scholarly journals Using cfRNA as a tool to evaluate clinical treatment outcomes in patients with metastatic lung cancers and other tumors

2021 ◽  
Author(s):  
Luis E. Raez ◽  
Kathleen Danenberg ◽  
Daniel Sumarriva ◽  
Joshua Usher ◽  
Jacob Sands ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Response To Therapy ◽  
Liquid Biopsies ◽  
Blood Samples ◽  
Lung Cancers ◽  
Metastatic Lung ◽  
Clinical Responses ◽  
Pre Treatment ◽  
Actin Expression

Aim: We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Methods: Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy, 52 with NSCLC, 50 with breast cancer, and 25 with CRC. cfRNA was purified from fractionated plasma, and following reverse transcription (RT), total cfRNA and gene expression of PD-L1were analyzed by real-time polymerase chain reaction (qPCR) using beta-actin expression as a surrogate for relative amounts of cfDNA and cfRNA. For the concordance study of liquid biopsies and tissue biopsies, the isolated RNA was analyzed by RNAseq for the expressions of 13 genes. We had to close the study early due to a lack of follow-up during the Covid-19 pandemic. Results: We collected a total of 373 blood samples. Mean cfRNA PCR signals after RT were about 50-fold higher than those of cfDNA. cfRNA was detected in all patients, while cfDNA was detected in 88% of them. A high concordance was found for the expression levels of 13 genes between blood and solid tumor tissue. Changes in cfRNA levels followed over the course of treatments were associated with response to therapy, increasing in progressive disease (PD) and falling when a partial response (PR) occurred. The expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with PD. Pre-treatment levels of PD-L1 were predictive of response in patients treated with immunotherapy. Conclusion: Changes in cfRNA correlate with clinical response to the therapy. Total cfRNA may be useful in predicting clinical outcomes. PD-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition.

scholarly journals 83 Spatially resolved transcriptomic and proteomic investigation of breast cancer and its immune microenvironment

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A91-A91
Author(s):  
Jennifer Chew ◽  
Cedric Uytingco ◽  
Rapolas Spalinskas ◽  
Yifeng Yin ◽  
Joe Shuga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Tumor Microenvironment ◽  
Protein Expression ◽  
Protein Detection ◽  
Response To Therapy ◽  
Pathological Examination ◽  
Multi Drug Resistance ◽  
Spatially Resolved ◽  
Gene And Protein Expression

BackgroundThe tumor microenvironment (TME) is composed of highly heterogeneous extracellular structures and cell types such as endothelial cells, immune cells, and fibroblasts that dynamically influence and communicate with each other. The constant interaction between a tumor and its microenvironment plays a critical role in cancer development and progression and can significantly affect a tumor’s response to therapy and capacity for multi-drug resistance. High resolution analyses of gene and protein expression with spatial context can provide deeper insights into the interactions between tumor cells and surrounding cells within the TME, where a better understanding of the underlying biology can improve treatment efficacy and patient outcomes. Here, we demonstrated the ability to perform streamlined multi-omic tumor analyses by utilizing the 10X Genomics Visium Spatial Gene Expression Solution for FFPE with multiplex protein enablement. This technique simultaneously assesses gene and protein expression to elucidate the immunological profile and microenvironment of different breast cancer samples in conjunction with standard pathological methods.MethodsSerial (5 µm) sections of FFPE human breast cancer samples were placed on Visium Gene Expression (GEX) slides. The Visium GEX slides incorporate ~5,000 molecularly barcoded, spatially encoded capture spots onto which tissue sections are placed, stained, and imaged. Following incubation with a human whole transcriptome, probe-based RNA panel and an immuno-oncology oligo-tagged antibody panel, developed with Abcam conjugated antibodies, the tissues are permeabilized and the representative probes are captured. Paired GEX and protein libraries are generated for each section and then sequenced on an Illumina NovaSeq at a depth of ~50,000 reads per spot. Resulting reads from both libraries are aligned and overlaid with H&E-stained tissue images, enabling analysis of both mRNA and protein expression. Additional analyses and data visualizations were performed on the Loupe Browser v4.1 desktop software.ConclusionsSpatial transcriptomics technology complements pathological examination by combining histological assessment with the throughput and deep biological insight of highly-multiplexed protein detection and RNA-seq. Taken together, our work demonstrated that Visium Spatial technology provides a spatially-resolved, multi-analyte view of the tumor microenvironment, where a greater understanding of cellular behavior in and around tumors can help drive discovery of new biomarkers and therapeutic targets.

The use of bioimpedance spectroscopy to monitor response to treatment interventions with breast cancer-related lymphedema.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 138-138
Author(s):  
Chirag Shah ◽  
Frank Vicini ◽  
Peter D. Beitsch ◽  
Beth Anglin ◽  
Alison Lisa Laidley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Fluid ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Bioimpedance Spectroscopy ◽  
Post Surgery ◽  
Before And After ◽  
The Mean ◽  
Breast Cancer Related Lymphedema ◽  
Pre Treatment

138 Background: Currently, limited tools are available to assess response to therapy in patients with breast cancer related lymphedema (BCRL). The purpose of this study was to perform an exploratory analysis to determine if, in clinical settings, bioimpedance spectroscopy (BIS) can detect changes in extracellular fluid volume in response to treatment of BCRL. Methods: Three centers that had experience with BIS (L-Dex U400, ImpediMed Limited, Brisbane, Australia) provided retrospective data on 50 patients with breast cancer who were evaluated with BIS at baseline and following loco-regional procedures. Patients had a pre-surgical L-Dex measurement as well as at least 2 post-surgical measurements (before and after BCRL intervention). Decisions regarding intervention were made by physicians with no L-Dex score cut-off utilized. An analysis was performed comparing changes in L-Dex scores for those patients undergoing treatment for BCRL (n=13) versus those not undergoing intervention (n=37). A second analysis was also performed on all patients with elevated L-Dex scores compared to baseline prior to intervention (n=32). Results: The mean age was 54 years old. Fifty four percent of patients underwent SLN biopsy with a mean of 7.9 nodes removed. The mean change in L-Dex score from baseline (pre-treatment) to the first post-surgical L-Dex score measurement was 3.3 +/- 6.8. When comparing the cohort treated for BCRL to those not treated, L-Dex scores were significantly reduced (-4.3 v. 0.1, p=0.005) following intervention. For the subset of patients with elevated L-Dex scores post-surgery, the change in L-Dex score following BCRL intervention was significantly reduced (-5.8 v. 0.1, p=0.001) compared with those observed. Conclusions: These results confirm that BIS can detect increases in L-Dex scores following breast surgery and can also detect reductions in L-Dex scores following intervention for early onset lymphedema. These results demonstrate that BIS has significant clinical utility as it can be used to monitor patients with early BCRL who undergo intervention and to follow these patients (through serial measurements) to document their short and long-term response to these treatments.

scholarly journals Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to Therapy in Metastatic Breast Cancer

2017 ◽  
Vol 63 (10) ◽  
pp. 1585-1593 ◽  
Author(s):  
Maren Bredemeier ◽  
Philippos Edimiris ◽  
Pawel Mach ◽  
Mikael Kubista ◽  
Robert Sjöback ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Clinical Staging ◽  
Significant Differential Expression

Abstract BACKGROUND Circulating tumor cells (CTCs) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTCs of MBC patients on the basis of the expression of 46 genes. METHODS From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest EMT-2/StemCellSelectTM (QIAGEN). Patients were grouped into (a) responder (R) and non-responder (NR) at TP1 and (b) overall responder (OR) and overall non-responder (ONR) at TP2. A 46-gene PCR assay was used for preamplification and high-throughput gene expression profiling. Data were analyzed by use of GenEx (MultiD) and SAS. RESULTS The CTC positivity was defined by the four-gene signature (EPCAM, KRT19, MUC1, ERBB2 positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC− patients (KRT19, FLT1, EGFR, EPCAM, GZMM, PGR, CD24, KIT, PLAU, ALDH1A1, CTSD, MKI67, TWIST1, and ERBB2). KRT19 was highly expressed in CTC+ patients and ADAM17 in the NR at TP1. A significant differential expression of 4 genes (KRT19, EPCAM, CDH1, and SCGB2A2) was observed between OR and ONR when stratifying the samples into CTC+ or CTC−. CONCLUSIONS ADAM17 could be a key marker in distinguishing R from NR, and KRT19 was powerful in identifying CTCs.

INFLUENCE OF LOW DOSE OESTROGEN ON CIRCULATING PROLACTIN, LH AND FSH LEVELS IN POST-MENOPAUSAL WOMEN

1976 ◽  
Vol 83 (1) ◽  
pp. 9-14 ◽  
Author(s):  
C. Robyn ◽  
M. Vekemans
Keyword(s):  
Breast Cancer ◽  
Treatment Period ◽  
Prolactin Level ◽  
Low Dose ◽  
Serum Prolactin ◽  
Blood Samples ◽  
Menopausal Women ◽  
Pre Treatment ◽  
Post Menopausal

ABSTRACT The effect on serum prolactin, LH and FSH levels of 25 μg ethinyloestradiol administered daily per os during 27 consecutive days was investigated in 5 post-menopausal women aged 52-78. Blood samples were collected before, during and after treatment. The hormones were assayed in serum by radioimmunological methods. Both LH and FSH decreased progressively and significantly from 120 and 115 mIU/ml before treatment to 52 and 51 mIU/ml, respectively after three weeks of oestrogen administration. Two weeks after interruption of treatment, LH (90 mIU/ml) and FSH (112 mIU/ml) were significantly higher than during the last week of treatment. Mean prolactin level increased from 127 μU/ml before treatment to 237 μU/ml after 10 days of oestrogen administration (P < 0.001). This increase was significant after 4 to 8 days and the levels remained about twice as high as the control values for the rest of the treatment period. Two weeks after interruption of treatment, serum prolactin had fallen (136 μU/ml) to the pre-treatment levels. Such results raise the question of possible effects of elevated levels of this hormone during long term oestrogen medication in post-menopausal women on the development of breast cancer.

scholarly journals The Anti-tumoral Effect of β-D-Mannuronic Acid (M2000) as a Novel NSAID on Treg Cells Frequency and MMP-2, MMP-9, CCL22 and TGFβ1 Gene Expression in Pre-surgical Breast Cancer Patients

2019 ◽  
Author(s):  
Sarvenaz Kashefi ◽  
Hamid Ahmadi ◽  
Ramesh Omranipour ◽  
Habibollah Mahmoodzadeh ◽  
Fahimeh Jafarnezhad-Ansariha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Matrix Metalloproteinase ◽  
Chronic Inflammation ◽  
Transforming Growth Factor ◽  
Matrix Metalloproteinase 2 ◽  
Therapeutic Effects ◽  
Main Role ◽  
Blood Samples ◽  
Mannuronic Acid

With respect to the role of chronic inflammation in the induction and progression of breast cancer (BC). The relationship between tumor and tumor microenvironment may be a hopeful strategy for BC therapy. According to the effect of β-D-Mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) on BC murine model and 4T1 cell line, we started to study that was a phase II, randomized, controlled clinical trial. 24 women with BC were included in this study and were followed by fixed oral doses of M2000, 500 mg two times a day (6-8 weeks). Blood samples were collected at baseline and weeks 6-8. To compare the patterns of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), C-C motif chemokine ligand 22 (CCL22) and The transforming growth factor-beta 1 (TGFβ1) gene expression and T regulatory cells (Tregs) frequency of healthy women normal controls with BC patients, a set of 10 blood samples of  women healthy volunteers was collected. The gene expression was evaluated by quantitative Real-time PCR (qRT-PCR) and the frequency of Tregs was assessed by flow cytometry. Our results showed, reduction in MMP-2 (p=0.08), MMP-9 (p=0.03), CCL22 (p=0.003) and TGFβ1 (p=0.1) gene expression and Tregs frequency (p=0.01) which play a main role in the development of chronic inflammation, angiogenesis, tumorigenesis and metastasis. Our findings demonstrated that M2000 therapy as a novel designed NSAID had valuable therapeutic effects on BC. No adverse effects were observed following the use of M2000 after 6-8 weeks.

High level analysis of genomic data reveals complex predictors of response to trastuzumab (T) and chemotherapy for early stage breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 544-544
Author(s):  
L. N. Harris ◽  
S. Carter ◽  
F. You ◽  
A. Eklund ◽  
S. Hilsenbeck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Pathologic Complete Response ◽  
Gene Expression Signature ◽  
Response To Therapy ◽  
Snp Analysis ◽  
Predictors Of Response ◽  
High Level

544 Background: Trastuzumab (T) with chemotherapy has been shown to improve survival in breast cancer patients but de novo resistance is common. Identifying predictors of response to T in primary cancers may lead to an understanding of mechanisms of resistance. We investigated whether combined microarray datasets from patients with early breast cancer treated with preoperative T and chemotherapy could predict for response to therapy. Methods: Two cohorts of patients with HER2 3+/FISH+, stage II-III breast cancer were included in this analysis: trial 1- T and docetaxel (n=38), trial 2 -T and vinorelbine (n=48), both for 12 weeks. Frozen tissue core biopsies were available and successfully amplified in 41 patients (trial 1: 20, trial 2: 21 patients), with standard sample processing, RNA extraction, amplification and hybridization to Affymetrix U133 chips. Differential expression of genes and chromosomal regions, (defined as >10 genes in a given chromosomal cytoband), between patients with pathologic complete response (pCR) vs. those with residual invasive disease were examined. A measure of total functional aneuploidy (tFA) was calculated by summing net deviation in expression of all chromosomal regions and a gene expression signature of genomic instability (CIN) was derived by the identification of genes showing a high level of correlation with tFA . Results: By unsupervised hierarchical analysis, both datasets interdigitated suggesting no inherent bias. Gene expression patterns of individual genes showed weak associations with pCR. However, distinct statistically significant chromosomal regions, Chr2p23 Chr6q24 Chr7q33 Chr2p2 Chr12q21.31 Chr14q32.2 Chr1p34.2 Chr8q21.3, were associated with pCR to T therapy (p<0.005), and were confirmed in more than 50% samples by SNP analysis. In addition, resistant tumors showed higher levels of the CIN signature (p<0.005). Conclusions: We have shown that gene expression data can be merged and used for discovery predictive chromosomal regions associated T response. In addition, chromosomal instability was associated with T resistance. If validated, these distinct dysregulated chromosomal regions may serve as predictive markers of response to trastuzumab therapy. [Table: see text]

Use of tumor gene expression signatures and drug-induced changes to discriminate early response in human breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2524-2524
Author(s):  
S. Lee ◽  
M. Watson ◽  
X. Xu ◽  
C. I. Wong ◽  
P. Iau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Calcium Binding ◽  
Early Response ◽  
Actin Binding ◽  
Expression Ratio ◽  
Pre Treatment ◽  
Tumor Gene Expression ◽  
Tumor Gene

2524 Background: To elucidate the genomics of tumor responses to different classes of chemotherapy, we analyzed breast cancer gene expression before and after in vivo treatment with adriamycin or docetaxel. Methods: Tumor biopsies were obtained before and 3 weeks after one chemotherapy cycle and tumor RNA amplified and hybridized on the Affymetrix HG-U133+2 array containing 33,000 genes. Results: Pre- and post-treatment tumors from 46 chemonaive patients with unresectable breast cancers were studied, of which 24 and 22 respectively received adriamycin and docetaxel in the first cycle, and 14 in each group had early response sensitive tumors (=25% shrinkage after 1 cycle). Comparison of our baseline gene signatures with drug-specific panels generated in vitro (Nevins, Nat Med 2006,12:1294) revealed 12 and 2 common genes (p<0.05) that predicted for adriamycin and docetaxel response respectively, with the 12 common adriamycin-response gene panel correctly predicting response in 76% of patients. Analysis of the relative change in tumor gene expression (ratio of post- and pre-treatment differential values to pre-treatment values) in our dataset revealed adriamycin to up- or down- regulate 209 transcripts (p<0.005) including genes that encode for nuclear protein, cell cycle regulation, aminopeptidases, and Ankyrin repeats, while docetaxel up- or down-regulated 469 transcripts (p<0.005) including genes that encode for extracellular matrix, transmembrane signaling, endocytosis, EGF-like calcium binding, tubulin and actin binding functions. Adriamycin and docetaxel concordantly up- or down-regulated 269 transcripts (p<0.01) that may be common response markers, including genes involved in cell cycle proliferation, mitosis, DNA damage, and carboxypeptidase activities. Adriamycin and docetaxel differentially induced 92 transcripts (p<0.01) that distinguished between the two drugs with 96% accuracy. 27 adriamycin- and 100 docetaxel-induced transcripts (p<0.005) predicted response to each drug with >90% accuracy. Conclusions: Drug-specific genomic changes can predict clinical response, and may yield insights to targets to overcome drug resistance. No significant financial relationships to disclose.

Mind-body medicine epigenetic technique (MET), cognitive flexibility, and brain-derived neurotrophic factor (BDNF) gene expression.

2017 ◽  
Vol 35 (5_suppl) ◽  
pp. 172-172
Author(s):  
Francisco Ventura Munoz
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Pilot Study ◽  
Los Angeles ◽  
Cognitive Flexibility ◽  
Selection Process ◽  
Breast Cancer Patients ◽  
Bdnf Gene ◽  
Blood Draw ◽  
Blood Samples

172 Background: This is a pilot study update on the potential of MET to up-regulate BDNF gene expression with breast cancer patients assessed with high cognitive flexibility. MET is a technique developed to manage chronic stress and anxiety. BDNF gene expression is associated with learning and memory. Cognitively flexibility is defined as the ability to focus and sustain attention. It also implies vivid imagination and holistic thinking. Methods: The selection process for the study participants was nonrandom. The following was the eligibility criteria. 1. Inclusion Criteria: Breast Cancer, Stages II, III 2. Exclusion Criteria: Cognitively impaired, weak or ill. The study utilized two groups. Each group was assigned two research participants. Group One received one session of MET. Group Two received two sessions of MET. Each MET session was approximately 25-35 minutes in duration. Blood samples were taken at baseline and post-MET sessions to provide evidence in gene expression changes. For Group Two, the post-MET session blood draw was done 7 days after baseline. 1. Primary Endpoint: To determine whether MET can up-regulate BDNF gene expression. 2. Secondary Endpoint:To determine whether there is a correlation between up-regulated BDNF gene expression and cognitive flexibility. The blood samples were sent to genomics labs at the Children’s Hospital of Los Angeles and the University of Nevada Las Vegas for mRNA extraction and microarray analysis. The gene expression was measured by DNA microarray results using the “PrimeView gene chip” and “Partek Genomics Suite” statistical software. Results: One participant from Group 1 evidenced a biologically significant up-regulation of BDNF gene expression. This participant was assessed with high cognitive flexibility. One major limitation of these findings is the statistical insignificance of the results due to the small number of participants. Conclusions: This pilot study evidenced the up-regulation of BDNF gene expression potentially due to MET and provided evidence for the potential correlation of BDNF gene expression and cognitive flexibility. This study also provided a foundation for a larger study with more participants.

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