Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells – A potential contribution to the predictive, preventive, and personalized medicine

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 55, P. 103 - 118

Published: March 4, 2023

Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically maintain their supply energy and precursor molecules for biosynthesis thus sustain rapid proliferation tumor growth. Among various metabolic adaptations observed in cells, altered glucose metabolism is most widely studied. The aberrant glycolytic modification has been associated with cell division, growth, progression, drug resistance. higher rates glycolysis as a hallmark modulated by transcription factor hypoxia inducible 1 alpha (HIF-1α), downstream target PI3K/Akt signaling, deregulated pathway cancer. We provide detailed overview current, primarily experimental, evidence on potential effectiveness flavonoids combat glycolysis-induced conventional targeted therapies. manuscript focuses reducing via affecting PI3K/Akt, HIF-1α (as critical that regulated pathway), key mediators PI3K/Akt/HIF-1α signaling (glucose transporters enzymes). working hypothesis proposes – an attractive application mitigate Phytochemicals represent source promising substances applicable primary, secondary, tertiary care. However, accurate patient stratification individualized profiling crucial steps paradigm shift from reactive predictive, preventive, personalized medicine (PPPM / 3PM). article focused targeting molecular patterns natural provides evidence-based recommendations 3PM relevant implementation.

Language: Английский

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Anti-prostate cancer protection and therapy in the framework of predictive, preventive and personalised medicine — comprehensive effects of phytochemicals in primary, secondary and tertiary care

The EPMA Journal, Journal Year: 2022, Volume and Issue: 13(3), P. 461 - 486

Published: July 8, 2022

Abstract According to the GLOBOCAN 2020, prostate cancer (PCa) is most often diagnosed male in 112 countries and leading cancer-related death 48 countries. Moreover, PCa incidence permanently increases adolescents young adults. Also, rates of metastasising continuously grow up populations. Corresponding socio-economic burden enormous: treatment costs increase more rapidly than for any other cancer. In order reverse current trends exploding cases costs, pragmatic decisions should be made, favour advanced populational screening programmes effective anti-PCa protection at level health-to-disease transition (sub-optimal health conditions) demonstrating highest cost-efficacy treatments. For doing this, paradigm change from reactive treatments clinically manifested predictive approach personalised prevention essential. Phytochemicals are associated with potent anti-cancer activity targeting each stage carcinogenesis including cell apoptosis proliferation, invasiveness metastatic disease. example, their positive effects demonstrated stabilising restoring mitochondrial quality, which if compromised strongly sub-optimal conditions strong predisposition aggressive sub-types. Further, phytochemicals significantly enhance response cells therapies radio- chemotherapy. Evident plant-based mitigation negative side-effects frequently observed conventional has been reported. Finally, dual anti-viral such as these silibinin have being highly relevant improved management secondary tertiary care, under pandemic conditions, since PCa-affected individuals per evidence vulnerable towards COVID-19 infection. Here, we present a comprehensive data analysis considered primary care well an disease framework predictive, preventive medicine.

Language: Английский

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Guidelines for genetic testing in prostate cancer: a scoping review

Prostate Cancer and Prostatic Diseases, Journal Year: 2023, Volume and Issue: 27(4), P. 594 - 603

Published: May 18, 2023

Abstract Background Genetic testing, to identify pathogenic or likely variants in prostate cancer, is valuable guiding treatment decisions for men with cancer and inform prevention early detection options their immediate blood relatives. There are various guidelines consensus statements genetic testing cancer. Our aim review recommendations across current the level of evidence supporting those recommendations. Methods A scoping was conducted following Preferred Reporting Items Systematic Reviews Meta-analyses extension (PRISMA-ScR) guidelines. Electronic database searches manual grey literature, including websites key organisations were conducted. Using Population, Concept, Context (PCC) framework, this included: at high risk biological families; existing from any geographical location worldwide. Results Of 660 citations identified, 23 met inclusion criteria review. Based on different levels about who should be tested how, a diverse range identified. general among that metastatic disease offered testing; however, there less relation localised While some which genes test, varied regarding methods implementation. Conclusion routinely recommended numerous exist, still considerable lack how they tested. Further needed value-based strategies implementation practice.

Language: Английский

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Phytochemical-based nanodrugs going beyond the state-of-the-art in cancer management—Targeting cancer stem cells in the framework of predictive, preventive, personalized medicine

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 23, 2023

Cancer causes many deaths worldwide each year, especially due to tumor heterogeneity leading disease progression and treatment failure. Targeted of heterogeneous population cells - cancer stem is still an issue in protecting affected individuals against associated multidrug resistance progression. Nanotherapeutic agents have the potential go beyond state-of-the-art approaches overall management. Specially assembled nanoparticles act as carriers for targeted drug delivery. Several nanodrugs already been approved by US Food Drug Administration (FDA) treating different types. Phytochemicals isolated from plants demonstrate considerable nanomedical applications oncology thanks their antioxidant, anti-inflammatory, anti-proliferative, other health benefits. Phytochemical-based NPs can enhance anticancer therapeutic effects, improve cellular uptake agents, mitigate side effects toxic treatments. Per evidence, phytochemical-based specifically target CSCs decreasing risks relapse metastatic manifestation. Therefore, this review focuses on current outlook targeting research studies consideration framework predictive, preventive, personalized medicine (3PM).

Language: Английский

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Generative Adversarial Networks Can Create High Quality Artificial Prostate Cancer Magnetic Resonance Images

Journal of Personalized Medicine, Journal Year: 2023, Volume and Issue: 13(3), P. 547 - 547

Published: March 18, 2023

The recent integration of open-source data with machine learning models, especially in the medical field, has opened new doors to studying disease progression and/or regression. However, ability use for approaches is limited by specificity a particular condition. In this context, most technologies, like generative adversarial networks (GANs), are being looked upon as potential way generate high-quality synthetic that preserve clinical variability despite some success, GAN model usage remains largely minimal when depicting heterogeneity such prostate cancer. Previous studies from our group members have focused on automating quantitative multi-parametric magnetic resonance imaging (mpMRI) using habitat risk scoring (HRS) maps cancer patients BLaStM trial. current study, we aimed images trial and other sources train images, validate their quality. used T2-weighted MRI training Single Natural Image GANs (SinGANs) make model. A deep semantic segmentation pipeline trained segment boundary 2D slices. Synthetic high-level were filtered quality control assessment participating scientists varying degrees experience (more than ten years, one year, or no experience) work images. Results showed experienced correctly identified conventional vs. 67% accuracy, year 58% prior reached 50% accuracy. Nearly half (47%) mistakenly evaluated conventional. Interestingly, blinded assessment, board-certified radiologist did not significantly differentiate between context mean Furthermore, usability generated MRIs, subjected these anomaly detection along original Importantly, success rate control-approved phase corresponded sum, study shows promise MRIs can be GANs. Such an AI may contribute various applications which involve supervised machine-learning approaches.

Language: Английский

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Targeting benign prostate hyperplasia treatments: AR/TGF-β/NOX4 inhibition by apocynin suppresses inflammation and proliferation

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 57, P. 135 - 147

Published: April 14, 2023

Apocynin (Apo), an NADPH oxidase (NOX) inhibitor, has been widely used to treat various inflammatory diseases. However, the therapeutic effects of Apo on benign prostatic hyperplasia (BPH), a multifactorial disease associated with chronic inflammation and hormone imbalance, remain unknown. The link between androgen signaling, reactive oxygen species (ROS), prostate cell proliferation may contribute pathogenesis BPH; therefore, aim this study was identify specific signaling pathway involved demonstrate whether anti-oxidant plays role in prevention treatment BPH. Ingenuity analysis si-RNA transfection were conducted receptor (AR) NOX4 linkage Pathological markers BPH measured by H&E staining, immunoblotting, ELISA, qRT-PCR, immunofluorescence examine effect Apo. Rats stimulated testosterone BPH-1 cells as models. AR network-mediated oxidative stress upregulated model. Next, we examined mouse In testosterone-induced rat model, alleviated pathological enlargement suppressed androgen/AR signaling. upregulation proinflammatory promoted expression factors. Furthermore, regulated TGF-β/Glut9/activin macrophage programming. cells, AR-mediated TGFB alleviating stress. activated anti-inflammatory systems polarization cells. knockdown partially abolished beneficial indicating AR-dependent contrast existing therapies, provide new application for treatment, especially BPH, targeting AR/TGF-β/NOX4 pathway.

Language: Английский

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In Vivo Growth Inhibition of Human Caucasian Prostate Adenocarcinoma in Nude Mice Induced by Amygdalin with Metabolic Enzyme Combinations

BioMed Research International, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 7

Published: May 21, 2022

Cancer of the prostate is an indicated type that often recorded as a kind cancer in men and second critical cause mortality through cases. Many pharmacological investigations have shown numerous herbal substances possess anticancer action. Amygdalin (AMD) has antitumour capabilities works antioxidant, antibacterial, anti-inflammatory, immune-regulating characteristics. The effects amygdalin its metabolizing enzymes, rhodanese (RHD) betaglucosidase (BGD), were examined vivo, well their processes. Novel, effective combination agents are necessary to increase existing treatment rates. This research was aimed at determining anticarcinogenic impact vivo. RHD BGD on AMD Subcutaneously, PC3 cell lines implanted into nude mice. Mice treated every day with 0.5 ml 50 mg/ml (AMD), AMD+ (RHD 0.1 mg/ml), AMD+(BGD doxorubicin (DOX mg/ml). normalized for negative control untreated In morphopathological alterations tumour tissue analyzed by histopathological staining methods. After 35 days therapy, growth size inhibition evident, indicating function metabolic enzymes regulating AMD's effect We concluded role elevating antigrowth Balb/c mice AMD.

Language: Английский

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Onco-immunity and therapeutic application of amygdalin: A review

Journal of Oral Biology and Craniofacial Research, Journal Year: 2022, Volume and Issue: 13(2), P. 155 - 163

Published: Dec. 28, 2022

Amygdalin is known as a chemical compound derived from various fruits. The glycosides existing in this plant have been historically utilized an anticancer agent. This review presented overview of amygdalin and its onco-immunity other therapeutic medical applications.A literature search for studies relating to cancer treatment was carried out using PubMed Google Scholar. Combinations the following terms were used strategies: "amygdalin," "rhodanese," "cyanide," "cyanogenic," "hypothiocyanite," "mandelonitrile," "glucosides," "cancer," "apoptosis," "cytotoxicity," combined with term such "seed," "almond," or "apricot," "cancer + cell line, antiproliferation inhibition," "BAX From March 3, 1981 until April 15, 2021, all English-language papers evaluated based on inclusion criteria. Publications included reviews, chapters books, original research papers.The FDA prohibits usage due lack proof cure cases. When natural-based conditional chemotherapeutic medicines causes synergistic effects. Besides, manage asthma, improve immune system, induce apoptosis human renal fibroblasts, inhibit hyperglycemia.Various uses found managing improving inducing inhibiting hyperglycemia. More effective vitro are required elucidate exact role herb applications.

Language: Английский

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The Role of Different Types of microRNA in the Pathogenesis of Breast and Prostate Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1980 - 1980

Published: Jan. 19, 2023

Micro ribonucleic acids (microRNAs or miRNAs) form a distinct subtype of non-coding RNA and are widely recognized as one the most significant gene expression regulators in mammalian cells. Mechanistically, regulation occurs through microRNA binding with its response elements 3’-untranslated region target messenger RNAs (mRNAs), resulting post-transcriptional silencing genes, expressing mRNAs. Compared to small interfering RNAs, microRNAs have more complex regulatory patterns, making them suitable for fine-tuning expressions different tissues. Dysregulation is well known causative factors malignant cell growth. Today, there numerous data points regarding cancer transcriptomes, specificity changes various tissues, predictive value specific biomarkers. Breast (BCa) common women worldwide seriously impairs patients’ physical health. Its incidence has been predicted rise further. Mounting evidence indicates that play key roles tumorigenesis development. Prostate (PCa) commonly diagnosed cancers men. Different an important role PCa. Early diagnosis BCa PCa using very useful improving individual outcomes framework predictive, preventive, personalized (3P) medicine, thereby reducing economic burden. This article reviews types progression.

Language: Английский

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Flavonoids attenuate cancer metabolism by modulating Lipid metabolism, amino acids, ketone bodies and redox state mediated by Nrf2

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 949, P. 175655 - 175655

Published: March 13, 2023

Language: Английский

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