tranilast and Carcinoma--Squamous-Cell

Recent evidence suggests that the targeting of membrane proteins specifically activated in cancer stem cells (CSCs) is an important strategy for cancer therapy. The objectives of the present study were to investigate the expression and activity of ion-transport-related molecules in the CSCs of esophageal squamous cell carcinoma.. Cells exhibiting strong aldehyde dehydrogenase 1 family member A1 (ALDH1A1) activity were isolated from TE8 cells by fluorescence-activated cell sorting, and CSCs were then generated with the sphere formation assay. The gene expression profiles of CSCs were examined by microarray analysis.. Among TE8 cells, ALDH1A1 messenger RNA and protein levels were higher in CSCs than in non-CSCs. The CSCs obtained were resistant to cisplatin and had the ability to redifferentiate. The results of the microarray analysis revealed that the expression of 50 genes encoding plasma membrane proteins was altered in CSCs, whereas that of several genes related to ion channels, including transient receptor potential vanilloid 2 (TRPV2), was upregulated. The TRPV2 inhibitor tranilast was more cytotoxic at a lower concentration in CSCs than in non-CSCs, and effectively decreased the number of tumorspheres. Furthermore, tranilast significantly decreased the cell population that strongly expressed ALDH1A1 among TE8 cells.. The results of the present study suggest that TRPV2 is involved in the maintenance of CSCs, and that its specific inhibitor, tranilast, has potential as a targeted therapeutic agent against esophageal squamous cell carcinoma.

Topics: Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Esophageal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Molecular Targeted Therapy; Neoplasm Proteins; Neoplastic Stem Cells; ortho-Aminobenzoates; Retinal Dehydrogenase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Spheroids, Cellular; TRPV Cation Channels

As circumferential or near-circumferential endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms might evoke refractory strictures, multiple sessions of endoscopic balloon dilation (EBD) are required. We aimed to assess the effectiveness and safety of oral agent tranilast with EBD for improving the efficacy of stricture dilation after esophageal ESD.. In an open-label prospective study at a single institution, 31 asymptomatic consecutive patients with superficial esophageal squamous cell carcinomas were enrolled from April 2007 to October 2010. After ESD, we performed scheduled EBD (twice weekly for 4 wk) with or without administration of oral agent tranilast for 8 weeks. Thereafter, we added additional EBD on the basis of solid criteria-for example, patient's awareness of vomiting >1/wk and inability of passage of routine endoscope through the ESD site. We compared the rates of post-ESD strictures and the numbers of additional EBD sessions for 48 weeks after ESD and the Dysphagia score between tranilast (T)-group and none (N)-group, based on patients' subjective symptoms, at 16, 24, and 48 weeks after ESD.. The percentage of post-ESD strictures in T-group was significantly lower than that in N-group (P=0.04). The median numbers of additional EBD sessions and Dysphagia score at 16 and 24 weeks after ESD in T-group were significantly smaller than those in N-group (P=0.0138, 0.002, 0.005, respectively). No adverse events and no recurrence were observed.. We demonstrated for the first time that scheduled EBD combined with oral agent tranilast might be effective and safe for improving the efficacy of stricture dilation after esophageal ESD.

Topics: Administration, Oral; Aged; Carcinoma, Squamous Cell; Catheterization; Dissection; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophageal Stenosis; Esophagus; Female; Humans; Male; Middle Aged; ortho-Aminobenzoates; Pilot Projects; Prospective Studies; Treatment Outcome

Development of a new therapeutic approach to improve the prognosis of high grade invasion of oral squamous cell carcinoma is needed. To elucidate the effect of a fibroblast inhibitor (tranilast), we investigated the proliferation and metastasis of oral squamous cell carcinoma in a mouse model. The effect of tranilast on tumour growth, lymph node metastases, microvessel density, and the proliferating cell nuclear antigen (PCNA) labelling index of oral squamous cell carcinoma implanted into the tongue of nude mice was evaluated. Tumour growth and the incidence of cervical lymph node metastases were significantly suppressed by the administration of tranilast. The amount of fibrous tissue, the microvessel density, and the PCNA labelling index of tumour were also significantly reduced. Administration of a fibroblast inhibitor may well be clinically effective for the treatment of oral squamous cell carcinoma.

Topics: Animals; Antineoplastic Agents; Body Weight; Carcinoma, Squamous Cell; Cell Division; Female; Fibroblasts; Humans; Lymphatic Metastasis; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Mouth Neoplasms; Neoplasm Transplantation; Neovascularization, Pathologic; ortho-Aminobenzoates; Tumor Cells, Cultured