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

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*

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 explore the differences in sensitivity to rapamycin of five esophageal squamous cell carcinoma cell lines with different differentiation and the changes of sensitivity of the cells after siRNA-interfered expression of p70S6K.

METHODSEffects of rapamycin on proliferation of ESCC cell lines with different differentiation, EC9706, TE-1, Eca109, KYSE790 and KYSE450 cells, were investigated using cell counting kit 8 (CCK-8) assay, and according to the above results, the EC9706 cells non-sensitive to rapamycin were chosen to be transfected with p70S6K-siRNA. The changes in sensitivity of cells to rapamycin were measured in vitro and in vivo using CCK-8 kit, flow cytometry and tumor formation in nude mice.

RESULTSCCK-8 results showed that all the five cell line cells were sensitive to low concentration of rapamycin (<100 nmol/L), but TE-1 and EC9706 cells, which were with poor differentiation, showed resistance to high concentration of rapamycin. After EC9706 cells were treated with 50, 100, 200, 500 and 1 000 nmol/L rapamycin and p70S6K-siRNA, the proliferation rates of EC9706 cells were (48.67 ± 1.68)%, (15.45 ± 1.54)%, (14.00 ± 0.91)%, (10.97 ± 0.72)% and (2.70 ± 0.32)%, respectively, and were significantly lower than that of cells treated with 50, 100, 200, 500 and 1 000 nmol/L rapamycin and control siRNA [(74.53 ± 1.71)%, (68.27 ± 1.35)%, (71.74 ± 2.44)%, (76.23 ± 1.02)% and (80.21 ± 2.77)%] (P<0.05 for all). The results of flow cytometry showed that the ratios of cells in G1 phase of the p70S6K-siRNA, rapamycin and p70S6K-siRNA+ rapamycin groups were (53.82 ± 1.78)%, (57.87 ± 4.01)% and (73.73 ± 3.68)%, respectively, significantly higher than that in the control group (46.09 ± 2.31)% (P<0.05 for all). The results of tumor formation test in vivo showed that the inhibitory effect of rapamycin on tumor growth was stronger after the cells were transfected with p70S6K-siRNA, and the inhibition rate was 96.5%.

CONCLUSIONESCC cells with different differentiation have different sensitivity to rapamycin, and p70S6K-siRNA can improve the sensitivity of cells to rapamycin in vitro and in vivo.

Animals ; Antibiotics, Antineoplastic ; pharmacology ; Carcinoma, Squamous Cell ; drug therapy ; metabolism ; pathology ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Esophageal Neoplasms ; drug therapy ; metabolism ; pathology ; Humans ; Mice ; Mice, Nude ; RNA, Small Interfering ; Ribosomal Protein S6 Kinases, 70-kDa ; genetics ; metabolism ; Signal Transduction ; Sirolimus ; pharmacology ; Transfection

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

Adenocarcinoma ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Adult ; Antigens, Neoplasm ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Female ; Humans ; Hysterectomy ; Iridium Radioisotopes ; therapeutic use ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Preoperative Period ; Radiotherapy, Adjuvant ; Retrospective Studies ; Serpins ; metabolism ; Treatment Outcome ; Uterine Cervical Neoplasms ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery

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

The prognostic value of T category for locoregional control in patients with nasopharyngeal carcinoma (NPC) has decreased with the extensive use of intensity-modulated radiotherapy (IMRT). We aimed to develop a prognostic scoring system (PSS) that incorporated tumor extension and clinical characteristics for locoregional control in NPC patients treated with IMRT. The magnetic resonance imaging scans and medical records of 717 patients with nonmetastatic NPC treated with IMRT at Sun Yat-sen University Cancer Center between January 2003 and January 2008 were reviewed. Age, pathologic classification, primary tumor extension, primary gross tumor volume (GTV-p), T and N categories, and baseline lactate dehydrogenase (LDH) level were analyzed. Hierarchical cluster analysis as well as univariate and multivariate analyses were used to develop the PSS. Independent prognostic factors for locoregional relapse included N2-3 stage, GTV-p ≥26.8 mL, and involvement of one or more structures within cluster 3. We calculated a risk score derived from the regression coefficient of each factor and classified patients into four groups: low risk (score 0), intermediate risk (score >0 and ≤1), high risk (score >1 and ≤2), and extremely high risk (score >2). The 5-year locoregional control rates for these groups were 97.4%, 93.6%, 85.2%, and 78.6%, respectively (P < 0.001). We have developed a PSS that can help identify NPC patients who are at high risk for locoregional relapse and can guide individualized treatments for NPC patients.
Adolescent ; Adult ; Aged ; Carcinoma ; Carcinoma, Squamous Cell ; diagnosis ; drug therapy ; metabolism ; pathology ; radiotherapy ; Chemoradiotherapy ; Female ; Humans ; Kaplan-Meier Estimate ; L-Lactate Dehydrogenase ; metabolism ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; drug therapy ; metabolism ; pathology ; radiotherapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; methods ; Risk Assessment ; methods ; Tumor Burden ; Young Adult

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 efficacy and toxicity of neoadjuvant chemotherapy with paclitaxel and carboplatin or cisplatin for patients with locally advanced cervical cancer.

METHODSA total of 70 patients with locally advanced cervical cancer were treated with neoadjuvant chemotherapy with paclitaxel and carboplatin or cisplatin in our department from July 2007 to May 2010. The stage distribution among the patients included 45 stage IB2, 21 stage IIa, and 4 stage IIb. Of the 70 patients, 6 were G1, 26 were G2, 32 were G3, and the rest 6 patients were not histologically classified. Sixty-five patients had squamous cell carcinoma, 3 had adenocarcinoma, and 2 patients had adenosquamous cell carcinoma. The clinicopathological parameters were analyzed, and their impact on tumor response were investigated.

RESULTSOf the 70 patients, 14 (20.0%) showed a complete response, 37 (52.9%) had a partial response to chemotherapy, making an overall response rate of 72.9%. Sixty-eight (95.7%) patients underwent surgery, and among them 12 (17.1%) pathological CR were identified. Eleven (16.2%) patients were found to have lymph node metastasis after surgery. Response rates of stage Ib2 and IIa patients were 73.7% and 52.3%, respectively, P<0.05. Patients with SCC exhibited a better response rate than patients with adenocarcinoma and adenosquamous cell carcinoma (73.8% vs. 60.0%). Initial tumor volume, histological classification and cycles of neoadjuvant chemotherapy were not significantly correlated with the response rate.

CONCLUSIONPaclitaxel and carboplatin or cisplatin regimen is a promising therapy with definite short-term efficacy, can improve the resection rate with tolerable side effects, and is an applicable option of treatment for patients with locally advanced cervical cancer in the neoadjuvant setting.

Adenocarcinoma ; drug therapy ; immunology ; pathology ; surgery ; Adult ; Antigens, Neoplasm ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Adenosquamous ; drug therapy ; immunology ; pathology ; surgery ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; pathology ; surgery ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Remission Induction ; Serpins ; metabolism ; Uterine Cervical Neoplasms ; drug therapy ; immunology ; pathology ; surgery