Application of Box-Behnken design in the optimization and development of albendazole-loaded zein nanoparticles as a drug repurposing approach for colorectal cancer management.

Colorectal cancer (CRC) is the second cancer worldwide representing a major global health challenge. Numerous effective anticancer drugs have been developed in the last decade, yet the problem remains due to their low therapeutic index and nonspecificity. A new anticancer therapeutic paradigm is based on repurposing and nanoformulating drugs.

Novel ST1926 Nanoparticle Drug Formulation Enhances Drug Therapeutic Efficiency in Colorectal Cancer Xenografted Mice.

Cancer is a major public health problem that ranks as the second leading cause of death. Anti-cancer drug development presents with various hurdles faced throughout the process. Nanoparticle (NP) formulations have emerged as a promising strategy for enhancing drug delivery efficiency, improving stability, and reducing drug toxicity.

Nutrition Knowledge, Attitudes, and Lifestyle Practices That May Lead to Breast Cancer Risk Reduction among Female University Students in Lebanon.

Research has identified both nonmodifiable and modifiable risk factors for breast cancer (BC), with accumulating evidence showing that adopting adequate dietary practices could decrease the risk of this disease. This study aimed to assess nutrition knowledge, attitudes, and lifestyle practices (KAP) that may lead to BC risk reduction among female university students in Lebanon and examine the determinants of their practices. A cross-sectional survey was conducted using a convenience sampling method, comprising 356 (response rate: 71.

Periprostatic adipose tissue thromboinflammation triggers prostatic neoplasia in early metabolic impairment: Interruption by rivaroxaban.

Aims: Prostate cancer is among the highest incidence malignancies in men with a prevalence rate increasing in parallel to the rising global trends in metabolic disorders. Whereas a sizeable body of evidence links metabolic impairment to negative prognosis of prostate cancer, the molecular mechanism underlying this connection has not been thoroughly examined. Our previous work showed that localized adipose tissue inflammation occurring in select adipose depots in early metabolic derangement instigated significant molecular, structural, and functional alterations in neighboring tissues underlying the complications observed at this stage.

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis.

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas' tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment.

The Antitumor Effect of the DNA Polymerase Alpha Inhibitor ST1926 in Glioblastoma: A Proteomics Approach.

Glioblastoma Multiforme (GBM) is the most aggressive form of malignant brain tumor. The median survival rate does not exceed two years, indicating an imminent need to develop novel therapies. The atypical adamantyl retinoid ST1926 induces apoptosis and growth inhibition in different cancer types.

Mannose Inhibits the Pentose Phosphate Pathway in Colorectal Cancer and Enhances Sensitivity to 5-Fluorouracil Therapy.

Colorectal cancer (CRC) is one of the leading cancers and causes of death in patients. 5-fluorouracil (5-FU) is the therapy of choice for CRC, but it exhibits high toxicity and drug resistance. Tumorigenesis is characterized by a deregulated metabolism, which promotes cancer cell growth and survival.

Inflammasomes as biomarkers and therapeutic targets in traumatic brain injury and related-neurodegenerative diseases: A comprehensive overview.

Given the ambiguity surrounding traumatic brain injury (TBI) pathophysiology and the lack of any Food and Drug Administration (FDA)-approved neurotherapeutic drugs, there is an increasing need to better understand the mechanisms of TBI. Recently, the roles of inflammasomes have been highlighted as both potential therapeutic targets and diagnostic markers in different neurodegenerative disorders. Indeed, inflammasome activation plays a pivotal function in the central nervous system (CNS) response to many neurological conditions, as well as to several neurodegenerative disorders, specifically, TBI.

Lessons learned from the discovery and development of the sesquiterpene lactones in cancer therapy and prevention.

Introduction: Sesquiterpene lactones (SLs) are one of the most diverse bioactive secondary metabolites found in plants and exhibit a broad range of therapeutic properties . SLs have been showing promising potential in cancer clinical trials, and the molecular mechanisms underlying their anticancer potential are being uncovered. Recent evidence also points to a potential utility of SLs in cancer prevention.

2-Nucleobase-substituted 4,6-Diaminotriazine Analogs: Synthesis and Anti-cancer Activity in 5-Fluorouracil-sensitive and Resistant Colorectal Cancer Cells.

Background: Cancer continues to be the second leading cause of death worldwide, with colorectal cancer (CRC) being the third most common type. Despite significant advances in cancer therapies, the current treatment of CRC remains suboptimal. In addition, the effectiveness of available chemotherapeutic drugs such as 5-Fluorouracil (5-FU) is limited by CRC-acquired resistance.

Development and Challenges of Synthetic Retinoid Formulations in Cancer.

Retinoids represent a class of chemical compounds derived from or structurally and functionally related to vitamin A. Retinoids play crucial roles in regulating a range of crucial biological processes spanning embryonic development to adult life. These include regulation of cell proliferation, differentiation, and cell death.

Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue.

The increased global prevalence of metabolic disorders including obesity, insulin resistance, metabolic syndrome and diabetes is mirrored by an increased incidence of prostate cancer (PCa). Ample evidence suggests that these metabolic disorders, being characterized by adipose tissue (AT) expansion and inflammation, not only present as risk factors for the development of PCa, but also drive its increased aggressiveness, enhanced progression, and metastasis. Despite the emerging molecular mechanisms linking AT dysfunction to the various hallmarks of PCa, thromboinflammatory processes implicated in the crosstalk between these diseases have not been thoroughly investigated.

Immunodeficiency Accelerates Vitamin A Deficiency.

Background: Vitamin A deficiency increases susceptibility to infection caused by impaired immune function.

Objectives: We investigated whether immunodeficiency could facilitate the development of vitamin A deficiency.

Methods: Vitamin A deficiency was followed in 2 mouse models of immunodeficiency: the athymic nude mouse () and the humoral immunodeficient SENCAR (SENsitive to CARcinogenesis) mouse.

The Pentose Phosphate Pathway in Cancer: Regulation and Therapeutic Opportunities.

Background: Tumorigenesis is associated with deregulation of nutritional requirements, intermediary metabolites production, and microenvironment interactions. Unlike their normal cell counterparts, tumor cells rely on aerobic glycolysis, through the Warburg effect.

Summary: The pentose phosphate pathway (PPP) is a major glucose metabolic shunt that is upregulated in cancer cells.

Antitumor activity of novel POLA1-HDAC11 dual inhibitors.

Hybrid molecules targeting simultaneously DNA polymerase α (POLA1) and histone deacetylases (HDACs) were designed and synthesized to exploit a potential synergy of action. Among a library of screened molecules, MIR002 and GEM144 showed antiproliferative activity at nanomolar concentrations on a panel of human solid and haematological cancer cell lines. In vitro functional assays confirmed that these molecules inhibited POLA1 primer extension activity, as well as HDAC11.

The unfolding role of ceramide in coordinating retinoid-based cancer therapy.

Sphingolipid-mediated regulation in cancer development and treatment is largely ceramide-centered with the complex sphingolipid metabolic pathways unfolding as attractive targets for anticancer drug discovery. The dynamic interconversion of sphingolipids is tightly controlled at the level of enzymes and cellular compartments in response to endogenous or exogenous stimuli, such as anticancer drugs, including retinoids. Over the past two decades, evidence emerged that retinoids owe part of their potency in cancer therapy to modulation of sphingolipid metabolism and ceramide generation.

The Effect of Different Ester Chain Modifications of Two Guaianolides for Inhibition of Colorectal Cancer Cell Growth.

Several sesquiterpene lactones (STLs) have been tested as lead drugs in cancer clinical trials. Salograviolide- (Sal- and salograviolide- (Sal- are two STLs that have been isolated from an indigenous medicinal plant of the Middle Eastern region. The parent compounds Sal- and Sal- were modified and successfully prepared into eight novel guaianolide-type STLs (compounds -) bearing ester groups of different geometries.

Terpenoids' anti-cancer effects: focus on autophagy.

Terpenoids are the largest class of natural products, most of which are derived from plants. Amongst their numerous biological properties, their anti-tumor effects are of interest for they are extremely diverse which include anti-proliferative, apoptotic, anti-angiogenic, and anti-metastatic activities. Recently, several in vitro and in vivo studies have been dedicated to understanding the 'terpenoid induced autophagy' phenomenon in cancer cells.

Anticancer activities of parthenolide in primary effusion lymphoma preclinical models.

The sesquiterpene lactone parthenolide is a major component of the feverfew medicinal plant, Tanacetum parthenium. Parthenolide has been extensively studied for its anti-inflammatory and anticancer properties in several tumor models. Parthenolide's antitumor activities depend on several mechanisms but it is mainly known as an inhibitor of the nuclear factor-κB (NF-κB) pathway.

Restoration of ceramide de novo synthesis by the synthetic retinoid ST1926 as it induces adult T-cell leukemia cell death.

Ceramide (Cer) is a bioactive cellular lipid with compartmentalized and tightly regulated levels. Distinct metabolic pathways lead to the generation of Cer species with distinguishable roles in oncogenesis. Deregulation of Cer pathways has emerged as an important mechanism for acquired chemotherapeutic resistance.

Novel adamantyl retinoid-related molecules with POLA1 inhibitory activity.

Atypical retinoids (AR) or retinoid-related molecules (RRMs) represent a promising class of antitumor compounds. Among AR, E-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid (adarotene), has been extensively investigated. In the present work we report the results of our efforts to develop new adarotene-related atypical retinoids endowed also with POLA1 inhibitory activity.

Thymoquinone induces apoptosis and DNA damage in 5-Fluorouracil-resistant colorectal cancer stem/progenitor cells.

The high recurrence rates of colorectal cancer have been associated with a small population of cancer stem cells (CSCs) that are resistant to the standard chemotherapeutic drug, 5-fluorouracil (5FU). Thymoquinone (TQ) has shown promising antitumor properties on numerous cancer systems both and ; however, its effect on colorectal CSCs is poorly established. Here, we investigated TQ's potential to target CSCs in a three-dimensional (3D) sphere-formation assay enriched for a population of colorectal cancer stem/progenitor cells.

Epigenetic mechanisms and the hallmarks of cancer: an intimate affair.

Epigenetic mechanisms comprising DNA methylation, histone modifications, and noncoding RNAs affect chromatin structure and regulate gene expression. These mechanisms control normal embryonic development and adult life and their deregulation contributes to several diseases including cancer. The process of tumorigenesis is complex and results from the evolution of different "hallmarks of cancer".

A Critical Review of Animal Models Used in Acute Myeloid Leukemia Pathophysiology.

Acute myeloid leukemia (AML) is one of the most frequent, complex, and heterogeneous hematological malignancies. AML prognosis largely depends on acquired cytogenetic, epigenetic, and molecular abnormalities. Despite the improvement in understanding the biology of AML, survival rates remain quite low.