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Biomedicines Sep 2022The tumor cells that drive classical Hodgkin lymphoma (cHL), namely, Hodgkin and Reed-Sternberg (HRS) cells, display hallmark features that include their rareness in... (Review)
Review
The tumor cells that drive classical Hodgkin lymphoma (cHL), namely, Hodgkin and Reed-Sternberg (HRS) cells, display hallmark features that include their rareness in contrast with an extensive and rich reactive microenvironment, their loss of B-cell phenotype markers, their immune escape capacity, and the activation of several key biological pathways, including the constitutive activation of the NFkB pathway. Both canonical and alternative pathways are deregulated by genetic alterations of their components or regulators, EBV infection and interaction with the microenvironment through multiple receptors, including CD30, CD40, BAFF, RANK and BCMA. Therefore, NFkB target genes are involved in apoptosis, cell proliferation, JAK/STAT pathway activation, B-cell marker expression loss, cellular interaction and a positive NFkB feedback loop. Targeting this complex pathway directly (NIK inhibitors) or indirectly (PIM, BTK or NOTCH) remains a challenge with potential therapeutic relevance. Nodular predominant HL (NLPHL), a distinct and rare HL subtype, shows a strong NFkB activity signature because of mechanisms that differ from those observed in cHL, which is discussed in this review.
PubMed: 36140254
DOI: 10.3390/biomedicines10092153 -
Annals of Oncology : Official Journal... Sep 2015
Topics: Humans; Lymphoma, Large B-Cell, Diffuse
PubMed: 26314773
DOI: 10.1093/annonc/mdv304 -
Haematologica Jan 2023Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical,...
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males, 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e., non-monomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ [98%] CD4- [94%] CD5- [97%] CD7+ [97%] CD8+ [90%] CD56+ [86%] CD103+ [80%] cytotoxic marker+ [98%]) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with non-monomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%), JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signaling and encompasses genetic and morphologic variants associated with very high clinical risk.
Topics: Male; Female; Humans; Aged; Enteropathy-Associated T-Cell Lymphoma; Genomics; Mutation; Signal Transduction
PubMed: 35708139
DOI: 10.3324/haematol.2022.281226 -
European Journal of Cancer (Oxford,... May 2021Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated.
MATERIALS AND METHODS
In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point.
RESULTS
A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm).
CONCLUSION
SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.
Topics: Adenocarcinoma; Adult; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Hysterectomy; Lymph Node Excision; Middle Aged; Morbidity; Neoplasm Recurrence, Local; Prognosis; Prospective Studies; Sentinel Lymph Node Biopsy; Survival Rate; Uterine Cervical Neoplasms
PubMed: 33773275
DOI: 10.1016/j.ejca.2021.02.009 -
The Journal of Molecular Diagnostics :... Mar 2018Authors' Reply to the Letter to the Editor by Y. Lynn Wang (MYD88 mutations and sensitivity to ibrutinib therapy).
Authors' Reply to the Letter to the Editor by Y. Lynn Wang (MYD88 mutations and sensitivity to ibrutinib therapy).
Topics: Adenine; Mutation; Myeloid Differentiation Factor 88; Piperidines; Pyrazoles; Pyrimidines
PubMed: 29482771
DOI: 10.1016/j.jmoldx.2017.12.001 -
Frontiers in Neurology 2021
PubMed: 34456855
DOI: 10.3389/fneur.2021.737556 -
Molecules (Basel, Switzerland) Jul 2018
Topics: Biomimetic Materials; Carbohydrates; Chemistry, Pharmaceutical; Drug Design; Humans
PubMed: 29986502
DOI: 10.3390/molecules23071658 -
Biotechnology Advances 2020Polyurethanes (PU) are a family of versatile synthetic polymers intended for diverse applications. Biological degradation of PU is a blooming research domain as it... (Review)
Review
Polyurethanes (PU) are a family of versatile synthetic polymers intended for diverse applications. Biological degradation of PU is a blooming research domain as it contributes to the design of eco-friendly materials sensitive to biodegradation phenomena and the development of green recycling processes. In this field, an increasing number of studies deal with the discovery and characterization of enzymes and microorganisms able to degrade PU chains. The synthesis of short lifespan PU material sensitive to biological degradation is also of growing interest. Measurement of PU degradation can be performed by a wide range of analytical tools depending on the architecture of the materials and the biological entities. Recent developments of these analytical techniques allowed for a better understanding of the mechanisms involved in PU biodegradation. Here, we reviewed the evaluation of biological PU degradation, including the required analytics. Advantages, drawbacks, specific uses, and results of these analytics are largely discussed to provide a critical overview and support future studies.
Topics: Biocompatible Materials; Biodegradation, Environmental; Polyurethanes; Recycling
PubMed: 31689471
DOI: 10.1016/j.biotechadv.2019.107457 -
Bioactive Materials Apr 2021Polyurethanes (PUs) are a major family of polymers displaying a wide spectrum of physico-chemical, mechanical and structural properties for a large range of fields. They... (Review)
Review
Polyurethanes (PUs) are a major family of polymers displaying a wide spectrum of physico-chemical, mechanical and structural properties for a large range of fields. They have shown suitable for biomedical applications and are used in this domain since decades. The current variety of biomass available has extended the diversity of starting materials for the elaboration of new biobased macromolecular architectures, allowing the development of biobased PUs with advanced properties such as controlled biotic and abiotic degradation. In this frame, new tunable biomedical devices have been successfully designed. PU structures with precise tissue biomimicking can be obtained and are adequate for adhesion, proliferation and differentiation of many cell's types. Moreover, new smart shape-memory PUs with adjustable shape-recovery properties have demonstrated promising results for biomedical applications such as wound healing. The fossil-based starting materials substitution for biomedical implants is slowly improving, nonetheless better renewable contents need to be achieved for most PUs to obtain biobased certifications. After a presentation of some PU generalities and an understanding of a biomaterial structure-biocompatibility relationship, recent developments of biobased PUs for non-implantable devices as well as short- and long-term implants are described in detail in this review and compared to more conventional PU structures.
PubMed: 33102948
DOI: 10.1016/j.bioactmat.2020.10.002 -
Molecules (Basel, Switzerland) Aug 2020Asymmetric transition-metal catalysis represents a fascinating challenge in the field of organic chemistry research. Since seminal advances in the late 60s, which were... (Review)
Review
Asymmetric transition-metal catalysis represents a fascinating challenge in the field of organic chemistry research. Since seminal advances in the late 60s, which were finally recognized by the Nobel Prize to Noyori, Sharpless and Knowles in 2001, the scientific community explored several approaches to emulate nature in producing chiral organic molecules. In a scenario that has been for a long time dominated by the use of late-transition metals (TM) catalysts, the use of 3d-TMs and particularly iron has found, recently, a widespread application. Indeed, the low toxicity and the earth-abundancy of iron, along with its chemical versatility, allowed for the development of unprecedented and more sustainable catalytic transformations. While several competent reviews tried to provide a complete picture of the astounding advances achieved in this area, within this review we aimed to survey the latest achievements and new concepts brought in the field of enantioselective iron-catalyzed transformations.
Topics: Catalysis; Chemistry, Organic; Iron; Stereoisomerism
PubMed: 32858925
DOI: 10.3390/molecules25173889