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372 results on '"Walker, Ba"'

2. B-cell malignancies: capture-sequencing strategies for identification of gene rearrangements and translocations into immunoglobulin gene loci

Author

Boyle EM, Walker BA, Wardell CP, Leleu X, Davies FE, and Morgan GJ

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Eileen M Boyle,1,2 Brian A Walker,1 Christopher P Wardell,1 Xavier Leleu,2 Faith E Davies,1 Gareth J Morgan1 1Centre for Myeloma Research, Institute of Cancer Research, Sutton, Surrey, UK; 2Service des Maladies du Sang, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France Abstract: Aberrant chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus and clonal rearrangements of the variable (V), diversity (D), joining (J) segments (V[D]J) of the immunoglobulin gene are implicated in the initiation of mature B-cell malignancies, including myeloma. Analysis of these events provides information useful for diagnosis and prediction of prognosis, and also provides a useful monitoring strategy for response to treatment in patients with these diseases. Current methods for identification of these events are not generally applicable and give a biased picture of the prognostic significance and clinical relevance of these events. Novel methodologies based on next-generation sequencing are a new and more efficient genetic tool that can be used to screen and characterize these changes at the nucleotide level, offering a deeper and better understanding of the genetic basis of these complex diseases. In this work, we provide a review of the molecular basis of B-cell neoplasms, the methods used to detect them, and how they translate into the clinic. Keywords: B-cell malignancies, minimal residual disease, molecular, IGH locus, next-generation sequencing

Published
2014

3. BRAF and DIS3 Mutations Associate with Adverse Outcome in a Long-term Follow-up of Patients with Multiple Myeloma

Author

Boyle, EM, Ashby, C, Tytarenko, R, Deshpande, S, Wang, Y, Sawyer, J, Tian, E, Johnson, S, Rutherford, MW, Wardell, CP, Bauer, MA, Thanendrarajan, S, Schinke, C, Zangari, M, van Rhee, F, Wang, H, Rosenthal, A, Hoering, A, Flynt, E, Thakurta, A, Dumontet, C, Facon, T, Cairns, DA, Jackson, GH, Barlogie, B, Davies, FE, Morgan, GJ, and Walker, BA

Subjects
neoplasms
Abstract

Purpose: Copy number changes and translocations have been studied extensively in many datasets with long term follow-up. The impact of mutations remains debated given the short time to follow-up of most datasets. Methods: we performed targeted panel sequencing covering 125 myeloma-specific genes and the loci involved in translocations in 223 newly diagnosed myeloma samples recruited into one of the Total Therapy Trials (TT). Results: As expected, the most commonly mutated genes were NRAS, KRAS, and BRAF making up 44% of patients. Double-Hit, BRAF and DIS3 mutations had an impact on outcome alongside classical risk factors in the context of an intensive treatment approach. We were able to identify both V600E and non-V600E BRAF mutations, 58% of which were predicted to be hypoactive or kinase dead. Interestingly, 44% of the hypoactive/kinase dead BRAF mutated patients showed co-occurring alterations in KRAS, NRAS or activating BRAF mutations suggesting they play a role in the oncogenesis of multiple myeloma (MM) by facilitating MAPK activation and may lead to chemo resistance. Conclusion: Overall, these data highlight the importance of mutational screening to better understand newly diagnosed MM (NDMM) and may lead to patient specific mutation-driven treatment approaches.

Published
2020

4. 'HIV Is Still Real': Perceptions of HIV Testing and HIV Prevention Among Black Men Who Have Sex With Men in New York City

Author

José Nanín EdD, CHES, Tokes Osubu MA, Ja'Nina Walker BA, Borris Powell MHS(c), Donald Powell CASAC-T, and Jeffrey Parsons PhD

Subjects
Medicine
Abstract

Rising HIV infection rates have been recently occurring among Black men who have sex with men (BMSM) in the United States. As a result, promoting HIV testing among members of this population is now considered a priority among local and federal health officials. A study was conducted to explore concerns about HIV testing among BMSM in New York City. In early 2006, data were gathered from focus groups with 29 BMSM. Discussions revealed factors affecting HIV testing, including stigma, sexuality, religion, race, and class, emphasizing responsibility, testing concerns, and media influences, among others. Recommendations were submitted to New York City health officials to inform HIV testing and prevention efforts.

Published
2009
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7. Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Author

Went, M, Sud, A, Försti, A, Halvarsson, BM, Weinhold, N, Kimber, S, van Duin, M, Thorleifsson, G, Holroyd, A, Johnson, DC, Li, N, Orlando, G, Law, PJ, Ali, M, Chen, B, Mitchell, JS, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Bandapalli, OR, Einsele, H, Gregory, WA, Gullberg, U, Hillengass, J, Hoffmann, P, Jackson, GH, Jöckel, KH, Johnsson, E, Kristinsson, SY, Mellqvist, UH, Nahi, H, Easton, D, Pharoah, P, Dunning, A, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, ZS, Muir, K, Pashayan, N, Nickel, J, Nöthen, MM, Rafnar, T, Ross, FM, da Silva Filho, MI, Thomsen, H, Turesson, I, Vangsted, A, Andersen, NF, Waage, A, Walker, BA, Wihlborg, AK, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Goldschmidt, H, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Hemminki, K, Nilsson, B, Houlston, RS, Henderson, BE, Haiman, CA, Benlloch, S, Schumacher, FR, Olama, AAA, Berndt, SI, Conti, DV, Wiklund, F, Chanock, S, Stevens, VL, Tangen, CM, The PRACTICAL Consortium, and Claessens, Frank

Subjects
Male, Quality Control, Risk, Chromatin Immunoprecipitation, Genotype, European Continental Ancestry Group, Quantitative Trait Loci, Bayes Theorem, Polymorphism, Single Nucleotide, Chromatin, Gene Expression Regulation, Humans, Female, Genetic Predisposition to Disease, Multiple Myeloma, Promoter Regions, Genetic, Genome-Wide Association Study
Abstract

© 2018, The Author(s). Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM. ispartof: Nature Communications vol:9 issue:1 ispartof: location:England status: published

Published
2018

8. Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes

Author

Went, M., Kinnersley, B., Sud, A., Johnson, D.C. (David), Weinhold, N, Försti, A. (Asta), Duin, M. (Mark) van, Orlando, G., Mitchell, JS, de Kuiper, R., Walker, BA, Gregory, WM, Hoffmann, P. (Per), Jackson, G. (Graham), Nöthen, M.M. (Markus), da Silva, MI, Thomsen, H, Broyl, A. (Annemiek), Davies, F.E., Thorsteinsdottir, U. (Unnur), Hansson, M, Kaiser, M, Sonneveld, P. (Pieter), Goldschmidt, H. (Hartmut), Zwart, J-A. (John-Anker), Hemminki, K. (Kari), Nilsson, B, Morgan, G.J., Houlston, R. (Richard), Went, M., Kinnersley, B., Sud, A., Johnson, D.C. (David), Weinhold, N, Försti, A. (Asta), Duin, M. (Mark) van, Orlando, G., Mitchell, JS, de Kuiper, R., Walker, BA, Gregory, WM, Hoffmann, P. (Per), Jackson, G. (Graham), Nöthen, M.M. (Markus), da Silva, MI, Thomsen, H, Broyl, A. (Annemiek), Davies, F.E., Thorsteinsdottir, U. (Unnur), Hansson, M, Kaiser, M, Sonneveld, P. (Pieter), Goldschmidt, H. (Hartmut), Zwart, J-A. (John-Anker), Hemminki, K. (Kari), Nilsson, B, Morgan, G.J., and Houlston, R. (Richard)

Abstract

Background: While genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS). Results: GWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80–491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus. Conclusions: Our findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.

Published
2019
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9. Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma (vol 9, 3707, 2018)

Author

Went, M, Sud, A, Foersti, A, Halvarsson, B-M, Weinhold, N, Kimber, S, van Duin, M, Thorleifsson, G, Holroyd, A, Johnson, DC, Li, N, Orlando, G, Law, PJ, Ali, M, Chen, B, Mitchell, JS, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Bandapalli, OR, Einsele, H, Gregory, WA, Gullberg, U, Hillengass, J, Hoffmann, P, Jackson, GH, Joeckel, K-H, Johnsson, E, Kristinsson, SY, Mellqvist, U-H, Nahi, H, Easton, D, Pharoah, P, Dunning, A, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, Z, Muir, K, Pashayan, N, Henderson, BE, Haiman, CA, Benlloch, S, Schumacher, FR, Al Olama, AA, Berndt, SI, Conti, DV, Wiklund, F, Chanock, S, Stevens, VL, Tangen, CM, Batra, J, Clements, J, Gronberg, H, Schleutker, J, Albanes, D, Weinstein, S, Wolk, A, West, C, Mucci, L, Cancel-Tassin, G, Koutros, S, Sorensen, KD, Grindedal, EM, Neal, DE, Hamdy, FC, Donovan, JL, Travis, RC, Hamilton, RJ, Ingles, SA, Rosenstein, B, Lu, Y-J, Giles, GG, Kibel, AS, Vega, A, Kogevinas, M, Penney, KL, Park, JY, Stanford, JL, Cybulski, C, Nordestgaard, BG, Brenner, H, Maier, C, Kim, J, John, EM, Teixeira, MR, Neuhausen, SL, De Ruyck, K, Razack, A, Newcomb, LF, Lessel, D, Kaneva, R, Usmani, N, Claessens, F, Townsend, PA, Gago-Dominguez, M, Roobol, MJ, Menegaux, F, Khaw, K-T, Cannon-Albright, L, Pandha, H, Thibodeau, SN, Nickel, J, Noethen, MM, Rafnar, T, Ross, FM, Filho, MIDS, Thomsen, H, Turesson, I, Vangsted, A, Andersen, NF, Waage, A, Walker, BA, Wihlborg, A-K, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Goldschmidt, H, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Hemminki, K, Nilsson, B, Houlston, RS, Went, M, Sud, A, Foersti, A, Halvarsson, B-M, Weinhold, N, Kimber, S, van Duin, M, Thorleifsson, G, Holroyd, A, Johnson, DC, Li, N, Orlando, G, Law, PJ, Ali, M, Chen, B, Mitchell, JS, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Bandapalli, OR, Einsele, H, Gregory, WA, Gullberg, U, Hillengass, J, Hoffmann, P, Jackson, GH, Joeckel, K-H, Johnsson, E, Kristinsson, SY, Mellqvist, U-H, Nahi, H, Easton, D, Pharoah, P, Dunning, A, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, Z, Muir, K, Pashayan, N, Henderson, BE, Haiman, CA, Benlloch, S, Schumacher, FR, Al Olama, AA, Berndt, SI, Conti, DV, Wiklund, F, Chanock, S, Stevens, VL, Tangen, CM, Batra, J, Clements, J, Gronberg, H, Schleutker, J, Albanes, D, Weinstein, S, Wolk, A, West, C, Mucci, L, Cancel-Tassin, G, Koutros, S, Sorensen, KD, Grindedal, EM, Neal, DE, Hamdy, FC, Donovan, JL, Travis, RC, Hamilton, RJ, Ingles, SA, Rosenstein, B, Lu, Y-J, Giles, GG, Kibel, AS, Vega, A, Kogevinas, M, Penney, KL, Park, JY, Stanford, JL, Cybulski, C, Nordestgaard, BG, Brenner, H, Maier, C, Kim, J, John, EM, Teixeira, MR, Neuhausen, SL, De Ruyck, K, Razack, A, Newcomb, LF, Lessel, D, Kaneva, R, Usmani, N, Claessens, F, Townsend, PA, Gago-Dominguez, M, Roobol, MJ, Menegaux, F, Khaw, K-T, Cannon-Albright, L, Pandha, H, Thibodeau, SN, Nickel, J, Noethen, MM, Rafnar, T, Ross, FM, Filho, MIDS, Thomsen, H, Turesson, I, Vangsted, A, Andersen, NF, Waage, A, Walker, BA, Wihlborg, A-K, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Goldschmidt, H, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Hemminki, K, Nilsson, B, and Houlston, RS

Abstract

The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.

Published
2019

10. Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes

Author

Went, M, Kinnersley, B, Sud, A, Johnson, DC, Weinhold, N, Forsti, A, van Duin, Mark, Orlando, G, Mitchell, JS, Kuiper, Ronella, Walker, BA, Gregory, WM, Hoffmann, P, Jackson, GH, Nothen, MM, da Silva, MI, Thomsen, H, Broijl, A., Davies, FE, Thorsteinsdottir, U, Hansson, M, Kaiser, M, Sonneveld, Pieter, Goldschmidt, H, Stefansson, K, Hemminki, K, Nilsson, B, Morgan, GJ, Houlston, RS, Went, M, Kinnersley, B, Sud, A, Johnson, DC, Weinhold, N, Forsti, A, van Duin, Mark, Orlando, G, Mitchell, JS, Kuiper, Ronella, Walker, BA, Gregory, WM, Hoffmann, P, Jackson, GH, Nothen, MM, da Silva, MI, Thomsen, H, Broijl, A., Davies, FE, Thorsteinsdottir, U, Hansson, M, Kaiser, M, Sonneveld, Pieter, Goldschmidt, H, Stefansson, K, Hemminki, K, Nilsson, B, Morgan, GJ, and Houlston, RS

Published
2019

11. Neutral tumor evolution in myeloma is associated with poor prognosis

Author

Johnson, DC, Lenive, O, Mitchell, J, Jackson, G, Owen, R, Drayson, M, Cook, G, Jones, JR, Pawlyn, C, Davies, FE, Walker, BA, Wardell, C, Gregory, WM, Cairns, D, Morgan, GJ, Houlston, RS, and Kaiser, MF

Abstract

Recent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics of multiple myeloma (MM) and its possible influence on patient outcome we analysed whole exome sequencing tumor data for 333 patients from Myeloma XI, a UK phase III trial and 434 patients from the CoMMpass study, all of which had received immunomodulatory therapy (IMiD). By analysing mutant allele frequency distributions in tumors we found that 17-20% of MM is under neutral evolutionary dynamics. These tumors are associated with poorer patient survival in non-intensively treated patients, consistent with reduced therapeutic efficacy of micro-environment modulating IMiD drugs. Our findings provide evidence that knowledge of the evolutionary history of MM has relevance for predicting patient outcome and personalising therapy.

Published
2017

12. Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1,905 trial patients

Author

Shah, V, Sherborne, AL, Walker, BA, Johnson, DC, Boyle, EM, Ellis, S, Begum, DB, Proszek, PZ, Jones, JR, Pawlyn, C, Savola, S, Jenner, MW, Drayson, MT, Owen, RG, Houlston, RS, Cairns, DA, Gregory, WM, Cook, G, Davies, F, Jackson, GH, Morgan, GJ, and Kaiser, MF

Abstract

Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1.60 (P=4.77 × 10−7), 1.74 (P=0.0005), 1.90 (P=0.0089), 2.10 (P=8.86 × 10−14) and 1.68 (P=2.18 × 10−14), respectively. Patients with ‘double-hit’ defined by co-occurrence of at least two adverse lesions have an especially poor prognosis with HRs for OS of 2.67 (P=8.13 × 10−27) for all patients and 3.19 (P=1.23 × 10−18) for intensively treated patients. Using comprehensive CNA and translocation profiling in Myeloma XI we also demonstrate a strong association between t(4;14) and BIRC2/BIRC3 deletion (P=8.7 × 10−15), including homozygous deletion. Finally, we define distinct sub-groups of hyperdiploid MM, with either gain(1q21) and CCND2 overexpression (P

Published
2017

13. The varied distribution and impact of RAS codon and other key DNA alterations across the translocation cyclin D subgroups in multiple myeloma

Author

Stein, CK, Pawlyn, C, Chavan, S, Rasche, L, Weinhold, N, Corken, A, Buros, A, Sonneveld, Pieter, Jackson, GH, Landgren, O, Mughal, T, He, J, Barlogie, B, Bergsagel, PL, Davies, FE, Walker, BA, Morgan, GJ, Stein, CK, Pawlyn, C, Chavan, S, Rasche, L, Weinhold, N, Corken, A, Buros, A, Sonneveld, Pieter, Jackson, GH, Landgren, O, Mughal, T, He, J, Barlogie, B, Bergsagel, PL, Davies, FE, Walker, BA, and Morgan, GJ

Published
2017

14. Cancer-selective targeting of the NF-kappa B survival pathway with GADD45 beta/MKK7 inhibitors (vol 26, pg 495, 2014)

Author

Tornatore, L, Sandomenico, A, Raimondo, D, Low, C, Rocci, A, Tralau-Stewart, C, Capece, D, D'Andrea, D, Bua, M, Boyle, E, Van Duin, M, Zoppoli, P, Jaxa-Chamiec, A, Thotakura, AK, Dyson, J, Walker, BA, Leonardi, A, Chambery, A, Driessen, C, Sonneveld, P, Morgan, G, Palumbo, A, Tramontano, A, Rahemtulla, A, Ruvo, M, Franzoso, G, Medical Research Council (MRC), and Cancer Research UK

Subjects
Science & Technology, Oncology, 1112 Oncology and Carcinogenesis, Cell Biology, Oncology & Carcinogenesis, 1109 Neurosciences, Life Sciences & Biomedicine
Published
2014

15. Sex and Magazine Promotion

Author

Tom Reichert and Kristin McRee Walker Ba

Subjects
ComputingMilieux_GENERAL, Marketing, Promotion (rank), ComputingMilieux_THECOMPUTINGPROFESSION, media_common.quotation_subject, ComputingMilieux_COMPUTERSANDSOCIETY, Advertising, Psychology, media_common
Abstract

This study tested the efficacy of sexual content on consumer responses to a magazine offer. The 2 ¥ 2 between-subjects design consisted of female and male respondents viewing a subscription card containing a sexual image of either a female or male model. As expected, respondents reported more favorable attitudes about the magazine, more interest in the magazine, and more purchase intention to the promotion card featuring an opposite-sex model. The results support the general notion that “sex sells,” and, more specifically, that sexual content can sell consumer magazine subscriptions.

Published
2005

17. A linkage study of the Marfan syndrome1

Author

Wilma B. Bias, Gary A. Chase, Walker Ba, Victor A. McKusick, Freidhoff Lb, D A Schleutermann, and J L Murdoch

Subjects
Linkage (software), Marfan syndrome, Genetics, business.industry, medicine, medicine.disease, business, Genetics (clinical)
Published
2008

19. The Geriatric Oncology Patient

Author

Licsw Elizabeth A. Rohan Msw, Sonya Walker Ba, William Holmes, and Barbara Berkman Dsw

Subjects
medicine.medical_specialty, Nursing (miscellaneous), Adult patients, Social work, business.industry, Geriatric oncology, Older patients, Treatment modality, Family medicine, Health care, medicine, Oncology patients, business, Social Sciences (miscellaneous)
Abstract

Elderly oncology patients are at risk of being treated inequitably by health care providers due to ageist attitudes and prac- tices. This study explores whether ageism exists in oncology social work by comparing practice with 305 adult patients under 65 years old to 197 patients 65 and older. The patients received services in three outpatient oncology treatment centers between June 1, 1990 and May 3 1,1991. Study focused on social work practice comparing problems addressed, treatment modalities utilized and intensity of treatment. Social workers engaged in signiftcantly more individual treatment, had a higher number of patient-social worker contacts, and engaged in longer duration of treatment with younger than with older patients. Concomitantly, social workers spent less time addres- sing significant problems related to adjustment to illness with elderly oncology patients. These findings suggest that social workers may not be effectively helping elderly oncology patients cope with important issues of ill...

Published
1995

20. Cancer-Selective Targeting of the NF-kappa B Survival Pathway with GADD45 beta/MKK7 Inhibitors

Author

Tornatore, L, Sandomenico, A, Raimondo, D, Low, C, Rocci, A, Tralau-Stewart, C, Capece, D, D'Andrea, D, Bua, M, Boyle, E, van Duin, Mark, Zoppoli, P, Jaxa-Chamiec, A, Thotakura, AK, Dyson, J, Walker, BA, Leonardi, A, Chambery, A, Driessen, Caroline, Sonneveld, Pieter, Morgan, G, Palumbo, A, Tramontano, A, Rahemtulla, A, Ruvo, M, Franzoso, G, Tornatore, L, Sandomenico, A, Raimondo, D, Low, C, Rocci, A, Tralau-Stewart, C, Capece, D, D'Andrea, D, Bua, M, Boyle, E, van Duin, Mark, Zoppoli, P, Jaxa-Chamiec, A, Thotakura, AK, Dyson, J, Walker, BA, Leonardi, A, Chambery, A, Driessen, Caroline, Sonneveld, Pieter, Morgan, G, Palumbo, A, Tramontano, A, Rahemtulla, A, Ruvo, M, and Franzoso, G

Abstract

Constitutive NF-B-K signaling promotes survival in multiple myeloma (MM) and other cancers; however, current NF-B-K-targeting strategies lack cancer cell specificity. Here, we identify the interaction between the NF-B-K-regulated antiapoptotic factor GADD45 beta and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug-discovery strategy, we developed DTP3, a D-tripeptide, which disrupts the GADD45 beta/ MKK7 complex, kills MM cells effectively, and, importantly, lacks toxicity to normal cells. DTP3 has similar anticancer potency to the clinical standard, bortezomib, but more than 100-fold higher cancer cell specificity in vitro. Notably, DTP3 ablates rnyeloma xenografts in mice with no apparent side effects at the effective doses. Hence, cancer-selective targeting of the NF-KB pathway is possible and, at least for myeloma patients, promises a profound benefit.

Published
2014

21. Cover

Author

Berggolts, Olga, Hodgson, Katharine, Kirschenbaum, Lisa, and Walker, Barbara

Published
2018

22. Preface

Author

Berggolts, Olga, Hodgson, Katharine, Kirschenbaum, Lisa, and Walker, Barbara

Published
2018

23. Index

Author

Berggolts, Olga, Hodgson, Katharine, Kirschenbaum, Lisa, and Walker, Barbara

Published
2018

24. 5. Blockade Bathhouse

Author

Berggolts, Olga, Hodgson, Katharine, Kirschenbaum, Lisa, and Walker, Barbara

Published
2018

26. Notes

Author

Berggolts, Olga, Hodgson, Katharine, Kirschenbaum, Lisa, and Walker, Barbara

Published
2018

28. Part II

Author

Berggolts, Olga, Hodgson, Katharine, Kirschenbaum, Lisa, and Walker, Barbara

Published
2018

32. Acknowledgments

Author

Berggolts, Olga, Hodgson, Katharine, Kirschenbaum, Lisa, and Walker, Barbara

Published
2018

34. Foreword

Author

Berggolts, Olga, Hodgson, Katharine, Kirschenbaum, Lisa, and Walker, Barbara

Published
2018

41. HIV testing and life insurance

Author

Walker Ba

Subjects
medicine.medical_specialty, business.industry, Health Personnel, Public Health, Environmental and Occupational Health, Hiv testing, United Kingdom, Occupational Diseases, Insurance, Life, Risk Factors, Family medicine, Life insurance, HIV Seropositivity, medicine, Humans, Mass Screening, Female, business
Published
1993

42. BA set to pilot online financial services for high fliers

Author

Fliers, Clive Walker BA Set To Pilot Online Financial Services For High

Subjects
British Airways PLC, BA Travel Finance, Advertising, marketing and public relations, Business, general
Abstract

British Airways is set to test telephone and online banking, following confirmation last week that it is dipping a toe into the financial sector by offering customer loans. Online and [...]

Published
1999

43. BA carries relations on the Ocean Wave

Author

Wave, Clive Walker BA Carries Relations On The Ocean

Subjects
British Airways PLC, Advertising, marketing and public relations, Business, general
Abstract

British Airways new multi-million pound consolidated relational database, to be unveiled next month, will be the powerhouse behind the carriers most ambitious direct marketing strategy to date. All 30 of [...]

Published
1999

45. Cover

Author

Walker, Barrington

Published
2013

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