scholarly journals Icaritin: A Novel Natural Candidate for Hematological Malignancies Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Xiao-Jing Yang ◽  
Ya-Ming Xi ◽  
Zi-Jian Li
Keyword(s):  
Hematological Malignancies ◽  
Treatment Options ◽  
Chinese Herb ◽  
Cell Types ◽  
Hematologic Malignancies ◽  
Cytotoxic Effects ◽  
Novel Treatment ◽  
Traditional Chinese Herb ◽  
Current Therapies ◽  
Underlying Mechanisms

Hematological malignancies including leukemia and lymphoma can severely impact human health. With the current therapies combined with chemotherapy, stem cell transplantation, radiotherapy, and immunotherapy, the prognosis of hematologic malignancies improved significantly. However, most hematological malignancies are still incurable. Therefore, research for novel treatment options was continuing with the natural product as one source. Icaritin is a compound extracted from a traditional Chinese herb,Epimedium Genus, and demonstrated an antitumor effect in various neoplasms including hematological malignancies such as leukemia, lymphoma, and multiple myeloma. In hematological malignancies, icaritin showed multiple cytotoxic effects to induce apoptosis, arrest the cell cycle, inhibit proliferation, promote differentiation, restrict metastasis and infiltration, and suppress the oncogenic virus. The proved underlying mechanisms of the cytotoxic effects of icaritin are different in various cell types of hematological malignancies but associated with the critical cell signal pathway, including PI3K/Akt, JAK/STAT3, and MAPK/ERK/JNK. Although the primary target of icaritin is still unspecified, the existing evidence indicates that icaritin is a potential novel therapeutic agent for neoplasms as with hematological malignancies. Here, in the field of hematology, we reviewed the reported activity of icaritin in hematologic malignancies and the underlying mechanisms and recognized icaritin as a candidate for therapy of hematological malignancies.

scholarly journals The Interaction Between Microglia and Macroglia in Glaucoma

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaohuan Zhao ◽  
Rou Sun ◽  
Xueting Luo ◽  
Feng Wang ◽  
Xiaodong Sun
Keyword(s):  
Glial Cells ◽  
Vision Loss ◽  
Inflammatory Responses ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Treatment Options ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Underlying Mechanisms ◽  
The Relationship

Glaucoma, a neurodegenerative disease that leads to irreversible vision loss, is characterized by progressive loss of retinal ganglion cells (RGCs) and optic axons. To date, elevated intraocular pressure (IOP) has been recognized as the main phenotypic factor associated with glaucoma. However, some patients with normal IOP also have glaucomatous visual impairment and RGC loss. Unfortunately, the underlying mechanisms behind such cases remain unclear. Recent studies have suggested that retinal glia play significant roles in the initiation and progression of glaucoma. Multiple types of glial cells are activated in glaucoma. Microglia, for example, act as critical mediators that orchestrate the progression of neuroinflammation through pro-inflammatory cytokines. In contrast, macroglia (astrocytes and Müller cells) participate in retinal inflammatory responses as modulators and contribute to neuroprotection through the secretion of neurotrophic factors. Notably, research results have indicated that intricate interactions between microglia and macroglia might provide potential therapeutic targets for the prevention and treatment of glaucoma. In this review, we examine the specific roles of microglia and macroglia in open-angle glaucoma, including glaucoma in animal models, and analyze the interaction between these two cell types. In addition, we discuss potential treatment options based on the relationship between glial cells and neurons.

scholarly journals Lycium barbarum Extracts Extend Lifespan and Alleviate Proteotoxicity in Caenorhabditis elegans

2022 ◽  
Vol 8 ◽  
Author(s):  
Haitao Zhou ◽  
Shanshan Ding ◽  
Chuanxin Sun ◽  
Jiahui Fu ◽  
Dong Yang ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Dietary Supplement ◽  
Chinese Herb ◽  
Lifespan Extension ◽  
Lycium Barbarum ◽  
Experimental Conditions ◽  
Traditional Chinese Herb ◽  
Extended Lifespan ◽  
Underlying Mechanisms ◽  
Extension Effect

Lycium barbarum berry (Ningxia Gouqi, Fructus lycii, goji berry, or wolfberry), as a traditional Chinese herb, was recorded beneficial for longevity in traditional Chinese medical scriptures and currently is a natural dietary supplement worldwide. However, under modern experimental conditions, the longevity effect of L. barbarum berry and the underlying mechanisms have been less studied. Here, we reported that total water extracts of L. barbarum berry (LBE), which contains 22% polysaccharides and other components, such as anthocyanins, extended the lifespan of Caenorhabditis elegans without side effects on worm fertility and pharyngeal pumping. Interestingly, we found that the lifespan extension effect was more prominent in worms with shorter mean lifespan as compared to those with longer mean lifespan. Furthermore, we showed that the lifespan extension effect of LBE depended on deacetylase sir-2.1. Remarkably, LBE rescued heat shock transcription factor-1 (hsf-1) deficiency in wild-type worms with different mean lifespans, and this effect also depended on sir-2.1. In addition, we found that LBE extended lifespan and alleviated toxic protein aggregation in neurodegenerative worms with hsf-1 deficiency. Our study suggested that LBE may be a potential antiaging natural dietary supplement especially to individuals with malnutrition or chronic diseases and a potential therapeutic agent for neurodegenerative diseases characterized by hsf-1 deficiency.

Human Monocytes and Monocyte-Like Cells Are Highly Sensitive to Plitidepsin-Induced Cell Death In In Vitro Assays

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4942-4942
Author(s):  
Pablo E Morande ◽  
Samanta Zanetti ◽  
Mercedes Borge ◽  
Paula Nannini ◽  
Carolina Jancic ◽  
...  
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Leukemic Cell ◽  
Cell Types ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
In Vitro Assays ◽  
Malignant Cells ◽  
Cytotoxic Effects

Abstract Abstract 4942 Plitidepsin (Aplidin®) is a marine-derived cyclic depsipeptide with strong cytotoxic effects against a variety of cancer cell types. It is currently in Phase II/III clinical trials for solid and hematologic malignancies. We evaluated the cytotoxic effects of Plitidepsin on lymphoid and monocyte cells from healthy donors and analysed the mechanisms involved. We found that monocyte cells showed a markedly higher sensitivity to Plitidepsin compared to lymphoid subsets as determined by incorporation of 7-AAD and flow cytometry analysis. Plitidepsin induced a dose- and time-dependent cell death on freshly isolated monocytes (7-AAD+ cells at 24 h: control: 3±1% versus Plitidepsin 10 nM: 47±5%, mean±SEM, n=6) and on macrophages (5±2 vs 49±3, n=5) and dendritic cells (4±1 vs 21±4, n=5) differentiated in vitro. By contrast, resting or mitogen-activated lymphocytes were not affected by Plitidepsin at 10 nM. The mechanisms of induced cell death in monocytes involved the early exposure of phosphatidylserine to the outer leaflet of plasma membrane, activation of caspase-3 and subsequent PARP fragmentation, indicative of death via apoptosis. Incubation of monocytes with Plitidepsin (10 or 100 nM) for 30 minuntes induced ROS production. On the other hand, the cytotoxic effect of Plitidepsin was significantly diminished when monocytes were pre-incubated with the antioxidant reagent Ebselen, which acts as an scavenger of peroxynitrite. We also determined Plitidepsin activity on malignant cells from chronic myelomonocytic leukemia (CMML) and chronic lymphocytic leukemia (CLL) patients. Monocyte-like cells obtained from 3 CMML samples resulted sensitive to Plitidepsin, though to a different extent (viable CD14+ cells at 24 h: control 100%, incubated with Plitidepsin 10 nM: sample 1: 79%, sample 2: 82%, sample 3: 29%). Finally we evaluated the effects of Plitidepsin on nurse-like cells (NLC) from CLL patients. These cells represent a subset differentiated from monocytes that favours leukemic cell progression through pro-survival signals. NLC were very sensitive to Plitidepsin and, more importantly, their death indirectly decreased neoplasic clone viability (7-AAD+ leukemic B cells co-cultured with control NLC: 36±10 versus 7-AAD+ leukemic B cells co-cultured with NLC exposed to Plitidepsin 100 nM for 24 h: 47±6, n=5, p<0.05). Myeloid cells are present in tumor microenvironment and actively affect the malignant cells, both directly and indirectly via the suppression of host immunity. Given their relevance in supporting tumor growth, the sensitivity of monocyte-like cells to Plitidepsin may contribute to its antitumoral effects. Disclosures: Galmarini: PharmaMar: Employment, Equity Ownership. Giordano: PharmaMar: Research Funding.

scholarly journals MicroRNAs as Potential Predictors of Response to CDK4/6 Inhibitor Treatment

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4114
Author(s):  
Angeliki Andrikopoulou ◽  
Almog Shalit ◽  
Eleni Zografos ◽  
Konstantinos Koutsoukos ◽  
Anna-Maria Korakiti ◽  
...  
Keyword(s):  
Cellular Response ◽  
Hematological Malignancies ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Predictive Biomarkers ◽  
Cyclin Dependent Kinase ◽  
Regulate Gene Expression ◽  
Novel Treatment ◽  
Predictors Of Response ◽  
Inhibitor Treatment

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as novel treatment options in the management of advanced or metastatic breast cancer. MicroRNAs are endogenous non-coding 19–22-nucleotide-long RNAs that regulate gene expression in development and tumorigenesis. Herein, we systematically review all microRNAs associated with response to CDK4/6 inhibitors in solid tumors and hematological malignancies. Eligible articles were identified by a search of the MEDLINE and ClinicalTrials.gov databases for the period up to1 January 2021; the algorithm consisted of a predefined combination of the words “microRNAs”, “cancer” and “CDK 4/6 inhibitors”. Overall, 15 studies were retrieved. Six microRNAs (miR-126, miR-326, miR3613-3p, miR-29b-3p, miR-497 and miR-17-92) were associated with sensitivity to CDK4/6 inhibitors. Conversely, six microRNAs (miR-193b, miR-432-5p, miR-200a, miR-223, Let-7a and miR-21) conferred resistance to treatment with CDK4/6 inhibitors. An additional number of microRNAs (miR-124a, miR9, miR200b and miR-106b) were shown to mediate cellular response to CDK4/6 inhibitors without affecting sensitivity to treatment. Collectively, our review provides evidence that microRNAs could serve as predictive biomarkers for treatment with CDK4/6 inhibitors. Moreover, microRNA-targeted therapy could potentially maximize sensitivity to CDK4/6 inhibition.

scholarly journals Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells

2017 ◽  
Vol 42 (3) ◽  
pp. 929-938 ◽  
Author(s):  
Yingjuan Yang ◽  
Yanhua Zhang ◽  
Lan Wang ◽  
Shaochin Lee
Keyword(s):  
Colon Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Natural Compound ◽  
Chinese Herb ◽  
Colon Cancer Cells ◽  
Traditional Chinese Herb ◽  
Underlying Mechanisms ◽  
Stress Pathway ◽  
Hct116 Cells

Background/Aims: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Levistolide A (LA), a natural compound isolated from the traditional Chinese herb Ligusticum chuanxiong Hort, is used for treating cancer. In this study, we investigated the anticancer effect of LA in HCT116 and its isogenic p53-/- colon cancer cells, as well as the underlying mechanisms. Methods: MTT assay was used to evaluate the effect of LA on the viability of cancer cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined by flow cytometry. Protein expression was detected by western blotting. Results: The results showed that LA inhibited viability and caused apoptosis of both wild-type and p53-/- HCT116 cells. LA was able to trigger production of ROS and endoplasmic reticulum (ER) stress. Inhibition of ROS using N-acetylcysteine abrogated LA-induced ER stress and apoptosis, as well as the reduction in cancer cell viability. Conclusion: Our results indicate that LA causes apoptosis of colon cancer cells via ROS-mediated ER stress pathway. It will be interesting to develop the natural compound for chemotherapy of cancers such as CRC.

scholarly journals The interplay of leukemia cells and the bone marrow microenvironment

Blood ◽  
2018 ◽  
Vol 131 (14) ◽  
pp. 1507-1511 ◽  
Author(s):  
Delfim Duarte ◽  
Edwin D. Hawkins ◽  
Cristina Lo Celso
Keyword(s):  
Bone Marrow ◽  
Cancer Cells ◽  
Disease Progression ◽  
Hematological Malignancies ◽  
Treatment Options ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Disease Models ◽  
Imaging Technology ◽  
Novel Treatment

Abstract The interplay of cancer cells and surrounding stroma is critical in disease progression. This is particularly evident in hematological malignancies that infiltrate the bone marrow and peripheral lymphoid organs. Despite clear evidence for the existence of these interactions, the precise repercussions on the growth of leukemic cells are poorly understood. Recent development of novel imaging technology and preclinical disease models has advanced our comprehension of leukemia-microenvironment crosstalk and has potential implications for development of novel treatment options.

scholarly journals The Yin and Yang of Autosomal Recessive Primary Microcephaly Genes: Insights from Neurogenesis and Carcinogenesis

2020 ◽  
Vol 21 (5) ◽  
pp. 1691 ◽  
Author(s):  
Xiaokun Zhou ◽  
Yiqiang Zhi ◽  
Jurui Yu ◽  
Dan Xu
Keyword(s):  
Autosomal Recessive ◽  
Brain Size ◽  
Cell Types ◽  
Primary Microcephaly ◽  
Current Therapies ◽  
Yin And Yang ◽  
The Common ◽  
Underlying Mechanisms ◽  
Different Cell Types ◽  
Autosomal Recessive Primary Microcephaly

The stem cells of neurogenesis and carcinogenesis share many properties, including proliferative rate, an extensive replicative potential, the potential to generate different cell types of a given tissue, and an ability to independently migrate to a damaged area. This is also evidenced by the common molecular principles regulating key processes associated with cell division and apoptosis. Autosomal recessive primary microcephaly (MCPH) is a neurogenic mitotic disorder that is characterized by decreased brain size and mental retardation. Until now, a total of 25 genes have been identified that are known to be associated with MCPH. The inactivation (yin) of most MCPH genes leads to neurogenesis defects, while the upregulation (yang) of some MCPH genes is associated with different kinds of carcinogenesis. Here, we try to summarize the roles of MCPH genes in these two diseases and explore the underlying mechanisms, which will help us to explore new, attractive approaches to targeting tumor cells that are resistant to the current therapies.

scholarly journals Novel treatment possibilities of invasive aspergillosis

2021 ◽  
Vol 16 (4) ◽  
pp. 31-39
Author(s):  
G. A. Klyasova
Keyword(s):  
Risk Factors ◽  
Fungal Infection ◽  
Invasive Aspergillosis ◽  
Hematological Malignancies ◽  
Treatment Options ◽  
New Drug ◽  
Novel Treatment

Invasive aspergillosis is the leading fungal infection in patients with hematological malignancies. The review represents the incidence of invasive aspergillosis in different groups of patients, risk factors for its development, treatment options, including the new drug isavuconazole.

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