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

High resolution two-dimensional electrophoresis of proteins.

WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

We constructed a series of recombinant genomes which directed expression of the enzyme chloramphenicol acetyltransferase (CAT) in mammalian cells. The prototype recombinant in this series, pSV2-cat, consisted of the beta-lactamase gene and origin of replication from pBR322 coupled to a simian virus 40 (SV40) early transcription region into which CAT coding sequences were inserted. Readily measured levels of CAT accumulated within 48 h after the introduction of pSV2-cat DNA into African green monkey kidney CV-1 cells. Because endogenous CAT activity is not present in CV-1 or other mammalian cells, and because rapid, sensitive assays for CAT activity are available, these recombinants provided a uniquely convenient system for monitoring the expression of foreign DNAs in tissue culture cells. To demonstrate the usefulness of this system, we constructed derivatives of pSV2-cat from which part or all of the SV40 promoter region was removed. Deletion of one copy of the 72-base-pair repeat sequence in the SV40 promoter caused no significant decrease in CAT synthesis in monkey kidney CV-1 cells; however, an additional deletion of 50 base pairs from the second copy of the repeats reduced CAT synthesis to 11% of its level in the wild type. We also constructed a recombinant, pSV0-cat, in which the entire SV40 promoter region was removed and a unique HindIII site was substituted for the insertion of other promoter sequences.

Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.

Overlapping complementary DNA clones were isolated from epithelial cell libraries with a genomic DNA segment containing a portion of the putative cystic fibrosis (CF) locus, which is on chromosome 7 Transcripts, approximately 6500 nucleotides in size, were detectable in the tissues affected in patients with CF The predicted protein consists of two similar motifs, each with (i) a domain having properties consistent with membrane association and (ii) a domain believed to be involved in ATP (adenosine triphosphate) binding A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients

https://science.sciencemag.org/content/sci/245/4922/1066.full.pdf

Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.

We have recently reported that an immunotoxin targeting mesothelin produced durable major tumor regressions in patients with extensive treatment-refractory mesothelioma. These unprecedented tumor responses have prompted us to review how mesothelin was discovered and the advances that led to these tumor responses. This review is not comprehensive but focuses on major developments over the past 20 years since mesothelin was first identified in our laboratory. Mesothelin is a cell-surface glycoprotein whose expression in normal human tissues is restricted to mesothelial cells. Because it is highly expressed by many solid tumors, it is an attractive immunotherapy target. Antibody-based therapies currently in clinical trials include an immunotoxin, a chimeric monoclonal antibody, and an antibody drug conjugate. In addition, a mesothelin tumor vaccine and a mesothelin- chimeric antigen receptor are being evaluated in the clinic. SS1P, an anti-mesothelin immunotoxin, was the first mesothelin-directed therapy to enter the clinic, and its use showed that mesothelin-targeted therapy was safe in patients. More importantly, our recent work has shown that SS1P in combination with pentostatin and cyclophosphamide can result in durable tumor regression in patients with advanced mesothelioma and opens up the possibility that such an approach can benefit patients with many common cancers.

https://cancerres.aacrjournals.org/content/canres/74/11/2907.full.pdf

Discovery of Mesothelin and Exploiting It as a Target for Immunotherapy

Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epithelia.

Regulation of transcription of members of the ras gene family undoubtably plays an important role in controlling cellular growth. Examination of this level of regulation requires identification of the promoter regions of the ras proto-oncogenes. Four major transcriptional start sites were detected in the human Harvey ras 1 proto-oncogene. The promoter region contains neither a TATA box nor a CAAT box in their characteristic upstream positions, has an extremely high G+C content (80 percent), and contains multiple GC boxes including seven CCGCCC repeats and three repeats of the inverted complement, GGGCGG. This region has strong promoter activity when placed upstream from the chloramphenicol acetyl transferase gene and transfected into monkey CV1 cells. In these ways the Harvey ras 1 proto-oncogene promoter resembles the promoter of the gene encoding the epidermal growth factor (EGF) receptor. The similarity between the two proto-oncogene promoters may be relevant to the mechanism by which the expression of such "growth control" genes is regulated.

Promoter region of the human Harvey ras proto-oncogene: similarity to the EGF receptor proto-oncogene promoter

The photoaffinity reagent 8-azido-alpha-[32P]ATP was used to label a protein of 170 kDa in membrane vesicle preparations from a highly multidrug-resistant cell line, KB-V1, but not from the drug-sensitive parental cell line KB-3-1. The 170-kDa labeled protein was immunoprecipitated with a monoclonal antibody (MRK-16) to P glycoprotein. Both ATP and GTP inhibited labeling by 8-azido-alpha-[32P]ATP. Labeling of P170 was not inhibited by 5 mM ADP, 5 mM ribose-5-phosphate, or 100 microM vinblastine. These data directly demonstrate that P glycoprotein has a nucleotide-binding site that could supply energy for drug transport.

Ira Pastan

Papers

Discovery of Mesothelin and Exploiting It as a Target for Immunotherapy

Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epithelia.

Promoter region of the human Harvey ras proto-oncogene: similarity to the EGF receptor proto-oncogene promoter

ATP-binding properties of P glycoprotein from multidrug-resistant KB cells.

Clinical trials of agents that reverse multidrug-resistance.