Sensitivity of scirrhous gastric cancer to 5-fluorouracil and the role of cancer cell-stromal fibroblast interaction

Nakajima, Koichi; Okita, Yutaka; Matsuda, Sachi

doi:10.3892/or.12.1.85

Cited by 6 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While former research has mainly focused on genetic or epigenetic alterations within cancer cells, it has become increasingly apparent that the tumor microenvironment plays a decisive role in conditions of cancer cell resistance to therapy . Therefore, various models have been established to mimic cell–cell and cell–matrix interactions, including 2D and 3D in vitro culture models, spheroid models and coculture experiments using cancer cells and primary fibroblasts . These studies have provided important information concerning both the impact of paracrine communication between tumor cells and fibroblasts, and the interaction between extracellular matrix, integrins, and multiple intracellular signal cascades in epithelial tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…26,27 Therefore, various models have been established to mimic cell-cell and cell-matrix interactions, including 2D and 3D in vitro culture models, 28 spheroid models 29 and coculture experiments using cancer cells and primary fibroblasts. 30 These studies have provided important information concerning both the impact of paracrine communication between tumor cells and fibroblasts, and the interaction between extracellular matrix, integrins, and multiple intracellular signal cascades in epithelial tumor cells. However, these systems fail to entirely reflect the complex tissue architecture of a solid tumor.…”

Section: Cancer Cell Biologymentioning

confidence: 99%

See 1 more Smart Citation

Phosphorylation of AKT(Ser473) serves as an independent prognostic marker for radiosensitivity in advanced head and neck squamous cell carcinoma

Freudlsperger

Horn

Weißfuß

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by high resistance to radiotherapy, which critically depends on both altered signaling pathways within tumor cells and their dynamic interaction with the tumor microenvironment. This study evaluated the prognostic value of the phosphorylation status of AKT on Ser473 and Thr308 for the clinical outcome of patients with advanced HNSCC on radiotherapy. Furthermore, we investigated the impact of AKT(Ser473) phosphorylation [p-AKT(Ser473)] in the context of radioresistance using ex vivo tissue cultures that resemble the complex tissue architecture and paracrine interaction with the tumor microenvironment. In a cohort of 120 patients with advanced HNSCC, who were treated with primary or adjuvant radiotherapy, a significant association was found between relative p-AKT(Ser473) levels and overall survival (p 5 0.006) as well as progression-free survival (p 5 0.021), while no significant correlation was revealed for relative p-AKT(Thr308) levels. In ex vivo tissue cultures p-AKT(Ser473) levels were increased upon irradiation and treatment with the PI3K inhibitor LY294002 inhibited both basal and irradiation induced AKT(Ser473) phosphorylation. Strikingly, pretreatment with LY294002 sensitized tissue cultures derived from primary and recurrent tumors to radiotherapy as determined by impaired tumor cell proliferation and enhanced DNA damage. In conclusion, phosphorylation status of AKT(Ser473) in tumor specimens serves as a novel biomarker to identify patients with advanced HNSCC at high risk for treatment failure following radiotherapy, and our data from ex vivo tissue cultures support the assumption that pharmacological inhibition of AKT(Ser473) phosphorylation might circumvent radioresistance to improve efficiency and reduce toxicity of current treatment modalities.Head and neck squamous cell carcinoma (HNSCC), an entity that comprises epithelial cancer of the oral cavity, oropharynx, hypopharynx and larynx is the sixth leading cancer by incidence worldwide.1 While advances in surgery and chemoradiation have provided better organ preservation, only modest improvement in the 5-year survival of HNSCC patients have been achieved in the last decades.2,3 Locoregional recurrence remains the major form of treatment failure as up to 60% of patients develop local recurrence within the first 2 years. 4 As radiosensitivity of tumor cells is a critical determinant for local control and clinical outcome there is an urgent need for novel strategies to understand and predict the characteristics of resistant cells.The cellular and molecular mechanisms of resistance to radiotherapy remain rather elusive. Several intracellular signaling pathways have been implicated in mediating

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Cancer Cell Biologymentioning

confidence: 99%

Phosphorylation of AKT(Ser473) serves as an independent prognostic marker for radiosensitivity in advanced head and neck squamous cell carcinoma

Freudlsperger

Horn

Weißfuß

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Since then, its inhibitory effects have been reported on the proliferation of a range of cell types: dermal fibroblasts [56,75], myofibroblasts [59], microvascular endothelial cells [76], vascular smooth muscle cells [77,78], and mesangial cells [79]. In addition to normal cells, tranilast exerts an anti-proliferative influence on several tumor cells, such as; smooth muscle cells hyperplasia [80], pancreatic cancer cells [81], uterine leiomyoma cells [82], malignant glioma cells [83], gastric cancer cells [84,85], prostate cancer cells [86], breast cancer cells [87][88][89], neurofibroma cells [90] and squamous cell carcinoma [58].…”

Section: Tranilast As An Anti-proliferative Drugmentioning

confidence: 99%

“…Furthermore, it inhibited gastric carcinoma growth, proliferation and invasion, and also induced apoptosis through blocking the growth-interactions between fibroblasts and scirrhous gastric cancer cells in vivo [84]. In addition, the combined treatment of tranilast with the chemotherapeutic agent CDDP decreased the xenografted tumor size [85].…”

Section: Gastric Cancermentioning

confidence: 99%

Tranilast: A review of its therapeutic applications

Darakhshan

Pour

2015

Pharmacological Research

248

225

View full text Add to dashboard Cite

“…The tumour microenvironment has gained increasing attention in gastric cancer. Macrophages, fibroblasts and granulocytes contribute to tumour development, and relationships between tumour cells and tumour‐infiltrating immune cells are known to influence outcome. Therefore, incorporating the influence of immune cells into a TNM predictive model may provide more prognostic information.…”

Section: Introductionmentioning

confidence: 99%

Tryptase expression as a prognostic marker in patients with resected gastric cancer

Lin

Liu

Zhang

et al. 2017

British Journal of Surgery

View full text Add to dashboard Cite

show abstract

Sensitivity of scirrhous gastric cancer to 5-fluorouracil and the role of cancer cell-stromal fibroblast interaction

Cited by 6 publications

References 0 publications

Phosphorylation of AKT(Ser473) serves as an independent prognostic marker for radiosensitivity in advanced head and neck squamous cell carcinoma

Phosphorylation of AKT(Ser473) serves as an independent prognostic marker for radiosensitivity in advanced head and neck squamous cell carcinoma

Tranilast: A review of its therapeutic applications

Tryptase expression as a prognostic marker in patients with resected gastric cancer

Contact Info

Product

Resources

About