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Высокоэффективная терапия для предотвращения образования лимфоидных органов менингеля после скрининга индекса CXCL13 при раннем множественном склерозе.

Посмертные исследования показали наличие подпийного воспаления с высшими лимфоидными органами (ТЛО) в менингах пациентов с прогрессивным множественным склерозом, играющих важную роль в патофизиологии болезни. Химокин (C-X-C-motif) лиганд 13 (CXCL13) вызывает образование этих лимфоидных органов, тем самым поощряя активность болезни. Заболеваемость при множественном склерозе сократилась благодаря воздействию изменяющейся терапии. Однако, несмотря на успехи в лечении болезней иммуномодуляционными агентами, у нас по-прежнему нет специальных лабораторных биомаркеров, которые могли бы указывать на с

CAR-T Cell Therapy-An Overview of Targets in Gastric Cancer.

Gastric cancer (GC) is one of the most commonly diagnosed malignancies and, unfortunately, still has a high mortality rate. Recent research points to CAR-T immunotherapy as a promising treatment for this disease. Using genetically engineered T cells designed to target a previously selected antigen, researchers are able to harness the natural anti-tumor activity of T cells. For therapy to be successful, however, it is essential to choose antigens that are present on tumor cells but not on healthy cells. In this review, we present an overview of the most important targets for CAR-T therapy in th

Risk Factors and Outcome of COVID-19 Infection in Haematological Patients : A Multicenter Retrospective Analysis in Malaysia

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Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives.

The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a

Tagraxofusp for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): A Brief Report on Emerging Data.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy, for which conventional chemotherapy has poor outcomes. CD123, the α-subunit of interleukin (IL)-3 receptor, is constantly overexpressed at the surface of tumoral cells. Tagraxofusp (or SL-401) is a recombinant cytotoxin which consists of human interleukin-3 fused to a truncated diphtheria toxin. It is currently the only novel therapy with a prospective evaluation of efficacy and safety in the treatment of BPDCN and is also the only one to achieve FDA approval. In this short review, the results of tagraxofusp are

Boosting Immunity against Multiple Myeloma.

Despite the improvement of patient's outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody-drug conjugates or bispecific antibodies broadened the possibility of improving patients' survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residua

Экстренные ситуации в гематологии: Почему, когда и как я лечусь?

Гематологические чрезвычайные ситуации являются критическими медицинскими условиями, требующими неотложного внимания в силу их быстрого развития и опасного для жизни характера. В качестве примера можно привести гиперкальцемию, которая часто ассоциируется с раком, таким как множественная миелома, что может привести к серьезной неврологической и сердечной дисфункции. Гиперлейкоцитоз, распространенный в острой миэлоидной лейкемии, повышает риск лейкостаза и многоорганического отказа. Кислородный кризис, обычное осложнение серповидноклеточной болезни, является результатом вазооккуляции, приводящей

Lenalidomide: a brief review of its therapeutic potential in myelodysplastic syndromes.

Lenalidomide is a novel thalidomide analogue with enhanced immunomodulatory and antiangiogenic action lacking most of the typical thalidomide-associated adverse events. In myelodysplastic syndromes (MDS), it has been used primarily in the IPSS low- and intermediate-1 risk setting. Several trials have demonstrated its potential to lead to both erythroid and cytogenetic responses in these disease groups. In a clinical trial of patients with a del(5q) chromosomal abnormality, lenalidomide treatment resulted in red blood cell (RBC) transfusion independence in 67% of patients. Moreover, 45% of pati

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… Moreover, it has been recognized that the bone marrow microenvironment is not an innocent bystander in the malignant process, but may play a crucial role in the development and the support of neoplastic stem cells and their progeny ( Estey 2004 ). …

Воспаление и иммунная микроокружающая среда в миелопролазерных неоплазмах: патогенные механизмы и терапевтические возможности.

Филадельфия-отрицательная (Ph-отрицательная) миелопролиферативные новообразования (MPNs) включают полицифемию (PV), основную тромбоцитемию (ET) и первичный миэлофиброз (PMF), которые являются клональными гематопоэтическими расстройствами, вызванными соматическими генными мутациями в генах JAK2, CALR или MPL. Мутации активируют путь JAK-STAT и прерывают сигнализацию NF-IB, что приводит к хроническому подстрекательству, вызванному провоспалительными цитокинами и реактивными видами кислорода (ROS). Эта изменившаяся микроокружающая среда вызывает серьезные клинические особенности заболевания, таки

Comparison of anti-anaerobic antimicrobial strategies in cancer patients with febrile neutropenia and gastrointestinal symptoms.

BackgroundThe current study sought to compare 28-day mortality rates in cancer patients with febrile neutropenia (FN) and gastrointestinal (GI) symptoms who underwent monotherapy using an antibiotic with antipseudomonal and anti-anaerobic activity (piperacillin-tazobactam or a carbapenem) and a group treated with a combination of cefepime-metronidazole.FindingsWe performed a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All consecutive adult cancer patients admitted with FN secondary to intensive chemotherapy and GI symptoms (abdominal pain, diarrhea

The evolving role and utility of off-label drug use in multiple myeloma.

The treatment landscape for multiple myeloma (MM) has dramatically changed over the last three decades, moving from no US Food and Drug Administration approvals and two active drug classes to over 19 drug approvals and at least eight different active classes. The advances seen in MM therapy have relied on both a structured approach to obtaining new labels and cautious off-label drug use. Although there are country and regional differences in drug approval processes, many of the basic principles behind off-label drug use in MM can be summarized into four main categories: 1) use of a therapy pri

Paraneoplastic Syndrome After Kidney Transplantation: Frequency, Risk Factors, Differences to Paraneoplastic Occurrence of Glomerulonephritis in the Native Kidney, and Implications on Long-Term Kidney Graft Function.

Posttransplant malignancies are an important complication of solid organ transplantation. Kidney transplant recipients are at particularly high risk of cancer development. The most relevant risk factors of carcinogenesis are the use of immunosuppressive agents and oncogenic viral infections. Additionally, immune dysregulation caused by these factors may predispose to various types of organ damage. Paraneoplastic glomerular diseases are one of the most interesting and understudied cancer manifestations. The appropriate diagnosis of paraneoplastic glomerular damage can be challenging in kidney t

Pulmonary Lymphangitic Spread of Multiple Myeloma as Early Relapse after Autologous Stem Cell Transplantation.

Clinical relapses early after autologous stem cell transplantation portrays an inferior clinical outcome. Early relapse in this setting with extramedullary disease (EMD) of lung involvement in multiple myeloma is rare. To our knowledge, this is the first reported case of lymphangitic spread of myeloma with pulmonary parenchymal and pleural involvement occurring at first relapse.

Treatment of Stage 2 Medication-Induced Osteonecrosis of the Jaw: A Case Series.

Medication-induced jaw osteonecrosis (MRONJ) is a rare and serious disease with a negative impact on patients' quality of life, whose exact cause remains unclear and which may have a multifactorial origin. Although there are different therapeutic protocols, there is still no consensus. This case series evaluated three patients diagnosed with staged 2 MRONJ treated at the University of Murcia dental clinic according to the protocols described by the Spanish Society of Oral and Maxillofacial Surgery and the American Association of Oral and Maxillofacial Surgeons. Within 12 months of the applicat

Cutaneous paraneoplastic syndromes in cats: a comparative clinical review.

PRACTICAL RELEVANCE: Cutaneous paraneoplastic syndromes (CPSs) in cats represent a diverse group of rare dermatological manifestations that occur as indirect consequences of underlying neoplasia. These syndromes are thought to arise due to tumour-associated systemic effects, including dysregulation of immune responses, metabolic disturbances and aberrant production of cytokines or growth factors. Recognising CPSs is clinically relevant, as they may serve as early indicators of occult neoplasia, guiding timely diagnosis and intervention. CLINICAL CHALLENGES: Diagnosing CPSs requires a high ind

Monocyte Involvement in the Pathogenesis of Myeloproliferative Neoplasms.

Classical BCR-ABL-negative myeloproliferative neoplasms are a heterogeneous group of hematologic malignancies, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Monocytes, immune cells derived from hematopoietic stem cells, exhibit significant heterogeneity and contribute to immune regulation through cytokine secretion and differentiation into dendritic cells and macrophages. Aberrant monocytes are associated with the prognosis of MPNs, particularly PMF. Furthermore, these altered monocytes play a critical role in the pathogenesis and progression of MPNs. This

DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers.

Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total anti

Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study.

BackgroundGlioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O6 methylguanine DNA methyltransferase (MGMT) that renders the tumors resistant to temozolomide (TMZ). We hypothesized that pretreatment with bortezomib (BTZ) 48 hours prior to TMZ to deplete MGMT levels would be safe and tolerated by patients with recurrent GBM harboring unmethylated MGMT promoter. The secondary objective was to investigate whether 26S proteasome blockade may enhance differentia

Cisplatin-associated anaemia treated with subcutaneous erythropoietin. A pilot study.

In 20 patients with cisplatin-associated anaemia (haemoglobin less than 90 gl-1), recombinant human erythropoietin was administered subcutaneously three times a week on an outpatient basis. The initial dose was 50 Units Kg-1 of body weight. If response was not achieved within 3 weeks, dose was increased to 75 Units Kg-1. Using the same criteria further escalation to 100 Units Kg-1 was performed. If there was no response erythropoietin was terminated. Fifteen patients obtained an increase in haemoglobin to above 100 gl-1 which was considered as a clinical response in this study, with a dose of

A case of paraprotein-negative POEMS syndrome: Case report and literature review.

RATIONALE: POEMS syndrome is a rare monoclonal plasma cell disease. The diagnosis of POEMS requires polyradiculoneuropathy and monoclonal plasma proliferating as 2 mandatory criteria, at least 1 of the major criteria (Castleman disease, elevated vascular endothelial growth factor level, and sclerotic bone lesion), and at least 1 of the minor criteria (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, and thrombocytosis/polycythemia). This multisystem disorder is of high heterogeneity, and few variants of POEMS with no evidence of monoclonal gammopathy have