scholarly journals Expression of Molecular Biomarkers in Primary Breast Tumors Implanted into a Surrogate Host: Increased Levels of Cyclins Correlate with Tumor Progression

1997 ◽  
Vol 3 (4) ◽  
pp. 273-283 ◽  
Author(s):  
G. Wani ◽  
I. Noyes ◽  
G. E. Milo ◽  
S. M. D’Ambrosio
Author(s):  
Mustafa Fadhil ◽  
Omar Abdul- Rasheed ◽  
Manwar Al-Naqqash

Background: During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. In response to multiple microenvironmental signals from the tumor and stromal cells, macrophages change their functional phenotypes. Based on their function, macrophages are commonly classified into both, classical M1 and alternative M2 macrophages. M2-like tumor-associated macrophages promote breast tumor growth and survival, and may migrate into the peripheral blood. However, the level of circulating M2/M1-like monocyte ratio in the peripheral blood of breast cancer patients has not been yet clarified. Aim: To compare peripheral blood M2/M1 monocyte ratio among breast cancer patients, benign breast tumor patients and healthy subjects. Also, to investigate the role of peripheral blood M2/M1 monocyte ratio as a circulating breast cancer tumor marker and to asses the validity of this marker in differentiation between benign and malignant breast tumors. Methods: Flow cytometry technique was used to determine the peripheral blood M2/M1 monocyte ratio in three groups of subjects, i.e. 45 patients with breast cancer, 40 patients with benign breast tumor, and 40 healthy subjects as a control group. The results of carbohydrate antigen15-3 (CA15-3) determination were analyzed comparatively. Results: The peripheral blood M2/M1 monocyte ratio in patients with breast cancer (0.27±0.1) was significantly higher (P<0.001) than that in healthy subjects (0.07±0.05) and than in benign tumor subjects (0.08±0.04). The area under the receiver operating characteristic (ROC) curve of peripheral blood M2/M1 monocyte ratio determination was significantly higher (P≤0.001) than that of CA15-3 levels. Conclusion: M2/M1-like monocyte ratio is of a high diagnostic value for breast cancer and is a promising differentiating marker between benign and breast cancer tumor groups.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22036-e22036
Author(s):  
C. P. Miller ◽  
K. Loeb ◽  
K. Edlefsen ◽  
N. Urban ◽  
C. A. Blau

e22036 Background: Adverse effects of erythropoiesis stimulating agents on tumor progression and/or survival were observed in recent Phase III clinical trials, however, mechanisms are not understood. Whether tumor erythropoietin receptor (EpoR) expression is associated with erythropoietin-dependent tumor progression remains unclear, owing in part to the lack of specificity of commercial antibodies for protein detection. To overcome issues of protein detection, we previously optimized a quantitative RTPCR approach for reliable measurements of low level EpoR mRNA in primary tumor samples, and observed a 30-fold range of EpoR expression among panels of both breast and head and neck cancer samples. Methods: To test whether EpoR mRNA is expressed in tumor epithelial cells, we performed laser capture microdissection to fractionate 3 breast tumors into tumor epithelial enriched vs. depleted fractions. In each fraction, lineage marker and EpoR mRNA expression was normalized to 3 endogenous control genes. Results: Vascular endothelial markers in tumor epithelial-enriched fractions were reduced by an average of 15.3-fold (vascular endothelial cadherin) and 18.5-fold (platelet cell adhesion molecule 1) while the stromal marker vimentin was reduced by 14.7-fold. EpoR expression was enriched by 4.9-, 7.2-, and 1.1-fold in epithelial enriched fractions. Conclusions: Despite the depletion of endothelial cells, EpoR mRNA was at the same level or enriched in tumor epithelial fractions. These results demonstrate that malignant epithelial cells are a major source of EpoR mRNA in primary tumors. Applying this approach to additional breast cancer specimens as well as other cancer types will improve our understanding of erythropoietin-associated tumor progression. [Table: see text]


2017 ◽  
Vol 16 (6) ◽  
pp. 47-56
Author(s):  
N. V. Litviakov ◽  
M. M. Tsyganov ◽  
M. K. Ibragimova ◽  
I. V. Deryusheva ◽  
P. V. Kazantseva ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10606-10606 ◽  
Author(s):  
Kleita Michaelidou ◽  
Alexandros Tzovaras ◽  
Nikolaos Tsoukalas ◽  
Konstantinos Mavridis ◽  
Grecory Tsoukalas ◽  
...  

10606 Background: Breast cancer (BC), the most common malignancy among the female population, remains a crucial public health problem. The identification and exploitation of novel molecular biomarkers can contribute in the multidimensional approach which is required for optimal management of BC patients. The abnormal expression of several KLK members has been documented for breast cancer. Interestingly, many of these genes are found to be potential prognostic markers for this malignancy. KLK6 expression is positively associated with tumor progression in various human malignancies; however in breast cancer, it can restrain tumor progression. We therefore sought to investigate the possible clinical value of KLK6 as a breast cancer biomarker. Methods: Total RNA was isolated from 107 breast tumors and their matched normal compartments. After testing the quality of the extracted RNA, cDNA was prepared by reverse transcription. Quantitative Real-time PCR was performed, for KLK6 mRNA quantification, using the SYBR Green chemistry. Relative quantification analysis was made using the comparative Ct (2-ΔΔCT) method. HPRT1 was used as an endogenous control gene and BT-474 breast cancer cell line served as a calibrator. Results: KLK6 mRNA levels were significantly downregulated in the cancerous breast tissue specimens compared to their normal counterparts (p<0.001). Additionally, a negative association was observed between KLK6 expression status and tumor stage, given the fact that 54.2% of less advanced breast tumors (TNM stage≤ T2a) were KLK6-positive compared to the 34.6% of more advanced-stage tumors (TNM >T2a) (p=0.034). Moreover, a statistically significant negative correlation was documented between KLK6 mRNA levels and estrogen (p<0.001) and progesterone receptor (p=0.003) statuses. Conclusions: The downregulation of KLK6 in cancerous compared to normal sections of breast tissue samples reflects the reported tumor suppressor properties of KLK6 gene in breast malignancies. Furthermore, the negative association of KLK6 mRNA expression with tumor stage, ER and PR statuses reveals the putative role of KLK6 as a promising prognostic breast cancer biomarker.


2021 ◽  
Vol 118 (45) ◽  
pp. e2100050118
Author(s):  
Katalin Erdélyi ◽  
Tamás Ditrói ◽  
Henrik J. Johansson ◽  
Ágnes Czikora ◽  
Noémi Balog ◽  
...  

Basal-like breast cancer (BLBC) is the most aggressive subtype of breast tumors with poor prognosis and limited molecular-targeted therapy options. We show that BLBC cells have a high Cys demand and reprogrammed Cys metabolism. Patient-derived BLBC tumors from four different cohorts exhibited elevated expression of the transsulfuration enzyme cystathione β-synthetase (CBS). CBS silencing (shCBS) made BLBC cells less invasive, proliferate slower, more vulnerable to oxidative stress and cystine (CySSCy) deprivation, prone to ferroptosis, and less responsive to HIF1-α activation under hypoxia. shCBS xenograft tumors grew slower than controls and exhibited impaired angiogenesis and larger necrotic areas. Sulfur metabolite profiling suggested that realigned sulfide/persulfide-inducing functions of CBS are important in BLBC tumor progression. Supporting this, the exclusion of serine, a substrate of CBS for producing Cys but not for producing sulfide/persulfide, did not exacerbate CySSCy deprivation–induced ferroptosis in shCBS BLBC cells. Impaired Tyr phosphorylation was detected in shCBS cells and xenografts, likely due to persulfidation-inhibited phosphatase functions. Overexpression of cystathione γ-lyase (CSE), which can also contribute to cellular sulfide/persulfide production, compensated for the loss of CBS activities, and treatment of shCBS xenografts with a CSE inhibitor further blocked tumor growth. Glutathione and protein-Cys levels were not diminished in shCBS cells or xenografts, but levels of Cys persulfidation and the persulfide-catabolizing enzyme ETHE1 were suppressed. Finally, expression of enzymes of the oxidizing Cys catabolism pathway was diminished, but expression of the persulfide-producing CARS2 was elevated in human BLBC tumors. Hence, the persulfide-producing pathways are major targetable determinants of BLBC pathology that could be therapeutically exploited.


2001 ◽  
Vol 120 (5) ◽  
pp. A573-A573
Author(s):  
J SHODA ◽  
T ASANO ◽  
T KAWAMOTO ◽  
Y MATSUZAKI ◽  
N TANAKA ◽  
...  

2007 ◽  
Vol 177 (4S) ◽  
pp. 51-51
Author(s):  
Shintaro Narita ◽  
Alan I. So ◽  
Shannon Sinnemann ◽  
Ladan Fazli ◽  
Eric G. Marcusson ◽  
...  

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