scholarly journals Selected Micro RNAs Regulate Drug Resistance Genes in Breast Cancer.

2021 ◽  
Author(s):  
Shumaila Zaib ◽  
Azra Yasmin ◽  
Nosheen Masood
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Progression Free Survival ◽  
Pten Gene ◽  
Over Expression ◽  
Micro Rnas ◽  
Exact Etiology

Abstract Background: Breast cancer initiation is an unresolved phenomenon although many genes are known to be involved in its initiation but its exact etiology is still unexplained in many aspects and recently microRNAs are found to regulate many genes expressions. Method: This case control study has been designed to evaluate the role of selected miRNAs in gene expression and subsequent association with drug resistance. Genetic polymorphisms were confirmed by PCR-SSCP followed by sequencing and microRNA expression was measured by realtime PCR with specific primers. Follow up was done for patients whose samples were used in the study. Results: This study revealed 15 germline mutations in mdr1, 5 in ABCG2, 8 in BRCA1 and 8 in PTEN gene. These mutations were significantly associated with breast cancer compared with control tissues (P<0.05). miR-21, miR-146a and miR-328 were over expressed whereas miR-451 was under expressed. Progression free survival (PFS) was linked with reduced polymorphisms in genes as well as microRNAs. Conclusion: Over expression of miRNA-21 and miRNA-146a may lead towards lower expression of PTEN and BRCA1 genes causing cancer progression. miRNA-328 and miRNA-451 reduced expression resulted in overexpressed ABCG2 and MDR1 genes in this study.

Evaluation of the tumor marker Ca27.29 for risk stratification and treatment monitoring in primary breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11005-11005
Author(s):  
E. M. Genss ◽  
B. Rack ◽  
H. L. Sommer ◽  
I. Schrader ◽  
R. Lorenz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Stratification ◽  
Tumor Marker ◽  
Primary Breast Cancer ◽  
Primary Diagnosis ◽  
Over Expression ◽  
Before And After ◽  
Node Metastases

11005 Background: Several trials have shown an earlier detection of metast. disease in breast cancer pts by the use of TU- markers. Whether this lead time advantage can be translated into improved outcome is discussed controversially. We prospectively evaluated the role of Ca27.29 in breast cancer pts at primary diagnosis and during adjuvant systemic treatment within the German SUCCESS-Trial (n=3658 pts planned). Methods: The SUCCESS-Trial compares sequential chemotherapy with FEC-Docetaxel(Doc) vs. FEC- DocGemcitabine, followed by zoledronate 2 vs. 5 years in primary high risk N0 and N+ breast cancer pts. Ca27.29 levels were assessed using the specific ST AIA-PACK Ca27.29 reagents directed against MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium). Cut-off levels for the assay was 24 U/ml. Results: We analyzed 1098 breast cancer pts prospectively before start and after completion of chemotherapy. 21% of pts (n=226; median 17U/ml; range 4–410) had tumor marker elevation = 24 U/ml before and 48% (n=524; median 23U/ml; range 4–198) after completion of chemotherapy. Ca27.29 levels before and after chemo correl. significantly (p<.001). Of those pts who presented with elevated values initially, 14% remained positive, while 84% had normal Ca27.29 after chemo. Those pts with initially negative blood sampling, returned with high Ca27.29 in 38% and normal values in 62% of cases. While Ca27.29 was well balanced between the two treatment arms at primary diagnosis with a rate of 10% with elevated Ca27.29 in each arm, significantly more pts showed high Ca27.29 with FEC-DocGemcitabine compared to FEC-Doc (27% vs. 21%, p<.001). Ca27.29 elevation did not correl. with most conventional prognostic factors such as tumor size (p=.23), histopath. grading (p=.98) or HR-status (p=.46). However, we found a significant correlation of Ca 27.29 with the presence of lymph node metastases (p=.01) and Her2/neu-over-expression of the primary tumor (p=.04). Conclusions: Measurement Ca27.29 in peripheral blood of primary breast cancer is feasible and reproducible. Whether it can be used for risk stratification leading to more tailored treatment approaches and for the monitoring of treatment efficacy in individual pts will show further follow-up of the SUCCESS-Study. No significant financial relationships to disclose.

Use of HE4 and CA125 to predict surgical outcome and for prognostic value for progression-free survival (PFS) and overall survival (OS) in primary epithelial ovarian cancer (EOC) patients (pts).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5034-5034
Author(s):  
Ioana Braicu ◽  
Radoslav Chekerov ◽  
Rolf Richter ◽  
Ignace B. Vergote ◽  
Sven Mahner ◽  
...  
Keyword(s):  
Surgical Outcome ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Free Survival ◽  
Over Expression ◽  
Primary Epithelial Ovarian Cancer ◽  
Predictive Role ◽  
First Diagnosis

5034 Background: Optimal surgical cytoreduction and response to platinum (P) based chemotherapy (ChTh) remain the cornerstones of therapeutic management of primary EOC. Aim of this study was to analyze the predictive role of HE4 and CA125 as biomarkers (BM) for clinical outcome in primary EOC pts at diagnosis and during subsequent follow-up. Methods: In the European OVCAD project 275 pts with primary EOC were enrolled. Pts were eligible if radical cytoreductive surgery and P-based ChTh were applied. Plasma collected at first diagnosis and 6 months after 1st line ChTh in P-sensitive pts was analyzed for HE4 and CA125 levels using ELISA and Luminex technique, respectively. Results: Complete cytoreduction with no residual tumor disease (RTD) was obtained in 69.9% pts. HE4 and CA125 expression in plasma at first diagnosis correlated with RTD, p = 0.002 and p=0.002, respectively. The sensitivity (SE) and specificity (SP) of the combinative use of both BM in predicting RTD was 64.8% and 73.5%, respectively. Pts having over-expression of both BM in plasma had a 6.1 greater risk for RTD (p<0.001, OR: 6.107, 95% CI 2.41-15.46). P-resistance occurred more frequently when both BM were over-expressed (p=0.028, OR= 3.1, 95%CI 1.13-8.46). Elevated BM levels during follow-up predicted recurrence (SE 90% and SP 71% for CA125 ≥55U/ml; SE 72.7% and SP 81.4% for HE4 ≥150pM) and when HE4 or CA125 were positive, a SE of 86.4% and SP of 72.9% were achieved. Elevated CA125 and HE4 at 6 months following adjuvant therapy was associated with significantly poorer PFS (p<0.001, HR 9.6, 95%CI 3.93-23.44 with elevated HE4 or CA125, and HR=50.52, 95%CI 14.44-176.78, with elevated HE4 and CA125) and OS (p<0.001, HR=7.42 95%CI 1.43-38.42 with elevated HE4 or CA125 and HR=28.38 95%CI 6.50-123.97 with elevated HE4 and CA125). Conclusions: The combinative use of HE4 and CA125 appears to have a significant value in predicting optimal surgical outcome and development of P resistance disease in EOC pts. Elevated plasma levels 6 months after 1st line ChTh significantly correlate with OS and PFS in P-sensitive pts.

scholarly journals Impact of radiotherapy-induced inflammatory responses on progression-free survival in a tri-racial/ethnic breast cancer population

2021 ◽  
Author(s):  
George R. Yang ◽  
Isildinha M. Reis ◽  
Laura G. Acosta ◽  
Emma A. Schindler ◽  
Cristiane Takita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Progression Free Survival ◽  
Tumor Stage ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Free Survival ◽  
Targeted Interventions

Abstract Background Inflammatory biomarker C-reactive protein (CRP) is associated with breast cancer risk and survival. We examined whether CRP levels before radiotherapy (pre-RT), after RT (post-RT), and RT-induced change impact breast cancer progression-free survival (PFS). Methods Plasma high-sensitivity CRP was measured, and patients were followed for up to 13 years after RT. PFS was calculated from the date of diagnosis to the date of disease progression or the last date of follow-up. Univariable and multivariable Cox proportional hazards regression models were used to evaluate the associations between CRP and PFS adjusted for other patient/clinical variables. Results In 469 patients (64 non-Hispanic Whites, 303 Hispanic Whites, and 102 African Americans), post-RT CRP levels were significantly higher in patients with progression compared to progression-free patients (mean±SD: 12.2±15.4 mg/L vs. 7.3±11.5, p=0.011). In univariable analyses, worse PFS was significantly associated with post-RT CRP ≥5.1 mg/L (hazard ratio [HR]: 2.67; 95% confidence interval [95% CI]: 1.65-4.30) and CRP change ≥2.3 mg/L (HR: 3.55; 95% CI: 2.25-5.64). In multivariable models, post-RT CRP ≥5.1 mg/L was associated with worse PFS in all (HR: 2.10; 95% CI: 1.29-3.42) or patients with tumor stage III (HR: 2.93, 95% CI: 1.20-7.18). CRP change ≥2.3 mg/L was associated with worse PFS in all (HR: 2.38; 95% CI: 1.45-3.92) or patients with tumor stage III (HR: 2.41, 95% CI: 1.09-5.33). Conclusions Our data suggest that an RT-induced hyper-inflammatory response may contribute to worse breast cancer PFS. Future larger studies are warranted to validate our findings and guide follow-up surveillance and targeted interventions.

scholarly journals Chameleon microRNAs in breast cancer: their elusive role as regulatory factors in cancer progression

2020 ◽  
Author(s):  
Cesare Miglioli ◽  
Gaetan Bakalli ◽  
Samuel Orso ◽  
Mucyo Karemera ◽  
Roberto Molinari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Breast Tissue ◽  
Biological Action ◽  
Normal Breast ◽  
Single Model ◽  
Machine Learning Technique ◽  
Micro Rnas ◽  
Learning Technique

Breast cancer is one of the most frequent cancers affecting women. Non-coding micro RNAs (miRNAs) seem to play an important role in the regulation of pathways involved in tumor occurrence and progression. Extending on the research in Haakensen et al. , where significant miRNAs were selected as being associated with the progression from normal breast tissue to breast cancer, in this work we put forward 112 sets of miRNA combinations, each including at most 5 expressions with high accuracy in discriminating healthy breast tissue from breast carcinoma. Our results are based on a recently developed machine learning technique which, instead of selecting a single model (or combination of features), delivers a set of models with equivalent predictive capabilities that allow to interpret and visualize the interaction of these features. These results shed new light on the biological action of the selected miRNAs which can behave in different ways according to the miRNA network with which they interact. Indeed, these revealed connections may contribute to explain why, in some cases, different studies attribute opposite functions to the same miRNA. It is therefore possible to understand how the role of a genomic variable may change when considered in interaction with other sets of variables, as opposed to only considering its effect when it is evaluated within a unique combination of features. The approach proposed in this work provides a statistical basis for the notion of chameleon miRNAs and is inspired by the emerging field of systems biology.

scholarly journals Drug-resistant cancer cell-derived exosomal EphA2 promotes breast cancer metastasis via the EphA2-Ephrin A1 reverse signaling

2020 ◽  
Author(s):  
Zicong Gao ◽  
Xingxing Han ◽  
Yuying Zhu ◽  
He Zhang ◽  
Ran Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Resistant Cell ◽  
Migration And Invasion ◽  
Drug Resistant ◽  
Resistant Cells

Abstract Background: The failure of chemotherapy is accompanied by the emergence of drug resistance and tumor relapse. Tumor metastasis induced by drug resistance is a major challenge in successful cancer treatment. Nevertheless, the mechanisms underlying the pro-invasive and metastatic ability of drug resistance remain elusive. Exosome-mediated intercellular communications between cancer cells and stromal cells in tumor microenvironment are required for cancer initiation and progression. Recent reports have shown that communications between cancer cells also promote tumor aggression. However, little attention has been regarded on this aspect. In this study, we aimed to investigate the mechanisms of exosomes derived from drug-resistant cells in regulating the invasion and metastasis of sensitive breast cancer cells.Methods: Exosomes isolated from drug-resistant breast cancer cells and their parental cells were used to treat breast cancer cells, and then the migration and invasion abilities were examined. The tandem mass tag (TMT)-based quantitative proteomic method was carried out to identify key molecules that regulate cancer aggressiveness. Lentivirus-mediated shRNAs, overexpression, point mutation, truncation mutation, Western blotting, tumor xenograft mice models, and in vivo breast cancer metastatic models were used to investigate the functional role of EphA2 on the invasion and metastatic potential of breast cancer cells.Results: We demonstrated that drug-resistant cell-derived exosomes promoted the migration and invasion of sensitive breast cancer cells. Quantitative proteomic analysis showed that EphA2 was rich in exosomes from drug-resistant cells. Exosomal EphA2 conferred the invasive/metastatic phenotype transfer from drug-resistant cells to sensitive cells. In addition, we provided considerable evidence that exosomal EphA2 activated ERK1/2 signaling through the ligand Ephrin A1-dependent reverse pathway rather than the forward pathway, thereby promoting breast cancer progression. Conclusions: Our findings indicate the key functional role of exosomal EphA2 in the transmission of aggressive phenotype between cancer cells that do not rely on direct cell–cell contact. Our study also suggests that the increase of EphA2 in drug-resistant cell-derived exosomes may be an important mechanism of chemotherapy/drug resistance-induced breast cancer progression.

scholarly journals Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Dong ◽  
Jiao Wu ◽  
Yin Chen ◽  
Jianyun Nie ◽  
Ceshi Chen
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Critical Role ◽  
Acquired Resistance ◽  
Mtor Inhibitors ◽  
Disease Recurrence ◽  
Mtor Pathway ◽  
Breast Cancer Patients

Although chemotherapy, targeted therapy and endocrine therapy decrease rate of disease recurrence in most breast cancer patients, many patients exhibit acquired resistance. Hyperactivation of the PI3K/AKT/mTOR pathway is associated with drug resistance and cancer progression. Currently, a number of drugs targeting PI3K/AKT/mTOR are being investigated in clinical trials by combining them with standard therapies to overcome acquired resistance in breast cancer. In this review, we summarize the critical role of the PI3K/AKT/mTOR pathway in drug resistance, the development of PI3K/AKT/mTOR inhibitors, and strategies to overcome acquired resistance to standard therapies in breast cancer.

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