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CD13 downregulation mediated by ubenimex inhibits autophagy to overcome 5-FU resistance by disturbing the EMP3/FAK/NF-κB pathway in gastric cancer cells.

BackgroundGastric cancer (GC) is one of the most common malignant tumours in China, but the efficacy of chemotherapy on GC is significantly reduced due to the occurrence of drug resistance. Some studies have shown that the expression level of CD13 is associated with tumour resistance, but whether ubenimex, as a CD13 inhibitor, reverses GC drug resistance and the underlying mechanism remain unclear.MethodsHerein, resistance to 5-fluorouracil (5-FU) was reversed in GC by ubenimex, and the underlying mechanism was determined using Cell Counting Kit-8 (CCK-8) assays, gene chip analysis, high conte

Acute Kidney Injury in Oncology Patients.

With rapid progress in cancer diagnosis and treatment in the last two decades, outcomes in oncological patients have improved significantly. However, the incidence of acute kidney injury (AKI) in this population has also increased significantly. AKI complicates many aspects of patients' care and adversely affects their prognoses; thus, accurately diagnosing the risk factors for AKI ensures appropriate management. AKI may be caused by pre-renal, intrinsic renal, and post-renal reasons, as well as for combined reasons. This review summarizes the potential etiologies of AKI according to the three

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… Conventional cancer drugs such as platinum compounds, ifosfamide, pemetrexed, and methotrexate, as well as targeted agents such as TKIs, anaplastic lymphoma kinase inhibitors, and BRAF gene inhibitors induce ATN. …

Ventricular Arrhythmia in Cancer Patients: Mechanisms, Treatment Strategies and Future Avenues.

Cardiovascular disease and cancer are the leading causes of morbidity and mortality in the US. Despite the significant progress made in cancer treatment leading to improved prognosis and survival, ventricular arrhythmias (VA) remain a known cardiovascular complication either exacerbated or induced by the direct and indirect effects of both traditional and novel cancer treatments. Although interruption of cancer treatment because of VA is rarely required, knowledge surrounding this issue is essential for optimising the overall care of patients with cancer. The mechanisms of cancer-therapeutic-i

Activin Receptor-Ligand Trap for the Treatment of β-thalassemia: A Serendipitous Discovery.

β-thalassemia is a hereditary disorder caused by defective production of β-globin chains of hemoglobin (Hb) that leads to an increased α/β globins ratio with subsequent free α-globins. Alpha globin excess causes oxidative stress, red blood cells membrane damage, premature death of late-stage erythroid precursors, resulting in ineffective erythropoiesis. The transforming growth factor β (TGF-β) superfamily signaling acts on biological processes, such as cell quiescence, apoptosis, proliferation, differentiation, and migration, and plays an essential role in regulating the hematopoiesis. This pa

Trial watch: beta-blockers in cancer therapy.

Compelling evidence supports the hypothesis that stress negatively impacts cancer development and prognosis. Irrespective of its physical, biological or psychological source, stress triggers a physiological response that is mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic adrenal medullary axis. The resulting release of glucocorticoids and catecholamines into the systemic circulation leads to neuroendocrine and metabolic adaptations that can affect immune homeostasis and immunosurveillance, thus impairing the detection and eradication of malignant cells. Moreover, catech

Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.

Cancer is more than just a collection of tumor cells. The complex tumor system, including the tumor immune microenvironment (TIME), is continually changing. Tumor cells are in constant communication with all stromal elements (e.g., fibroblasts, endothelial cells, and extracellular matrix) and immune effector cells (e.g., T cells, B cells, natural killer cells, dendritic cells, macrophages, and myeloid-derived suppressor cells). Together, these intricate interactions among cell and molecular signaling pathways collectively drive tumor growth, tumor invasion, and metastasis and significantly aff

Natural biomolecules and derivatives as anticancer immunomodulatory agents.

Despite advancements in chemotherapy, the issue of resistance and non-responsiveness to many chemotherapeutic drugs that are currently in clinical use still remains. Recently, cancer immunotherapy has gathered attention as a novel treatment against select cancers. Immunomodulation is also emerging as an effective strategy to improve efficacy. Natural phytochemicals, with known anticancer properties, been reported to mediate their effects by modulating both traditional cancer pathways and immunity. The mechanism of phytochemical mediated-immunomodulatory activity may be attributed to the remode

Amino acids metabolism: a potential target for cancer treatment.

Metabolic reprogramming of amino acids has been recognized as a significant characteristic in various types of cancers. Numerous studies have indicated that the metabolic reprogramming of amino acids in tumors significantly supports certain malignant behaviors, including tumor proliferation, survival, invasion, and even immune escape. Amino acids can provide biomolecules such as nucleotides and glutathione (GSH) for tumors, and the bioavailability of amino acids influences tumor progression. Meanwhile, as essential metabolites, amino acids are closely associated with immune cell activation and

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design.

Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death.

Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer.

The strategy of using existing drugs originally developed for one disease to treat other indications has found success across medical fields. Such drug repurposing promises faster access of drugs to patients while reducing costs in the long and difficult process of drug development. However, the number of existing drugs and diseases, together with the heterogeneity of patients and diseases, notably including cancers, can make repurposing time consuming and inefficient. The key question we address is how to efficiently repurpose an existing drug to treat a given indication. As drug efficacy rem

Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent.

Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in mul

In Vivo and In Vitro Pharmacokinetic Studies of a Dual Topoisomerase I/II Inhibitor.

Due to high mortality rates, new and more effective drugs are urgently needed in cancer therapy. The novel dual topoisomerase inhibitor P8-D6, a dimethylaminoethyl-substituted pyridophenanthroline, showed in vitro impressive induction of apoptosis in tumors such as ovarian cancer or multiple myeloma compared to the current standard therapy. The purpose of this study was to investigate its in vitro and in vivo pharmacokinetics and to discover further potential drug candidates. Samples of plasma, various tissues, urine, feces, and cell culture supernatants were examined by HPLC. In addition, the

New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms.

Opinion statementNeuroendocrine neoplasms (NEN) are a heterogeneous group of tumours derived from cells of neuroendocrine origin and can potentially arise everywhere in the human body. The diagnostic assessment of NEN can be performed using a variety of PET radiopharmaceuticals. Well-differentiated NEN (NET) present a high expression of SSTR (somatostatin receptors) and can therefore be studied with 68Ga-DOTA-peptides ([68Ga]Ga-DOTANOC, [68Ga]Ga-DOTATOC, [68Ga]Ga-DOTATATE). Current guidelines recommend the use of SSTR imaging to assess disease extension at staging/restaging, follow-up, assessm

Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis.

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers

Cachexia as Evidence of the Mechanisms of Resistance and Tolerance during the Evolution of Cancer Disease.

During its evolution, cancer induces changes in patients' energy metabolism that strongly affect the overall clinical state and are responsible for cancer-related cachexia syndrome. To better understand the mechanisms underlying cachexia and its metabolic derangements, research efforts should focus on the events that are driven by the immune system activation during the evolution of neoplastic disease and on the phenomena of "resistance" and "tolerance" typically involved in the human body response against stress, pathogens, or cancer. Indeed, in the case where resistance is not able to elimin

Breaking the obesity-cancer link: assessing European school-based and complementary obesity-prevention strategies and their implementation obstacles

Nowadays, obesity among children and adolescents is considered an additional factor in cancer development during adulthood. These facts are supported by current epidemiological studies. To address these challenges, a wide range of obesity prevention programmes have been launched in Europe, promoting actions for personalized healthy dietary behaviors, physical exercise, and combinations of both, often using e-health platforms. Another pillar of interventions is school-based policies, such as limiting access to high-fat and high-sugar foods or providing healthy food vouchers, which represent ano

Role of Bruton's tyrosine kinase in B cells and malignancies.

Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor a

Screening the Active Phytochemicals From Eclipta prostrata and Unraveling Their Molecular Insight Into Human Malignancies.

Current drugs against multiple human malignancies are limited, and developing new treatment strategies is improbable within a short time. So, considering the current situation, phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies. Therefore, we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually. We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search, and these compounds have chemoth

Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.

Cancer therapy and cancer drug discovery and development have been historically focused on specific cancers (tissue/organ of origin). However, with advances in molecular biology and multi-omics of cancer, there is a trend to develop pan-cancer therapeutic modalities. In targeted therapy, pan-cancer strategies target common molecular alterations across different cancer types and specific cancer strategies are tailored to the unique biological characteristics of individual tumor types. Each approach offers distinct advantages and limitations, and understanding these differences is critical in th

Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.

BackgroundCancer metabolism is a field focused on the unique alterations in metabolic pathways that occur in cancer cells, distinguishing them from the metabolic processes in normal cells.MethodsAn extensive review of the current literature on the metabolic adaptation of cancer cells was carried out in the current study.ResultsThe rapidly proliferating cells require high levels of molecules, such as glucose, amino acids, lipids, and nucleotides, along with increased energy demand (ATP). These requirements are met through alterations in the processes involving glucose, amino acid, lipid, and nu