抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.

/pdf/microrna-expression-profiles-classify-human-cancers-43jqfv3rwu.pdf

MicroRNA expression profiles classify human cancers

MicroRNA (miRNA ) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.

MicroRNA signatures in human cancers

MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.

I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.

Oncomirs : microRNAs with a role in cancer

An Unusual Sonographic Manifestation of Lymphoma of the Breast.

of ferroportin up-regulation iron absorption mediated by down-regulation of hepcidin and -thalassemia is characterized by increased β Ineffective erythropoiesis in

O1 The genetic landscape of immune-competent and HIV lymphoma Jenny Zhang, Vladimir Grubor, Cassandra L Love, Anjishnu Banerjee, Kristy L Richards, Piotr Miezcowski, Cherie H Dunphy, William WL Choi, Wing-Yan Auv, Gopesh Srivastava, Patricia L Lugar, David A Rizzieri, Anand S Lagoo, Leon Bernal-Mizrachi, Karen P Mann, Christopher R Flowers, Kikkeri N Naresh, Andrew M Evens, Leo I Gordon, Magdalena B Czader, Javed I Gill, Eric D Hsi, Qingquan Liu, Alice Fan, Katherine Walsh, Dereje D Jima, Micah Luftig, Ting Ni, Jun Zhu, Amy Chadburn, Shawn Levy, David B Dunson, Sandeep S Dave Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA; Department of Statistical Science, Duke University, Durham, NC, USA; University of North Carolina, Chapel Hill, NC, USA; The University of Hong Kong, Queen Mary Hospital, Hong Kong, China; Duke University Medical Center, Durham NC, USA; Emory University, Atlanta GA, USA; Imperial College, London, UK; University of Massachusetts, Worcester, MA, USA; Northwestern University, Chicago, IL, USA; Indiana University, Indianapolis, IN, USA; Baylor University Medical Center, Dallas, TX, USA; Cleveland Clinic, Cleveland, OH, USA; Genetics and Development Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Hudson Alpha Institute for Biotechnology, Huntsville, AL, USA E-mail: ssd9@duke.edu Infectious Agents and Cancer 2012, 7(Suppl 1):O1

Proceedings of the 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI)

Hemoglobin C after a red blood cell transfusion for sickle cell disease

Purpose: This single-center, dose-escalation study examines the safety, efficacy, and pharmacokinetics of epratuzumab (anti-CD22 humanized monoclonal antibody) in patients with recurrent indolent non-Hodgkin’s lymphoma (NHL). Patients and Methods: Patients had indolent NHL and recurrent disease after at least one chemotherapy regimen. Epratuzumab was administered intravenously at 120 to 1,000 mg/m 2 over 30 to 60 minutes weekly for four treatments. Results: Fifty-five patients received epratuzumab and were assessable for safety; 51 patients were assessable for response. Patients were heavily pretreated (50% had at least four prior regimens) and 49% had bulky disease (> 5 cm). Epratuzumab was well tolerated, with no dose-limiting toxicity. Circulating B cells transiently decreased without significant effects on T cells or immunoglobulin levels. More than 95% of infusions were completed in approximately 1 hour. Mean serum half-life was 23 days. Across all dose levels and histologies, nine patients (18%; 95% confidence interval, 8% to 31%) achieved objective response, including three complete responses (CRs). All responses were in patients with follicular NHL: 24% of these patients responded, including 43% in the 360 mg/m 2 dose group and 27% in the 480 mg/m 2 dose group. No responses were observed in other indolent histologies. Median duration of objective response was 79.3 weeks (range, 11.1 to 143.3 weeks), with median time to progression for responders of 86.6 weeks by Kaplan-Meier estimate. Conclusion: Epratuzumab was well tolerated at up to 1,000 mg/m 2 /wk (for 4 weeks) and had clinical activity. One third of responding patients achieved CR. A 43% objective response rate in follicular NHL patients treated at 360 mg/m 2 /wk indicates that this dose should be explored in additional studies. J Clin Oncol 21:3051-3059. © 2003 by American Society of Clinical Oncology.

Amy Chadburn

Papers

An Unusual Sonographic Manifestation of Lymphoma of the Breast.

of ferroportin up-regulation iron absorption mediated by down-regulation of hepcidin and -thalassemia is characterized by increased β Ineffective erythropoiesis in

Proceedings of the 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI)

Hemoglobin C after a red blood cell transfusion for sickle cell disease

Phase I /II T rial o f E pratuzumab ( Humanized A nti-CD22 Antibody) i n I ndolent N on-Hodgkin's L ymphoma