130553 research outputs found
Sort by
IBCL-294: Analysis of follicular lymphoma patients transforming to diffuse large B-Cell lymphoma: A single-center experience
No full textBackground:
Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma with a well-recognized risk of histological transformation to diffuse large B-cell lymphoma (DLBCL), which is associated with more aggressive disease and poorer outcomes. This study aimed to access the outcome of transformation to DLBCL from FL in a retrospective analysis.
Methods:
We conducted a retrospective cohort study of patients diagnosed with FL at a tertiary care center between January 2012 and December 2023. Patients with biopsy-proven transformation to DLBCL were included. Clinicopathological characteristics and survival outcomes were analyzed.
Results:
Out of 107 patients diagnosed with FL with median follow-up of 60 months, 11 (10%) developed histologic transformation to DLBCL. The median age at FL diagnosis was 56 years, with a median time of 17 months from FL diagnosis to transformation. Transformation was often heralded by rapidly progressive lymphadenopathy, B symptoms, and elevated serum lactate dehydrogenase. All transformed patients received immunochemotherapy, most commonly R-CHOP. The median overall survival following transformation was 40 months. High FLIPI 1 score at baseline was associated with worse post-transformation survival. Five-year survival was significantly worse for patients with vs without transformation (81%, 95% CI 60–100 vs 93%, 95% CI 89–99). At last follow-up, six patients were alive and in remission, while five had died of disease progression or related complications.
Conclusions:
In this single-center cohort, approximately 10% of FL patients experienced transformation to DLBCL, predominantly within the first 2 years post-diagnosis. Despite standard immunochemotherapy, survival after transformation remained suboptimal
Management of relapsed/refractory myeloma in resource constrained setting: Median age (years) age (years) immunoglobulin subtype Hb (G/dL) serum creatininee GFR mL/minute serum albumin (g/dL) serum LDHP platelets counts circulating plasma cells cytogenetics hypercalcemia co-morbidities diabetes hypertension hypothyroidism F/H of malignancy
No full textBackground:
Treatment of relapse/refractory multiple myeloma (MM) is complex and requires consideration of disease, patients related factors and front-line treatment used. We aimed to assess the efficacy and safety of salvage regimens in symptomatic MM patients.
Methods:
We evaluated records of relapse/refractory MM patients treated between 2014 and 2019. One hundred ninety-five patients received salvage therapy, another 61 (21.8%) asymptomatic patients with biochemical progression were kept on close follow up. Primary outcome was progression free survival (PFS). Response and toxicity to treatment and overall survival (OS) were secondary outcome measures.
Results:
Patients median age was 59.5 years (range; 23-84 years) and 65.7% were males. Among 176 (90.3%) evaluable patients; 98(55.6%) responded; complete response (CR)-19(10.8%), very good partial response (VGPR)-14(7.9%), and partial response (PR) 65(36.9%). Median PFS was superior for complete responders; 31.2 versus 8.2 months, P < .005. Median PFS for refractory myeloma was 5.09 months compared to 11.4 months for nonrefractory myeloma, P < .001. Median PFS was 6.70 months for those with clinical relapse versus 9.50 months for biochemical relapse (P = .62). Median OS was not reached. Circulating plasma cells > 5%, thrombocytopenia, refractory disease were predictors of inferior PFS. Most common grade 3/4 treatment-related adverse events were thrombocytopenia (5.7%), anemia (7.5%), and febrile neutropenia (5.2%). About 10(2.4%) patients required change of therapy due to adverse reactions.
Conclusion:
Achievement of CR in symptomatic, relapsed myeloma was associated with superior PFS. Careful observation for asymptomatic patients with biochemical relapse is a reasonable approach. Newer novel molecules for those with refractory disease are needed
Transcriptional and epigenomic changes in response to polyethylene glycol-triggered osmotic stress in Brassica napus L.
No full textDrought hinders growth, development, and productivity of higher plants. While the physiological and molecular background of plant responses to drought has been extensively studied, the role of post-translational modifications of histones or DNA methylation in response to dehydration remains largely elusive. In this study, we deciphered genome-wide changes in transcriptome and histone modifications in response to dehydration in rapeseed (Brassica napus L.). High-throughput transcript profiling (RNA-seq) and ChIP followed by sequencing (ChIP-seq) of polyethylene glycol (PEG)-treated rapeseed plants revealed genome-scale changes in transcription and histone methylation patterns, specifically in histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 tri-methylated lysine 27 (H3K27me3) sites. We have identified gene sets with altered transcript profiles as well as histone methylation marks in response to osmotic stress. Several proline biosynthesis regulatory genes coding for Delta 1-Pyrroline-5-Carboxylate Synthetases (P5CS) displayed changes in H3K4me3 and/or H3K36me3 enrichment post-PEG treatment. Targeted bisulfite sequencing further identified stress-dependent gene body DNA methylation in one of the BnP5CSA gene copies that correlates with its stress-induced activation. By integrating physiological, transcriptional, and epigenomic data, our study contributes to a better understanding of the drought response control in crop plants
An Oryza-specific histone H4 variant predisposes H4 lysine 5 acetylation to modulate salt stress responses
No full textParalogous variants of canonical histones guide accessibility to DNA and function as additional layers of genome regulation. Across eukaryotes, mechanism of action and functional significance of several variants of core histones are well-known except that of histone H4. Here we show that, a novel variant of H4 (H4.V) expressing tissue-specifically among Oryza members, mediated specific epigenetic changes contributing to salt tolerance. H4.V was incorporated to specific heterochromatic sites where it blocked deposition of active histone marks. Stress dependent re-distribution of H4.V enabled incorporation of active H4 Lysine5 Acetylation (H4K5Ac) marks. Mis-expression of H4.V led to defects in reproductive development and in mounting salt stress responses. H4.V formed homotypic nucleosomes and mediated these alterations by conferring distinct molecular properties to the nucleosomes, as seen with cryo-EM structures and biochemical assays. These results not only uncovered the presence of a H4 variant among plants, but also of a novel chromatin regulation that might have contributed to the adaptation of semi-aquatic Oryza members
The inhomogeneous t-PushTASEP and Macdonald polynomials at q=1
No full textWe study a multispecies -PushTASEP system on a finite ring of n sites with site-dependent rates x1,…,xn. Let λ = (λ1,…,λn) be a partition whose parts represent the species of the n particles on the ring. We show that, for each composition η obtained by permuting the parts of λ, the stationary probability of being in state η is proportional to the ASEP polynomial Fη(x1,…,xn; q,t) at q=1; the normalising constant (or partition function) is the Macdonald polynomial Pλ( x1,…,x n; q,t) at q=1 . Our approach involves new relations between the families of ASEP polynomials and of nonsymmetric Macdonald polynomials at . We also use multiline diagrams, showing that a single jump of the PushTASEP system is closely related to the operation of moving from one line to the next in a multiline diagram. We derive symmetry properties for the system under permutation of its jump rates, as well as a formula for the current of a single-species system
BBX32 integrates ethylene and light signaling to delay apical hook opening and optimize seedling soil emergence
No full textIn terrestrial plants, seeds often germinate and initiate early development in the darkness under layers of soil. Soil overlay promotes ethylene accumulation to maintain the hook until the seedlings reach the soil surface. During this phase of etiolated growth and soil emergence, seedlings perceive changing light fluence. Coordinated interplay of the ethylene and light signaling pathways ensures optimal timing of apical hook opening and enhanced emergence.
Here, we report that ethylene and light cooperatively act on the B-box protein BBX32 to regulate apical hook opening and enhance soil emergence. Ethylene induces expression and accumulation of BBX32 in the apical hook in the dark. CONSTITUTIVE PHOTOMORPHOGENIC 1 degrades BBX32 in the dark while light enhances BBX32 expression and accumulation in the apical hook during de-etiolation. bbx32 mutants exhibit accelerated apical hook opening, while BBX32 overexpressing lines show delayed opening.
Genetic analyses reveal that BBX32 functions in concert with PHYTOCHROME-INTERACTING FACTOR 3 to negatively regulate apical hook opening during de-etiolation. BBX32 enhances HOOKLESS 1 expression in a PIF3-dependent manner to delay hook opening. Under soil cover, bbx32 and 35S:BBX32 seedlings exhibit reduced and enhanced seedling emergence, respectively.
Our study illustrates the role of BBX32 in synchronizing light and ethylene-mediated apical hook opening and seedling emergence
Evaluation of gum odina/carbopol composite mucoadhesive hydrogel on pharmaceutical performance: Focusing on potential periodontal treatment
No full textAntimicrobial buccal hydrogel made of polymers have gained tremendous utilisation in biomedical field. Dual drug loaded, porous materials are important areas of research for medical and pharmaceutical industries. In this regard, a series of hydrogels (F1, F2, F3) were prepared with gum odina and carbopol 940 in aqueous solution with calcium chloride as the cross linker and glycerol as plasticizer by ionotropic gelation method. The buccal hydrogel was evaluated for thermal stability (TGA/DSC) revealing them to be thermally stable. The SEM and AFM studies of the optimized formulation (F2) exhibits cracks and porous structure. It also depicted good injectability and self-healing. The XRD result displayed amorphous nature of the formulation (F2) making them soluble in buccal fluids. The chemical nature and interactions were analysed by FTIR study. The release profile portrayed controlled release patterns for amoxicillin trihydrate and fluconazole. Appreciable mucoadhesion time (6 ± 0.7 h) and strength (12.03 ± 0.45 g) was observed in case of F2. The optimized formulation F2 displayed good antifungal and antibacterial properties. Thus, it is concluded that the hydrogel formed were mucoadhesive and highly potent to carry drug molecules for controlled release in the buccal mucosa to treat several periodontal infections
Emerging techniques in cellular and biomolecular research
No full textCell and biomolecular research are rapidly evolving areas of study focusing on how cellular mechanisms work at the molecular level. The field encompasses various aspects of biology, including genetics, biochemistry, biophysics, and microbiology, with a primary emphasis on understanding how cells function and how biomolecules within them interact. Recent discoveries made in the last decade have progressed our comprehension of how cells maintain their physiological homeostasis and how cellular mechanisms can be manipulated to treat diseases. Several experimental methods have been used to study the cell and molecular basis of cellular mechanisms. In this chapter, we will discuss the important biochemical and biophysical methods that are employed to study the structure, function, dynamics, and interactions of biomolecules within cells. We present a summary of the fundamental principles and practical applications of these methods and explore the recent developments in cellular and molecular biology
Decoding the immune landscape in Ewing sarcoma pathogenesis: The role of tumor infiltrating immune cells and immune milieu
No full textEwing sarcoma (EwS) is the second most prevalent pediatric bone malignancy, characterized by its aggressive behavior and unfavorable prognosis. The tumor microenvironment (TME) of EwS is shaped by immunosuppressive components, including myeloid-derived suppressor cells, tumor-associated macrophages, and immune checkpoint molecules such as PD-1/PD-L1 and HLA-G. These elements impair anti-tumor immune responses by modulating the function of tumor-infiltrating immune cells, such as regulatory T cells (Tregs), CD8+ T cells, and natural killer cells. Chemokines, including CXCL9 and CXCL12, and cytokines, such as transforming growth factor-beta and interleukin-10, further contribute to immune suppression and promote metastatic dissemination. Recent advances in immunotherapy have highlighted the therapeutic potential of modulating immune cells and signaling pathways to enhance anti-tumor immunity. This review provides a comprehensive analysis of the complex immune landscape within the EwS TME, focusing on the mechanistic roles of key immune components and their potential as therapeutic targets. Understanding these interactions could pave the way for innovative treatment strategies to improve clinical outcomes in patients with EwS
266TiP A phase II, randomized, open- labelled study to evaluate low-dose pembrolizumab in addition to neoadjuvant chemotherapy for triple-negative breast cancer (TNBC)
No full textBackground
Breast cancer is the most common malignancy diagnosed in women worldwide. Triple negative breast cancer is the most aggressive subtype, accounting for nearly 15% of all breast cancers worldwide with upto one third of all breast cancers in South east Asian region.The addition of pembrolizumab to neoadjuvant chemotherapy improved the pathological response rates and event free survival in patients with triple negative breast cancer. However in most low and middle income countries, immunotherapy remains inaccesible due to its high cost. Lower doses of immune checkpoint inhibitors (nivolumab and pembrolizumab) have been shown to be effective in several cancers, including head and neck cancers, Hodgkin’s lymphoma, etc. Ex vivo IL2 stimulation for the purpose of evaluating PD-1 receptor modulation revealed total peripheral target engagement beginning at 1 mg/kg and lasting for at least 21 days, with no discernible difference between 1, 3, and 10 mg/kg. Therefore, we designed this study to evaluate a lower dose of pembrolizumab in addition to neoadjuvant chemotherapy in patients with TNBC as a cost-effective intervention.
Trial design
This is a phase II, randomized, open-labelled, parallel-group trial. Eligible patients will be randomized (1:1) to either of the two treatment groups. Patients in the control arm will be administered standard of care chemotherapy [4 cycles of dose-dense doxorubicin(60mg/m2) and cyclophosphamide(600mg/m2), followed by 4 cycles of dose-dense paclitaxel (175mg/m2)]. Patients in the experimental arm will receive 3 doses of pembrolizumab 50mg every 6 weeks along with neoadjuvant dose-dense chemotherapy. The primary objective of the study is to compare the pathological complete response with the addition of low-dose pembrolizumab to neoadjuvant chemotherapy in patients with TNBC.Secondary objectives include invasive disease-free survival and quality of life assessment