Casticin impairs cell growth and induces cell apoptosis via cell cycle arrest in human oral cancer SCC‐4 cells

Casticin, a polymethoxyflavone, present in natural plants, has been shown to have biological activities including anti‐cancer activities. Herein, we investigated the anti‐oral cancer activity of casticin on SCC‐4 cells in vitro. Viable cells, cell cycle distribution, apoptotic cell death, reactive oxygen species (ROS) production, and Ca²⁺ production, levels of ΔΨ_m and caspase activity were measured by flow cytometric assay. Cell apoptosis associated protein expressions were examined by Western blotting and confocal laser microscopy. Results indicated that casticin induced cell morphological changes, DNA condensation and damage, decreased the total viable cells, induced G₂/M phase arrest in SCC‐4 cells. Casticin promoted ROS and Ca²⁺ productions, decreases the levels of ΔΨ_m, promoted caspase‐3, ‐8, and ‐9 activities in SCC‐4 cells. Western blotting assay demonstrated that casticin affect protein level associated with G2/M phase arrest and apoptosis. Confocal laser microscopy also confirmed that casticin increased the translocation of AIF and cytochrome c in SCC‐4 cells. In conclusion, casticin decreased cell number through G₂/M phase arrest and the induction of cell apoptosis through caspase‐ and mitochondria‐dependent pathways in SCC‐4 cells.     

4项肿瘤标志物在肺癌诊断中的临床应用价值

目的探讨肿瘤标志物的联合检测在肺癌诊断及鉴别诊断中的应用价值。方法采用化学发光法检测109例肺癌患者血清中癌胚抗原(CEA)、神经特异性烯醇化酶(NSE)、细胞角蛋白21-1片段(CYFRA21-1)和鳞状细胞癌抗原(SCC)的含量,并与66例肺部良性疾病患者和45例健康者进行对比分析。结果肺癌患者血清CEA、NSE、CYFRA21-1、SCC的阳性率分别为49.5%,45.9%,56.9%和21.1%,其中在非小细胞肺癌(NSCLC)的鳞癌中CYFRA21-1阳性率最高,腺癌中CEA最高,小细胞肺癌(SCLC)中NSE最高;前3项标志物联合检测可将敏感性提高到90.1%,特异性为82.9%。4项标志物联合检测敏感性达91.7%,但特异性只有72.9%。结论血清肿瘤标志物CEA、NSE和CYFRA21-1联合检测可提高肺癌诊断的敏感度,SCC检测有助于鉴别肺癌的病理分型,建议联合检测方式以CEA、NSE和CYFRA21-1为佳。     

皮肤癌诊治探讨

目的探讨皮肤癌的临床诊断及有效治疗方法。方法对根据临床表现及病理确诊的58例基底细胞癌及鳞状细胞癌患者进行手术治疗。结果瘤体切除后，7例直接切除拉拢缝合者均达Ⅰ期愈合，23例行局部皮瓣转移修复者，皮瓣成活良好且外观满意。28例植皮修复者2例表皮营养不良，3例部分植皮坏死，均经换药愈合。随访42例，38例未见复发及转移。结论皮肤癌手术治疗效果满意。     

食管癌患者血清CEA、SCC和Cyfra21-1含量检测及临床意义

目的：探讨血清肿瘤标志物癌胚抗原(CEA)、鳞状细胞癌相关性抗原(SCC)和角化素蛋白片段19(Cyfra21-1)在食管癌的诊断、治疗和预后判断及随访中的作用。方法：以电发光免疫测定法(ECLIA)和微粒酶联免疫测定法(MEIA)检测206例食管癌患者术前和其中71例术后血清中CEA、Cyfra21-1和SCC的水平。检测结果采用SPSS10．0统计软件进行t检验和X^2检验。结果：肿瘤体积愈大、病期愈晚、肿瘤浸润愈深,患者术前血清CEA、SCC和Cyfra21-1总体水平愈高,早期患者水平较低。三者中,CEA和Cyfra21-1的个体差异较大,Cyfra21-1相关性最好。术后检测血清的71例中,92．9％的患者三种血清标志物降至正常。全组患者CEA和Cyfra21-1的阳性率分别为29．1％和45．1％,两者联合检测阳性率为57．3％。165例手术切除者Ⅰ、Ⅱ、Ⅲ期的CEA阳性率分别为16．6％、26．8％和30．8％;Cyfra21-1分别为27．8％、37．5％和50．5％;两者联合检测阳性率分别为38．9％、50．0％和63．7％。结论血清CEA、SCC、Cyfra21-1联合检测可用于食管癌的辅助诊断以及对病期及预后的判断。三者中Cyfra21-1更有意义。     

The syndrome of inappropriate antidiuretic hormone secretion associated with induction chemotherapy for squamous cell carcinoma of the head and neck

Two patients with squamous cell carcinoma of the head and neck are reported in whom the syndrome of inappropriate antidiuretic hormone (SIADH) secretion occurred transiently during the rapid cytolytic phase of tumor destruction after chemotherapy with cis-platinum diamminedichloride and bleomycin. Immunoperoxidase staining for ADH of the original biopsy specimens from both patients was negative. Possible mechanisms for and the implications of the production of SIADH in this setting are discussed.     

Anti-benzopyrene-7,8-diol-9,10-epoxide induces apoptosis via mitochondrial pathway in human bronchiolar epithelium cells independent of the mitochondria permeability transition pore

Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a ubiquitous environmental pollutant contained in tobacco smoke, automobile exhausts and barbecued foods. The carcinogenicity of BPDE on animals has been well characterized, whereas its apoptotic effect is not well defined. A recent study has shown that BPDE-mediated apoptotic pathway has varying specificity across different cell lines. Squamous cell carcinoma (SCC) arises from bronchiolar epithelium cells, therefore, we set out to investigate the pulmonary toxicity and apoptotic effect of BPDE in human bronchiolar epithelium cells (16HBE). Our results show BPDE induces mitochondrial-mediated apoptosis in a dose-dependent manner in 16HBE cells. The cleavage of caspase-3,-9 and release of Cytochrome c (cyt c) was regulated during apoptotic stimulation. However, the opening of mitochondria permeability transition pore (mPTP) has not been detected. Furthermore, our data also indicate that the formation of reactive oxygen species (ROS), decline of mitochondrial membrane potential (ΔΨ_m), increasing p53 and decreasing c-Myc levels play important roles in response to BPDE toxicity. In conclusion, these results suggest that BPDE-mediated apoptosis occurs via caspase-9 dependent mitochondria pathway associated with ROS formation, loss of ΔΨ_m, up-regulation of p53 and down-regulation of c-Myc, but independent of the opening of mPTP in 16HBE cells.     

Epidermal growth factor receptor (EGFR) and squamous cell carcinoma of the skin: molecular bases for EGFR-targeted therapy

Cutaneous squamous cell carcinoma (SCC) ranks second in the frequency of all skin tumors. Its incidence has risen significantly due to an increased sun exposure and the number of immunocompromised patients. It has a well-defined progression with known precursor lesions called actinic keratosis. The degree of cellular differentiation, tumor thickness, location, and other features has prognostic value. It has a better prognosis than mucosal SCC of the head and neck, also called head and neck squamous cell carcinoma (HNSCC).Ultraviolet light plays a fundamental role as an initiator and promoter of carcinogenesis of SCC, allowing the accumulation of genetic alterations that allows a selective growth advantage. The TP53 (p53) gene often mutates and Ras is frequently activated, but with low frequency of mutations. Normally, the extracellular signals determine whether the cells move from a quiescent state into an active proliferative state. In tumor cells an increase in the production of growth factors and its receptors can be often seen that gives rise to such an autocrine circuit facilitating cellular division. Recently, frequent mutations in the epidermal growth factor receptor (EGFR) have been detected in lung cancer, mainly deletions in exon 19 and L858R mutation in exon 21. These are located at the EGFR tyrosine kinase domain (TK). EGFR TK mutations produce activation of the signaling pathways downstream and preferentially activated antiapoptotic pathways (PI3K/AKT, JAK-STAT and ERK/MAPK). These mutations are correlated with the clinical response of patients to tyrosine kinase inhibitors (gefinitib and erlotinib), because the tumor cells are addicted to the constant activation of specific signaling pathways. Glioblastoma shows another EGFR mutation (EGFRvIII), corresponding to a deletion of the extracellular domain, and it is present in 24-67% of these tumors. This variant has been found in 42% of HNSCC, related to the poor response to monoclonal antibody cetuximab.Many observations show that there are abnormalities in the expression of epidermal growth factor receptor (EGFR) and/or its ligands in HNSCC with frequent activation of multiple pathways downstream EGFR, and unrelated to RAS mutation. This suggests the possibility of activation by mutation or overexpression of a component of the pathway located upstream-Ras. While in other tumors, especially lung cancer and glioblastoma, the EGFR mutations are frequent genetic events, it is unknown whether EGFR is mutated or amplified in SCC of the skin and what would be its pathogenic role in this malignancy and its precursors.