Primary Central Nervous System Lymphoma

Although non-Hodgkin’s lymphoma (NHL) is a frequent cancer worldwide, primary central nervous system (CNS) lymphoma (PCNSL) is a rare presentation, with an incidence of less than 0.5 per 100,000 persons-years in the western world. In the vast majority of cases, it has the histology of a diffuse large B-cell lymphoma (DLBCL) and is a hardly curable disease with high relapse risk. Therapeutic options are limited by blood-brain barrier penetration of drugs and because of its low-incidence high-grade evidence from large studies is lacking, current management being based on reports on rather small cohorts. The current standard first-line treatment for PCNSL consists of high-dose methotrexate (HD-MTX) in combination with a variety of drugs and consolidation whole-brain radiotherapy, the latter being progressively replaced by chemotherapy. For patients relapsing after first-line treatment, intensive chemotherapy with autologous stem cell support is a feasible and relatively safe salvage therapy. In the present chapter, we briefly discuss primary central nervous system lymphoma management and review current therapeutic options and evidence-based recommendations. We discuss the role of whole-brain radiotherapy (WBRT) and new prospects to avoid this side effect-ridden approach. Also, we will look at new therapeutic approaches currently under investigation, including immunotherapy

Noncoding RNAs in Lung Cancer Angiogenesis

Lung cancer is the major death-related cancer in both men and women, due to late diagnostic and limited treatment efficacy. The angiogenic process that is responsible for the support of tumor progression and metastasis represents one of the main hallmarks of cancer. The role of VEGF signaling in angiogenesis is well‐established, and we summarize the role of semaphorins and their related receptors or hypoxia‐related factors role as prone of tumor microenvironment in angiogenic mechanisms. Newly, noncoding RNA transcripts (ncRNA) were identified to have vital functions in miscellaneous biological processes, including lung cancer angiogenesis. Therefore, due to their capacity to regulate almost all molecular pathways related with altered key genes, including those involved in angiogenesis and its microenvironment, ncRNAs can serve as diagnosis and prognosis markers or therapeutic targets. We intend to summarize the latest progress in the field of ncRNAs in lung cancer and their relation with hypoxia‐related factors and angiogenic genes, with a particular focus on ncRNAs relation to semaphorins

Role of the tissue microenvironment as a therapeutic target in hepatocellular carcinoma

Hepatocellular carcinoma is difficult to treat, primarily because the underlying molecular mechanisms driving clinical outcome are still poorly understood. Growing evidence suggests that the tissue microenvironment has a role in the biological behavior of the tumor. The main clinical issue is to identify the best target for therapeutic approaches. Here, we discuss the hypothesis that the entire tissue microenvironment might be considered as a biological target. However, the tissue microenvironment consists of several cellular and biochemical components, each of which displays a distinct biological activity. We discuss the major components of this environment and consider how they may interact to promote tumor/host crosstalk

Molecular profiling and the TP53 gene in diffuse large B-cell lymphoma

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Limfom difuz cu celule B mari reprezintă o neoplazie eterogenă compusă din mai multe entități biologice distincte. Mai multe studii moleculare au încercat să identifice factori prognostici și ținte de tratament potențiale. Rolul genei TP53, adesea alterată în multe malignități umane, rămâne controversat. Scopul studiului. Evaluarea progreselor actuale în subtipizarea a limfomului difuz cu celule B mari și analiza rolului patogenic și prognostic al alterărilor TP53. Material și metode. Analiza a articolelor relevante din baze de date: PubMed/MEDLINE, Cochrane Library, Web of Science. Rezultate. Mutațiile TP53 reprezintă un factor independent pentru prognostic nefavorabil și supraviețuire inferioară în limfom, cu o prevalență de aproximativ 20-25%. A fost demonstrată o îmbunătățire generală a efectului clinic și a supraviețuirii, dar nici adăugarea de rituximab, nici regimurile de chimioterapie intensificată nu au reușit să depășească efectele adverse ale mutațiilor TP53. Parametrii clinici, cum ar fi scorurile prognostice și stadiul, nu au fost asociate cu prezența alterărilor TP53. Perspectivele de tratament în cazurile cu mutații TP53 includ acționarea asupra receptorului de celulă B prin intermediul BTK și SYK, inhibiția căilor BCL2 și AKT și terapia cu celule CAR T, printre altele. Concluzii. Statutul mutațional TP53 în limfomul difuz cu celule B mari nu influențează în prezent conduita pacientului. Studii de validare suplimentare și explorarea unor abordări alternative de tratament care vizează TP53 și alte căi moleculare sunt necesare pentru a îmbunătăți rezultatele în acest subgrup.Background. Diffuse large B-cell lymphoma is a heterogeneous tumor comprised of several distinct biological entities. Multiple molecular studies have attempted to identify potential prognostic factors and treatments targets. The role of TP53, a gene often mutated in many human malignancies, remains controversial. Objective of the study. Evaluation of the current advances in subtyping of diffuse large B-cell lymphoma and analysis of the pathogenetic and prognostic role of TP53 alterations. Material and methods. Review of relevant articles in the following databases: PubMed/MEDLINE, Cochrane Library, Web of Science. Results. TP53 mutations were shown to be an independent factor for negative outcomes and inferior survival in lymphoma, with an overall prevalence of around 20-25%. An overall improvement in outcome and survival has been shown, but neither the addition of rituximab, nor the intensified chemotherapy regimens were able to overcome the adverse effects of TP53 mutations. Clinical parameters, such as prognostic scores and stage, did not seem to be associated with TP53 alterations. Potential treatment prospects in TP53-mutated cases included targeting the B-cell receptor through BTK and SYK, inhibition of BCL2 and AKT pathways, and CAR T therapy, among others. Conclusions. The mutational status of TP53 in diffuse large B-cell lymphoma does not currently influence patient management. Further validation studies and exploration of alternative treatment approaches targeting TP53 and other molecular pathways are necessary to improve clinical outcomes in this patient group

The Malignant Role of Exosomes as Nanocarriers of Rare RNA Species

Publisher's version (útgefin grein)Nowadays, advancements in the oncology sector regarding diagnosis methods allow us to specifically detect an increased number of cancer patients, some of them in incipient stages. However, one of the main issues consists of the invasive character of most of the diagnosis protocols or complex medical procedures associated with it, that impedes part of the patients to undergo routine checkups. Therefore, in order to increase the number of cancer cases diagnosed in incipient stages, other minimally invasive alternatives must be considered. The current review paper presents the value of rare RNA species isolated from circulatory exosomes as biomarkers of diagnosis, prognosis or even therapeutic intervention. Rare RNAs are most of the time overlooked in current research in favor of the more abundant RNA species like microRNAs. However, their high degree of stability, low variability and, for most of them, conservation across species could shift the interest toward these types of RNAs. Moreover, due to their low abundance, the variation interval in terms of the number of sequences with differential expression between samples from healthy individuals and cancer patients is significantly diminished and probably easier to interpret in a clinical context.This research was funded by three national research grants from the Romanian Government: the first one awarded for Frontiers Research Projects 2018-2022 (grant number PN-III-P4-ID-PCCF-2016-112) to Babes Bolyai University, Cluj-Napoca, in collaboration with the Ion Chiricuta Oncology Institute, Cluj-Napoca; the second one awarded for Young Research Teams 2020-2022 (grant number PN-III-P1-1.1-TE2019-0271) to Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, and the third one awarded for Postdoctoral Research Projects 2020-2022 (grant number PN-III-P1-1.1-PD-2019-0805) to Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca. The APC was funded by an international collaborative grant from the European Economic Space between Romania and Iceland 2020-2022 (grant number 19-COP-0031)."Peer Reviewed

Unlocking protein-based biomarker potential for graft-versus-host disease following allogenic hematopoietic stem cell transplants

Despite the numerous advantages of allogeneic hematopoietic stem cell transplants (allo-HSCT), there exists a notable association with risks, particularly during the preconditioning period and predominantly post-intervention, exemplified by the occurrence of graft-versus-host disease (GVHD). Risk stratification prior to symptom manifestation, along with precise diagnosis and prognosis, relies heavily on clinical features. A critical imperative is the development of tools capable of early identification and effective management of patients undergoing allo-HSCT. A promising avenue in this pursuit is the utilization of proteomics-based biomarkers obtained from non-invasive biospecimens. This review comprehensively outlines the application of proteomics and proteomics-based biomarkers in GVHD patients. It delves into both single protein markers and protein panels, offering insights into their relevance in acute and chronic GVHD. Furthermore, the review provides a detailed examination of the site-specific involvement of GVHD. In summary, this article explores the potential of proteomics as a tool for timely and accurate intervention in the context of GVHD following allo-HSCT

Castleman’s disease in the HIV-endemic setting

Castleman’s disease (CD), first described by Benjamin Castleman in 1954, is a giant or angiofollicular lymph node hyperplasia, described as a rare monotypic polyclonal B-cell lymphoproliferative disorder with an incompletely understood pathogenesis and variable clinical behavior. This study aimed to determine the incidence of CD diagnosis over an 11-year period. Additionally, the study aimed to describe the demographic, laboratory, and pathological features of CD. Methods: This is a retrospective study where the demographic and laboratory data were retrieved from the Tygerberg Academic Hospital (TAH) patient electronic records and Tygerberg Lymphoma Study Group (TLSG) and statistical analysis performed on the patients diagnosed with CD. Results: Fifty-four patients were diagnosed with CD during this period. The median age at presentation was 39 years (range: 9–58). HIV serology was available in 53 patients, of which 51 were HIV-positive and two were HIV-negative. The history of initiation of antiretroviral therapy at diagnosis was available in 43 patients (38 on treatment, four were not on treatment, and one defaulted treatment). The median CD4 count was 232.50 cells/μL (range: 2–883). The HIV viral load was performed in 43 patients at diagnosis, which was <49 HIV-1 RNA copies/ μL in more than half of the patients (58%). Diagnosis was made on lymph node biopsies in 53 patients, with one case diagnosed on a spleen biopsy. Kaposi sarcoma was found on the same tissue biopsy in 13 cases. A bone marrow biopsy was performed in 31 patients. The predominant features noted were a disorganized hypercellular marrow with plasmocytosis. Conclusion: CD is a rare polyclonal B-cell lymphoproliferative disorder. However, we demonstrated a significant increase in the incidence of HIV-associated multicentric CD over the last decade in our area in South Africa

Overview of the Side-Effects of FDA- and/or EMA-Approved Targeted Therapies for the Treatment of Hematological Malignancies.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadIn the last decade there has been tremendous effort in offering better therapeutic management strategies to patients with hematologic malignancies. These efforts have ranged from biological to clinical approaches and resulted in the rapid development of new approaches. The main "problem" that comes with the high influx of newly approved drugs, which not only influences hematologists that frequently work with these drugs but also affects other healthcare professionals that work with hematologists in patient management, including intensive care unit (ICU) physicians, is they have to keep up within their specialty and, in addition, with the side-effects that can occur when encountering hematology-specific therapies. Nonetheless, there are few people that have an in-depth understanding of a specialty outside theirs. Thus, this manuscript offers an overview of the most common side-effects caused by therapies used in hematology nowadays, or that are currently being investigated in clinical trials, with the purpose to serve as an aid to other specialties. Nevertheless, because of the high amount of information on this subject, each chapter will offer an overview of the side-effects of a drug class with each reference of the section being intended as further reading. Keywords: hematological malignancies; life-threatening side-effects; novel therapies.MDPI A

Continuous renal replacement therapy in cytokine release syndrome following immunotherapy or cellular therapies?

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadRecently, an increasing number of novel drugs were approved in oncology and hematology. Nevertheless, pharmacology progress comes with a variety of side effects, of which cytokine release syndrome (CRS) is a potential complication of some immunotherapies that can lead to multiorgan failure if not diagnosed and treated accordingly. CRS generally occurs with therapies that lead to highly activated T cells, like chimeric antigen receptor T cells or in the case of bispecific T-cell engaging antibodies. This, in turn, leads to a proinflammatory state with subsequent organ damage. To better manage CRS there is a need for specific therapies or to repurpose strategies that are already known to be useful in similar situations. Current management strategies for CRS are represented by anticytokine directed therapies and corticosteroids. Based on its pathophysiology and the resemblance of CRS to sepsis and septic shock, as well as based on the principles of initiation of continuous renal replacement therapy (CRRT) in sepsis, we propose the rationale of using CRRT therapy as an adjunct treatment in CRS where all the other approaches have failed in controlling the clinically significant manifestations.School of Doctoral Studies - Iuliu Hatieganu University Romanian Government Ion Chiricuta Oncology Institute Cluj Napoca Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca European Economic Spac