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WT1: The Hinge Between Anemia Correction and Cancer Development in Chronic Kidney Disease.

Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) emerge as promising agents to treat anemia in chronic kidney disease (CKD) but the major concern is their correlated risk of cancer development and progression. The Wilms' tumor gene, WT1, is transcriptionally regulated by HIF and is known to play a crucial role in tumorigenesis and invasiveness of certain types of cancers. From the mechanism of action of HIF-PHIs, to cancer hypoxia and the biological significance of WT1, this review will discuss the link between HIF, WT1, anemia correction, and cancer. We aimed to reveal the re

Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances p

Habb-e-Asgandh Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Multiple Myeloma Cells (RPMI8226).

ObjectiveThis study was conducted to assess the anti-neoplastic properties of Habb-e-Asgandh in multiple myeloma cells (RPMI8226).MethodsMultiple myeloma cells (RPMI8226) were cultured according to the ATCC's instruction. The anti-proliferative effect of HeA was assessed by MTT assay and proliferating cellnuclear antigen (PCNA) activity. Cell cycle analysis, cellular apoptosis, and mitochondria membrane potential analysis was done by flow cytometry. Total antioxidants, migratory potential, angiogenesis and inflammatory biomarkers were also estimated after treatment of RPMI8226 with HeA.Results

Long non-coding RNAs in bone metastasis: progresses and perspectives as potential diagnostic and prognostic biomarkers.

In a precision medicine perspective, among the biomarkers potentially useful for early diagnosis of cancers, as well as to define their prognosis and eventually to identify novel and more effective therapeutic targets, there are the long non-coding RNAs (lncRNAs). The term lncRNA identifies a class of non-coding RNA molecules involved in the regulation of gene expression that intervene at the transcriptional, post-transcriptional, and epigenetic level. Metastasis is a natural evolution of some malignant tumours, frequently encountered in patients with advanced cancers. Onset and development of

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

Molecular imaging in oncology: Common PET/CT radiopharmaceuticals and applications.

PET/CT is a commonly used modality in cancer imaging, as it can help in diagnosis, staging and assessment of treatment response in many cancer types. A better understanding of the tumor microenvironment and identification of multiple selective targets are promoting further investigation into different radiotracers for diagnosis and therapy. In the past few decades many radiopharmaceuticals have emerged for specific oncologic indications providing superior detection rate than some morphologic modalities. The purpose of this review is to provide an update on the most current radiopharmaceuticals

Modern Treatment of Skeletal Metastases: Multidisciplinarity and the Concept of Oligometastasis in the Recent Literature.

Bone metastases are a major concern in cancer management since they significantly contribute to morbidity and mortality. Metastatic lesions, commonly arising from breast, prostate, lung, and kidney cancers, affect approximately 25% of cancer patients, leading to severe complications such as pain, fractures, and neurological deficits. This narrative review explores contemporary approaches to bone metastases, emphasizing a multidisciplinary strategy and the evolving concept of oligometastatic disease. Oligometastases, defined by limited metastatic spread (1-5 lesions), offer a potential window f

Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-Translational Modifications and Protein-Protein Interactions.

Histone deacetylase 6 (HDAC6) is a large multidomain protein that deacetylates lysine residues on cytoplasmic proteins, influencing numerous cellular processes. Both the catalytic and noncatalytic functions of HDAC6 have been implicated in cancer development and progression. Over a decade of research on catalytic domain inhibitors has shown that these drugs are well tolerated, exhibit anticancer activity, and can alleviate chemotherapy-induced peripheral neuropathies. However, their effectiveness in treating solid tumours remains uncertain. HDAC6 activity is regulated by protein-protein intera

Intravenous zoledronic acid for the treatment of osteoporosis: The evidence of its therapeutic effect.

INTRODUCTION: Osteoporosis is a disease characterized by low bone mineral density and poor bone quality resulting in reduced bone strength and increased risk of fracture. Oral bisphosphonates, first-line therapy for most patients with osteoporosis, are associated with suboptimal adherence to therapy due to factors that include a complex dosing regimen and gastrointestinal intolerance in some patients. Intravenous bisphosphonates address these limitations through infrequent injectable dosing that assures 100% bioavailability. Intravenous zoledronic acid is the newest bisphosphonate to be approv

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… Concomitant therapy with nasal calcitonin, selective estrogen receptor modulators, hormone replacement, tibolone, and external hip protectors was allowed. Prior use of bisphosphonates or PTH was allowed according to a prespecified washout period. …

Obesity: pathophysiology and therapeutic interventions.

Over the past few decades, obesity has transitioned from a localized health concern to a pressing global public health crisis affecting over 650 million adults globally, as documented by WHO epidemiological surveys. As a chronic metabolic disorder characterized by pathological adipose tissue expansion, chronic inflammation, and neuroendocrine dysregulation that disrupts systemic homeostasis and impairs physiological functions, obesity is rarely an isolated condition; rather, it is frequently complicated by severe comorbidities that collectively elevate mortality risks. Despite advances in nutr

The 'speck'-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis.

The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a single supramolecular punctum, known as a speck, per cell, which is the site where the pro-inflammatory cytokines IL-1β and IL-18 are converted into their bioactive form. Speck also provides the platform for gasdermin D protein activation, whose N-terminus domain perforates the plasma membrane, allowing the release of mature cytokines alongside with a highly inflammatory form of cell death

The Role of Hypoxia-Inducible Factor-1α (HIF-1α) in the Progression of Ovarian Cancer: Perspectives on Female Infertility.

Hypoxia-Inducible Factor-1α (HIF-1α) is crucial in the progression of ovarian cancer, especially in influencing its tumor microenvironment and promoting pathogenic pathways that worsen female infertility. In hypoxic settings, HIF-1α is stabilized and activates the transcription of genes associated with angiogenesis, metabolic reprogramming, epithelial-to-mesenchymal transition, and therapeutic resistance. Angiogenesis and glycolytic reprogramming mediated by HIF-1 tumor proliferation, survival, and metastasis. Its dysfunction concurrently impairs ovarian homeostasis, undermining follicular gro

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs hav

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment.

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC).

Triple-negative breast cancer (TNBC) is characterized by poor outcome and the most challenging breast cancer type to treat worldwide. TNBC manifests distinct profile of mitochondrial functions, which dictates reprogrammed metabolism, fosters tumor progression, and notably serves as therapeutic targets. Mitochondrial microRNAs (mitomiRs) are a group of microRNAs that critically modulate mitochondrial homeostasis. By a pathway-centric manner, mitomiRs tightly orchestrate metabolic reprogramming, redox status, cell apoptosis, mitochondrial dynamics, mitophagy, mitochondrial DNA (mtDNA) maintenanc

Phytochemicals in Cancer Treatment and Cancer Prevention-Review on Epidemiological Data and Clinical Trials.

Phytochemicals are a non-nutritive substances that are present in plants and contribute significantly to their flavor and color. These biologically active compounds are classified into five major groups, namely phenolics, carotenoids, organosulfur compounds, nitrogen-containing compounds, and alkaloids, and are known for their potential health benefits in the prevention of various diseases, including cancer. The purpose of this review article is to explore the potential therapeutic benefits of the dietary phytochemicals, such as flavonoids, phenolic acids, phytosterols, carotenoids, and stilbe

Targeting Protein Degradation Pathways in Tumors: Focusing on their Role in Hematological Malignancies.

Cells must maintain their proteome homeostasis by balancing protein synthesis and degradation. This is facilitated by evolutionarily-conserved processes, including the unfolded protein response and the proteasome-based system of protein clearance, autophagy, and chaperone-mediated autophagy. In some hematological malignancies, including acute myeloid leukemia, misfolding or aggregation of the wild-type p53 tumor-suppressor renders cells unable to undergo apoptosis, even with an intact p53 DNA sequence. Moreover, blocking the proteasome pathway triggers lymphoma cell apoptosis. Extensive studie

Recombinant Interferon-β in the Treatment of Polycythemia Vera and Related Neoplasms: Rationales and Perspectives.

About 30 years ago, the first clinical trials of the safety and efficacy of recombinant interferon-α2 (rIFN-α2) were performed. Since then, several single-arm studies have shown rIFN-α2 to be a highly potent anticancer agent against several cancer types. Unfortunately, however, a high toxicity profile in early studies with rIFN-α2 -among other reasons likely due to the high dosages being used-disqualified rIFN-α2, which was accordingly replaced with competitive drugs that might at first glance look more attractive to clinicians. Later, pegylated IFN-α2a (Pegasys) and pegylated IFN-α2b (PegIntr

Identified Medications Causing Medication-Related Osteonecrosis of the Jaw: A Literature Review.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse event that occurs in patients treated with certain medications, leading to a major side effect that can result in substantial morbidity. MRONJ is known to be associated with antiresorptive (AR) and antiangiogenic (AA) medicines, but recent evidence suggests that other medications may also be involved. Recognizing a broad range of drug-induced risk factors is important, notably in light of the increasing number of drugs associated with MRONJ. The primary objective of this review is to update and synthesize findings from th

Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving