ABSTRACT
Haptics applications such as surgery simulations require collision detections that are more precise than others. An efficient collision detection method based on the clustering of bounding spheres was proposed in our prior study. This paper analyzes and compares the applied effects of the five most common subdivision surface methods on some 3D models for haptic collision detection. The five methods are Butterfly, Catmull-Clark, Mid-point, Loop, and LS3 (Least Squares Subdivision Surface). After performing a number of experiments, we have concluded that LS3 method is the most appropriate for haptic simulations. The more we applied surface subdivision, the more the collision detection results became precise. However, it is observed that the performance becomes better until a certain threshold and degrades afterward. In order to reduce the performance degradation, we adopted our prior work, which was the fast and precise collision detection method based on adaptive clustering. As a result, we obtained a notable improvement of the speed of collision detection.
Subject(s)
Algorithms , Surface PropertiesABSTRACT
High aldehyde dehydrogenase (ALDH) activity has been recognized as a marker of cancer stem cells (CSCs) in breast cancer. In this study, we examined whether inhibition of ALDH activity suppresses stem-like cell properties in a 4T1 syngeneic mouse model of breast cancer. We found that ALDH-positive 4T1 cells showed stem cell-like properties in vitro and in vivo. Blockade of ALDH activity reduced the growth of CSCs in breast cancer cell lines. Treatment of mice with the ALDH inhibitor diethylaminobenzaldehyde (DEAB) significantly suppressed 4T1 cell metastasis to the lung. Recent evidence suggests that ALDH affects the response of stem cells to hypoxia; therefore, we examined a possible link between ALDH and hypoxia signaling in breast cancer. Hypoxia-inducible factor-2α (HIF-2α) was highly dysregulated in ALDH-positive 4T1 cells. We observed that ALDH was highly correlated with the HIF-2α expression in breast cancer cell lines and tissues. DEAB treatment of breast cancer cells reduced the expression of HIF-2α in vitro. In addition, reduction of HIF-2α expression suppressed in vitro self-renewal ability and in vivo tumor initiation in ALDH-positive 4T1 cells. Therefore, our findings may provide the evidence necessary for exploring a new strategy in the treatment of breast cancer.
Subject(s)
Aldehyde Dehydrogenase/physiology , Basic Helix-Loop-Helix Transcription Factors/physiology , Breast Neoplasms/pathology , Neoplastic Stem Cells/physiology , Aldehyde Dehydrogenase/antagonists & inhibitors , Animals , Apoptosis , Basic Helix-Loop-Helix Transcription Factors/analysis , Cell Line, Tumor , Enzyme Activation , Female , Humans , Mice , Mice, Inbred BALB C , Octamer Transcription Factor-3/physiologyABSTRACT
Breast cancer is the leading cause of deaths from cancer in women. Cancer recurrence is the most common cause of mortality in breast cancer patients. The cancer stem cell (CSC) hypothesis proposes that CSCs are the center of cancer development and recurrence. Targeting CSCs, in combination with standard chemotherapy, may prevent cancer recurrence and improve long-term survival. Stem cells can be enriched in non-adherent sphere cultures. To identify molecular targets in breast CSCs, we evaluated the transcription levels of stem cell-related genes in 4T1 mouse mammary cancer cells grown as spheres or in a monolayer culture. The most differentially expressed gene was found to be wingless-type MMTV integration site family member 1 (Wnt1) in the 4T1 sphere culture. Functionally, knockdown of Wnt1 in breast cancer cell lines suppressed the in vitro properties of the stem-like cells, including their sphere-forming ability and ALDH activity, whereas the addition of recombinant Wnt1 to breast cancer cell lines enhanced the in vitro properties of these stem-like cells. In addition, knockdown of Wnt1 in 4T1 cells affected the properties of the stem-like cells in vivo, including their tumorigenic potential and tumor initiation ability. Collectively, these results suggest that Wnt1 expression may give rise to the properties of CSCs in breast tumors. Therefore, targeting Wnt1-associated signaling proteins may provide an effective therapeutic approach for the treatment of advanced breast cancer.
