Comparison of different Pancreatic cancer treatments: a three-year retrospective study in the oncology center of Tangier university hospital, Morocco.

BACKGROUND: Pancreatic cancer is among the most lethal malignancies, with a 5-year overall survival (OS) of less than 10% for all stages. The present study aims to evaluate the epidemiological and clinical characteristics, as well as the results of different treatments of patients diagnosed and treated between 2019 and 2021 in the Oncology Center of Tangier, University Hospital, Morocco. METHODS: To compare the evolution of the pancreatic cancer between the different chemotherapy regimens, a retrospective study was performed using data collected over a period of 3 years. For each patient, the data were described and statistically analyzed in the dedicated operating sheet. RESULTS: 55 pancreatic cancer patients were included in this study, and the median follow up was 3 months. The mean age of patients was 59.5 ± 10.3 years (extremes 34-79) and the sex ratio male/female was 0.9. Most patients were diagnosed with adenocarcinoma (92.3%), but metastatic stage was the most frequent (56.4%). The surgery was applied to 16.36% of patients. 10.9% of patients have received adjuvant chemotherapy and 76.4% received palliative chemotherapy. Chemotherapy regimens included mainly Gemcitabine and Folfirinox. The median OS was significantly longer for patients treated with Folfirinox versus Gemcitabine (6 months versus 3 months, p-value < 0.016). The median OS for patients that received Folfirinox and Gemcitabine successively (19.7 months) was significantly longer compared to patients that received a monotherapy with either Folfirinox or Gemcitabine alone (p-value < 0.016). CONCLUSION: These findings reinforce the use of advanced methods for earlier detection of pancreatic cancer and the development of effective immunotherapies or more targeted therapies.

Phytosterols activating nuclear receptors are involving in steroid hormone-dependent cancers: Myth or fact?

Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.

Genkwanin: An emerging natural compound with multifaceted pharmacological effects.

Plant bioactive molecules could play key preventive and therapeutic roles in chronological aging and the pathogenesis of many chronic diseases, often accompanied by increased oxidative stress and low-grade inflammation. Dietary antioxidants, including genkwanin, could decrease oxidative stress and the expression of pro-inflammatory cytokines or pathways. The present study is the first comprehensive review of genkwanin, a methoxyflavone found in several plant species. Indeed, natural sources, and pharmacokinetics of genkwanin, the biological properties were discussed and highlighted in detail. This review analyzed and considered all original studies related to identification, isolation, quantification, investigation of the biological and pharmacological properties of genkwanin. We consulted all published papers in peer-reviewed journals in the English language from the inception of each database to 12 May 2023. Different phytochemical demonstrated that genkwanin is a non-glycosylated flavone found and isolated from several medicinal plants such as Genkwa Flos, Rosmarinus officinalis, Salvia officinalis, and Leonurus sibiricus. In vitro and in vivo biological and pharmacological investigations showed that Genkwanin exhibits remarkable antioxidant and anti-inflammatory activities, genkwanin, via activation of glucokinase, has shown antihyperglycemic activity with a potential role against metabolic syndrome and diabetes. Additionally, it revealed cardioprotective and neuroprotective properties, thus reducing the risk of cardiovascular diseases and assisting against neurodegenerative diseases. Furthermore, genkwanin showed other biological properties like antitumor capability, antibacterial, antiviral, and dermato-protective effects. The involved mechanisms include sub-cellular, cellular and molecular actions at different levels such as inducing apoptosis and inhibiting the growth and proliferation of cancer cells. Despite the findings from preclinical studies that have demonstrated the effects of genkwanin and its diverse mechanisms of action, additional research is required to comprehensively explore its therapeutic potential. Primarily, extensive studies should be carried out to enhance our understanding of the molecule's pharmacodynamic actions and pharmacokinetic pathways. Moreover, toxicological and clinical investigations should be undertaken to assess the safety and clinical efficacy of genkwanin. These forthcoming studies are of utmost importance in fully unlocking the potential of this molecule in the realm of therapeutic applications.

Health Benefits and Pharmacological Aspects of Chrysoeriol.

A flavone, chrysoeriol is synthetized in several plant species. It comes from several natural sources, especially medicinal plants. The identification and isolation of this compound has been carried out and verified by several research teams using different spectral methods. It seems that the concentration of this molecule is variable and fluctuating depending on the source, the part extracted, the region, and the methods of extraction and characterization. The aim of this paper is to highlight the in vitro and in vivo pharmacological properties of chrysoeriol and to provide insight into its pharmacokinetics. Anticancer, anti-inflammatory, antibacterial, antifungal, anti-osteoporosis, anti-insecticide, and neuroprotective actions have been shown in a number of studies on this chemical. Different mechanisms in theses pharmacological effects include subcellular, cellular, and molecular targets. In vivo pharmacokinetic analysis has proved the good stability of this molecule, showing its promising potential to prevent or treat diseases including cancer, diabetes, inflammation, osteoporosis, Parkinson's disease, and cardiovascular diseases.

Inflammatory auto-immune diseases of the intestine and their management by natural bioactive compounds.

Autoimmune diseases are caused by the overactivity of the immune system towards self-constituents. Risk factors of autoimmune diseases are multiple and include genetic, epigenetic, environmental, and psychological. Autoimmune chronic inflammatory bowel diseases, including celiac and inflammatory diseases (Crohn's disease and ulcerative colitis), constitute a significant health problem worldwide. Besides the complexity of the symptoms of these diseases, their treatments have only been palliative. Numerous investigations showed that natural phytochemicals could be promising strategies to fight against these autoimmune diseases. In this respect, plant-derived natural compounds such as flavonoids, phenolic acids, and terpenoids exhibited significant effects against three autoimmune diseases affecting the intestine, particularly bowel diseases. This review focuses on the role of natural compounds obtained from medicinal plants in modulating inflammatory auto-immune diseases of the intestine. It covers the most recent literature related to the effect of these natural compounds in the treatment and prevention of auto-immune diseases of the intestine.

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions.

Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a posteriori genetic instability. In this work, we aimed to explain the mechanistic involvement of epigenetic pathways in the cancer process, as well as the abilities of natural bioactive compounds isolated from medicinal plants (flavonoids, phenolic acids, stilbenes, and ketones) to specifically target the epigenome of tumor cells. The molecular events leading to transformation, angiogenesis, and dissemination are often complex, stochastic, and take turns. On the other hand, the decisive advances in genomics, epigenomics, transcriptomics, and proteomics have allowed, in recent years, for the mechanistic decryption of the molecular pathways of the cancerization process. This could explain the possibility of specifically targeting this or that mechanism leading to cancerization. With the plasticity and flexibility of epigenetic modifications, some studies have started the pharmacological screening of natural substances against different epigenetic pathways (DNA methylation, histone acetylation, histone methylation, and chromatin remodeling) to restore the cellular memory lost during tumor transformation. These substances can inhibit DNMTs, modify chromatin remodeling, and adjust histone modifications in favor of pre-established cell identity by the differentiation program. Epidrugs are molecules that target the epigenome program and can therefore restore cell memory in cancerous diseases. Natural products isolated from medicinal plants such as flavonoids and phenolic acids have shown their ability to exhibit several actions on epigenetic modifiers, such as the inhibition of DNMT, HMT, and HAT. The mechanisms of these substances are specific and pleiotropic and can sometimes be stochastic, and their use as anticancer epidrugs is currently a remarkable avenue in the fight against human cancers.

Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates.

Cancer is one of the most complex and systemic diseases affecting the health of mankind, causing major deaths with a significant increase. This pathology is caused by several risk factors, of which genetic disturbances constitute the major elements, which not only initiate tumor transformation but also epigenetic disturbances which are linked to it and which can induce transcriptional instability. Indeed, the involvement of epigenetic disturbances in cancer has been the subject of correlations today, in addition to the use of drugs that operate specifically on different epigenetic pathways. Natural molecules, especially those isolated from medicinal plants, have shown anticancer effects linked to mechanisms of action. The objective of this review is to explore the anticancer effects of alkaloids, terpenoids, quinones, and isothiocyanates.