MicroRNAs as Therapeutic Agents: The Future of the Battle Against Cancer

2019 ◽  
Vol 18 (30) ◽  
pp. 2544-2554 ◽  
Author(s):  
Sumit Biswas
Keyword(s):  
Drug Resistance ◽  
Cancer Biology ◽  
Therapeutic Agents ◽  
Nucleotide Level ◽  
Target Mrnas ◽  
Sequencing Technologies ◽  
Tumour Suppressors ◽  
The Future ◽  
New Strategies

Since their discovery in the 1990’s, the study of a class of non-coding, single-stranded RNAs, christened the microRNAs has opened up new vistas in the field of cancer biology. MicroRNAs bind to their target mRNAs to act as either oncogenes or tumour suppressors. With the near-complete elucidation of the biogenesis pathway, and the advent of rapid sequencing technologies, microRNAs have slowly cemented their place as essential biomarkers for delineating the progression, metastasis, relapse or drug resistance of cancer. Being crucial players in the cancer pathway, there has been considerable urgency in designing molecules - both at the nucleotide and non-nucleotide level to counter the effects of their binding. A number of different approaches have yielded quite a body of compounds which have been found to be effective in the treatment of various tumours across many different organs. In this study, the focus is on the review of the timeline of discovery and characterization of microRNAs, underlining their importance in different cancers, shedding light on the discovery of anti-microRNA compounds and illustrating their uses in deriving new strategies to combat cancer.

Drug Resistance in Bacteria: History, Genetics and Biochemistry

1993 ◽  
Vol 21 (1) ◽  
pp. 1-14 ◽  
Author(s):  
S Mitsuhashi
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Chemotherapy ◽  
Therapeutic Agents ◽  
Chemotherapeutic Agents ◽  
Protective Effects ◽  
The Future ◽  
History Of ◽  
Modern Era

The significance of the discovery of prontosil in 1932 as the initiating step in the development of the modern era of antimicrobial chemotherapy is reviewed. The history of the discovery and the development of chemotherapeutic agents, from penicillin in 1929 to present-day antibiotics, are summarized. The various mechanisms by which bacteria are able to overcome the protective effects of these therapeutic agents (from the sulphonamides to the new fluoroquinolones) and develop resistance to them are discussed in detail. Attempts to elucidate the mechanisms by which resistance to chemotherapeutic agents develops are vital to the future of antimicrobial chemotherapy.

scholarly journals Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

2021 ◽  
Vol 22 (22) ◽  
pp. 12586
Author(s):  
Viviana De Martino ◽  
Michela Rossi ◽  
Giulia Battafarano ◽  
Jessica Pepe ◽  
Salvatore Minisola ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Scientific Community ◽  
Therapeutic Agents ◽  
Tumor Proliferation ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Diagnostic Agents ◽  
Metastatic Process

Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.

scholarly journals Reassortment of Genome Segments Creates Stable Lineages Among Strains of Orchid Fleck Virus Infecting Citrus in Mexico

2020 ◽  
Vol 110 (1) ◽  
pp. 106-120 ◽  
Author(s):  
Avijit Roy ◽  
Andrew L. Stone ◽  
Gabriel Otero-Colina ◽  
Gang Wei ◽  
Ronald H. Brlansky ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Sensu Stricto ◽  
Genome Segment ◽  
Rt Pcr ◽  
Sequence Comparisons ◽  
Orchid Fleck Virus ◽  
Reverse Transcription Pcr ◽  
Sequencing Technologies ◽  
Negative Sense

The genus Dichorhavirus contains viruses with bipartite, negative-sense, single-stranded RNA genomes that are transmitted by flat mites to hosts that include orchids, coffee, the genus Clerodendrum, and citrus. A dichorhavirus infecting citrus in Mexico is classified as a citrus strain of orchid fleck virus (OFV-Cit). We previously used RNA sequencing technologies on OFV-Cit samples from Mexico to develop an OFV-Cit–specific reverse transcription PCR (RT-PCR) assay. During assay validation, OFV-Cit–specific RT-PCR failed to produce an amplicon from some samples with clear symptoms of OFV-Cit. Characterization of this virus revealed that dichorhavirus-like particles were found in the nucleus. High-throughput sequencing of small RNAs from these citrus plants revealed a novel citrus strain of OFV, OFV-Cit2. Sequence comparisons with known orchid and citrus strains of OFV showed variation in the protein products encoded by genome segment 1 (RNA1). Strains of OFV clustered together based on host of origin, whether orchid or citrus, and were clearly separated from other dichorhaviruses described from infected citrus in Brazil. The variation in RNA1 between the original (now OFV-Cit1) and the new (OFV-Cit2) strain was not observed with genome segment 2 (RNA2), but instead, a common RNA2 molecule was shared among strains of OFV-Cit1 and -Cit2, a situation strikingly similar to OFV infecting orchids. We also collected mites at the affected groves, identified them as Brevipalpus californicus sensu stricto, and confirmed that they were infected by OFV-Cit1 or with both OFV-Cit1 and -Cit2. OFV-Cit1 and -Cit2 have coexisted at the same site in Toliman, Queretaro, Mexico since 2012. OFV strain-specific diagnostic tests were developed.

scholarly journals Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1292 ◽  
Author(s):  
Shirin Hafezi ◽  
Mohamed Rahmani
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Targeted Therapies ◽  
Single Agent ◽  
Therapeutic Agents ◽  
Malignant Cells ◽  
Future Perspectives ◽  
Comprehensive Overview ◽  
Antiapoptotic Proteins ◽  
Preclinical And Clinical Studies

The major form of cell death in normal as well as malignant cells is apoptosis, which is a programmed process highly regulated by the BCL-2 family of proteins. This includes the antiapoptotic proteins (BCL-2, BCL-XL, MCL-1, BCLW, and BFL-1) and the proapoptotic proteins, which can be divided into two groups: the effectors (BAX, BAK, and BOK) and the BH3-only proteins (BIM, BAD, NOXA, PUMA, BID, BIK, HRK). Notably, the BCL-2 antiapoptotic proteins are often overexpressed in malignant cells. While this offers survival advantages to malignant cells and strengthens their drug resistance capacity, it also offers opportunities for novel targeted therapies that selectively kill such cells. This review provides a comprehensive overview of the extensive preclinical and clinical studies targeting BCL-2 proteins with various BCL-2 proteins inhibitors with emphasis on venetoclax as a single agent, as well as in combination with other therapeutic agents. This review also discusses recent advances, challenges focusing on drug resistance, and future perspectives for effective targeting the Bcl-2 family of proteins in cancer.

scholarly journals HIV-1 Drug Resistance Genotyping in Resource Limited Settings: Current and Future Perspectives in Sequencing Technologies

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1125
Author(s):  
Sontaga Manyana ◽  
Lilishia Gounder ◽  
Melendhran Pillay ◽  
Justen Manasa ◽  
Kogieleum Naidoo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Sanger Sequencing ◽  
Clinical Diagnostics ◽  
Treatment Programs ◽  
People Living With Hiv ◽  
Resource Limited Settings ◽  
Gold Standard Method ◽  
Sequencing Technologies ◽  
Resource Limited ◽  
Hiv 1

Affordable, sensitive, and scalable technologies are needed for monitoring antiretroviral treatment (ART) success with the goal of eradicating HIV-1 infection. This review discusses use of Sanger sequencing and next generation sequencing (NGS) methods for HIV-1 drug resistance (HIVDR) genotyping, focusing on their use in resource limited settings (RLS). Sanger sequencing remains the gold-standard method for detecting HIVDR mutations of clinical relevance but is mainly limited by high sequencing costs and low-throughput. NGS is becoming a more common sequencing method, with the ability to detect low-abundance drug-resistant variants and reduce per sample costs through sample pooling and massive parallel sequencing. However, use of NGS in RLS is mainly limited by infrastructure costs. Given these shortcomings, our review discusses sequencing technologies for HIVDR genotyping, focusing on common in-house and commercial assays, challenges with Sanger sequencing in keeping up with changes in HIV-1 treatment programs, as well as challenges with NGS that limit its implementation in RLS and in clinical diagnostics. We further discuss knowledge gaps and offer recommendations on how to overcome existing barriers for implementing HIVDR genotyping in RLS, to make informed clinical decisions that improve quality of life for people living with HIV.

scholarly journals Identification and Characterization of Multiple Myeloma Stem Cell-Like Cells

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3523
Author(s):  
Wancheng Guo ◽  
Haiqin Wang ◽  
Peng Chen ◽  
Xiaokai Shen ◽  
Boxin Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Stem Cell ◽  
New Drugs ◽  
Cell Therapies ◽  
High Relapse Rate ◽  
High Incidence ◽  
Poorly Differentiated ◽  
Identification And Characterization

Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.

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