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Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells

  1. Top of page
  2. Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells
  3. Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer
  4. HA1077, a Rho kinase inhibitor, suppresses glioma-induced angiogenesis by targeting the Rho–ROCK and MEK/ERK signal pathways

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Page 407–13

Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a transmembrane Kunitz-type serine protease inhibitor expressed on the basolateral surface of most epithelial cells and placental cytotrophoblasts. The main functional domain of HAI-1 is the first Kunitz domain (KD1), an extracellular region containing an N-terminal cysteine-rich area. Although it is expressed in a range of epithelial tumors, the biological role of HAI-1 is largely unknown. In previous research, Fukushima et al. have shown that knockdown of HAI-1 in the human pancreatic carcinoma cell line SUIT-2 resulted in epithelial to mesenchymal transition. Expanding on their previous work, Fukushima et al. now report that knockdown of HAI-1 promoted pulmonary metastasis in an experimental pulmonary metastasis assay. Furthermore, the researchers showed that co-injection of recombinant KD1 abolished metastasis produced by HAI-1 knockdown in SUIT-2 cells and reduced the cells’ invasiveness. The authors conclude that HAI-1 regulates pulmonary metastases of SUIT-2 and that KD1 may have therapeutic applications.

Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer

  1. Top of page
  2. Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells
  3. Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer
  4. HA1077, a Rho kinase inhibitor, suppresses glioma-induced angiogenesis by targeting the Rho–ROCK and MEK/ERK signal pathways

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Page 324–29

Oral cancer is one of the ten most frequently diagnosed cancers worldwide. Despite surgical and chemoradiation treatments, most patients with locally advanced oral cancer remain at high risk for locoregional recurrence and distant metastasis. In this issue, Miyazaki et al. report the results of a phase I clinical trial of a survivin-2B80-88 peptide vaccine in patients with advanced or recurrent oral cancer. Survivin, a recently characterized member of the inhibitor of apoptosis family, is abundantly expressed in most malignancies but nearly undetectable in normal adult tissue. Of the ten patients who completed the vaccination protocol, one showed tumor regression indicative of a partial response. Six patients had an increase of peptide-specific cytotoxic T lymphocyte frequency. Although the trial results indicate that survivin-2B peptide vaccination is safe and has therapeutic potential for oral cancer patients, further trials combining the vaccination with various adjuvant drugs are necessary to improve the treatment’s immunological and therapeutic efficacy.

HA1077, a Rho kinase inhibitor, suppresses glioma-induced angiogenesis by targeting the Rho–ROCK and MEK/ERK signal pathways

  1. Top of page
  2. Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells
  3. Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer
  4. HA1077, a Rho kinase inhibitor, suppresses glioma-induced angiogenesis by targeting the Rho–ROCK and MEK/ERK signal pathways

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Page 393–99

Rho-GTPases play a critical role in the regulation of numerous cellular functions, including actin reorganization, cell motility, cell–extracellular matrix adhesion, and cell cycle progression. As a downstream effector of small Rho-GTPases, Rho kinase (ROCK) is also important in cellular functions and therefore presents a potential pharmacological target. Currently, the ROCK inhibitor HA1077 is being used clinically without apparent side-effects. Although numerous studies have examined the effect of ROCK inhibitors on tumors, no study has focused on the effect of HA1077 on tumor-induced angiogenesis. Nakabayashi and Shimizu present the first experimental evidence that HA1077 suppresses glioma-induced angiogenesis. The researchers show that HA1077 suppressed tube formation of endothelial cells in a HUVEC–glioma cell co-culture assay. Further investigation provided evidence that the HA1077 anti-angiogenic effect might result from the combination of ROCK inhibition and MEK/ERK pathway inhibition. The authors suggest that HA1077 has therapeutic potential as an anti-angiogenic agent for malignant gliomas.