前沿科技及其它

Antisense gene therapy involves the selective inhibition of expression or function of disease-causing genes by treatment with an antisense molecules (RNA or oligodeoxynucleotides) complementary to its target nucleic acids, usually to some specific mRNA molecules or mRNA prec ...

According to the current view, an efficient T-lymphocyte activation requires not only a specific signal delivered through the engagement of a T-cell receptor (TCR) by antigenic peptide-major histocompatibility complex (MHC), but also signals provided by costimulatory molecul ...

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in numerous countries. The incidence of HCC is rapidly increasing andp proximately results in 350,000 deaths each year worldwide (1–4). The conventional chemotherapy and radiation treatment for HCC have been dis ...

Selective gene therapy represents a potent approach in cancer treatment that utilizes a cell’s own nontoxic suicide genes. Currently, the suicide genes under investigation mediate sensitivity by encoding viral or bacterial enzymes that convert inactive prodrug into toxic antim ...

This chapter is intended to help other workers with the preparation of human gene therapy proposals. What follows is an abridged version of a protocol describing the use of gene replacement with p53 for liver tumors. This was submitted to the Gene Therapy Advisory Committee (GTAC) of the Departme ...

The transforming growth factor β (TGF-β) receptors are an important class of tumor suppressor gene. TGF-β markedly inhibits the growth of many epithelial cell types; whereas in contrast, cancers of many different tissue types are commonly TGF-β resistant (10). Many cancer cell lines are resi ...

Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition affecting approx 1 in 3500 persons (1). Individuals with NF1 have a small but significant risk of developing cancers, primarily derived from neural crest tissues, such as astrocytic brain tumors and malignant perip ...

During the last two decades, novel nonclonogenic methods for pretherapeutic chemosensitivity testing have been developed that are likely to overcome major technical limitations of older assays such as low evaluability rates, low degree of standardization and reproducibilit ...

Reliable assessment of cell death is now pivotal to many research programs aiming at generating new antitumor compounds or at screening cDNA libraries to identify genes with pro - or antiapoptotic functions. Such approaches need to rely on reproducible, easy handling, and rapid micropla ...

Metastatic renal cell carcinoma (RCC) is incurable and there are few treatment options that assure even a short prolongation in survival. It is the most common malignancy of the adult kidney and accounts for approximately 12,000 deaths per year (1). Due to a lack of diagnostic markers for early dete ...

The DNA damage-dependent checkpoint of Saccharomyces cerevisiae is a paradigm for eukaryotic checkpoint pathways that regulate cell cycle progression in the presence of insults to the genetic material. In order to better understand this pathway, we undertook a biochemical study of t ...

The spindle checkpoint is assayed in Saccharomyces cerevisiae using several criteria. Sensitivity to benzimidazole drugs is assayed in cells grown in liquid medium and cells grown on solid medium on petri plates. Cell cycle delays are measured using cells synchronized by treatment with ...

In response to genotoxic insults, cells activate DNA damage checkpoint pathways that stimulate DNA repair, lead to a transient cell cycle arrest, and/or elicit programmed cell death (apoptosis) of affected cells. The Caenorhabditis elegans germ line was recently established as a model s ...

In the presence of DNA damage, cells delay the entry into mitosis, presumably to allow time for repair. Methods to detect the delay of mitosis in a multicellular model organism, Drosophila melanogaster, are described here. These include the collection of embryos and larvae, irradiation with x- ...

The checkpoint protein Chfr delays entry into mitosis in the presence of mitotic stress. We have analyzed the Chfr checkpoint pathway in the Xenopus cell-free system. We showed that Chfr is a ubiquitin ligase that targets polo-like kinase (Plk1) for degradation, leading to delayed activation ...

Owing to their importance in normal cell division, DNA damage checkpoint and repair genes are often required for the earliest stages of embryonic development. For example, conventional deletion of ATR (1), Chk1 (2), Mad2 (3), NBS (4), Rad50 (5), BRCA1 (6), BRCA2 (7), or Rad51 (8) leads to developmental arr ...

Germline mutations of the breast tumor suppressor gene BRCA1 predispose women to breast and ovarian cancers. However, loss-of-function mutations of mouse Brca1 results in recessive embryonic lethality, which obscures the functions of BRCA1 in breast cancer formation. Cre-loxP-m ...

Maintenance of genomic integrity is essential to avoid cellular transformation, neoplasia, or cell death. DNA synthesis, mitosis, and cytokinesis are important cellular processes required for cell division and the maintenance of cellular homeostasis; they are governed by many ex ...

The spindle checkpoint is an evolutionarily conserved regulatory mechanism that ensures correct segregation of chromosomes at mitosis and meiosis. The kinetochore plays an integral role in spindle checkpoint signaling by integrating chromosome attachment to the spindle wi ...

The G2 checkpoint prevents cells from entering mitosis when DNA is damaged, providing an opportunity for repair and stopping the proliferation of damaged cells. Because the G2 checkpoint helps to maintain genomic stability, it is an important focus in understanding the molecular causes ...