Comprehensive Investigation of White Blood Cell and Gene Expression Profiles As Risk Factors for Multiple Myeloma in African Americans
Linda KachuriZhaohui DuNiels WeinholdGregory SongKristin Alyse RandDavid Van Den BergAmie E. HwangXin ShengVictor HomSikander AilawadhiAjay K. NookaSeema SinghalEdward PetersCathryn H. BockAnn MohrbacherAlexander StramSonja I. BerndtWilliam J. BlotEsther M. JohnLeslie BernsteinAntoinette M. StroupMaurizio ZangariFrits van RheeAndrew F. OlshanWei ZhengSue A. InglesMichael F. PressJohn D. CarptenStephen J. ChanockJayesh MehtaGraham A. ColditzJeffrey WolfThomas G. MartinMark A. FialaHoward R. TerebeloNalini JanakiramanLaurence KolonelKenneth C. AndersonLoı̈c Le MarchandDaniel AuclairBrian C.‐H. ChiuDaniel O. StramRavi VijLeon Bernal‐MizrachiGareth J. MorganJeffrey A. ZonderCarol Ann HuffSagar LonialRobert Z. OrlowskiDavid V. ContiChristopher A. HaimanElad ZivJohn S. WitteWendy Cozen
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[Objective] To investigate the levels of macrophage inflammatory protein (MIP)-1alpha in the marrow plasma of the patients with multiple myeloma and the clinic significance. [Methods] MIP -1α was quantified using ELISA assay in 43 multiple myeloma, 15 controls, and 37 post therapy of three course. [Results] ⑴About 65.1% patients with multiple myeloma had increased levels of MIP -1α. A significantly larger proportion of multiple myeloma patients had increased levels of MIP-1α compared to the control (t=3.569,P=0 0.01), a significantly larger proportion of multiple myeloma patients with active disease had increased levels of MIP-1α compared to normal controls, other hematological diseases controls and patients with multiple myeloma with inactive disease(P 0.05). A significantly larger proportion of multiple myeloma patients with more than 2 sites bone destruction had increased levels of MIP-1α compared to the less 2 sites bone destruction (t=5.56,P =0).(2)The levels of MIP -1α in responded patients with multiple myeloma after 3 course of treatment was much higher than those in unresponded patients(t =3.237,P=0 0.05).⑶MIP -1α levels significantly correlated with red blood cell, albumin, β2-microglobulin, the presence of bone lesions and Durie-Salmon stages(P 0.05). [Conclusion] ⑴Most of patients with multiple myeloma had increased levels of MIP -1α in marrow plasma. The levels of MIP-1α can indicate bone disease and myeloma burden. The levels of MIP-1α quantified regularly can forecast curative efficiency.
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Objective To study the clinical characteristics of multiple myeloma with double clones and analyze its related laboratory diagnostic and therapeutic methods.Methods A case of multiple myeloma with double clones of IgG-κ and IgG-λ was reported and its related literature was reviewed.Results The myeloma protein ingredients were different between multiple myeloma with double clones and typical multiple myeloma.Immune fixation electrophoresis was of diagnostic value for multiple myeloma with double clones.The treatment outcome was usually a decreased or disappeared myeloma protein ingredient.The prognosis of patients was rather good.Conclusion Multiple myeloma with double clones is a rare plasma cell disorder,which is different from typical multiple myeloma in clinical manifestations,diagnosis,treatment and prognosis,and should thus be differentially diagnosed from typical multiple myeloma.
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Evolutionary rates provide important information about the pattern and mechanism of evolution. Although the rate of gene sequence evolution has been well studied, the rate of gene expression evolution is poorly understood. In particular, it is unclear whether the gene expression level and tissue specificity influence the divergence of expression profiles between orthologous genes. Here we address this question using a microarray data set comprising the expression signals of 10,607 pairs of orthologous human and mouse genes from over 60 tissues per species. We show that the level of gene expression and the degree of tissue specificity are generally conserved between the human and mouse orthologs. The rate of gene expression profile change during evolution is negatively correlated with the level of gene expression, measured by either the average or the highest level among all tissues examined. This is analogous to the observation that the rate of gene (or protein) sequence evolution is negatively correlated with the gene expression level. The impacts of the degree of tissue specificity on the evolutionary rate of gene sequence and that of expression profile, however, are opposite. Highly tissue-specific genes tend to evolve rapidly at the gene sequence level but slowly at the expression profile level. Thus, different forces and selective constraints must underlie the evolution of gene sequence and that of gene expression.
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To study the genes differentially expressed in the liver of Kkay diabetic and normal mice by genomic-scale gene expression analysis.cDNA microarray chips containing 8,192 cDNAs were used to explore the gene expression pattern of Kkay mouse liver.One hundred and fifty-four genes were screened out, including 68 complete cDNAs and expressed sequence tags, and among them 40 genes were up-regulated and 114 genes were down-regulated respectively.Most of the gene expression analysis results were consistent with previous study, and the gene expression pattern of Kkay mouse based on cDNA microarray could be used for high-throughout screening out the genes associated with type 2 diabetes.
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Objective To analyze the differential gene expression profiling of liver in rats subjected to hemorrhagic shock(HS) and sham hemorrhage shock(SHAM) by gene chip technology, thus to evaluate the possible molecular pathogenesis of HS. Method 20 male Wistar rats were randomly divided into a SHAM group and a HS group, with 10 rats in each group. Hepatic gene expression profiles were detected by oligonucleotide microarrays of 5705 mouse genes in two groups for three times. Genes with ratio(R) > 2 were identified as up-regulated and R < 0.5 were identified as down-regulated. Biological function of differentially expressed genes was analyzed and 9 genes were selected to undergo semi-quantitative RT-PCR. Results Among the total 5705 probes detected,86 genes showed differential expression in HS group comparison with SHAM group. The expression levels of 72 genes were up-regulated while those of 14 genes were down-regulated significantly. Differentially expressed genes were classified according to their biological function: transport genes, transcription regulator genes, signaling genes, response to stress genes, metabolic genes, development genes and cell adhesion genes. Conclusions cDNA microarray is an efficient and high-throughout method to survey gene expression profiles in HS.The variation of those gene expressions might be a potential pathogenic mechanism for HS that may offer a novel target for further study of therapeutic strategies of HS.
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Multiple myeloma (MM) is the leading cause of death among hematologic neoplasms. Recently, microRNA has been reported to be useful in the diagnosis of multiple myeloma. This study examined whether miR-221 could be used as a diagnostic marker for multiple myeloma. The study was performed on 20 patients with multiple myeloma without any other hematological diseases. MicroRNA extraction was performed using formalin-fixed paraffin-embedded (FFPE) tissues obtained from the bone marrow of patients with multiple myeloma. miR-15a, miR-16, miR-21, miR-181a, and miR-221 were selected as the microRNA target genes for multiple myeloma. The significance of microRNA was based on a fold change of <1.5. to="" quantify="" the="" fold="" changes="" data="" normalized="" to="" the="" human="" gene="" italic="">SNORD43, were used as the values of the patient group. Fold change values greater than 1.5 were defined as “overexpression”, whereas values less than -1.5 were defined as “underexpression”. Of note, 65.0% (13/20) of samples showed significant “overexpression” in the levels of miR-221 expression and plasma cells with a group of more and less than 30% in MM patients did not show any significance of plasma cell (P<0.05). The results of other studies showing a correlation between the expression of miR-221 and MM in Caucasians were confirmed. These results suggest that miR-221 may be a useful indicator for diagnosing patients with MM. In conclusion, miR-221 is useful in the diagnosis and determining the prognosis of multiple myeloma in Koreans.
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High dosage melfalan chemotherapy with subsequent autologous blood stem cell transplantation in suitably selected patients with multiple myeloma greatly increases the probability that complete remission will be achieved and it prolongs the mean survival period as compared with classical chemotherapy. Till recently patients with multiple myeloma and renal insufficiency were not included in transplantation programmes. Only recently several papers were published abroad which indicate the possibility to implement transplantations also in these patients. The authors describe the treatment, incl. the first autologous transplantation of blood stem cells in a patient with multiple myeloma and renal insufficiency.
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