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Toshihiko Terao - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of metastasis of Lewis Lung carcinoma by urinary trypsin inhibitor in experimental and spontaneous metastasis models.
    International Journal of Cancer, 1995
    Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Michio Fujie, Hiromitsu Shinohara, Mariko Itoh, Kinya Takeuchi, Toshihiko Terao
    Abstract:

    : A purified human urinary trypsin inhibitor (UTI) and its related synthetic peptides were examined to determine whether they could inhibit production of experimental and spontaneous Lung metastases by murine Lewis Lung carcinoma (3LL) cells. Three peptides, peptide I, peptide 2 and peptide 3, representing the amino acid sequences within the UTI molecule, were synthesized. UTI and peptide 2 inhibited human leukocyte elastase (HLE). UTI and peptide 3 specifically inhibited human and murine plasmin activity. Peptide I had essentially no inhibitory activity. In an in vivo spontaneous metastasis model, multiple s.c. injections of UTI or peptide 3 for 7 days immediately after s.c. Tumor cell inoculation significantly inhibited the formation of Lung metastasis in C57BL/6 mice in a dose-dependent manner. UTI reduced Lung Tumor colonization more effectively than peptide 3. Peptides 1 and 2, however, did not affect the formation of Lung metastasis. Inhibition of Lung metastasis was not due to direct anti-Tumor effects of UTI and peptide 3. In an in vivo experimental metastasis assay, multiple s.c. injections of UTI for 7 days after i.v. Tumor cell inoculation inhibited Metastatic Lung Tumor colonization, while peptide 3 did not affect metastasis. Peptides 1 and 2 did not affect the formation of Lung metastasis. When examined with an in vitro assay system using a modified Boyden chamber, UTI and peptide 3 suppressed the invasion of Tumor cells through Matrigel. UTI and peptide 3 inhibited neither cell proliferation nor the binding of Tumor cells to Matrigel and showed no significant suppression of chemotactic migration of Tumor cells to fibronectin. Our results suggest that UTI efficiently regulates the mechanism involved in not only the entry into vascular circulation of Tumor cells (intravasation, though, at least in part, inhibition of the proteolytic enzyme plasmin) but also the extravasation step of the Metastatic process.

  • Inhibition of metastasis of Lewis Lung carcinoma by a synthetic peptide within growth factor-like domain of urokinase in the experimental and spontaneous metastasis model.
    International Journal of Cancer, 1994
    Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Michio Fujie, Hiromitsu Shinohara, Nobuhiko Moniwa, Toshihiko Terao
    Abstract:

    : Four synthetic peptides (residues 20-30 and 17-34) within the growth factor-like domain (GFD) of murine and human urokinase-type plasminogen activator (uPA) were examined to determine whether they inhibit production of experimental and spontaneous Lung metastasis by murine Lewis Lung carcinoma (3LL) cells. In an in vivo experimental metastasis assay, which determines mainly the later steps of the Metastatic migration process (extravasation from the bloodstream and then growth into pulmonary Tumor), none of the peptides introduced by i.v. single co-injection into syngeneic C57B1/6 mice inhibited pulmonary metastasis, when 3LL cells were pre-incubated with the peptides followed by i.v. co-injection of the peptide and cells. In addition, none of the peptides, when injected i.p. daily for 7 days after i.v. Tumor cell inoculation, reduced the number of Lung Tumor colonies. In a second in vivo assay that measures metastasis from a primary Tumor (spontaneous metastasis model), multiple i.p. injections of the mouse peptide 17-34 for 7 days after s.c. Tumor cell inoculation significantly inhibited Metastatic Lung Tumor colonization in a dose-dependent manner, whereas human peptide 17-34 had no effect. Mouse and human peptide 20-30 had no effect either. The inhibition of Lung metastasis was not due to direct antiTumor effects of mouse peptide 17-34. Our results indicate that occupation of uPA receptors on 3LL cells by the enzymatically inactive mouse peptide 17-34 or prevention of rebinding of uPA synthesized by Tumor cells to their receptor specifically reduced Tumor cell invasion and formation of metastasis and that uPA may regulate more efficiently the mechanism involved in the entry of Tumor cells into vascular circulation than extravasation during the Metastatic process.

Hiroshi Kobayashi - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of metastasis of Lewis Lung carcinoma by urinary trypsin inhibitor in experimental and spontaneous metastasis models.
    International Journal of Cancer, 1995
    Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Michio Fujie, Hiromitsu Shinohara, Mariko Itoh, Kinya Takeuchi, Toshihiko Terao
    Abstract:

    : A purified human urinary trypsin inhibitor (UTI) and its related synthetic peptides were examined to determine whether they could inhibit production of experimental and spontaneous Lung metastases by murine Lewis Lung carcinoma (3LL) cells. Three peptides, peptide I, peptide 2 and peptide 3, representing the amino acid sequences within the UTI molecule, were synthesized. UTI and peptide 2 inhibited human leukocyte elastase (HLE). UTI and peptide 3 specifically inhibited human and murine plasmin activity. Peptide I had essentially no inhibitory activity. In an in vivo spontaneous metastasis model, multiple s.c. injections of UTI or peptide 3 for 7 days immediately after s.c. Tumor cell inoculation significantly inhibited the formation of Lung metastasis in C57BL/6 mice in a dose-dependent manner. UTI reduced Lung Tumor colonization more effectively than peptide 3. Peptides 1 and 2, however, did not affect the formation of Lung metastasis. Inhibition of Lung metastasis was not due to direct anti-Tumor effects of UTI and peptide 3. In an in vivo experimental metastasis assay, multiple s.c. injections of UTI for 7 days after i.v. Tumor cell inoculation inhibited Metastatic Lung Tumor colonization, while peptide 3 did not affect metastasis. Peptides 1 and 2 did not affect the formation of Lung metastasis. When examined with an in vitro assay system using a modified Boyden chamber, UTI and peptide 3 suppressed the invasion of Tumor cells through Matrigel. UTI and peptide 3 inhibited neither cell proliferation nor the binding of Tumor cells to Matrigel and showed no significant suppression of chemotactic migration of Tumor cells to fibronectin. Our results suggest that UTI efficiently regulates the mechanism involved in not only the entry into vascular circulation of Tumor cells (intravasation, though, at least in part, inhibition of the proteolytic enzyme plasmin) but also the extravasation step of the Metastatic process.

  • Inhibition of metastasis of Lewis Lung carcinoma by a synthetic peptide within growth factor-like domain of urokinase in the experimental and spontaneous metastasis model.
    International Journal of Cancer, 1994
    Co-Authors: Hiroshi Kobayashi, Junko Gotoh, Michio Fujie, Hiromitsu Shinohara, Nobuhiko Moniwa, Toshihiko Terao
    Abstract:

    : Four synthetic peptides (residues 20-30 and 17-34) within the growth factor-like domain (GFD) of murine and human urokinase-type plasminogen activator (uPA) were examined to determine whether they inhibit production of experimental and spontaneous Lung metastasis by murine Lewis Lung carcinoma (3LL) cells. In an in vivo experimental metastasis assay, which determines mainly the later steps of the Metastatic migration process (extravasation from the bloodstream and then growth into pulmonary Tumor), none of the peptides introduced by i.v. single co-injection into syngeneic C57B1/6 mice inhibited pulmonary metastasis, when 3LL cells were pre-incubated with the peptides followed by i.v. co-injection of the peptide and cells. In addition, none of the peptides, when injected i.p. daily for 7 days after i.v. Tumor cell inoculation, reduced the number of Lung Tumor colonies. In a second in vivo assay that measures metastasis from a primary Tumor (spontaneous metastasis model), multiple i.p. injections of the mouse peptide 17-34 for 7 days after s.c. Tumor cell inoculation significantly inhibited Metastatic Lung Tumor colonization in a dose-dependent manner, whereas human peptide 17-34 had no effect. Mouse and human peptide 20-30 had no effect either. The inhibition of Lung metastasis was not due to direct antiTumor effects of mouse peptide 17-34. Our results indicate that occupation of uPA receptors on 3LL cells by the enzymatically inactive mouse peptide 17-34 or prevention of rebinding of uPA synthesized by Tumor cells to their receptor specifically reduced Tumor cell invasion and formation of metastasis and that uPA may regulate more efficiently the mechanism involved in the entry of Tumor cells into vascular circulation than extravasation during the Metastatic process.

Friedrich Grimminger - One of the best experts on this subject based on the ideXlab platform.

  • metastasis associated protein 2 represses nf κb to reduce Lung Tumor growth and inflammation
    Cancer Research, 2020
    Co-Authors: Nefertiti Elnikhely, Annika Karger, Poonam Sarode, Indrabahadur Singh, Andreas Weigert, Astrid Wietelmann, Thorsten Stiewe, Reinhard Dammann, Ludger Fink, Friedrich Grimminger
    Abstract:

    Although NF-κB is known to play a pivotal role in Lung cancer, contributing to Tumor growth, microenvironmental changes, and metastasis, the epigenetic regulation of NF-κB in Tumor context is largely unknown. Here we report that the IKK2/NF-κB signaling pathway modulates metastasis-associated protein 2 (MTA2), a component of the nucleosome remodeling and deacetylase complex (NuRD). In triple transgenic mice, downregulation of IKK2 (Sftpc-cRaf-IKK2DN) in cRaf-induced Tumors in alveolar epithelial type II cells restricted Tumor formation, whereas activation of IKK2 (Sftpc-cRaf-IKK2CA) supported Tumor growth; both effects were accompanied by altered expression of MTA2. Further studies employing genetic inhibition of MTA2 suggested that in primary Tumor growth, independent of IKK2, MTA2/NuRD corepressor complex negatively regulates NF-κB signaling and Tumor growth, whereas later dissociation of MTA2/NuRD complex from the promoter of NF-κB target genes and IKK2-dependent positive regulation of MTA2 leads to activation of NF-κB signaling, epithelial-mesenchymal transition, and Lung Tumor metastasis. These findings reveal a previously unrecognized biphasic role of MTA2 in IKK2/NF-κB-driven primary-to-Metastatic Lung Tumor progression. Addressing the interaction between MTA2 and NF-κB would provide potential targets for intervention of Tumor growth and metastasis. SIGNIFICANCE: These findings strongly suggest a prominent role of MTA2 in primary Tumor growth, Lung metastasis, and NF-κB signaling modulatory functions.

Satoshi Shiono - One of the best experts on this subject based on the ideXlab platform.

  • is there a role for pulmonary metastasectomy with a curative intent in patients with Metastatic urinary transitional cell carcinoma
    The Annals of Thoracic Surgery, 2011
    Co-Authors: Haruhisa Matsuguma, Jun Nakajima, Norihiko Ikeda, Satoshi Shiono, Ichiro Yoshino, Sakae Okumura, Hideyuki Ito, Tomoyuki Goya, Yukiko Matsui, Hiroaki Nomori
    Abstract:

    Background Systemic chemotherapy remains the standard treatment for Metastatic transitional cell carcinoma (TCC) of the urinary tract. For pulmonary metastases of several malignancies, surgical therapy for selected patients has become a treatment of choice to achieve cure. However, data on pulmonary metastasectomy for urinary TCC remain limited. Methods From 1990 to 2005, 2,288 patients who underwent pulmonary metastasectomy for all types of malignancy were registered in the Metastatic Lung Tumor Study Group of Japan. Of these, we extracted 32 patients with TCC who underwent pulmonary metastasectomy with a curative intent from the database. We investigated the surgical outcomes of the patients, focusing on long-term progression-free survival (PFS) and modified PFS as a parameter for achieving a cure. In modified PFS, when the disease-free status had continued for longer than two years after repeated resection at the last follow-up, the first recurrence was not considered as an event. Results The five-year overall survival and PFS rates were 50% and 26%, respectively. Including 3 patients who underwent a second pulmonary metastasectomy for recurrence, 9 patients survived without recurrence for more than 5 years, resulting in a modified five-year PFS rate of 40%. Multivariate analysis revealed that a pulmonary metastasis greater than 3 cm was a significantly poor prognostic factor. The modified five-year PFS rate for patients with a pulmonary metastasis smaller than 3 cm in diameter was 65%. Conclusions Pulmonary metastasectomy may have a curative role in the treatment of Metastatic TCC in appropriately selected patients, especially those with a small solitary pulmonary metastasis.

  • pulmonary metastasectomy for pulmonary metastases of head and neck squamous cell carcinomas
    The Annals of Thoracic Surgery, 2009
    Co-Authors: Satoshi Shiono, Jun Nakajima, Hirotoshi Horio, Norihiko Ikeda, Masafumi Kawamura, Toru Sato, Ichiro Yoshino, Hirohiko Akiyama, Sakae Okumura, Koichi Kobayashi
    Abstract:

    Background The Lung is the major organ for distant metastasis from head and neck cancers, and pulmonary metastasectomy is indicated for selected cases. The efficacy of surgical treatment for pulmonary Metastatic lesions from head and neck cancers has not been thoroughly examined. Methods The database developed by the Metastatic Lung Tumor Study Group of Japan was retrospectively reviewed. Between November 1980 and September 2006, 237 patients underwent resection of pulmonary metastases from primary head and neck cancers. After excluding nonsquamous cell carcinomas, 114 cases were analyzed, and the survival and prognostic factors for pulmonary metastasectomy for metastases from head and neck cancers were determined. Results The overall 5-year survival rate after pulmonary metastasectomy was 26.5%, and the median survival time was 26 months. As determined by univariate analysis, poor prognostic factors were oral cavity cancers, lymph node metastasis, a disease-free interval of 24 months or less, and incomplete resection. Multivariate analysis revealed that poor prognostic factors were being male, having oral cavity cancers, lymph node metastasis, and incomplete resection. When patients were divided into males with oral cavity cancers (n = 17) and all others (n = 97), the 5-year survival rates were 0% and 31.6%, respectively. Survival of male patients with oral cavity cancer that metastasized was significantly reduced (p Conclusions Male sex, oral cavity cancers, lymph node metastasis, and incomplete resection were poor prognostic factors for pulmonary metastases, but there is the potential for a good surgical outcome in carefully selected patients.

  • disease free interval length correlates to prognosis of patients who underwent metastasectomy for esophageal Lung metastases
    Journal of Thoracic Oncology, 2008
    Co-Authors: Satoshi Shiono, Jun Nakajima, Hirotoshi Horio, Norihiko Ikeda, Masafumi Kawamura, Toru Sato, Ken Nakagawa, Ichiro Yoshino, Hirohiko Akiyama, Koichi Kobayashi
    Abstract:

    Background Pulmonary metastasectomy is a standard method for treatment of selected pulmonary metastases cases. Nevertheless, because prognosis for patients with Lung metastases from esophageal cancer who have undergone pulmonary metastasectomy is poor, candidates for this method of treatment are rare. Therefore, the efficacy of surgical treatment for pulmonary Metastatic lesions from esophageal cancer has not been thoroughly examined. Methods Between March 1984 and May 2006, 57 patients underwent resection of pulmonary metastases from primary esophageal cancer. These cases were registered in the database developed by the Metastatic Lung Tumor Study Group of Japan and were retrospectively reviewed from the registry. After excluding eight cases because of missing information, we reviewed the remaining 49 cases and examined the prognostic factors for pulmonary metastasectomy for metastases from esophageal cancer. Results There were no perioperative deaths. After pulmonary metastasectomy, disease recurred in 16 (33%) of the 49 patients. The overall 5-year survival was 29.6%. Median survival time was 18 months. The survival of patients with a disease-free interval (DFI) less than 12 months was significantly lower than patients with a DFI greater than 12 months. Through multivariate analysis, we identified DFI as a clinical factor significantly related to overall survival ( p = 0.04). Conclusions We identified that patients with a DFI less than 12 months who underwent pulmonary metastasectomy for metastases from esophageal cancer had a worse prognosis. Pulmonary metastasectomy for esophageal cancer should be considered for selected patients with a DFI ≥12 months.

Koichi Kobayashi - One of the best experts on this subject based on the ideXlab platform.

  • pulmonary metastasectomy for pulmonary metastases of head and neck squamous cell carcinomas
    The Annals of Thoracic Surgery, 2009
    Co-Authors: Satoshi Shiono, Jun Nakajima, Hirotoshi Horio, Norihiko Ikeda, Masafumi Kawamura, Toru Sato, Ichiro Yoshino, Hirohiko Akiyama, Sakae Okumura, Koichi Kobayashi
    Abstract:

    Background The Lung is the major organ for distant metastasis from head and neck cancers, and pulmonary metastasectomy is indicated for selected cases. The efficacy of surgical treatment for pulmonary Metastatic lesions from head and neck cancers has not been thoroughly examined. Methods The database developed by the Metastatic Lung Tumor Study Group of Japan was retrospectively reviewed. Between November 1980 and September 2006, 237 patients underwent resection of pulmonary metastases from primary head and neck cancers. After excluding nonsquamous cell carcinomas, 114 cases were analyzed, and the survival and prognostic factors for pulmonary metastasectomy for metastases from head and neck cancers were determined. Results The overall 5-year survival rate after pulmonary metastasectomy was 26.5%, and the median survival time was 26 months. As determined by univariate analysis, poor prognostic factors were oral cavity cancers, lymph node metastasis, a disease-free interval of 24 months or less, and incomplete resection. Multivariate analysis revealed that poor prognostic factors were being male, having oral cavity cancers, lymph node metastasis, and incomplete resection. When patients were divided into males with oral cavity cancers (n = 17) and all others (n = 97), the 5-year survival rates were 0% and 31.6%, respectively. Survival of male patients with oral cavity cancer that metastasized was significantly reduced (p Conclusions Male sex, oral cavity cancers, lymph node metastasis, and incomplete resection were poor prognostic factors for pulmonary metastases, but there is the potential for a good surgical outcome in carefully selected patients.

  • disease free interval length correlates to prognosis of patients who underwent metastasectomy for esophageal Lung metastases
    Journal of Thoracic Oncology, 2008
    Co-Authors: Satoshi Shiono, Jun Nakajima, Hirotoshi Horio, Norihiko Ikeda, Masafumi Kawamura, Toru Sato, Ken Nakagawa, Ichiro Yoshino, Hirohiko Akiyama, Koichi Kobayashi
    Abstract:

    Background Pulmonary metastasectomy is a standard method for treatment of selected pulmonary metastases cases. Nevertheless, because prognosis for patients with Lung metastases from esophageal cancer who have undergone pulmonary metastasectomy is poor, candidates for this method of treatment are rare. Therefore, the efficacy of surgical treatment for pulmonary Metastatic lesions from esophageal cancer has not been thoroughly examined. Methods Between March 1984 and May 2006, 57 patients underwent resection of pulmonary metastases from primary esophageal cancer. These cases were registered in the database developed by the Metastatic Lung Tumor Study Group of Japan and were retrospectively reviewed from the registry. After excluding eight cases because of missing information, we reviewed the remaining 49 cases and examined the prognostic factors for pulmonary metastasectomy for metastases from esophageal cancer. Results There were no perioperative deaths. After pulmonary metastasectomy, disease recurred in 16 (33%) of the 49 patients. The overall 5-year survival was 29.6%. Median survival time was 18 months. The survival of patients with a disease-free interval (DFI) less than 12 months was significantly lower than patients with a DFI greater than 12 months. Through multivariate analysis, we identified DFI as a clinical factor significantly related to overall survival ( p = 0.04). Conclusions We identified that patients with a DFI less than 12 months who underwent pulmonary metastasectomy for metastases from esophageal cancer had a worse prognosis. Pulmonary metastasectomy for esophageal cancer should be considered for selected patients with a DFI ≥12 months.