scholarly journals Carrying G allele in rs786204926 involved in alternative splicing of PTEN is associated with chemosensitivity in breast cancer

Author(s):  
Jing Wang ◽  
Shasha Zhang ◽  
Jiaxin Zhang ◽  
Zhongliang Zhang ◽  
Qinglong Ma ◽  
...  

Abstract Background Chemoresistance is still the main reason for the failure of breast cancer treatment and is the main cause of death of breast cancer patients. Although many studies have shown the association between genetic polymorphisms of PTEN and chemoresistance, the molecular mechanism of breast cancer chemotherapy has not been further studied. This study aims to investigate the potential association between novel PTEN gene polymorphism and breast chemoresistance in Chinese population, and explore whether alternative splicing of the PTEN gene is affected by the gene polymorphism. Methods The study included 234 patients with breast cancer chemotherapy, 157 chemosensitive cases and 77 chemoresistant case. rs786204926, rs701848, rs12402181, rs35770269 were analysed using Sanger sequence and Sequenom MassArray typing technology. Silicon analysis was used to predict whether and how the polymorphism affects alternative splicing. Semi-quantitative RT-PCR and Western blot were further used to validate the silicon analysis. Results It is showed that there was a significant association between rs786204926 polymorphism and breast cancer chemoresistance. Carrying G allele or AG genotype will increase the risk of chemosensitivity in breast cancer. Additionally, Logistic multivariate regression analysis showed that age, lymph node metastasis and rs786204926 genotype are risk factors for breast cancer chemoresistance. Furthermore, Silico analysis showed that carrying G allele or AG genotype in chemosensitivity samples produced a new receptor site of alternative splicing, which increases the possibility of a new mutant PTEN isoform production. Interestingly, further experiments also verify this possibility. Conclusion We speculate that the mechanism of breast cancer chemosensitivity might be caused by a change in alternative splicing caused by the rs786204926 of PTEN gene. Thus, our study might provide theoretical guidance for the individualized treatment of clinical breast cancer patients.

2021 ◽  
Author(s):  
Jing Wang ◽  
Shasha Zhang ◽  
Zhongliang Zhang ◽  
Qinglong Ma ◽  
Xiaohua Chen ◽  
...  

Abstract Background Chemoresistance is still the main reason for the failure of breast cancer treatment and is the main cause of death of breast cancer patients. Although many studies have shown the association between genetic polymorphisms of PTEN and chemotherapy resistance, the molecular mechanism of breast cancer chemotherapy has not been further studied. This study aims to investigate the potential association between PTEN gene polymorphism and breast chemotherapy resistance in the Chinese population, and explore whether alternative splicing of the PTEN gene is affected by the gene polymorphism. Methods The study included 234 patients with breast cancer chemotherapy, 157 chemotherapy sensitive cases and 77 chemotherapy resistant cases. rs786204926 of the PTEN gene was analysed by Sanger sequence and Sequenom MassArray typing technology. Furthermore, we used silicon analysis to predict whether polymorphism affect the process of alternative splicing and to analyze how it affects. Results In genotyping and allelic analysis, there was a significant association between rs786204926 polymorphism and breast cancer chemotherapy resistance. Carrying the G allele or AG genotype will reduce the risk of breast cancer-based resistance to chemotherapy with anthracyclines. Silicon analysis showed that the mutation of rs786204926 produced a new receptor site, which might affect alternative splicing of PTEN gene. Conclusions We speculate that the mechanism of breast cancer chemotherapy resistance might be caused by a change in the alternative splicing caused by the rs786204926 of the PTEN gene. Thus, our study might provide theoretical guidance for the individualized treatment of clinical breast cancer patients.


2018 ◽  
Vol 8 (6) ◽  
pp. 77 ◽  
Author(s):  
Pearman D. Parker ◽  
Sue P. Heiney ◽  
Daniela B. Friedman ◽  
Tisha M. Felder ◽  
Robin Dawson Estrada ◽  
...  

Background: Chemotherapy is commonly used in combination with other treatments for breast cancer. However, low adherence to chemotherapy is a growing concern, particularly among breast cancer patients. Side effects such as nausea and vomiting, fatigue, and arthralgia can contribute to reduced adherence. Other factors such as provider communication and limited insurance coverage can affect adherence. Studies have shown that as much as 28% of patients with breast cancer did not continue with their prescribed dose of chemotherapy. Research suggests that chemotherapy education materials can be critical to addressing problems with non-adherence, and may include written materials, verbal instruction, and multimedia programs. Despite this wide variety, the effectiveness and benefit of chemotherapy education hinges on the patients’ health literacy.  Breast cancer patients with low health literacy may be unclear about chemotherapy or face difficulty adhering to treatment if they do not understand the information provided to them. Thus, this scoping review summarizes the existing research on how health literacy principles are incorporated into breast cancer chemotherapy education materials.Methods: Using a combination of keywords (e.g. chemotherapy, education) and Medical subject headings (MeSH) terms (e.g., drug therapy, antineoplastic agents), we searched five databases (1977-2017): CINAHL, PubMed, PsycINFO, Cochrane Library, and Web of Science.Results: Eight of 4,624 articles met the inclusion criteria. Five articles incorporated health literacy principles (e.g., plain language, maintaining an active voice, using white space) into the development of written materials. Few articles used a theoretical framework to guide education material development (n = 3). Of the three articles that described pilot-testing of educational materials, two used post-tests only and one used a pre/post-test design.Conclusions: Findings indicated that limited research exists regarding the use of health literacy principles in chemotherapy education materials. Much of the development of chemotherapy education is not grounded in theory and the application of health literacy principles is limited. Implementing health literacy principles may improve overall comprehension of education thereby increasing adherence.


2021 ◽  
Vol 1 (2) ◽  
pp. 36-41
Author(s):  
Angga Dian Prastowo

AbstrakKanker payudara adalah penyebab kematian terbesar pada wanita. Salah satu hal yang penting untuk diperhatikan adalah pada pasien kanker payudara yang menjalani kemoterapi akan mengalami efek samping mual muntah, rambut rontok, nyeri, kehilangan nafsu makan dan lain- lain. Penelitian saat ini bertujuan untuk mengetahui pengaruh konseling terhadap tingkat pemahaman penyakit dan efek samping kemoterapi pasien kanker payudara Penderita kanker payudara perlu mengetahui penyakitnya dengan baik agar kualitas hidupnya dapat tetap terjaga. Edukasi yang dilakukan secara perseorangan maupun kelompok pada penderita tentang efek samping obat kemoterapi sangat diperlukan supaya penderita tidak merasa cemas apabila mengalami efek dari kemoterapi tersebut. Pemberian konseling oleh Apoteker pada pasien kemoterapi kanker payudara sangat penting karena dapat meningkatkan pengetahuan pasien, kepatuhan pasien dalam pengobatannya serta dapat meningkatkan kualitas hidup pasien. Tujuan penelitian ini untuk mengetahui pengaruh pemberian konseling oleh Apoteker terhadap tingkat pemahaman penyakit dan efek samping kemoterapi pada pasien kanker payudara di Unit Kemoterapi Salah Satu Rumkit Pemerintah Di Kota Malang..Penelitian ini merupakan studi kuantitatif dengan desain Pre-Experimental berupa pretest-postes design. Banyaknya sampel yang diambil didasarkan atas waktu yaitu selama satu bulan dan sampel diambil dengan metode consecutive sampling. Hasil penelitian menggunakan uji Wilcoxon menunjukkan terdapat perbedaan nilai sebelum dan sesudah diberikan konseling oleh apoteker terhadap pasien kemoterapi kanker payudara dengan nilai signifikansi sebesar 0,000 (P value< 0,05). Kesimpulan pada penelitian ini adalah pemberian konseling oleh apoteker dapat meningkatkan tingkat pemahaman penyakit dan efek samping dari kemoterapi kanker payudara.Kata kunci : konseling, pemahaman, penyakit kanker payudara, efek samping kemoterapi Abstract Breast cancer is the leading cause of death in women. One important thing to note is that breast cancer patients who undergo chemotherapy experience side effects of nausea and vomiting, hair loss, pain, loss of appetite and others. The current study aims to determine the effect of counseling on the level of understanding of the disease and the side effects of breast cancer chemotherapy patients Breast cancer patients need to know the disease well to the quality of life can be maintained. Education is done individually or in groups to the patient about the side effects of chemotherapy drugs is indispensable so that the patient does not feel anxious when experiencing the effects of chemotherapy. Provision of counseling by pharmacists in patients with breast cancer chemotherapy is very important because it can improve patient knowledge, patient compliance in the treatment and can improve the quality of life of patients. The purpose of this study to determine the effect of counseling by pharmacists to the level of understanding of the disease and the side effects of chemotherapy in breast cancer patients on Chemotherapy Unit One Government Hospital In Malang .. This research is a quantitative study with Pre-Experimental design in the form of a pretestposttest design. The number of samples taken based on the time that is for one month and samples were taken with consecutive sampling method. The results using the Wilcoxon test shows that there are differences in values before and after counseling by pharmacists to patients with breast cancer chemotherapy with a significance value of 0.000 (p value <0.05). Conclusion of this research is the provision of counseling by pharmacists can improve the level of understanding of the disease and the side effects of breast cancerchemotherapy. The results using the Wilcoxon test shows that there are differences in values before and after counseling by pharmacists to patients with breast cancer chemotherapy with a significance value of 0.000 (p value <0.05). Conclusion of this research is the provision of counseling by pharmacists can improve the level of understanding of the disease and the side effects of breast cancer chemotherapy. The results using the Wilcoxon test shows that there are differences in values before and after counseling by pharmacists to patients with breast cancer chemotherapy with a significance value of 0.000 (p value <0.05). Conclusion of this research is the provision of counseling by pharmacists can improve the level of understanding of the disease and the side effects of breast cancer chemotherapy. Keywords : Counseling, understanding, breast cancer, chemotherapy side effects


2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.


2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.


2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.


2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.


2010 ◽  
Vol 1 (4) ◽  
pp. 40 ◽  
Author(s):  
MushtaqA Siddiqi ◽  
Nidda Syeed ◽  
Safiya Abdullah ◽  
ASyed Sameer ◽  
SyedAkhtar Husain ◽  
...  

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