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Biomedical subjects

S Vincent Rajkumar

Publications and source records attributed to S Vincent Rajkumar.

99 records · Page 6Linked to original sources
PubMed2002

Monoclonal gammopathies of undetermined significance.

The term 'monoclonal gammopathy of undetermined significance' denotes the presence of a monoclonal protein in patients without evidence of multiple myeloma, macroglobulinemia, amyloidosis or related plasma cell proliferative disorders. The disorder has been found in approximately 3% of persons older than 70 years and in approximately 1% of persons older than 50 years. A population-based study included 1384 patients from south-eastern Minnesota who had the disorder diagnosed at the Mayo Clinic from 1960 through 1994. Risk of progression was about 1% per year, but patients were at risk of progression even after 25 years or more of stable monoclonal gammopathy of undetermined significance. The risk for development of multiple myeloma was increased 25-fold; the risk of macroglobulinemia, 46-fold; and the risk of primary amyloidosis, 8.4-fold. Concentration and type of monoclonal protein were the only independent predictors of progression. The presence of a urine monoclonal protein and the reduction of one or more uninvolved immunoglobulins were not risk factors for progression. Monoclonal gammopathy of undetermined significance may be associated with various disorders, including lymphoproliferative diseases, leukemia, von Willebrand disease, connective tissue diseases and neurologic disorders.

Disease Progression↗
PubMed2002

Myeloma and the newly diagnosed patient: a focus on treatment and management.

An evidence-based approach to the management of newly diagnosed multiple myeloma, developed at the Mayo Clinic (Rochester, MN), is summarized in this article. The optimum pretransplant induction regimen for multiple myeloma is described, and outcomes for early and delayed transplantation, one versus two transplants, the role of thalidomide in smoldering multiple myeloma, and the role of maintenance therapy are discussed. The role of supportive care strategies for patients with bone disease, such as the use of bisphosphonates, is also discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

A review of angiogenesis and anti-angiogenic therapy in hematologic malignancies.

Tumor angiogenesis is currently not only a concept but has also become a rationale for the therapeutic use of both old and new drugs that might affect new blood vessel formation. There is growing evidence that angiogenesis is as important in hematologic malignancies as it is in solid tumors. Both myeloid and lymphoid disorders may be accompanied by a prognostically detrimental increase in bone marrow microvessel density. In this review, we summarize the current literature as well as our own studies regarding bone marrow angiogenesis and the use of anti-angiogenic treatment in hematologic disorders. Background information on pathogenesis and laboratory methods of quantifying bone marrow angiogenesis is also discussed.

Angiogenesis Inhibitors↗
PubMed2002

Current therapy for multiple myeloma.

Multiple myeloma is an incurable plasma cell malignancy that accounts for 10% of all hematologic cancers. For decades the mainstay of therapy has been the use of melphalan and prednisone; with this regimen, the median survival is approximately 3 years. Recently, important advances were made that have substantially altered the manner in which patients with myeloma are treated. Newly diagnosed patients with good performance status are now treated with autologous stem cell transplantation, resulting in improved survival. Because of the increasing use of transplantation as initial therapy, several therapeutic issues have emerged: the role of tandem transplantation, early vs delayed transplantation, and the role of allogeneic transplantation. The pronounced activity of thalidomide in patients with refractory myeloma represents another important advance. This has prompted the study of several novel agents in the treatment of myeloma, at least 2 of which appear promising. Supportive care measures also have improved, including the use of bisphosphonates to prevent osteolytic lesions. The purpose of this review is to summarize recent advances and provide an evidence-based approach to the treatment of multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis.

PURPOSE: To determine whether bone marrow (BM) angiogenesis progressively increases along the spectrum of plasma cell disorders ranging from monoclonal gammopathy of undetermined significance (MGUS) to advanced myeloma. EXPERIMENTAL DESIGN: Four hundred patients with the following disorders were studied: MGUS (76 patients); smoldering (indolent; early-stage) multiple myeloma (SMM; 112 patients); newly diagnosed, active multiple myeloma (MM; 99 patients); relapsed (advanced) multiple myeloma (RMM; 26 patients); and primary amyloidosis (AL; 87 patients). Forty-two normal control BM samples were studied for comparison. BM angiogenesis was studied in a blinded manner by immunohistochemical staining for CD34 to identify microvessels. RESULTS: The median (range) microvessel density (MVD) per x400 high power field was 1.3 (0-11) in the controls, 1.7 (0-10) in AL, 3 (0-23) in MGUS, 4 (1-30) in SMM, 11 (1-48) in newly diagnosed MM, and 20 (6-47) in RMM; P < 0.001. MVD was significantly higher in MGUS, SMM, newly diagnosed MM, and RMM compared with controls and AL; P < 0.001. MVD was not significantly different between controls and AL. By grading, high-grade angiogenesis was present in 0% of controls and AL, 1% of MGUS, 3% of SMM, 29% of newly diagnosed MM, and 42% of RMM; P < 0.001. MVD correlated with the BM plasma cell labeling index (rho = 0.46, P < 0.001) and BM plasma cell percentage (rho 0.5, P < 0.001). Survival was 28 months in SMM and newly diagnosed MM with high-grade angiogenesis, compared with 53 months for those with low- and intermediate-grade angiogenesis; P = 0.02. CONCLUSIONS: BM angiogenesis progressively increases along the spectrum of plasma cell disorders, from the more benign MGUS stage to advanced myeloma, indicating that angiogenesis may be related to disease progression.

Amyloidosis↗
PubMed2002

Promising preclinical activity of 2-methoxyestradiol in multiple myeloma.

PURPOSE: 2-Methoxyestradiol (2ME2), a natural endogenous product of estradiol metabolism, has demonstrated activity against tumor cell lines and can inhibit angiogenesis. There are limited treatment options for patients with multiple myeloma (MM) who relapse after high-dose therapy and stem cell transplantation. We studied the preclinical activity of 2ME2 as a therapeutic agent for myeloma. EXPERIMENTAL DESIGN: Five established myeloma cell lines as well as primary plasma cells from patients with MM were exposed to 2ME2 at various concentrations. We evaluated the activity of the drug to inhibit cell replication and induction of apoptosis in vitro as well as the ability of the drug to inhibit myeloma tumor xenograft growth in severe combined immunodeficient mice. RESULTS: 2ME2 inhibited tritiated thymidine uptake in all myeloma cell lines tested in a dose-dependent fashion and induced G(2)-M phase cell cycle arrest. The drug induced apoptosis in all cell lines tested and in half of the primary plasma cells evaluated in a dose-response manner. Forty-eight h after drug exposure, a large proportion of the cells were dead by propidium iodide staining. Injection of the drug i.p. suppressed myeloma tumor xenograft growth, and the effect was sustained after cessation of therapy. CONCLUSIONS: 2ME2 has significant activity against myeloma cell lines and primary myeloma cells both in vitro and in an animal model. Clinical trials are required to evaluate its activity in patients with MM.

2-Methoxyestradiol↗
PubMedDate not supplied

Influence of postoperative acute-phase response on angiogenesis and tumor growth: open vs. laparoscopic-assisted surgery in mice.

Inflammatory responses and tumor growth are increased after laparotomy compared with laparoscopy in some animal models. Proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) upregulate the expression of vascular endothelial growth factor (VEGF). Our aim was to investigate the influence of postoperative inflammatory responses on angiogenesis and tumor growth. 5 x 10(6) B51LiM cells were injected into the cecal wall of Balb/c mice. After 2 weeks, the animals were randomized into the following three groups: open cecectomy (OC), CO(2)-laparoscopic-assisted cecectomy (LC), and helium-laparoscopic-assisted cecectomy (LH). On postoperative day 12, the mice were killed. Tumor load scores and weight were significantly greater after laparotomy than after laparoscopy. Serum IL-6 levels 6 hours after surgery (OC: 4157+/-1297 pg/ml vs. LC: 2514+/-1417 pg/ml vs. LH: 2255+/-1714 pg/ml) and VEGF levels on postoperative day 12 (OC: 231+/-125 pg/ml vs. LC: 45+/-9 pg/ml vs. LH: 49+/-8 pg/ml), measured by enzyme-linked immunosorbent assay, were significantly higher in the laparotomy group. Microvessel density was also significantly higher in the OC group (OC: 34.3+/-11.5 vs. LC: 15.5+/-12.5 vs. LH: 18.5+/-11.9). There was a positive correlation between IL-6 and VEGF postoperative serum levels (rho=0.67; P<0.001). We concluded that increased systemic levels of proinflammatory cytokines and VEGF are associated with increased angiogenesis and tumor growth after laparotomy compared to laparoscopy in mice.

Acute-Phase Reaction↗
PubMedDate not supplied

Management of thalidomide toxicity.

Thalidomide has re-emerged as a novel antineoplastic agent with immunomodulatory and antiangiogenic activities. In the early sixties, it was withdrawn from the market after its infamous association with congenital abnormalities that left about 10,000 children affected world-wide. With strict regulations and precautions, thalidomide is now approved by the FDA for the treatment of erythema nodosum leprosum. Its role in cancer therapy is promising, with clinical trials in the past 5 years showing significant activity in multiple myeloma. Several trials are ongoing in other malignancies, such as myelodysplastic syndrome, agnogenic myeloid metaplasia, renal cell carcinoma, and prostate cancer. The major toxicities of thalidomide are birth defects, sensorimotor peripheral neuropathy, somnolence, rash, fatigue, and constipation. Less common side effects include deep venous thrombosis, Stevens-Johnson syndrome, elevated liver enzymes, malaise, and peripheral edema. The incidence and severity of adverse events are related to dose and duration of therapy. Doses of the drug of 200 mg/day or less are usually well tolerated. In this review, we will discuss the incidence and management of the side effects of thalidomide and the precautions and interventions needed to minimize the toxicities of this drug.

Clinical Trials as Topic↗