scholarly journals Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs

Author(s):  
Hua-yang Fan ◽  
Zhuo-li Zhu ◽  
Hong-chun Xian ◽  
Hao-fan Wang ◽  
Bing-jun Chen ◽  
...  

Podophyllotoxin (PTOX) is a biologically active compound derived from the podophyllum plant, and both it and its derivatives possess excellent antitumor activity. The PTOX derivatives etoposide (VP-16) and teniposide (VM-26) have been approved by the U.S. Food and Drug Administration (FDA) for cancer treatment, but are far from perfect. Hence, numerous PTOX derivatives have been developed to address the major limitations of PTOX, such as systemic toxicity, drug resistance, and low bioavailability. Regarding their anticancer mechanism, extensive studies have revealed that PTOX derivatives can induce cell cycle G2/M arrest and DNA/RNA breaks by targeting tubulin and topoisomerase II, respectively. However, few studies are dedicated to exploring the interactions between PTOX derivatives and downstream cancer-related signaling pathways, which is reasonably important for gaining insight into the role of PTOX. This review provides a comprehensive analysis of the role of PTOX derivatives in the biological behavior of tumors and potential molecular signaling pathways, aiming to help researchers design and develop better PTOX derivatives.

2020 ◽  
Vol 11 ◽  
Author(s):  
Lihui Chen ◽  
Jie Li ◽  
Wu Zhu ◽  
Yehong Kuang ◽  
Tao Liu ◽  
...  

Psoriasis affects the health of myriad populations around the world. The pathogenesis is multifactorial, and the exact driving factor remains unclear. This condition arises from the interaction between hyperproliferative keratinocytes and infiltrating immune cells, with poor prognosis and high recurrence. Better clinical treatments remain to be explored. There is much evidence that alterations in the skin and intestinal microbiome play an important role in the pathogenesis of psoriasis, and restoration of the microbiome is a promising preventive and therapeutic strategy for psoriasis. Herein, we have reviewed recent studies on the psoriasis-related microbiome in an attempt to confidently identify the “core” microbiome of psoriasis patients, understand the role of microbiome in the pathogenesis of psoriasis, and explore new therapeutic strategies for psoriasis through microbial intervention.


1999 ◽  
Vol 17 (3) ◽  
pp. 1071-1071 ◽  
Author(s):  
Darrin M. Beaupre ◽  
Razelle Kurzrock

PURPOSE AND DESIGN: The purpose of this review is to provide an overview of the literature linking Ras signaling pathways and leukemia and to discuss the biologic and potential therapeutic implications of these observations. A search of MEDLINE from 1966 to October 1998 was performed. RESULTS: A wealth of data has been published on the role of Ras pathways in cancer. To be biologically active, Ras must move from the cytoplasm to the plasma membrane. Importantly, a posttranslational modification—addition of a farnesyl group to the Ras C-terminal cysteine—is a requisite for membrane localization of Ras. Farnesylation of Ras is catalyzed by an enzyme that is designated farnesyltranferase. Recently, several compounds have been developed that can inhibit farnesylation. Preclinical studies indicate that these molecules can suppress transformation and tumor growth in vitro and in animal models, with little toxicity to normal cells. CONCLUSION: An increasing body of data suggests that disruption of Ras signaling pathways, either directly through mutations or indirectly through other genetic aberrations, is important in the pathogenesis of a wide variety of cancers. Molecules such as farnesyl transferase inhibitors that interfere with the function of Ras may be exploitable in leukemia (as well as in solid tumors) as novel antitumor agents.


2014 ◽  
Author(s):  
Juanjuan Zhao ◽  
Yongju Li ◽  
Yan Hu ◽  
Chao Chen ◽  
Ya Zhou ◽  
...  

Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.


2014 ◽  
Author(s):  
Juanjuan Zhao ◽  
Yongju Li ◽  
Yan Hu ◽  
Chao Chen ◽  
Ya Zhou ◽  
...  

Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.


2021 ◽  
Vol 12 (3) ◽  
pp. 1757-1769
Author(s):  
Preeti Tanaji Mane ◽  
Sangram Prakash Patil ◽  
Balaji Sopanrao Wakure ◽  
Pravin Shridhar Wakte

Breast cancer has messed the life of a greater number of women being the most common cancer affecting them worldwide. A number of risk factors contribute the breast malignancy, however, genetic drift is accountable the most. Depending on the cell origin, invasiveness and receptors involved, breast cancer is classified into various subtypes. The accurate diagnosis of breast cancer is important as it defines the prognosis and directs the type of treatment required. A number of major signaling pathways involved in breast tumorigenesis and its development include estrogen receptors (ERs), HER2, Wnt/β-catenin, Notch, Hedgehog (Hh), PI3K and mTOR pathway. Furthermore, certain enzymes like Cyclin dependent kinases and breast tumor kinases also play a vital role in cell cycle regulation and therefore, in the development of breast neoplasms. Recent studies have also enlightened the role of non-coding RNAs in breast cancer development. This review discusses various aspects of breast cancer such as its etiology, subtypes, various signaling pathways involved, targets projected by these pathways and the current treatment options based on a few of these targets. Also, the role of different genes, enzymes and non-coding RNAs related to breast tumorigenesis and development is discussed.


FEBS Letters ◽  
2004 ◽  
Vol 562 (1-3) ◽  
pp. 118-124 ◽  
Author(s):  
Vesna Katavic ◽  
Dennis L. Barton ◽  
E.Michael Giblin ◽  
Darwin W. Reed ◽  
Arvind Kumar ◽  
...  

2002 ◽  
Vol 357 (1420) ◽  
pp. 493-503 ◽  
Author(s):  
Hans Slabbekoorn ◽  
Thomas B. Smith

The study of bird song dialects was once considered the most promising approach for investigating the role of behaviour in reproductive divergence and speciation. However, after a series of studies yielding conflicting results, research in the field slowed significantly. Recent findings, on how ecological factors may lead to divergence in both song and morphology, necessitate a re–examination. We focus primarily on species with learned song, examine conflicting results in the literature and propose some potential new directions for future studies. We believe an integrative approach, including an examination of the role of ecology in divergent selection, is essential for gaining insight into the role of song in the evolution of assortative mating. Habitat–dependent selection on both song and fitness–related characteristics can lead to parallel divergence in these traits. Song may, therefore, provide females with acoustic cues to find males that are most fit for a particular habitat. In analysing the role of song learning in reproductive divergence, we focus on post–dispersal plasticity in a conceptual framework. We argue that song learning may initially constrain reproductive divergence, while in the later stages of population divergence it may promote speciation.


Author(s):  
Roopasree OJ ◽  
Adivitiya . ◽  
Soura Chakraborty ◽  
Suneel Kateriya ◽  
Shobi Veleri

Metazoans have an elaborate and functionally segmented body. It evolves from a single cell by systematic divisions. Metazoans attain structural complexity with exquisite precision, which is a molecular mystery. The indispensable role of centrioles in cell division and ciliogenesis can shed insight into this riddle. Cell division helps in growth of the body and is a highly regulated and integrated process. Its errors cause malignancies. The cell mass is organized during organogenesis. Prior to it, the centrioles are retrieved from the cell cycle to initiate ciliogenesis. The cilia-modulated developmental signaling pathways elaborate the body plan. The secluded compartment of the cilium reduces noise during signaling and is essential for a precise body plan development. The dysfunctional centrioles and cilia can distort body plan. Thus, centriole has a dual role in growth and cellular organization. This concept review analyses the comprehensive interactome and the key domain features (like C2 domain) of molecules which connect and disarm the centriole from the cell cycle and ciliogenesis by switching on or off the essential regulators of the pathways. The concentration of these signaling pathways at the centriole reinforces the hypothesis that centriole is the molecular workstation to carve out structural design and complexity in metazoans.


2021 ◽  
Vol 70 (3) ◽  
pp. 121-134
Author(s):  
Maria A. Shalina ◽  
Maria I. Yarmolinskaya ◽  
Elena A. Netreba ◽  
Alexandra K. Beganova

The prevalence of genital endometriosis and adenomyosis, in particular, is tending to increase. The lack of a complete understanding of the pathogenetic mechanisms and multifactorial causes of adenomyosis, the low effectiveness of existing drug therapy, and the importance of preserving reproductive function make it necessary to further study the pathogenesis of the disease, search for new non-invasive highly informative diagnostic methods and develop a new strategy for pathogenically based drug therapy. The review presents current data on the role of signaling pathways in the pathogenesis of the development of adenomyosis based on domestic and foreign literature sources retrieved from the electronic databases PubMed, CyberLeninka, and Google Scholar in the period from 1999 to 2020. Considerable emphasis is placed on the discussion of the research results in recent years. Based on the analysis, the role of transforming growth factor (TGF), vascular endothelial growth factor (VEGF), dual-specificity protein phosphatase (PTEN), Notch receptors, and eukaryotic translation initiation factors (eIFs) in the signaling of adenomyosis is presented. Further advanced study of signaling pathways in the pathogenesis of adenomyosis will allow developing highly specific and highly sensitive markers for non-invasive diagnostics, as well as new directions for drug treatment of the disease.


Author(s):  
Folasayo Enoch Olalere

In this chapter, the author examines the levels of a cognitive process (visceral, behavioural, and reflection design) in experience-centred design and their applicability in developing effective products. The study further explores the role of computer-aided tools (CAD) in engaging users as the fundamental participants in the creative process. This was achieved by developing two products digitally (CAD models) based on Norman's three design levels, and evaluated using a semantic differential scale to test the emotive response towards the designs. The findings show that CAD is a viable tool for gaining insight into users' perceptions towards a design idea. Also, the results revealed that the process of supporting or sustaining cultural values through design also enhances the affective quality (reflective level) of the design.


Sign in / Sign up

Export Citation Format

Share Document