HIF-1α在原发性肝细胞癌中的表达及意义

目的探讨低氧诱导因子-1α（HIF-1α）在原发性肝细胞癌中的表达,以及HIF-1α与血管内皮生长因子（VEGF）和微血管密度（MVD）表达的相关性。方法采用免疫组化法检测HIF-1α、VEGF和MVD在原发性肝细胞癌、肝硬化及肝正常组织中表达情况。结果HIF-1α在肝细胞癌、肝正常组织和肝硬化组织中的表达差异有显著性（P〈0.05）,HIF-1α与VEGF和MVD在肝癌中的表达有相关性。结论HIF-1α在肝细胞癌中高表达在肝癌肿瘤血管生成中有重要作用。     

Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images

Purpose

Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -immuno-PET using count-reduced clinical images.

Procedures

Data were acquired from three previously reported clinical studies with [⁸⁹Zr]antiCD20 (74 MBq, n?=?7), [⁸⁹Zr]antiEGFR (37 MBq, n?=?7), and [⁸⁹Zr]antiCD44 (37 MBq, n?=?13), with imaging obtained 1 to 6 days post injection (D0–D6). Volumes of interest (VOIs) were manually delineated for liver, spleen, kidney, lung, brain, and tumor. For blood pool and bone marrow, fixed-size VOIs were used. Original PET list mode data were split and reconstructed, resulting in two count-reduced images at 50 % of the original injected dose (e.g., 37 MBq_74inj).Repeatability coefficients (RC) were obtained from Bland-Altman analysis on standardized uptake values (SUV) derived from VOIs applied to these images.

Results

The RC for the combined manually delineated organs for [⁸⁹Zr] antiCD20 (37 MBq_74inj) increased from D0 to D6 and was less than 6 % at all time points. Blood pool and bone marrow had higher RC, up to 43 % for 37 MBq_74inj at D6. For tumor, the RC was up to 42 % for [⁸⁹Zr]antiCD20 (37 MBq_74inj). For [⁸⁹Zr]antiCD20, (18 MBq_74inj), [⁸⁹Zr]antiEGFR (18 MBq_37inj), and [⁸⁹Zr]antiCD44 (18 MBq_37inj), measurement variability was independent of the investigated antibody.

Conclusions

Based on this study, noise-induced variability results in a RC for Zr-89-immuno-PET (37 MBq) around 6 % for manually delineated organs combined, increasing up to 43 % at D6 for blood pool and bone marrow, assuming similar biodistribution of antibodies. The signal-to-noise ratio leads to tumor RC up to 42 %.

     

Simultaneous occurrence of acute monoblastic leukemia and an abnormal B-cell clone with both cell types characterized by specific cytogenetic and immunological markers

2 different, unrelated, abnormal clones of cells were found in a patient with acute leukemia, each clone being characterized by specific cytogenetic abnormalities and a distinct immunological phenotype. Bone marrow morphology and cytochemistry indicated an acute monoblastic leukemia, a diagnosis supported by the finding of a t(9;11) in bone marrow cells. In PHA-stimulated blood culture, another abnormal karyotype was found in 16% of the metaphases: 47,XY, + 12, inv(13), t(14;18). Immunologically, the blood contained 3 types of mononucleated cells (MNC): 1) large cells (about 70% of the MNC) with a phenotype consistent with monoblastic/monocytic leukemic cells (My7+, My8+, My906+, My4+, Leu-M3+); 2) small lymphocytic cells with either T-cell characteristics (6% of the MNC); or 3) B-cell monoclonal features (24% of the MNC). The monoclonal B-cell population was Sm kappa +, mu +, delta +, BA-1+, B1+, Y29/55+ and FMC7+. The possible origin of this abnormal (malignant) B-cell population is discussed. However, this B-cell clone was clinically silent and the patient' death precluded further observations.     

Clinical Spectrum of LIG4 Deficiency Is Broadened with Severe Dysmaturity,Primordial Dwarfism,and Neurological Abnormalities

DNA double‐strand break repair via non‐homologous end joining (NHEJ) is involved in recombination of immunoglobulin and T‐cell receptor genes. Mutations in NHEJ components result in syndromes that are characterized by microcephaly and immunodeficiency. We present a patient with lymphopenia, extreme radiosensitivity, severe dysmaturity, corpus callosum agenesis, polysyndactily, dysmorphic appearance, and erythema, which are suggestive of a new type of NHEJ deficiency. We identified two heterozygous mutations in LIG4. The p.S205LfsX29 mutation results in lack of the nuclear localization signal and appears to be a null mutation. The second mutation p.K635RfsX10 lacks the C‐terminal region responsible for XRCC4 binding and LIG4 stability and activity, and therefore this mutant might be a null mutation as well or have very low residual activity. This is remarkable since Lig4 knockout mice are embryonic lethal and so far in humans no complete LIG4 deficiencies have been described. This case broadens the clinical spectrum of LIG4 deficiencies.