scholarly journals Nanomedicine to Overcome Multidrug Resistance Mechanisms in Colon and Pancreatic Cancer: Recent Progress

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2058
Author(s):  
Raúl Ortíz ◽  
Francisco Quiñonero ◽  
Beatriz García-Pinel ◽  
Marco Fuel ◽  
Cristina Mesas ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Treatment ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Resistance Mechanisms ◽  
New Horizons ◽  
Dna Repair Mechanisms ◽  
Pancreatic Cancers ◽  
Different Types ◽  
Repair Mechanisms

The development of drug resistance is one of the main causes of cancer treatment failure. This phenomenon occurs very frequently in different types of cancer, including colon and pancreatic cancers. However, the underlying molecular mechanisms are not fully understood. In recent years, nanomedicine has improved the delivery and efficacy of drugs, and has decreased their side effects. In addition, it has allowed to design drugs capable of avoiding certain resistance mechanisms of tumors. In this article, we review the main resistance mechanisms in colon and pancreatic cancers, along with the most relevant strategies offered by nanodrugs to overcome this obstacle. These strategies include the inhibition of efflux pumps, the use of specific targets, the development of nanomedicines affecting the environment of cancer-specific tissues, the modulation of DNA repair mechanisms or RNA (miRNA), and specific approaches to damage cancer stem cells, among others. This review aims to illustrate how advanced nanoformulations, including polymeric conjugates, micelles, dendrimers, liposomes, metallic and carbon-based nanoparticles, are allowing to overcome one of the main limitations in the treatment of colon and pancreatic cancers. The future development of nanomedicine opens new horizons for cancer treatment.

scholarly journals RADIATION GENETICS IN MICROORGANISMS AND EVOLUTIONARY CONSIDERATIONS

Genetics ◽  
1974 ◽  
Vol 78 (1) ◽  
pp. 149-161
Author(s):  
Sohei Kondo
Keyword(s):  
Dna Repair ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Resistance Mechanisms ◽  
Plant Viruses ◽  
Protective Capacity ◽  
E Coli ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Solar Uv

ABSTRACT Recent knowledge of UV-resistance mechanisms in microorganisms is reviewed in perspective, with emphasis on E. coli. Dark-repair genes are classified into "excision" and "tolerance" (ability to produce a normal copy of DNA from damaged DNA). The phenotype of DNA repair is rather common among the microorganisms compared, and yet their molecular mechanisms are not universal. In contrast, DNA photoreactivation is the simplest and the most general among these three repair systems. It is proposed that DNA repair mechanisms evolved in the order: photoreactivation, excision repair, and tolerance repair. The UV protective capacity and light-inducible RNA photoreactivation possessed by some plant viruses are interpreted to be the result of solar UV selection during a rather recent era of evolution.

scholarly journals Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

2021 ◽  
Vol 11 (8) ◽  
pp. 693
Author(s):  
Corina Daniela Ene ◽  
Simona Roxana Georgescu ◽  
Mircea Tampa ◽  
Clara Matei ◽  
Cristina Iulia Mitran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lupus Nephritis ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Control Group ◽  
Dna Repair Mechanisms ◽  
Glycation End Products ◽  
Repair Mechanisms ◽  
Low Levels ◽  
Defective Dna Repair

The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.

scholarly journals Cancer Stem Cells and Radioresistance: DNA Repair and Beyond

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 862 ◽  
Author(s):  
Alexander Schulz ◽  
Felix Meyer ◽  
Anna Dubrovska ◽  
Kerstin Borgmann
Keyword(s):  
Stem Cells ◽  
Dna Repair ◽  
Cancer Stem Cells ◽  
Radiation Oncology ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Clinical Findings ◽  
Cell Reprogramming ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms

The current preclinical and clinical findings demonstrate that, in addition to the conventional clinical and pathological indicators that have a prognostic value in radiation oncology, the number of cancer stem cells (CSCs) and their inherent radioresistance are important parameters for local control after radiotherapy. In this review, we discuss the molecular mechanisms of CSC radioresistance attributable to DNA repair mechanisms and the development of CSC-targeted therapies for tumor radiosensitization. We also discuss the current challenges in preclinical and translational CSC research including the high inter- and intratumoral heterogeneity, plasticity of CSCs, and microenvironment-stimulated tumor cell reprogramming.

Updates on the molecular mechanisms of aspirin in the prevention of colorectal cancer: Review

2021 ◽  
pp. 107815522098484
Author(s):  
Yaschilal Muche Belayneh ◽  
Gedefew Getnet Amare ◽  
Birhanu Geta Meharie
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Vascular Endothelial ◽  
Akt Activation ◽  
Dna Repair Mechanisms ◽  
Anticancer Effects ◽  
Cancer Review ◽  
Repair Mechanisms ◽  
Anti Inflammatory ◽  
Endothelial Growth Factor

Colorectal cancer is one of the commonest malignancies worldwide. The estimated lifetime risk of the disease is about 5% with an incidence of one million new cases and 600,000 deaths worldwide every year. It is estimated that in 2019, approximately 134,490 new cases of colorectal cancer will be diagnosed with 49,190 mortalities. Though the disease is regarded as a disorder of the more developed world, the occurrence is steadily increasing in many developing countries. Since chronic inflammation is a known aggravating risk factor for colorectal cancer, anti-inflammatory agents such as aspirin have been used to prevent the development of colorectal cancer and related mortality. The potential mechanisms for the effect of aspirin in the prevention of colorectal cancer have been proposed and broadly classified as cyclooxygenase (COX) dependent and COX-independent. Some of the primary effectors of COX-dependent mechanisms in carcinogenesis are likely to be prostaglandins. In contrast to the reversible action of other nonsteroidal anti-inflammatory drugs, aspirin is known to irreversibly inactivate COX enzymes to suppress production of prostaglandins. COX-independent mechanisms of anticancer effects of aspirin include down-regulation of nuclear factor kappa B activity and Akt activation, modulation of Bcl-2 and Bax family proteins, suppression of vascular endothelial growth factor, induction of apoptosis, disruption of DNA repair mechanisms, and induction of spermidine/spermine N1-acetyltransferase that modulates polyamine catabolism.

scholarly journals On the Discovery, Biological Effects, and Use of Cisplatin and Metallocenes in Anticancer Chemotherapy

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Santiago Gómez-Ruiz ◽  
Danijela Maksimović-Ivanić ◽  
Sanja Mijatović ◽  
Goran N. Kaluđerović
Keyword(s):  
Immune Response ◽  
Dna Repair ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Cellular Proteins ◽  
Antitumor Drugs ◽  
Anticancer Chemotherapy ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
High Antitumor Activity

The purpose of this paper is to summarize mode of action of cisplatin on the tumor cells, a brief outlook on the metallocene compounds as antitumor drugs as well as the future tendencies for the use of the latter in anticancer chemotherapy. Molecular mechanisms of cisplatin interaction with DNA, DNA repair mechanisms, and cellular proteins are discussed. Molecular background of the sensitivity and resistance to cisplatin, as well as its influence on the efficacy of the antitumor immune response was evaluated. Furthermore, herein are summarized some metallocenes (titanocene, vanadocene, molybdocene, ferrocene, and zirconocene) with high antitumor activity.

scholarly journals ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination deficient cells

2020 ◽  
Author(s):  
Priyanka Verma ◽  
Yeqiao Zhou ◽  
Zhendong Cao ◽  
Peter V. Deraska ◽  
Moniher Deb ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Parp Inhibitor ◽  
Resistance Mechanisms ◽  
Chromatin Accessibility ◽  
New Approach ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Mutant Cells ◽  
Distinct Aspect

AbstractThe response to Poly (ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous recombination (HR) DNA repair mechanisms and the abundance of lesions that trap PARP enzymes on chromatin. It remains unclear, however, if the established role of PARP in promoting chromatin accessibility impacts viability in these settings. Using a CRISPR based screen, we identify the PAR-binding Snf2-like ATPase, ALC1/CHD1L, as a key determinant of PARPi toxicity in HR-deficient cells. ALC1 loss reduced viability of BRCA mutant cells and enhanced their sensitivity to PARPi by up to 250-fold, while overcoming several known resistance mechanisms. ALC1 loss was not epistatic to other repair pathways that execute the PARPi response. Instead, ALC1 deficiency reduced chromatin accessibility concomitant with a decrease in the association of repair factors. This resulted in an accumulation of replication associated DNA damage and a reliance on HR. These findings establish PAR-dependent chromatin remodeling as a mechanistically distinct aspect of PARPi responses, implicating ALC1 inhibition as a new approach to overcome therapeutic resistance in HR-deficient cancers.

scholarly journals Tamoxifen resistance mechanisms in breast cancer treatment

2020 ◽  
Vol 8 (2) ◽  
pp. 224-232
Author(s):  
Asima Tayyeb
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Tamoxifen Resistance ◽  
Resistance Mechanisms ◽  
Breast Cancer Treatment ◽  
Therapeutic Interventions ◽  
Survival Outcomes ◽  
Breast Cancer Patients ◽  
Current Review

Therapies targeting estrogen receptor (ER) are being widely used to treat ER+ breast cancer patients. Despite early detection and improved survival outcomes, tamoxifen resistance, either intrinsic or acquired- is a major obstacle in effective disease management. Current review will summarize different molecular mechanisms of tamoxifen resistance both intrinsic and acquired in breast cancer treatment. This review not only provides basis to understand the nature of tamoxifen drug resistance but also suggests the mechanisms for its control leading to improved therapeutic interventions.

scholarly journals Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 563 ◽  
Author(s):  
Dinh-Toi Chu ◽  
Tiep Tien Nguyen ◽  
Nguyen Le Bao Tien ◽  
Dang-Khoa Tran ◽  
Jee-Heon Jeong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Treatment ◽  
Cell Biology ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Cancer Recurrence ◽  
Therapy Resistance ◽  
Therapeutic Approaches ◽  
Potential Applications

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms underlying the use of various types of stem cells in cancer treatment. In addition, we summarize recent progress in the clinical applications of stem cells, as well as common risks of this therapy. We finally give general directions for future studies, aiming to improve overall outcomes in the fight against cancer.

scholarly journals Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Birgit Lohberger ◽  
Dietmar Glänzer ◽  
Nicole Eck ◽  
Sylvia Kerschbaum-Gruber ◽  
Elisabeth Mara ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Molecular Mechanisms ◽  
Proton Irradiation ◽  
Particle Therapy ◽  
Dna Damages ◽  
X Ray ◽  
Dna Repair Mechanisms ◽  
Key Players ◽  
Repair Mechanisms

AbstractAlthough particle therapy with protons has proven to be beneficial in the treatment of chondrosarcoma compared to photon-based (X-ray) radiation therapy, the cellular and molecular mechanisms have not yet been sufficiently investigated. Cell viability and colony forming ability were analyzed after X-ray and proton irradiation (IR). Cell cycle was analyzed using flow cytometry and corresponding regulator genes and key players of the DNA repair mechanisms were measured using next generation sequencing, protein expression and immunofluorescence staining. Changes in metabolic phenotypes were determined with nuclear magnetic resonance spectroscopy. Both X-ray and proton IR resulted in reduced cell survival and a G2/M phase arrest of the cell cycle. Especially 1 h after IR, a significant dose-dependent increase of phosphorylated γH2AX foci was observed. This was accompanied with a reprogramming in cellular metabolism. Interestingly, within 24 h the majority of clearly visible DNA damages were repaired and the metabolic phenotype restored. Involved DNA repair mechanisms are, besides the homology directed repair (HDR) and the non-homologous end-joining (NHEJ), especially the mismatch mediated repair (MMR) pathway with the key players EXO1, MSH3, and PCNA. Chondrosarcoma cells regenerates the majority of DNA damages within 24 h. These molecular mechanisms represent an important basis for an improved therapy.

scholarly journals An Investigation of Point Mutations Discovers Novel Genes and Their Corresponding Motifs in Pancreatic Cancer

2021 ◽  
Author(s):  
Amin Ghareyazi ◽  
Amir Mohseni ◽  
Hamed Dashti ◽  
Abdollah Dehzangi ◽  
Hamid R. Rabiee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Point Mutations ◽  
Growth Factor Receptor ◽  
Causative Mutation ◽  
Cancer Subtypes ◽  
P53 Signaling ◽  
Pancreatic Cancers

It has now known that at least 10% of samples with pancreatic cancers (PC) contain a causative mutation in the known susceptibility genes, suggesting the importance of identifying cancer-associated genes that carry the causative mutations in high-risk individuals for early detection of PC. In this study, we develop a statistical pipeline using a new concept, called gene-motif, that utilizes both mutated genes and mutational processes to identify 4,211 3-nucleotide PC-associated gene-motifs within 203 significantly mutated genes in PC. Using these gene-motifs as distinguishable features for pancreatic cancer subtyping results in identifying five PC subtypes with distinguishable phenotypes and genotypes. Our comprehensive biological characterization reveals that these PC subtypes are associated with different molecular mechanisms including unique cancer related signaling pathways, in which for most of the subtypes targeted treatment options are currently available. Some of the pathways we identified in all five PC subtypes, including cell cycle and the Axon guidance pathway are frequently seen and mutated in cancer. We also identified Protein kinase C, EGFR (epidermal growth factor receptor) signaling pathway and P53 signaling pathways as potential targets for treatment of the PC subtypes. Altogether, our results uncover the importance of considering both the mutation type and mutated genes in the identification of cancer subtypes and biomarkers.

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