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Exploiting Literature-derived Knowledge and Semantics to Identify Potential Prostate Cancer Drugs.

In this study, we report on the performance of an automated approach to discovery of potential prostate cancer drugs from the biomedical literature. We used the semantic relationships in SemMedDB, a database of structured knowledge extracted from all MEDLINE citations using SemRep, to extract potential relationships using knowledge of cancer drugs pathways. Two cancer drugs pathway schemas were constructed using these relationships extracted from SemMedDB. Through both pathway schemas, we found drugs already used for prostate cancer therapy and drugs not currently listed as the prostate cancer

Recent Insights into the Creation of Histone Deacetylase Inhibitors for the Treatment of Human Diseases.

This review examines publications over the past two years devoted to histone deacetylase inhibitors for the treatment of cancer, diseases of the nervous, cardiovascular, digestive, and respiratory systems, and autoimmune diseases. The review covers various classes of histone deacetylase inhibitors depending on the zinc-binding group, in particular hydroxamic acids, benzamides, hydrazides, carboxylic acids, and cyclic peptides. The review pays special attention to the mechanisms of development of pathologies involving various isoforms of histone deacetylases. The review shows that, for the trea

Cancer Chemoprevention: A Strategic Approach Using Phytochemicals.

Cancer chemoprevention approaches are aimed at preventing, delaying, or suppressing tumor incidence using synthetic or natural bioactive agents. Mechanistically, chemopreventive agents also aid in mitigating cancer development, either by impeding DNA damage or by blocking the division of premalignant cells with DNA damage. Several pre-clinical studies have substantiated the benefits of using various dietary components as chemopreventives in cancer therapy. The incessant rise in the number of cancer cases globally is an issue of major concern. The excessive toxicity and chemoresistance associat

Nature-Inspired Strategies in Cancer Management: The Potential of Plant Extracts in Modulating Tumour Biology.

Cancer is a serious group of diseases that is a huge problem on a global scale and is the second most common cause of death. Commonly used therapies do not always lead to the complete elimination of diseased cells or tissues and are also burdened with side effects that reduce the quality of life of patients. Due to these difficulties, new therapeutic approaches are still being sought. In recent years, there has been a return to interest in natural methods of treating various diseases, among which phytochemicals are particularly interesting. This article reviews plant extracts with anticancer p

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… Hexane extract of Avicennia marina leaves showed antiproliferative activity against HCT116 cells by arresting the G0–G1 phase of the cell cycle, while in the case of MCF-7 and HepG2 cells, the basis of this activity was the arrest of the S phase of the cell cycle [ 70 ]. …

Monitoring residues of pesticides in food in Brazil: A multiscale analysis of the main contaminants, dietary cancer risk estimative and mechanisms associated.

IntroductionPesticides pose a risk for cancer development and progression. People are continuously exposed to such substances by several routes, including daily intake of contaminated food and water, especially in countries that are highly pesticide consumers and have very permissive legislation about pesticide contamination as Brazil. This work investigated the relationship among pesticides, food contamination, and dietary cancer risk.MethodsAnalyzed two social reports from the Brazilian Government: the Program for Analysis of Residues of Pesticides in Food (PARA) and The National Program for

The Polyphenols α-Mangostin and Nordihydroguaiaretic Acid Induce Oxidative Stress, Cell Cycle Arrest, and Apoptosis in a Cellular Model of Medulloblastoma.

Medulloblastoma is a common malignant brain tumor in the pediatric age. The current therapeutics present serious collateral effects. Polyphenols α-mangostin and nordihydroguaiaretic acid (NDGA) exert potent antitumoral activity in different cancer models, although their antitumoral effects have not been described in medulloblastoma cells yet. This study aimed to examine the proapoptotic effects of these polyphenols on human medulloblastoma cells. Medulloblastoma cell line Daoy was incubated with increasing concentrations of α-mangostin or NDGA for 24 h. The cell viability was analyzed using cr

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… On the other hand, and similar to our results, Mizushina et al. [ 39 ] reported a cell cycle arrest in the G2/M phase in human colon carcinoma HCT116 cells exposed to 18.5 μM of α-mangostin in 24 h. …

Apigenin Inhibits IL-6 Transcription and Suppresses Esophageal Carcinogenesis.

Esophagus cancer is the seventh cause of cancer-related deaths globally. In this study, we analyzed interleukin 6 (IL-6) gene expression in human esophagus cancer patients and showed that IL-6 mRNA levels are significantly higher in tumor tissues and negatively correlated with overall survival, suggesting that IL-6 is a potential therapeutic target for esophagus cancer. We further demonstrated that apigenin, a nature flavone product of green plants, inhibited IL-6 transcription and gene expression in human esophagus cancer Eca-109 and Kyse-30 cells. Apigenin significantly and dose-dependently

Gene editing in cancer therapy: overcoming drug resistance and enhancing precision medicine.

The CRISPR system has revolutionized cancer gene therapy, offering unparalleled precision in genetic manipulation for targeted oncogene disruption, mutation correction, and immune system modulation. This breakthrough tool has demonstrated remarkable potential in overcoming drug resistance, enhancing chemotherapy sensitivity, and improving immunotherapy strategies such as CRISPR-engineered CAR-T cells. Additionally, oncolytic virus-mediated CRISPR delivery has emerged as a novel approach for tumor-specific gene editing, minimizing off-target effects. The rapid transition of CRISPR-based cancer

In vivo activity of miR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs) against multiple myeloma.

Multiple myeloma (MM) is a disease with an adverse outcome and new therapeutic strategies are urgently awaited. A rising body of evidence supports the notion that microRNAs (miRNAs), master regulators of eukaryotic gene expression, may exert anti-MM activity. Here, we evaluated the activity of synthetic miR-34a in MM cells. We found that transfection of miR-34a mimics in MM cells induces a significant change of gene expression with relevant effects on multiple signal transduction pathways. We detected early inactivation of pro-survival and proliferative kinases Erk-2 and Akt followed at later

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… These results are not surprising since it was recently demonstrated that the replacement of miR-34a in erithroleukemic K562 and colon cancer HCT116 cells causes deep modulation of gene expression including some of the genes that we found modulated in our in vitro model [45] . …

Roles and Clinical Significances of ATF6, EMC6, and APAF1 in Prognosis of Pancreatic Cancer.

Background: Pancreatic cancer (PC) is prevalent among malignant tumors with poor prognosis and lacks efficient therapeutic strategies. Endoplasmic reticulum (ER) stress and apoptosis are associated with chronic inflammation and cancer progression. However, the prognostic value of ER stress-related, and apoptosis-related genes in PC remains to be further elucidated. Our study aimed at confirming the prognostic values of the ER stress-related genes, ATF6, EMC6, XBP1, and CHOP, and the apoptosis-related gene, APAF1, in PC patients. Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2

Intravenous Vitamin C for Cancer Therapy - Identifying the Current Gaps in Our Knowledge.

The use of intravenous vitamin C (IVC) for cancer therapy has long been an area of intense controversy. Despite this, high dose IVC has been administered for decades by complementary health care practitioners and physicians, with little evidence base resulting in inconsistent clinical practice. In this review we pose a series of questions of relevance to both researchers and clinicians, and also patients themselves, in order to identify current gaps in our knowledge. These questions include: Do oncology patients have compromised vitamin C status? Is intravenous the optimal route of vitamin C a

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation.

Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basi

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… Treatment with TQ-4-α-linolenoylhydrazone or TQ-4-palmitoylhydrazone was effective in p53-competent HCT116 cells, mediated by an upregulation of p21cip1/waf1 and a downregulation of cyclin E, and associated with an S/G2 arrest of the cell cycle. …

Sorcin: a novel potential target in therapies of cancers.

Soluble resistance-related calcium-binding protein (sorcin) is a member of the penta-EF-hand protein family. Sorcin is widely distributed in normal human tissues, such as the brain, heart, lymphocytes, kidneys, breast and skin. Findings suggest that sorcin is associated with the regulation of calcium homeostasis, cell cycle and vesicle trafficking. It has been reported that many types of non-neoplastic diseases such as diabetes, viral infection, infertility, and nervous system diseases were affected by the expression of sorcin. One of the main issues is the role of sorcin in neoplastic disease

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties

Simultaneous targeting of PI3Kδ and a PI3Kδ-dependent MEK1/2-Erk1/2 pathway for therapy in pediatric B-cell acute lymphoblastic leukemia.

B cell acute lymphoblastic leukemia (B-ALL) is the most common hematological malignancy diagnosed in children, and blockade of the abnormally activated PI3Kδ displayed promising outcomes in B cell acute or chronic leukemias, but the mechanisms are not well understood. Here we report a novel PI3Kδ selective inhibitor X-370, which displays distinct binding mode with p110δ and blocks constitutively active or stimulus-induced PI3Kδ signaling. X-370 significantly inhibited survival of human B cell leukemia cells in vitro, with associated induction of G1 phase arrest and apoptosis. X-370 abrogated b

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… The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest New Drug. 2011;29(6):1276–1283. doi: 10.1007/s10637-010-9481-8. Associated Data Supplementary Materials …

Current Status and Perspectives of Protease Inhibitors and Their Combination with Nanosized Drug Delivery Systems for Targeted Cancer Therapy.

In cancer treatments, many natural and synthetic products have been examined; among them, protease inhibitors are promising candidates for anti-cancer agents. Since dysregulated proteolytic activities can contribute to tumor development and metastasis, antagonization of proteases with tailored inhibitors is an encouraging approach. Although adverse effects of early designs of these inhibitors disappeared after the introduction of next-generation agents, most of the proposed inhibitors did not pass the early stages of clinical trials due to their nonspecific toxicity and lack of pharmacological

HDAC6-an Emerging Target Against Chronic Myeloid Leukemia?

Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Several studies have highlighted the role of histone deacetylase 6 (HDAC6) in various pathologies, including cancer. This protein effectively intervenes in cellular activities by its primarily cytoplasmic localization. In this review, we will discuss the

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… Pyrimidinedione-mediated selective histone deacetylase 6 inhibitors with antitumor activity in colorectal cancer HCT116 cells. Org. Biomol. Chem. 2015;13:10226–10235. doi: 10.1039/C5OB01509J. 148. Yu C.W., Chang P.T., Hsin L.W., Chern J.W. … Azaindolylsulfonamides, with a more selective inhibitory effect on histone deacetylase 6 activity, exhibit antitumor activity in colorectal cancer HCT116 cells. J. Med. Chem. 2014;57:4009–4022. doi: 10.1021/jm401899x. 153. …

Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies.

The increasing cancer incidence has certified oncological management as one of the most critical challenges for the coming decades. New anticancer strategies are still needed, despite the significant advances brought to the forefront in the last decades. The most recent, promising therapeutic approaches have benefitted from the application of human perinatal derivatives (PnD), biological mediators with proven benefits in several fields beyond oncology. To elucidate preclinical results and clinic outcomes achieved in the oncological field, we present a narrative review of the studies resorting

HMMR in human cancers: regulatory mechanism and biological function.

Hyaluronan-mediated motility receptor (HMMR), also referred to as RHAMM or CD168, has gained recognition as a multifunctional protein that mediates the transmission of extracellular matrix-derived hyaluronan (HA) signals to intracellular pathways regulating tumor growth, migration, and mitosis. Overexpression of HMMR is observed in various cancers, including head and neck squamous cell carcinoma, breast cancer, lung cancer, and prostate cancer, as well as several hematologic malignancies. This elevated expression correlates with poor prognosis, rendering it a valuable marker for survival predi

Renaissance of Traditional Mineral Drugs in Cancer: Advanced Delivery Strategies and Bioengineering Approaches.

Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomod