Mechanism of metastasis and angiogenesis inhibition by particle irradiation

Purpose: Both surgery and radiotherapy have limitation to treat metastasized malignant tumors. Therefore, the inhibition of cancer cells\u27 metastasis is a highly significant issue. We previously demonstrated that particle (carbon ion beam) irradiation suppressed angiogenesis and metastasis. The purpose of this study is to clarify the mechanism of these suppressions.Methods: Human lung adenocarcinoma cells (A549) and human umbilical vascular endothelial cells (HUVEC) were irradiated with 290MeV carbon particle at HIMAC and 4MV X-ray. After irradiation, WST assay, boyden chamber assay, matrigel invasion assay, and cell adhesion assay were performed. RNA was extracted and cDNA micro array and RT-PCR were carried out.Results: The proliferation of A549 and HUVEC cells were down-regulated by carbon particle irradiation in dose-dependent manner, though sublethal X-irradiation enhanced proliferation of both two cell lines. The migration of each cells were also suppressed by only 0.25Gy carbon beam. The invasiveness of A549 was suppressed by 0.25Gy carbon beam 48 hours after irradiation. As far as cDNA expressions are concerned, anillin, actin-binding protein, was decreased in A549 cells by carbon particle. In HUVEC, some of angiogenesis related gene expressions were decreased, including neuropilin-1, CTGF, and ephrin-B2.Conclusion: Particle (carbon ion beam) irradiation may suppress cancer cells\u27 aggressiveness through down-regulation of the metastasis and angiogenesis related gene expression.The 5th Japan-US Cancer Therapy Symposium & The 5th S.Takahashi Memorial Joint Symposiu

The Role of Agricultural Land Use Pattern Dynamics on Elephant Habitat Depletion and Human-Elephant Conflict in Sri Lanka

The drastic depletion of elephant habitats in the dry zone of Sri Lanka has led to intense human-elephant conflict (HEC) in a region that is home to one of the celebrated agrarian settlements in Asia. Known as the tank villages, these settlements have a long history of human coexistence with elephants and other wild animals. However, the escalating incidence of human-elephant fatalities and crop losses to farmers indicates that the mode of interaction between the tank village inhabitants and the elephants has transformed from coexistence to conflict. Both population and agricultural land use pattern dynamics have contributed to agricultural expansion and loss of elephant habitat in the dry zone of Sri Lanka. However, our knowledge of how the agricultural land use pattern dynamics has contributed to the drastic depletion of elephant range in the dry zone is limited. This research attempted to gain insight into the role of agricultural land use dynamics on elephant habitat depletion and HEC in Sri Lanka through the study of Kuttikulama, a dry zone tank village. The data were collected through focus group discussions, key informant interviews and a cross sectional survey. The study revealed that agricultural land use patterns in traditional dry zone villages have changed in major ways over the last few decades. Such changes included the transition from a shifting-cultivation mode of farming to a fixed sequential mode of farming, the expansion of the per capita cropping area, and the disappearance of communality in agricultural land use patterns. The changes were found to have significantly contributed to a shift in human−elephant interactions from relatively harmonious ones to contentious ones. The study reveals the potential of traditional and alternative cropping and land use systems to minimize human-elephant conflict in Sri Lanka

Carbon Ion Irradiation Suppresses Metastatic Potential of Human Non-small Cell Lung Cancer A549 Cells through the Phosphatidylinositol-3-Kinase/Akt Signaling Pathway

We previously showed that carbon ion irradiation can inhibit the expression of the anillin (ANLN) gene, which is regulated by the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling path- way associated with metastasis. The purpose of this study is to compare the effects of carbon ion irradia- tion on the PI3K/Akt signaling pathway to those of photon irradiation. Our study showed that carbon ion irradiation of human lung adenocarcinoma cells A549 decreased their invasion more effectively than pho- ton irradiation did. We found that carbon ion irradiation reduced the nuclear localization of ANLN at lower dose, but did not affect its expression. Low-dose carbon ion irradiation also reduced the level of phosphorylated Akt compared to untreated controls, whereas photon irradiation did not. These results sug- gest that carbon ion irradiation effectively suppresses the metastatic potential of A549 cells by suppressing the PI3K/Akt signaling pathway

Carbon-ion beam irradiation effectively suppresses migration and invasion of human non-small-cell lung cancer cells

PURPOSE: Control of cancer metastasis is one of the most important issues in cancer treatment. We previously demonstrated that carbon particle irradiation suppresses the metastatic potential of cancer cells, and many studies have reported that photon irradiation promotes it. The purpose of this study was to investigate the effect of carbon beam on non-small-cell lung cancer (NSCLC) cell aggressiveness and gene expression. METHODS AND MATERIALS: A549 (lung adenocarcinoma) and EBC-1 (lung squamous cell carcinoma) cells were treated with 290 MeV/nucleon carbon ion beam at the Heavy Ion Medical Accelerator in Chiba or with 4-MV X-ray at Osaka University. We tested proliferative, migratory, and invasive activities by cell proliferation assay, Boyden chamber assay, and Matrigel chemoinvasion assay, respectively. cDNA microarray and reverse transcription polymerase chain reaction were also performed to assess mRNA expression alteration. RESULTS: X-irradiation increased cell proliferation of A549 cells at 0.5 Gy, whereas high-dose X-ray reduced migration and invasion of A549 cells. By contrast, carbon beam irradiation did not enhance proliferation, and it reduced the migration and invasion capabilities of both A549 and EBC-1 cells more effectively than did X-irradiation. Carbon beam irradiation induced alteration of various gene expression profiles differently from X-ray irradiation. mRNA expression of ANLN, a homologue of anillin, was suppressed to 60% levels of basal expression in carbon beam-irradiated A549 cells after 12 h. CONCLUSION: Carbon beam effectively suppresses the metastatic potential of A549 and EBC-1 cells. Carbon beam also has different effects on gene expressions, and downregulation of ANLN was induced only by carbon beam irradiation