The endogenous soluble VEGF receptor-2 isoform suppresses lymph node metastasis in a mouse immunocompetent mammary cancer model

BACKGROUND: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer. METHODS: Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. In vivo gene electrotransfer was performed on the tumors after each injection. RESULTS: Deaths from metastasis were much lower in the pesVEGFR-2 and pEndo groups than in those of the pVec. Tumor volume was significantly lower in the pesVEGFR-2 and the pEndo groups throughout the study. Multiplicity of lymph node and lung metastatic nodules was significantly suppressed in the pesVEGFR-2 and pEndo groups. Moreover, the total number of overall metastasis including the other organs was also decreased in these groups. However, pesVEGFR-2 was not able to decrease the number of lungs, ovaries, kidneys and adrenals with metastasis as counted by unilateral or bilateral metastasis. The number of CD34+/Lyve-1⁻ blood microvessels was significantly decreased in the pEndo group, while the number of CD34⁻/Lyve-1+ lymphatic vessels was significantly decreased in the pesVEGFR-2 and pEndo groups. In addition, a significant reduction in the number of dilated lymphatic vessels containing intraluminal cancer cells was observed in the pesVEGFR-2 and pEndo groups. Levels of apoptosis were significantly increased in the pEndo group, whereas the rates of cell proliferation were significantly decreased in the pesVEGFR-2 and pEndo groups. CONCLUSIONS: Our data demonstrate that esVEGFR-2 can inhibit mainly lymph node metastasis. The antimetastatic activity of esVEGFR-2 may be of high clinical significance in the treatment of metastatic breast cancer because lymph node involvement is a most important prognostic factor in cancer patients

The Relationship between Symptom Flare of Atopic Dermatitis and Airborne Japanese Cedar and Cypress Pollen Counts: A Self-Scoring Diary Study

Background. With an increase in Japanese cedar and cypress (JC) pollinosis, the relationship between JC pollen and atopic dermatitis (AD) has been studied. Some reports suggest that JC pollen can be one exacerbating factor for AD, but there has been no report that discusses JC pollen counts relating to AD symptom flare although actual airborne JC pollen counts can widely fluctuate throughout the pollen season. Objective. The relationship between symptom flare of AD and airborne JC pollen counts was examined. Methods. We monitored JC pollen counts in real time and divided the counts into low and high level. We then analyzed self-scored “itch intensity” recorded by 14 AD patients through a self-scoring diary. Results. Among the 14 patients, 7 had significantly higher itch intensity while the pollen counts were high. Conclusion. Even during the pollen season, actual airborne pollen counts can widely fluctuate. Our study suggested that symptom flare of AD could be influenced by the actual pollen counts

Morphologic change of Yoshida sarcoma cells and coelothelioma cells after exposing to the cell toxin from X-ray-irradiated animal

The unsaturated fatty acid fraction extracted from the liver of rabbit irradiated with X-rays exerts a strong cytotoxic effect on human coelothelioma cells and Yoshida sarcoma cells both in vitro and in vivo. The cell damage seems to initiate at the nucleus, finally leading to the complete cytolysis. The inhibiting effect of this substance on the mitosis of Yoshida sarcoma cells can be observed, especially marked from prophase up to metaphase giving almost the same results obtained after X-ray irradiation. From these results and the observations reported by several authors on the cell damage by X-ray irradiation, weshould call special attention to the fact that the essential mechanism of X-ray irradiation can be attributed to the cell toxin produced after the irradiation.</p

Raloxifene inhibits tumor growth and lymph node metastasis in a xenograft model of metastatic mammary cancer

<p>Abstract</p> <p>Background</p> <p>The effects of raloxifene, a novel selective estrogen receptor modulator, were studied in a mouse metastatic mammary cancer model expressing cytoplasmic ERα.</p> <p>Methods</p> <p>Mammary tumors, induced by inoculation of syngeneic BALB/c mice with BJMC3879luc2 cells, were subsequently treated with raloxifene at 0, 18 and 27 mg/kg/day using mini-osmotic pumps.</p> <p>Results</p> <p><it>In vitro </it>study demonstrated that the ERα in BJMC3879luc2 cells was smaller (between 50 and 64 kDa) than the normal-sized ERα (66 kDa) and showed cytoplasmic localization. A statistically significant but weak estradiol response was observed in this cell line. When BJMC3879luc2 tumors were implanted into mice, the ERα mRNA levels were significantly higher in females than in males. <it>In vitro </it>studies showed that raloxifene induced mitochondria-mediated apoptosis and cell-cycle arrest in the G1-phase and a decrease in the cell population in the S-phase. In animal experiments, tumor volumes were significantly suppressed in the raloxifene-treated groups. The multiplicity of lymph node metastasis was significantly decreased in the 27 mg/kg group. Levels of apoptosis were significantly increased in the raloxifene-treated groups, whereas the levels of DNA synthesis were significantly decreased in these groups. No differences in microvessel density in tumors were observed between the control and raloxifene-treated groups. The numbers of dilated lymphatic vessels containing intraluminal tumor cells were significantly reduced in mammary tumors in the raloxifene-treated groups. The levels of ERα mRNA in mammary tumors tended to be decreased in the raloxifene-treated groups.</p> <p>Conclusion</p> <p>These results suggest that the antimetastatic activity of raloxifene in mammary cancer expressing cytoplasmic ERα may be a crucial finding with clinical applications and that raloxifene may be useful as an adjuvant therapy and for the chemoprevention of breast cancer development.</p