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Wada, Norihito; Otani, Yoshihide; Kubota, Tetsuro; Kimata, Masaru; Minagawa, Akiko; Yoshimizu, Nobunari; Kameyama, Kaori; Saikawa, Yoshiro; Yoshida, Masashi; Furukawa, Toshiharu; Fujisawa, Masato; Kumai, Koichiro; Okada, Yasunori; Kitajima, Masaki

doi:10.1023/a:1025453500148

Cited by 15 publications

(4 citation statements)

References 19 publications

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“…Angiogenesis was evaluated by an index of MVD described in previous reports. , The tumor sections (5 μm) prepared for immunohistochemistry were stained with CD31 to quantify the vessel density inside tumors. In brief, the paraffin-embedded sections were prepared for antigen retrieval after being dewaxed, rehydrated, and microwaved.…”

Section: Methodsmentioning

confidence: 99%

“…Marimastat (MATT), a broad-spectrum synthetic enzyme inhibitor, can achieve greater than 50% enzyme inhibition of collagenases, gelatinases, and MMPs, even at a nanomolar concentration; it mimics MMP substrates and thus displays competitive and potent, but reversible, suppression. ,, MATT inhibits tumor progression by inhibiting metastasis. Nevertheless, it is not cytotoxic and therefore cannot kill tumor cells, which dramatically compromises its antitumor efficacy.…”

mentioning

confidence: 99%

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Nanoplatform Assembled from a CD44-Targeted Prodrug and Smart Liposomes for Dual Targeting of Tumor Microenvironment and Cancer Cells

et al. 2018

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The tumor microenvironment (TME) plays a critical role in tumor initiation, progression, invasion, and metastasis. Therefore, a therapy that combines chemotherapeutic drugs with a TME modulator could be a promising route for cancer treatment. This paper reports a nanoplatform self-assembled from a hyaluronic acid (HA)-paclitaxel (PTX) (HA-PTX) prodrug and marimastat (MATT)-loaded thermosensitive liposomes (LTSLs) (MATT-LTSLs) for the dual targeting of the TME and cancer cells. Interestingly, the prodrug HA-PTX can self-assemble on both positively and negatively charged liposomes, forming hybrid nanoparticles (HNPs, 100 nm). Triggered by mild hyperthermia, HA-PTX/MATT-LTSLs HNPs rapidly release their payloads into the extracellular environment, and the released HA-PTX quickly enters 4T1 cells through a CD44-HA affinity. The HNPs possess promoted tumor accumulation (1.6-fold), exhibit deep tumor penetration, and significantly inhibit the tumor growth (10-fold), metastasis (100%), and angiogenesis (10-fold). Importantly, by targeting the TME and maintaining its integrity via inhibiting the expression and activity of matrix metalloproteinases (>5-fold), blocking the fibroblast activation by downregulating the TGF-β1 expression (5-fold) and suppressing the degradation of extracellular matrix, the HNPs allow for significant metastasis inhibition. Overall, these findings indicate that a prodrug of an HA-hydrophobic-active compound and liposomes can be self-assembled into a smart nanoplatform for the dual targeting of the TME and tumor cells and efficient combined treatment; additionally, the co-delivery of MATT and HA-PTX with the HNPs is a promising approach for the treatment of metastatic cancer. This study creates opportunities for fabricating multifunctional nanodevices and offers an efficient strategy for disease therapy.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Nanoplatform Assembled from a CD44-Targeted Prodrug and Smart Liposomes for Dual Targeting of Tumor Microenvironment and Cancer Cells

et al. 2018

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“…For example, Yanagihara et al (22) reported that a cDNA microarray analysis demonstrated dramatic upregulation of MMP-1 (ratio: 29.63) in the 44As3 gastric cancer cell subline which shows frequent metastasis to the peritoneum, in comparison to parental HSC-44PE cells. In addition, previous studies reported that an MMP inhibitor reduced the peritoneal dissemination of human gastric cancer cell lines in mice (18,23). Taken together, our results and the previous findings indicate that the upregulation of MMP-1 expression following the loss of HIF-1α might be an important step in the development of peritoneal dissemination from MKN45 and MKN74 gastric cancer cells.…”

Section: Discussionmentioning

confidence: 92%

Knockdown of hypoxia-inducible factor-1α accelerates peritoneal dissemination via the upregulation of MMP-1 expression in gastric cancer cell lines

Hiraki

Kitajima

Kai

et al. 2012

Experimental and Therapeutic Medicine

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This study was performed to clarify the role of hypoxia-inducible factor-1 α (HIF-1α) in the development of peritoneal dissemination in a xenograft mouse model of gastric cancer. HIF-1α knockdown (KD) and control (SC) gastric cancer cells, which were established using the MKN45 and MKN74 cell lines, were studied. The two paired cell lines were directly inoculated into the peritoneal cavity of nude mice. The number and the weight of disseminated nodules were compared between tumors generated from the KD and SC cells. In addition, the molecular mechanism was addressed through analysis of the expression levels of metastasis-related genes. The MKN45-KD cell line demonstrated significantly greater numbers of disseminated nodules and formed a larger tumor mass than the MKN45-SC cell line (p<0.05). MKN74-KD cells also tended to induce a greater number of nodules and to produce those with a heavier weight than the SC cells. An in vitro adhesion assay revealed differing results regarding the adhesion activity to extracellular matrix and monolayer mesothelium cells of the gastric cancer cells derived from the various parental cells. However, the expression of MMP-1 mRNA in the disseminated nodules was significantly increased in the KD cells compared to the SC cells derived from the two parental cell lines (p<0.01). An immunohisto-chemical study further demonstrated that there was stronger staining for MMP-1 in the MKN74-KD in comparison to MKN74-SC cells. Loss of HIF-1α may contribute to the development of aggressive peritoneal dissemination via the upregulation of MMP-1 in gastric cancer cells.

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“…Furthermore, marimastat decreased the tumour growth in mice injected with MGLVA1 human gastric tumours (Wada et al 2003). In the clinical setting a phase I study of marimastat showed an acceptable safety proWle in 35 patients with advanced GC or carcinoma of the GEJ.…”

Section: Matrix Metalloproteinase (Mmp) Inhibitorsmentioning

confidence: 99%

Gastric cancer in the era of molecularly targeted agents: current drug development strategies

Arkenau

2009

J Cancer Res Clin Oncol

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Gastric cancer is the second most common cause of cancer death worldwide with approximately one million cases diagnosed annually. Despite considerable improvements in surgical techniques, innovations in clinical diagnostics and the development of new chemotherapy regimens, the clinical outcome for patients with advanced gastric cancer and cancer of the GEJ is generally poor with 5-year survival rates ranging between 5 and 15%. The understanding of cancer relevant events has resulted in new therapeutic strategies, particularly in developing of new molecular targeted agents. These agents have the ability to target a variety of cancer relevant receptors and downstream pathways including the epidermal growth factor receptor (EGFR), the vascular endothelial growth factor receptor (VEGFR), the insulin-like growth factor receptor (IGFR), the c-Met pathway, cell-cycle pathways, and down-stream signalling pathways such as the Akt-PI3k-mTOR pathway. In the era of new molecularly targeted agents this review focuses on recent developments of targeting relevant pathways involved in gastric cancer and cancer of the GEJ.

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Untitled

Cited by 15 publications

References 19 publications

Nanoplatform Assembled from a CD44-Targeted Prodrug and Smart Liposomes for Dual Targeting of Tumor Microenvironment and Cancer Cells

Nanoplatform Assembled from a CD44-Targeted Prodrug and Smart Liposomes for Dual Targeting of Tumor Microenvironment and Cancer Cells

Knockdown of hypoxia-inducible factor-1α accelerates peritoneal dissemination via the upregulation of MMP-1 expression in gastric cancer cell lines

Gastric cancer in the era of molecularly targeted agents: current drug development strategies

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