The Effect of Topical Administration of an Ointment Prepared From Trifolium repens Hydroethanolic Extract on the Acceleration of Excisional Cutaneous Wound Healing

2020 ◽  
pp. 253-261
Keyword(s):  
Antioxidant Activity ◽  
Wound Healing ◽  
Mast Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Topical Administration ◽  
Control Group ◽  
Cell Distribution ◽  
Carbohydrate Storage ◽  
Hydroethanolic Extract

Introduction: Natural agents with antioxidant and anti-inflammatory properties are safer than synthetic agents and may improve wound healing. Objective: The purpose of this study is to evaluate the in vivo wound healing potential of an ointment prepared from Trifolium repens hydroethanolic extract (T repens) concerning excisional wounds in a rat model. Materials and methods: Seventy-two adult Wistar rats were divided into 4 groups: a control group and 3 groups of animals treated with 1.5% T repens, 3% T repens, and 6% T repens. A full-thickness wound with an area of 314 mm2 was created in each rat. To investigate the effect of T repens on wound healing, the wound area, histological analyses (eg, angiogenesis, fibroblast, fibrocyte, mast-cell distribution), intracytoplasmic carbohydrate storage, and B-cell lymphoma 2-like protein 4 (BAX), B-cell lymphoma 2 (Bcl-2), and p53 gene expression in the wound tissue were evaluated for 21 days. Antioxidant activity was further measured by 2,20-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-Di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) assays. Results: The animals in the treated groups showed higher wound contraction ratios (P ⟨ .05), angiogenesis, fibroblast, fibrocyte, and mast-cell distribution and intracytoplasmic carbohydrate storage compared with the control group (P ⟨ .05). Moreover, the topical administration of T repens increased the messenger ribonucleic acid (mRNA) level of Bcl-2 and reduced the BAX and p53 mRNA levels (P ⟨ .05). These findings further revealed the strong antioxidant activity of T repens. Conclusions: The topical administration of T repens accelerated wound healing by increasing angiogenesis; fibroblast, fibrocyte, and mast-cell distribution; intracytoplasmic carbohydrate storage; and modulation in genes involved in apoptosis in a rat model.

scholarly journals PROGNOSTIC VALUE OF RED CELL DISTRIBUTION WIDTH AT DIAGNOSIS (RDW) IN DIFFUSE LARGE B‐CELL LYMPHOMA

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
J.M. Raya ◽  
P. López‐García ◽  
C. D. Reyes ◽  
M.J. Rodríguez‐Salazar ◽  
C. De Bonis ◽  
...  
Keyword(s):  
B Cell ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Red Cell Distribution Width ◽  
Red Cell ◽  
Cell Distribution ◽  
Distribution Width ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Association between Drug-Metabolizing Enzymes Polymorphisms and Diffuse Large B-Cell Lymphoma Risk in the Middle Eastern Population.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2043-2043
Author(s):  
Abdul K. Siraj ◽  
Rong Bu ◽  
Maha Al-Rasheed ◽  
Muna Ibrahim ◽  
Prashant Bavi ◽  
...  
Keyword(s):  
B Cell ◽  
Gene Polymorphisms ◽  
Cell Lymphoma ◽  
Middle Eastern ◽  
B Cell Lymphoma ◽  
Control Group ◽  
Healthy Population ◽  
Environmental Carcinogens ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract The last four decades have seen significant increase in the incidence of non-Hodgkin’s lymphoma (NHL) as a possible result of increasing environmental carcinogens exposure. Based on the increasing evidence for the association between carcinogens exposure related cancer risk and xenobiotic gene polymorphisms. We have undertaken a case control study on xenobiotic gene polymorphisms in Saudi individuals with a diagnosis of diffuse large B-cell lymphoma (DLBCL). Polymorphisms in five genes (CYP1A1, GSTT1, GSTP1, GSTM1 and NQO1) were characterized in 187 individuals with DLBCL and 513 normal controls using polymerase chain reaction (PCR) based method. We chose the Saudi population as our study population because of its high consanguinity and its relative genetic homogeneity. The CYP1A1*2C, GSTT1 null and GSTP1 TT genotype were all found to be significant predictors of DLBCL risk (odds ratio 6.62, 11.94 and 3.42 respectively). None of the other alleles tested for proved to be significant indicators of DLBCL risk. These results suggest that the risk of DLBCL may indeed be associated with xenobiotics - metabolism and thus with environmental exposures. Table 1 Distribution of polymorphisms in healthy population and lymphoma patients. Polymorphism Genotype Control group Lymphoma patients p OR CYP1A1 −/− 384(76.5%) 104(78.8%) *2A −/2A 105(20.9%) 24(18.18%) 0.543 0.844 2A/2A 13(2.6%) 3(2.27%) 1.000 0.852 2A allele 13% 11.36% 0.659 0.839 CYP1A1 −/− 443(88.2%) 121(91.66%) *2B −/2B 50(10%) 10(7.58%) 0.505 0.732 2B/2B 9(1.8%) 1(0.76%) 0.697 0.407 2B allele 6.8% 4.55% 0.424 0.646 CYP1A1 −/− 497(99%) 125(94.7%) *2C −/2C 5(1%) 4(3.03%) 0.090 3.181 2C/2C 0 3(2.27%) 0.008 ND 2C allele 0.5% 3.8% 0.011 6.627 NQO1 C609T CC 295 (58.5%) 94 (62.7%) CT 177 (35.1%) 37 (24.7%) 0.051 0.656 TT 32 (6.4%) 19 (8.7%) 0.059 1.863 CT+TT 209 (41.5%) 56 (37.3%) 0.395 0.841 GSTP1 2293 CC 389 (76.3%) 113 (77.9%) CT 113 (22.2%) 24 (16.6%) 0.240 0.731 TT 8 (1.5%) 8 (5.5%) 0.017 3.422 CT+TT 121 (23.7%) 32 (22%) 0.739 0.910 GSTP1 A1578G AA 170 (33.5%) 56 (35%) AG 271 (53.5%) 96 (60%) 0.772 1.075 GG 66 (13%) 8 (5%) 0.013 0.368 AG+GG 337 (66.5%) 104 (65%) 0.774 0.937 GSTT1 P 385 (75%) 36 (20.1%) D 128 (25%) 143 (79.9%) <0.001 11.948 GSTM1 P 233 (45.4%) 91 (50%) D 280 (54.6%) 91 (50%) 0.300 0.832 Table 2 Distribution of combined GSTT1 and GSTM1 polymorphisms in case and control group. Genotype Control Case p OR Null: Complete deletion of GSTT1 and GSTM1 allele Present 423 (82.8%) 109 (60.9%) Double Null 88 (17.2%) 70 (39.1%) <0.001 3.087

SNS01-T Exhibits Significant Anti-Tumoral Activity In Models Of Multiple Myeloma and Non-Hodgkins B Cell Lymphoma and Induces Cell Death In Malignant But Not Normal B Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 880-880
Author(s):  
Catherine A Taylor ◽  
Terence Tang ◽  
Sarah Francis ◽  
Zhongda Liu ◽  
Qifa Zheng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Tumor Volume ◽  
Cell Lymphoma ◽  
Xenograft Model ◽  
B Cell Lymphoma ◽  
Control Group ◽  
Rpmi 8226

Abstract SNS01-T is a novel nanoparticle that is designed to selectively initiate apoptosis in B-cell cancers such as multiple myeloma and non-Hodgkins B-cell lymphomas. SNS01-T comprises a plasmid DNA (pExp5A) encoding a pro-apoptotic form of the eukaryotic translation initiation factor 5A (eIF5A) containing a single-point mutation that prevents hypusination, an eIF5A siRNA that inhibits expression of the pro-survival hypusine-eIF5A protein, and a polymer that serves to assemble the nucleic acids into a nanoparticle. SNS01-T is currently being investigated in a multi-site, open-label Phase1b/2a dose escalation study in subjects with relapsed or refractory multiple myeloma (MM), mantle cell lymphoma (MCL), or diffuse large B cell lymphoma (DLBCL). SNS01-T has demonstrated activity in MM xenograft models as well as in B cell lymphoma models of MCL and DLBCL, when administered twice weekly at doses ≥ 0.18 mg(nucleic acid)/kg. In this study we compared the ability of SNS01-T to transfect, regulate eIF5A expression, and kill MM, DLBCL, and MCL cell lines. Furthermore, the activity of SNS01-T in normal B cells was investigated. A previous study using a KAS-6/1 MM xenograft model demonstrated that the eIF5A siRNA and plasmid pExp5A both have anti-tumoral activity in MM but had a greater impact on tumour growth when combined together as SNS01-T. This finding was confirmed in this study in a second MM model (RPMI 8226) as well as in a DLBCL xenograft model. To determine the efficiency of SNS01-T transfection into malignant or normal B cells, the pExp5A plasmid and eIF5A siRNA were labeled with FITC and DY547, respectively, packaged into nanoparticles using polyethylenimine polymer, and used to transfect cultured cells. FACS analysis was used to determine the percent of the cell population transfected with plasmid, siRNA, or both. RT-qPCR was used to assess biological activity of SNS01-T by quantifying the expression of eIF5AK50R mRNA transgene and endogenous eIF5A mRNA in a variety of B cell lines. The IC50 of SNS01-T in a panel of MM, MCL, and DLBCL cell lines was determined by XTT assay. SCID mice bearing either RPMI 8226 MM tumours or SuDHL6 GCB DLBCL tumours were treated with pExp5A plasmid (formulated with PEI and control siRNA), eIF5A siRNA (formulated with PEI and a control plasmid), or SNS01-T at 0.375 mg/kg twice per week by intravenous injection. SNS01-T was able to transfect MM, MCL, and DLBCL cell lines, although the proportion of cells transfected with both plasmid and siRNA was higher in MM cells. Transfection of SNS01-T resulted in expression of the transgene as well as a statistically significant reduction in expression of eIF5A mRNA compared to untreated controls for all three cell types. In contrast, normal B cells were found to take up fluorescently-labeled SNS01-T with reduced efficiency compared to RPMI 8226 MM cells. Futhermore, SNS01-T was observed to induce cell death in RPMI 8226 MM cells but not in normal B cells. In the RPMI 8226 xenograft model, treatment with either the pExp5A plasmid alone or eIF5A siRNA alone resulted in a 66 % reduction (p < 0.0001) or 44 % reduction (p < 0.05) in tumor volume compared to the control group at day 24 of the study. In contrast, treatment with SNS01-T, which contains both the pExp5A plasmid and the eIF5A siRNA, resulted in an 86 % (p < 0.0001) reduction in tumor volume. A similar result was observed in the SuDHL6 model with a 14 % reduction or 27 % reduction (p < 0.05) in tumor volume compared to the control group at day 20 of the study following treatment with pExp5A plasmid or eIF5A siRNA, respectively. In contrast, treatment with SNS01-T resulted in a 79 % (p < 0.0001) reduction in tumor volume. Collectively, these preclinical studies indicate that SNS01-T therapy has significant potential against MM, MCL, and DLBCL. Disclosures: Taylor: Senesco Technologies: stock options Other. Dondero:Senesco Technologies: Employment. Thompson:Senesco Technologies: Consultancy, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

scholarly journals A Systematical Review of The Effect of Ketogenic Diet on Bcl-2 (B-cell lymphoma-2) Expression as An Apoptosis Marker in Cancer Treatment

2021 ◽  
Vol 4 (2) ◽  
pp. 130
Author(s):  
Vania Islamey Kusuma ◽  
Reny I’tishom ◽  
Ema Qurnianingsih ◽  
Purwo Sri Rejeki
Keyword(s):  
B Cell ◽  
Ketogenic Diet ◽  
Cancer Progression ◽  
Protein Level ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Total Sample ◽  
Control Group ◽  
P Value ◽  
High Fat

Introduction: Ketogenic diet seems to be in a great demand nowadays as a lot of people are interested in adopting it into their lifestyle. It is also found that the ketogenic diet shows several beneficial effects including cancer prevention. However, the detail mechanism still remains unknown. Therefore, this review was aimed to find out the effect of ketogenic diet on Bcl-2 (B-cell lymphoma-2) expression in cancer.Methods: We searched published literatures in PubMed through 2011-2020 using specific keywords. The literatures were filtered according to inclusion and exclusion criteria. Animal model, total sample size, underlying condition/inflammatory process occurs, details of the intervention/diet including diet contents in control group and high-fat group, and the duration of the intervention, Bcl-2 results, and p-value were extracted.Results: 7 studies were included in this review. Bcl-2 expression found decrease in 5 out of 6 studies. Similar result also obtained in Bcl-2 protein level, which measured by western blot. Bcl-2 protein level shows a decrease in 2 out of 3 studies.Conclusion: This review shows that high-fat diet that contained in ketogenic diet most likely lead to decrease in Bcl-2 expression. Therefore, indicating the ability of ketogenic diet to affect cancer progression by inducing apoptosis process.

scholarly journals Insulin-like Growth Factor-1 Receptor (IGF-1R) As a Potential Therapeutic Target in Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4828-4828
Author(s):  
Xiangxiang Zhou ◽  
Lingyun Geng ◽  
Xinyu Li ◽  
Peipei Li ◽  
Kang Lu ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
Annexin V ◽  
B Cell Lymphoma ◽  
Control Group ◽  
Protein Levels ◽  
Proliferation And Apoptosis ◽  
Dose Dependent Decrease

Abstract Introduction : The receptor tyrosine kinase (RTK) insulin-like growth factor-1 receptor (IGF1R) is dysregulated in various tumor entities and hematological malignancies including chronic lymphocytic leukemia and mantle cell lymphoma. The implication of IGF1R in the development and progression of cancer has led to its current evaluation in clinical trials as a potential therapeutic target for solid tumors. However, its functional significance in diffuse large B-cell lymphoma (DLBCL) remains poorly characterized. We hypothesized that IGF1R plays a key role in the pathogenesis and progression of DLBCL. In this present study, we evaluated the expression and function of IGF1R in both B cell lines and DLBCL tissues, as well as assessed the proliferation and apoptosis of DLBCL cells when treated with IGF-1R inhibitor, AG1024. Methods : Expression of IGF1R in B-cell lymphoma cell lines (LY1, LY8, Mino, Jeko-1, and SP53) was evaluated by Western blotting. Peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers with informed consents. Blood samples and araffin-embedded tissues from 30 initial-diagnosed DLBCL patients prior to therapeutic interventions as a study group, and from 15 patients with reactive hyperplasia lymphnode as a control group were collected with informed consents. Immunohistochemisty (IHC) was conducted to assess the expression of IGF-1R in lymphoma tissues. Correlations between IGF1R expression and the clinical characteristics of DLBCL patients were further analyzed. DLBCL cell lines (LY1 and LY8) were treated with an IGF1R specific small molecular inhibitor, AG1024, cell proliferation was analyzed by cell counting kit (CCK-8). Effects of inhibitor or stimulator on the apoptosis of LY1 and LY8 cells were assessed by Annexin-V/PI and Annexin-V/7AAD, respectively. Expression of apoptosis-related protein, including Caspase-3 and Mcl-1, was evaluated by western blotting. Protein levels of downstream targets of IGF-1 signaling were also detected. Results : Significantly upregulation of both phoaphprylated and total IGF1R protein levels were found in B-cell lymphoma cells (LY1, LY8, Mino, Jeko-1 and SP53) (Fig 1.A). IHC was conducted and revealed significantly enhancement of IGF1R expression in DLBCL patients (Fig 1.B). Among the included DLBCL patients and control group with inreactive hyperplastic lymphadenitis, the positive rate of IGF1R was 90% and 20%, respectively. We then investigated the function of IGF1R inhibitors on the proliferation and apoptosis of DLBCL cells. LY8 cells were treated with different doses of AG1024 at 24-96 hours. Cell proliferation was inhibited by 60% when treated with AG1024 at the concentration of 15µM for 72-hours (Fig 1.C). Culture of LY1 and LY8 cells in the presence of 10µM and 15µM AG1024 concentration for 24-hours resulted in 13% (p<0.05) and 33% (p<0.001) cell apoptosis, respectively (Fig 1.D). Inhibition of IGF1R by AG1024 also resulted in induction of cleaved-Caspase-3, as well as reduction of Mcl-1(Fig 1.E-F). In order to investigate the mechanisms involved in the dysregultaion of IGF1R in DLBCL, LY8 cells were treated with 5 to 15 µM AG1024, the results revealed that AG1024 caused a dose-dependent decrease in the levels of phosphorylated IGF1R, AKT and ERK (Fig 1.G). Treatment of LY8 cells with recombinant human IGF-1 led to enhanced phosporylation levels of IGF1R, AKT and ERK (Fig 1.H). Conclusion s: Our investigation observed that expression levels of IGF-1R were up-regulated in both B-cell lymphoma cells and DLBCL tissues. DLBCL cells treated with IGF-1R inhibitor, AG1024, revealed reduced proliferation and increased apoptosis rate. In addition, induction of cleaved-Caspase-3 was also found in LY1 treated with AG1024. AG1024 caused a dose-dependent decrease in the phosphorylation levels of IGF1R, AKT and ERK. This study suggests that IGF1R could be a potential molecular target for the treatment of DLBCL. The IGF-1R inhibitor is a promising therapeutic approach for DLBCL. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic significance of the red blood cell distribution width in diffuse large B-cell lymphoma patients

Oncotarget ◽  
2017 ◽  
Vol 8 (25) ◽  
pp. 40724-40731 ◽  
Author(s):  
Shujuan Zhou ◽  
Fang Fang ◽  
Huiyao Chen ◽  
Wei Zhang ◽  
Yang Chen ◽  
...  
Keyword(s):  
Blood Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Cell Distribution ◽  
Distribution Width ◽  
Large B Cell Lymphoma ◽  
Red Blood Cell Distribution ◽  
Large B Cell

scholarly journals Red blood cell distribution width and platelet counts are independent prognostic factors and improve the predictive ability of IPI score in diffuse large B-cell lymphoma patients

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Manman Li ◽  
Hailong Xia ◽  
Huimin Zheng ◽  
Yafeng Li ◽  
Jun Liu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Cell Lymphoma ◽  
Predictive Ability ◽  
B Cell Lymphoma ◽  
Cell Distribution ◽  
Distribution Width ◽  
Large B Cell Lymphoma ◽  
Kaplan Meier ◽  
Red Blood Cell Distribution ◽  
Large B Cell

Abstract Background Elevated red blood cell distribution width (RDW) and decreased platelet count (PLT) can be clinically relevant to the prognosis in cancer patients. However, their prognostic values in patients with diffuse large B-cell lymphoma (DLBCL) need to be further explored. Methods Healthy donors (n = 130) and patients with DLBCL (n = 349) were included and evaluated retrospectively in this study. The prognostic influence of clinical and pathological factors including RDW and PLT on overall survival (OS) and progression-free survival (PFS) were studied by Kaplan-Meier curves. To evaluate the independent prognostic relevance of RDW and PLT, univariate and multivariate Cox proportional hazards regression models were applied. The adjusted IPI model was established based on the results of multivariate analysis, and verified by Harrell’s C statistical analysis. Results Kaplan-Meier curves indicated that an elevated RDW value and thrombocytopenia are poor factors for OS (P < 0.001, P = 0.006) and PFS (P = 0.003, P < 0.001) in DLBCL patients. Multivariate analysis confirmed that elevated RDW value (HR = 2.026, 95%CI = 1.263–3.250, P = 0.003) and decreased PLT count (HR =1.749, 95%CI = 1.010–3.028, P = 0.046) were both independent prognostic factors. The c-index of IPI and NCCN-IPI were increased when RDW level and PLT were supplemented in our cohort. Conclusions Our study shows that elevated RDW level and decreased PLT are independent poor prognostic factors in newly diagnosed DLBCL patients. Adding RDW and PLT to the IPI score may improve its predictive ability, and the adjusted IPI may be more powerful in predicting the survival of DLBCL patients in the rituximab era.

The Effect of Different Extracts of Beetroots as Antioxidant and Anti-Anaemia On Phenylhydrazine-Induced Rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ni Putu Ermi Hikmawanti ◽  
Lusi Putri Dwita ◽  
Dimas W. Wisnunanda ◽  
Fanny Farista
Keyword(s):  
Antioxidant Activity ◽  
Normal Control ◽  
Antioxidant Activities ◽  
Negative Control Group ◽  
Negative Control ◽  
Pharmaceutical Product ◽  
Normal Control Group ◽  
Male Rats ◽  
Control Group ◽  
Hydroethanolic Extract

Abstract Aim evaluate antioxidant and anti-anaemia activity of dichloromethane, hydroethanolic, and alkaloids-free hydroethanolic extracts of beetroot (Beta vulgaris (L.) subsp. vulgaris) on phenylhydrazine-induced rats. Methods Male rats were divided into five groups: normal control group, negative control group, dichloromethane extract group, hydroethanolic extract group, and alkaloids-free hydroethanolic extract group. All groups were induced with phenylhydrazine (30 mg.Kg−1 BW) for three days, except for the normal control group. After induction, each treatment group received each extract (200 mg.Kg−1 BW) for 21 days. The haematology parameters (haemoglobin levels, the number of erythrocytes, and haematocrit levels) were measured using Haematology Analyzer, and the antioxidant activity was measured through MDA level parameters in rats. Data were analysed using one-way ANOVA and then continued with the Tukey test. Results The results showed that the hydroethanolic extract of beetroot increased the percentage of erythrocytes (33.5%), haemoglobin (25%), and haematocrit (24.4%) to the negative control group, which was comparable to the normal control group (p > 0.05). In addition, the best antioxidant activity was shown in the hydroethanolic extract of beetroot, which is comparable to the normal group (p > 0.05). Conclusion The beetroot hydroethanolic crude extract could be potentially produced in a natural pharmaceutical product as a beneficial resource within anti-anaemia and antioxidant activities.

Does Rituximab Influence the Prognostic Effect of Germinal Centre Phenotype in Diffuse Large B-Cell Lymphoma?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2743-2743 ◽  
Author(s):  
Heidi Nyman ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Minna Taskinen ◽  
Mattias Berglund ◽  
Magdalena Adde ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Positive Impact ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Germinal Centre ◽  
Control Group ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract PURPOSE: Germinal centre (GC) and non-GC phenotypes are predictors of outcome in diffuse large B-cell lymphoma (DLBCL), and can be used to stratify chemotherapy-treated patients into low- and high-risk groups. Our aim was to determine how combination of rituximab with chemotherapy influences GC-associated clinical outcome. METHODS: 95 DLBCL patients treated with rituximab in combination with CHOP or CHOEP regimen (immunochemotherapy) were included in the study. The median follow-up time was 27 months. 107 patients previously treated with chemotherapy served as a historical control group. BCL-6, CD10, and MUM1 expression was analyzed immunohistochemically by means of identifying GC and non-GC phenotypes. In addition, BCL-2 expression was determined. Expression data was correlated with survival parameters. RESULTS: Consistent with previous studies, chemotherapy-treated patients with GC phenotype displayed a significantly better overall survival (OS) than the non-GC group (70% vs 47% p=0.012). In contrast, GC-phenotype did not predict outcome in immunochemotherapy-treated patients. The OS for GC-group was 82% compared with 80% for those with non-GC phenotype (p=ns). Conversely, the relapse free survival (RFS) for patients with GC and non-GC phenotypes were 74% and 65% (p=ns), respectively. When the patients were grouped according to BCL-2 expression, survival rates among the group of BCL-2 negative patients tended to be better than in BCL-2 positive patients (OS, 94% vs 77%, p=0.097; RFS, 94% vs 66%, p=0.029). CONCLUSIONS: Rituximab in combination with chemotherapy seems to interfere with the prognostic value of GC- and non-GC phenotypes in DLBCL. However, rituximab may have a positive impact on outcome among the patients with BCL-2 negativity.

Identification of Circulating Autoantibodies in Patients with Lymphoma Using Antigen Arrays.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2397-2397
Author(s):  
Karen Pulford ◽  
Hong Chen ◽  
Kamel Ait-Tahar ◽  
Amanda P. Liggins ◽  
Christopher D.O. Cooper ◽  
...  
Keyword(s):  
Germinal Center ◽  
Cell Lymphoma ◽  
Correct Diagnosis ◽  
B Cell Lymphoma ◽  
Autoimmune Response ◽  
Control Group ◽  
Serum Samples ◽  
Igg Antibody ◽  
Alk Positive ◽  
Circulating Autoantibodies

Abstract Over thirty types of lymphoma are now recognized and correct diagnosis is therefore essential. We have developed a novel approach, using arrays containing thousands of recombinant proteins (Bussow K, Cahill D, Nietfeld W et al. Nucleic Acids Res 1998 26:5007–8; Gutjahr C, Murphy D, Lueking A et al. Genomics 2005 85:285–96), to identify new potential disease markers in a number of different lymphomas. Specifically, by screening patient serum samples against human protein/antigen arrays containing over 10,000 different human proteins we are able to identify disease-associated auto-IgG antibody interactions (Horn S, Lueking A, Murphy D et al. Proteomics 2006 6:605–13). Our approach exploits the autoimmune response which has been observed in many cancer types. For example, patients with anaplastic large cell lymphoma (ALCL) produce circulating autoantibodies against the aberrantly expressed ALK tyrosine kinase (Pulford K, Falini B, Banham A et al. Blood 2000 96:1605–7; Ait-Tahar K, Hatton CSR, Banham A et al. Int J Cancer 2006 118:688–95). Also, patients suffering from follicular lymphoma (FL) have been shown to produce antibodies reactive with BCL-2 (Pulford K, Roberton H, Banham A et al. Br J Haematol 2002 116:135–41). In this study we are screening serum samples from patients with ALK-positive ALCL, ALK-negative ALCL, germinal center and non-germinal center subtypes of diffuse large B cell lymphoma (DLBCL), transformed DLBCL, peripheral T-cell lymphoma, mantle cell lymphoma and FL. Initially, a pool of 5 patient samples from each lymphoma type and a sex- and age-matched control group are screened against the antigen arrays. These experiments yield lists of putative disease-associated autoantigens. Screening larger numbers of individual serum samples from lymphoma patients and control cohorts against these autoantigens will enable an estimate of the frequency and disease specificity associated with circulating antibodies against each of the autoantigens identified. An initial study of 5 patients with ALK-positive ALCL, 5 patients with ALK-positive ALCL and 5 age- and sex-matched controls revealed the identification of 140 putative ALK-positive ALCL-associated autoantigens, 125 putative ALK-negative ALCL-associated autoantigens, and 27 autoantigens common to both ALK-positive and ALK-negative ALCL. We are currently ranking these results through individual screens of ALCL patient samples. We will also present the results obtained from the other 6 lymphoma types being screened, identifying autoantigens which show a disease-specific pattern, as well as those that are common to one or more of these lymphoma types. The approach described here should contribute not only towards the discovery of novel lymphoma markers, the discovery of potentially novel proteins involved in the development of the disease but also to the identification of therapeutic targets.

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