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NTP Toxicology and Carcinogenesis Studies of Malonaldehyde, Sodium Salt (3-Hydroxy-2-propenal, Sodium Salt) (CAS No. 24382-04-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Malonaldehyde occurs as a natural metabolic byproduct of prostaglandin biosynthesis and as an end product of polyunsaturated lipid peroxidation. Toxicology and carcinogenesis studies of malonaldehyde were conducted by administering the chemical as malonaldehyde, sodium salt, a stabilized form of malonaldehyde, in distilled water by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 weeks, and two years. The study material was 63%-79% malonaldehyde, sodium salt, 22%-38% water, and 1% or less other impurities. The water content was taken into account when the dose mixtur

Platinum-induced ototoxicity and hearing impairment in children and adolescents.

Platinum compounds play a crucial role in the treatment of solid tumours in paediatric patients, significantly improving survival rates. However, these treatments can result in hearing loss as a side-effect that can significantly impact the quality of life of young cancer survivors. Whilst the therapeutic benefits of platinum compounds in paediatric oncology are indisputable, addressing the challenge of ototoxicity remains a priority. Early and regular auditory function assessments, with tools such as audiometry, otoacoustic emissions and auditory brainstem response testing, are critical durin

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… Notably, genes such as ERCC1 , ERCC2 , ERCC4 , ERCC5 and XPC are crucial for the detoxification of platinum adducts through the nucleotide excision repair DNA pathway. …

Complementarity of surgical therapy, photobiomodulation, A-PRF and L-PRF for management of medication-related osteonecrosis of the jaw (MRONJ): an animal study.

BACKGROUND: This study aimed to evaluate the complementarity of surgical therapy, photobiomodulation (PBM), advanced platelet-rich fibrin (A-PRF), and Leukocyte and platelet-rich fibrin (L-PRF) for the management of medication-related osteonecrosis of the jaw (MRONJ). METHODS: Sixty rats underwent injection of zoledronate followed by left mandibular first and second molar extractions to induce MRONJ lesions. All rats were examined for the signs of MRONJ 8 weeks post-dental extraction. Forty-nine rats with positive signs of MRONJ were appointed to seven different groups as follows: control (Ct

Mechanisms of Chemotherapy-Induced Neurotoxicity.

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide ana

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… Some of these adducts are less efficiently repaired by the nucleotide excision repair pathway (NER), thus the DNA-platinum adducts that are not removed by NER do not allow correct transcription of the ribosomal RNA. …

Targeting the E2F1/Rb/HDAC1 axis with the small molecule HR488B effectively inhibits colorectal cancer growth.

Colorectal cancer (CRC), the third most common cancer worldwide, remains highly lethal as the disease only becomes symptomatic at an advanced stage. Growing evidence suggests that histone deacetylases (HDACs), a group of epigenetic enzymes overexpressed in precancerous lesions of CRC, may represent promising molecular targets for CRC treatment. Histone deacetylase inhibitors (HDACis) have gradually become powerful anti-cancer agents targeting epigenetic modulation and have been widely used in the clinical treatment of hematologic malignancies, while only few studies on the benefit of HDACis in

Emergency Care

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Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention.

The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death pr

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… Likewise, DNA-damage repair (DDR) is critically regulated by HDACs due to its role in modulating chromatin reorganization, maintaining the dynamic equilibrium of acetylation of DNA-damage repair proteins, as well as influencing almost all events in DNA repair such as base excision repair, nucleotide … excision repair, and mismatch repair [ 27 ]; Autophagy, with demonstrated involvement in the development, maintenance, and progression of cancer, is susceptible to regulation by HDACs. …

Cell Therapy: Types, Regulation, and Clinical Benefits.

Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non-stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review

Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma.

Glioblastoma is currently an incurable disease despite the development of a wide variety of therapeutic approaches, from surgical methods to immunotherapy. In current clinical practice, treatment typically involves a combination of existing methods, often comprising three stages: tumor resection, radiotherapy, and chemotherapy. Modern research offers improved chemotherapy strategies, as well as combinations of chemotherapy with immunotherapy. However, the efficacy of these therapies is profoundly influenced by factors such as tumor and peritumoral heterogeneity, alongside complex molecular sig

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… To overcome resistance in pediatric and adolescent patients, it may be necessary to target additional resistance mechanisms—for example, deficiencies in base excision repair. …

Unlocking the potential: advancements and applications of gene therapy in severe disorders.

INTRODUCTION: Several severe disorders, such as inherited diseases (e.g. cystic fibrosis and beta thalassemia), genetic diseases (e.g. malignant tumors and diabetes), and infectious diseases (e.g. HIV) are pose significant challenges to human health. BACKGROUND: Over the past few decades, researchers have been working on gene therapies, and currently, terrible dreams have come true. To date, the Food and Drug Administration (FDA) has approved multiple gene therapies such as Kynamro for familial hypercholesterolaemia, Exondys51 for duchenne muscular dystrophy, Spinraza for spinal muscular atro

Treatment of relapsed or refractory Hodgkin's lymphoma with lenalidomide combined with PD-1 monoclonal antibody: a case report and literature review.

The current standard treatment for relapsed or refractory Hodgkin's lymphoma involves salvage chemotherapy followed by high-dose chemotherapy and sequential autologous stem cell transplantation. However, for patients who cannot tolerate intense chemotherapy or do not meet the conditions for autologous stem cell transplantation, there is a need to explore new treatment options. We report a case of an elderly patient with multiple relapses of classical Hodgkin's lymphoma who experienced repeated disease progression despite undergoing multiple lines of treatment including novel agents such as CD3

A novel approach to enhance glioblastoma multiforme treatment efficacy: non-coding RNA targeted therapy and adjuvant approaches.

BackgroundGlioblastoma multiforme (GBM) is a lethal brain tumor. With the current gold standard chemotherapy treatment, temozolomide (TMZ), many patients do not survive beyond one year. While the urgency of researching novel treatments is understandable, the prohibitively high costs and the prolonged duration of research and clinical trials significantly delay the availability of medical advancements to the general public. This highlights the urgent need for adjuvant therapies to enhance treatment effectiveness.Main bodyRecent research has suggested the potential of repurposing FDA-approved dr

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… Methylation at N7-G and N3-A is typically reversible through the base excision repair (BER) pathway. However, methylation at the O6 position of guanine, resulting in O6-methylguanosine (O6-MeG), plays a pivotal role in TMZ's antitumor efficacy. …

Neutropenic events associated with new anticancer treatments, from pathophysiology to practice: a scoping review-NEW Group (Neutropenic Events Working Group).

INTRODUCTION: New anticancer agents are increasingly being prescribed, either in combination or as a replacement or maintenance therapy after conventional chemotherapy. Although they present certain previously unknown complications, they are also responsible for more classic hematological toxicities, such as neutropenia. Unlike conventional chemotherapy, the comprehension and management of NAN (Neutropenia Associated with Novel anticancer agent) is currently poorly codified and understood. METHODS: A literature scoping review was conducted by the NEW Group (Neutropenic Events multidisciplinar

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… Indeed, it has been shown in a mouse model that when haematopoietic stem cells (HSCs) are deficient in the base excision repair (BER) mechanism—as mediated by PARP inhibition—neutrophil production and proliferation is severely impaired compared to BER competent HSCs [ 37 ]. …

Current and Novel Alkylators in Multiple Myeloma.

A large number of novel treatments for myeloma have been developed and approved; however, alkylating drugs continue to be part of standard regimens. Additionally, novel alkylators are currently being developed. We performed a non-systematized literary search for relevant papers and communications at large conferences, as well as exploiting the authors' knowledge of the field, to review the history, current use and novel concepts around the traditional alkylators cyclophosphamide, bendamustine and melphalan and current data on the newly developed pro-drug melflufen. Even in the era of targeted

Виром ДНК связан с аутоиммунными заболеваниями и COVID-19.

Аберрантная иммунная реакция на вирусные патогены способствует патогенезу, но наше понимание патологических иммунных реакций, вызванных вирусами в вироме человека, особенно в масштабе населения, остается ограниченным. Мы проанализировали наборы данных о последовательности целых генов 6,321 Японцы, включая пациентов с аутоиммунными заболеваниями (псориаз вульгарис, ревматоидный артрит (RA), системный волшебный эритематос (SLE), легочный альвеолярный протеиноз (PAP) или множественный склероз) и коронавирусное заболевание 2019 (В тыс.COVID-19) или здоровый контроль. Систематическая количественная

[Retracted] miR‑23a suppresses pancreatic cancer cell progression by inhibiting PLK‑1 expression.

BACKGROUND: One presentation of Avoidant/Restrictive Food Intake Disorder (ARFID) is characterized by picky eating, i.e., selective eating based on the sensory properties of food. The present study has two aims. The first is to describe distress and impairment in individuals with ARFID secondary to picky eating. The second is to determine whether eating behaviors hypothesized to be specific to picky eating can differentiate picky eaters with and without ARFID from typical eaters (e.g., individuals not reporting picky or disordered eating) and individuals who strongly endorse attitudes associat

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… Homozygous mutations in the base excision repair (BER) pathway gene mutY DNA glycosylase ( MUTYH ) leads to MUTYH-associated polyposis syndrome, and heterozygous MUTYH mutations are observed in familial colorectal cancer The molecular characterisation of colorectal cancer may help identify familial …

Multidisciplinary Approach to Spinal Metastases and Metastatic Spinal Cord Compression-A New Integrative Flowchart for Patient Management.

Metastatic spine disease (MSD) and metastatic spinal cord compression (MSCC) are major causes of permanent neurological damage and long-term disability for cancer patients. The development of MSD is pathophysiologically framed by a cooperative interaction between general mechanisms of bone growth and specific mechanisms of spinal metastases (SM) expansion. SM most commonly affects the thoracic spine, even though multiple segments may be affected concomitantly. The great majority of SM are extradural, while intradural-extramedullary and intramedullary metastases are less frequently seen. The ma

Hypothesis: are neoplastic macrophages/microglia present in glioblastoma multiforme?

Most malignant brain tumours contain various numbers of cells with characteristics of activated or dysmorphic macrophages/microglia. These cells are generally considered part of the tumour stroma and are often described as TAM (tumour-associated macrophages). These types of cells are thought to either enhance or inhibit brain tumour progression. Recent evidence indicates that neoplastic cells with macrophage characteristics are found in numerous metastatic cancers of non-CNS (central nervous system) origin. Evidence is presented here suggesting that subpopulations of cells within human gliomas

Cardiac Involvement in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Cardiac involvement of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is recognized extremely rarely. In addition, most CLL/SLL patients with heart infiltration are asymptomatic. In this review, we present the results of a literature search for English language articles concerning CLL/SLL or Richter transformation with symptomatic cardiac involvement. In total, 18 well-described cases with CLL/SLL and heart infiltration were identified. Only three patients were not diagnosed with CLL/SLL before the cardiac manifestation. In other patients, cardiac CLL/SLL was diagnosed betwe

Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense.

In the present study, we evaluated the potential of the plant E. arvense against the cytotoxic and mutagenic effects induced by cyclophosphamide (chemotherapeutic agent) in the bone marrow cells of mice using the Chromosome assay (CA) and Mitotic index (MI) in vivo as the biomarkers. The study was performed following 3 protocols: pre-treatment, simultaneous treatment and post-treatment with the ethanolic extract of the plant. The results demonstrated that the plant extract was not cytotoxic and mutagenic and has a protective effect against the mutagenicity induced by cyclophosphamide in pre, s