mRNA expression of signal transducer and activator of transcription (STAT5), disheveled-3 (Dvl-3) and dicer in early-stage non-small-cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17038-17038
Author(s):  
F. Cecere ◽  
R. Rosell ◽  
M. Taron ◽  
A. Ceribelli ◽  
M. Milella ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tyrosine Kinases ◽  
Early Stage ◽  
Wnt Signaling Pathway ◽  
Growth Factor Receptor ◽  
Close Correlation ◽  
Mrna Levels ◽  
Internal Reference ◽  
Primary Tumors ◽  
Early Stage Nsclc

17038 Background: STAT5 plays a role in angiogenesis and metastasis. Activation of STAT5 occurs through dysregulation of growth factor receptor tyrosine kinases (TK) (including EGFR TK mutations), non-receptor TKs or Janus kinases. Dvl-3, a critical mediator of the Wingless-type (Wnt) signaling pathway, contributes to self-renewal of stem cells. Dicer has a key role in processing microRNAs required for stem cell regulation. We assessed mRNA expression of STAT5, Dvl-3 and Dicer in early-stage NSCLC. Methods: cDNA was derived from paraffin-embedded primary tumors of 47 surgically resected, early-stage NSCLC patients. Real-time quantitative reverse transcriptase PCR was used to measure STAT5, Dvl-3 and Dicer mRNA levels relative to the internal reference gene β-actin. Results: Median expression levels were: STAT5, 0.66 (0.15–6.03); Dvl-3, 3.69 (1.02–25.83); Dicer, 4.53 (1.22–21.96). STAT5 levels for squamous cell carcinoma (SCC) were 0.57 vs 0.89 for non-SCC (P=0.01), while Dicer levels were higher in SCC (4.25) than in non-SCC (2.60) (P = 0.01). A strong correlation between the levels of Dvl-3 and Dicer was found (rho = 0.49; P < 0.001). 90% of females had low Dicer mRNA levels (P = 0.01). No other correlation between mRNA levels and patient characteristics was found. Conclusions: High levels of Dvl-3 are associated with SCC. The close correlation between Dvl-3 and Dicer levels may indicate that Dicer could process a class of microRNA that activates the Wnt pathway. In non-SCC, overexpression of STAT5 could be involved in tumor angiogenesis. These 3 transcripts could be potential predictors of metastasis and ideal targets for individualized treatment. No significant financial relationships to disclose.

Endocrine Resistance: What Do We Know?

2013 ◽  
pp. e37-e42 ◽  
Author(s):  
Todd W. Miller
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Tyrosine Kinases ◽  
De Novo ◽  
Early Stage ◽  
Effective Means ◽  
Endocrine Resistance ◽  
Large Body ◽  
Growth Factor Receptor ◽  
Oncogenic Signaling

Adjuvant therapy with antiestrogens targeting estrogen receptor α (ER) signaling prevents disease recurrence in many patients with early-stage ER+ breast cancer. However, a significant number of cases exhibit de novo or acquired endocrine resistance. While other clinical subtypes of breast cancer (HER2+, triple-negative) have disproportionately higher rates of mortality, ER+ breast cancer is responsible for at least as many deaths because it is the most common subtype. Therefore, identifying mechanisms that drive endocrine resistance is a high clinical priority. A large body of experimental evidence indicates that oncogenic signaling pathways underlie endocrine resistance, including growth factor receptor tyrosine kinases (HER2, epidermal growth factor receptor [EGFR], fibroblast growth factor receptor 1/2 [FGFR], insulin-like growth factor-1 receptor [IGF-1R]/ insulin receptor [InsR]), PI3K/AKT/ mTOR, MAPK/ERK, Src, CDK4/CDK6, and ER itself. Combined targeting of ER and such pathways may be the most effective means to combat antiestrogen resistance, and clinical trials testing such strategies show promising results. Herein, we discuss pathways associated with endocrine resistance, biomarkers that may be useful to predict response to targeted agents, and avenues for further exploration to identify strategies for the treatment of patients with endocrine-resistant disease.

scholarly journals ASCO 2021—selection of personal highlights in early stage non-small cell lung cancer

2021 ◽  
Author(s):  
Gudrun Absenger ◽  
Andreas Pircher
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Adjuvant Setting ◽  
Small Cell Lung ◽  
Early Stage Nsclc

SummaryThis article intends to summarize personal non-small cell lung cancer (NSCLC) highlights of the virtual ASCO 2021 meeting. Immunotherapy is now a mainstay of advanced stage NSCLC treatment and there are several ongoing studies investigating the role of immunotherapy in early stage NSCLC. At ASCO 2021 the first data on atezolizumab in the adjuvant setting were presented and give a positive signal that immunotherapy will also become an option for patient in early stage NSCLC. Furthermore, overall survival (OS) updates of two studies investigating the effects of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant setting of EGFR-mutated NSCLC patients were presented. In conclusion ASCO 2021 provided the lung cancer community with inspiring new data especial in early stages and challenges the community with integration of these data into our daily clinical routine.

Gene expression levels of ribonucleotide reductase subunit M1 (RRM1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T-cells (NFAT), and BubR1 mRNA expression in completely resected chemo-naive non-small cell lung cancer (NSCLC) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18016-18016
Author(s):  
I. Chaib ◽  
E. Jassem ◽  
M. Spkrzypski ◽  
R. Rosell ◽  
M. Taron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Cox Model ◽  
Chromosome Instability ◽  
Mrna Levels ◽  
Internal Reference ◽  
Activated T Cells ◽  
Real Time Quantitative Pcr ◽  
Resected Nsclc ◽  
Actin Expression

18016 Background: A relationship between gene transcripts and survival in operable NSCLC is now emerging. RRM1 is involved in DNA repair, Tdp1 is implicated in the repair of CPT-induced topoisomerase damage, and NFAT promotes cancer invasion. BubR1 is a key spindle checkpoint gene, and altered BubR1 mRNA levels are associated with lymph node metastasis and chromosome instability. Methods: In order to identify p with a high risk of relapse, we examined the expression of these four genes in frozen resected tumors from 126 resected NSCLC p by real-time quantitative PCR. Gene expression was normalized using β-actin expression as internal reference. Results: Adenocarcinoma (adeno), 33 p; squamous cell carcinoma (SCC), 93 p. Stage: IA, 18 p; IB, 53 p; IIB, 33 p; IIIA, 22 p. Tumor transcript expression: RRM1, 2.10; Tdp1, 1.77; NFAT, 0.56; BubR1, 16.40. Expression of RRM1, Tdp1 and BubR1 was higher in SCC than in adeno (P<0.001). Median time to relapse (TTR) was longer for p with low levels of RRM1 (P=0.11), Tdp1 (P=0.86), NFAT (P=0.29), or BubR1 (P=0.44) (Table). A significant trend towards longer survival was also observed in stage I p with low RRM1 P=0.06). In a multivariate Cox model, tumor size > 4 cm and stage III predicted shorter TTR and survival. Conclusion: Increased mRNA expression of these genes is associated with shorter TTR; this knowledge could be useful for customizing adjuvant chemotherapy. [Table: see text] No significant financial relationships to disclose.

A retrospective evaluation of PD-L1 expression on primary non-small cell lung cancer (NSCLC) samples and associated involved hilar or mediastinal lymph nodes (N1 or N2) (REPLICA).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9044-9044
Author(s):  
Eleni Karapanagiotou ◽  
Andrea Bille ◽  
Philippe Taniere ◽  
Clare Flash ◽  
Abdel Douiri ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Primary Tumor ◽  
Early Stage ◽  
Lung Resection ◽  
Kappa Statistic ◽  
Stage Ii ◽  
Primary Tumors ◽  
Early Stage Nsclc ◽  
Consensus Score ◽  
The Relationship

9044 Background: Little is known about the PD-L1 expression in early stage NSCLC as well as the possible heterogeneity of PD-L1 expression in different sites. This study provides information on both PD-L1 expression in stage II and III NSCLC and the relationship between PD-L1 expression in the primary site (lung) and metastatic lymph nodes (LNs) N1 and/or N2. Methods: Samples (primary tumor and N1/N2) from 500 patients who underwent lung resection and lymphadenectomy for NSCLC without prior treatments were collected and analyzed for PD-L1 expression using the 22C3 pharmdx Agilent assay. The tumor proportion score (TPS) is documented for each sample according to the following categories: PD-L1: < 1%, 1-49%, ≥ 50%. PD-L1 stained slides were reviewed by two pathologists independently; for discrepant cases the two pathologists reviewed the stains jointly and the consensus score used for the data analysis. Agreement between the two pathologists was assessed by overall agreement and kappa statistic. The association between PD-L1 expression in the primary tumor and lymph node was assessed by cross-tabulation. Results: A total of 456 tumors and involved LNs were included in the analysis. Pathologist one assessed 435 primary tumor and LN pairs and pathologist 2 assessed 453 tumor and LNs pairs. The overall agreement between pathologists on PD-L1 expression in primary tumor samples was 77%; K = 0.59 (95% CI 0.57 – 0.63) and in LNs 83%; k = 0.62 (95% CI 0.56 – 0.70). Primary tumors showed PD-L1 < 1% in 235/422 (55,6%), PD-L1 1-49% in 146/422 (34,6%) and PD-L1 > = 50% in 41/422 (9.8%). 77% (327/422) showed no heterogeneity in PD-L1 expression between the primary tumor and involved LNs. In tumors with PD-L1 < 1% expression, 94% of the LNs showed PD-L1 < 1% expression and less than 1% showed PD-L1 > = 50%, 6% of the LNs showed PD-L1 1-49%. When the primary tumor was PD-L1 > = 50% nearly half (46%) of the involved LNs showed the same degree of PD-L1 positivity and 10% of them showed PD-L1 < 1%; 44% of the LNs showed PD-L1 1-49%. When the primary tumor showed 1-49% PD-L1 staining, 60% of the LNs showed the same staining pattern, 36% showed PD-L1 < 1% and only 4% showed PD-L1 > = 50% expression. Conclusions: In stage II and III NSCLC, half of the primary tumors show negative PD-L1 expression. Discrepant PD-L1 expression between primary tumors and LN metastases was seen in 23% of the cases, and when present, PD-L1 expression in LN tumors tended to be lower than that in primary tumors.

scholarly journals The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn.

1993 ◽  
Vol 178 (2) ◽  
pp. 723-730 ◽  
Author(s):  
J L Chu ◽  
J Drappa ◽  
A Parnassa ◽  
K B Elkon
Keyword(s):  
Mrna Expression ◽  
Tumor Necrosis Factor Receptor ◽  
Growth Factor Receptor ◽  
Surface Protein ◽  
Northern Blotting ◽  
Nucleotide Sequencing ◽  
Mrna Levels ◽  
Wild Type ◽  
Fas Mrna ◽  
A Cell

Fas is a cell surface protein of the tumor necrosis factor receptor, nerve growth factor receptor, CD40 family, and is involved in the control of lymphocyte apoptosis. A mutation in the Fas gene in MRL/lpr mice results in massive lymphoproliferation (lpr) and accelerated autoimmunity. To further study the nature of this defect, Fas mRNA expression was evaluated by reverse transcriptase polymerase chain reaction as well as by Northern blotting. These studies revealed that the wild-type Fas message was produced at approximately 10-fold lower levels in the lpr compared with the ++ substrain of MRL mice. In addition to the wild-type transcript, lpr mice also synthesized chimeric transcripts containing an insertion of the early retrotransposon (ETn). Molecular cloning and nucleotide sequencing of a Fas-ETn chimeric cDNA suggested that the striking reduction in wild-type Fas mRNA levels and the presence of aberrant transcripts in MRL/lpr mice are most likely explained by the insertion of the ETn retrotransposon into an intron of the Fas gene and induction of alternative splicing involving the 5' ETn long terminal repeat.

Dynamic Alterations in the Expression of P2Y12 Receptor but Not COX-1 in Platelets from Streptozocin-Induced Diabetic Rats.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2638-2638
Author(s):  
Chi Chen ◽  
Zili He ◽  
Candice Ruby ◽  
Waqas Arslan ◽  
Madhumati Kalavar ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Messenger Rna ◽  
Early Stage ◽  
Diabetic Rats ◽  
Dense Granule ◽  
Receptor Expression ◽  
P2y12 Receptor ◽  
Mrna Levels ◽  
Cyclooxygenase 1 ◽  
Cox 1

Abstract In patients or animals with established diabetes mellitus, platelets have been shown to be hyperreactive to ADP. This alteration of the platelet function occurs independent of activation of the arachidonate pathway or release of dense granule contents. In the present study, we examined the expression of the platelet ADP-binding receptor, P2Y12, in early stage of streptozocin(STZ)-induced diabetes in rats. Platelet messenger RNA (mRNA) levels for P2Y12 and cyclooxygenase-1 (COX-1) were determined by comparative RT-PCR in 7 control rats on day 0, 6 diabetic rats each on days 2, 3, 4, and 4 diabetic rats on day 7 after intraperitoneal injection of streptozocin (50 mg/kg). The plasma glucose level was 406 ± 10 mg/dl in diabetic rats, significantly greater than 151 ± 12 mg/dl in control rats. After induction of diabetes, the expression of P2Y12 mRNA significantly decreased to 76 ± 9% of the level of control on day 2, 54 ± 6% of control on day 3, reached a nadir of 28 ± 6% of control on day 4, and rose to 43 ± 10% of control on day 7. These dynamic changes of P2Y12 mRNA in platelets reflected the expression of P2Y12 mRNA in megakaryocytes isolated to a high state of purity (&gt;96 %) from rat bone marrow. Specifically, the megakaryocytic P2Y12 mRNA expression in the diabetic rats on days 1, 2 and 3 were 74 ± 8 %, 93 ± 1%, and 117 ± 6% of those in control rats, respectively. Treatment of diabetic rats with insulin reduced the trend of decline in the platelet P2Y12 expression. By contrast, the platelet COX-1 mRNA expression measured on days 2, 3, 4 and 7 after the induction of diabetes was similar to that in the control rats. These results in diabetic rats demonstrate dynamic alterations of the mRNA expression of megakaryocyte-platelet P2Y12, but not of COX-1. The decrease in the P2Y12 receptor expression in early stage of STZ-induced diabetes may serve to attenuate the hyperaggregability of platelets and reduce the risk of vascular thrombosis.

scholarly journals Altered Sirtuin 7 Expression is Associated with Early Stage Breast Cancer

2015 ◽  
Vol 9 ◽  
pp. BCBCR.S23156 ◽  
Author(s):  
Ahmad Aljada ◽  
Ayman M. Saleh ◽  
Moath Alkathiri ◽  
Heba Bani Shamsa ◽  
Ahmad Al-Bawab ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Progression ◽  
Early Stage ◽  
Cdna Array ◽  
Normal Breast ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Cancer Disease ◽  
Expression Status

Background To evaluate sirtuin-7 (SirT7) mRNA expression status in breast cancer patients with different metastatic stages and survey SirT7 mRNA expression status in eight different types of cancer. Methods The expression of SirT7 in the commercially available TissueScan qPCR Breast Cancer Disease cDNA arrays containing 16 normal, 23 Stage I, 36 IIA, 22 IIB, 8 IIIA, 23 IIIA, 6 IIIB, 13 IIIC, and 5 IV were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Similar analysis was performed in TissueScan qPCR Cancer Survey cDNA array, which includes breast, colon, kidney, liver, lung, ovarian, prostate, and thyroid specimens. Results The mRNA expression levels of SirT7 were significantly higher in breast cancer samples compared to normal breast specimens ( P < 0.001). Stratification of patients into groups according to metastatic stages indicated statistically significantly higher levels of SirT7 mRNA in CS-I, CS-II, and CS-III when compared to normal breast tissue ( P < 0.05). Notably, SirT7 mRNA levels were higher in CS-I, CS-IIA, CS-IIB, and CS-IIIA ( P < 0.05). Additionally, there were significantly lower SirT7 mRNA levels in thyroid carcinoma when compared to their corresponding normal tissue ( P < 0.05). Conclusions Our results indicate an increase in the mRNA expression level of SirT7 in breast cancer, particularly in CS-I, CS-IIA, CS-IIB, and CS-IIIA. The relationship of altered SirT7 with breast cancer progression and patient survival should be prospectively explored in future studies.

scholarly journals PUFA Treatment Affects C2C12 Myocyte Differentiation, Myogenesis Related Genes and Energy Metabolism

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 192
Author(s):  
Marua Abu Risha ◽  
Puntita Siengdee ◽  
Dirk Dannenberger ◽  
Klaus Wimmers ◽  
Siriluck Ponsuksili
Keyword(s):  
Energy Metabolism ◽  
Wnt Signaling ◽  
Cell Fate ◽  
Early Stage ◽  
Mrna Level ◽  
Wnt Signaling Pathway ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Mrna Levels ◽  
Dependent Manner

Polyunsaturated fatty acids (PUFAs) are the main components of cell membrane affecting its fluidity, signaling processes and play a vital role in muscle cell development. The effects of docosahexaenoic acid (DHA) on myogenesis are well known, while the effects of arachidonic acid (AA) are largely unclear. The purpose of this study is to evaluate the effect of two PUFAs (DHA and AA) on cell fate during myogenic processes, Wnt signaling and energy metabolism by using the C2C12 cells. The cells were treated with different concentrations of AA or DHA for 48 h during the differentiation period. PUFA treatment increased mRNA level of myogenic factor 5 (Myf5), which is involved in early stage of myoblast proliferation. Additionally, PUFA treatment prevented myoblast differentiation, indicated by decreased myotube fusion index and differentiation index in parallel with reduced mRNA levels of myogenin (MyoG). After PUFA withdrawal, some changes in cell morphology and myosin heavy chain mRNA levels were still observed. Expression of genes associated with Wnt signaling pathway, and energy metabolism changed in PUFA treatment in a dose and time dependent manner. Our data suggests that PUFAs affect the transition of C2C12 cells from proliferation to differentiation phase by prolonging proliferation and preventing differentiation.

scholarly journals SYK, CSK and FYN are differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Protein Tyrosine Kinases ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Transcriptional Responses ◽  
Primary Tumors ◽  
Protein Tyrosine

The mechanism of action underlying trastuzumab (Herceptin) function is ascribed to binding of the Fab region of trastuzumab to the extracellular domain of the human epidermal growth factor receptor (HER2) (1). The transcriptional responses that follow signals transduced after trastuzumab binding of HER2 are less well understood. Protein tyrosine kinases are one major class of cellular components utilized in the transduction of signals from the cell surface to the nucleus. We mined published microarray and multiplexed gene expression data (2-5) to understand in an unbiased fashion genes most differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab. We observed significantly increased and differential expression of multiple protein tyrosine kinases in the primary tumors of patients with breast cancer, including SYK, CSK and FYN. These data document previously undescribed up-regulation of protein tyrosine kinases following treatment with trastuzumab in patients with breast cancer.

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