Methylation-specific polymerase chain reaction (MSP) is a method that can rapidly assess the methylation status of virtually any group of CpG sites within a CpG island, independent of the use of methylation-sensitive restriction enzymes. This assay entails the initial modification ...
Defects in the mismatch repair system are associated with a microsatellite unstable phenotype. In this chapter, we describe the preparation of purified plasma cells using CD138 magnetic microbeads as a source of tumor DNA. We also describe a robust, sensitive method for compar- ing microsa ...
Expanded T-cell clones in the peripheral blood of patients with multiple myeloma and smoldering myeloma are usually CD8 positive and persist over long periods, suggesting that they are the result of chronic antigenic stimulation. The presence of enlarged T-cell clones can be demonstrat ...
Multiple myeloma (MM) is a B-cell neoplasm in which malignant plasma cells accumulate in the bone marrow and produce lytic bone lesions and excessive amounts of a monoclonal protein (usually an immunoglobulin of the IgG or IgA type or free light chain). Approximately 14,000 new cases of MM are diagn ...
Much of the morbidity and mortality associated with the plasma cell (PC) malignancy, multiple myeloma (MM), is owing to the severe osteolytic bone disease seen in patients with this disease. Although the molecular mechanisms responsible for osteolysis remain to be fully elucidated, it is cl ...
Tumor cells engineered to express immunogenes have been used for cancer vaccines to induce antitumor immunity and to study the antitumor immune mechanisms derived from immunogene expression. In this chapter, we describe the design and methods for cloning a cDNA gene coding for the mouse CD4 ...
Dendritic cell (DC)—tumor fusion hybrid vaccine that facilitates antigen presentation represents a new, powerful strategy in cancer therapy. We investigated the antitumor immunity derived from vaccination of fusion hybrids between wild-type J558 or engineered J558-IL-4 mye ...
Telomerase is an enzyme that has been attracting much attention in recent years because its activities are so central to the processes of malignant transformation. It is a reverse transcriptase enzyme that can synthesize telomeric DNA using its own RNA component as a template. Without telom ...
Multiple myeloma is a B-cell neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, the development of osteolytic lesions, and the induction of angiogenesis. These different processes require three-dimensional interactions, with both humor ...
The severe combined immune deficient human (SCID-hu) myeloma model is the only available model in which primary myeloma cells grow in vivo in a human bone marrow microenvironment. A SCID mouse receives an implanted human fetal bone into which myeloma cells are directly injected. Through inte ...
Patients with multiple myeloma have a clonal proliferation of malignant plasma cells, each with an identical rearrangement of immunogloblin heavy and light chain genes. When these unique sequences are determined, a valuable molecular tool is available that can been used to detect the pr ...
Analysis of Ig genes in B-cell malignancies has become an essential method in molecular diagnosis, and polymerase chain reaction (PCR) amplification of Ig heavy chain gene (IgH) rearrangements is now widely used for detection of clonality and minimal residual disease (MRD). Although sev ...
The evaluation of minimal residual disease (MRD) is critical in the evaluation of treatments aimed at maximal cytoreduction in multiple myeloma (MM). Qualitative evaluation of MRD now has a 10-yr-long history, but it remains a relatively sophisticated procedure. More recently, real-t ...
In multiple myeloma (MM) the rearranged immunoglobulin heavy chain (IgH) variable, diversity, and joining (VDJ) DNA sequence of malignant plasma cells (PCs) serves as a marker for cells in the MM clone. This clonotypic sequence can be isolated from MM PCs by reverse transcriptase polymerase c ...
The primary aim of tissue fixation is to preserve tissue in the long term, ideally without causing alterations in morphology or biochemical integrity. Optimal fixation should therefore inhibit autolysis while preserving enzyme activity and antigen reactivity. However, some of the ...
The histopathological diagnosis of malignancy has traditionally been said to be the gold standard by which all other methods of investigation and diagnosis are defined and assessed. Although this is still largely true, the other chapters in this book attest to the fact that it may not be true for much ...
It is now well established that, in addition to genetic changes that may include germ line and somatic DNA alterations, cancers can also arise as a result of a series of epigenetic DNA mutations (1). In mammals, DNA is methylated at cytosine residues in the 5′ position of CpG dinucleotides. The genomic met ...
The widespread acceptance of prostate-specific antigen (PSA) testing by clinicians as evidence of prostatic pathology and recognition that elevated levels in serum often precede overt disease has permitted a much earlier identification of patients with prostatic epithelial c ...
To date, prostate-specific antigen (PSA) has proven to be the most useful tumor marker for prostate cancer (1–3). However, the PSA test does not discriminate well between men with benign disease and early prostate cancer, and it does not discriminate between aggressive and slow-growing cance ...
The androgen receptor (AR) gene comprises eight exons located at chromosome Xq11-12 and encodes an mRNA transcript of approx 11 kb (1–5). Situated within exon 1 of the AR gene is a polymorphic CAG trinucleotide repeat, which encodes a polyglutamine (poly-Q) tract of variable length in the N-termin ...