scholarly journals MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 48
Author(s):  
Tibor Szarvas ◽  
Michèle J. Hoffmann ◽  
Csilla Olah ◽  
Eszter Szekely ◽  
Andras Kiss ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Checkpoint Inhibitors ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Poor Overall Survival ◽  
Platinum Sensitivity ◽  
Therapeutic Decisions ◽  
Platinum Based Chemotherapy

Chemotherapy resistance is a main cause of therapeutic failure and death in bladder cancer. With the approval of immune checkpoint inhibitors, prediction of platinum treatment became of great clinical importance. Matrix metalloproteinase-7 (MMP-7) was shown to be involved in cisplatin resistance. Therefore, tissue and circulating MMP-7 levels were evaluated in 124 bladder cancer patients who received postoperative platinum-based chemotherapy. Tissue MMP-7 levels were analyzed by immunohistochemistry in 72 formalin-fixed, paraffin-embedded chemo-naïve tumor samples, while MMP-7 serum concentrations were determined in 132 serum samples of an independent cohort of 52 patients. MMP-7 tissue and serum levels were correlated with clinicopathological and follow-up data. MMP-7 gene expression was determined by RT-qPCR in 20 urothelial cancer cell lines and two non-malignant urothelial cell lines. MMP-7 was overexpressed in RT-112 and T-24 cells by stable transfection, to assess its functional involvement in platinum sensitivity. High MMP-7 tissue expression and pretreatment serum concentrations were independently associated with poor overall survival (tissue HR = 2.296, 95%CI = 1.235–4.268 and p = 0.009; serum HR = 2.743, 95%CI = 1.258–5.984 and p = 0.011). Therefore, MMP-7 tissue and serum analysis may help to optimize therapeutic decisions. Stable overexpression in RT-112 and T-24 cells did not affect platinum sensitivity.

scholarly journals Clinical Significance of Annexin A2 Expression in Breast Cancer Patients

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 2
Author(s):  
Lee D. Gibbs ◽  
Kelsey Mansheim ◽  
Sayantan Maji ◽  
Rajesh Nandy ◽  
Cheryl M. Lewis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Cell Lines ◽  
Breast Cancer Subtypes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Cancer Subtypes ◽  
Tumor Tissues

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.

scholarly journals Increased Levels of Erythropoietin in Nipple Aspirate Fluid and in Ductal Cells from Breast Cancer Patients

2008 ◽  
Vol 30 (1) ◽  
pp. 51-61
Author(s):  
Ferdinando Mannello ◽  
Laura Fabbri ◽  
Eleonora Ciandrini ◽  
Gaetana A. Tonti
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Intracellular Signaling ◽  
Tnm Classification ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Serum Samples ◽  
Ductal Cells

Background: Erythropoietin (Epo) is an important regulator of erythropoiesis, and controls proliferation and differentiation of both erythroid and non-erythroid tissues. Epo is actively synthesized by breast cells during lactation, and also plays a role in breast tissues promoting hypoxia-induced cancer initiation. Our aims are to perform an exploratory investigation on the Epo accumulation in breast secretions from healthy and cancer patients and its localization in breast cancer cells.Methods: Epo was determined by ELISA, immunoprecipitation, western blot and immunocytochemical analyses in 130 Nipple Aspirate Fluids (NAF) from 102 NoCancer and 28 Breast Cancer (BC) patients, comparing results with those found in 10 milk, 45 serum samples and breast cancer cell lines.Results: Epo levels in NAFs were significantly higher than those in milk and serum. No difference in Epo electrophoretic mobility was found among NAF, milk and serum samples, and conditioned cell culture medium. Immunolocalization of intracellular Epo in ductal cells floating in BC NAFs was similar to those of cancer cell lines. No significant correlation between TNM classification and Epo in NAFs from BC patients was found. Significantly higher Epo concentration was found in NAF from BC patients compared to NoCancer.Conclusion: We demonstrate that breast epithelial cells are a source of Epo in breast microenvironment, suggesting the presence of a paracrine/autocrine Epo function in NAFs, triggering off intracellular signaling cascade with subsequent BC initiation.

scholarly journals Increase expression of IL-17A, IL6, STAT3,  TGF-β and VEGF in Bladder Cancer: potential biomarkers?

2020 ◽  
Author(s):  
Yanbo Liu ◽  
Zishen Xiao ◽  
Jijuan Yang ◽  
Jiayu Lin ◽  
Weigao Shen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Inflammatory Cells ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Elevated Expression ◽  
Degree Of Malignancy ◽  
Ifn Γ ◽  
Cancer Tissues ◽  
And Control ◽  
Potential Biomarkers

Abstract Background: Bladder cancer is the most common urinary system malignant disease all over the world. Our former research results showed that IL-17 family relative cytokines involved in the occurrence and development of bladder cancer, moreover A variety of inflammatory cells (such as lymphocyte, macrophage, mast cell and neutrophil ) infiltrated in bladder cancer tissues and were closely related to bladder cancer.Results: Immunohistochemistry (HIS) was employed to measure expression and location of IL-17A, IL-6, STAT3 and VEGF in pathological specimens of bladder cancer patients with different degree of malignancy (n=80), cystitis (n=23) and relative normal adjacent tissues (n=4). ELISA was used for measuring concentrations of MMP-9, TGF-β, VEGF and IFN-γ in serum samples collected from patients with bladder cancer (n=34) and control subjects (n=5). Immunoreactivity for IL-17A, IL-6, STAT3 and VEGF significant increased in tissues of bladder cancer compared with that of cystitis and normal adjacent tissues (p = 0.001. respectively), which was positively associated with the degrees of malignancy of the cancer. Serum concentrations of TGF-β and VEGF were significantly higher in patients with bladder cancer compared with that of controls (p=0.002 and p=0.0001 respectively), while concentrations of MMP-9 and IFN-γ were not significantly different between the groups of subjects. In the meanwhile, serum concentrations of MMP-9, TGF-β, VEGF, but not IFN-γ were significantly higher in patients with high degree of malignancy (stage Ⅲ and Ⅳ) than that of patients with low malignancy (stage Ⅰ and Ⅱ) (p=0.001, p=0.030, and p=0.011 respectively).Conclusion: Elevated expression of IL-17A, IL-6, STAT3 in tissues and of TGF-β, VEGF in serum might be considered as potential biomarkers for clinical stages of bladder carcinoma progress.Trial registration: ISRCTN, ISRCTN2012BH006. Registered 10 January 2012

Meta-analysis of clinicopathological and survival data of bladder cancer patients treated with platinum-based chemotherapy

2018 ◽  
Vol 17 (12) ◽  
pp. e2707
Author(s):  
O. Modos ◽  
Á. Bozsaki ◽  
C. Nagy ◽  
N. Nagy ◽  
A. Csizmarik ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Survival Data ◽  
Meta Analysis ◽  
Platinum Based Chemotherapy

scholarly journals Update Breast Cancer 2019 Part 3 – Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel

2019 ◽  
Vol 79 (05) ◽  
pp. 470-482 ◽  
Author(s):  
Hans-Christian Kolberg ◽  
Andreas Schneeweiss ◽  
Tanja N. Fehm ◽  
Achim Wöckel ◽  
Jens Huober ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Checkpoint Inhibitors ◽  
Local Therapy ◽  
Breast Cancer Patients ◽  
Long Term Effects ◽  
Cancer Review ◽  
Therapeutic Decisions ◽  
Study Results

AbstractThe treatment of breast cancer patients in a curative situation is special in many ways. The local therapy with surgery and radiation therapy is a central aspect of the treatment. The complete elimination of tumour cells at the site of the primary disease must be ensured while simultaneously striving to keep the long-term effects as minor as possible. There is still focus on the continued reduction of the invasiveness of local therapy. With regard to systemic therapy, chemotherapies with taxanes, anthracyclines and, in some cases, platinum-based chemotherapies have become established in the past couple of decades. The context for use is being continually further defined. Likewise, there are questions in the case of antihormonal therapy which also still need to be further defined following the introduction of aromatase inhibitors, such as the length of therapy or ovarian suppression in premenopausal patients. Finally, personalisation of the treatment of early breast cancer patients is also being increasingly used. Prognostic tests could potentially support therapeutic decisions. It must also be considered how the possible use of new therapies, such as checkpoint inhibitors and CDK4/6 inhibitors could look in practice once study results in this regard are available. This overview addresses the backgrounds on the current votes taken by the international St. Gallen panel of experts in Vienna in 2019 for current questions in the treatment of breast cancer patients in a curative situation.

Serum calretinin as a predictor for recurrence and overall survival in ovarian cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17033-e17033
Author(s):  
Pauline Wimberger ◽  
Simon Passek ◽  
Theresa Link ◽  
Yana Vassileva ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Calcium Binding ◽  
Tumor Resection ◽  
High Volume ◽  
Primary Diagnosis ◽  
Platinum Resistance ◽  
Serum Samples ◽  
Platinum Based Chemotherapy

e17033 Background: Calretinin (CRT) is a calcium-binding protein, controlling intracellular calcium signaling. Besides its prominent expression in neurons, CRT has diagnostic implications in cancer, particularly in mesothelioma. In a recent liquid biopsy approach, plasma CRT level has been suggested for pre-diagnostic detection of mesothelioma. CRT is also expressed in serous ovarian cancer in about 23% of cases; however, clinical relevance of serum CRT is completely unknown and shall therefore be analyzed, herein. Methods: Serum calretinin (sCRT) was determined by calretinin enzyme-linked immunoabsorbent assay (DLD-Diagnostika GmbH, Hamburg) in a total of 380 serum samples from 134 ovarian cancer patients (thereof n = 115 (86%) with FIGO III or IV), including samples at primary diagnosis and at 4 follow-up reading points in the course of adjuvant treatment. Results: sCRT levels were significantly increased in ovarian cancer patients compared to healthy controls (ED = 0.3ng/ml, p < 0.001) and enabled an accurate discrimination between ovarian cancer and controls (AUC = 0.85). High sCRT levels at primary diagnosis predicted suboptimal debulking surgery without achieving macroscopically complete tumor resection (p < 0.001) and were associated with advanced FIGO-stage (p < 0.001) and high volume of ascites (p < 0.001). Increased sCRT levels at primary diagnosis were an independent predictor of poor PFS (HR:1.99, p = 0.018) and also indicated poor OS (HR:2.49, p = 0.008). Increased sCRT levels before and after platinum-based chemotherapy were independent predictors of poor OS (HR:15.4, p = 0.01; HR:5.59, p = 0.026). Moreover, elevated sCRT levels at primary diagnosis indicated platinum-resistance (p = 0.002). Conclusions: This is the first study, suggesting sCRT as an innovative liquid biopsy marker for ovarian cancer by showing its independent prognostic relevance and its association with primary platinum-resistance.

scholarly journals Novel Options in Metastatic and Non-surgically Curable Bladder Cancer

2018 ◽  
Vol 14 (2) ◽  
pp. 87
Author(s):  
Elise Vong ◽  
Jens Samol ◽  
◽  
Keyword(s):  
Bladder Cancer ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Current Evidence ◽  
Predictors Of Response ◽  
Programmed Death ◽  
Platinum Based Chemotherapy ◽  
Programmed Cell Death 1 ◽  
Urothelial Bladder

For over two decades, the prognosis of patients with metastatic or locally advanced non-resectable bladder cancer has remained poor, with no significant advances in life-prolonging treatment, especially following progression on platinum-based chemotherapy or for cisplatin-ineligible patients. In recent years, immunotherapy has changed the standard of care for an increasing number of tumour types, including bladder cancer. Here, we will review the current evidence of the clinical usage of immune checkpoint inhibitors with a focus on programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, as well as their toxicities, potential biomarkers and predictors of response, and provide an outline of future directions in the treatment of patients with metastatic and/or non-surgically curable urothelial bladder cancer.

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