Loss or down-regulation of human leukocyte antigen (HLA) class I expression has been demonstrated in a variety of solid tumors. To date, such altered HLA expression has not been studied extensively in freshly isolated leukemic blasts. If it occurs, leukemic cells could escape T-cell surveillance as a consequence. Genotypes of nine leukemic cell lines were determined using a polymerase chain reaction for HLA classes I and II. Cells were also examined for HLA β β β β2-microglobulin, and allele-specific HLA protein expression using flow cytometry. Next, 44 samples of freshly isolated leukemic blasts from 43 patients with malignant hematological diseases were examined for allele-specific HLA expression using flow cytometry.
The prognostic value of stage of lymph node metastases was evaluated in 357 patients who underwent curative resection for colorectal cancer. Subdivision of Dukes C patients according to the number of positive nodes revealed that the five-year disease-free survival rate (5DFS) was 63 percent in the patients with one to three nodes and 53 percent in those with four or more nodes (not significantly different). Classification according to the location revealed that 5DFS was 70 percent in those who had only local node metastases (n1+), compared with 40 percent in those who had distant node metastases along the major vessels (n2+) (P < 0.001). Twelve of 38 n2+ patients had only one distant node metastasis with no local node involvement (skip metastasis). They had lower 5DFS than the n1+ patients who had three or more positive local nodes (35 percent vs. 57 percent). We conclude that the location, rather than the number, of nodal metastases has a higher impact on prognosis in colorectal cancer patients.
Abstract. Both inflammatory and anti-inflammatory cytokines have been reported to be associated with acute graft-versushost disease (aGVHD). However, their role and possible mutual interactions during aGVHD are not well understood. Eight patients with aGVHD and eight without who had undergone allogeneic HLA-identical peripheral blood stem cell transplantation were studied. The patients had no other complications known to affect serum concentration of cytokines, including infection. Serum concentrations of IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-· and IFN-Á were concurrently measured by a new technique, the cytometric bead array (CBA). We found that serum concentrations of IL-5, IL-6 and IL-10 were significantly higher in patients with aGVHD than in patients without it. By ratiometric analysis, the ratios of IL-5/IL-2, IL-5/IL-4, IL-6/ IL-4 in patients with aGVHD were increased compared to the patients with no evidence of aGVHD. ROC analysis demonstrated that the ratio of IL-5/IL-4 was the most sensitive parameter associated with aGVHD. The second best marker of aGVHD was increased IL-5 concentration. Thus, our results indicate that the ratio of a particular cytokine/ cytokine could be a potential diagnostic marker for aGVHD, more sensitive that the serum level of a given cytokine. This observation is consistent with a cross-talk among some cytokines and their possible interactions via respective receptors on cytokine-producing cells; these interactions may play an important role in pathogenesis of aGVHD. Further studies including a large number of patients and concurrent measurement of a variety of cytokines are needed to fully assess the diagnostic value of the cytokine ratiometric analysis. The CBA methodology provides a convenient and useful tool in such studies.
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