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Novel Combinatorial Approaches to Tackle the Immunosuppressive Microenvironment of Prostate Cancer.

Prostate cancer (PCa) is the second-most common cancer in men worldwide and treatment options for patients with advanced or aggressive prostate cancer or recurrent disease continue to be of limited success and are rarely curative. Despite immune checkpoint blockade (ICB) efficacy in some melanoma, lung, kidney and breast cancers, immunotherapy efforts have been remarkably unsuccessful in PCa. One hypothesis behind this lack of efficacy is the generation of a distinctly immunosuppressive prostate tumor microenvironment (TME) by regulatory T cells, MDSCs, and type 2 macrophages which have been i

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… The generation of reactive nitrogen species (RNS) and ROS by MDSCs is a potent modulator of T-cell activity through the modification of the T-cell receptor (TCR)/peptide-bound major histocompatibility complex-I (pMHC-I) and immune-activating chemokines. …

Monoclonal Antibodies Approved for Cancer Therapy

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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

The Agony of Choice-Where to Place the Wave of BCMA-Targeted Therapies in the Multiple Myeloma Treatment Puzzle in 2022 and Beyond.

Since the introduction of first-generation proteasome inhibitors and immunomodulatory agents, the multiple myeloma (MM) treatment landscape has undergone a remarkable development. Most recently, immunotherapeutic strategies targeting the B cell maturation antigen (BCMA) entered the clinical stage providing access to highly anticipated novel treatment strategies. At present, numerous different approaches investigate BCMA as an effective multi-modal target. Currently, BCMA-directed antibody-drug conjugates, bispecific and trispecific antibodies, autologous and allogeneic CAR-T cell as well as CA

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… The T cell-recruiting BsAbs activate T cells by binding CD3ε in the T-cell receptor complex, which leads to T cell activation independent of major histocompatibility complex (MHC) restriction. Furthermore, BsAbs have the ability of T cell activation in the absence of co-stimulation [ 38 , 39 ]. …

Возможности и препятствия для глубокого изучения биологии и медицины.

Глубокое обучение описывает класс алгоритмов машинного обучения, которые способны объединять исходные ресурсы в слои промежуточных характеристик. Эти алгоритмы недавно продемонстрировали впечатляющие результаты в различных областях. Биология и медицина являются богатыми данными дисциплинами, однако данные являются сложными и зачастую недопонятными. Поэтому методы глубокого обучения могут быть особенно подходящими для решения проблем в этих областях. Мы изучаем возможности углубленного изучения различных биомедицинских проблем - стационарная классификация, фундаментальные биологические процессы

Piper nigrum Extract: Dietary Supplement for Reducing Mammary Tumor Incidence and Chemotherapy-Induced Toxicity.

A low piperine fractional Piper nigrum extract (PFPE) was prepared by mixing cold-pressed coconut oil and honey in distilled water, namely, PFPE-CH. In this study, PFPE-CH was orally administered as a dietary supplement to decrease the risk of tumor formation and reduce the side effects of chemotherapeutic drugs during breast cancer treatment. The toxicity study demonstrated no mortality or adverse effects after administrating PFPE-CH at 5000 mg/kg during a 14-day observation period. Additionally, PFPE-CH at 86 mg/kg BW/day did not cause any harm to the kidney or liver function of the rats for

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… However, many tumors downregulate the expression of class 1 major histocompatibility complex (MHC) molecules, causing reduced recognition of T lymphocytes and leading to a possible decrease in the lymphocyte count [ 89 ]. …

Specific epigenetic regulators serve as potential therapeutic targets in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF), a disorder observed mostly in older human beings, is characterised by chronic and progressive lung scarring leading to an irreversible decline in lung function. This health condition has a dismal prognosis and the currently available drugs only delay but fail to reverse the progression of lung damage. Consequently, it becomes imperative to discover improved therapeutic compounds and their cellular targets to cure IPF. In this regard, a number of recent studies have targeted the epigenetic regulation by histone deacetylases (HDACs) to develop and categorise

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… The expansion of some abbreviations used in the preceding sentence are as follows: NACHT, An acronym standing for NAIP (neuronal apoptosis inhibitor protein), C2TA [major histocompatibility complex (MHC) class 2 transcription activator], HET-E (incompatibility locus protein from Podospora anserina ) …

Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy and the most common subtype of non-Hodgkin's lymphoma in adults, with one of the highest mortality rates in most developed areas of the world. More than half of DLBLC patients can be cured with standard R-CHOP regimens, however approximately 30 to 40 % of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality due to the limited therapeutic options.Recent advances in gene expression profiling have led to the identification of at least three distinct molecular

Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.

This comprehensive review investigates the complex interactions between oncogenesis and stem cells, underscoring the crucial importance of cancer stem cells (CSCs) in the mechanisms of tumorigenesis, metastatic dissemination, and resistance to therapeutic interventions. CSCs constitute a distinct subset within neoplasms, defined by unique characteristics such as the ability to self-renew, the potential to differentiate into various cellular phenotypes, and an inherent resistance to conventional treatment strategies. It is hypothesized that these properties are regulated by a multitude of signa

Recent Review on Biological Barriers and Host-Material Interfaces in Precision Drug Delivery: Advancement in Biomaterial Engineering for Better Treatment Therapies.

Preclinical and clinical studies have demonstrated that precision therapy has a broad variety of treatment applications, making it an interesting research topic with exciting potential in numerous sectors. However, major obstacles, such as inefficient and unsafe delivery systems and severe side effects, have impeded the widespread use of precision medicine. The purpose of drug delivery systems (DDSs) is to regulate the time and place of drug release and action. They aid in enhancing the equilibrium between medicinal efficacy on target and hazardous side effects off target. One promising approa

Tackling the cytokine storm in COVID-19, challenges and hopes.

The outbreak of Coronavirus disease 2019 (COVID-19) is the current world health concern, presenting a public health dilemma with ascending morbidity and mortality rates exceeding any previous viral spread, without a standard effective treatment yet. SARS-CoV-2 infection is distinguished with multiple epidemiological and pathological features, one of them being the elevated levels of cytokine release, which in turn trigger an aberrant uncontrolled response known as "cytokine storm". This phenomenon contributes to severe acute respiratory distress syndrome (ARDS), leading to pneumonia and respir

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… CQ and HCQ interfere with lysosomal activity and inhibit their function, resulting in reduced expression of the major histocompatibility complex class II (MHC II), and impaired antigen presentation [ 89 ], thus decreasing T cell activation and expression of co-stimulatory proteins [ 90 ]. …

Update on Contrast-Induced Nephropathy: Recent Developments in Its Prevention, Early Diagnosis, and Therapy.

Contrast-induced nephropathy (CIN), now more accurately referred to as contrast-induced acute kidney injury (CI-AKI), remains a major cause of hospital-acquired acute kidney injury (AKI) and is associated with increased morbidity and mortality, particularly in high-risk patients. This condition occurs following the intravascular administration of iodinated radiocontrast media (RCM), especially in individuals with pre-existing chronic kidney disease (CKD), diabetes mellitus, heart failure, advanced age, or exposure to high contrast volumes. The pathophysiology of CI-AKI is multifactorial and in

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… Biomarkers of Tubular Injury: Early Detection of Structural Damage 5.3.1. β-2 Microglobulin (β-2M) β-2M is a low-molecular-weight protein that constitutes an essential component of the major histocompatibility complex class I molecule. …

Targeting cytokine and chemokine signaling pathways for cancer therapy.

Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles in both normal physiology and the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, and growth factors like TGF-β, VEGF, and EGF, can promote or inhibit tumor growth, influence the tumor microenvironment, and impact the efficacy of cancer treatments. Recent advances in targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate the immune system, inhibit tumor progression, and o

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… In murine melanoma models, silencing the IFNGR1 gene nullified the efficacy of anti-CTLA-4. 105 IFN-γ has been validated as a promoter of T cell infiltration, upregulating major histocompatibility complex class (MHC) and PD-L1 expression in tumors while limiting the accumulation of immunosuppressive …

Translational Advances in Oncogene and Tumor-Suppressor Gene Research.

Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes-tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival-can help to unde

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

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… These scFv domains target extracellular antigens of cell-surface proteins which are expressed by cancer cells, eliminating the need for antigen presentation by major histocompatibility complex (MHC) [ 13 ] ( Figure 1 ). 2.1. Development and Recent Advances CAR T Cell Therapy 2.1.1. …

The Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia.

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment

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… Deregulation of pathways involved in T cell-mediated allorecognition has been identified as a feature and driver of AML relapses after allo-HCT, 65 including downregulation of major histocompatibility complex class II genes involved in antigen presentation, loss of HLA class I antigens in the case of …

Navigating the treatment landscape in multiple myeloma: which combinations to use and when?

Multiple myeloma is one of the most common hematological malignancies, affecting mainly elderly patients. The treatment landscape for the management of this disease has evolved significantly over the past 15 years, and a vast array of therapeutics is now available, including immunomodulatory drugs, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies. As a result, deciding which drugs to use and when, and whether these should be used in a particular order or combination, can be challenging. Although combination regimens are often associated with deeper responses and

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… Immunomodulatory drugs stimulate natural killer cells and proteasome inhibitors may enhance natural killer cell-mediated cytotoxicity by reducing expression of host protein fragments on major histocompatibility complex (MHC) class I molecules [ 20 ]. …

Chimeric antigen receptor modified T-cells for cancer treatment.

T cells engineered with the chimeric antigen receptor (CAR) are rapidly emerging as an important immunotherapy for hematologic malignancies. The anti-cluster of differentiation (CD)19 CAR-T cell therapy has been remarkably successful against refractory/relapsed acute lymphoblastic leukemia (ALL), and a complete remission rate as high as 90% was observed, in both children and adults. Although the achievement of clinical efficacy using CAR-T cell therapy for solid tumors has encountered several obstacles that were associated with the multiple mechanisms contributing to an immunosuppressive micro

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… Anatomical features of CAR constructs CARs, which effectively target specific antigens in a major histocompatibility complex (MHC)-independent manner, are recombinant receptor constructs consisting of an extracellular binding domain, a hinge region, a transmembrane (TM) domain, and an intracellular …

GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review.

Multiple myeloma is a genetically complex and heterogenous malignancy with a 5-year survival rate of approximately 60%. Despite advances in therapy, patients experience cycles of remission and relapse, with each successive line of therapy associated with poorer outcomes; therefore, therapies with different mechanisms of action against new myeloma antigens are needed. G protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a novel therapeutic target for the treatment of multiple myeloma. We review the biology and target validation of GPRC5D, and clinical data from early phas

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… T-cell–redirecting antibodies may overcome some forms of tumor-mediated evasion from the immune system because they do not require antigen presentation by major histocompatibility complex molecules, which are often downregulated or lost in tumor cells, to carry out effector functions [ 36 ]. …

Abscopal Effects in Metastatic Cancer: Is a Predictive Approach Possible to Improve Individual Outcomes?

Patients with metastatic cancers often require radiotherapy (RT) as a palliative therapy for cancer pain. RT can, however, also induce systemic antitumor effects outside of the irradiated field (abscopal effects) in various cancer entities. The occurrence of the abscopal effect is associated with a specific immunological activation in response to RT-induced cell death, which is mainly seen under concomitant immune checkpoint blockade. Even if the number of reported apscopal effects has increased since the introduction of immune checkpoint inhibition, its occurrence is still considered rare and

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… Moreover, hypoxia impacts the antigen-presenting ability of APCs by reducing major histocompatibility complex (MHC) class I molecules. This reduction is correlated with a lower recognition of cytotoxic T cells and hence a reduced killing of tumor cells by these T cells [ 135 ]. …