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Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies.

Cancer represents the leading cause of disease-related death and treatment-associated morbidity in children with an increasing trend in recent decades worldwide. Nevertheless, the 5-year survival of childhood cancer patients has been raised impressively to more than 80% during the past decades, primarily attributed to improved diagnostic technologies and multiagent cytotoxic regimens. This strong benefit of more efficient tumor control and prolonged survival is compromised by an increased risk of adverse and fatal late sequelae. Long-term survivors of pediatric tumors are at the utmost risk fo

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… On the other, loci and pathways may be affected that modify the cellular response to DNA damage and downstream signaling cascades, e.g., XPD for nucleotide excision repair, MSH2 for DNA mismatch repair, XRCC1 for DNA single-strand repair, or Rad51 for homologous recombination [ 108 ]. …

The Monoterpenoid Perillyl Alcohol: Anticancer Agent and Medium to Overcome Biological Barriers.

Perillyl alcohol (POH) is a naturally occurring monoterpenoid related to limonene that is present in the essential oils of various plants. It has diverse applications and can be found in household items, including foods, cosmetics, and cleaning supplies. Over the past three decades, it has also been investigated for its potential anticancer activity. Clinical trials with an oral POH formulation administered to cancer patients failed to realize therapeutic expectations, although an intra-nasal POH formulation yielded encouraging results in malignant glioma patients. Based on its amphipathic nat

Anticancer natural products from the Middle East and North Africa: biodiversity, mechanisms, and translational challenges.

Cancer remains one of the leading causes of morbidity and mortality worldwide, imposing substantial clinical, societal, and economic burdens. Despite major advances in surgical oncology, systemic chemotherapy, radiation therapy, molecularly targeted therapeutics, and immune checkpoint inhibition, contemporary cancer treatment remains constrained by dose-limiting toxicities, intratumoral and intertumoral heterogeneity, and the inexorable emergence of multifaceted drug resistance mechanisms. These persistent therapeutic challenges have reinstated interest in natural products (NPs) as evolutionar

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… This tetrahydroisoquinoline alkaloid binds the DNA minor groove, inducing unprecedented bending toward the major groove and disrupting transcription-coupled nucleotide excision repair and homologous recombination pathways ( 127 – 130 ). …

Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). Alkylphosphocholine (APC) derivatives represent a novel class of a

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… Most of the clinical studies in PubMed focused on its apoptotic effect; only Wei et al. reported that the expression of apurinic/apyrimidinic endonuclease (APE1), which regulates the DNA base excision repair process, reduces survival in gastric cancer patients and the APE1 inhibitor AT-101 may be a potential …

Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.

The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor progn

Does Regular Exercise Counter T Cell Immunosenescence Reducing the Risk of Developing Cancer and Promoting Successful Treatment of Malignancies?

Moderate intensity aerobic exercise training or regular physical activity is beneficial for immune function. For example, some evidence shows that individuals with an active lifestyle exhibit stronger immune responses to vaccination compared to those who are inactive. Encouragingly, poor vaccine responses, which are characteristic of an ageing immune system, can be improved by single or repeated bouts of exercise. In addition, exercise-induced lymphocytosis, and the subsequent lymphocytopenia, is thought to facilitate immune surveillance, whereby lymphocytes search tissues for antigens derived

RESEARCH COMMUNICATIONS OF THE 34th ECVIM-CA CONGRESS.

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Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to ac

Lipid nanoparticle-mediated mRNA/siRNA dual-bioengineered dendritic cell vaccines combined of PD-1/PD-L1 blockade for boosting tumor immunotherapy.

DC vaccines occupy a pivotal position in the realm of cancer treatment, leveraging the immune system to precisely target and effectively eliminate tumor cells. However, current challenges in tumor DC vaccine development include issues such as limited efficacy and potential upregulation of immunosuppressive molecules like PD-L1 on tumor cells. Herein, we employed microfluidic technology to fabricate lipid nanoparticles (LNPs) that simultaneously encapsulate OVA mRNA (mOVA), encoding the model antigen OVA, and siRNA targeting PD-L1. The LNP/mOVA/siPD-L1 nanoparticles were utilized to transfect b

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then,

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… RASSF1A is a negative regulator of the RAS-MAPK signaling pathway and can mediate DNA repair through the mechanism of nucleotide excision repair [ 68 ]. …

Proceedings of International Conference on Cell Death in Cancer and Toxicology. February 20-22, 2018. Guest Editors: Kausar M. Ansari, CSIR-IITR, India and Dhyan Chandra, Roswell Park, USA.

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Электронные постеры

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Unc-51 like kinase 3 (ULK3) contributes to autophagy and cell survival in multiple myeloma.

Despite effective therapies such as proteasome inhibitors, multiple myeloma (MM) patients relapse with refractory disease. Analysis of RNA sequencing data from CD138 + MM patient cells (n = 813) across disease stages identifies an autophagy gene signature. Particularly elevated ULK3 expression is strongly associated with disease progression. Functional studies reveal that ULK3 supports MM cell survival via the ULK-ATG13-FIP200 complex. We generate small-molecule kinase inhibitors (SG3-014/MA9-060) exhibiting nanomolar potency against ULK3, with binding confirmed by co-crystallization. While ex

Targeting neuroinflammation: 3-monothiopomalidomide a new drug candidate to mitigate traumatic brain injury and neurodegeneration.

BACKGROUND: Traumatic Brain Injury (TBI) is a major risk factor for neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD), with neuroinflammation playing a critical role in the secondary cell death that exacerbates the initial injury. While targeting neuroinflammation holds significant therapeutic promise, clinical trials of available anti-inflammatory agents have fallen short. 3-Mono-thiopomalidomide (3-MP), a novel immunomodulatory imide drug (IMiD), was designed to curb inflammation without the adverse effects of traditional IMiDs and was evaluated across

A Review on Curability of Cancers: More Efforts for Novel Therapeutic Options Are Needed.

Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with loca

Repurposing Pharmaceuticals Previously Approved by Regulatory Agencies to Medically Counter Injuries Arising Either Early or Late Following Radiation Exposure.

The increasing risks of radiological or nuclear attacks or associated accidents have served to renew interest in developing radiation medical countermeasures. The development of prospective countermeasures and the subsequent gain of Food and Drug Administration (FDA) approval are invariably time consuming and expensive processes, especially in terms of generating essential human data. Due to the limited resources for drug development and the need for expedited drug approval, drug developers have turned, in part, to the strategy of repurposing agents for which safety and clinical data are alrea

Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dos

Infarcts and ischemia in the abdomen: an imaging perspective with an emphasis on cross-sectional imaging findings.

Infarcts and ischemia of abdominal organs may present with acute abdominal pain, and early diagnosis is crucial to prevent morbidity and mortality. Unfortunately, some of these patients present in poor clinical conditions to the emergency department, and imaging specialists are crucial for optimal outcomes. Although the radiological diagnosis of abdominal infarcts is often straightforward, it is vital to use the appropriate imaging modalities and correct imaging techniques for their detection. Additionally, some non-infarct-related abdominal pathologies may mimic infarcts, cause diagnostic con

Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer's, Parkinson's, and Huntington's Diseases and Amyotrophic Lateral Sclerosis.

Neurodegenerative diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to experience exponential growth thanks to numerous advancements in technology, shifts in the understanding of the disease as a phenomenon, and the change in the perspective regarding gene editing and the advantages of this action. The aim of this paper is to analyze the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Hunti