Oral squamous cell carcinoma (OSCC) progresses from preneoplastic precursors via genetic and epigenetic alterations. Previous studies have focused on the treatment of terminally developed OSCC. However, the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied. Our study identified lysine-specific demethylase 1 (LSD1) as a crucial promoter of OSCC, demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia. LSD1 inhibition by SP2509 disrupted cell cycle, reduced immunosuppression, and enhanced CD4+ and CD8+ T-cell infiltration. In a feline model of spontaneous OSCC, a clinical LSD1 inhibitor (Seclidemstat or SP2577) was found to be safe and effectively inhibit the STAT3 network. Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling, which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4. Notably, LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422, offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition. This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
STAT3 Transcription Factor/metabolism* ; Animals ; Histone Demethylases/genetics* ; Phosphorylation ; Mouth Neoplasms/immunology* ; Mice ; Carcinoma, Squamous Cell/immunology* ; Disease Progression ; Cyclin-Dependent Kinase-Activating Kinase ; Precancerous Conditions/metabolism* ; Humans ; Cyclin-Dependent Kinases/metabolism* ; Disease Models, Animal

OBJECTIVE: To examine the expression of soluble major histocompatibility complex class I-related chain A (sMICA) in the serum in patients with oral squamous cell carcinoma (OSCC) and to explore its clinicopathological significance. METHODS: Seventy-eight OSCC patients were selected as an experiment group, and 19 healthy persons as a control group. The sMICA in the serum in the experiment group and the control group was detected by enzyme-linked immunosorbent assay. RESULTS: The detection rate of sMICA in the serum in the experiment group was 98.7% (77/78), with the 95% confidence interval 74.30-93.95 pg/mL and the median 82.17 pg/mL, The detection rate in the control group was 94.7% (18/19), with the 95% confidence interval 29.48-50.30 pg/mL and the median 37.54 pg/mL. The sMICA in the serum in the experiment group was higher than that in the control group (P<0.01). There was statistic difference in the serum sMICA in the experiment group among the different clinicopathological parameters such as tumor size, disease stage and regional lymph node status (P<0.05), but no difference was found in gender, age, and tumor differentiation (P>0.05). CONCLUSION The sMICA in the serum in the OSCC patients increases, and is related with the tumor size, disease stage and regional lymph node status. Determination of sMICA in the serum may provide useful information to evaluate the immune state of OSCC patients.
Aged ; Carcinoma, Squamous Cell ; blood ; immunology ; pathology ; Case-Control Studies ; Female ; Histocompatibility Antigens Class I ; blood ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Mouth Neoplasms ; blood ; immunology ; pathology ; Solubility

AIMTo study the antitumor effect of an immunoconjugate composed of pingyangmycin (PYM) and anti-type IV collagenase monoclonal antibody (mAb) 3G11.

METHODS3G11-PLG-PYM immunoconjugate was prepared by linking 2-iminothiolane (2-IT) modified mAb to PYM via N-succinimidyl-3-(2-pyridyldithiol) -propionate (SPDP) derived poly-alpha-L-glutamic acid (PLG) backbone as the intermediate drug carrier. Characterization of the conjugate was performed by SDS-PAGE and spectrophotometry. Immunoreactivity of the conjugate against type IV collagenase was determined by ELISA. The cytotoxicity of the conjugate to hepatoma 22 (H22) and KB cells was examined by MTT assay. Antitumor effect of the conjugate in vivo was evaluated in mice bearing subcutaneously implanted H22 tumor, the candidate drugs were administered intravenously by "q2d x 6" regimen.

RESULTSThe molecular weight of the conjugate was approximately 170 kD. The molecular ratio of 3G11-PLG-PYM was 1 : 2. 4 : 10. The conjugate retained part of the immunoreactivity of mAb 3G11 against the antigen. The cytotoxicity of the conjugate to H22 and KB cells was moderate comparing with free PYM. In vivo however, free PYM inhibited the growth of H22 by 60.6% on day 22 at the dose of 10 mg x kg(-1), while the equivalent dose of 3G11-PLG-PYM conjugate reached 90.8%. The median survival time of the mice treated with the conjugate was prolonged by 71.7% as compared with that of the untreated group, whereas that of free PYM prolonged only 10.9%. 3G11-PLG-PYM conjugate was notably more effective than free PYM in tumor suppression and life span prolongation.

CONCLUSION3G11-PLG-PYM displayed more marked antitumor efficacy than free PYM in vivo and might be a novel candidate for cancer treatment.

Animals ; Antibiotics, Antineoplastic ; pharmacology ; Antibodies, Monoclonal ; Bleomycin ; analogs & derivatives ; pharmacology ; Carcinoma, Squamous Cell ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Collagen Type IV ; immunology ; Female ; Humans ; Immunoconjugates ; chemistry ; pharmacology ; Liver Neoplasms, Experimental ; pathology ; Mice ; Molecular Weight ; Mouth Neoplasms ; pathology ; Neoplasm Transplantation

Abdominal Neoplasms ; diagnosis ; diagnostic imaging ; Adolescent ; Autoantibodies ; blood ; Diagnosis, Differential ; Female ; Humans ; Mouth Mucosa ; pathology ; Paraneoplastic Syndromes ; diagnosis ; immunology ; pathology ; Pemphigus ; diagnosis ; immunology ; pathology ; Skin ; pathology ; Tomography, X-Ray Computed

OBJECTIVETo study the effect of nm23-h1 transfection on proliferation characteristics of adnoid carcinoma cell lines in vitro and in vivo.

METHODSIn vitro ACC-M cell lines were incubated after putative anti-metastatic gene nm23-h1 was introduced into the cells with the help of G418 selective incubation base. The ACC-M cells were transplanted into 10 BALB/C nude mices subcutaneously and non-transfected cell lines were taken as control. Immunohisto chemistry and Ki67 antibody were employed to study the proliferation character of cell crawling pieces and paraffin-bedded slice, meanwhile, the solid tumor of both groups were prepared for flow cytometry(FCM).

RESULTSTransfected cells grew slower than non-transfected cells and this trend became more obvious as passages passed on. In vitro the expression of Ki67 of transfected cells was little stronger than non-transfected cells, while the expression of Ki67 in solid slices was almost negative in both groups. Transfected cells presented slower growth than non-transfected cells in the early stage (2 weeks) and 2 weeks later there was no obvious difference in size(P > 0.05). FCM value accorded well with the result.

CONCLUSIONIntroduction of nm23-h1 into the ACC-M cell lines may have transient inhibitory effects on its proliferation.

Animals ; Antibodies ; analysis ; Carcinoma, Adenoid Cystic ; genetics ; pathology ; Cell Division ; Cell Line, Tumor ; Female ; Genetic Therapy ; Ki-67 Antigen ; immunology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mouth Neoplasms ; genetics ; pathology ; NM23 Nucleoside Diphosphate Kinases ; Neoplasm Transplantation ; Nucleoside-Diphosphate Kinase ; Proteins ; genetics ; Transfection

OBJECTIVETo elucidate the functional status of dendritic cells (DC) in the tissue of oral squamous cell carcinoma by analyzing characteristic phenotype of them.

METHODS34 specimens from oral squamous cell carcinoma cases primarily treated with surgery were selected as test group. In addition, 30 specimens of normal mucosa from oral mucocele cases were used as control. Distribution of DC expressing CD1a+, HLA-DR+ and CD83+ in tumor tissue and normal mucous membrane was observed by immunohistochemistry. The number of DC expressing the antigens, which represented the density of DC infiltrating into tissue, was counted by microscope. The density of DC and the rate of DC expressing HLA-DR in oral carcinoma group and control were statistically compared.

RESULTSThere was no CD83+ DC in all cases, but CD1a+ DC was found in all samples. The density of CD1a+ DC in tumor tissue was significantly lower than that in normal mucous membrane (P < 0.05). HLA-DR antigen expressed on the surface of DC in tumoral epithelium of 27-case carcinoma specimens and in normal mucous epithelium of 23 cases. The rate of HLA-DR positive expression of TIDC had no statistic significance between the two groups.

CONCLUSIONThe lower density of DC infiltrating in tumor tissue might reflect the microenviromental immunodeficiency of hosts with oral squamous cell carcinoma, and the functional mature of DC might be inhibited by the immunosuppressive action of oral squamous cell carcinoma.

Adult ; Aged ; Antigens, CD ; Antigens, CD1 ; analysis ; Carcinoma, Squamous Cell ; immunology ; pathology ; Cell Count ; Dendritic Cells ; immunology ; metabolism ; Female ; HLA-DR Antigens ; analysis ; Humans ; Immunoglobulins ; analysis ; Immunohistochemistry ; Male ; Membrane Glycoproteins ; analysis ; Middle Aged ; Mouth Mucosa ; immunology ; pathology ; Mouth Neoplasms ; immunology ; pathology ; Phenotype

OBJECTIVETo study the Ag-NORs expressive character of T lymphocyte in patients with oral and maxillofacial tumor and evaluate its diagnostic value for the patients.

METHODSNucleolar organizer regions(NORs) of T lymphocyte from 86 normal adults, 102 patients with oral and maxillofacial benign tumors and 87 patients with oral and maxillofacial malignant tumors were analyzed through KL imaging system.

RESULTSThere was significant difference among normal adults, benign and malignant patients (P < 0.01). Their average I.S% values were 7.87 +/- 0.12, 5.72 +/- 0.14, 4.19 +/- 0.13, respectively.

CONCLUSIONThe expression of Ag-NORs of T lymphocyte has definite relation with oral and maxillofacial tumors; detection of Ag-NORs might play valuable in diagnosis of oral and maxillofacial tumors.

Adolescent ; Adult ; Antigens, Nuclear ; Diagnosis, Differential ; Female ; Humans ; Male ; Maxillary Neoplasms ; diagnosis ; immunology ; metabolism ; Middle Aged ; Mouth Neoplasms ; diagnosis ; immunology ; metabolism ; Nuclear Proteins ; biosynthesis ; genetics ; metabolism ; Nucleolus Organizer Region ; metabolism ; Silver Staining ; T-Lymphocytes ; diagnostic imaging ; metabolism ; Ultrasonography

OBJECTIVETo evaluate the effect of locoregional immunotherapy of interleukin 2 (IL-2) in combination with chemotherapy upon intratumoral lymphocytes in oral squamous cell carcinomas.

METHODSThirty-four patients with stage T3 or T4 oral squamous cell carcinoma were randomly divided into two groups, and treated with two therapies. 23 cases of them received immunochemotherapy and 11 cases received PVP chemotherapy. Changes of T lymphocyte subsets and B cells at tumor site in the two groups were compared before and after therapy.

RESULTSThe relative numbers of CD4+, CD8+, CD20+ before and after treatment in immunochemotherapy were respectively 36.96, 35.65, 28.65 and 56.61, 38.52, 38.70. The numbers of CD4+, CD20+ increased significantly after immunochemotherapy. However, in chemotherapy group, there was no significant difference in numbers of CD4+, CD8+ and CD20+ cells between pre and post treatment.

CONCLUSIONImmunochemotherapy for oral squamous cell carcinomas may play an important role in increasing local immunity.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; administration & dosage ; analogs & derivatives ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; pathology ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Female ; Humans ; Injections, Intralesional ; Interleukin-2 ; administration & dosage ; Male ; Middle Aged ; Mouth Neoplasms ; drug therapy ; immunology ; pathology ; T-Lymphocyte Subsets ; immunology ; Vincristine ; administration & dosage

OBJECTIVETo investigate the effect of anti-ICAm-1/LAF-1 McAb on the cytotoxicity of tumor infiltrating lymphocytes from oral squamous cell carcinoma.

METHODSTIL were isolated from fresh tumor tissues in 15 patients with oral squamous cell carcinoma and cultured in vitro. The expression of ICAM-1/LAF-1 in fresh and activated TIL was examined by FACS. The cytotoxicity of TIL against auto tumor cells and the level of TNF-alpha produced by TIL were compared before and after interrupted with anti-ICAM-1/LAF-1 McAb.

RESULTSThe expression of ICAM-1 and LAF-1 in the activated TIL significantly increased comparing with fresh TIL (P < 0.05). Interrupted by anti-ICAM-1 McAb, the cytotoxicity of TIL against auto tumor cell was not significantly changed. Interrupted by anti-ICAM-1 and anti-LAF-1 McAb, the level of TNF-alpha produced by TIL showed no differences comparing with the control (P < 0.05), but the cytotoxicity of TIL against auto tumor cells significantly decreased (P < 0.05).

CONCLUSIONThe effect of anti-LAF-1 McAb may result from steric interference of antigen-nonspecific adhesion process.

Antibodies, Monoclonal ; pharmacology ; Carcinoma, Squamous Cell ; immunology ; pathology ; Cells, Cultured ; Cytotoxicity, Immunologic ; Female ; Humans ; Intercellular Adhesion Molecule-1 ; biosynthesis ; genetics ; Lymphocyte Function-Associated Antigen-1 ; biosynthesis ; genetics ; Lymphocytes, Tumor-Infiltrating ; immunology ; pathology ; Male ; Mouth Neoplasms ; immunology ; pathology

OBJECTIVEThe purpose of this study was to investigate the transcription and expression levels of human leukocyte antigen-DR at different stages of oral squamous cell carcinomas.

METHODSThe specific monoclonal antibody and beta-locus specific oligonucleotide probes of human leukocyte antigen-DR were employed in this study. A total of 32 primary oral squamous cell carcinomas, 15 metastatic focuses and 26 histologically normal oral epithelia, were detected for the presence of the human leukocyte antigen-DR molecule by using immunohistochemistry and in situ hybridization.

RESULTSThe human leukocyte antigen-DR expression of the primary focuses was significantly higher than that of the normal epithelia (P < 0.05), but their expression did not show statistically difference between the metastatic focuses and the normal epithelia. The immunohistochemistric results were identical with those of in situ hybridization.

CONCLUSIONThe abnormal higher expression of the HLA-DR is a common character of primary oral squamous cell carcinomas, but it may be not relevant to the metastasis of tumors.

Carcinoma, Squamous Cell ; genetics ; immunology ; HLA-DR Antigens ; biosynthesis ; genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Mouth Mucosa ; immunology ; Mouth Neoplasms ; genetics ; immunology