scholarly journals A modified fluctuation test for elucidating drug resistance in microbial and cancer cells

2020 ◽  
Author(s):  
Pavol Bokes ◽  
Abhyudai Singh
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Colony Size ◽  
Random Number ◽  
Initial Conditions ◽  
Fano Factor ◽  
Persister Cells ◽  
Efficient Treatment ◽  
Fluctuation Test ◽  
The Mean

AbstractClonal populations of microbial and cancer cells are often driven into a drug-tolerant persister state in response to drug therapy, and these persisters can subsequently adapt to the new drug environment via genetic and epigenetic mechanisms. Estimating the frequency with which drug-tolerance states arise, and its transition to drug-resistance, is critical for designing efficient treatment schedules. Here we study a stochastic model of cell proliferation where drug-tolerant persister cells transform into a drug-resistant state with a certain adaptation rate, and the resistant cells can then proliferate in the presence of the drug. Assuming a random number of persisters to begin with, we derive an exact analytical expression for the statistical moments and the distribution of the total cell count (i.e., colony size) over time. Interestingly, for Poisson initial conditions the noise in the colony size (as quantified by the Fano factor) becomes independent of the initial condition and only depends on the adaptation rate. Thus, experimentally quantifying the fluctuations in the colony sizes provides an estimate of the adaptation rate, which then can be used to infer the starting persister numbers from the mean colony size. Overall, our analysis introduces a modification of the classical Luria–Delbrück experiment, also called the “Fluctuation Test”, providing a valuable tool to quantify the emergence of drug resistance in cell populations.

scholarly journals PYCR1 Promotes Proliferation, Invasion and Drug-Resistance of Lung Cancer Cells by Regulating STAT3-Mediated PI3K/AKT and NF-κB Signaling Pathway

2020 ◽  
Author(s):  
Zhanwu Yu ◽  
Gebang Wang ◽  
Chenlei Zhang ◽  
Yu Liu ◽  
Wei Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Target Genes ◽  
Western Blot Assay ◽  
Aberrant Expression ◽  
Efficient Treatment ◽  
Underlying Mechanisms

Abstract Background: Aberrant expression of PYCR1 has been proved to be one of the most pivotal regulators of tumor progress and metastasis. However, the detailed role of PYCR1 in promotion of NSCLC progress is not investigated thoroughly. The present study was aimed to thoroughly investigate the effect of PYCR1 in the growth of NSCLC and the underlying mechanisms, so that provide valuable theoretical basis for efficient treatment of NSCLC. Methods: The expressions of PYCR1 and its target genes and downstream signals were respectively determined by Western-blot assay and RT-qPCR experiment. Cell growth of NSCLC cells was investigated using the CCK-8 kit while the proliferation assay was performed with the help of EDU staining. The NSCLC-bearing mice mode was established to evaluate the effect of PYCR1 on the progress of NSCLC and the underlying mechanisms in vivo.Results: It was firstly demonstrated that the PYCR1 was overexpressed in lung cancer tissues and cells and overexpression of PYCR1 contributed to significantly enhanced proliferation, invasion, and drug-resistance of cancer cells and progress of NSCLC tissues. Further studies revealed that up-regulation of PYCR1 level resulted to the elevation of bioactivity of STAT3. Additionally, the positive correlation between the expression of PYCR1 and STAT3 indicated that the PYCR1 promotes the growth of NSCLC through targeting regulation the STAT3 levels. Furthermore, activation of STAT3 by PYCR1 was proved to be able of awaking the PI3K/AKT and NF-κB signaling pathway, which was extremely important to the metabolism, proliferation, cell survival, and growth of many cancer cell types.Conclusion: In conclusion, our study demonstrated that PYCR1 was specifically overexpressed in lung cancer and closely related to rapid progress and drug-resistance thorough regulating the STAT3-mediated PI3K/AKT and NF-κB signaling pathway. It may provide a valuable strategy for treatment of malignant lung cancer.

Oncogenic LncRNA CASC9 in Cancer Progression

2020 ◽  
Vol 26 ◽  
Author(s):  
Yuying Qi ◽  
Chaoying Song ◽  
Jiali Zhang ◽  
Chong Guo ◽  
Chengfu Yuan
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Cell Growth ◽  
Cancer Cells ◽  
Therapeutic Potential ◽  
Squamous Metaplasia ◽  
Neoplastic Transformation ◽  
Over Expression ◽  
Human Cancers ◽  
Current Review

Background: Long non-coding RNA (LncRNAs), with the length over 200 nucleotides, originate from intergenic, antisense, or promoter-proximal regions, is a large family of RNAs that lack coding capacity. Emerging evidences illustrated that LncRNAs played significant roles in a variety of cellular functions and biological processes in profuse human diseases, especially in cancers. Cancer susceptibility candidate 9 (CASC9), as a member of the LncRNAs group, was firstly found its oncogenic function in esophageal cancer. In following recent studies, a growing amount of human malignancies are verified to be correlated with CASC9, most of which are derived from the squamous epithelium tissue. This present review attempts to highlight the latest insights into the expression, functional roles, and molecular mechanisms of CASC9 in different human malignancies. Methods: In this review, the latest findings related to the pathophysiological processes of CASC9 in human cancers were summarized and analyzed, the associated studies were collected in systematically retrieval of PubMed used lncRNA and CASA9 as keywords. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depress cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 closely relates to neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of CASC9 in various human cancers. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depress cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 closely relates to neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of CASC9 in various human cancers. Conclusion: Long non-coding RNACASC9 likely served as useful disease biomarkers or therapy targets that could effectively apply in treatment of different kinds of cancers.

Strategies to Overcome Multi-Drug Resistance in Cancer Cells: the Contribution of siRNA and Nanotechnologies

2016 ◽  
Vol 20 (28) ◽  
pp. 2971-2982
Author(s):  
Cristina Mambet ◽  
Mihaela Chivu-Economescu ◽  
Lilia Matei ◽  
Mihai Stoian ◽  
Coralia Bleotu
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Multi Drug Resistance

The Expression of Dopamine Receptors Gene and their Potential Role in Targeting Breast Cancer Cells with Selective Agonist and Antagonist Drugs. Could it be the Novel Insight to Therapy?

2019 ◽  
Vol 16 (2) ◽  
pp. 184-197 ◽  
Author(s):  
Hossein Bakhtou ◽  
Asiie Olfatbakhsh ◽  
Abdolkhaegh Deezagi ◽  
Ghasem Ahangari
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Dopamine Receptors ◽  
Breast Cancer Cells ◽  
D2 Receptors ◽  
Healthy Individuals ◽  
Agonist And Antagonist ◽  
The Mean ◽  
Mcf 7

Background:Breast cancer is one of the common causes of mortality for women in Iran and other parts of the world. The substantial increasing rate of breast cancer in both developed and developing countries warns the scientists to provide more preventive steps and therapeutic measures. This study is conducted to investigate the impact of neurotransmitters (e.g., Dopamine) through their receptors and the importance of cancers via damaging immune system. It also evaluates dopamine receptors gene expression in the women with breast cancer at stages II or III and dopamine receptor D2 (DRD2) related agonist and antagonist drug effects on human breast cancer cells, including MCF-7 and SKBR-3.Methods:The patients were categorized into two groups: 30 native patients who were diagnosed with breast cancer at stages II and III, with the mean age of 44.6 years and they were reported to have the experience of a chronic stress or unpleasant life event. The second group included 30 individuals with the mean age of 39 years as the control group. In order to determine the RNA concentration in all samples, the RNA samples were extracted and cDNA was synthesized. The MCF-7 cells and SKBR-3 cells were treated with dopamine receptors agonists and antagonists. The MTT test was conducted to identify oxidative and reductive enzymes and to specify appropriate dosage at four concentrations of dopamine and Cabergoline on MCF-7 and SKBR-3 cells. Immunofluorescence staining was done by the use of a mixed dye containing acridine orange and ethidiume bromide on account of differentiating between apoptotic and necrotic cells. Flow cytometry assay was an applied method to differentiate necrotic from apoptotic cells.Results:Sixty seven and thirty three percent of the patients were related to stages II and III, respectively. About sixty three percent of the patients expressed ER, while fifty seven percent expressed PR. Thirty seven percent of the patients were identified as HER-2 positive. All types of D2-receptors were expressed in PBMC of patients with breast cancer and healthy individuals. The expression of the whole dopamine receptor subtypes (DRD2-DRD4) was carried out on MCF-7 cell line. The results of RT-PCR confirmed the expression of DRD2 on SKBR-3 cells, whereas the other types of D2- receptors did not have an expression. The remarkable differences in gene expression rates between patients and healthy individuals were revealed in the result of the Real-time PCR analysis. The over expression in DRD2 and DRD4 genes of PBMCs was observed in the patients with breast cancer at stages II and III. The great amount of apoptosis and necrosis occurred after the treatment of MCF-7 cells by Cabergoline from 25 to 100 µmolL-1 concentrations.Conclusion:This study revealed the features of dopamine receptors associated with apoptosis induction in breast cancer cells. Moreover, the use of D2-agonist based on dopamine receptors expression in various breast tumoral cells could be promising as a new insight of complementary therapy in breast cancer.

Emodin Enhances the Chemosensitivity of Endometrial Cancer by Inhibiting ROS-Mediated Cisplatin-resistance

2018 ◽  
Vol 18 (7) ◽  
pp. 1054-1063 ◽  
Author(s):  
Ning Ding ◽  
Hong Zhang ◽  
Shan Su ◽  
Yumei Ding ◽  
Xiaohui Yu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Annexin V ◽  
Chemotherapeutic Agents ◽  
Endometrial Cancer Cell ◽  
Animal Survival ◽  
Apoptosis Level

Background: Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective: Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method: CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results: Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drugresistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion: This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes.

scholarly journals Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation

2013 ◽  
Vol 43 (4) ◽  
pp. 1111-1116 ◽  
Author(s):  
WARAPORN MALILAS ◽  
SANG SEOK KOH ◽  
SEOKHO KIM ◽  
RATAKORN SRISUTTEE ◽  
IL-RAE CHO ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Colon Cancer Cells

Silencing PEX26 as an Unconventional Mode to Kill Drug-Resistant Cancer Cells and Forestall Drug Resistance

Autophagy ◽  
2021 ◽  
Author(s):  
Michael S. Dahabieh ◽  
Fan Huang ◽  
Christophe Goncalves ◽  
Raúl Ernesto Flores González ◽  
Sathyen Prabhu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Drug Resistant

scholarly journals Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1792
Author(s):  
Debashri Manna ◽  
Devanand Sarkar
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Development ◽  
Epigenetic Alterations ◽  
Hallmarks Of Cancer ◽  
Comprehensive Description ◽  
Molecular Abnormalities ◽  
Selective Pressures ◽  
Resistance To Chemotherapy

Cancer development results from the acquisition of numerous genetic and epigenetic alterations in cancer cells themselves, as well as continuous changes in their microenvironment. The plasticity of cancer cells allows them to continuously adapt to selective pressures brought forth by exogenous environmental stresses, the internal milieu of the tumor and cancer treatment itself. Resistance to treatment, either inherent or acquired after the commencement of treatment, is a major obstacle an oncologist confronts in an endeavor to efficiently manage the disease. Resistance to chemotherapy, chemoresistance, is an important hallmark of aggressive cancers, and driver oncogene-induced signaling pathways and molecular abnormalities create the platform for chemoresistance. The oncogene Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) is overexpressed in a diverse array of cancers, and its overexpression promotes all the hallmarks of cancer, such as proliferation, invasion, metastasis, angiogenesis and chemoresistance. The present review provides a comprehensive description of the molecular mechanism by which AEG-1 promotes tumorigenesis, with a special emphasis on its ability to regulate chemoresistance.

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