Integrin ανβ6 Acts as a Prognostic Indicator in Gastric Carcinoma

Zhang, Z.-Y.; Xu, Kesen; Wang, J.-S.; Yang, Guangli; Wang, W.; Wang, J.-Y.; Niu, Wei; Liu, E.-Y.; Mi, Yuetang; Ni, Jun

doi:10.1016/j.clon.2007.09.008

Cited by 93 publications

(79 citation statements)

References 22 publications

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“…As a result, this approach may be useful for the delivery of various drugs for enhanced therapeutic index against colon cancer. Moreover, because ITGB6 is also specifically expressed in a variety of epithelial carcinomas (45)(46)(47)(48), ITGB6-targeted immunoliposomes may represent a potential strategy for the clinical treatment of additional cancers.…”

Section: Discussionmentioning

confidence: 99%

Integrinβ6-Targeted Immunoliposomes Mediate Tumor-Specific Drug Delivery and Enhance Therapeutic Efficacy in Colon Carcinoma

Liang

Shahbaz

Wang

et al. 2015

Clinical Cancer Research

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Purpose: Adjuvant chemotherapy is one of the significant treatments for colon cancer in clinic. However, it does not achieve the desired therapeutic efficacy, largely due to chemotherapeutic resistance. Integrinb6 (ITGB6) is expressed in malignant colonic epithelia, but not in normal epithelia, and is associated with the progression, metastasis, and chemotherapeutic resistance of colon cancer. Accordingly, it is necessary to design therapeutic approaches for efficient and targeted drug delivery into ITGB6-positive cancer cells to improve chemotherapeutic efficacy in colon cancer.Experimental Design: PEGylated liposomes were employed to design ITGB6-targeted immunoliposomes, which have ITGB6 monoclonal antibodies (mAbs) conjugated. We evaluated the ITGB6-targeted immunoliposomes internalization into colon cancer cells and examined 5-fluorouracil (5-FU)-induced cellular apoptosis produced by ITGB6-targeted immunoliposomesþ5-FU. In addition, the biodistribution and antitumor efficiency of ITGB6-targeted immunoliposomes were observed in vivo.Results: ITGB6-targeted immunoliposomes enhanced cellular internalization in ITGB6-positive colon cancer cells compared with liposomes. Furthermore, the ITGB6-targeted immunoliposome internalization was dependent on the ITGB6 expression level on cellular surface. ITGB6-targeted immunoliposomes decreased the 5-FU IC 50 more than 90% in HT-29 and SW480b6 cells relative to liposomes. Moreover, when loaded with 5-FU, ITGB6-targeted immunoliposomes produced an approximately 1.5-fold higher 5-FU-induced cellular apoptosis rate than liposomes. In vivo, the therapeutic activity of ITGB6-targeted immunoliposomesþ5-FU was significantly superior, resulting in 25% to 35% reduction of tumor weight compared with 5-FU or liposomesþ5-FU.Conclusions: ITGB6-targeted immunoliposomes provide a highly efficient approach for targeted drug delivery in colon cancer and thus offer the potential of a novel and promising anticancer strategy for clinical therapy.

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Section: Discussionmentioning

confidence: 99%

Integrinβ6-Targeted Immunoliposomes Mediate Tumor-Specific Drug Delivery and Enhance Therapeutic Efficacy in Colon Carcinoma

Liang

Shahbaz

Wang

et al. 2015

Clinical Cancer Research

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“…We assessed the Gal-9 staining using a method as previously described (Zhang et al, 2008). In brief, intensity of the staining: 0, no staining; 1, weak staining; 2, moderate staining; 3, strong staining; ratio of staining cells: 0, no staining cells; 1, 2% staining cells; 2, 2~10% staining cells; 3, 11~29% staining cells; 4, ≥ 30% staining cells.…”

Section: Assessment Of Galectin-9 Staining In the Tissue Sectionsmentioning

confidence: 99%

Galectin-9 Acts as a Prognostic Factor with Antimetastatic Potential in Hepatocellular Carcinoma

Zhang¹,

Dong²,

Chen³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

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“…Although the ␣ v ␤ 6 integrin was chosen as the model target for this HTS study, this approach can be applied to the identification of molecular imaging agents that target any cell surface receptor. The ␣ v ␤ 6 integrin is an interesting target because although its expression is generally low or undetectable in normal epithelium, upregulation of this integrin has been linked with multiple types of cancer and was recently identified as a prognostic indicator for such diseases (26)(27)(28)(29)(30). Herein we report the combination of OBOC chemistry and solid-phase radiolabeling for the implementation of a high-throughput in vivo methodology for the identification of previously uncharacterized fluorine-18 radiolabeled molecular imaging agents for the ␣ v ␤ 6 integrin.…”

mentioning

confidence: 99%

High-throughput in vivo screening of targeted molecular imaging agents

Gagnon¹,

Hausner²,

Mařı́k³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The rapid development and translation of targeted molecular imaging agents from bench to bedside is currently a slow process, with a clear bottleneck between the discovery of new compounds and the development of an appropriate molecular imaging agent. The ability to identify promising new molecular imaging agents, as well as failures, much earlier in the development process using high-throughput screening techniques could save significant time and money. This work combines the advantages of combinatorial chemistry, sitespecific solid-phase radiolabeling, and in vivo imaging for the rapid screening of molecular imaging agents. A one-bead-one-compound library was prepared and evaluated in vitro, leading to the identification of 42 promising lead peptides. Over 11 consecutive days, these peptides, along with a control peptide, were successfully radiolabeled with 4-[ 18 F]fluorobenzoic acid and evaluated in vivo using microPET. Four peptides were radiolabeled per day, followed by simultaneous injection of each individual peptide into 2 animals. As a result, 4 promising new molecular imaging agents were identified that otherwise would not have been selected based solely on in vitro data. This study is the first example of the practical application of a high-throughput screening approach using microPET imaging of [ 18 F]-labeled peptides for the rapid in vivo identification of potential new molecular imaging agents.high-throughput screening ͉ in vivo imaging ͉ microPET ͉ radiolabeled peptides ͉ positron emission tomography C ombinatorial chemistry (1, 2) and phage display (3) techniques have become essential tools for the production of large compound libraries, which can be rapidly produced for the discovery of new drugs. Designing and implementing high-throughput screening (HTS) approaches to identify lead compounds that show affinity for a biological target from these large libraries, wherein millions of new compounds may exist, is often accomplished through in vitro screening. In general, the 2 approaches by which this can be accomplished are either solution-phase screening techniques (4-11), generally used by drug discovery programs, or solid-phase screening, which has garnered interest for the evaluation of libraries prepared using combinatorial chemistry.Though there are many reports outlining high-throughput approaches for in vitro screening, few exist where the sole purpose is to develop high-throughput in vivo methodologies for the identification of new molecular imaging agents. While the feasibility of using magnetic resonance imaging (MRI) for high-throughput applications has been explored with both the development of scanner technology and the scanning of multiple animals in parallel (12)(13)(14)(15)(16)(17)(18)(19)(20), positron emission tomography (PET) has received very little attention for high-throughput applications. This is likely the result of the unique set of problems that arise when considering using the latter imaging modality. The half-lives of the radioactive isotopes commonly used for PET ar...

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Integrin ανβ6 Acts as a Prognostic Indicator in Gastric Carcinoma

Cited by 93 publications

References 22 publications

Integrinβ6-Targeted Immunoliposomes Mediate Tumor-Specific Drug Delivery and Enhance Therapeutic Efficacy in Colon Carcinoma

Integrinβ6-Targeted Immunoliposomes Mediate Tumor-Specific Drug Delivery and Enhance Therapeutic Efficacy in Colon Carcinoma

Galectin-9 Acts as a Prognostic Factor with Antimetastatic Potential in Hepatocellular Carcinoma

High-throughput in vivo screening of targeted molecular imaging agents

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