Search results for: BRCA1
#33984694 2021/05/01 To Up
PARP inhibitor olaparib has a potential to increase the effectiveness of electrochemotherapy in BRCA1 mutated breast cancer in mice.Electrochemotherapy (ECT), a local therapy, has different effectiveness among tumor types. In breast cancer, its effectiveness is low; therefore, combined therapies are needed. The aim of our study was to combine ECT with PARP inhibitor olaparib, which could inhibit the repair of bleomycin or cisplatin induced DNA damage and potentiate the effectiveness of ECT. The effects of combined therapy were studied in BRCA1 mutated (HCC1937) and non-mutated (HCC1143) triple negative breast cancer cell lines. Therapeutic effectiveness was studied in 2D and 3D cell cultures and in vivo on subcutaneous HCC1937 tumor model in mice. The underlying mechanism of combined therapy was determined with the evaluation of γH2AX foci. Combined therapy of ECT with bleomycin and olaparib potentiated the effectiveness of ECT in BRCA1 mutated HCC1937, but not in non-mutated HCC1143 cells. The combined therapy had a synergistic effect, which was due to the increased number of DNA double strand breaks. Addition of olaparib to ECT with bleomycin in vivo in HCC1937 tumor model had only minimal effect, indicating repetitive olaparib treatment would be needed. This study demonstrates that DNA repair inhibiting drugs, like olaparib, have the potential to increase the effectiveness of ECT with bleomycin.
Masa Bosnjak, Tanja Jesenko, Bostjan Markelc, Larisa Janzic, Maja Cemazar, Gregor Sersa
2509 related Products with: PARP inhibitor olaparib has a potential to increase the effectiveness of electrochemotherapy in BRCA1 mutated breast cancer in mice.
#33984284 2021/05/04 To Up
The Fanconi anemia ubiquitin E3 ligase complex as an anti-cancer target.Agents that induce DNA damage can cure some cancers. However, the side effects of chemotherapy are severe because of the indiscriminate action of DNA-damaging agents on both healthy and cancerous cells. DNA repair pathway inhibition provides a less toxic and targeted alternative to chemotherapy. A compelling DNA repair target is the Fanconi anemia (FA) E3 ligase core complex due to its critical-and likely singular-role in the efficient removal of specific DNA lesions. FA pathway inactivation has been demonstrated to specifically kill some types of cancer cells without the addition of exogenous DNA damage, including cells that lack BRCA1, BRCA2, ATM, or functionally related genes. In this perspective, we discuss the genetic and biochemical evidence in support of the FA core complex as a compelling drug target for cancer therapy. In particular, we discuss the genetic, biochemical, and structural data that could rapidly advance our capacity to identify and implement the use of FA core complex inhibitors in the clinic.
Michael F Sharp, Rohan Bythell-Douglas, Andrew J Deans, Wayne Crismani
2749 related Products with: The Fanconi anemia ubiquitin E3 ligase complex as an anti-cancer target.0.1ml (1mg/ml)1 ml100ug Lyophilized0.1ml (1mg/ml)1ml100ug Lyophilized200 100ug Lyophilized
#33983705 2021/05/13 To Up
Multiplex Electrochemiluminescence Polarization Assay Based on the Surface Plasmon Coupling Effect of Au NPs and [email protected] NPs.A novel multiplex electrochemiluminescence (ECL) polarization assay was developed to detect breast cancer-related genes BRCA1 and BRCA2 simultaneously based on the polarization characteristics of surface plasmon-coupled electrochemiluminescence (SPC-ECL). In this work, boron nitride quantum dots (BN QDs) were used as ECL emitters, and gold nanoparticles (Au NPs) and gold-coated silver nanoparticles ([email protected] NPs) were employed as surface plasmon materials. The surface plasmon coupling resonance of different metal NPs not only enhanced the ECL intensity but also converted the isotropic emission into directional emission. This study revealed the relation between the structure of metal nanomaterials and SPC-ECL, and a high polarization-resolved sensing system was designed to detect multitarget DNA from 100 aM to 1 nM simultaneously. Polarization-based multiple ECL analysis has broad prospects in related cancer diagnosis and treatment evaluation.
Zihui Liang, Yixin Nie, Xin Zhang, Peilin Wang, Qiang Ma
2574 related Products with: Multiplex Electrochemiluminescence Polarization Assay Based on the Surface Plasmon Coupling Effect of Au NPs and [email protected] NPs.540 tests1 kit300 tests430 tests200ul1 mg100ul1 mg
#33983674 2021/05/13 To Up
A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin.Predictive biomarkers of trabectedin represents an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5 and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced soft-tissue sarcoma. Patients in the high-risk gene signature group showed a significantly worse progression-free survival (PFS) compared to patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.
David S Moura, Maria Peña-Chilet, Juan Antonio Cordero Varela, Ramiro Alvarez-Alegret, Carolina Agra-Pujol, Francisco Izquierdo, Rafael Ramos, Luis Ortega-Medina, Francisco Martin-Davila, Carolina Castilla-Ramirez, Carmen Nieves Hernandez-Leon, Cleofe Romagosa, Maria Angeles Vaz Salgado, Javier Lavernia, Silvia Bagué, Empar Mayodormo-Aranda, Luis Vicioso, Jose Emilio Hernández Barceló, Jordi Rubio-Casadevall, Ana de Juan, Maria Concepcion Fiaño-Valverde, Nadia Hindi, Maria Lopez-Alvarez, Serena Lacerenza, Joaquin Dopazo, Antonio Gutierrez, Rosa Alvarez, Claudia Valverde, Javier Martinez-Trufero, Javier Martín-Broto
1371 related Products with: A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin.
#33983595 // To Up
BRCA and Breast Cancer-Related High-Penetrance Genes.Genetic susceptibility explains 5-10% of all breast cancer cases. High-penetrance breast cancer susceptibility genes deliberate a greater than tenfold relative risk of breast cancer. BRCA1 and BRCA2 genes are the most common cause of hereditary breast cancer, and TP53, PTEN, and SKT11 (LKB1) are rarely present. The prevalence of BRCA1 and BRCA2 genetic alterations differ in various ethnic groups. The Korean Hereditary Breast Cancer (KOHBRA) Study, nationwide-scale study, was established to acquire evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea prospectively since 2007. In this chapter, we review previous research related to hereditary breast cancer and summarize the present concepts and research results centered on the Korean Hereditary Breast Cancer Research at this time.
Sang-Ah Han, Sung-Won Kim25
#33983594 // To Up
Multigene Panel Testing for Hereditary Cancer and Genetic Counseling.As sequencing technology and information of the genomic causes for cancer development expand, multi-gene panel testing for hereditary cancer is increasing in clinical practice. In this chapter, we reviewed the application of multi-gene panel with pre-/post- testing considerations and summarized genetic counseling based on panel testing results in clinical field. In addition, we introduce multi-gene panel for hereditary cancer developed in Seoul National University Hospital.
Eun-Shin Lee, Jongjin Kim, Wonshik Han100ug 25 G 6 ml Ready-to-use
#33983592 // To Up
Breast Cancer-Related Low Penetrance Genes.Susceptibility genes involved in disease etiology and prognosis are categorized into two groups: high penetrance genes (i.e., BRCA1, CHEK2, ATM, etc.) and low penetrance genes (i.e., NATs, GSTs, CYPs, etc., and variants identified by genome-wide association studies). Since low penetrance genes have high population attributable risk, the usefulness of those genes to research on breast cancer prevention is not small. In this chapter, the previous studies on low-penetrance genetic susceptibility through a candidate gene approach and genome-wide association of breast cancer were summarized. The contribution of low-penetrance susceptibility genes to the breast cancer risk prediction models will also be discussed on the utility in clinical or public health application.
Daehee Kang, Ji-Yeob Choi
#33983578 // To Up
DNA Damage Repair Inhibitor for Breast Cancer Treatment.Cancer has been defined as a genetic disorder caused by the accumulation of genetic alterations, which result from various internal and external DNA damage that is left unrepaired. One of the main characteristics of cancer is a partial loss of DNA damage repair (DDR) pathway, resulting in increased DNA damage levels and replication stress. DDR inhibitors have been suggested as a new anticancer strategy, under the concept of synthetic lethality. The poly-(ADP-ribose) polymerase (PARP) inhibitor is the first DDR inhibitor to be used in clinical practice. PARP inhibitors have been tested in patients with BRCA1/2 germline mutations (gBRCA1/2mt) and shown robust clinical benefits in breast cancer with gBRCA1/2mt and serous ovarian cancer patients. The concept of synthetic lethality is not limited to gBRCAmt for PARP inhibitor, and discovering homologous recombination deficiency (HRD) markers beyond BRCA1/2 and identifying best candidates for DDR inhibitors are the active research areas. At the same time, various combinations of DDR inhibitors and other anticancer drugs are being tested in both preclinical and clinical studies. In addition, based on recent evidence of the immune-modulatory effect of PARP inhibitors, the combination of DDR inhibitors and immune checkpoint inhibitors is being actively investigated. Acquired resistance mechanism of DDR inhibitors, as well as defining best candidates and best combinations, would be future research topics for DDR inhibitors. Furthermore, it would also be crucial to establish a clinically relevant standardized method to detect HRD for future clinical use.
Ahrum Min, Kyung-Hun Lee, Seock-Ah Im
#33980423 2021/04/12 To Up
Clinical Contribution of Next-Generation Sequencing Multigene Panel Testing for BRCA Negative High-Risk Patients With Breast Cancer.Breast cancer is the most common malignancy in women and thought to be hereditary in 10% of patients. Recent next-generation sequencing studies have increased the detection of pathogenic or likely pathogenic (P/LP) variants in genes other than BRCA1/2 in patients with breast cancer. This study evaluated pathogenic variants, likely pathogenic variants, and variants of unknown significance in 18 hereditary cancer susceptibility genes in patients with BRCA1/2-negative breast cancer.
Aslı Ece Solmaz, Levent Yeniay, Erhan Gökmen, Osman Zekioğlu, Ayfer Haydaroğlu, Işıl Bilgen, Ferda Özkınay, Hüseyin Onay
2384 related Products with: Clinical Contribution of Next-Generation Sequencing Multigene Panel Testing for BRCA Negative High-Risk Patients With Breast Cancer.
#33979701 2021/05/09 To Up
BRCC3 promotes activation of the NLRP6 inflammasome following Cerebral Ischemia/Reperfusion (I/R) Injury in Rats.NOD-like receptor family pyrin domain containing 6 (NLRP6), a novel member of the NLR family, has been confirmed to have an inflammasome-dependent proinflammatory effect in cerebral ischemia/reperfusion injury. NLRP6 assembles a multimeric inflammasome complex comprising the adaptor ASC and the effector pro-caspase-1 to mediate the activation of caspase-1. The molecular mechanism regulating activation of the NLRP6 inflammasome remains unclear. Previous studies have shown that BRCA1-BRCA2-containing complex subunit 3 (BRCC3), a JAMM domain-containing Zn metalloprotease deubiquitinating enzyme, participates in a variety of cellular activities. In this study, we found that BRCC3 expression was increased in the middle cerebral artery occlusion (MCAO) model. BRCC3 siRNA could reduce nerve damage and inflammation. Interestingly, the result of co-immunoprecipitation showed that the interaction between BRCC3 and NLRP6 was enhanced after model, and the result of immunofluorescence showed that the co-localization of BRCC3 and NLRP6 was increased. At the same time, the expression of NLRP6, cleavated-caspase-1 and IL-1β was decreased after BRCC3 interference. These results illustrate a regulatory mechanism involving the BRCC3-NLRP6 pathway and highlight NLRP6 as a potential therapeutic target for inflammatory diseases.
Xiaohuan Huang, Hui Gan, Junyi Tan, Tingting Wang, Jing Zhao, Yong Zhao
2408 related Products with: BRCC3 promotes activation of the NLRP6 inflammasome following Cerebral Ischemia/Reperfusion (I/R) Injury in Rats.2 mg100μg96T100ug25 Bags/Unit100ug
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