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Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

Immunosuppression in Glomerular Diseases: Implications for SARS-CoV-2 Vaccines and COVID-19.

BackgroundGlomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients.SummaryThe advent of vaccines demonstrated to be safe and efficacious against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has favorably impacted the COVID-19 pandemic epidemiology. However,

Drug repurposing for disease-modifying effects in multiple system atrophy.

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder lacking any proven disease-modifying therapy. Drug repurposing offers a strategy to accelerate the development of treatments by utilizing agents originally approved for other indications. This review summarizes repurposed drugs investigated as disease-modifying therapies for MSA, spanning preclinical in vitro and animal studies and clinical trials. We focus on agents targeting key pathogenic mechanisms in MSA-including α-synuclein aggregation (e.g., sirolimus/rapamycin, rifampicin, lithium, nilotinib, epigallocat

Drugs and Epigenetic Molecular Functions. A Pharmacological Data Scientometric Analysis.

Interactions of drugs with the classical epigenetic mechanism of DNA methylation or histone modification are increasingly being elucidated mechanistically and used to develop novel classes of epigenetic therapeutics. A data science approach is used to synthesize current knowledge on the pharmacological implications of epigenetic regulation of gene expression. Computer-aided knowledge discovery for epigenetic implications of current approved or investigational drugs was performed by querying information from multiple publicly available gold-standard sources to (i) identify enzymes involved in c

Bendamustine: safety and efficacy in the management of indolent non-hodgkins lymphoma.

Bendamustine (Treanda, Ribomustin) was recently approved by the US Food and Drug Administration (FDA) for treatment of patients with rituximab refractory indolent lymphoma and is expected to turn into a frontline therapy option for indolent lymphoma. This compound with amphoteric properties was designed in the former Germany Democratic Republic in 1960s and re-discovered in 1990s with multiple successive well-designed studies. Bendamustine possesses a unique mechanism of action with potential antimetabolite properties, and only partial cross-resistance with other alkylators. Used in combinatio

Метаболомическое исследование синдромов миэлодипластика, множественной миеломы и гомозиговой β-Талассемии.

Хроническая анемия, как правило, диагностируется у пожилых людей и служит важным показателем как реактивных, так и клональных заболеваний. Многие основные заболевания, такие, как миэллодипластические синдромы и множественная миелома, более распространены среди пожилых людей, в то время как новые терапевтические подходы превратили педиатрические расстройства слабого прогноза, такие, как бета-талассемия, в хроническое заболевание пожилых людей. Таким образом, растущая распространенность хронической анемии в пожилом возрасте в значительной степени объясняется более частыми диагностическими и тера

Septic shock in the immunocompromised cancer patient: a narrative review.

Immunosuppressed patients, particularly those with cancer, represent a momentous and increasing portion of the population, especially as cancer incidence rises with population growth and aging. These patients are at a heightened risk of developing severe infections, including sepsis and septic shock, due to multiple immunologic defects such as neutropenia, lymphopenia, and T and B-cell impairment. The diverse and complex nature of these immunologic profiles, compounded by the concomitant use of immunosuppressive therapies (e.g., corticosteroids, cytotoxic drugs, and immunotherapy), superimpose

Keyword Index for Volume 106

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Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.

Disease overviewChronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells.DiagnosisThe diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers.Prognosis and stagingTwo clinical staging systems, Rai

Ammonium metabolism rewiring in the prostate cancer microenvironment: Mechanisms and clinical prospects.

Ammonium metabolism represents a critically understudied yet pivotal driver of prostate tumorigenesis and tumor microenvironment (TME) remodeling. The interplay between tumor metabolic reprogramming and the tumor microenvironment has emerged as a critical frontier in oncology research. While previous studies on prostate cancer metabolism have predominantly focused on lipid metabolism and the Warburg effect, the role of ammonium metabolism, particularly the urea cycle in tumor immune regulation remains insufficiently explored. This metabolic reprogramming constitutes a central node connecting c

Utility of Bruton's Tyrosine Kinase Inhibitors in Light Chain Amyloidosis Caused by Lymphoplasmacytic Lymphoma (Waldenström's Macroglobulinemia).

Of the variety of immunoglobulin related amyloidosis (AL), immunoglobulin M (IgM) related AL represents only 6 to 10% of affected patients, and the majority of these cases are associated with underlying non-Hodgkin's Lymphoma including Waldenström's macroglobulinemia (WM). Ibrutinib, acalabrutinib, and zanubrutinib are Bruton tyrosine kinase (BTK) inhibitors approved for certain indolent B cell non-Hodgkin's lymphoma (NHL). BTK is a nonreceptor kinase involved in B-cell survival, proliferation, and interaction with the microenvironment. We retrospectively evaluated the tolerability and effecti

Glutamine and cancer: metabolism, immune microenvironment, and therapeutic targets.

Glutamine is the most abundant amino acid in human serum, and it can provide carbon and nitrogen for biosynthesis, which is crucial for proliferating cells. Moreover, it is widely known that glutamine metabolism is reprogrammed in cancer cells. Many cancer cells undergo metabolic reprogramming targeting glutamine, increasing its uptake to meet their rapid proliferation demands. An increasing amount of study is being done on the particular glutamine metabolic pathways in cancer cells.Further investigation into the function of glutamine in immune cells is warranted given the critical role these

Совпадение в полном тексте источника
… While the carbon in glutamine can be utilized to synthesize fatty acids and amino acids, the nitrogen in glutamine is directly engaged in the creation of purines and pyrimidines. … Glutamine also creates α-KG through redox processes, which serves as a precursor for purines, pyrimidines, and aspartate biosynthesis [ 35 ]. …

Parthenolide: pioneering new frontiers in hematological malignancies.

Hematological malignancies are the fifth most prevalent cancer category in developed countries, presenting significant treatment challenges. The side effects of chemotherapy and its non-selective nature have led researchers to explore combination therapies to enhance efficacy and improve patient outcomes. Parthenolide (PTL) emerges as a promising candidate, being the first small molecule identified for its selective action against leukemic stem cells. This article provides an overview of PTL's effects and its potential as a complementary treatment for hematological malignancies. A systematic s

Janus kinase inhibition in the treatment and prevention of graft-versus-host disease.

Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). For many years, corticosteroids have been the mainstay treatment for GVHD, but cases of steroid-refractory GVHD and the severe adverse effects of high-dose corticosteroids have increased the need for preventative and therapeutic strategies for GVHD. Due to the nature of alloreactive T cells, GVHD is inherently linked to the graft-versus-leukemia (GVL) effect, the therapeutic driving force behind stem cell transplantation. A considerable clinical ch

Совпадение в полном тексте источника
… MTX is a dihydrofolate reductase inhibitor which reduces production of thymidylate and purines, suppressing T cell reactivity and proliferation. MMF is converted to its active metabolite mycophenolic acid, which inhibits inosine monophosphate dehydrogenase, suppressing purine synthesis in T cells. …

Pneumonia in Transplant Recipients: A Comprehensive Review of Diagnosis and Management.

Transplant recipients have an increased risk of complications, including graft dysfunction and infections, which can be life-threatening if not recognized early. Pneumonia ranks as one of the most frequent complications in both solid organ and hematopoietic stem cell transplants. Clinical symptoms manifest late during infections in immunocompromised patients. An aggressive approach centered on early confirmatory diagnosis and a low threshold for empiric therapy is often the most effective strategy. The isolation of a pathogen in an upper airway sample does not necessarily mean the same organis

Pemphigus vulgaris.

Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can

Wnt inhibitors reduce the unfolded protein response and enhance bortezomib-induced cell death in multiple myeloma.

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Efficacy and Safety of Melphalan, Cyclophosphamide and Dexamethasone (MCD) as a Salvage Treatment for Patients with Relapsed/Refractory Multiple Myeloma.

This study investigated the efficacy and safety of melphalan, cyclophosphamide, and dexamethasone (MCD) as a salvage regimen for heavily treated relapsed or refractory multiple myeloma patients. We retrospectively analyzed a total of 27 patients who received the MCD regimen between April 2011 and November 2013. The MCD regimen consisted of oral melphalan 6.75 mg/m2 on days 1-4, once-weekly dose of oral cyclophosphamide 300 mg/m2 and dexamethasone 20 mg/m2 on days 1-4 and days 15-18. Each cycle was repeated every 28 days. The median age of the patients was 66 years and the MCD regimen was initi

What is the Reason That the Pharmacological Future of Chemotherapeutics in the Treatment of Lung Cancer Could Be Most Closely Related to Nanostructures? Platinum Drugs in Therapy of Non-Small and Small Cell Lung Cancer and Their Unexpected, Possible Interactions. The Review.

Over the course of several decades, anticancer treatment with chemotherapy drugs for lung cancer has not changed significantly. Unfortunately, this treatment prolongs the patient's life only by a few months, causing many side effects in the human body. It has also been proven that drugs such as Cisplatin, Carboplatin, Oxaliplatin and others can react with other substances containing an aromatic ring in which the nitrogen atom has a free electron group in its structure. Thus, such structures may have a competitive effect on the nucleobases of DNA. Therefore, scientists are looking not only for

Совпадение в полном тексте источника
… data in the literature, respectively. 25 , 33 , 34 , 47 , 66 , 117 , 125–135 After passing through the membrane, these compounds are inactivated during the hydrolysis process and then show significant affinity for proteins (cysteine sulfhydryl groups) 47 , 125–133 and nucleic acids (nitrogen atoms of purines … As we know, Platinum-derived compounds have low selectivity and react with many different compounds, structurally similar to purines containing an aromatic ring with lone pairs of electrons on the N7 atom. 57 , 102 , 198–200 One of such groups are B vitamins, which are supplied, for example, with food …

Сравнительная эффективность ритуксимаба и кладрибина при повторном излучающем многообразном склерозе: пробная эмуляция.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: В настоящее время не проводится сопоставительный анализ высокоэффективных методов лечения повторных выбросов нескольких склерозов (РРМС). Мы провели эксперимент с целью сравнения долгосрочной эффективности ритуксимаба и кладрибина. Мы оценивали эффект инициирования лечения ритуксимаба против кладрибина с использованием данных наблюдений, полученных из норвежского регистра MS и Biobank в двух университетских больницах с различными стратегиями лечения. Совокупные различия в частотности и рисках (RD) оценивались с использованием взвешенных оценок Каплан-Мейер с учетом базов