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Комплексный номер копий с высоким разрешением и гистомолекулярный анализ диффузной глиомы в масштабах полушария, H3 G34-mutant обнаруживает общие аномалии TP53.

Диффузная глиома в масштабах полушария, Н3 G34-mutant (В тыс.DHG-H3 G34 характеризуется главным образом молекулярным профилированием метилирования и исследованиями последовательности. Мы описываем комплексную гистомолекулярную оценку, включая профили копий с высоким разрешением серии 60 DHG-H3 G34 для дальнейшего понимания спектра генетических изменений, связанных с этим типом опухолей. Случаи были подвергнуты клиническому тестированию с использованием: 187-gene мутация и синтез были нацелены на нейроонтологию следующего поколения (n = 60) и онкосканского хромосомного микроаррара (n = 26) одно

Clinical Features and Treatment Progress of Invasive Mucormycosis in Patients with Hematological Malignancies.

The incidence rate of invasive mucormycosis (IM) in patients with hematological malignancies (HMs) is increasing year by year, ranging from 0.07% to 4.29%, and the mortality rate is mostly higher than 50%. With the ongoing pandemic of COVID-19, COVID-19-associated mucormycosis (CAM) also became a global health threat. Patients with high risk factors such as active HMs, relapsed/refractory leukemia, prolonged neutropenia may still develop breakthrough mucormycosis (BT-MCR) even under the prophylaxis of Mucorales-active antifungals, and such patients often have higher mortality. Rhizopus spp. is

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design.

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology cl

Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?

Despite significant progress in cancer prevention, screening, and treatment, the still limited number of therapeutic options is an obstacle towards increasing the cancer cure rate. In recent years, many efforts were put forth to develop therapeutics that selectively target different components of the oncogenic Wnt/β-catenin signaling pathway. These include small molecule inhibitors, antibodies, and more recently, gene-based approaches. Although some of them showed promising outcomes in clinical trials, the Wnt/β-catenin pathway is still not targeted in routine clinical practice for cancer mana

Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical a

A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings.

BackgroundCytokine release triggered by a hyperactive immune response is thought to contribute to severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2)-related respiratory failure. Bruton tyrosine kinase (BTK) is involved in innate immunity, and BTK inhibitors block cytokine release. We assessed the next-generation BTK inhibitor zanubrutinib in SARS-CoV-2-infected patients with respiratory distress.MethodCohort 1 had a prospective, randomized, double-blind, placebo-controlled design; cohort 2 had a single-arm design. Adults with SARS-CoV-2 requiring hospitalization (without mechanica

An overview of the potential anticancer properties of cardamonin.

Cancer is one of the leading causes of mortality, contributing to 9.6 million deaths globally in 2018 alone. Although several cancer treatments exist, they are often associated with severe side effects and high toxicities, leaving room for significant advancements to be made in the field. In recent years, several phytochemicals from plants and natural bioresources have been extracted and tested against various human malignancies using both in vitro and in vivo preclinical model systems. Cardamonin, a chalcone extracted from the Alpinia species, is an example of a natural therapeutic agent that

Нацеливание БКМА на многочисленные миеломы: всеобъемлющий обзор иммунотерапевтических стратегий и клинических результатов.

Множественная миелома (ММ) является второй по распространенности гематологическая гелингология и остается неизлечимой, что подчеркивает настоятельную потребность в новых терапевтических стратегиях. В. Антиген созревания клеток (BCMA), выраженный преимущественно на зрелых лимфоцитах B, играет важнейшую роль в активации и созревании клеток B. Растущие данные указывают на участие BCMA в росте опухоли, метастазе и раковом стебле, что делает его многообещающей терапевтической целью. В настоящем обзоре содержится всеобъемлющий обзор ориентированных на БКМА иммунотерапевтических стратегий в ММ, включ

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… At low concentration, amanitin effectively binds to RNA polymerase II in eukaryotic cells, inhibiting RNA transcription regardless of the proliferation state of the target cells. …

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

Oncolytic Viruses for Cancer Therapy in Dogs.

Cancer remains the leading cause of death in domestic dogs. Conventional therapeutic approaches, including surgery, chemotherapy, and radiotherapy, frequently fail to achieve sustained remission or stabilization. Oncolytic virotherapy, a rapidly advancing therapeutic modality in human oncology, is emerging as a novel strategy in veterinary medicine. This systematic review summarizes current knowledge on the application of oncolytic viruses (OVs) in canine cancer treatment, focusing on their mechanisms of action, safety profiles, and clinical efficacy. We evaluate diverse OV platforms, includin

Molecular Profiling of Circulating Tumour Cells and Circulating Tumour DNA: Complementary Insights from a Single Blood Sample Utilising the Parsortix® System.

The study of molecular drivers of cancer is an area of rapid growth and has led to the development of targeted treatments, significantly improving patient outcomes in many cancer types. The identification of actionable mutations informing targeted treatment strategies are now considered essential to the management of cancer. Traditionally, this information has been obtained through biomarker assessment of a tissue biopsy which is costly and can be associated with clinical complications and adverse events. In the last decade, blood-based liquid biopsy has emerged as a minimally invasive, fast,

Navigating the Landscape of Exosomal microRNAs: Charting Their Pivotal Role as Biomarkers in Hematological Malignancies.

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically

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… The first step occurs in the nucleus, where miRNA genes are transcribed into primary transcripts (pri-mRNA) by RNA polymerase II. These transcripts may present hairpin-like structures, which are subsequently processed and lead to the formation of 80-nucleotide-long stem-loop precursor miRNAs. …

Long non-coding RNAs in bone metastasis: progresses and perspectives as potential diagnostic and prognostic biomarkers.

In a precision medicine perspective, among the biomarkers potentially useful for early diagnosis of cancers, as well as to define their prognosis and eventually to identify novel and more effective therapeutic targets, there are the long non-coding RNAs (lncRNAs). The term lncRNA identifies a class of non-coding RNA molecules involved in the regulation of gene expression that intervene at the transcriptional, post-transcriptional, and epigenetic level. Metastasis is a natural evolution of some malignant tumours, frequently encountered in patients with advanced cancers. Onset and development of

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… lncRNAs classification lncRNAs are transcribed mainly by RNA polymerase II, following they are 5′ capped, spliced, and 3′ polyadenylated, but as result they do not encode proteins because of the lacking of an open reading frame (ORF) ( 17 ). …

Molecular glue degrader for tumor treatment.

Targeted Protein Degradation (TPD) represented by Proteolysis-Targeting Chimeras (PROTAC) is the frontier field in the research and development of antitumor therapy, in which oral drug HP518 Receives FDA Proceed Authorization for its IND Application for Prostate Cancer Treatment. Recently, molecular glue, functioning via degradation of the target protein is emerging as a promising modality for the development of therapeutic agents, while exhibits greater advantages over PROTAC, including improved efficiency, resistance-free properties, and the capacity to selectively target "undruggable" prote

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… CDK12 assumes a critical role in transcriptional regulation by promoting the phosphorylation of RNA polymerase II, thereby influencing RNA splicing, DNA damage response, and maintaining genomic stability ( 77 – 79 ). …

Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation.

Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthet

miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1.

MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified S

Clinical application of minimal residual disease detection by ctDNA testing in non-small cell lung cancer: a narrative review.

Background and objectiveIn recent years, significant advancements have been achieved in the treatment of non-small cell lung cancer (NSCLC), leading to prolonged patient survival; however, a subset of NSCLC patients may experience recurrence or distant metastasis following initial successful treatment. This phenomenon may be attributed to the presence of minimal residual disease (MRD) that remains undetectable by conventional imaging or laboratory techniques post-treatment. The potential sources of tumor recurrence (MRD), are significantly associated with adverse patient prognosis; therefore,

Anti-BCMA/CD19 CAR T cell therapy in patients with refractory generalized myasthenia gravis: a single-arm, phase 1 trial.

BACKGROUND: Treating refractory generalized myasthenia gravis is still a big challenge, so new treatments are needed. Several studies have shown the potential of chimeric antigen receptor (CAR) T cell therapy in the treatment of autoimmune diseases. However, no clinical trial of bispecific CAR T cells targeting refractory myasthenia gravis has been done. We developed autologous anti-B-cell maturation antigen (BCMA) and CD19 bispecific CAR T cells to evaluate the safety and efficacy in refractory myasthenia gravis. METHODS: This single-arm, phase 1 trial (ChiCTR2200061267) was conducted at the

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

Перепрофилированный активатор Nrf2 диметилфумарат спасает мышцы воспаление и фиброз в отягченной мышиной модели мышечной дистрофии Дученна.

В унаследованных нейромускульных болезнях мышечная дистрофия Дюченна (ДМД) глюкокортикоиды значительно медленнее прогрессируют, но в то же время создают достаточно серьезные побочные эффекты, исключающие применение в значительной части пациентов. Распространяя наши выводы о том, что в результате острого лечения с УЛХ были одобрены многочисленные склерозные препараты, диметилфумарат (ДМФ), спасающая мышечную патологию у молодых мышей Mdx, мы намеревались провести доклиническое тестирование на перевод. Чтобы усилить фенотип болезни у взрослых мышц mdx, у которых обычно нет эквивалентной человече