We studied 1809 oral cancer patients who visited and were treated in 2002 at the 148 institutions certified as training facilities by the Japanese Society of Oral and Maxillofacial Surgeons, which is composed of 39 dental university hospitals, 44 medical university hospitals, 64 general hospitals, and 1 unknown institution. The patients consisted of 1071 (59.2 %) males and 738 (40.8 %) females (male:female ratio, 1.45:1), who had a mean age of 65.2 years old. The tongue (40.2 %) was the most common site affected, followed by the gingiva (32.7 %), buccal mucosa (10.1 %), and oral floor (9.0 %). There were 6 cases of intraoral multiple cancer. In histopathological examinations, squamous cell carcinoma (88.7 %) was the most common type found, followed by adenoid cystic carcinoma (2.1 %), and mucoepidermoid carcinoma (1.7 %). In addition, non-epithelial tumors comprised 1.8 % , among which malignant melanoma was the most common type. Cases classified as T2N0 were the most common (32.1 %), followed by T1N0 (21.4 %), T4N0 (8.0 %), and T2N1 (7.6 %). Distant metastasis occurred in 17 patients (1.0 %). The sizes of the non-epithelial malignant tumors ranged from 1.0 to 7.0 cm, with a mean size of 3.7 cm.
Asian Continental Ancestry Group ; Carcinoma, Adenoid Cystic ; Carcinoma, Mucoepidermoid ; Carcinoma, Squamous Cell ; Epidemiologic Studies ; Female ; Floors and Floorcoverings ; Gingiva ; Hospitals, General ; Hospitals, University ; Humans ; Male ; Melanoma ; Mouth Mucosa ; Mouth Neoplasms ; Neoplasm Metastasis ; Surgery, Oral ; Tongue

We studied 1809 oral cancer patients who visited and were treated in 2002 at the 148 institutions certified as training facilities by the Japanese Society of Oral and Maxillofacial Surgeons, which is composed of 39 dental university hospitals, 44 medical university hospitals, 64 general hospitals, and 1 unknown institution. The patients consisted of 1071 (59.2 %) males and 738 (40.8 %) females (male:female ratio, 1.45:1), who had a mean age of 65.2 years old. The tongue (40.2 %) was the most common site affected, followed by the gingiva (32.7 %), buccal mucosa (10.1 %), and oral floor (9.0 %). There were 6 cases of intraoral multiple cancer. In histopathological examinations, squamous cell carcinoma (88.7 %) was the most common type found, followed by adenoid cystic carcinoma (2.1 %), and mucoepidermoid carcinoma (1.7 %). In addition, non-epithelial tumors comprised 1.8 % , among which malignant melanoma was the most common type. Cases classified as T2N0 were the most common (32.1 %), followed by T1N0 (21.4 %), T4N0 (8.0 %), and T2N1 (7.6 %). Distant metastasis occurred in 17 patients (1.0 %). The sizes of the non-epithelial malignant tumors ranged from 1.0 to 7.0 cm, with a mean size of 3.7 cm.
Asian Continental Ancestry Group ; Carcinoma, Adenoid Cystic ; Carcinoma, Mucoepidermoid ; Carcinoma, Squamous Cell ; Epidemiologic Studies ; Female ; Floors and Floorcoverings ; Gingiva ; Hospitals, General ; Hospitals, University ; Humans ; Male ; Melanoma ; Mouth Mucosa ; Mouth Neoplasms ; Neoplasm Metastasis ; Surgery, Oral ; Tongue

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused a worldwide pandemic. Our aim in this study is to produce new fusion inhibitors against SARS-CoV-2, which can be the basis for developing new antiviral drugs. The fusion core comprising the heptad repeat domains (HR1 and HR2) of SARS-CoV-2 spike (S) were used to design the peptides. A total of twelve peptides were generated, comprising a short or truncated 24-mer (peptide #1), a long 36-mer peptide (peptide #2), and ten peptide #2 analogs. In contrast to SARS-CoV, SARS-CoV-2 S-mediated cell-cell fusion cannot be inhibited with a minimal length, 24-mer peptide. Peptide #2 demonstrated potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 µM concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 µM). Peptide #2 inhibited the SARSCoV-2 pseudovirus assay at IC50=1.49 µM. Given their potent inhibition of viral activity and safety and lack of cytotoxicity, these peptides provide an attractive avenue for the development of new prophylactic and therapeutic agents against SARS-CoV-2.

A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused a worldwide pandemic. Our aim in this study is to produce new fusion inhibitors against SARS-CoV-2, which can be the basis for developing new antiviral drugs. The fusion core comprising the heptad repeat domains (HR1 and HR2) of SARS-CoV-2 spike (S) were used to design the peptides. A total of twelve peptides were generated, comprising a short or truncated 24-mer (peptide #1), a long 36-mer peptide (peptide #2), and ten peptide #2 analogs. In contrast to SARS-CoV, SARS-CoV-2 S-mediated cell-cell fusion cannot be inhibited with a minimal length, 24-mer peptide. Peptide #2 demonstrated potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 µM concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 µM). Peptide #2 inhibited the SARSCoV-2 pseudovirus assay at IC50=1.49 µM. Given their potent inhibition of viral activity and safety and lack of cytotoxicity, these peptides provide an attractive avenue for the development of new prophylactic and therapeutic agents against SARS-CoV-2.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC50 values of 12.6, 21.8, and 11.12 μM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 μM with no observed toxicity in Vero cells at 10 μM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.

Azoospermia/therapy* ; Female ; Humans ; Male ; Microdissection ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Sperm Injections, Intracytoplasmic ; Sperm Motility ; Sperm Retrieval ; Spermatozoa ; Testis