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

BACKGROUND: Lung cancer is one of the highest morbidity and mortality in the world and it is very important to find an effective anti-tumor method. Microwave hyperthermia, a new treatment technology, has been getting more and more attention. This study was designed to investigate the effects of microwave hyperthermia combined with gemcitabine on the proliferation and apoptosis of human lung squamous cell carcinoma (NCI-H1703 and NCI-H2170) in vitro. METHODS: The proliferation of cells treated with microwave hyperthermia, the effect of gemcitabine on cell proliferation and the proliferation of cells treated with different methods of microwave hyperthermia and gemcitabine were detected by CCK-8 assay. Colony formation assay was used to measure the colony formation of human lung squamous cell carcinoma cells. Flow cytometry assay was used to detect the total apoptosis rates of the treated cells. Caspase-3, Caspase-8 activity assay was used to detect the activity of Caspase-3, Caspase-8 enzyme in each group of cells. CCK-8 assay was used to detect the effect of control group, AC-DEVD (Caspase-3 inhibitor) group, thermalization combined group, and thermal AC-DEVD combined group on cell proliferation. The levels of p53, Caspase-3, Cleaved-Caspase-3, PARP, Bax and BCL-2 protein expression were detected using Western blot assay. RESULTS: Our results demonstrated that microwave hyperthermia inhibited the proliferation of lung squamous cell carcinoma. The IC₅₀ values of gemcitabine for the two cells were 8.89 μmol/L and 44.18 μmol/L, respectively. The first chemotherapy after microwave hyperthermia has synergistic effect on the two lung squamous cell carcinoma cells and can significantly inhibit the cell clone formation (P<0.001), promote cell apoptosis (P<0.001) and increase Caspase-3 enzyme activity (P<0.001). However, it has no effect on Caspase-8 enzyme activity (P>0.05). Furthermore, Western blot analysis showed that microwave hyperthermia combined with gemcitabine could up-regulate the p53, Caspase-3, Cleaved-Caspase-3, Cleaved-PARP and Bax protein expression. CONCLUSIONS Microwave hyperthermia combined with gemcitabine remarkably inhibit the proliferation and induce apoptosis of human lung squamous cell carcinoma in vitro. This effect may be associated with the activation of p53, cleavage of PARP protein, and induced the Caspase-3 dependent apoptosis.
Apoptosis ; drug effects ; radiation effects ; Carcinoma, Squamous Cell ; pathology ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; radiation effects ; Combined Modality Therapy ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Humans ; Hyperthermia, Induced ; Lung Neoplasms ; pathology ; Microwaves

OBJECTIVETo investigate the effects of survivin short hairpin RNA (shRNA) on survivin expression, cell apoptosis, and chemosensitivity of human tongue cancer cell Tca8113 to cisplatin.

METHODSSurvivin-directed shRNA plasmid vector was delivered into Tca8113 cells with lipofectamine(TM) 2000 reagent. Survivin expression was detected with the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Flow cytometry was used to examine cell apoptosis, and the sensitivity to anticancer agents was evaluated by methyl thiazolyl tetrazolium (MTT) assay.

RESULTSAfter survivin shRNA vector transfection in Tca8113 cells, the expression of mRNA/protein declined significantly, and the apoptotic rate increased in time-dependent manner up to 37.9% at 48 hours. RNAi-mediated survivin reduction selectively inhibited growth and enhanced chemosensitivity of cisplatin but not of 5-fluorouracil.

CONCLUSIONSSurvivin shRNA could inhibit the expression of survivin mRNA and it's protein and enhance the chemosensitivity of cisplatin.

Apoptosis ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; pathology ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; Genetic Vectors ; Humans ; Liposomes ; Microtubule-Associated Proteins ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; Tongue Neoplasms ; drug therapy ; genetics ; pathology ; Transfection

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/pathology* ; Anaplastic Lymphoma Kinase/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Mutation ; Cytoskeletal Proteins/genetics* ; Lung/pathology* ; Oncogene Proteins, Fusion/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Tumor Suppressor Protein p53/genetics*

OBJECTIVETo observe the effect of Fuzheng Yiliu Granule (FZYLG) on cell cycle and nuclear transcription factor-kappa B (NF-kappa B) in tissue of esophageal-gastric carcinoma.

METHODSSeventy-six patients with esophageal gastric carcinoma were randomly divided into two groups, the FZYLG group and the control group. FZYLG was given to the former for 15 days. The tumor tissue in both groups was resected and cell cycle and apoptosis rate as well as NF-kappa B were determined by flowcytometry.

RESULTSLevel of NF-kappa B in the treated group was significantly higher than that in the control group (P < 0.05). In the treated group, the percentage of G0/G1 stage cells were significantly increased and that of S stage significantly decreased (both P < 0.05). At the same time, obvious cell apoptosis was found in the treated group, the apoptosis rate of which was significantly higher than that in the control group (P < 0.01).

CONCLUSIONFZYLG can increase the NF-kappa B expression, block the proliferation to promote the apoptosis of tumor cells.

Adenocarcinoma ; drug therapy ; pathology ; Adult ; Aged ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; Cell Cycle ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Esophageal Neoplasms ; drug therapy ; pathology ; Female ; Humans ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Phytotherapy ; Stomach Neoplasms ; drug therapy ; pathology

BACKGROUND AND OBJECTIVEThe effect of gefitinib on advanced non-small cell lung cancer (NSCLC) was various. How to choose the sensitive patients and improve the effect was difficulty in clinic. This study was to assess the correlation of epidermal growth factor receptor (EGFR) mutations and HER2/3 protein expression with the effect of gefitinib on Chinese patients with advanced NSCLC.

METHODSFrom May 2002 to February 2005, a total of 106 Chinese NSCLC patients who had failed at least one chemotherapy regimen were treated with gefitinib 250 mg once a day. The mutations in the exons 18-24 of EGFR gene were detected in the tumor tissues from 106 patients before the treatment of gefitinib, and HER2/3 expression in 84 tumor samples were detected by immunohistochemistry.

RESULTSMutation was identified in 32 (30.2%) tumor tissues. Overall remission rate was significantly higher in the HER2 high expression patients than in the HER2 low expression patients (36.8% vs 17.4%, P=0.044). HER2 and HER3 expression levels were not associated with time to progression (TTP) and overall survival (OS). The patients with HER2/3 single high expression had relatively longer TTP and OS than those with HER2/3 single low expression (6.1 vs 9.1 months, P=0.725; 6.1 vs 9.0 months, P=0.862), while those with concomitant HER2/3 high expression had significant longer TTP and OS. EGFR-mutated patients with HER2 expression or high HER2 and HER3 expressions were more sensitive to gefitinib.

CONCLUSIONEGFR mutations combined with HER2/3 expressions is a significant predictor for gefitinib efficacy on Chinese patients with advanced NSCLC.

Adenocarcinoma ; drug therapy ; genetics ; metabolism ; pathology ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; metabolism ; pathology ; Exons ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Receptor, ErbB-2 ; metabolism ; Receptor, ErbB-3 ; metabolism ; Remission Induction ; Survival Rate

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

Ras is best known for its ability to regulate cell growth, proliferation and differentiation. Mutations in Ras are associated with the abnormal cell proliferation which can result in incidence of all human cancers. Extracellular signal-regulated kinase (ERK) is a downstream effector of Ras and plays important roles in prognosis of tumors. Recently, evidence has gradually accumulated to demonstrate that there are other effectors between Ras and ERK, these proteins interact each other and constitute the thorough Ras/Raf/MEK/ERK signaling pathway. The pathway has profound effects on incidence of esophageal carcinoma and clinical applications of some chemotherapeutic drugs targeting the pathway. Further understanding of the relevant molecular mechanisms of Ras/Raf/MEK/ERK signaling pathway can be helpful for the development of efficient targeting therapeutic approaches which contribute to the treatment of esophageal cancer. In this article, roles of Ras/Raf/MEK/ERK signaling pathway in esophageal carcinoma as well as pharmacological targeting point in the pathway are reviewed.
Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; enzymology ; pathology ; Cell Line, Tumor ; Enzyme Activation ; drug effects ; Esophageal Neoplasms ; drug therapy ; enzymology ; pathology ; Extracellular Signal-Regulated MAP Kinases ; antagonists & inhibitors ; metabolism ; Humans ; Mitogen-Activated Protein Kinase Kinases ; antagonists & inhibitors ; metabolism ; Proto-Oncogene Proteins c-raf ; antagonists & inhibitors ; metabolism ; Signal Transduction ; drug effects ; ras Proteins ; antagonists & inhibitors ; metabolism

Esophageal carcinosarcoma is a rare malignant esophageal neoplasm consisting of both carcinomatous and sarcomatous elements, with an incidence of 0.5%. There have been only a few case reports of carcinosarcoma and squamous cell carcinoma coexisting in the esophagus. However, all of these are cases of synchronous or metachronous development of carcinosarcoma after chemoradiotherapy in patients of esophageal squamous cell carcinoma. A 53-year-old man underwent esophagogastroduodenoscopy because of chest pain for several months. Endoscopic examination revealed a huge pedunculated esophageal polypoid mass. Endoscopic submucosal dissection (ESD) was performed and histopathologic examination confirmed spindle cell carcinoma (carcinosarcoma). He refused additional esophagectomy. After 21 months, third follow-up endoscopy showed poorly-demarcated flat, faint discolored lesions at different location from the previous ESD site and endoscopic biopsies confirmed squamous cell carcinoma. To the best of our knowledge, this is the first case of metachronous development of esophageal squamous cell carcinoma in a patient with esophageal carcinosarcoma.
Antineoplastic Agents/therapeutic use ; Carcinoma, Squamous Cell/*diagnosis/drug therapy/pathology ; Carcinosarcoma/*diagnosis/drug therapy/pathology ; Cisplatin/therapeutic use ; Drug Therapy, Combination ; Endoscopy, Digestive System ; Esophageal Neoplasms/*diagnosis/drug therapy/pathology ; Fluorouracil/therapeutic use ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; S100 Proteins/metabolism ; Tomography, X-Ray Computed ; Tumor Suppressor Protein p53/metabolism

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