Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).
Humans ; Mouth Neoplasms/pathology* ; Carcinoma, Squamous Cell/metabolism* ; Luteolin/therapeutic use* ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; Cell Line, Tumor

OBJECTIVETo probe the possible mechanism of growth-inhibitory and apoptosis of oral squamous cell carcinoma by arsenic trioxide.

METHODSThe induction of apoptosis in two tongue squamous carcinoma cells treated by arsenic trioxide was investigated. The morphology changes of the cells was observed under electron microscope. The mitochondrial transmembrane potential was detected using rhodamine 123 and flow cytometry. The cell cycle was detected by flow cytometry, and p16, p53, BCL-2, Caspase-3, and PARP changes were examined by western blot.

RESULTS1. The antiproliferative effect on the oral squamous carcinoma cells by arsenic trioxide was carried out through two ways: induction of apoptosis and toxicity damage. 2. Activation of the caspase-3 and PARP, while no changes of p16, p53, BCL-2 occurred. 3. Mitochondrial transmembrane potential collapse and G(2)-M stagnation were correlated with apoptosis of oral squamous cell carcinoma.

CONCLUSIONS1. Tubulins and mitochondria may be the chief action position of arsenic trioxide, which is the start-up factors of mechanism. 2. Activation of the caspase-3 proteolytic pathway may be one of the pivotal ways of apoptosis procedure induced by arsenic trioxide.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Blotting, Western ; Carcinoma, Squamous Cell ; drug therapy ; metabolism ; pathology ; Caspase 3 ; Caspases ; metabolism ; Cell Cycle ; drug effects ; DNA, Neoplasm ; drug effects ; metabolism ; Flow Cytometry ; Humans ; Intracellular Membranes ; drug effects ; physiology ; Membrane Potentials ; drug effects ; Mitochondria ; drug effects ; physiology ; Mouth Neoplasms ; drug therapy ; metabolism ; pathology ; Oxides ; pharmacology ; Poly(ADP-ribose) Polymerases ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Tumor Cells, Cultured ; drug effects ; ultrastructure ; Tumor Suppressor Protein p53 ; metabolism

PURPOSE: Surgical therapy is the primary treatment for oral cancer, but it can cause facial distortion. Therefore, if anticancer drugs are effective against oral cancer, they may be used preferentially. However, oral squamous carcinoma cells (OSCCs) are resistant to these drugs, so finding a way to enhance the sensitivity of these cells to anticancer drugs is important. The bacterial protein azurin is known to selectively enter cancer cells and induce apoptosis. In this study, we show the anticancer effect of azurin in OSCC. MATERIALS AND METHODS: OSCC cell line (YD-9) was subjected to azurin treatment. Cell viability, morphology and protein expression levels were monitored after treatment of azurin. Cells were also subjected to combination treatment of azurin with either 5-fluorouracil or etopside. RESULTS: Azurin-treated cells showed decreased cell viability accompanied by apoptotic phenotypes including morphological change, DNA breakage, and increases in p53 and cyclin B1 protein levels. Combination treatment of azurin with other anti-tumor agents caused an increase in sensitivity to anticancer drugs in azurin-treated YD-9 cells. CONCLUSION: Azurin has a strong synergistic anticancer effect on oral cancer cells when it is used along with anticancer drugs.
Antineoplastic Agents/*administration & dosage ; Apoptosis/drug effects ; Azurin/*administration & dosage/genetics ; Carcinoma, Squamous Cell/*drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cyclin B1/metabolism ; Drug Synergism ; Etoposide/administration & dosage ; Fluorouracil/administration & dosage ; Humans ; Mouth Neoplasms/*drug therapy/metabolism/pathology ; Tumor Suppressor Protein p53/metabolism

OBJECTIVETo investigate the treatment and prognosis of the patients with oral mucosal melanoma (OMM).

METHODSThe clinicopathological and follow-up data of patients with OMM in Sun Yat-sen University Cancer Center from January 1976 to December 2005 were analyzed retrospectively.

RESULTSFifty-one cases were analyzed. The pathological lymph node metastasis rate was 61% (31/51) and the affected sites were confined to level I(b)-III (94%). The overall three year and five yearsurvival rates were 35% and 21% respectively. No significant difference of three year and five year survival rates were found between the group of incisional biopsy and the group of excisional biopsy. The prognosis was not affected by pigmentation. The survival rate of the patients receiving surgery combined with biotherapy or biochemotherapy was significantly higher than that of the patients treated by other modalities (P = 0.003).

CONCLUSIONSIn patients with OMM, lymph node metastasis was mostly confined to level I(b)-III. Incisional biopsy and pigmentation were not associated with an unfavorable prognosis. The prognosis of the patients with OMM was poor and the patients may get a better prognosis by receiving surgery combined with biotherapy or biochemotherapy.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; BCG Vaccine ; therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Interferon-gamma ; therapeutic use ; Interleukin-2 ; therapeutic use ; Lung Neoplasms ; secondary ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Melanoma ; drug therapy ; pathology ; surgery ; Melanoma-Specific Antigens ; metabolism ; Middle Aged ; Mouth Mucosa ; pathology ; surgery ; Mouth Neoplasms ; drug therapy ; pathology ; surgery ; Retrospective Studies ; S100 Proteins ; metabolism ; Survival Rate

OBJECTIVETo observe the expression changes of VEGF, iNOS and the level of MVD and NO during the evolution of Golden hamster cheek pouch carcinogenesis. To study the effect of NO in carcinogenesis in the pouch of hamster, and to investigate the effect of NOS inhibitor L-NAME in interfering with carcinogenesis.

METHODS90 golden hamsters were divided into three groups: 40 in experiment group, 40 in control group and 10 in blank group. DMBA was painted on hamster's cheek pouch in experiment and control group, L-NAME was given to hamster in experiment group at the dose of 0.02 ml/g. Hamsters were killed at 6, 9, 12 and 16th weeks, respectively. The blank group was killed at the 16th week. SABC immunohistochemistry assay was used to detect the expression of iNOS, VEGF and factor VIII-related antigen. MVD was measured. The level of NO was measured by Spectrophotometry.

RESULTSThe difference between control group and experiment group at the 12th week and 16th week was observed. The difference of positive expression rate of iNOS in all group was significant and difference between blank group and control group was significant. The difference of positive expression rate of VEGF in all group was significant and difference between blank group and control group at the 12th and 16th week was significant; there was significant difference in every group MVD from the 6th week control group to the 16th week control. There were significant difference among the control group, except the 6th week of experiment and control group.

CONCLUSIONThere is an increased expression of iNOS and the level of NO, as well MVD during the evolution of Golden hamster cheek pouch carcinogenesis from slightly dysplasia to invasive carcinoma. NO plays an important role during the evolution of carcinogenesis, and iNOS inhibitor L-NAME can inhibit the carcinogenesis.

Animals ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; Cricetinae ; Enzyme Inhibitors ; pharmacology ; Mesocricetus ; Mouth Neoplasms ; drug therapy ; pathology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Nitric Oxide Synthase Type II ; antagonists & inhibitors ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVEThe aim of this study was to investigate the delivery of Cucurbitacin BE to cervical lymph nodes by peri-cancer submucosal injection of the average diameter 85 nm Cucurbitacin BE polylactic acid nanoparticles (CuBE-PLA-NP).

METHODSCervical lymph node metastasis model of mice oral cancer was established and CuBE-PLA-NP and CuBE were injected in peri-cancer submucosal of the mice respectively, the concentration in blood, heart, liver, spleen, lung, kidney and cervical lymph node were measured by high performance liquid chromatography at fifteen time points, Targeted cervical lymph nodes were evaluated by targeting index, selectivity index, targeting efficiency, relative targeting efficiency and ratio of maximum concentration.

RESULTS(1) The CuBE concentration in the cervical lymph nodes after CuBE-PLA-NP injection was far higher than that after CuBE injection at every time point, the CuBE duration in the cervical lymph nodes in CuBE-PLA-NP group was far longer than that in CuBE group; (2) The five targeted values of the cervical lymph nodes in CuBE-PLA-NP group was far higher than that in CuBE group; (3) The CuBE concentration in blood, heart, liver, spleen, lung and kidney in CuBE-PLA-NP group was far lower than that in CuBE group.

CONCLUSIONThe CuBE-PLA-NP can specifically deliver CuBE to the cervical lymph nodes by peri-cancer submucosal injection, increase CuBE concentration and duration in metastasized cervical lymph nodes, and decrease drug concentration of other organs.

Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; Carcinoma, Squamous Cell ; drug therapy ; surgery ; Cucurbitacins ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Female ; Lactic Acid ; administration & dosage ; pharmacokinetics ; Lymph Nodes ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Mice ; Mouth Neoplasms ; drug therapy ; surgery ; Nanotechnology ; Neck ; Particle Size ; Polyesters ; Polymers ; administration & dosage ; pharmacokinetics ; Triterpenes ; administration & dosage ; pharmacokinetics

OBJECTIVEThe aim of this study was to investigate the target delivery of Cucurbitacin BE (CuBE) to cervical lymph nodes by peri-oral-cancer submucosal injection of the average diameter 85 nm Cucurbitacin BE poly-lactic acid nanoparticles (CuBE-PLA-NP) and evaluate its clinical therapy efficacy.

METHODSCuBE and CuBE-PLA-NP were respectively injected into peri-oral-cancer submucosa at 2, 12, 24, 48, 72, 96, 120, 144, 168 and 192 hours before operation in 26 patients with oral cancer. The concentrations of CuBE in cervical lymph nodes and blood were measured by high performance liquid chromatography (HPLC) at every time point. Cancer cell degeneration and necrosis in metastasis foci of cervical lymph nodes were observed using light microscope and electron microscope.

RESULTS(1) The CuBE concentrations in cervical lymph nodes after CuBE-PLA-NP injection were far higher than those after CuBE injection at every time point, the duration of CuBE existing in the cervical lymph nodes in CuBE-PLA-NP group was far longer than those in CuBE group, the area under the CuBE concentrations-time curve of the cervical lymph nodes in CuBE-PLA-NP group was 43.67 times as many as that in CuBE group; (2) The CuBE ratio of maximum concentrations in the cervical lymph nodes in CuBE-PLA-NP group was 106.46 times as high as that in CuBE group; (3) The CuBE concentrations in the blood in CuBE-PLA-NP group was far lower than that in CuBE group; (4) Cancer cell necrosis and degeneration in the metastasis foci of cervical lymph nodes were found in CuBE-PLA-NP group, necrosis and degeneration were not found in CuBE group.

CONCLUSIONThe peri-oral-cancer submucosa injection of the average diameter of 85 nm CuBE-PLA-NP can specifically delivery CuBE to the cervical lymph nodes, enhance treatment efficiency, and reduce general toxicity.

Adult ; Aged ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; Carcinoma, Squamous Cell ; drug therapy ; surgery ; Chromatography, High Pressure Liquid ; Cucurbitacins ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Female ; Humans ; Lactic Acid ; administration & dosage ; Lymph Nodes ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Mouth Neoplasms ; drug therapy ; surgery ; Nanotechnology ; Neck ; Particle Size ; Polyesters ; Polymers ; administration & dosage ; Triterpenes ; administration & dosage ; pharmacokinetics