnusonol, and alnusdione, previously isolated from the actinorhizal plant A. sieboldiana branch wood, are secondary metabolites that accumulate in a limited number of plant species. However, since relatively widely distributed in actinorhizal plants, we investigated whether adding A. sieboldiana root extracts and these BP-CDHs could affect plant seedlings inoculated with Frankia. The results showed that the addition of root extract or alnusonol significantly increased the number of nodules and lobes more than two times compared with that upon Frankia supplementation only. We also proved that the extracted components of this plant affected nodule symbiosis. Finally, we confirmed through LC-MS that the root extract component contained BP-CDH, alnusonol. The above-described results indicate that BP-CDHs, at leaset alnusonol, might function as signal compounds from the plant side of the actinorhizal symbiosis between A. sieboldiana and Frankia.


Subject(s)
Alnus , Frankia , Diarylheptanoids/pharmacology , Frankia/metabolism , Molecular Structure , Nitrogen/metabolism , Nitrogen Compounds/metabolism , Plant Extracts , Plants , Symbiosis
16.
Case Rep Dent ; 2022: 9098201, 2022.
Article in English | MEDLINE | ID: mdl-35634459

ABSTRACT

Dialysis-related amyloidosis (DRA) represents a group of relatively rare disorders characterized by the systemic extracellular deposition of insoluble fibrils of amyloid protein in long-term dialysis patients. We describe herein a case of relatively early DRA on the tongue of a long-term dialysis patient. A 67-year-old man with a 39-year history of dialysis was referred for diagnosis of a tongue mass. On examination, a collection of whitish-yellow papules was identified on the ventral surface of the tongue tip. The pathological diagnosis was DRA. Clinicians should be aware that long-term dialysis can cause oral amyloidosis of the tongue.

17.
Gerodontology ; 39(2): 218-221, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35526228

ABSTRACT

INTRODUCTION: Identifying the causes of accidental oral bleeding can be difficult in patients with dementia. The aim of this study was to highlight the effectiveness of multidisciplinary consultation, which proved extremely useful in investigating the cause of bleeding in this case. CASE PRESENTATION: An 86-year-old woman on anticoagulants who had been admitted to a geriatric facility experienced repeated oral bleeding of unknown cause, initially attributed to periodontitis. CONCLUSION: Along with anticoagulant use, a multidisciplinary consultation attributed the bleeding to the use of a spoon at mealtimes and possible scratching at the wound by the patient with her fingers.


Subject(s)
Anticoagulants , Dementia , Administration, Oral , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Dementia/complications , Female , Hemorrhage/chemically induced , Humans , Retrospective Studies
18.
Mod Pathol ; 35(2): 177-185, 2022 02.
Article in English | MEDLINE | ID: mdl-34404905

ABSTRACT

Next-generation sequencing of oral squamous cell carcinoma (OSCC) has revealed TP53 as the most frequently mutated gene in OSCC mutually exclusive with human papillomavirus infection. Oral epithelial dysplasia (OED) is defined as a precancerous lesion of OSCC by the current World Health Organization (WHO) classification; therefore, it is assumed that TP53 mutations occur in early precancerous conditions such as OED. Here, we conducted an integrated analysis of TP53, including whole coding sequencing of TP53, FISH analysis of the 17p13.1 locus, and immunohistochemical analysis for p53 (p53-IHC), in 40 OED cases. We detected 20 mutations in 16 (40%) OED cases, and four cases, each harbored two mutations. FISH analysis revealed six of 24 cases (25%) had a deletion on 17p13.1, and four cases had concurrent TP53 mutations and 17p13.1 deletion (2-hit). Also, the increased frequency of TP53 mutations in higher degrees of OED implies acquisition of the mutation is a major event toward OSCC. p53-IHC revealed that overall cases could be categorized into four patterns that correlate well with the mutational status of TP53. Especially, two patterns, broad p53 expression type (pattern HI) and p53 null type (pattern LS), strongly correlated with a missense mutation and nonsense mutation, respectively. Furthermore, seven of the 40 cases progressed to SCC, and six of these seven cases presented pattern HI or LS. Therefore, patterns HI and LS have a high risk for malignant transformation if excisional treatment is not performed irrespective of the dysplasia grade. Although the current WHO classification mainly focuses on morphological criteria for the diagnosis of OED, interobserver discrepancy appears in some instances of the OED diagnosis. Our immunohistochemical analysis supports a more accurate pathological diagnosis for OED in cases of low dysplastic changes or of differential diagnosis with non-dysplastic lesions.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , Humans , Immunohistochemistry , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Mutation , Staining and Labeling , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
19.
J Oral Maxillofac Surg ; 80(1): 127-136, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34627743

ABSTRACT

PURPOSE: Among previous reports on dental injuries associated with mandibular fractures, there are few investigating the conditions under which dental injuries commonly occur. The aim of this study was to determine specific characteristics of mandibular fractures accompanied by dental injuries. METHODS: This retrospective cohort study included dentate patients with mandibular fractures treated at a tertiary trauma center between 2011 and 2019. The data were analyzed according to 2 outcome variables: patients with additional dental injuries and patients without. The predictor variables were patient age, sex, accident mechanism, number and location of mandibular fractures, and presence of submental lacerations. Odds ratios for the risk factors for dental injury were calculated in conjunction with descriptive statistics. Binary logistic regression analysis was also performed to identify the factors associated with dental injuries as dependent variables. RESULTS: Of 252 patients who had only mandibular fractures, 95 (37.7%) had associated dental injuries. In the group with dental injuries, 55.8% of mandibular fractures were caused by a fall (P = .003). Condyle fractures (77.9%) with dislocation (67.6%) and bilateral involvement (41.9%) were more common than in the group without dental injuries (P < .001). In patients with dental injuries, the incidence of 3 or more fractures (29.5%) was significantly higher than in the group without dental injuries. Dental injuries were more likely to occur in patients with concomitant submental lacerations (confidence interval (CI) 1.135-4.983, P = .02), and the risk of dental injury was significantly lower in the presence of angle fractures (CI 0.113-0.999, P = .045). CONCLUSIONS: A frontal impact involving the anterior part of the mandible is often associated with condyle and multiple mandibular fractures. This seems to be the typical mechanism for concomitant dental injuries. Submental laceration can be considered a prime sign of associated dental injuries.


Subject(s)
Mandibular Fractures , Tooth Injuries , Humans , Incidence , Mandible , Mandibular Condyle/injuries , Mandibular Fractures/epidemiology , Mandibular Fractures/etiology , Retrospective Studies , Tooth Injuries/epidemiology , Tooth Injuries/etiology
20.
J Immunother Cancer ; 9(9)2021 09.
Article in English | MEDLINE | ID: mdl-34593621

ABSTRACT

BACKGROUND: Modulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment. METHODS: We profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T- (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163. RESULTS: We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p<0.001) compared with T-. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T-. CONCLUSIONS: TACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Chemoembolization, Therapeutic/methods , Immunogenic Cell Death/drug effects , Immunotherapy/methods , Liver Neoplasms/drug therapy , Adult , Aged , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/pathology , Male , Middle Aged
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