The Impact of Centrosome Abnormalities on Breast Cancer Development and Progression with a Focus on Targeting Centrosomes for Breast Cancer Therapy

Author(s):  
Heide Schatten
2021 ◽  
Author(s):  
Gaik-Hong Soon ◽  
Seok Hwee Koo ◽  
Pei Ting Tan ◽  
Lawrence Soon-U Lee ◽  
Chee Kian Tham ◽  
...  

Abstract Background: Breast cancer is the top cancer suffered by women worldwide and has been identified to be the greatest killer for women living in Singapore. Unfortunately, most of breast cancer cases were detected only at later stage of disease development. This has crippled the effort of breast cancer therapy. As early detection of breast cancer could greatly improve the outcome of breast cancer therapy, it is of utmost importance to identify relevant biomarkers at the primitive stage of breast cancer development before the transformation of normal breast cells into cancerous cells. These biomarkers provide important clues leading to an efficient and targeted treatment approach in breast cancer preventive care.Methods: 455 breast cancer patients were consented to join this study. Buccal swabs were collected for genotyping on CYP2B6*6, CYP2C19 *2 & CYP2C19*3. The genotyping data were then compared to data collected from healthy individuals. Clinical data were collected from patient notes and analysed. All the statistical analyses were done using SPSS statistical software, version 19.0. Chi-square or Fisher’s Exact test were performed to examine the difference between subject’s characteristics for categorical variables and One-Way Anova was performed to assess age difference across alleles of CYP2B6*6, CYP2C19*2 and CYP2C19*3. Binary logistics regression was performed to identify demographic factors associated with breast cancer.Results: We reported thatCYP2B6*6 could be a risk factor leading to earlier onset of breast cancer among Indian population with OR found to be 1.69 (95% C.I.= 0.549-5.191, p=0.359). In the case of CYP2C19*2, OR is 1.57 for Malay (95% C.I. = 0.696-3.522, p=0.278); 1.15 for Chinese population (95% C.I. =0.862-1.545, p=0.335) and 1.03 for Indian (95% C.I. =0.301-3.496, p=0.968). CYP2C19*3 OR in Chinese population is 1.34 (95% C.I. =0.830-2.155, p=0.231) and 0.77 (95% C.I. =0.172-3.394, p=0.724) for Malay population. No CYP2C19*3 was detected in both cohorts of Indian patients and healthy controls. Conclusions: CYP2B6*6 and CYP2C19*2 polymorphisms may confer a risk for breast cancer development in Singaporean breast cancer patients. This is an exploratory study to identify potential breast cancer susceptibility gene polymorphisms, a bigger sample size study could be done to corroborate these findings in future studies.


1997 ◽  
Vol 3 (1) ◽  
pp. 68-81
Author(s):  
Fatma M. El Sharkawi ◽  
Mahmoud F. Sakr ◽  
Hoda Y. Atta ◽  
Hafez M. Ghanem

The impact of breast cancer therapy on the quality of life [QL] of Egyptian women was studied. Patients were divided into four groups:1:mastectomy alone;2:surgery plus radiotherapy;3:surgery plus chemotherapy;and 4:triple modality. The results revealed that all the four domains of QL of women having adjuvant therapy [groups 2, 3, or 4] were significantly altered compared to those who underwent mastectomy alone. Triple modality adversely affected global QL the most compared to radiotherapy or chemotherapy;radiotherapy had significantly less effect on QL compared to chemotherapy. Triple modality predicted the worst QL. QL measures should be incorporated with the traditional end points for evaluation of treatment and patients given health education on the effects of each therapy


Author(s):  
Marcin Śniadecki ◽  
Michał Brzeziński ◽  
Katarzyna Darecka ◽  
Dagmara Klasa-Mazurkiewicz ◽  
Patryk Poniewierza ◽  
...  

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the most important of these genes, the BARD1 and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. Through ubiquitination, this heterodimer has significant effects on individual proteins, enabling, among others, the destruction of damaged DNA fragments. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.


2018 ◽  
Author(s):  
S Heublein ◽  
S Burgert ◽  
F Marme ◽  
F Schütz ◽  
J Heil ◽  
...  

Author(s):  
Raquel Santana da Cruz ◽  
Hong Cao ◽  
Camile C. Fontelles ◽  
Apsra Nasir ◽  
Alexandra Krebs ◽  
...  

AbstractBackgroundDNA sequence accounts for the majority of disease heritability, including cancer. However, it is becoming clear that environmentally-induced epigenetic inheritance can also occur. Epidemiological studies have shown that maternal exposure to the pesticide DDT in pregnancy is associated with increased breast cancer risk in women. Yet, the effects of paternal exposure to this and other pesticides on the progeny’s breast cancer development has not been investigated.MethodsMale mice (c57bl/6) were exposed to DDT or to a control-vehicle (CO) solution and used for sperm collection or mating with unexposed females to produce the DDT or CO daughters. In another experiment, normal mouse embryos (zygote stage) were injected with miRNA-10b and implanted into surrogate mothers to produce miR-10b offspring. DDT daughters or miRNA-10b females were used to study breast cancer development and metabolic parameters. Paternal sperm was used for RNA-seq analysis and miRNA expression levels.ResultsPre-conception paternal DDT exposure altered the sperm small non-coding RNA load, with an increase in miRNAs and a specific surge in miRNA-10b levels. DDT offspring weighed less at birth and at weaning, but became overweight and showed metabolic dysfunction in adulthood compared to CO. DDT daughters also showed increased mammary tumorigenesis, developing more aggressive tumors that grew faster than in CO. This tumor phenotype was linked to suppression of the AMPK energy sensing pathway and mTOR activation in mammary tissues. Remarkably, embryonic injection of miRNA-10b recapitulated the mammary gland and tumor phenotypes observed in DDT daughters.ConclusionsTo our knowledge, this is the first report of an association between paternal DDT exposure and breast cancer in offspring. Paternal DDT-induced programming of breast cancer development in daughters is mechanistically linked to sperm miRNA-10b. The impact of DDT and other endocrine disrupting chemicals on sperm and programming of breast and other cancers in offspring needs to be evaluated in humans.


Sign in / Sign up

Export Citation Format

Share Document