TITLE

Impaired CD95 expression predisposes for recurrence in curatively resected colon carcinoma: clinical evidence for immunoselection and CD95L mediated control of minimal residual disease

AUTHOR(S)
Sträter, J.; Hinz, U.; Hasel, C.; Bhanot, U.; Mechtersheimer, G.; Lehnert, T.; Möller, P.
PUB. DATE
May 2005
SOURCE
Gut;May2005, Vol. 54 Issue 5, p661
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: Insulin-like growth factor (IGF) I receptor (IGF-Ir) signalling is required for carcinogenicity and proliferation of many tumours but this pathway has not been studied in detail in gastric cancer. We have previously shown successful therapy for colorectal, pancreatic, and lung cancer using recombinant adenoviruses expressing dominant negative (dn) IGF-Ir. In this study, we sought to better dissect the role of IGF-lr on progression of gastric cancer and determine whether IGF-Ir targeted adenoviruses represent potentially effective therapeutics for human gastric cancer. Methods: We assessed the effect of IGF-Ir ligancis on proliferation and survival in gastric cancer cells in culture. Then, recombinant adenoviruses expressing truncated IGF-Ir (482 and 950 amino acids long, IGF-Ir/dn) that function as dn inhibitors were studied in the treatment of human gastric cancer xenografts. We characterised the effects of IGF-Ir/dn on signalling blockade, growth, apoptosis induction, and in vivo therapeutic efficacy. Results: IGF-Ir signalling promoted tumour growth and survival in gastric cancer. IGF-Ir/dn expression suppressed humorigenicity both in vitro and in vivo and upregulated stressor induced apoptosis. IGF-Ir/dn blocked Akt-I activation induced by IGF-I, IGF-II, and des(1 -3)IGF-I, but not by insulin. IGF-Ir/ dn expression increased radiation and chemotherapy induced apoptosis and the combination of IGF-lr/dn and chemotherapy was very effective against tumours in mice. In an intraperitoneal model, IGF-Ir/dn therapy also suppressed peritoneal dissemination. Conclusions: IGF-Ir is involved in the regulation of survival and cell growth in human gastric cancer and may be a good molecular therapeutic target. Adenovirus-IGF-Ir/dn may thus have therapeutic use in gastric cancer.
ACCESSION #
16886340

 

Related Articles

  • MicroRNA Regulatory Network in Human Colorectal Cancer. Jie-Ting Tang; Jing-Yuan Fang // Mini Reviews in Medicinal Chemistry;Jul2009, Vol. 9 Issue 8, p921 

    Epigenetic modifications include DNA methylation, histone modifications, and noncoding RNAs containing microRNAs (miRNA). miRNAs are small noncoding RNAs that are 21 to 25 nt in length; they downregulate gene expression during cell development, cell proliferation, cell differentiation, and...

  • Colon polyps and colon cancer. Niedzielska, Iwona; Orawczyk, Tomasz; Szaniewski, Krzysztof; Ziaja, Krzysztof // Polish Surgery / Chirurgia Polska;2008, Vol. 10 Issue 1, p30 

    Among the various pathologies of the large intestine, special attention should be paid to polyps of the colon. Although the ability of polyps to progress from benign tissue to invasive malignancy is a very well known phenomenon, diagnostic tools allowing to identify suspicious specimens have not...

  • Sphingolipids in cancer. Furuya, Hideki; Shimizu, Yoshiko; Kawamori, Toshihiko // Cancer & Metastasis Reviews;Dec2011, Vol. 30 Issue 3/4, p567 

    The bioactive sphingolipids including, ceramide, sphingosine, and sphingosine-1-phosphate (S1P) have important roles in several types of signaling and regulation of many cellular processes including cell proliferation, apoptosis, senescence, angiogenesis, and transformation. Recent accumulating...

  • Regulatory roles of microRNA-708 and microRNA-31 in proliferation, apoptosis and invasion of colorectal cancer cells. SAN-LIN LEI; HUA ZHAO; HONG-LIANG YAO; YONG CHEN; ZHEN-DONG LEI; KUI-JIE LIU; QUN YANG // Oncology Letters;2014, Vol. 8 Issue 4, p1768 

    MicroRNAs (miRs) function as key regulators of gene expression and their deregulation is associated with the carcinogenesis of various cancers. In the present study, the aim was to validate the potential roles and regulatory mechanisms of mi-708 and mi-31 in colorectal cancer (CRC) cells. mi-708...

  • MicroRNA in colorectal cancer: from benchtop to bedside. Wu, William K.K.; Law, Priscilla T.Y.; Lee, Chung W.; Cho, Chi H.; Fan, Daiming; Wu, Kaichun; Yu, Jun; Sung, Joseph J.Y. // Carcinogenesis;Mar2011, Vol. 32 Issue 3, p247 

    Colon carcinogenesis represents a stepwise progression from benign polyps to invasive adenocarcinomas and distant metastasis. It is believed that these pathologic changes are contributed by aberrant activation or inactivation of protein-coding proto-oncogenes and tumor suppressor genes. However,...

  • Apoptosis of human colorectal carcinoma cells is induced by blocking hepatoma-derived growth factor. Liao, Fei; Dong, Weiguo; Fan, Lifang // Medical Oncology;Dec2010, Vol. 27 Issue 4, p1219 

    Hepatoma-derived growth factor (HDGF) is a novel multifunctional growth factor that elicits pleiotropic effects on biological processes such as lung remodeling and renal development. Recent studies demonstrated that HDGF is related to tumor proliferation, invasion, angiogenesis, and apoptosis....

  • Upregulation of miR-582-5p inhibits cell proliferation, cell cycle progression and invasion by targeting Rab27a in human colorectal carcinoma. Zhang, X; Zhang, Y; Yang, J; Li, S; Chen, J // Cancer Gene Therapy;Oct2015, Vol. 22 Issue 10, p475 

    Colorectal carcinoma (CRC) is known as the most common cancer. MicroRNAs (miRNAs) have been proven to have important roles in human carcinogenesis by regulating various target genes. Recently, the downregulation of miR-582-5p had been demonstrated in CRC. However, its function and the underlying...

  • RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. Olga Turovskaya; Dirk Foell; Pratima Sinha; Thomas Vogl; Robbin Newlin; Jonamani Nayak; Mien Nguyen; Anna Olsson; Peter P. Nawroth; Angelika Bierhaus; Nissi Varki; Mitchell Kronenberg; Hudson H. Freeze; Geetha Srikrishna // Carcinogenesis;Oct2008, Vol. 29 Issue 10, p2035 

    Patients with inflammatory bowel diseases are at increased risk for colorectal cancer, but the molecular mechanisms linking inflammation and cancer are not well defined. We earlier showed that carboxylated N-glycans expressed on receptor for advanced glycation end products (RAGE) and other...

  • Cell Signaling: An overview. Dhanasekaran, N // Oncogene;9/17/98 Review, Vol. 17 Issue 11, p1329 

    Reviews the articles about the mechanisms by which different receptors and signal-transducers regulate signal-interaction to form the signaling networks involved in cell proliferation, oncogenesis and apoptosis. Mechanisms by which G protein-coupled receptors mediate signal transduction and...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics