Polyreactive igm antibodies in the circulation are masked by antigen binding

Human plasma containing IgM showed only minimal, if any, reactivity with a panel of antigens as measured by ELISA. In contrast, affinity-purified IgM showed many times more reactivity with the same panel of antigens. When plasma was added back to the affinity-purified IgM, the reactivity of the IgM with antigens was completely inhibited by undiluted plasma and by as much as 40% with as little as a 1100 dilution of plasma. When the affinity-purified IgM was affinity-purified a second time by passage through antigen-specific columns (e.g., insulin or Fc or -galactosidase), the eluted antibodies bound not only to the antigen used for purification, but also to a panel of unrelated antigens, indicating that the antibodies were polyreactive. It is concluded that polyreactive IgM antibodies are present in the circulation but are masked by binding to circulating antigens.     

The impact of Aldehyde dehydrogenase 1 expression on prognosis for metastatic colon cancer

Background

Cancer stem cells may be associated with tumor progression and prognosis for colon cancer. We hypothesized that expression of Aldehyde dehydrogenase 1 (ALDH1) would increase with tumor progression and be associated with survival.

Methods

Tissue was obtained from resection specimens for isolation of cancer stem cells. In addition, paraffin blocks from resected colon cancers with normal colon, primary tumor, and lymph node and liver metastasis from 2000 to 2010 were identified and stained with ALDH1.

Results

In in vitro models (adherent and tumor spheres) ALHD1+ cells grew more efficiently than ALDH1− cells. ALDH1 expression was highest in peritumoral crypt cells (0.137 μm², 95% confidence interval [CI] 0.125–0.356) and normal crypts (median 0.091 μm², 95% CI 0.064–0.299) followed by lymph node metastasis (median 0.025 μm², 95% CI 0–0.131) and the primary cancers (median 0.014 μm², 95% CI 0.0123–0.154). Samples were divided into high and low ALDH1 expression. Survival was associated with expression in the primary tumor (9 versus 23 mo, P = 0.0016) expression but not peritumoral tissue (21 versus 20.5 mo, P = 0.32), normal colon (19 versus 27 mo, P = 0.289), or lymph node metastasis (23 versus 21 mo, P = 0.69). On univariate analysis, ALDH1 expression and grade were associated with survival but ages, number of lymph node metastasis, race, or grade were not associated. On multivariate analysis, only ALDH1 status continued to be associated with survival, odds ratio 4.4, and P = 0.011.

Conclusions

ALDH1 is indicative of stemness and is a biomarker marker in colon cancer. Expression did not increase with progression from normal colon to primary tumors and metastasis.     

Hemin acts synergistically with interleukin-3 to promote the growth of multipotent stem cells (CFU-GEMM) in "serum-free" cultures of normal murine bone marrow

The role of hemin (iron protoporphyrin 9) in the enhancement of interleukin-3 (IL-3)-stimulated multipotent stem cell colony formation was assessed in both serum-containing as well as in "serum-free" marrow culture systems. A greater than 7-fold enhancement in colony number was observed when cultures were supplemented with both IL-3 and hemin compared with either factor alone. In addition, this effect was observed over a wide concentration range. Hemin by itself failed to promote CFU-GEMM in the "serum-free" marrow culture system. The results suggest that hemin acts synergistically with IL-3 to promote the growth of CFU-GEMM in a dose-dependent manner.