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What's New In Research - November 1, 2003
Effects of all-trans retinoic acid (ATRA) on human myeloma cells are presented.
Copyright 2003 Cancer Vaccine Week via NewsRx.com

According to a study from Japan, "All-trans retinoic acid (ATRA) is a natural oxidative metabolite of vitamin A (retinol) and is known to be a regulator of cell proliferation differentiation, especially in various malignant cells.

"The cyto-differentiating action of ATRA has led to its usage in the treatment of several malignancies, particularly acute promyelocytic leukemia (APL)," wrote T. Otsuki and colleagues, Kawasaki Medical University, Department of Hygiene.

"There have been many reports regarding the cell biological effects of ATRA on human myeloma cells and a few clinical trials," the researchers wrote.

The researchers concluded: "Most of these reports have revealed growth inhibition by ATRA mediated by down-regulation of the IL-6/IL-6R auto/paracrine loop, and upregulation of p21/Cip1. Here, we review previous reports and introduce experimental results obtained using various myeloma cell lines established in our laboratory."

Otsuki and colleagues published their study in Leukemia & Lymphoma (Effects of all-trans retinoic acid (ATRA) on human myeloma cells. Leuk Lymphoma, 2003;44(10):1651-1656).

For more information, contact T. Otsuki, Kawasaki Medical University, Department of Hygiene, 577 Matsushima, Okayama 7010192, Japan.

Idiopathic inflammatory neuropathies are different diseases that may benefit from plasma exchange or intravenous immunoglobulin therapy.
(c) Copyright 2003, Biotech Week via NewsRx.com

According to published research from the United States, "Evaluation of peripheral neuropathy is a common reason for referral to a neurologist. Recent advances in immunology have identified an inflammatory component in many neuropathies and have led to treatment trials using agents that attenuate this response.

"This article reviews the clinical presentation and treatment of the most common subacute inflammatory neuropathies, Guillain-Barre syndrome (GBS) and Fisher syndrome, and describes the lack of response to corticosteroids and the efficacy of treatment with plasma exchange and intravenous immunoglobulin (IVIG). Chronic inflammatory demyelinating polyneuropathy, although sharing some clinical, electrodiagnostic, and pathologic similarities to GBS, improves after treatment with plasma exchange and IVIG and numerous immunomodulatory agents," wrote P.D. Donofrio and colleagues.

The researchers concluded: "Controlled trials in multifocal motor neuropathy have shown benefit after treatment with IVIG and cyclophosphamide. Also discussed is the treatment of less common inflammatory neuropathies whose pathophysiology involves monoclonal proteins or antibodies directed against myelin-associated glycoprotein or sulfatide. Little treatment data exist to direct the clinician to proper management of rare inflammatory neuropathies resulting from osteo-sclerotic myeloma; POEMS syndrome; vasculitis; Sjogren syndrome; and neoplasia (paraneoplastic neuropathy)."

Donofrio and coauthors published their findings in Muscle & Nerve (Immunotherapy of idiopathic inflammatory neuropathies. Muscle Nerve, 2003;28(3):273-292).

Additional information can be obtained by contacting P.D. Donofrio, Wake Forest University, Bowman Gray School of Medicine, Dept Neurology, Med Center Blvd., Winston Salem, NC 27157, USA.

Immunogene vaccine improves outcome after combination therapy for myeloma
(c) Copyright 2003, Drug Week via NewsRx.com

According to a study from Canada, "Increasing evidence suggests a role for immunologic vaccination and therapy in the management of minimal residual myeloma. We have previously demonstrated a synergistic effect of combining the Th1 stimulating cytokine IL-12 with the co-stimulatory molecule CD80 in murine myeloma vaccination therapy."

"We reasoned that the efficacy of such treatment might be further improved by incorporating additional gene products which enhance the function of antigen presenting cells," said Zhi Hua Li and colleagues at Princess Margaret Hospital in Toronto. "Studies were therefore conducted with murine myeloma BM1 cells expressing Flt3L (membrane bound or soluble forms) or GM-CSF and the IL-12.CD80 combination. Single agent and combined therapeutic approaches were explored."

"All gene-modified BM1 cells, except BM1/IL-12.CD80, developed tumors when subcutaneously injected into BALB/c mice," reported the researchers. "As prophylactic tumor vaccines, the combined use of gene-modified BM1/sFlt3L+GM-CSF+IL-12.CD80 was most effective, providing 100% protection against subsequent parental BM1 tumor challenge. By comparison, only partial protection was observed with any single gene-engineered tumor vaccine. Notably, IL-12.CD80 co-expressing BM1 cell vaccines were the most effective therapeutic vaccine in a minimal disease model. Such protective vaccination was achieved by stimulation of lymphocyte proliferation and enhancement of cytotoxic lymphocyte activity."

Li and associates published their study in Leukemia and Lymphoma (Improved therapeutic outcome following combination immunogene vaccination therapy in murine myeloma. Leuk Lymphoma, 2003;44(10):1775-1784).

For more information, contact A. Keith Stewart, Princess Margaret Hospital, McLaughlin Center for Molecular Medicine, 5th Floor, Room 126, 610 University Avenue, Toronto, ON M5G 2M9, Canada. E-mail: kstewart@uhnres.utoronto.ca.

Tl-201 chloride scintigraphy may be superior in diagnosing multiple myeloma.
(c) Copyright 2003 Medical Devices & Surgical Technology Week via NewsRx.com

"The objectives of this study were to investigate the role of whole-body Tl-201-chloride scintigraphy in comparison with bone scintigraphy in the detection of bone marrow involvement in patients with multiple myeloma and to assess the follow-up evaluation using Tl-201-chloride," scientists writing in the journal Nuclear Medicine Communications report.

"Twenty-one patients with untreated multiple myeloma were evaluated. Tl-201-chloride images were acquired 10 min (early) and 2 h (delayed) after the injection of Ill MBq Tl-201-chloride," wrote Y. Nishiyama and colleagues, Kagawa Medical University, Medical Faculty.

"Bone images were acquired 3 h after the intravenous injection of 740 MBq Tc-99m-hydroxymethylene diphosphonate (HMDP). The Tl-201-chloride scan patterns were classified as normal, diffuse (presence of bone marrow), focal (localized areas of uptake) and diffuse + focal," the researchers wrote.

"The bone scan patterns were classified as normal and abnormal. Eight of the 21 patients also underwent Tl-201-chloride scintigraphy after chemotherapy for the evaluation of the therapeutic response. On the early Tl-201-chloride image, two patients showed a normal, 13 a diffuse, two a focal, and four a diffuse + focal pattern," the researchers wrote.

"On the delayed Tl-201-chloride image, nine patients showed a normal, six a diffuse, four a focal, and two a diffuse + focal pattern. Bone scintigraphy showed an abnormal accumulation in only 5 of the 21 patients," the researchers stated.

"Of the eight patients who underwent follow-up Tl-201-chloride studies, the abnormal diffuse pattern was changed to a normal pattern on post-treatment scintigraphy in three, and the degree of abnormal Tl-201-chloride accumulation decreased in comparison with the pretreatment scan in three," the researchers wrote.

"These six patients were considered to be in clinical remission. In the two remaining patients, the degree of abnormal Tl-201-chloride accumulation increased in comparison with the pretreatment scan, and they were considered to be in clinical progression," they added.

The researchers concluded: "Tl-201-chloride scintigraphy is a noninvasive tool, which may be more useful than bone scintigraphy for the diagnosis of multiple myeloma, and may be helpful in the follow-up of multiple myeloma."

Nishiyama and colleagues published their study in Nuclear Medicine Communications (Comparative whole-body Tl-201 and bone scintigraphies for the detection of bone marrow involvement in multiple myeloma. Nucl Med Commun, 2003;24(9):977-986).

Additional information can be obtained by contacting Y. Nishiyama, Kagawa Medical University, Medical Faculty Department of Radiology, 1750-1 Ikenobe, Miki, Kagawa 7610793, Japan.

Newly discovered pathogenetic mechanism of anemia in MM is based on persistent erythroblast cytotoxicity within the bone marrow.
© Copyright 2003 Cancer Vaccine Week via NewsRx.com

According to recent research published in the International Journal of Hematology, "Anemia is a prominent feature of multiple myeloma (MM) and is commonly associated with clinical progression of MM.

"In addition to being affected by a number of pathogenetic events, including imbalance of the cytokine network, inappropriate erythropoietin (EPO) levels, blood loss, and hemolysis, the erythroid matrix is chronically deteriorated by the malignant plasma cell clone that activates a cytotoxic mechanism directed at the erythroid progenitors," wrote F. Silvestris and colleagues, University of Bari.

"In particular, malignant plasma cells express very high levels of apoptogenic receptors, including both Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand, which trigger apoptosis of immature erythroblasts by stimulating specific death receptors, namely Fas and the complex DR4/DR5," the researchers stated.

"Erythroid cells also weakly express the transcription factor GATA-1, which drives erythroblast maturation by inhibiting apoptosis through antiapoptotic molecules such as EPO and Bcl-x(L) This newly discovered pathogenetic mechanism of anemia in MM is based on persistent erythroblast cytotoxicity within the bone marrow that leads to progressive destruction of the erythroid matrix," the researchers concluded.

Silvestris and colleagues published their study in the International Journal of Hematology (Recent advances in understanding the pathogenesis of anemia in multiple myeloma. Int J Hematol, 2003;78(2):121-125).

For additional information, contact F. Silvestris, University of Bari, DIMO, Section of Internal Medicine & Clinical Oncology, Department of Biomedical Science & Human Oncology, Piazza G Cesare 11, I-70124 Bari, Italy.

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