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Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induc

Biological characteristics of γδT cells and application in tumor immunotherapy.

Human γδT cells are a special immune cell type which exist in small quantities in the body, do not require processing and presentation for antigen recognition, and have non-major histocompatibility complex (MHC)-restricted immune response. They play an important role in the body's anti-tumor, anti-infection, immune regulation, immune surveillance and maintenance of immune tolerance. This article reviews the generation and development of human γδT cells, genetic characteristics, classification, recognition and role of antigens, and research progress in tumor immunotherapy.

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… The antigens recognized by γδT cells currently found mainly include MHC and MHC-like molecules, heat shock proteins (HSP), DNA mismatch repair related proteins (MSH2), phosphorylated antigens, and those presented by CD1a, CD1c, and CD1d in the CD1 family Lipid antigens and so on ( Sebestyen et al., 2020 …

The Fifth International Meeting of ISEV, ISEV2016, Rotterdam, The Netherlands, 4 - 7 May, 2016.

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Current trends in theranostic applications of extracellular vesicles in cancer.

BackgroundExtracellular vesicles (EVs) play an integral role in cancer biology, influencing tumor progression, metastasis, and tumor microenvironment. Due to their distinctive molecular composition, including proteins, nucleic acids, and lipids, EVs present a promising candidate for cancer diagnostics and precision therapeutics.MethodsThis review was conducted by looking up recent studies obtained through PubMed, Scopus, and Web of Science databases using targeted keywords such as "Extracellular Vesicles," "Cancer Therapy," "Biomarkers," "Exosomes," "Tumor Microenvironment," and "Precision Med

Hijacking the helpers: platelet and neutrophil trafficking in AML and therapeutic exploitation.

Acute myeloid leukemia (AML) remains one of the most aggressive and treatment-resistant hematologic malignancies, driven by clonal expansion of immature myeloid blasts in the bone marrow and peripheral blood. Current therapies-chemotherapy and targeted agents-are limited by poor marrow penetration, systemic toxicity, and rapid development of resistant clones, leaving long-term survival rates low. Clinicians face the persistent challenge of delivering effective therapy while minimizing harm. Platelets and neutrophils-beyond their classical roles in hemostasis and innate immunity-actively suppor

Genome agnostic, multi-level non-oncogene addiction-based systems pharmacology for rescuing metastatic relapsed/refractory neoplasias.

Rescue therapies for relapsed/refractory (r/r) metastatic neoplasias present significant unmet needs. Tumor tissue editing regimen for 13 r/r tumor types, carcinomas, sarcomas and hematologic neoplasias, included in 15 phase I/II trials, nuclear/cytokine receptor agonists, pioglitazone, plus/minus dexamethasone or all-trans retinoic acid or interferon-α to counterbalance tumor tissue homeostasis and reprogramming of cancer hallmarks, stress response inhibitors, COX-2 inhibitor, everolimus, lenalidomide, or clarithromycin, and a stress response inducer, low-dose metronomic chemotherapy with tre

The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.

Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potent

Implementing Curcumin in Translational Oncology Research.

Most data published on curcumin and curcumin-based formulations are very promising. In cancer research, the majority of data has been obtained in vitro. Less frequently, researchers used experimental animals. The results of several clinical studies are conclusive, and these studies have established a good foundation for further research focusing on implementing curcumin in clinical oncology. However, the issues regarding timely data reporting and lack of disclosure of the exact curcumin formulations used in these studies should not be neglected. This article is a snapshot of the current status

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… However, no statistically significant difference between treated and placebo group was found [ 64 ] COMBINED Cell Culture Models | Animal Models Chemosensitization to 5-FU (5-fluorouracil) of DNA mismatch repair (MMR)-deficient and MMR-proficient HCT116 colon cancer cell line through targeting the cancer …

Are RNA Therapies a Solid Foundation or a Frontier Yet to Be Conquered?

The identification of microRNAs (miRNAs) has resulted in significant advancements in research, particularly regarding their utilization as diagnostic and therapeutic targets. This has generated enthusiasm for exploring the potential of non-coding RNAs (ncRNAs) in treating cancer and other diseases, with miRNAs and long non-coding RNAs (lncRNAs) showing particular promise. Over the past twelve years, there has been significant research into RNA-based treatments. Antisense oligonucleotides and small interfering RNAs are the most commonly used. Certain products have received Federal and Drug Admi

The broad spectrum of cancer and immunotherapy: achievements and limitations.

Cancer immunotherapy has revolutionized cancer treatment over the past decades, offering renewed hope to patients with previously untreatable malignancies. This therapeutic approach could be categorized into three primary strategies: immune checkpoint blockade, adoptive cell therapy, and cancer vaccines. Immune checkpoint inhibitors have been highly successful in boosting anti-tumour immune responses by blocking the immunosuppressive signals that cancer cells exploit to evade immune surveillance, mainly that exerted by cytotoxic T lymphocytes. Adoptive cell therapy, particularly chimeric antig

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… For instance, the treatment of pancreatic cancer (PC) with ICIs revealed better outcomes in patients with high-TMB caused by heightened DNA mismatch repair gene mutations, while KRAS mutations seen in low-TMB patients may be associated to limited ICIs outcomes ( 47 ). …

Targeting cancer stem cells with CAR-based immunotherapy: biology, evidence, and future directions.

Cancer stem cells (CSCs) are pivotal in tumor initiation, progression, and relapse, underscoring the need for targeted therapies to achieve lasting responses. This review delves into CSC biology, highlighting their tumor-initiating potential demonstrated through limiting dilution assays and their role in resistance to therapies. Although successful CAR therapies, such as anti-CD19 CAR T-cells, can induce complete responses without directly targeting CSCs, CAR strategies focusing on CSCs may offer promising avenues to prevent recurrence. We assess CAR therapies targeting CSC-specific antigens,

Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy.

Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. Although surgical resection is a potentially curative approach for localized cases of GC, most cases of GC are diagnosed in an advanced, non-curable stage and the response to traditional chemotherapy is limited. Fortunately, recent advances in our understanding of the molecular mechanisms that mediate GC hold great promise for the development of more effective treatment strategies. In this review, an overview of the morphological classification, current treatment approaches, and molecular alterations that have been c

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… Previous studies have reported that the main cause of MSI in GC involves hypermethylation of the MLH1 promoter, which is one of the genes involved in the DNA mismatch repair system [ 4 , 55 ]. Depending on the level of MSI, GC cases can be categorized as high or low (MSI-H and MSI-L, respectively). …

Esid 2014 oral presentations.

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The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.

The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug deli

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically

2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference.

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Демографическая точность в онкологических оврагах, клинических и генетических детерминантах системной терапии.

Токсичность при лечении сдерживает применение эффективных методов лечения рака, однако ее клинические и генетические детерминанты по-прежнему недостаточно четко определены. Мы разработали подход, основанный на большой языковой модели, для производства MSK-Tox, панракорного ресурса, фиксирующего частотность, временнóсть и сорт токсичности для антираковой терапии в большей степени, чем 50,000 Пациенты. Анализ six Репрезентативные неблагоприятные явления - пневмонит, адренальная недостаточность, токсичность для печени, колит, гипертироидизм и гипотироидозные отдельные токсические ландшафты, опред

Oral Presentations

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mRNA вакцины для профилактики и лечения заболеваний.

mRNA вакцины стали высокоэффективными стратегиями в области профилактики и лечения болезней, в значительной степени, хотя и не полностью благодаря их выдающимся показателям в последние годы в борьбе с глобальной чумой. COVID-19. Огромное превосходство вакцин MRNA в том, что касается их эффективности, безопасности и крупномасштабного производства, побуждает фармацевтическую промышленность и биотехнологические компании распространять их применение на различные заболевания, несмотря на несомненные проблемы в проектировании, изготовлении и способе управления. В настоящем обзоре рассматриваются тех

Cytotoxic CD4+ T cells: origin, biological functions, diseases and therapeutic targets.

Cytotoxic CD4+ T lymphocytes are a unique subset of CD4+ T cells characterized by their cytokine secretion and cytolytic activity. Unlike traditional CD4+ helper T cells, cytotoxic CD4+ T lymphocytes exhibit similar cytotoxicity to that of CD8+ T cells, revealing unexpected plasticity in CD4+ T-cell functions. This flexibility suggests that CD4+ T cells can transform and acquire effector functions beyond their conventional functions, emphasizing their importance in various immune responses. Despite the identification of cytotoxic CD4+ T lymphocytes decades ago, recent advancements have broaden