Epigenetic Effects in Children With Cow's Milk Allergy Treated With Different Formulas
Cow Milk AllergyLactobacillus GG (LGG) is able to exert long lasting effects in children with atopic disorders. Nutramigen LGG accelerates tolerance acquisition in infants with cow's milk allergy. The mechanisms of these effects are still largely undefined. The effect of LGG could be related at least in part by the immunoregulatory role played by LGG. This probiotic can balance the generation of cytokines possibly involved in IgE- or non-IgE-mediated cow's milk allergy Interleulkin (IL)-4, IL-5, IL-10, IFN-γ , TGF-β, and TNF-Υ), which can contribute to modulation of inflammatory processes. The investigators have demonstrated that children with IgE-mediated CMA produce significantly higher level of IL-4 and IL-13 in response to cow's milk protein, and that tolerance is associated with a marked reduction of IL-13 production and a concomitant increased frequency of IFN-γ releasing cells. Epigenetics studies the heritable (and potentially reversible) changes of the genome inherited from one cell generation to the next which alter gene expression but do not involve changes in primary DNA sequences, highlighting the complexity of the inter-relationship between genetics and nutrition. There are three distinct, but closely interacting, epigenetic mechanisms (histone acetylation, DNA methylation, and non-coding microRNAs) that are responsible for modifying the expression of critical genes associated with physiologic and pathologic processes. The profile of epigenetic modifications associated with Th lineage commitment, coupled with the sensitivity of the early developmental period, has led to speculation that factors that disrupt these pathways may increase the risk of allergic diseases. Specifically, effects on DNA methylation and endogenous histone deacetylase inhibitors acting on specific pathways (Th1 and T regulatory cell differentiation) may favour Th2-associated allergic differentiation. MicroRNAs are another structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. It has been recently identified a specific Th2-associated microRNA (miR-21) that is critical for the regulation of Th cell polarization. It has been previously demonstrated an inverse DNA methylation pattern of cytokines involved in Th2 response (IL-4, IL-5) compared with cytokines involved in Th1 response (IL-10, INF- y) in children with CMA acquiring oral tolerance, with the most pronounced effects in those treated with Nutramigen LGG.
CAR-37 T Cells In Hematologic Malignancies
Hematologic MalignancyLeukemia7 moreThis research study is studying Chimeric Antigen Receptor (CAR)-37 T Cells (CAR-37 T Cells) for treating people with relapsed or refractory CD37+ hematologic malignancies and to understand the side effects when treated with CAR-37 T Cells. - Chimeric Antigen Receptor (CAR)-37 T Cells (CAR-37 T Cells) is an investigational treatment
MIL62 Plus Lenalidomide for Patients With Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma (FL...
Follicular Lymphoma and Marginal Zone LymphomaThis phase 1b/2 trial studies the safety and best dose of lenalidomide when given together with MIL62 and how well this combination works in treating patients with Relapsed/Refractory low-grade Follicular Lymphoma(FL) and Marginal Zone Lymphoma(MZL). Giving MIL62 plus lenalidomide may work better in indolent Non-Hodgkin Lymphoma(NHL).
Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior...
Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaMantle Cell Lymphoma2 moreThe primary objective of this study is to evaluate the safety of zanubrutinib (also known as BGB-3111) in chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, mantle cell lymphoma, or marginal zone lymphoma patients who have become intolerant of prior ibrutinib and/or acalabrutinib treatment, by comparing intolerance to adverse event profile as assessed by the recurrence and the change in severity of adverse events.
A Personalised Radiosurgery Procedure for People With Trigeminal Neuralgia to Improve Pain, Quality...
Trigeminal NeuralgiaMultiple Sclerosis1 moreThe aim of this study is to evaluate prospectively the feasibility and impact of personalised gamma knife radiosurgery treatment protocol versus current standard protocol for people with idiopathic or Multiple Sclerosis-related Trigeminal Neurolgia (MS related TN) on effectiveness in pain relief, the development of morbidity and quality of life. Patients with TN or MS-related TN are referred to the National Centre for Stereotactic Radiosurgery in Sheffield for clinical consultation, and will undergo gamma knife radiosurgery (GNRS) for treating trigeminal neuralgia if eligible. The GKRS treatment is provided as a standard National Health Service (NHS) routine care. The current procedure has been proven to be safe and effectiveness in reducing the pain caused by TN. The current GKRS treatment protocol performs the treatment on the trigeminal nerve close to the brainstem, which might result in higher complication rate (mainly facial numbness). This study will conduct a pilot randomised controlled trial to evaluate an alternative treatment protocol, which will perform the GKRS treatment at the retrogasserian zone (further away from the brainstem). This treatment protocol has been widely used in Europe and USA, and is safe and effective. Most studies adopting this protocol have shown less complication rate after treatment.
[CREMA]Combination of R-M Followed by R-A in Elderly Patients With Primary CNS Lymphoma
Primary CNS LymphomaThis study was conducted to evaluate the 2-year progression free survival rate of elderly patients with primary CNS lymphoma followed by combination of rituximab and methotrexate followed by rituximab and cytarabine.
A Study of Voruciclib Alone or in Combination With Venetoclax in Subjects With B-Cell Malignancies...
Follicular Lymphoma (FL)Mantle Cell Lymphoma (MCL)5 moreThis is a Phase 1, open-label, dose escalation study to determine the safety and preliminary efficacy of voruciclib monotherapy in subjects with relapsed/refractory B cell malignancies or AML after failure of standard therapies or voruciclib in combination with venetoclax in subjects with relapsed or refractory AML
Phase II Study of Second- Line Pembrolizumab Plus GVD for Relapsed or Refractory Hodgkin Lymphoma...
Hodgkin LymphomaRelapsed or Refractory Hodgkin LymphomaThe purpose of this study is to test any good and bad effects of the study drug, pembrolizumab, in combination with GVD in the treatment of Hodgkin lymphoma.
Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL...
Acute Lymphoblastic LeukemiaPediatricThe understanding of acute lymphoblastic leukemia (ALL) in childhood and adolescence has largely changed due to extensive genetic research in recent years: ALL is now considered to be a very heterogeneous disease group. The leukemia cells present themselves with quite differently activated regulatory mechanisms of the malignant phenotype. The introduction of more accurate methods of assessing therapy response ("minimal residual disease [MRD] tests") has provided new insights into very different mechanisms of action, including factors influenced by host factors; this has had practical clinical consequences for the use of more individualized therapy. Multimodal therapies have enabled a cure level of over 80% for ALL in this age group. However, the own and international study data show that the therapy toxicity of the contemporary chemotherapy concepts has become unacceptably high, in particular with respect to those intensified therapies used for the treatment of patients at high risk of ALL relapse. The AIEOP-BFM ALL 2017 study therefore aims for an innovative integrated approach that will not only adapt the risk stratification to new prognostic markers using more comprehensive diagnostics, but above all, qualitatively reorient the therapy. The most important consequence will be that this study is testing immunotherapy with the bispecific antibody blinatumomab as an alternative to particularly intensive and toxic chemotherapy elements in precursor B-cell ALL (pB-ALL) patients with detectable chemotherapy resistance and at high risk of relapse. With the aim to complement the effects of the conventional chemotherapy, Blinatumomab is in addition tested in the large group of pB-ALL patients at intermediate relapse risk with seemingly unremarkable leukemia, but who account for a large proportion of all relapses. Targeted therapy is also used in the form of the proteasome inhibitor bortezomib for patients with pB-ALL and slow response to the drugs of the induction chemotherapy with the aim to overcome intrinsic chemotherapy resistance of the ALL cells. In patients with T-lineage ALL, who have particularly poor chances for cure after relapse, the established consolidation chemotherapy has proved to be particularly effective. This chemotherapy phase is therefore tested in a longer and more intensive form in such T-ALL patients with intermediate or slow early treatment response with the aim to reduce the relapses rate in this subgroup.
Efficacy and Safety of KD025 in Subjects With cGVHD After At Least 2 Prior Lines of Systemic Therapy...
Chronic Graft-versus-host-diseaseThis is a Phase 2, randomized, multicenter study to evaluate the efficacy and safety of KD025 in subjects with Chronic Graft Versus Host Disease (cGVHD) after at least 2 prior lines of systemic therapy