Результаты поиска

Observational study of the bisphosphonate-related osteonecrosis of jaws.

INTRODUCTION: The bisphosphonate-related osteonecrosis of the jaw was first referred to in 2003. Bisphosphonates action is focused on the osteoclasts. The drastic inhibition of the osteoclastic function is harmful for the jaws which are the only bones of the human skeleton in relative contact with the external environment. The adverse effects of the bisphosphonate-related therapy include the pathology for which they are prescribed, the atypical fractures in pathological bone. METHOD: The aim of this research was to analyze the risk factors and the treatment methods in case of osteonecrosis of

Glucosylceramide Synthase Inhibitors Induce Ceramide Accumulation and Sensitize H3K27 Mutant Diffuse Midline Glioma to Irradiation.

H3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation. Miglustat was included in the therapy protocol of two pediatric patients. The effect of H3.3K27 trimethylation on GSL composition was analyzed in ependymoma. GSI reduced the expression of the ganglioside GD2

Multiple Myeloma and Kidney Impairment at Diagnosis: A Nephrological Perspective from an Eastern European Country.

Background and Objectives: The clinical presentation and survival factors in patients with myeloma-related kidney impairment (MRKI) at diagnosis remain a topic of ongoing research, given the complex interplay between nephrology and hematology. To date, no studies have specifically reported outcomes for these patients in Eastern Europe. Materials and Methods: We conducted a retrospective, unicentric study of consecutive newly diagnosed patients with MRKI in our tertiary nephrology service in Romania between 2015 and 2020; follow-up extended until 1 September 2022, covering a study period of 90

Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article.

Multiple myeloma (MM) is a hematologic malignancy characterized by the abnormal clonal proliferation of plasma cells that may result in focal bone lesions, renal failure, anemia, and/or hypercalcemia. Recently, the diagnosis and treatment of MM have evolved due to a better understanding of disease pathophysiology, improved risk stratification, and new treatments. The incorporation of new drugs, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and high-dose chemotherapy followed by hematopoietic stem cell transplantation, has resulted in a significant improvement in

Treatment-Associated Acute Lymphoblastic Leukemia Following Autologous Hematopoietic Stem Cell Transplant and Lenalidomide Maintenance in Patients With Multiple Myeloma.

Secondary malignancies including leukemia are an increasing concern in patients with prior primary malignancies treated with alkylating agents or topoisomerase II inhibitors. These can also be referred to as therapy-related leukemia. Therapy-related leukemia most commonly results in myelodysplastic syndrome or acute myeloid leukemia. The alkylating agent can cause chromosomal aberrations typically manifest as deletions in chromosome 11 or loss of part of complete loss of chromosomes 5 and 7. Conversely, acute lymphoblastic leukemia (ALL) has been described following maintenance therapy with im

Bortezomib: the evidence of its clinical impact in multiple myeloma.

INTRODUCTION: Multiple myeloma is a relatively common and incurable form of hematologic malignancy for which there is currently no single standard therapy. Bortezomib inhibits the 20S proteasome involved in the degradation of intracellular proteins, induces apoptosis, reverses drug resistance in multiple myeloma cells, and influences their microenvironment by blocking cytokine circuits, cell adhesion and angiogenesis in vivo. AIMS: The objective of this review is to evaluate the evidence for the use of bortezomib in the treatment of multiple myeloma. EVIDENCE REVIEW: In patients with relapse

Multiple Myeloma Plasmacytoid Infiltration of the Gallbladder Presenting as Acute Cholecystitis.

Secondary distal plasmacytoma that arise from multiple myeloma is a common hematological malignancy that manifests in later stages of the disease. These plasmacytomas are known to cause extensive systemic organ damage. When extramedullary plasmacytomas reach the gallbladder or biliary ducts, expansion can mimic acute acalculous cholecystitis or cholangiocarcinoma. We report a case of a 56-year-old female with a history of aggressive course IgA κ chain multiple myeloma who presented with right upper quadrant abdominal pain with nausea and vomiting for one week duration. Her laboratory panel rev

What Is New in the Treatment of Smoldering Multiple Myeloma?

Smoldering multiple myeloma (SMM), an asymptomatic plasma cell neoplasm, is currently diagnosed according to the updated IMWG criteria, which reflect an intermediate tumor mass between monoclonal gammopathy of undetermined significance (MGUS) and active MM. However, SMM is a heterogeneous entity and individual case may go from an "MGUS-like" behavior to "early MM" with rapid transformation into symptomatic disease. This wide range of clinical outcomes poses challenges for prognostication and management of individual patients. However, initial studies showed a benefit in terms of progression or

Insulin Resistance at the Crossroads of Metabolic Inflammation, Cardiovascular Disease, Organ Failure and Cancer.

Insulin resistance (IR) describes impaired hormone signaling that triggers compensatory homeostatic responses resulting in hyperinsulinemia, increased accumulation of fatty substrates, lipotoxicity, oxidative stress, inflammation, cell death and fibrosis in target tissues. These processes ultimately lead to organ dysfunction and predispose certain individuals to various types of cancer. In this context, we will review the molecular pathogenesis and clinical significance of IR, its role in 'metaflammation', and the damage caused by IR in the pancreas, cardiovascular system, liver, and kidneys.

Association between advanced lung cancer inflammation index and acute gouty arthritis in Dalian, China: a cross-sectional study.

IntroductionAcute gouty arthritis (AGA) is an inflammatory joint disease. The advanced lung cancer inflammation index (ALI) evaluates inflammation. This study investigates the association between ALI and AGA.MethodsWe included 652 participants in this cohort study, dividing them into two groups: those with AGA and a control group without AGA. We employed logistic regression to examine the ALI-AGA relationship, using restricted cubic splines (RCS) to assess dose-response relationships, performing subgroup analyses, and conducting interaction tests. K-fold cross-validation was applied for model

Efficacy and safety of laquinimod versus placebo in relapsing-remitting multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the safety and efficacy of laquinimod in treating relapsing-remitting multiple sclerosis (RRMS). METHODS: An extensive electronic search was conducted across PubMed, Embase, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov to identify suitable studies. Risk of bias was assessed using Cochrane's Risk of Bias tool. Statistical analysis was performed using RevMan 5.4.1. RESULTS: The meta-analysis of four randomized controlled trials including 3665 patients found that laquinimod significantly reduced the annualized relapse rate compared with placebo (mean

Эффективное использование BCMA-нацеливаемого би-специализированного T антитела в реанимации LRP4+ yasthenia gravis.

Myastenia gravis (MG) — аутоиммунное заболевание, вызванное антителом, которое воздействует на нейромышечное соединение. Рефракторный MG, особенно в случаях, связанных с редким антинизкоплотным белком, связанным с рецептором липопротеина 4 (LRP4) Антитела сталкиваются со значительными трудностями в лечении. Teclistamab, биконкретный антитело, нацеленное на антигены созревания клеток B (BCMA) и CD3, перенаправляет Т клетки на плазменные клетки и утверждается для лечения нескольких миелом. Растущий интерес связан с использованием методов лечения на основе Т клеток в клеточных заболеваниях с ауто

Преодоление сопротивления CD44-overexpressing миэлома через комбинированную терапию с клетками ATRA, борцезомиба и NK.

CD44 — гликпротеин, часто переоцениваемый раком и связанный с плохим прогнозом. Мы проанализировали прогнозируемую значимость CD44 в перевыражении в миеломе (MM) и изучили терапевтическую эффективность сочетания естественной клеточной терапии убийцы (NK) с транс-ретиновой кислотой (ATRA) и борцезомибом (Bor) против CD44-overexpressing Мм. Для оценки результатов выживаемости по отношению к выражению CD44 были проанализированы клинические данные из базы данных CoMMpass. Ячейки NK были расширены за счет здоровых доноров с использованием K562-OX40L-mbIL-18/21 кормовые клетки, дополненные интерлейк

Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies.

Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients' quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition. Bisphosphonates were the main

Exploring the molecular biomarker utility of circCCT3 in multiple myeloma: A favorable prognostic indicator, particularly for R-ISS II patients.

Circular RNAs (circRNAs) are associated with the pathobiology of multiple myeloma (MM). Recent findings regarding circCCT3 support its involvement in the development and progression of MM, through microRNA sponging. Thus, we aimed to examine the expression of circCCT3 in smoldering and symptomatic MM and to assess its clinical importance. Three cell lines from plasma cell neoplasms were cultured and bone marrow aspirate (BMA) samples were collected from 145 patients with MM or smoldering MM. Next, CD138+ enrichment was performed in BMA samples, followed by total RNA extraction and reverse tran

From Bench to Bedside and Beyond: Therapeutic Scenario in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous group of clonal disorders characterized by abnormal proliferation of undifferentiated myeloid progenitors, impaired hematopoiesis, and variable response to therapy. To date, only about 30% of adult patients with AML become long-term survivors and relapse and/or disease refractoriness are the major cause of treatment failure. Thus, this is an urgent unmet clinical need and new drugs are envisaged in order to ameliorate disease survival outcomes. Here, we review the latest therapeutic approaches (investigational and approved agents) for AML treatme

Hematologic malignancies magnify the effect of body mass index on insulin resistance in cancer survivors.

Cancer survivors are at increased risk of type 2 diabetes, which usually develops from obesity and insulin resistance. Whether diabetes susceptibility is due to shared risk factors for cancer and insulin resistance or directly related to cancer and its treatment is unknown. We investigated effect modification between malignancy and body mass index (BMI) as determinants of insulin sensitivity in patients with hematologic malignancies and controls without cancer. In a cross-sectional study of 43 individuals without diabetes (20 patients with treated hematologic malignancies; 23 controls without

Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma.

BackgroundThe attenuated, genetically engineered vaccinia virus has been shown to be a promising oncolytic virus for the treatment of patients with solid tumors, through both direct cytotoxic and immune-activating effects. Whereas systemically administered oncolytic viruses can be neutralized by pre-existing antibodies, locoregionally administered viruses can infect tumor cells and generate immune responses. We conducted a phase I clinical trial to investigate the safety, feasibility and immune activating effects of intrapleural administration of oncolytic vaccinia virus (NCT01766739).MethodsE

Совпадение в полном тексте источника
… ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio. …

SC134-TCB Targeting Fucosyl-GM1, a T Cell-Engaging Antibody with Potent Antitumor Activity in Preclinical Small Cell Lung Cancer Models.

Small cell lung cancer (SCLC) is an aggressive disease with limited treatment options. Fucosyl-GM1 (FucGM1) is a glycolipid overexpressed in the majority of SCLC tumors but virtually absent from normal healthy tissues. In this study, we validate a FucGM1-targeting T cell-redirecting bispecific (TCB) antibody for the treatment of SCLC. More than 80% of patient-derived xenograft tissues of SCLC expressed FucGM1, whereas only three normal human tissues: pituitary, thymus, and skin expressed low and focal FucGM1. A FucGM1-targeting TCB (SC134-TCB), based on the Fc-silenced humanized SC134 antibody

The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial.

BACKGROUND: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed diseas