来源: NCI Understand Cancer Series: Molecular Diagnostics
Human Genome Project 让科学家知道了人类的所有基因。虽然所有细胞都包含全部基因的DNA序列,不同细胞正在表达的基因各不相同,正常细胞与癌细胞表达的基因(或表达水平)也不相同。通过基因芯片技术,我们可以检测出癌细胞基因表达的不同,也可以检测出同一癌症不同患者的基因表达差别。根据这个差别,科学家已经可以预测部分癌症不同患者的治疗效果。同时也可以设计针对癌症特异性基因表达或表达产物(蛋白质)的靶向治疗新药。
Slide 1
|
|
|
|
Normal Cell Communication
|
|
Crucial to all normal cell growth is a communication network that functions properly. This network is an intricate collection of pathways built with interactive proteins. Along these pathways, precise protein-to-protein signaling enables a very carefully guarded regulation of growth. Here are some examples of cellular pathways.
Slide 13
|
|
|
|
Using DNA to Compare Cancer Cells to Normal Cells
|
|
Besides being used to assess the activity of genes being expressed in a single sample, DNA microarrays can also be used to compare the patterns of gene expression in two different cell populations, such as a population of cancer cells with a population of normal cells. In this case, two different fluorescent dyes are used. For example, a red dye can label cDNAs derived from corresponding normal cells, and a green dye, those derived from cancer cells. When the red and green cDNAs are mixed together and placed on a DNA microarray, the green cDNAs will bind to genes expressed in cancer cells and the red cDNAs will bind to genes expressed in normal cells. Green spots represent more copies of a gene being made in a cancer cell, and red spots mean more copies are being made in the normal cell. Yellow spots, caused by mixing red and green fluorescence, represent genes whose expression is roughly the same in both cell types, and black spots, or absence of fluorescence, represent genes expressed in neither cell type.
After laser capture microdissection, scientists can extract the proteins and use 2-D gels, protein lysate microarrays, and/or mass spectrometry to separate and identify subsets of proteins that may then serve as unique markers for a particular cancer cell type.
A major problem in the identification of cancer biomarkers is the very low concentrations of markers coming from tissues with small, early-stage cancer lesions. Fortunately, investigators have found a new way to amplify and concentrate these biomarkers in the blood. When scientists searched for protein patterns in the serum of ovarian cancer patients, they came upon an interesting discovery. The albumin molecule and other long-lived carrier proteins that circulate in the bloodstream act as molecular mops, grabbing a lot of low-molecular-weight proteins as they are degraded and prepared for elimination from the blood. The "mop" actually helped them collect and amplify, more than 100-fold, the low-abundance serum protein patterns needed for analysis.
Picture this: A cancer patient visits her oncologist, gives a few drops of blood or a biopsy specimen, and is told that her genetic expression pattern shows she has a certain subtype of disease. Meanwhile, another expression pattern predicts that her genetic profile should respond well to chemotherapy regimens A and B (with minimal side effects). During her treatments, protein expression patterns are used to make sure that her treatment is effectively disrupting the targeted cellular pathway in her tumor. After treatment, more gene and protein expression patterns verify that the cancer is in remission.
|