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Targeted therapies in pediatric oncology: A start.

The treatment of cancers was revolutionized by the use of combination "conventional" chemotherapy, first in children, during the 20th century. That foundation of therapy, while having achieved significant advances in survival, has reached its limits. Innovations in targeted therapies are now building upon that foundation to further improve outcomes in pediatric oncology. These targeted agents are designed to narrowly utilize specific biologic processes for greater efficacy and optimally fewer generalized toxicities. I will provide an overview of the current spectrum of targeted therapies avail

Acute Plasma Cell Leukemia Presenting as Primary Hyperammonemic Encephalopathy.

Primary plasma cell leukemia (PPCL) is a rare form of multiple myeloma (MM) and is a rare aggressive disease with a median overall survival of 6 - 11 months. We present a case of acute hyperammonemic encephalopathy as the initial presentation of PPCL in a 78-year-old woman to highlight an atypical presentation of this disorder.

IgA-producing lymphoplasmacytic lymphoma carrying the chromosomal abnormality t(8;14).

IgA-producing lymphoplasmacytic lymphoma (LPL) is rare and IgH/c-myc translocation is rare in LPL. This is the first report of a case of IgA-producing LPL carrying t(8;14). An 86-year-old woman presented inguinal and intra-abdominal lymph node swelling, and lytic bone lesions in the lumbar vertebrae. A diagnosis of IgA-producing LPL was immunohistochemically made by inguinal lymph node biopsy. The serum IgA level was 1,180 mg/dL, which was revealed to be composed of IgA-λ monoclonal protein. Bone marrow chromosomal analysis demonstrated a complex abnormal karyotype, including t(8;14)(q24;q32),

Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out.

Anticancer treatments have shown a variable therapeutic outcome that may be partly attributable to the activity of the gut microbiota on the pathology and/or therapies. In recent years, microbiota-drug interactions have been extensively investigated, but most of the underlying molecular mechanisms still remain unclear. In this review, we discuss the relationship between the gut microbiota and some of the most commonly used drugs in oncological diseases. Different strategies for manipulating the gut microbiota layout (i.e., prebiotics, probiotics, antibiotics, and fecal microbiota transplantati

Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure.

Macrophages facilitate essential homeostatic functions e.g., endocytosis, phagocytosis, and signaling during inflammation, and express a variety of scavenger receptors including CD163 and CD206, which are upregulated in response to inflammation. In healthy individuals, soluble forms of CD163 and CD206 are constitutively shed from macrophages, however, during inflammation pathogen- and damage-associated stimuli induce this shedding. Activation of resident liver macrophages viz. Kupffer cells is part of the inflammatory cascade occurring in acute and chronic liver diseases. We here review the ex

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… Soluble CD163 and soluble mannose receptor predict survival and decompensation in patients with liver cirrhosis, and correlate with gut permeability and bacterial translocation. Aliment. Pharmacol. Ther. 2017;47:657–664. doi: 10.1111/apt.14474. 80. … The soluble mannose receptor is released from the liver in cirrhotic patients, but is not associated with bacterial translocation. Liver Int. 2016;37:569–575. doi: 10.1111/liv.13262. 102. …

Unraveling the Anti-Cancer Mechanisms of Antibiotics: Current Insights, Controversies, and Future Perspectives.

Cancer persists as a significant global health challenge, claiming millions of lives annually despite remarkable strides in therapeutic innovation. Challenges such as drug resistance, toxicity, and suboptimal efficacy underscore the need for novel treatment paradigms. In this context, the repurposing of antibiotics as anti-cancer agents has emerged as an attractive prospect for investigation. Diverse classes of antibiotics have exhibited promising anti-cancer properties in both in vitro and in vivo studies. These mechanisms include the induction of apoptosis and cell cycle arrest, generation o

Витамин D как модулятор иммуно-эндокрина: открытие его роли в аутоиммунных расстройствах и механизмах защиты заложников.

Фон/цели: Витамин D, получивший всеобщее признание за свою роль в гомеостазе кальция-фосфата и здоровье скелета, стал одним из ключевых модуляторов иммуноэндокринной системы. Его активный метаболит взаимодействует с рецептором витамина D (VDR) через иммунную и эндокринную клетку, оказывая влияние на транскрипцию генов, баланс цитокина и иммунную терпимость. В настоящем докладе обобщаются механистические, эпидемиологические и клинические данные о роли витамина D в иммунной модуляции различных аутоиммунных и инфекционных заболеваний. Методы: Этот описательный обзор включал структурированный и вс

Разъяснение роли GRK2: от иммунного регулирования к терапии рака.

G белковые рецепторы (GPCR) представляют собой наиболее заметное семейство мембранных белков. В противоположность этому, G-белковые рецепторы (GRKs) играют ключевую роль в быстрой десенсибилизации ГПКР. GRK2 является особенно важным членом семьи GRK. Недавние исследования показали, что GRK2 в первую очередь регулирует функции иммунных клеток и гомеостаз через десенсибилизацию рецептора. За последнее десятилетие был достигнут существенный прогресс в разъяснении роли GRK2 в различных заболеваниях человека. В частности, GRK2 имеет отношение к целому ряду аутоиммунных расстройств, включая ревматуи

Gut microbiota shapes cancer immunotherapy responses.

The gut microbiota significantly influences cancer immunotherapy efficacy by modulating immune responses, remodeling the tumor microenvironment (TME), and producing key metabolites. Strategies such as FMT, probiotics, and dietary interventions show promise in enhancing responses to ICIs and ACTs while reducing immune-related adverse events (irAEs). This review summarizes clinical and preclinical findings and discusses microbiota-based interventions and future directions for precision immunotherapy.

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… Additionally, ABX can reduce bacterial translocation to the liver and intestine, thereby inhibiting CRC metastasis 241 . While antibiotics offer potential benefits in modulating tumor-associated microbiota, their application in cancer treatment must be carefully tailored. …

Mucosal-Associated Invariant T Cells in Health and Disease.

Mucosal-associated invariant T (MAIT) cells are a population of evolutionarily conserved, unconventional innate-like T lymphocytes that are restricted by major histocompatibility complex Class I-related (MR1) molecules. They can be activated either in a T-cell receptor-MR1- or cytokine-dependent manner. Activated MAIT cells play crucial roles in maintaining homeostasis and the fine regulation of the immune system. This review presents a systematic exploration of the development, biological characteristics, and multiple effects of MAIT cells in health and various diseases. In healthy individual

Septic shock in the immunocompromised cancer patient: a narrative review.

Immunosuppressed patients, particularly those with cancer, represent a momentous and increasing portion of the population, especially as cancer incidence rises with population growth and aging. These patients are at a heightened risk of developing severe infections, including sepsis and septic shock, due to multiple immunologic defects such as neutropenia, lymphopenia, and T and B-cell impairment. The diverse and complex nature of these immunologic profiles, compounded by the concomitant use of immunosuppressive therapies (e.g., corticosteroids, cytotoxic drugs, and immunotherapy), superimpose

The microbiota-gut-brain-axis theory: role of gut microbiota modulators (GMMs) in gastrointestinal, neurological, and mental health disorders.

The modulation of gut microbiota presents promising therapeutic possibilities for various health conditions, ranging from gastrointestinal infections to neurodegenerative and mental health disorders. Among the available interventions, gut microbiota modulators (GMMs) such as probiotics and prebiotics have demonstrated significant potential in infection prevention and neuroprotection. Despite these encouraging findings, the clinical application of GMMs remains challenging due to safety concerns and inconsistent effectiveness across diverse patient populations. These factors create substantial b

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… These molecular interactions collectively impact intestinal barrier integrity, bacterial translocation, neurotransmitter production, and vagus nerve/CNS signaling. …

The Applications of Machine Learning in the Management of Patients Undergoing Stem Cell Transplantation: Are We Ready?

Hematopoietic stem cell transplantation (HSCT) is a life-saving therapy for hematologic malignancies, such as leukemia and lymphoma and other severe conditions but is associated with significant risks, including graft versus host disease (GVHD), relapse, and treatment-related mortality. The increasing complexity of clinical, genomic, and biomarker data has spurred interest in machine learning (ML), which has emerged as a transformative tool to enhance decision-making and optimize outcomes in HSCT. This review examines the applications of ML in HSCT, focusing on donor selection, conditioning re

Histone deacetylase in inflammatory bowel disease: novel insights.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is characterized by chronic nonspecific intestinal inflammation. Despite considerable efforts, IBD remains a heavy burden on society and human health, with increasing morbidity. Posttranslational modification, especially histone acetylation, is a key process in controlling DNA transcriptional activity. Histone deacetylases (HDACs) play a vital role in the mechanism of IBD pathogenesis through histone and nonhistone protein deacetylation. Herein, we present a summary of different categories of HDACs as well as H

Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.

There are overwhelming reports on the promotional effect of hypoxia on the malignant behavior of various forms of cancer cells. This has been proposed and tested exhaustively in the light of cancer immunotherapy. However, there could be more interesting functions of a hypoxic cellular micro-environment than malignancy. There is a highly intricate crosstalk between hypoxia inducible factor (HIF), a transcriptional factor produced during hypoxia, and nuclear factor kappa B (NF-κB) which has been well characterized in various immune cell types. This important crosstalk shares common activating an

NF-κB in Thyroid Cancer: An Update.

The dysregulated NF-κB basal activity is a common feature of human thyroid carcinomas, especially in poorly differentiated or undifferentiated forms that, even if rare, are often resistant to standard therapies, and, therefore, are uncurable. Despite the molecular mechanisms leading to NF-κB activation in thyroid cancer being only partially understood, during the last few years, it has become clear that NF-κB contributes in different ways to the oncogenic potential of thyroid neoplastic cells. Indeed, it enhances their proliferation and viability, promotes their migration to and colonization o

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review.

Immunotherapy is emerging as a promising avenue in oncology, gaining increasing importance and offering substantial advantages when compared to chemotherapy or radiotherapy. However, in the context of immunotherapy, there is the potential for the immune system to either support or hinder the administered treatment. This review encompasses recent and pivotal studies that assess the influence of dietary elements, including vitamins, fatty acids, nutrients, small dietary molecules, dietary patterns, and caloric restriction, on the ability to modulate immune responses. Furthermore, the article und

Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra.

High-dose chemotherapy causes intestinal inflammation and subsequent breakdown of the mucosal barrier, permitting translocation of enteric pathogens, clinically manifesting as fever. Antibiotics are mainstay for controlling these complications, however, they are increasingly recognized for their detrimental effects, including antimicrobial resistance and dysbiosis. Here, we show that mucosal barrier injury induced by the mucotoxic chemotherapeutic agent, high-dose melphalan (HDM), is characterized by hyper-active IL-1b/CXCL1/neutrophil signaling. Inhibition of this pathway with IL-1RA, anakinr

Disorders of the Gastrointestinal System

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The impact of the gut microbiome on tumor immunotherapy: from mechanism to application strategies.

Immunotherapy is one of the fastest developing areas in the field of oncology. Many immunological treatment strategies for refractory tumors have been approved and marketed. Nevertheless, much clinical and preclinical experimental evidence has shown that the efficacy of immunotherapy in tumor treatment varies markedly among individuals. The commensal microbiome mainly colonizes the intestinal lumen in humans, is affected by a variety of factors and exhibits individual variation. Moreover, the gut is considered the largest immune organ of the body due to its influence on the immune system. In t