前沿科技及其它

Urinary cytology is used in combination with cystoscopy for the diagnosis of primary bladder cancer and to monitor the patients for early detection of recurrence after initial transurethral resection. Urinary cytology is highly specific for the detection of poorly differentiated ...

In recent years, immunohistochemistry as applied to the Bcl-2 family of proteins has represented a burgeoning area of interest to cancer researchers. The majority of studies have focused on the original member Bcl-2, first identified via its involvement in the common t(14;18) chromosomal t ...

Microsatellites are simple, tandemly repeated DNA sequences which are abundantly distributed throughout the human genome, and because of their polymorphic nature have been widely utilized as genetic markers (1). They consist of a repeating unit of 1–5 base pairs, averaging 25–60 bases in ...

DNA damaging agents have been widely used in cancer chemotherapy for many years and have proved successful in the treatment of both solid tissue and haematological malignancies. Many commonly used clinical agents, such as members of the nitrogen mustard, chloroethylnitrosourea, dim ...

Many anticancer drugs and environmental carcinogens exert cytotoxic and or mutagenic effects through the direct reaction with DNA via in the formation of drug-DNA adducts or stabilized protein-DNA complexes (1,2). The ability to determine the extent with which drugs, such as alkylating ...

A large proportion of anti-cancer drugs act by causing chemical modifications to DNA, often involving the addition of part of the drug molecule to DNA to form DNA adducts. As discussed in Chapter 1, resistance mechanisms can act to diminish the extent of drug-target access or to alter the responses of c ...

The uracil analog 5-fluorouracil (5-FU) is used as part of combination therapy for the treatment of breast, head/neck, and gastrointestinal malignancies, and has single-agent activity in colorectal cancer. 5-FU itself is inactive and requires intracellular conversion to form cytot ...

DNA topoisomerases I and II (top1 and top2, respectively) are ubiquitous enzymes that play an essential role in transcription, replication, chromosome segregation, and DNA repair. The basic enzymatic reaction of topoisomerases, namely reversible DNA nicking, is a transesterific ...

Drug resistance is a major factor that limits the effectiveness of cancer chemotherapy, and there is considerable evidence to suggest a genetic basis for many drug-resistant phenotypes. A major drawback to many of the conventional approaches used to investigate drug-resistance mech ...

The recognition over the past decade that apoptosis represents a critical element in cell number control in physiological and pathological situations has been well-reviewed (1–4). In addition there is increasing recognition that many of the effects of chemo- and radiotherapeutic ag ...

Accurate determination of the expression of P-glycoprotein and its encoding mRNA, MDR-1, is key to determining the importance of this mechanism of drug resistance in the clinic. This understanding is critical to development of P-glycoprotein antagonists to block drug efflux and to overc ...

Glutathione is an intracellular, nonprotein thiol that appears to play an important role in protection of the cell against cytotoxic drugs (1) and has been implicated in the control of cell cycling (2,3) and apoptosis (4,5). It can exist in an oxidized (disulfide, ) and a reduced (sulphydryl, ) form. In ge ...

The MDR1-encoded P-glycoprotein (Pgp), when overexpressed in tumor cells, confers resistance to many clinically important classes of anticancer drugs. This phenomenon is called multidrug resistance (MDR). The finding that this gene was expressed in many types of human cancers has sti ...

Tumor progression is driven by the accumulation of genetic changes, which, in aggregate, confer the malignant phenotype (1). Thus, tumor development proceeds via clonal divergence with selection for cells with, for example, a proliferative advantage, metastatic potential, or drug re ...

As outlined in Chapter 8, glutathione in the intact cell is maintained predominantly in its reduced form by the cytosolic enzyme, glutathione reductase. Cell lysis can lead to rapid oxidation to the oxidized form, GSSG, and degradation by γ-glutamyl transpeptidase. In order to obtain a true mea ...

Cancer patients’ outcome and survival depends on the early diagnosis of malignant lesions. Several investigation methods used for the prevention and early detection strategies have specific limitations. More recently, epigenetic changes have been considered one of the most prom ...

Epigenetics is an emerging science that can help to explain carcinogenesis. The possibility that carcinogenesis may originate in a stem cell process was proposed recently. Stem cells are generated and contribute to tumor formation during the process of tumor development. This chapter ...

Accumulation of genetic and epigenetic alterations transforms normal colonic epithelial cells to adenocarcinoma cells. Genetic alterations include mutations in tumor suppressor genes and oncogenes, whereas epigenetic mechanisms are defined as heritable alterations ...

In addition to genetic alterations of gains and losses, epigenetic events of promoter methylation appear to further undermine a destabilized genomic repertoire in squamous head and neck carcinoma (HNSCC). This chapter provides an overview of frequently methylated tumor suppres ...

Epigenetics studies and defines inherited changes in gene expression that are not encoded in the DNA sequence. The most studied epigenetic change in mammalian DNA is cytosine methylation in CpG dinucleotide areas. The other main group in epigenetic changes includes the posttranslati ...