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Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13.

Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe.Design Retrospective cohort study.Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after marke

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets.

Unlike traditional cancer therapies, such as surgery, radiation and chemotherapy that are typically non-specific, cancer immunotherapy harnesses the high specificity of a patient's own immune system to selectively kill cancer cells. The immune system is the body's main cancer surveillance system, but cancers may evade destruction thanks to various immune-suppressing mechanisms. We therefore need to deploy various immunotherapy-based strategies to help bolster the anti-tumour immune responses. These include engineering T cells to express chimeric antigen receptors (CARs) to specifically recogni

Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination.

The stromal microenvironment regulates mammary gland development and tumorigenesis. In normal mammary glands, the stromal microenvironment encompasses the ducts and contains fibroblasts, the main regulators of branching morphogenesis. Understanding the way fibroblast signaling pathways regulate mammary gland development may offer insights into the mechanisms of breast cancer (BC) biology. In fact, the unregulated mammary fibroblast signaling pathways, associated with alterations in extracellular matrix (ECM) remodeling and branching morphogenesis, drive breast cancer microenvironment (BCM) rem

Vaccination in Oncology Patients: Evidence, Clinical Challenges, and Future Directions.

This narrative review provides a comprehensive synthesis of patients with cancer disproportionately affected by vaccine-preventable infectious diseases due to malignancy-related immune dysfunction and treatment-induced immunosuppression. Vaccination represents a cornerstone of supportive care in oncology; however, vaccine uptake remains suboptimal and immune responses are frequently attenuated, particularly in patients with hematological malignancies and those receiving highly immunosuppressive therapies. This review provides a comprehensive synthesis of current evidence on vaccine immunogenic

Senescent T cells: Beneficial and detrimental roles.

As the thymus involutes during aging, the T-cell pool has to be maintained by the periodic expansion of preexisting T cells during adulthood. A conundrum is that repeated episodes of activation and proliferation drive the differentiation of T cells toward replicative senescence, due to telomere erosion. This review discusses mechanisms that regulate the end-stage differentiation (senescence) of T cells. Although these cells, within both CD4 and CD8 compartments, lose proliferative activity after antigen-specific challenge, they acquire innate-like immune function. While this may confer broad i

Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.

Recent advances in immunotherapy have transformed the therapeutic landscape of gynecological cancers; however, durable responses remain limited by tumor heterogeneity and immune evasion mechanisms. Emerging evidence highlights epigenetic modifications comprising of DNA methylation, histone modifications, and RNA methylation as pivotal regulators of the tumor immune microenvironment and immunotherapy efficacy. This review comprehensively explores how these epigenetic alterations modulate immune cell infiltration, antigen presentation, immune checkpoint expression, and tumor immunogenicity acros

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… HDACi’s role in immunotherapy is underscored by their ability to amplify tumor-specific immunity through enhanced antigen release and cross-priming by antigen-presenting cells (APCs), linking direct tumor cell targeting with robust immune activation, a synergy that holds potential for combination with …

Interleukins in cancer: from biology to therapy.

Interleukins and associated cytokines serve as the means of communication for innate and adaptive immune cells as well as non-immune cells and tissues. Thus, interleukins have a critical role in cancer development, progression and control. Interleukins can nurture an environment enabling and favouring cancer growth while simultaneously being essential for a productive tumour-directed immune response. These properties of interleukins can be exploited to improve immunotherapies to promote effectiveness as well as to limit side effects. This Review aims to unravel some of these complex interactio

A review of evidence supporting amyloid beta reduction as a surrogate endpoint in Alzheimer's disease.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease driven by pathological depositions of proteins that accumulate over decades. Compelling genetic and neurobiological evidence suggests that amyloid accumulation in the brain initiates and drives early-stage AD. Measurement of fibrillar amyloid has been pivotal to the development and approval of disease-slowing treatments. Various biomarkers of AD pathophysiology provide evidence of target engagement and downstream effects on disease progression, and their use as surrogate endpoints may help identify and expeditiously bring ne

Ageing, autoimmunity and arthritis: senescence of the B cell compartment - implications for humoral immunity.

Immunosenescence is associated with a decline in both T and B lymphocyte function. Although aged individuals have normal numbers of B cells in the periphery and are capable of mounting robust humoral responses, the antibodies produced are generally of lower affinity and are less protective than those produced by young animals. Here we review multiple studies that address the mechanisms that contribute to this decline. Taken together, these studies suggest that age-associated loss of the ability to generate protective humoral immunity results in part from reduced B lymphopoiesis. As the output

Выражение Brd4 в CD4 T клеток и в микроглии поощряет нейроинфламмацию в экспериментальном аутоиммунном энцефаломиелите.

Микроглии являются постоянными врожденными иммунными клетками центральной нервной системы (СНС), которые обеспечивают антимикробную защиту, но также способствуют нейроинфламмации. BRD4 — читатель хроматинов, связывающий себя с ацетилированными гистонами и направляющий транскрипцию множества генов. Однако неизвестно, регулирует ли и каким образом БРД4 функцию микроглии. Мы рассмотрели роль микроглии и BRD4 в нейро-воспалительном заболевании, экспериментальном аутоиммунном энцефаломиелите (EAE), модели мыши для множественных склерозов. Ранее сообщалось, что в EAE при первоначальной активации Т к

The impact of gut microbial signals on hematopoietic stem cells and the bone marrow microenvironment.

Hematopoietic stem cells (HSCs) undergo self-renewal and differentiation in the bone marrow, which is tightly regulated by cues from the microenvironment. The gut microbiota, a dynamic community residing on the mucosal surface of vertebrates, plays a crucial role in maintaining host health. Recent evidence suggests that the gut microbiota influences HSCs differentiation by modulating the bone marrow microenvironment through microbial products. This paper comprehensively analyzes the impact of the gut microbiota on hematopoiesis and its effect on HSCs fate and differentiation by modifying the b

IL-6/IL-12 суперсемейство цитокинов и регламентируемых лимфоцитов играет важнейшую роль в этиологии и борьбе с аутоиммунными заболеваниями CNS.

Цитокины влияют на решения наивных лимфоцитов о клеточной порче и определяют исход иммунной реакции путем подачи сигналов, регулирующих инициирование, интенсивность и продолжительность иммунной реакции. Вместе с тем аномальное регулирование физиологических уровней цитокина способствует развитию аутоиммунных и других подстрекательских заболеваний. Сверхсемейство цитокинов Interleukin 6 (IL-6)/IL-12 оказывает глубокое влияние на все аспекты иммунитета хостинга, и в ходе этого обзора мы уделяем особое внимание сигнальным путям, которые способствуют выполнению их функций, с уделением особого внима

Tumor Vaccines: Unleashing the Power of the Immune System to Fight Cancer.

This comprehensive review delves into the rapidly evolving arena of cancer vaccines. Initially, we examine the intricate constitution of the tumor microenvironment (TME), a dynamic factor that significantly influences tumor heterogeneity. Current research trends focusing on harnessing the TME for effective tumor vaccine treatments are also discussed. We then provide a detailed overview of the current state of research concerning tumor immunity and the mechanisms of tumor vaccines, describing the complex immunological processes involved. Furthermore, we conduct an exhaustive analysis of the con

Dissecting the role of bone marrow stromal cells on bone metastases.

Tumor-induced bone disease is a dynamic process that involves interactions with many cell types. Once metastatic cancer cells reach the bone, they are in contact with many different cell types that are present in the cell-rich bone marrow. These cells include the immune cells, myeloid cells, fibroblasts, osteoblasts, osteoclasts, and mesenchymal stem cells. Each of these cell populations can influence the behavior or gene expression of both the tumor cells and the bone microenvironment. Additionally, the tumor itself can alter the behavior of these bone marrow cells which further alters both t

Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine.

CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated proteins) has undergone marked advancements since its discovery as an adaptive immune system in bacteria and archaea, emerged as a potent gene-editing tool after the successful engineering of its synthetic guide RNA (sgRNA) toward the targeting of specific DNA sequences with high accuracy. Besides its DNA editing ability, further-developed Cas variants can also edit the epigenome, rendering the CRISPR-Cas system a versatile tool for genome and epigenome manipulation and a pioneering force in precision medic

Leveraging the bacteria for enhanced cancer immunotherapy: from a perspective of synthetic biology.

In recent years, synthetic biology has been widely applied to engineer and program cellular behaviors. Using this approach, bacteria can be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites. To further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors). This review su

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… This cascade promotes CD8⁺ T cell cross-priming and IFN- γ production, establishing a proimmunogenic milieu. …

A Comprehensive Biological and Clinical Perspective Can Drive a Patient-Tailored Approach to Multiple Myeloma: Bridging the Gaps between the Plasma Cell and the Neoplastic Niche.

There is a broad spectrum of diseases labeled as multiple myeloma (MM). This is due not only to the composite prognostic risk factors leading to different clinical outcomes and responses to treatments but also to the composite tumor microenvironment that is involved in a vicious cycle with the MM plasma cells. New therapeutic strategies have improved MM patients' chances of survival. Nevertheless, certain patients' subgroups have a particularly unfavorable prognosis. Biological stratification can be subdivided into patient, disease, or therapy-related factors. Alternatively, the biological sig

Compulsive sexual behavior, religiosity, and spirituality: A systematic review.

Abstract Background and aims In recent years, increasing attention has been given to the relationship between compulsive sexual behavior (CSB), religiosity, and spirituality. This review summarizes research examining the relationship CSB has with religiosity and spirituality, clarifying how these constructs inform the assessment and treatment of this syndrome. Methods The present paper reviews research published through August 1, 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Only studies providing quantitative analyses were included. Re

Oleocanthal as a Multifunctional Anti-Cancer Agent: Mechanistic Insights, Advanced Delivery Strategies, and Synergies for Precision Oncology.

Oleocanthal (OC), a secoiridoid phenolic compound exclusive to extra virgin olive oil (EVOO), has emerged as a promising nutraceutical with multifaceted anti-cancer properties. Despite its well-characterized anti-inflammatory and antioxidant effects, the mechanistic breadth and translational potential of OC in oncology remain underexplored and fragmented across the literature. This comprehensive review synthesizes and critically analyzes recent advances in the molecular, pharmacological, and translational landscape of OC's anti-cancer activities, providing an integrative framework to bridge pr

Evaluating the safety and feasibility of allogeneic NK cell infusion in high-risk lymphoma patients post-autologous stem cell transplantation.

Lymphoma, a cancer with poor prognosis is a growing global health challenge that encompasses two primary types, Hodgkin (HL) and non-Hodgkin lymphoma (NHL), each further divided into various subtypes with distinct biological behaviors. Conventional therapeutic strategies include chemotherapy, radiation, surgery, and autologous hematopoietic stem cell transplantation (auto-HSCT). Natural killer (NK) cells exhibit intrinsic cytotoxicity against tumor cells without the need for prior immunization or activation. In this prospective clinical trial, we evaluated the feasibility of allogeneic NK cell