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Contemporary patient-tailored treatment strategies against high risk and relapsed or refractory multiple myeloma.

Recurrence of disease due to chemotherapy drug resistance remains a major obstacle to a more successful survival outcome of multiple myeloma (MM). Overcoming drug resistance and salvaging patients with relapsed and/or refractory (R/R) MM is an urgent and unmet medical need. Several new personalized treatment strategies have been developed against molecular targets to overcome this drug resistance. There are several targeted therapeutics with anti-MM activity in clinical pipeline, including inhibitors of anti-apoptotic proteins, monoclonal antibodies, antibody-drug conjugates, bispecific antibo

Comprehensive analysis of pan-cancer reveals potential of ASF1B as a prognostic and immunological biomarker.

BackgroundAnti-silencing function 1 (ASF1) is a conserved histone H3-H4 chaperone protein. ASF1B, a paralog of ASF1, acts by promoting cell proliferation and influencing cell cycle progression. Although there is some evidence demonstrating that ASF1B plays a key role in the development, progression, and prognosis of certain cancers, there are no pan-cancer analyses of ASF1B.MethodsWe used a range of bioinformatics approaches to investigate the predictive role of ASF1B, including its correlation with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironm

Потенциальная роль TNFRSF12A в установлении связи между глиобластомой и болезнью Альцгеймера через общие пути подавления опухолей.

Гены, подавляющие опухоль, являются критическими регуляторами клеточного гомеостаза и широко изучаются в области онкологической биологии. Однако их роль в нейродегенеративных заболеваниях, особенно в болезни Альцгеймера, остается слабой. Недавние данные об обратной связи между раком и АД указывают на существование общих молекулярных механизмов. Мы провели комплексный анализ для выявления ТГС, которые могут участвовать как в AD, так и в глиобластоме (GBM), с использованием менделийской случайности, транскриптомного профилирования (булка и одноклеточная RNA-seq), вывода в отношении связи между к

MMSET: role and therapeutic opportunities in multiple myeloma.

Recurrent chromosomal translocations are central to the pathogenesis, diagnosis, and prognosis of hematologic malignancies. The translocation t(4; 14)(p16; q32) is one of the most common translocations in multiple myeloma (MM) and is associated with very poor prognosis. The t(4; 14) translocation leads to the simultaneous overexpression of two genes, FGFR3 (fibroblast growth factor receptor 3) and MMSET (multiple myeloma SET domain), both of which have potential oncogenic activity. However, approximately 30% of t(4; 14) MM patients do not express FGFR3 and have poor prognosis irrespective of F

Моноклональная антитела в Смолдингах Множественная Миелома и Моноклональная Гаммопатия Неопределенной Значимости: Текущий статус и будущие направления.

Моноклональные антитела (MoAbs), предназначенные для нескольких клеточных рецепторов, значительно улучшили прогноз множественных миелом (MM). Их высокая эффективность и безопасность поднимают вопрос о том, влияет ли на естественный ход болезни более раннее терапевтическое вмешательство в моноколональную гаммопатию неопределенного значения (МГУС) и задушающую миелому (ШМ). ММ предшествует клинически признанным условиям, таким, как МГУС и SMM. В рамках многочисленных исследований изучается биология заболеваний и иммунный профиль SMM и MGUS, с тем чтобы разгадать сложную связь между иммуноконтрол

Therapeutic Potential of CAR-CIK Cells in Acute Leukemia Relapsed Post Allogeneic Stem Cell Transplantation.

Adoptive cellular therapy with donor-derived T cells has always been an attractive strategy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to reduce the risk of relapse in acute myeloid and lymphoid leukemias. Donor lymphocyte infusion (DLI) is still the best-established option, especially in the preemptive phase when measurable residual disease (MRD) becomes positive and in the prophylactic setting-when MRD is not detectable. However, the clinical benefit of DLI is counterbalanced by the possible onset of graft-versus-host disease (GvHD), which continues to restrict its

Advancements in metastatic spinal cord compression treatment: a narrative review of innovations, challenges, and future directions.

ObjectiveTo synthesize recent advancements in metastatic spinal cord compression (MSCC) treatment, evaluating their efficacy in improving neurological function, pain relief, survival, and quality of life.BackgroundMSCC is an oncologic emergency caused by the progression of cancer to the spine and is prevalent in approximately 3-5% of all cancer patients, with a relatively higher incidence of breast, prostate, and lung cancers. MSCC can lead to irreversible paralysis due to loss of vital sensory and motor functions, thus requiring an immediate diagnosis and treatment.MethodsA systematic PubMed

Chimeric Antigen Receptor T-Cell Revolution Remodeling Immunity to Conquer Autoimmune Disease.

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking technology in tumor immunotherapy, has demonstrated unprecedented potential in the field of autoimmune diseases in recent years. This article provides a systematic review of the developmental trajectory and core concepts of CAR-T-cell therapy in autoimmune diseases, emphasizing its conceptual evolution from traditional "killing" strategies to "precision immune remodeling". Leveraging multitarget approaches (e.g., CD19 and B-cell maturation antigen) and chimeric autoantigen receptor technology, it achieves efficient elimination

Recent progress on the effects of microRNAs and natural products on tumor epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a biological process of phenotypic transition of epithelial cells that can promote physiological development as well as tissue healing and repair. In recent years, cancer researchers have noted that EMT is closely related to the occurrence and development of tumors. When tumor cells undergo EMT, they can develop enhanced migration and local tissue invasion abilities, which can lead to metastatic growth. Nevertheless, two researches in NATURE deny its necessity in specific tumors and that is discussed in this review. The degree of EMT and the detection

Castleman Disease and Kaposi Sarcoma: A Review of the Literature and a Case Series.

Castleman disease and Kaposi sarcoma (KS) are both associated with infection by human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). This virus plays a critical role in the pathogenesis of both conditions, particularly in immunocompromised individuals, such as those with HIV/AIDS. Multicentric Castleman disease (MCD) generally presents with systemic inflammatory symptoms, lymphadenopathy, and organ dysfunction, while Kaposi sarcoma typically appears as vascular tumors on the skin, with occasional involvement of mucous membranes or internal organs. We prese

Центральная ингибиция TYK2 идентифицирует TYK2 как ключевой нейроиммунный модулятор.

GWAS выявила тирозиновую киназу 2 (TYK2) в многочисленных провокационных расстройствах, в частности защитную гипоморфическую аллею TYK2 (P1104A) в множественных склерозах (MS). Поврежденный TYK2 сигнал в центральной нервной системе (CNS) может вызывать защитное воздействие аллеля TYK2 P1104A в MS. Мы использовали ингибиторы TYK2 (cTYK2i) в дополнение к периферически ограниченному ингибитору TYK2 (pTYK2i; BMS-986165) для того, чтобы рассеять влияние центрального ингибитора TYK2 в различных моделях нейроинфламмации. В то время как PTYK2i не оказывал существенного воздействия, cTYK2i уменьшили кл

How I approach smoldering multiple myeloma.

The current standard of care in smoldering multiple myeloma (SMM) is close surveillance, outside of clinical trials. Efforts are being made to understand the pathobiologic process that leads to the progression of SMM to active MM. This review provides a critical description of available data, including risk factors and risk models of progression, as well as clinical trials investigating interventions for this patient population. We describe 2 cases in which patients were seen before the concept of a myeloma-defining event was established. Today, based on the International Myeloma Working Group

Machine Learning Meets Cancer.

The role of machine learning (a part of artificial intelligence-AI) in the diagnosis and treatment of various types of oncology is steadily increasing. It is expected that the use of AI in oncology will speed up both diagnostic and treatment planning processes. This review describes recent applications of machine learning in oncology, including medical image analysis, treatment planning, patient survival prognosis, and the synthesis of drugs at the point of care. The fast and reliable analysis of medical images is of great importance in the case of fast-flowing forms of cancer. The introductio

Current and Emerging Therapeutic Targets for the Treatment of Cholangiocarcinoma: An Updated Review.

Cholangiocarcinoma is a malignancy of the bile ducts that is often associated with late diagnosis, poor overall survival, and limited treatment options. The standard of care therapy for cholangiocarcinoma has been cytotoxic chemotherapy with modest improvements in overall survival with the addition of immune checkpoint inhibitors. The discovery of actionable mutations has led to the advent of targeted therapies against FGFR and IDH-1, which has expanded the treatment landscape for this patient population. Significant efforts have been made in the pre-clinical space to explore novel immunothera

Risk Assessment and Risk-Adapted Treatment Selection: A Case-Based Approach for Chronic Lymphocytic Leukemia.

Selected Patient Cases From the APSHO Regional Lecture Series INTRODUCTION As the official publication of the Advanced Practitioner Society for Hematology and Oncology (APSHO), JADPRO is pleased to offer Part 3 of an accredited educational activity based on the recently concluded APSHO Regional Lecture Series. Hosted in collaboration with major cancer centers around the country, the APSHO Regional Lecture Series brought case-based didactic presentations and skills workshops to advanced practitioners. In the spirit of JADPRO, three accredited Grand Rounds articles by Beth Eaby-Sandy, MSN, CRNP,

Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.

The tumor suppressor p53, often referred to as the “guardian of the genome,” is mutated in more than half of human cancers. These mutations have a significant impact on cancer biology and response to therapy. p53 mutations involve a range of changes that interfere with DNA binding, eliminate tumor suppressor functions, and, in many cases, confer dominant-negative or gain-of-function characteristics that actively promote oncogenesis. These mutations are closely linked to poor clinical outcomes and resistance to standard treatments. This review examines the impact of p53 mutations on cancer ther

Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.

Colorectal cancer (CRC) remains a significant global health challenge, ranking third in incidence and second in mortality among cancers worldwide. This review addresses the complex landscape of CRC, focusing on incidence, mortality trends, preventive strategies, and the evolving therapeutic approaches, particularly highlighting the role of platinum-based drugs like oxaliplatin (OXP). It also underscores the increasing burden of CRC, with factors such as westernized diets, aging populations, and genetic predispositions contributing to its prevalence. Therapeutically, early detection greatly enh

New approaches for cancer treatment: antitumor drugs based on gene-targeted nucleic acids.

Currently, the main way to fight cancer is still chemotherapy. This method of treatment is at the height of its capacity, so, setting aside the need for further improvements in traditional treatments for neoplasia, it is vital to develop now approaches toward treating malignant tumors. This paper reviews innovational experimental approaches to treating malignant malformations based on the use of gene-targeted drugs, such as antisense oligonucleotides (asON), small interfering RNA (siRNA), ribozymes, and DNAzymes, which can all inhibit oncogene expression. The target genes for these drugs are t

Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells' Escape from the Bone Marrow Microenvironment.

Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling survival compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population of MM survivors exceeding the 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized by extramedullary disease and dominant proliferative clones, despite these highly effective treatments. To build upon these advances, it is crucial to develop m

Окисляющий стресс и воспаление в патогенезе неврологических расстройств: механизмы и последствия.

Нейрозащита — это активный подход к защите нервной системы, включая мозг, спинной мозг и периферийные нервы, путем предотвращения или ограничения повреждения нервных клеток и других компонентов. Она защищает центральную нервную систему от повреждений от острых и прогрессивных нейродегенеративных расстройств. Окисляющий стресс, дисбаланс между естественными механизмами защиты тела и образованием реактивных видов кислорода, имеет решающее значение для развития неврологических расстройств. Из-за высокой скорости метаболизма и потребления кислорода мозг особенно уязвим к окисляющему стрессу. Чрезм

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… Technological advances like Comparative Genomic Hybridization array (aCGH) and Next-Generation Sequencing (NGS) enable biomarker development and diagnostic applications. Nonetheless, healthcare structures need to be revised to ensure equitable access to NGS-based diagnosis. …