Pro-Oxidant Milieu Blunts Scissors: Insight into Tumor Progression, Drug Resistance, and Novel Druggable Targets

AbstractIncreasing evidence demonstrates that long noncoding RNAs (lncRNAs) play critical roles in human breast cancer (BC) tumorigenesis. However, the mechanisms by which lncRNA and N6-methyladenosine (m6A) regulate BC tumorigenesis are still unclear. In the present research, LINC00958 was markedly overexpressed in BC tissue and cells, and LINC00958 upregulation promoted the tumor progression of BC cells. Mechanistically, m6A methyltransferase-like 3 (METTL3) gave rise to the upregulation of LINC00958 by promoting its RNA transcript stability. Moreover, LINC00958 acted as a competitive endogenous RNA for miR-378a-3p to promote YY1. Overall, these data provide novel insight into how m6A-mediated LINC00958 regulates BC tumorigenesis.

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Expression profiling of muscle invasive and non-invasive bladder tumors for biomarkers identification related to drug resistance, sensitivity and tumor progression

Biotechnology & Biotechnological Equipment ◽

10.1080/13102818.2020.1778528 ◽

2020 ◽

Vol 34 (1) ◽

pp. 506-514

Author(s):

Olga Antonova ◽

Blaga Rukova ◽

Boris Mladenov ◽

Simeon Rangelov ◽

Zora Hammoudeh ◽

...

Keyword(s):

Drug Resistance ◽

Tumor Progression ◽

Expression Profiling ◽

Bladder Tumors ◽

Non Invasive ◽

Muscle Invasive

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Mechanistic Insight into Antimicrobial and Antioxidant Potential of Jasminum Species: A Herbal Approach for Disease Management

Plants ◽

10.3390/plants10061089 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1089

Author(s):

Acharya Balkrishna ◽

Akansha Rohela ◽

Abhishek Kumar ◽

Ashwani Kumar ◽

Vedpriya Arya ◽

...

Keyword(s):

Oxidative Stress ◽

Drug Resistance ◽

Free Radicals ◽

Free Radical ◽

Microbial Pathogens ◽

Free Radical Scavengers ◽

Bioactive Constituents ◽

Global Issues ◽

Iridoid Glucosides ◽

Insight Into

Drug resistance among microbial pathogens and oxidative stress caused by reactive oxygen species are two of the most challenging global issues. Firstly, drug-resistant pathogens cause several fatalities every year. Secondly aging and a variety of diseases, such as cardiovascular disease and cancer, are associated with free radical generated oxidative stress. The treatments currently available are limited, ineffective, or less efficient, so there is an immediate need to tackle these issues by looking for new therapies to resolve resistance and neutralize the harmful effects of free radicals. In the 21st century, the best way to save humans from them could be by using plants as well as their bioactive constituents. In this specific context, Jasminum is a major plant genus that is used in the Ayurvedic system of medicine to treat a variety of ailments. The information in this review was gathered from a variety of sources, including books, websites, and databases such as Science Direct, PubMed, and Google Scholar. In this review, a total of 14 species of Jasminum have been found to be efficient and effective against a wide variety of microbial pathogens. In addition, 14 species were found to be active free radical scavengers. The review is also focused on the disorders related to oxidative stress, and it was concluded that Jasminum grandiflorum and J. sambac normalized various parameters that were elevated by free radical generation. Alkaloids, flavonoids (rutoside), terpenes, phenols, and iridoid glucosides are among the main phytoconstituents found in various Jasminum species. Furthermore, this review also provides insight into the mechanistic basis of drug resistance, the generation of free radicals, and the role of Jasminum plants in combating resistance and neutralizing free radicals.

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C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma

Blood ◽

10.1182/blood-2014-03-564583 ◽

2014 ◽

Vol 123 (26) ◽

pp. 4120-4131 ◽

Cited By ~ 122

Author(s):

Aldo M. Roccaro ◽

Antonio Sacco ◽

Cristina Jimenez ◽

Patricia Maiso ◽

Michele Moschetta ◽

...

Keyword(s):

Drug Resistance ◽

Tumor Growth ◽

Tumor Progression ◽

Driver Mutation ◽

Lymphoplasmacytic Lymphoma ◽

Wild Type ◽

Key Points ◽

Activating Mutation

Key Points C1013G/CXCR4 acts as an activating mutation in WM leading to enhanced tumor growth, and as an inducer of drug resistance. BMS936564/MDX1338, a novel anti-CXCR4 moAb, successfully targets WM cells, either C1013G/CXCR4 mutated or wild-type.

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Pathways Involved in Formation of Mammary Organoid Architecture Have Keys to Understanding Drug Resistance and to Discovery of Druggable Targets

Cold Spring Harbor Symposia on Quantitative Biology ◽

10.1101/sqb.2016.81.030825 ◽

2016 ◽

Vol 81 ◽

pp. 207-217 ◽

Cited By ~ 10

Author(s):

Saori Furuta ◽

Mina J. Bissell

Keyword(s):

Drug Resistance ◽

Druggable Targets

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Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma: Erratum

Theranostics ◽

10.7150/thno.68810 ◽

2022 ◽

Vol 12 (1) ◽

pp. 419-420

Author(s):

Libin Yan ◽

Beichen Ding ◽

Haoran Liu ◽

Yangjun Zhang ◽

Jin Zeng ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Drug Resistance ◽

Tumor Progression ◽

Cell Carcinoma ◽

Renal Cell ◽

Multi Drug Resistance

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Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling

The Journal of Cell Biology ◽

10.1083/jcb.201703206 ◽

2018 ◽

Vol 217 (3) ◽

pp. 1129-1142 ◽

Cited By ~ 69

Author(s):

Frederik Johannes Verweij ◽

Maarten P. Bebelman ◽

Connie R. Jimenez ◽

Juan J. Garcia-Vallejo ◽

Hans Janssen ◽

...

Keyword(s):

Total Internal Reflection ◽

Single Cells ◽

Cell Communication ◽

Exosome Biogenesis ◽

Real Time Visualization ◽

Target Membrane ◽

Syntaxin 4 ◽

Optical Reporters ◽

Druggable Targets ◽

Insight Into

Exosomes are small endosome-derived extracellular vesicles implicated in cell–cell communication and are secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology are based on isolation procedures after secretion, precluding direct and dynamic insight into the mechanics of exosome biogenesis and the regulation of their release. In this study, we propose real-time visualization of MVB–PM fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive optical reporters that detect MVB–PM fusion using live total internal reflection fluorescence and dynamic correlative light–electron microscopy. Quantitative analysis demonstrates that MVB–PM fusion frequency is reduced by depleting the target membrane SNAREs SNAP23 and syntaxin-4 but also can be induced in single cells by stimulation of the histamine H1 receptor (H1HR). Interestingly, activation of H1R1 in HeLa cells increases Ser110 phosphorylation of SNAP23, promoting MVB–PM fusion and the release of CD63-enriched exosomes. Using this single-cell resolution approach, we highlight the modulatory dynamics of MVB exocytosis that will help to increase our understanding of exosome physiology and identify druggable targets in exosome-associated pathologies.

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Drug Resistance in Non-Hodgkin Lymphomas

International Journal of Molecular Sciences ◽

10.3390/ijms21062081 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2081 ◽

Cited By ~ 4

Author(s):

Pavel Klener ◽

Magdalena Klanova

Keyword(s):

Drug Resistance ◽

Molecular Mechanisms ◽

Front Line ◽

Mechanisms Of Resistance ◽

Treatment Algorithms ◽

Acquired Drug Resistance ◽

Complex Process ◽

Medical Need ◽

Druggable Targets

Non-Hodgkin lymphomas (NHL) are lymphoid tumors that arise by a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. The WHO classification of NHL recognizes more than 90 nosological units with peculiar pathophysiology and prognosis. Since the end of the 20th century, our increasing knowledge of the molecular biology of lymphoma subtypes led to the identification of novel druggable targets and subsequent testing and clinical approval of novel anti-lymphoma agents, which translated into significant improvement of patients’ outcome. Despite immense progress, our effort to control or even eradicate malignant lymphoma clones has been frequently hampered by the development of drug resistance with ensuing unmet medical need to cope with relapsed or treatment-refractory disease. A better understanding of the molecular mechanisms that underlie inherent or acquired drug resistance might lead to the design of more effective front-line treatment algorithms based on reliable predictive markers or personalized salvage therapy, tailored to overcome resistant clones, by targeting weak spots of lymphoma cells resistant to previous line(s) of therapy. This review focuses on the history and recent advances in our understanding of molecular mechanisms of resistance to genotoxic and targeted agents used in clinical practice for the therapy of NHL.

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