Specific down-regulation of XIAP with RNA interference enhances the sensitivity of canine tumor cell-lines to TRAIL and doxorubicin

Background  

Apoptosis resistance occurs in various tumors. The anti-apoptotic XIAP protein is responsible for inhibiting apoptosis by reducing caspase-3 activation. Our aim is to evaluate whether RNA inhibition against XIAP increases the sensitivity of canine cell-lines for chemotherapeutics such as TRAIL and doxorubicin. We used small interfering RNA's (siRNA) directed against XIAP in three cell-lines derived from bile-duct epithelia (BDE), mammary carcinoma (P114), and osteosarcoma (D17). These cell-lines represent frequently occurring canine cancers and are highly comparable to their human counterparts. XIAP down-regulation was measured by means of quantitative PCR (Q-PCR) and Western blotting. The XIAP depleted cells were treated with a serial dilution of TRAIL or doxorubicin and compared to mock- and nonsense-treated controls. Viability was measured with a MTT assay.     

Phenotypic markers and BCL-1 gene rearrangements in B-cell chronic lymphocytic leukemia: a Cancer and Leukemia Group B study

The markers, CD11b, CD11c, CD14, CD21, CD23, CD25, CD38, and FMC7 were correlated with morphologic and other laboratory and clinical characteristics of 127 patients with untreated CD5+ chronic lymphocytic leukemia (CLL). Only CD38 and CD21 were significantly associated with atypical CLL morphology. The integrin associated markers CD11b and CD11c were associated with lower leukocyte count (white blood cell count [WBC]) and lower Rai stage. By contrast, the activation antigen CD23 was associated with a higher WBC, higher Rai stage, younger age group, and the presence of lymphadenopathy. Therefore, we conclude that CD23 positivity may reflect a more aggressive form of CLL, and CD11b and CD11c positivity a less aggressive form. The BCL-1 gene rearrangement was present in 5 of 84 (6%) CLL cases examined and was associated with atypical morphology and surface expression of CD11b. Patients with a BCL-1 gene rearrangement may represent a CLL subset or possibly a different B-cell disease.     

Hemorrhagic intracranial malignant neoplasms: spin-echo MR imaging

Twelve patients with 15 separate, spontaneously hemorrhagic, intracranial malignant lesions (seven primary gliomas, eight metastatic lesions) were examined with spin-echo magnetic resonance imaging at 1.5 T, and with computed tomography. The signal intensity patterns of these lesions, as seen on both short repetition time (TR)/short echo time (TE) and long-TR/long-TE spin-echo pulse sequences, were compared with the previously described appearance at 1.5 T of non-neoplastic intracerebral hematomas. The images of hemorrhagic intracranial malignancies showed notable signal heterogeneity, often with identifiable nonhemorrhagic tissue corresponding to tumor; diminished, irregular, or absent hemosiderin deposition; delayed hematoma evolution; and pronounced or persistent edema, compared with non-neoplastic hematomas. The demonstration of these characteristics in the appropriate clinical setting may suggest malignancy as the cause of an intracranial hematoma.     

Complete and partial ureteral obstruction: evaluation of renal effects with P-31 MR spectroscopy and Tc-DMSA scintigraphy

Phosphorus-31 magnetic resonance (MR) spectroscopy was used to study the effects of partial and complete ureteral obstruction on the porcine kidney; results were compared with renal tubular function as determined with technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy. Twenty-seven pigs were used: nine as sham-operated controls, six with partial ureteral obstruction, and 12 with complete ureteral obstruction. P-31 MR spectra and Tc-DMSA scintiscans were obtained weekly over 3 weeks. Partial obstruction caused no significant change in P-31 MR spectra, whereas Tc-DMSA scintiscans showed a 74% decrease in tubular function by the end of 3 weeks. Complete obstruction caused a 43% reduction in the mean adenosine triphosphate (ATP) to inorganic phosphate (Pi) ratio, which paralleled the 96% decrease in Tc-DMSA uptake over 3 weeks. The difference in ATP/Pi ratios between control and completely obstructed kidneys was significant (P less than .01) at 2 and 3 weeks after ligation. These results indicate that radionuclide Tc-99m DMSA uptake is very sensitive to the pathophysiologic changes in renal tubular function, while the organ average cellular bioenergetic state (ATP/Pi) is not as strongly affected.     

Evidence for posttranslational control of Hb C synthesis in an individual with Hb C trait and alpha-thalassemia

The level of Hb C in the erythrocytes of individuals with Hb C trait decreases significantly in the presence of coexisting alpha- thalassemia. This relationship may result from the higher affinity of beta A than beta C for limiting amounts of alpha-globin during hemoglobin assembly. This mechanism would predict that the beta A and beta C synthetic capacity in alpha-thalassemic individuals with Hb C trait should be balanced despite the low levels of Hb C in their circulating erythrocytes. To directly test this prediction, we have measured the beta A and beta C synthetic capacity of reticulocyte RNA isolated from two individuals with Hb C trait, one with a normal alpha- globin genotype and one with alpha-thalassemia. The balanced expression of beta A and beta C in both cases supports the proposed posttranslational control over Hb C expression.     

维甲酸与二甲基亚砜诱导HL-60细胞及其抗性亚型MDR 1的表达和对Rhodamine-123外排的影响

利用Dot blot 和流式细胞术，研究了分化诱导剂维甲酸，DMSO对HL-60细胞及其抗性亚型抗药性程度的影响，表明1μmol·ml^-1 RA 作用H-60及其亚型24h， MDR 1 mRNA 明显增高，但流式检测多药抗性细胞系对Rho-123的外排有所下降。2%DMSO作用HL-60及其亚型 24h，流式细胞术检测显示各细胞系对Rho-123 的外排明显增强，提示RA 虽然提高MDR 1基因的表达，但可能通过磷酸化/脱磷酸化方式抑制Pgp-170功能的表达，而DMSO能诱导完整功能的Pgp表达。