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Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy.

After several decades without maintained responses or long-term survival of patients with lung cancer, novel therapies have emerged as a hopeful milestone in this research field. The appearance of immunotherapy, especially immune checkpoint inhibitors, has improved both the overall survival and quality of life of patients, many of whom are diagnosed late when classical treatments are ineffective. Despite these unprecedented results, a high percentage of patients do not respond initially to treatment or relapse after a period of response. This is due to resistance mechanisms, which require unde

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the desi

Nanomedicine and Onco-Immunotherapy: From the Bench to Bedside to Biomarkers.

The broad relationship between the immune system and cancer is opening a new hallmark to explore for nanomedicine. Here, all the common and synergy points between both areas are reviewed and described, and the recent approaches which show the progress from the bench to the beside to biomarkers developed in nanomedicine and onco-immunotherapy.

Abstract

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Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses.

In this review, we discuss the importance of capsaicin to the current understanding of neuronal modulation of pain and explore the mechanisms of capsaicin-induced pain. We will focus on the analgesic effects of capsaicin and its clinical applicability in treating pain. Furthermore, we will draw attention to the rationale for other clinical therapeutic uses and implications of capsaicin in diseases such as obesity, diabetes, cardiovascular conditions, cancer, airway diseases, itch, gastric, and urological disorders.

The current socioeconomic and regulatory landscape of immune effector cell therapies.

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T ce

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… They promote cancer cell growth by secreting chemokines and cytokines like IL-1α, IL-1β, and TNFα and inhibit CD8+ T cells by releasing immunosuppressive factors and triggering T cell apoptosis through FAS receptors, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). …

Cobalamin deficiency, hyperhomocysteinemia, and dementia.

IntroductionAlthough consensus guidelines recommend checking serum B12 in patients with dementia, clinicians are often faced with various questions: (1) Which patients should be tested? (2) What test should be ordered? (3) How are inferences made from such testing? (4) In addition to serum B12, should other tests be ordered? (5) Is B12 deficiency compatible with dementia of the Alzheimer's type? (6) What is to be expected from treatment? (7) How is B12 deficiency treated?MethodsOn January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hype

CAR T-Cells in Multiple Myeloma: State of the Art and Future Directions.

Despite recent therapeutic advances, the prognosis of multiple myeloma (MM) patients remains poor. Thus, new strategies to improve outcomes are imperative. Chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape of B-cell malignancies, providing a potentially curative option for patients who are refractory to standard treatment. Long-term remissions achieved in patients with acute lymphoblastic leukemia and Non-Hodgkin Lymphoma encouraged its further development in MM. B-cell maturation antigen (BCMA)-targeted CAR T-cells have established outstanding results in heavi

Oncolytic myxoma virus and engineering strategies for advanced cancer immunotherapy.

In cancer immunotherapy, oncolytic viruses (OVs) offer an alternative approach to kill malignant cells by inducing cancer-specific host immune system activation. Given the ongoing need for safe and effective viral vectors for immunotherapy, non-zoonotic animal viruses have attracted significant interest. Here, we review the oncolytic myxoma virus (MYXV) and emphasize its emerging role in cancer immunotherapy. We critically discuss recent advances in cancer therapy using MYXV, primarily focused on engineered viral modifications. Furthermore, we briefly review alternative delivery strategies for

The complex price setting and reimbursement of non-industrial advanced therapy medicinal products.

BACKGROUND: Advanced Therapy Medicinal Products (ATMPs) developed under the Hospital Exemption (HE) offer innovative treatments for patients with unmet medical needs, but their pricing and reimbursement (P&R) remain fragmented and poorly understood. This paper examines the P&R landscape for HE-ATMPs developed by academic developers in Spain, based on the Spanish costing guideline and extends the analysis to HE-ATMPs developed by academic and non-profit developers across Europe. METHODS: We conducted a mixed-method, exploratory study combining literature review with interviews and email enquiri

Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy.

Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin w

Использование биомаркеров для прогнозирования ответа на транскраниальную прямую токовую стимуляцию (tDCS): систематический обзор скопинга.

ВВЕДЕНИЕ: Транскраниальная прямая токовая стимуляция (tDCS) — это неперерывная нейромодуляция с увеличивающимся количеством доказательств эффективности при лечении нейропсихиатрических состояний. Нужны биомаркеры для прогнозирования и мониторинга эффективности tDCS. Наша цель — провести систематический обзор для оценки доказательств о способности биомаркеров прогнозировать реакцию на tDCS и выявить перспективные кандидатные биомаркеры в популяции пациентов с нейропсихиатрическими заболеваниями. МЕТОДЫ: Комплексные поиски были проведены в базах данных MEDLINE и EMBASE 24/09/2023. Статьи были о

Association between platelet-white cell ratio and all-cause mortality in critically ill patients with atrial fibrillation: a retrospective cohort study.

BACKGROUND: Atrial fibrillation is common in intensive care units and portends poor prognosis. The platelet-to-white blood cell ratio is an emerging inflammatory-coagulatory biomarker with prognostic value in cardiovascular diseases. This study examines the association between platelet-white cell ratio (PWR) and all-cause mortality in this high-risk population. METHODS: In this retrospective cohort study, clinical data were obtained from the MIMIC-IV database. We included adult intensive care unit (ICU) patients with a diagnosis of atrial fibrillation. The PWR was evaluated as the primary expo

Indications and recent evidence for apheresis in children and adults with kidney diseases: a comprehensive review.

IntroductionPlasmapheresis has been a therapeutic option in kidney diseases to eliminate disease-causing autoantibodies, circulating factors, and abnormal components involved in complement pathways. We aim to systematically review the effectiveness and adverse events associated with plasmapheresis and related apheresis therapies in treating kidney diseases in paediatric and adult populations.MethodsWe searched databases including EMBASE, CINAHL, PubMed, and Cochrane Central for studies from 2010 to October 2023. The search terms included terms related to glomerulonephritis treated with plasmap

Tailored treatment strategies for cancer patients during COVID-19 pandemic.

The global pandemic of respiratory disease caused by the novel human coronavirus (SARS-CoV-2) has caused indefinite global distress, uncertainty, and disturbance. This pandemic has had direct and indirect impacts for the healthcare systems across the world, but certain subgroups of patients have been particularly affected. Among these groups are patients with cancer, who as a result of their immunosuppressed status either from the disease itself or as a consequence of treatment, are at increased risk of severe COVID-19 infection and complications. The pandemic has also led to limited resources

Essential Concepts for the Management of Metastatic Spine Disease: What the Surgeon Should Know and Practice.

Study designLiterature review.ObjectiveTo provide an overview of the recent advances in spinal oncology, emphasizing the key role of the surgeon in the treatment of patients with spinal metastatic tumors.MethodsLiterature review.ResultsTherapeutic advances led to longer survival times among cancer patients, placing significant emphasis on durable local control, optimization of quality of life, and daily function for patients with spinal metastatic tumors. Recent integration of modern diagnostic tools, precision oncologic treatment, and widespread use of new technologies has transformed the tre

Dental care for patients taking antiresorptive drugs: a literature review.

Antiresorptive drugs (ARDs), such as bisphosphonates or denosumab, that prevent bone resorption are widely used in patients with osteoporosis or with cancer that has metastasized to the bones. Although osteonecrosis of the jaw (ONJ) is a well-documented complication of ARD use, the benefits ARDs outweigh the complication. Thus, research has focused on finding ways to prevent or reduce the risk of developing ONJ. Dentists, as part of a multi-professional team, have a critical role in preventing ONJ. However, many dentists tend to hesitate to provide dental care to patients with ONJ, or tend to

Lost in Translation (LiT): IUPHAR Review 6.

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but t

Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies.

Bone metastasis is a common complication of many types of advanced cancer, including breast cancer. Bone metastasis may cause severe pain, fractures, and hypercalcemia, rendering clinical management challenging and substantially reducing the quality of life and overall survival (OS) time of breast cancer patients. Studies have revealed that bone metastasis is related to interactions between tumor cells and the bone microenvironment, and involves complex molecular biological mechanisms, including colonization, osteolytic destruction, and an immunosuppressive bone microenvironment. Agents inhibi

Sphingolipid metabolism and hematologic disorders: current understanding and future directions.

Sphingolipids are not only key structural components of cell membranes but also serve as important signaling molecules, and their metabolic homeostasis is essential for the maintenance of cellular functions. In recent years, with the advancement of technologies such as metabolomics, studies have revealed that sphingolipid metabolic abnormalities are extensively involved in the occurrence and development of various hematological disorders, including immune thrombocytopenia, myeloproliferative neoplasms, graft-versus-host disease, hereditary hematological diseases, and hematologic malignancies.