The biology of the normal colonic mucosa suggests that colon cancer originates from normal colon stem cells. CD44 cancer stem cells have been identified in breast and prostate cancer, and we therefore examined whether CD44 similarly identified colon cancer stem cells. Initial assays found CD44hi colon tumor cells to have enhanced soft agar colony‐forming ability. Subsequently, CD44hi cells isolated from 4 primary colon adenocarcinoma xenografts were found to be highly tumorigenic in immune deficient mice. CD44hi cells consistently formed tumors with 1,000 cells, and in multiple experiments, as few as 10 and 100 CD44hi cells formed tumors in 7/10 and 21/28 mice, respectively. In contrast, CD44− colon tumor cells were either nontumorigenic or 10–50‐fold less tumorigenic. CD44hi cells could be serially passaged up to 4 times in vivo, suggesting self‐renewal capacity, and formed tumors that recapitulated the heterogeneity of the original patient tumor. CD44hi cells were significantly enriched for nuclear activated β‐catenin, a key element in normal stem/progenitor cells and in early colon tumor progression. Bromodeoxyuridine (BrdU) labeling studies indicated that CD44hi cells divide slowly relative to the CD44− cells, suggesting their tumorigenicity is not simply due to faster proliferation. Aldehyde dehydrogenase (ALDH) sort further increased the tumorigenicity of CD44hi cells from 2/2 patient tumors, but CD133 tumor cells in our hands did not have increased tumorigenicity. Our observations indicate that CD44 is a marker of stem‐like cells in colon cancer, and support the use of additional markers to further purify colon cancer stem cells.
1 November 1999 in Journal of Physical Oceanography
The seasonal ocean circulation and the seasonal thermal structure in the South China Sea (SCS) were studied numerically using the Princeton Ocean Model (POM) with 20-km horizontal resolution and 23 sigma levels conforming to a realistic bottom topography. A 16-month control run was performed using climatological monthly mean wind stresses, restoring-type surface salt and heat, and observational oceanic inflow/outflow at the open boundaries. The seasonally averaged effects of isolated forcing terms are presented and analyzed from the following experiments: 1) nonlinear dynamic effects removed, 2) wind effects removed, and 3) open boundary inflow/outflow set to zero. This procedure allowed analysis of the contribution of individual parameters to the general hydrology and specific features of the SCS: for example, coastal jets, mesoscale topographic gyres, and countercurrents. The results show that the POM model has the capability of simulating seasonal variations of the SCS circulation and thermoha... Abstract The seasonal ocean circulation and the seasonal thermal structure in the South China Sea (SCS) were studied numerically using the Princeton Ocean Model (POM) with 20-km horizontal resolution and 23 sigma levels conforming to a realistic bottom topography. A 16-month control run was performed using climatological monthly mean wind stresses, restoring-type surface salt and heat, and observational oceanic inflow/outflow at the open boundaries. The seasonally averaged effects of isolated forcing terms are presented and analyzed from the following experiments: 1) nonlinear dynamic effects removed, 2) wind effects removed, and 3) open boundary inflow/outflow set to zero. This procedure allowed analysis of the contribution of individual parameters to the general hydrology and specific features of the SCS: for example, coastal jets, mesoscale topographic gyres, and countercurrents. The results show that the POM model has the capability of simulating seasonal variations of the SCS circulation and thermoha...
1 September 2000 in Journal of Physical Oceanography
This paper investigates the seasonal variabilities of the South China Sea isopycnal-surface circulations and of the Kuroshio intrusion through the Luzon Strait using the U.S. Navy’s climatological temperature and salinity dataset (public domain) with ½° × ½° resolution by the P-vector method. The representative pattern is a persistent basin-scale cyclonic circulation away from the surface, and a seasonally varying circulation with a weak anticylonic gyre in the summer and a strong cyclonic gyre in the winter near the surface. This pattern is consistent with a classical view of mean cyclonic circulation in large stratified lakes and semienclosed marginal seas by Emery and Csanady and with a recent numerical simulation using the navy’s Layered Ocean Model by Metzger and Hurlburt. The computed monthly volume transport through the Luzon Strait is negative (inflow) all year round with a minimum value of −13.7 Sv in February (strongest intrusion) and a maximum value of −1.4 Sv in September (weakest int... Abstract This paper investigates the seasonal variabilities of the South China Sea isopycnal-surface circulations and of the Kuroshio intrusion through the Luzon Strait using the U.S. Navy’s climatological temperature and salinity dataset (public domain) with ½° × ½° resolution by the P-vector method. The representative pattern is a persistent basin-scale cyclonic circulation away from the surface, and a seasonally varying circulation with a weak anticylonic gyre in the summer and a strong cyclonic gyre in the winter near the surface. This pattern is consistent with a classical view of mean cyclonic circulation in large stratified lakes and semienclosed marginal seas by Emery and Csanady and with a recent numerical simulation using the navy’s Layered Ocean Model by Metzger and Hurlburt. The computed monthly volume transport through the Luzon Strait is negative (inflow) all year round with a minimum value of −13.7 Sv in February (strongest intrusion) and a maximum value of −1.4 Sv in September (weakest int...