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1.
The anti-cancerous activity of adaptogenic herb Astragalus membranaceus.
Sheik, A, Kim, K, Varaprasad, GL, Lee, H, Kim, S, Kim, E, Shin, JY, Oh, SY, Huh, YS
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2021;:153698
Abstract
BACKGROUND Cancer is the most dreadful disease increasing rapidly causing an economic burden globally. A standardized chemotherapy regimen planned with curative intent weakens the immune system and damages healthy cells making the patient prone to infections and severe side effects with pain and fatigue. PURPOSE Astragalus membranaceus (AM) has a long history of use in the treatment of severe adverse diseases. For thousands of years, it has been used in mixed herbal decoctions for the treatment of cancer. Due to growing interest in this plant root for its application to treat various types of cancers and tumors, has attracted researcher's interest. METHOD The literature search was done from core collections of electronic databases such as Web of Science, Google Scholar, PubMed and Science Direct using keywords given below and terms like pharmacological and phytochemical details of this plant. OUTCOME Astragalus membranaceus has demonstrated the ability to modulate the immune system during drug therapy making the patient physically fit and prolonged life. It has become a buzzword of herbalists as it is one of the best of seven important adaptogenic herbs with a protective effect against chronic stress and cancer. It demonstrated significant amelioration of the perilous toxic effects induced by concurrently administered chemo onco-drugs. CONCLUSION The natural phytoconstituents of this plant formononetin, astragalus polysaccharide, and astragalosides which show high potential anti-cancerous activity are studied and discussed in detail. One of them are used in clinical trials to overcome cancer related fatigue. Overall, this review aims to provide an insight into Astragalus membranaceus status in cancer therapy.
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Therapeutic Potential of Thymoquinone in Triple-Negative Breast Cancer Prevention and Progression through the Modulation of the Tumor Microenvironment.
Adinew, GM, Taka, E, Mochona, B, Badisa, RB, Mazzio, EA, Elhag, R, Soliman, KFA
Nutrients. 2021;(1)
Abstract
To date, the tumor microenvironment (TME) has gained considerable attention in various areas of cancer research due to its role in driving a loss of immune surveillance and enabling rapid advanced tumor development and progression. The TME plays an integral role in driving advanced aggressive breast cancers, including triple-negative breast cancer (TNBC), a pivotal mediator for tumor cells to communicate with the surrounding cells via lymphatic and circulatory systems. Furthermore, the TME plays a significant role in all steps and stages of carcinogenesis by promoting and stimulating uncontrolled cell proliferation and protecting tumor cells from the immune system. Various cellular components of the TME work together to drive cancer processes, some of which include tumor-associated adipocytes, fibroblasts, macrophages, and neutrophils which sustain perpetual amplification and release of pro-inflammatory molecules such as cytokines. Thymoquinone (TQ), a natural chemical component from black cumin seed, is widely used traditionally and now in clinical trials for the treatment/prevention of multiple types of cancer, showing a potential to mitigate components of TME at various stages by various pathways. In this review, we focus on the role of TME in TNBC cancer progression and the effect of TQ on the TME, emphasizing their anticipated role in the prevention and treatment of TNBC. It was concluded from this review that the multiple components of the TME serve as a critical part of TNBC tumor promotion and stimulation of uncontrolled cell proliferation. Meanwhile, TQ could be a crucial compound in the prevention and progression of TNBC therapy through the modulation of the TME.
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In silico identification of natural products from Traditional Chinese Medicine for cancer immunotherapy.
Cai, C, Wu, Q, Hong, H, He, L, Liu, Z, Gu, Y, Zhang, S, Wang, Q, Fan, X, Fang, J
Scientific reports. 2021;(1):3332
Abstract
Advances in immunotherapy have revolutionized treatments in many types of cancer. Traditional Chinese Medicine (TCM), which has a long history of clinical adjuvant application against cancer, is emerging as an important medical resource for developing innovative cancer treatments, including immunotherapy. In this study, we developed a quantitative and systems pharmacology-based framework to identify TCM-derived natural products for cancer immunotherapy. Specifically, we integrated 381 cancer immune response-related genes and a compound-target interaction network connecting 3273 proteins and 766 natural products from 66 cancer-related herbs based on literature-mining. Via systems pharmacology-based prediction, we uncovered 182 TCM-derived natural products having potential anti-tumor immune responses effect. Importantly, 32 of the 49 most promising natural products (success rate = 65.31%) are validated by multiple evidence, including published experimental data from clinical studies, in vitro and in vivo assays. We further identified the mechanism-of-action of TCM in cancer immunotherapy using network-based functional enrichment analysis. We showcased that three typical natural products (baicalin, wogonin, and oroxylin A) in Huangqin (Scutellaria baicalensis Georgi) potentially overcome resistance of known oncology agents by regulating tumor immunosuppressive microenvironments. In summary, this study offers a novel and effective systems pharmacology infrastructure for potential cancer immunotherapeutic development by exploiting the medical wealth of natural products in TCM.
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Clarifying the molecular mechanism of tomentosin‑induced antiproliferative and proapoptotic effects in human multiple myeloma via gene expression profile and genetic interaction network analysis.
Virdis, P, Migheli, R, Bordoni, V, Fiorentino, FP, Sanna, L, Marchesi, I, Pintore, G, Galleri, G, Muroni, MR, Bagella, L, et al
International journal of molecular medicine. 2021;(6)
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Abstract
Multiple myeloma (MM) is an aggressive B cell malignancy. Substantial progress has been made in the therapeutic context for patients with MM, however it still represents an incurable disease due to drug resistance and recurrence. Development of more effective or synergistic therapeutic approaches undoubtedly represents an unmet clinical need. Tomentosin is a bioactive natural sesquiterpene lactone extracted by various plants with therapeutic properties, including anti‑neoplastic effects. In the present study, the potential antitumor activity of tomentosin was evaluated on the human RPMI‑8226 cell line, treated with increasing tomentosin concentration for cytotoxicity screening. The data suggested that both cell cycle arrest and cell apoptosis could explain the antiproliferative effects of tomentosin and may result in the inhibition of RPMI‑8226 cell viability. To assess differentially expressed genes contributing to tomentosin activity and identify its mechanism of action, a microarray gene expression profile was performed, identifying 126 genes deregulated by tomentosin. To address the systems biology and identify how tomentosin deregulates gene expression in MM from a systems perspective, all deregulated genes were submitted to enrichment and molecular network analysis. The Protein‑Protein Interaction (PPI) network analysis showed that tomentosin in human MM induced the downregulation of genes involved in several pathways known to lead immune‑system processes, such as cytokine‑cytokine receptor interaction, chemokine or NF‑κB signaling pathway, as well as genes involved in pathways playing a central role in cellular neoplastic processes, such as growth, proliferation, migration, invasion and apoptosis. Tomentosin also induced endoplasmic reticulum stress via upregulation of cyclic AMP‑dependent transcription factor ATF‑4 and DNA damage‑inducible transcript 3 protein genes, suggesting that in the presence of tomentosin the protective unfolded protein response signaling may induce cell apoptosis. The functional connections analysis executed using the Connectivity Map tool, suggested that the effects of tomentosin on RPMI‑8226 cells might be similar to those exerted by heat shock proteins inhibitors. Taken together, these data suggested that tomentosin may be a potential drug candidate for the treatment of MM.
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Anticancer property of ginsenoside Rh2 from ginseng.
Li, X, Chu, S, Lin, M, Gao, Y, Liu, Y, Yang, S, Zhou, X, Zhang, Y, Hu, Y, Wang, H, et al
European journal of medicinal chemistry. 2020;:112627
Abstract
Ginseng has been used as a well-known traditional Chinese medicine since ancient times. Ginsenosides as its main active constituents possess a broad scope of pharmacological properties including stimulating immune function, enhancing cardiovascular health, increasing resistance to stress, improving memory and learning, developing social functioning and mental health in normal persons, and chemotherapy. Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides from Panax ginseng. When applied to cancer treatment, Rh2 not only exhibits the anti-proliferation, anti-invasion, anti-metastasis, induction of cell cycle arrest, promotion of differentiation, and reversal of multi-drug resistance activities against multiple tumor cells, but also alleviates the side effects after chemotherapy or radiotherapy. In the past decades, nearly 200 studies on Rh2 in the treatment of cancer have been published, however no specific reviews have been conducted by now. So the purpose of this review is to provide a systematic summary and analysis of the anticancer effects and the potential mechanisms of Rh2 extracted from Ginseng then give a future prospects about it. In the end of this paper the metabolism and derivatives of Rh2 also have been documented.
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Curcumin and Photobiomodulation in Chronic Viral Hepatitis and Hepatocellular Carcinoma.
Ailioaie, LM, Litscher, G
International journal of molecular sciences. 2020;(19)
Abstract
Immune modulation is a very modern medical field for targeting viral infections. In the race to develop the best immune modulator against viruses, curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. As a bright yellow component of turmeric spice, curcumin has been the subject of thousands of scientific and clinical studies in recent decades to prove its powerful antioxidant properties and anticancer effects. Curcumin has been shown to influence inter- and intracellular signaling pathways, with direct effects on gene expression of the antioxidant proteins and those that regulate the immunity. Experimental studies have shown that curcumin modulates several enzyme systems, reduces nitrosative stress, increases the antioxidant capacity, and decreases the lipid peroxidation, protecting against fatty liver pathogenesis and fibrotic changes. Hepatitis B virus (HBV) affects millions of people worldwide, having sometimes a dramatic evolution to chronic aggressive infection, cirrhosis, and hepatocellular carcinoma. All up-to-date treatments are limited, there is still a gap in the scientific knowledge, and a sterilization cure may not yet be possible with the removal of both covalently closed circular DNA (cccDNA) and the embedded HBV DNA. With a maximum light absorption at 420 nm, the cytotoxicity of curcumin as photosensitizer could be expanded by the intravenous blue laser blood irradiation (IVBLBI) or photobiomodulation in patients with chronic hepatitis B infection, Hepatitis B e-antigen (HBeAg)-positive, noncirrhotic, but nonresponsive to classical therapy. Photobiomodulation increases DNA repair by the biosynthesis of complex molecules with antioxidant properties, the outset of repairing enzyme systems and new phospholipids for regenerating the cell membranes. UltraBioavailable Curcumin and blue laser photobiomodulation could suppress the virus and control better the disease by reducing inflammation/fibrosis and stopping the progression of chronic hepatitis, reversing fibrosis, and diminishing the progression of cirrhosis, and decreasing the incidence of hepatocellular carcinoma. Photodynamic therapy with blue light and curcumin opens new avenues for the effective prevention and cure of chronic liver infections and hepatocellular carcinoma. Blue laser light and UltraBioavailable Curcumin could be a new valuable alternative for medical applications in chronic B viral hepatitis and hepatocarcinoma, saving millions of lives.
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[Research progress on anti-tumor effects and mechanisms of triptolide and its combined application].
Shi, JF, Luo, YY, Li, JX, Luo, RF, Chen, L, Li, J, Zhang, JM, Fu, CM
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. 2019;(16):3391-3398
Abstract
Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.
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Saffron (Crocus sativus) in the treatment of gastrointestinal cancers: Current findings and potential mechanisms of action.
Naeimi, M, Shafiee, M, Kermanshahi, F, Khorasanchi, Z, Khazaei, M, Ryzhikov, M, Avan, A, Gorji, N, Hassanian, SM
Journal of cellular biochemistry. 2019;(10):16330-16339
Abstract
Gastrointestinal (GI) cancers are major causes of cancer-related mortality worldwide and include malignancies of the GI tract such as the stomach, liver, pancreas, small intestine, colon, and rectum. Promising and selective anticancer effects of pharmacologically active components of saffron (Crocus sativus L.) have been shown in preclinical in vitro and in vivo studies. Saffron and its active components including crocin, crocetin, and safranal exert their anticancer effects through different mechanisms, including induction of apoptosis, influence on the cell cycle, and regulation of host immune response and anti-inflammatory activities. This review summarizes the recent literature on the chemopreventive properties of saffron in GI cancers to have a better understanding of the potential underlying mechanisms and hence the appropriate management of these malignancies.
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Etoposide combined with ruxolitinib for refractory hemophagocytic lymphohistiocytosis during pregnancy: a case report and literature review.
Wang, S, Wu, J, Jing, X, Zhang, Y, Tang, H, Wu, J
Hematology (Amsterdam, Netherlands). 2019;(1):751-756
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder caused by uncontrolled inflammatory responses and the activation of T lymphocytes. This life-threatening disease, characterized by fever, cytopenia and hepatosplenomegaly, is extremely rare during pregnancy with high mortality. Despite the improvement of treatment regimen in recent years, HLH is still a great challenge for clinicians. Here, we described a 26-year-old woman who admitted to our hospital at her first pregnancy with pyrexia. Her condition continued to deteriorate after receiving broad-spectrum antimicrobials, presenting with fever, pancytopenia, hepatosplenomegaly, ferritin ≥ 500 μg/L, hemophagocytosis and low NK-cell activity. HLH was eventually diagnosed by clinical manifestation and laboratory examination results. Then the patient recovered well after treatment with etoposide combined with ruxolitinib therapy and underwent successful induced-labor operation. Additionally, we summarized similar cases from the literature to improve the management of HLH during pregnancy. In conclusion, this study highlights the challenges and difficulties in the diagnosis and management of patients with HLH during pregnancy. Moreover, this is the first case report of etoposide combined with ruxolitinib in the treatment of patients with refractory secondary HLH during pregnancy.
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Pan-European Expert Meeting on the Use of Metronomic Chemotherapy in Advanced Breast Cancer Patients: The PENELOPE Project.
Cazzaniga, ME, Munzone, E, Bocci, G, Afonso, N, Gomez, P, Langkjer, S, Petru, E, Pivot, X, Sánchez Rovira, P, Wysocki, P, et al
Advances in therapy. 2019;(2):381-406
Abstract
INTRODUCTION Metronomic chemotherapy (mCHT) is a treatment regimen in which drugs are administered frequently or continuously and that maintains low, prolonged, and pharmacologically active plasma concentrations of drugs to avoid toxicity associated with traditional chemotherapy regimens, while achieving tumor response. Despite the increasing use of mCHT in patients with metastatic breast cancer (MBC) and the endorsement of mCHT in guidelines, no consensus exists about which patients may substantially benefit from mCHT, which agents can be recommended, and in which treatment setting mCHT is most appropriate. METHODS In October 2017, ten international experts in the management of breast cancer convened to develop a report describing the current status of the use of mCHT for the treatment of advanced breast cancer, based not only on current literature but also on their opinion. The Delphi method was used to reach consensus. RESULTS A full consensus was reached concerning the acknowledgement that mCHT is not simply a different way of administering chemotherapy but a truly new treatment option. The best-known effect of mCHT is on angiogenesis inhibition, but exciting new data are on the way regarding potential activity on immune system activation. The experts strongly suggest that the ideal patients for mCHT are those with hormone receptor (HR)-positive tumors or those with triple-negative disease. Independently of HR status, mCHT could be an advantageous option for elderly patients, who are often under-treated simply because of their age. CONCLUSION Current data support the use of mCHT in selected patients with MBC. FUNDING Pierre Fabre.