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Background: Previous work has demonstrated immunomodulatory, anti-tumor, anti-metastatic and anti-angiogenic effects of the small molecule quinoline-3-carboxamide tasquinimod in pre-clinical cancer models. To better understand the anti-tumor effects of tasquinimod in transplantable tumor models, we have evaluated the impact of the compound both on recruitment of myeloid cells to tumor tissue and on tumor-induced myeloid cell expansion as these cells are known to promote tumor development.Methods: Mice bearing subcutaneous 4 T1 mammary carcinoma tumors were treated with tasquinimod in the drinking water. A BrdU-based flow cytometry assay was utilized to assess the impact of short-term tasquinimod treatment on myeloid cell recruitment to tumors. Additionally, long-term treatment was performed to study the anti-tumor effect of tasquinimod as well as its effects on splenic myeloid cells and their progenitors. Myeloid cell populations were also immune-depleted by in vivo antibody treatment.Results: Short-term tasquinimod treatment did not influence the proliferation of splenic Ly6C(hi) and Ly6G(hi) cells, but instead reduced the influx of Ly6C(hi) cells to the tumor. Treatment with tasquinimod for various periods of time after tumor inoculation revealed that the anti-tumor effect of this compound mainly operated during the first few days of tumor growth. Similar to tasquinimod treatment, antibody-mediated depletion of Ly6C(hi) cells within that same time frame, caused reduced tumor growth, thereby confirming a significant role for these cells in tumor development. Additionally, long-term tasquinimod treatment reduced the splenomegaly and expansion of splenic myeloid cells during a later phase of tumor development. In this phase, tasquinimod normalized the tumor-induced alterations in myeloerythroid progenitor cells in the spleen but had only limited impact on the same populations in the bone marrow.Conclusions: Our results indicate that tasquinimod treatment reduces tumor growth by operating early after tumor inoculation and that this effect is at least partially caused by reduced recruitment of Ly6C(hi) cells to tumor tissue. Long-term treatment also reduces the number of splenic myeloid cells and myeloerythroid progenitors, but these effects did not influence established rapidly growing tumors. [ABSTRACT FROM AUTHOR]

Background: A mouse model of metastasis of human gastric cancer is one of the most important tools for studying the biological mechanisms underlying human gastric cancer metastasis. In this paper, we established a mouse model of metastatic human gastric cancer in nude mice that has a higher rate of tumor formation and metastasis than existing models.Methods: To generate the mouse model of metastatic human gastric cancer, fresh tumor tissues from patients that have undergone surgery for gastric cancer were subcutaneously implanted in the right and left groins of nude mice. When the implanted tissue grew to 1 cubic centimeter, the mice were killed, and the tumor tissues were examined and resected. The tumor tissues were implanted into nude mice and subjected to pathological examination, immunohistochemical staining, and real-time PCR for cytokeratin 8/18 (CK8/18), E-cadherin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). The mice were also analyzed for metastasis in their peritoneum, abdominal cavity, and internal organs by histopathological examination. Tissues collected from these organs were examined for pathology.Results: After ten generations of implantation, all mice developed tumor growth at the implanted position, 94% of the mice developed metastasis to the retroperitoneum and viscera. The implanted and metastatic tumor maintained the same histological features across all generations, and metastasis was observed in the esophagus, stomach, spleen, liver, kidney, adrenal, intestine, and pancreas. These metastatic tumors revealed no detectable expression of CK8/18, E-cadherin, VCAM-1, and ICAM-1.Conclusions: This model will serve as valuable tool for understanding the metastatic process of human gastric cancer. [ABSTRACT FROM AUTHOR]