591 research outputs found
Role of 4-1BB:4-1BBL in cancer immunotherapy
No full textThe activation of T cells plays a central role in antitumor immunity. In order to activate naïve T cells, two key signals are required. Signal one is provided through the T-cell receptor (TCR) while signal two is that of costimulation. The CD28:B7 molecules are one of the best-studied costimulatory pathways, thought to be the main mechanism through which primary T-cell stimulation occurs. However, a number of molecules have been identified which serve to amplify and diversify the T-cell response, following initial T-cell activation. These include the more recently described 4-1BB:4-1BB ligand (4-1BBL) molecules. 4-1BB:4-1BBL are a member of the TNFR:TNF ligand family, which are expressed on T cells and antigen-presenting cells (APCs), respectively. Therapies utilizing the 4-1BB:4-1BBL signaling pathway have been shown to have antitumor effects in a number of model systems. In this paper, we focus on the 4-1BB:4-1BBL costimulatory molecules. In particular, we will describe the structure and function of the 4-1BB molecule, its receptor and how 4-1BB:4-1BBL costimulation has and may be used for the immunotherapy of cance
Mufti Muhammad Ibrahim Qadri (2021) in response to queries on ‘forced conversion’ raised Muhammad Ziauddin Siyalwi
No full textMufti Muhammad Ibrahim Qadri (2021) in response to queries on ‘forced conversion’ raised Muhammad Ziauddin Siyalwi, p.14 . available at Hussain, Ghulam (2021), “Mufti Muhammad Ibrahim Qadri (2021) in response to queries on ‘forced conversion’ raised Muhammad Ziauddin Siyalwi”, Mendeley Data, V1, doi: 10.17632/4mtfdxvp4n.1THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV
Serum profiling reveals distinctive proteomic markers in the serum from chronic myeloid leukaemia patients
No full textWe have shown that proteomic profiling of sera from chronic myeloid leukaemia patients at presentation identifies five serum markers whose expression profile is significantly different from that seen in normal controls, non-malignant neutrophilia and in CML patients in HR following treatment with Gleevec. Of particular interest is the persistence of three of the five biomarkers following successful induction of HR, suggesting that those changes are disease specific. We have demonstrated that serum profiling can robustly identify disease groups and disease state in patients with CML compared with non-malignant and normal controls. In addition our data suggest that serum profiling of other haematological malignancies may provide new biomarkers for disease state and stag
Supplemental material for The role of a critical care outreach service in the management of patients with haematological malignancy
No full textSupplemental Material for The role of a critical care outreach service in the management of patients with haematological malignancy by Leila Taheri, Rathai Anandanadesan, Hugues de Lavallade, Eirini Pagkalidou, Antonio Pagliuca, Ghulam Mufti, Georg Auzinger and Victoria Metaxa in Journal of the Intensive Care Society</p
The tumour antigens RAGE-1 and MGEA6 are expressed more frequently in the less lineage restricted subgroups of presentation acute myeloid leukaemia
No full textWe have analysed the frequency of present calls for RAGE-1 and MGEA6 in patients based on FAB subclass. MGEA6 and RAGE-1 present calls were significantly higher in the M0/M1/M2 versus the M3/M4/M5/M6/M7 groups for both RAGE-1 (p<0.0001) and MGEA6 (p<0.0001). However dividing patients into three WHO subgroups as follows (i) ‘recurrent’ representing acute myeloid leukaemia with recurrent genetic abnormalities, (ii) ‘AML’ representing acute myeloid leukaemia, minimally differentiated; acute myeloid leukaemia without maturation; acute myeloid leukaemia with maturation broadly representing FAB M0, M1 and M2 and (iii) ‘lineage’ representing acute myelomonocytic leukaemia; acute monoblastic leukaemia; acute erythroid leukaemia (erythroid/myeloid and pure erythroid leukaemia); acute megakaryoblasic leukaemia and acute basophilic leukaemia broadly representing FAB M4 – M7 indicated that a significant number of patients in the AML group had MGEA6 present calls compared with patients in the lineage and recurrent groups (p=0.0185). However RAGE-1 expression did not segregate based on WHO this grouping. We examined whether in our patients population the M0/1/2 FAB subgroups were associated with a poorer survival rate than M3/4/5/6/7 and this was not found to be the case (p=0.27). RAGE-1 and MGEA6 present calls were also not found to be associated with poorer survival (p=0.891 and 0.956, respectively). RAGE-1 present calls did not to segregate with any single cytogenetic risk group (good, standard or poor). However using Chi2 pairwise comparisons the frequency of MGEA6 present calls in good versus poor, good versus standard and standard versus poor cytogenetic risk groups were all highly significant (each p<0.0001). This is the first study to suggest a differential expression of a CT antigen based on FAB or WHO subgroup or cytogenetic risk group. In addition, MGEA6 and RAGE-1 may provide suitable targets for the immunotherapy of AML particularly for patients in the M0, M1 and M2 subgroup
Mirza Athar Baig’s novel “Ghulam Bhag” and Post Colonialism Discourse : Mirza Athar Baig’s novel “Ghulam Bhag” and Post Colonialism Discourse
No full textGhulam Bagh is an important novel created in the Post-Colonial period in which Mirza Athar Baig has presented the intellectual and mental attitudes of this era.We can say that Post-Colonial literature refers to the literary texts that are created in the former colonies of Europe. In these writings, the background of Post-Colonialism and the background of Colonialism are presented in a literary Perspective. Post-Colonial literature shows an attempt to understand, examine and describe the feelings and experiences of those belonging to the former colonies. Mirza Athar Baig\u27s novel Ghulam Bagh was published in 2006 and six editions have been published so far. Ghulam Bagh is a masterpiece novel of fictional literature created in the former British colonial Pakistan, There are also characters living in the Post-Colonial era. Each character shows change, evolution and conflict. Ghulam Bagh is an imaginary place in terms of archeology. If we examine the title of the novel in a broader context, Ghulam Bagh is a metaphor for the desire of western nations to dominate the inferior, weak and noble races of the world. Is based on desire. In this paper, the novel will be studied in the Post-Colonial context to find out how far the author has succeeded in recovering the Colonial discourse.
 
Epigenetics in focus: Pathogenesis of myelodysplastic syndromes and the role of hypomethylating agents
No full textDysregulation of cellular epigenetic machinery is considered a major pathogenetic determinant in many malignancies, including myelodysplastic syndromes (MDS). The importance of epigenetic dysfunction in MDS is reflected by the success of hypomethylating agents as standard of care for their treatment. Although these agents improve both survival and quality of life, knowledge gaps remain regarding the precise role of epigenetics in the pathogenesis of MDS and mechanisms by which hypomethylating agents exert their clinical effects. This article reviews the pathogenic role of epigenetic alterations in MDS, including the relationship between genetic and epigenetic abnormalities, and highlights emerging evidence that hypomethylating agents may reprogram the "methylome" while re-establishing hematopoiesis. (C) 2013 Published by Elsevier Ireland Ltd
Optimised SEREX technique for the identification of leukaemia associated antigens
No full textThe serological analysis of antigens by recombinant expression cloning (SEREX) has been used by many laboratories to immunoscreen lambda phage cDNA libraries produced from a range of tumour cell types. We and others have found it difficult to extract an optimal quality and quantity of mRNA for the preparation of cDNA libraries which represent the genes transcribed in haematological samples. The difficulty is believed to be due to residual haem groups in the isolated RNA sample which inhibit the activity of reverse transcriptase used in the later production of cDNA. During our preparation of a cDNA library for SEREX studies, we optimised the isolation of mRNA from samples from patients with haematological malignancies. We compared the efficacy of different methods of mRNA extraction using a range of haematological sample sizes and describe the most efficient techniques to maximise mRNA yield and quality for cDNA library production. The phage library we prepared contained a range of cDNA insert sizes, including high molecular weight sequences which, following immunoscreening with autologous patient sera, led to the isolation of 17 novel antigens. Using the methodology described, we have shown SEREX to be effective for the isolation of leukaemia-associated antigens, which may act as targets for immunotherap
The leukaemia associated antigen, SSX2IP, is expressed during mitosis on the surface of myeloid leukaemia cells
No full textWe have shown for the first time the surface expression pattern of SSX2IP during mitosis which provides an interesting insight into SSX2IP protein expression in human malignancy. Therapeutically the removal of SSX2IP positive cells from AML patient stem cell harvests has the potential to reduce the tumour burden for patients whose graft fails or for patients who lack a suitable stem cell donor, although these possibilities require further investigatio
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