1: Folia Haematol Int Mag Klin Morphol Blutforsch 1986;113(6):766-75 Plasma transcobalamins in haematological disorders. Ghosh K, Mohanty D, Rana KS, Hassan SW, Garewal G, Das KC. Plasma UBBC-B12 and transcobalamins were measured in 112 patients suffering from different haematological disorders. The data showed different patterns of changes in plasma transcobalamin profile in different haematological disorders. Plasma UBBC-B12 and transcobalamins were significantly higher than normal in untreated chronic myeloid leukaemia, acute promyelocytic leukaemia, nutritional megaloblastic anaemia and in refractory anaemias with hypercellular marrow. Normal levels of these proteins were noted in chronic lymphatic leukaemias, in primary and secondary hypereosinophilic states and in multiple myeloma. Subnormal levels of these proteins were observed in hypoplastic anaemia and acute lymphoblastic leukaemia. Chronic myeloid leukaemia patients during blast crisis and acute myeloid leukaemia patients except those suffering from acute promyelocytic leukaemia showed varying pattern of plasma transcobalamins depending on type of blast crisis or FAB subtype of AML. The significance of these changes in plasma transcobalamins have been discussed along with the experience of other workers in this field. PMID: 2436989 [PubMed - indexed for MEDLINE] 1: Eur J Gastroenterol Hepatol 1999 Feb;11(2):205-7 Multiple myeloma involving the stomach with vitamin B12 deficiency. Doberauer C, Sanner B, Henning B. Department I of Internal Medicine, Ruhr-University Bochum, Marienhospital, Herne, Germany. Involvement of the gastrointestinal tract by plasmocytoma is rare. In a 78-year-old man with IgA lambda multiple myeloma stage IIIB, the evaluation of a megaloblastic anaemia revealed a subnormal vitamin B12 level. Urinary excretion of isotope-labelled vitamin B12 was reduced. Tests for gastric parietal cell and intrinsic factor antibodies were negative. There were no clinical signs of an insufficient absorption in the ileum. Biopsy specimens of the stomach showed a dense, diffuse infiltrate of malignant plasma cells in the lamina propria of fundus and corpus. A urease test for Helicobacter pylori was positive. There was a minor haematological improvement when vitamin B12 was given parenterally. Several combinations of cytostatic drugs had no effect on the manifestations of the multiple myeloma. In our patient the vitamin B12 deficiency may be related to a displacement or destruction of parietal cells by malignant plasma cells. PMID: 10102234 [PubMed - indexed for MEDLINE] 1: Exp Cell Res 2000 Feb 1;254(2):279-86 Cell cycle arrest induced by the vitamin D(3) analog EB1089 in NCI-H929 myeloma cells is associated with induction of the cyclin-dependent kinase inhibitor p27. Park WH, Seol JG, Kim ES, Jung CW, Lee CC, Binderup L, Koeffler HP, Kim BK, Lee YY. Cancer Research Center and Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-799, Korea. EB1089, a 1,25-dihydroxyvitamin D(3) analog, has been known to have potent antiproliferative properties in a variety of malignant cells in vitro and in vivo. In the present study, we analyzed the effect of EB1089 on human myeloma cell lines. EB1089 inhibited the proliferation of NCI-H929 cells and RPMI8226 cells in a dose-dependent manner among three myeloma cell lines tested. The antiproliferative effect of EB1089 on myeloma cells was related to the expression level of vitamin D receptor. To investigate the mechanism of the antiproliferative effect of EB1089, cell cycle analysis was attempted in EB1089-sensitive NCI-H929 cells. EB1089 (1 x 10(-8) M) efficiently induced G(1) arrest of the cell cycle. Analysis of G(1) regulatory proteins demonstrated that protein levels of CDK2, CDK4, cyclin D1, and cyclin A were decreased in a time-dependent manner, but not those of CDK6 and cyclin E, by EB1089. In addition, EB1089 (1 x 10(-8) M, 72 h) increased the protein level of the CDKI p27 and markedly enhanced the binding of p27 with CDK2 compared to EB1089-untreated cells. Furthermore, the activity of CDK2-associated cyclin kinase was decreased, which was accompanied by the reduction of cyclin-D1-, cyclin-E-, and cyclin-A-associated kinase activities, resulting in the hypophosphorylation of Rb protein. These results suggest that EB1089 can inhibit the proliferation of human myeloma cells, especially NCI-H929 cells, via a G(1) block in association with the induction of p27 and the reduction of CDK2 activity. Copyright 2000 Academic Press. PMID: 10640426 [PubMed - indexed for MEDLINE] 1: Eur J Epidemiol 1997 Oct;13(7):853-4 Vitamin E serum levels in patients with leukemia, lymphoma and myeloma. Marco N, Gimferrer E, Mestres J, Ubeda J, Martino R, Altes A, Royo MT. Ferropathology and Radicalosis Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. The serum alpha-tocopherol levels were determined in a group of 182 patients with hematological neoplasms: 87 lymphoid or myeloid leukemias, 65 lymphomas and 30 myelomas. The levels did not differ from those of controls, when compared either globally or for diagnosis. Low alpha-tocopherol serum levels were observed in 6 patients (3.3%). PMID: 9384278 [PubMed - indexed for MEDLINE] 1: Leuk Res 1998 Mar;22(3):287 Rapid evolution of multiple myeloma after cobalamin therapy for megaloblastic erythropoiesis with macrocytic anemia. Schleinitz N, Costello R, Veit V, Swiader L, Harle JR, Bouabdallah R, Sainty D, Gastaut JA, Weiller PJ. Publication Types: Letter PMID: 9619920 [PubMed - indexed for MEDLINE] 1: Tidsskr Nor Laegeforen 1999 Nov 30;119(29):4321-2 [Myelomatosis and low level of vitamin B12] [Article in Norwegian] Heyerdahl F, Kildahl-Andersen O. Medisinsk avdeling Harstad sykehus. Many patients with multiple myeloma tend to have low serum cobalamin. The cause of this remains unclear. The important issue is whether cobalamin therapy should be used or not. We describe one case of megaloblastic erythropoiesis and multiple myeloma, and refer to some of the few studies describing the subject. Most of the patients with multiple myeloma are elderly, and the frequency of hypo- and achlorhydria is therefore increased. It has been demonstrated that cobalamin uptake and consumption is higher in myeloma cells than in normal bone marrow cells, and that cobalamin may be required for paraprotein synthesis. These facts may suggest that patients with multiple myeloma are more vulnerable to developing megaloblastic anemia than others. Our patient received cobalamin therapy in addition to cytostatic therapy for multiple myeloma without complications. However, we cannot exclude that cobalamin therapy may accelerate multiple myeloma; this should be considered when such therapy is given. However, accurate guidelines require more studies. PMID: 10667130 [PubMed - indexed for MEDLINE] 315399">   Free Full-text Articles Chapter 6, Smallpox and Vaccinia by Donald A. Henderson and Bernard Moss from the book Vaccines 3rd ed (Stanley A. Plotkin and Walter A. Orenstein, eds) can now be browsed and searched in the Bookshelf.  Q 1: Blood 2001 Aug 1;98(3):805-13 Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells. Grad JM, Bahlis NJ, Reis I, Oshiro MM, Dalton WS, Boise LH. Department of Microbiology and Immunology, Division of Hematology and Oncology, Sylvester Cancer Center, University of Miami School of Medicine, Miami, FL 33101, USA. Multiple myeloma (MM) is a clonal B-cell malignancy characterized by slow-growing plasma cells in the bone marrow (BM). Patients with MM typically respond to initial chemotherapies; however, essentially all progress to a chemoresistant state. Factors that contribute to the chemorefractory phenotype include modulation of free radical scavenging, increased expression of drug efflux pumps, and changes in gene expression that allow escape from apoptotic signaling. Recent data indicate that arsenic trioxide (As(2)O(3)) induces remission of refractory acute promyelocytic leukemia and apoptosis of cell lines overexpressing Bcl-2 family members; therefore, it was hypothesized that chemorefractory MM cells would be sensitive to As(2)O(3). As(2)O(3) induced apoptosis in 4 human MM cell lines: 8226/S, 8226/Dox40, U266, and U266/Bcl-x(L). The addition of interleukin-6 had no effect on cell death. Glutathione (GSH) has been implicated as an inhibitor of As(2)O(3)-induced cell death either through conjugating As(2)O(3) or by sequestering reactive oxygen induced by As(2)O(3). Consistent with this possibility, increasing GSH levels with N-acetylcysteine attenuated As(2)O(3) cytotoxicity. Decreases in GSH have been associated with ascorbic acid (AA) metabolism. Clinically relevant doses of AA decreased GSH levels and potentiated As(2)O(3)-mediated cell death of all 4 MM cell lines. Similar results were obtained in freshly isolated human MM cells. In contrast, normal BM cells displayed little sensitivity to As(2)O(3) alone or in combination with AA. Together, these data suggest that As(2)O(3) and AA may be effective antineoplastic agents in refractory MM and that AA might be a useful adjuvant in GSH-sensitive therapies. (Blood. 2001;98:805-813) PMID: 11468182 [PubMed - indexed for MEDLINE]