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1.
Inhibitory effect of polyphenols (phenolic acids, lignans, and stilbenes) on cancer by regulating signal transduction pathways: a review.
Hazafa, A, Iqbal, MO, Javaid, U, Tareen, MBK, Amna, D, Ramzan, A, Piracha, S, Naeem, M
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2022;(3):432-445
Abstract
Natural products, especially polyphenols (phenolic acids, lignans, and stilbenes) are suggested to be more potent anticancer drugs because of their no or less adverse effects, excess availability, high accuracy, and secure mode of action. In the present review, potential anticancer mechanisms of action of some polyphenols including phenolic acids, lignans, and stilbenes are discussed based on clinical, epidemiological, in vivo, and in vitro studies. The emerging evidence revealed that phenolic acids, lignans, and stilbenes induced apoptosis in the treatment of breast (MCF-7), colon (Caco-2), lung (SKLU-1), prostate (DU-145 and LNCaP), hepatocellular (hepG-2), and cervical (A-431) cancer cells, cell cycle arrest (S/G2/M/G1-phases) in gastric (MKN-45 and MKN-74), colorectal (HCT-116), bladder (T-24 and 5637), oral (H-400), leukemic (HL-60 and MOLT-4) and colon (Caco-2) cancer cells, and inhibit cell proliferation against the prostate (PC-3), liver (LI-90), breast (T47D and MDA-MB-231), colon (HT-29 and Caco-2), cervical (HTB-35), and MIC-1 cancer cells through caspase-3, MAPK, AMPK, Akt, NF-κB, Wnt, CD95, and SIRT1 pathways. Based on accumulated data, we suggested that polyphenols could be considered as a viable therapeutic option in the treatment of cancer cells in the near future.
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2.
Decoding the Phosphatase Code: Regulation of Cell Proliferation by Calcineurin.
Masaki, T, Shimada, M
International journal of molecular sciences. 2022;(3)
Abstract
Calcineurin, a calcium-dependent serine/threonine phosphatase, integrates the alterations in intracellular calcium levels into downstream signaling pathways by regulating the phosphorylation states of several targets. Intracellular Ca2+ is essential for normal cellular physiology and cell cycle progression at certain critical stages of the cell cycle. Recently, it was reported that calcineurin is activated in a variety of cancers. Given that abnormalities in calcineurin signaling can lead to malignant growth and cancer, the calcineurin signaling pathway could be a potential target for cancer treatment. For example, NFAT, a typical substrate of calcineurin, activates the genes that promote cell proliferation. Furthermore, cyclin D1 and estrogen receptors are dephosphorylated and stabilized by calcineurin, leading to cell proliferation. In this review, we focus on the cell proliferative functions and regulatory mechanisms of calcineurin and summarize the various substrates of calcineurin. We also describe recent advances regarding dysregulation of the calcineurin activity in cancer cells. We hope that this review will provide new insights into the potential role of calcineurin in cancer development.
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3.
Next steps for clinical translation of adenosine pathway inhibition in cancer immunotherapy.
Augustin, RC, Leone, RD, Naing, A, Fong, L, Bao, R, Luke, JJ
Journal for immunotherapy of cancer. 2022;(2)
Abstract
Increasing evidence supports targeting the adenosine pathway in immuno-oncology with several clinical programs directed at adenosine A2 receptor (A2AR, A2BR), CD73 and CD39 in development. Through a cyclic-AMP-mediated intracellular cascade, adenosine shifts the cytokine and cellular profile of the tumor microenvironment away from cytotoxic T cell inflammation toward one of immune tolerance. A perpetuating cycle of tumor cell proliferation, tissue injury, dysregulated angiogenesis, and hypoxia promote adenosine accumulation via ATP catabolism. Adenosine receptor (eg, A2AR, A2BR) stimulation of both the innate and adaptive cellular precursors lead to immunosuppressive phenotypic differentiation. Preclinical work in various tumor models with adenosine receptor inhibition has demonstrated restoration of immune cell function and tumor regression. Given the broad activity but known limitations of anti-programmed cell death protein (PD1) therapy and other checkpoint inhibitors, ongoing studies have sought to augment the successful outcomes of anti-PD1 therapy with combinatorial approaches, particularly adenosine signaling blockade. Preliminary data have demonstrated an optimal safety profile and enhanced overall response rates in several early phase clinical trials with A2AR and more recently CD73 inhibitors. However, beneficial outcomes for both monotherapy and combinations have been mostly lower than expected based on preclinical studies, indicating a need for more nuanced patient selection or biomarker integration that might predict and optimize patient outcomes. In the context of known immuno-oncology biomarkers such as tumor mutational burden and interferon-associated gene expression, a comparison of adenosine-related gene signatures associated with clinical response indicates an underlying biology related to immunosuppression, angiogenesis, and T cell inflammation. Importantly, though, adenosine associated gene expression may point to a unique intratumoral phenotype independent from IFN-γ related pathways. Here, we discuss the cellular and molecular mechanisms of adenosine-mediated immunosuppression, preclinical investigation of adenosine signaling blockade, recent response data from clinical trials with A2AR, CD73, CD39 and PD1/L1 inhibitors, and ongoing development of predictive gene signatures to enhance combinatorial immune-based therapies.
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4.
The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer.
Hu, Y, Guo, N, Yang, T, Yan, J, Wang, W, Li, X
Oxidative medicine and cellular longevity. 2022;:1458143
Abstract
Artemisinin (ART) is a bioactive molecule derived from the Chinese medicinal plant Artemisia annua (Asteraceae). ART and artemisinin derivatives (ARTs) have been effectively used for antimalaria treatment. The structure of ART is composed of a sesquiterpene lactone, including a peroxide internal bridge that is essential for its activity. In addition to their well-known antimalarial effects, ARTs have been shown recently to resist a wide range of tumors. The antineoplastic mechanisms of ART mainly include cell cycle inhibition, inhibition of tumor angiogenesis, DNA damage, and ferroptosis. In particular, ferroptosis is a novel nonapoptotic type of programmed cell death. However, the antitumor mechanisms of ARTs by regulating ferroptosis remain unclear. Through this review, we focus on the potential antitumor function of ARTs by acting on ferroptosis, including the regulation of iron metabolism, generation of reactive oxygen species (ROS), and activation of endoplasmic reticulum stress (ERS). This article systematically reviews the recent progress in ferroptosis research and provides a basis for ARTs as an anticancer drug in clinical practice.
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5.
Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism: A Latin American Perspective.
Athanazio, RA, Ceresetto, JM, Marfil Rivera, LJ, Cesarman-Maus, G, Galvez, K, Marques, MA, Tabares, AH, Ortiz Santacruz, CA, Santini, FC, Corrales, L, et al
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2022;:10760296221082988
Abstract
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.
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6.
SP and KLF Transcription Factors in Cancer Metabolism.
Orzechowska-Licari, EJ, LaComb, JF, Mojumdar, A, Bialkowska, AB
International journal of molecular sciences. 2022;(17)
Abstract
Tumor development and progression depend on reprogramming of signaling pathways that regulate cell metabolism. Alterations to various metabolic pathways such as glycolysis, oxidative phosphorylation, lipid metabolism, and hexosamine biosynthesis pathway are crucial to sustain increased redox, bioenergetic, and biosynthesis demands of a tumor cell. Transcription factors (oncogenes and tumor suppressors) play crucial roles in modulating these alterations, and their functions are tethered to major metabolic pathways under homeostatic conditions and disease initiation and advancement. Specificity proteins (SPs) and Krüppel-like factors (KLFs) are closely related transcription factors characterized by three highly conserved zinc fingers domains that interact with DNA. Studies have demonstrated that SP and KLF transcription factors are expressed in various tissues and regulate diverse processes such as proliferation, differentiation, apoptosis, inflammation, and tumorigenesis. This review highlights the role of SP and KLF transcription factors in the metabolism of various cancers and their impact on tumorigenesis. A better understanding of the role and underlying mechanisms governing the metabolic changes during tumorigenesis could provide new therapeutic opportunities for cancer treatment.
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7.
Nutritional Approach to Cancer Cachexia: A Proposal for Dietitians.
Tanaka, K, Nakamura, S, Narimatsu, H
Nutrients. 2022;(2)
Abstract
Cachexia is one of the most common, related factors of malnutrition in cancer patients. Cancer cachexia is a multifactorial syndrome characterized by persistent loss of skeletal muscle mass and fat mass, resulting in irreversible and progressive functional impairment. The skeletal muscle loss cannot be reversed by conventional nutritional support, and a combination of anti-inflammatory agents and other nutrients is recommended. In this review, we reviewed the effects of nutrients that are expected to combat muscle loss caused by cancer cachexia (eicosapentaenoic acid, β-hydroxy-β-methylbutyrate, creatine, and carnitine) to propose nutritional approaches that can be taken at present. Current evidence is based on the intake of nutrients as supplements; however, the long-term and continuous intake of nutrients as food has the potential to be useful for the body. Therefore, in addition to conventional nutritional support, we believe that it is important for the dietitian to work with the clinical team to first fully assess the patient's condition and then to safely incorporate nutrients that are expected to have specific functions for cancer cachexia from foods and supplements.
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8.
Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations.
Zhu, H, Bi, D, Zhang, Y, Kong, C, Du, J, Wu, X, Wei, Q, Qin, H
Signal transduction and targeted therapy. 2022;(1):11
Abstract
The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.
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9.
Traditionally Used Natural Products in Preventing Ionizing Radiation-Induced.
Kalekhan, F, Kudva, AK, Raghu, SV, Rao, S, Hegde, SK, Simon, P, Baliga, MS
Anti-cancer agents in medicinal chemistry. 2022;(1):64-82
Abstract
UNLABELLED In the treatment of cancer, the use of ionizing radiation is an important modality. However, on the downside, radiation, when used for curative purposes, causes acute dermatitis or radiodermatitis at the site of radiation in most individuals. From a clinical viewpoint, severe dermatitis causes a burning and itching sensation is very painful and severely affects the quality of life of the individual undergoing treatment. In worse situations, acute radiation dermatitis can cause gaps or breaks in the planned treatment and this can adversely affect the treatment objective and outcome. BACKGROUND In various traditional and folk systems of medicine, plants and plant products have been used since time immemorial for treating various skin ailments. Further, many cosmeceutical creams formulated based on knowledge from ethnomedicinal use are marketed and used to treat various ailments. In the current review, an attempt is made at summarizing the beneficial effects of some plants and plant products in mitigating acute radiation dermatitis in humans undergoing curative radiotherapy. Additionally, emphasis is also placed on the mechanisms responsible for the beneficial effects. OBJECTIVE The objective of this review is to summarize the clinical observations on the prevention of radiodermatitis by plant products. In this review, the protective effects of Adlay (Coix lachryma-jobi L.) bran extract, Aloe vera, Calendula officinalis, Cucumis sativus, green tea constituent the epigallocatechin-3-gallate, honey, Achillea millefolium, Matricaria chamomilla, olive oil, and some polyherbal creams are addressed by also focusing on the mechanism of action for the beneficial effects. METHODS Two authors' data mined for information in Google Scholar, PubMed, Embase, and the Cochrane Library for publications in the field from 1901 up to July 2020. The focus was on acute radiation dermatitis, ionizing radiation, curative radiotherapy, human cancer. The articles were collected and analyzed. RESULTS For the first time, this review addresses the usefulness of natural products like adlay bran, Aloe vera, Calendula officinalis, Cucumis sativus, green tea constituent the epigallocatechin-3-gallate, honey, Achillea millefolium, Matricaria chamomilla, olive oil, and some experimentally constituted and commercially available polyherbal creams as skincare agents against the deleterious effects of ionizing radiation on the skin. The protective effects are possibly due to the free radical scavenging, antioxidant, anti-inflammatory, wound healing and skin protective effects. CONCLUSION The authors suggest that these plants have been used since antiquity as medicinal agents and require in-depth investigation with both clinical and preclinical validated models of study. The results of these studies will be extremely useful to cancer patients requiring curative radiotherapy, the dermatology fraternity, agro-based and pharmaceutical sectors at large.
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10.
Mushroom Polysaccharide-Assisted Anticarcinogenic Mycotherapy: Reviewing Its Clinical Trials.
Sivanesan, I, Muthu, M, Gopal, J, Oh, JW
Molecules (Basel, Switzerland). 2022;(13)
Abstract
Of the biologically active components, polysaccharides play a crucial role of high medical and pharmaceutical significance. Mushrooms have existed for a long time, dating back to the time of the Ancient Egypt and continue to be well explored globally and experimented with in research as well as in national and international cuisines. Mushroom polysaccharides have slowly become valuable sources of nutraceuticals which have been able to treat various diseases and disorders in humans. The application of mushroom polysaccharides for anticancer mycotherapy is what is being reviewed herein. The widespread health benefits of mushroom polysaccharides have been highlighted and the significant inputs of mushroom-based polysaccharides in anticancer clinical trials have been presented. The challenges and limitation of mushroom polysaccharides into this application and the gaps in the current application areas that could be the future direction have been discussed.