[PD-1/PD-L1 expression and its implications in patients with chronic lymphocytic leukemia].

Objective: To observe the expression levels of PD-1/PD-L1 costimulatory molecules and explore the clinical significance in patients with chronic lymphocytic leukemia (CLL) . Methods: The expression of PD-1/PD-L1 in peripheral blood CD8(+) T cells, CD4(+)T cells, CD19(+)B, and dendrites cells (DC) was detected by flow cytometry in 57 CLL patients and 20 healthy controls. The correlations of PD-1/PD-L1 expression with disease stage, CD38 expression, ZAP-70 expression, chromosome karyotype abnormality and ß(2)-MG expression were analyzed. Results: ①Compared with control, CLL patients, including 39 males and 18 females with the median age of (63.7±10.7) years, had no statistically significant difference in age and gender (P>0.05) . CLL patients had the higher PD-1/PD-L1 expression than healthy controls (P<0.05) . ②In Rai staging, the later the stage, the higher expression of PD-1/PD-L1 (P<0.05) . ③PD-1 expression in CD8(+)CD38(+) group (11 cases) was higher than that in CD8(+)CD38(-) group (46 cases) (P=0.004) , and CD8(+) poor prognosis chromosome group (14 cases) also had significant higher PD-1 expression than CD8(+)good prognosis chromosome group (28 cases) (P=0.004) . ④The expression of PD-L1 was higher in CD38(+)group, ZAP-70(+)group, and poor prognosis group, as compared to that in CD38(-)group (P=0.002) , in ZAP-70(-)group (P<0.001) , in good prognosis group (P=0.023) . There was no correlation between the expression of PD-1/PD-L1 and ß(2)-MG (P>0.05) . Conclusion: This data reveals that PD-1/PD-L1 was highly expressed in CLL patients. Its expression levels were correlated with Rai stage, CD38, ZAP-70, chromosome karyotype, but not with ß(2)-MG. PD-1/PD-L1 may be a prognostic factor in patients with CLL.

Mathematical model of heterogeneous cancer growth with an autocrine signalling pathway.

OBJECTIVES: Cancer is a complex biological occurrence which is difficult to describe clearly and explain its growth development. As such, novel concepts, such as of heterogeneity and signalling pathways, grow exponentially and many mathematical models accommodating the latest knowledge have been proposed. Here, we present a simple mathematical model that exhibits many characteristics of experimental data, using prostate carcinoma cell spheroids under treatment. MATERIALS AND METHODS: We have modelled cancer as a two-subpopulation system, with one subpopulation representing a cancer stem cell state, and the other a normal cancer cell state. As a first approximation, these follow a logistical growth model with self and competing capacities, but they can transform into each other by using an autocrine signalling pathway. RESULTS AND CONCLUSION: By analysing regulation behaviour of each of the system parameters, we show that the model exhibits many characteristics of actual cancer growth curves. Features reproduced in this model include delayed phase of evolving cancer under 17AAG treatment, and bi-stable behaviour under treatment by irradiation. In addition, our interpretation of the system parameters corresponds well with known facts involving 17AAG treatment. This model may thus provide insight into some of the mechanisms behind cancer.