Gene Expression Levels of Cytokines in Peritoneal Washings from Patients with Gastric Cancer

Peritoneal seeding is frequently detected in patients with gastric cancer. The peritoneal cavity is a compartment in which the immunologic host-tumor interaction can occur. Here, we investigated the gene expression levels of cytokines, and compared these gene expressions with the progression of gastric cancer. Total RNA was extracted from 50 ml of peritoneal washings from 78 patients with gastric cancer and 11 noncancerous patients. The gene expression levels of transforming growth factor-β (TGF-β), interleukin (IL)-2, IL-6 and IL-12 were analyzed by real-time reverse transcription-polymerase chain reaction. The gene expression levels of TGF-β and IL-12 in 16 patients with peritoneal seeding (peritoneal metastasis or free cancer cells) did not differ from those in controls (n = 11) and stage I and II (n = 43) patients. However, the relative gene expression level of IL-2 in patients with peritoneal seeding (0.9) was lower than that in controls (1.4, p = 0.066) and stage I and II patients (1.4, p = 0.036). In contrast, the relative gene expression level of IL-6 in patients with peritoneal seeding (3.3) was higher than that in control (2.4, p = 0.064) and stage I and II patients (2.6, p = 0.065). Low IL-2 gene and high IL-6 gene expressions in the peritoneal cavity may correlate with cancer development in the peritoneal cavity in patients with gastric cancer.

[1]  B. Robinson,et al.  IL-2 Intratumoral Immunotherapy Enhances CD8+ T Cells That Mediate Destruction of Tumor Cells and Tumor-Associated Vasculature: A Novel Mechanism for IL-2 1 , 2003, The Journal of Immunology.

[2]  Shiu-Feng Huang,et al.  Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways , 2003, Oncogene.

[3]  S. Hart,et al.  Improved antitumour immunity in murine neuroblastoma using a combination of IL-2 and IL-12 , 2003, British Journal of Cancer.

[4]  D. Merlin,et al.  TGF‐β down‐regulates IL‐6 signaling in intestinal epithelial cells: Critical role of SMAD‐2 , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[5]  S. Tsujitani,et al.  Detection of cancer cells in the peripheral blood of gastric cancer patients. , 2003, International journal of molecular medicine.

[6]  F. Tas,et al.  Adjuvant Intraperitoneal Chemotherapy With Cisplatinum, Mitoxantrone, 5-Fluorouracil, and Calcium Folinate in Patients With Gastric Cancer: A Phase II Study , 2002, American journal of clinical oncology.

[7]  J. Norton,et al.  Macrophages as effector cells in interleukin 12-induced T cell-dependent tumor rejection. , 2002, Cancer research.

[8]  M. Ogawa,et al.  Extensive intraoperative peritoneal lavage and chemotherapy for gastric cancer patients with peritoneal free cancer cells , 2002, Gastric Cancer.

[9]  S. Noh,et al.  Treatment of advanced gastric cancer by palliative gastrectomy, cytoreductive therapy and postoperative intraperitoneal chemotherapy , 2002, The British journal of surgery.

[10]  T. Majima,et al.  Interleukin‐10 and interferon‐gamma levels within the peritoneal cavity of patients with gastric cancer , 2001, Journal of surgical oncology.

[11]  W. Gillanders,et al.  Quantitative real‐time RT‐PCR detection of breast cancer micrometastasis using a multigene marker panel , 2001, International journal of cancer.

[12]  S. Barni,et al.  Progress Report on the Palliative Therapy of 100 Patients with Neoplastic Effusions by Intracavitary Low-Dose Interleukin-2 , 2001, Oncology.

[13]  O. Dapunt,et al.  Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  P. Drew,et al.  Impaired interleukin-12 production is associated with a defective anti-tumor response in colorectal cancer , 1998, Diseases of the colon and rectum.

[15]  M. Klagsbrun,et al.  Endothelial cell surface alkaline phosphatase activity is induced by IL-6 released during wound repair. , 1997, The Journal of investigative dermatology.

[16]  P. Klingler,et al.  Transforming growth factor-beta synthesis by human peritoneal mesothelial cells. Induction by interleukin-1. , 1996, The American journal of pathology.

[17]  S. Tsujitani,et al.  Relationship between area of serosal invasion and intraperitoneal free cancer cells in patients with gastric cancer. , 1994, Anticancer research.

[18]  K. Nagano,et al.  Cytohistologic assessment of antitumor effects of intraperitoneal hyperthermic perfusion with mitomycin C for patients with gastric cancer with peritoneal metastasis , 1992, Cancer.

[19]  H. Fujiwara,et al.  Transforming growth factor-beta-induced inhibition of T cell function. Susceptibility difference in T cells of various phenotypes and functions and its relevance to immunosuppression in the tumor-bearing state. , 1991, Journal of immunology.

[20]  C. Marth,et al.  Transforming growth factor-beta and ovarian carcinoma cells: regulation of proliferation and surface antigen expression. , 1990, Cancer letters.

[21]  T. Matsui,et al.  Relationship between the cytologic characteristics of intraperitoneal free cancer cells and the prognosis in patients with gastric cancer. , 1990, Acta cytologica.

[22]  R L Vessella,et al.  Advances in Brief Amplification and Overexpression of Androgen Receptor Gene in Hormone-Refractory Prostate Cancer 1 , 2001 .

[23]  D. Kobayashi,et al.  Quantitative reverse transcription-PCR assay of the RNA component of human telomerase using the TaqMan fluorogenic detection system , 1998 .

[24]  R. Oyasu,et al.  Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro. , 1997, Cancer research.