scholarly journals Expression of Apoptotic Protease Activating Factor-1 in adenoid cystic carcinoma of the salivary glands and its clinicopathological relevance

2020 ◽  
pp. 130-130
Author(s):  
Branko Dozic ◽  
Boban Anicic ◽  
Vladimir Sinobad ◽  
Nikola Mikovic ◽  
Srdjan Milanovic ◽  
...  
Keyword(s):  
Overall Survival ◽  
Salivary Glands ◽  
Tumor Cells ◽  
Statistical Significance ◽  
Clinicopathological Parameters ◽  
Tumor Type ◽  
Immunohistochemical Expression ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
Histological Tumor Type

Background/Aim. Apoptotic Protease Activating Factor-1 (Apaf-1) is a key molecule in the intrinsic or mitochondrial pathway of apoptosis. Some pathological conditions such as cancer, stroke, and neurodegenerative diseases, are the result of disregulation in the intrinsic apoptosis pathway. The aim of this study was to analyse the immunohistochemical expression of Apaf-1 in ACC tumor cells of the salivary glands and its correlation with clinicopathological parameters (gender, age, localization, histological type and overall survival). Methods. Formalin-fixed, paraffin-embedded tissues from 50 human ACC of the salivary glands, male and female, average age 58 years, were used for our present study. We used the technique of tissue microarray (TMA blocks). Sections from the TMA mould, 5?m thick, were stained with the streptavidin-biotin immunohistochemical technique using primary antibodies specific for Apaf-1 (Leica Biosystems, Newcastle, UK). Stained tissue sections were analyzed by the light microscope (Olympus type BH-2). Based on the data collected, the database was created in SPSS software v. 22.0 (SPSS Inc., Chicago, ILL, USA), which was used for a further statistical analysis. The statistical data analysis included methods of descriptive and analytical (inferential) statistics. Results. The results of the immunohistochemical analysis of Apaf-1 expression in the samples of patients with ACC of the salivary glands were compared with the clinicopathological parameters of these patients. The immunohistochemical expression of Apaf-1 showed no statistical significance with regard to the patients gender (p=0.552), age (p=0.106), histological tumor type (p=0.654) and localization of ACC in the salivary glands (p=0.486). There was no statistically significant correlation observed between overall survival of ACC patients and Apaf-1 expression in tumor cells (p=0.340,Long-Rank test). Conclusion. With regard to ACC, Apaf-1 expression is not in correlation with clinicopathological parameters (gender, age, localization, histological tumor type, outcome of the disease, and overall survival). Therefore, we believe Apaf-1 cannot be regarded as an independent prognostic factor.

scholarly journals CD44 and CD24 Expression and Prognostic Significance in Canine Mammary Tumors

2018 ◽  
Vol 56 (3) ◽  
pp. 377-388 ◽  
Author(s):  
Bernadette Rogez ◽  
Quentin Pascal ◽  
Audrey Bobillier ◽  
François Machuron ◽  
Chann Lagadec ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Significance ◽  
Mammary Tumors ◽  
Clinicopathological Parameters ◽  
Tumor Type ◽  
High Grade ◽  
Mammary Carcinomas ◽  
Canine Mammary Tumors ◽  
Valuable Marker ◽  
High Level

CD44+/CD24– phenotype has been used to identify human and canine mammary cancer stem-like cells. In canine mammary tumors, CD44+/CD24– phenotype has been associated with high grade and lymph node infiltration. However, several studies have reported opposing results regarding the clinical significance of phenotypic groups formed by the combination of CD44 and CD24 in both human and canine mammary tumors. So far, no study has investigated the correlation between these phenotypes and survival in dogs. The aim of this study was to investigate the expression and distribution of CD44 and CD24 in canine mammary carcinomas and to correlate them with histological diagnosis and survival in a well-characterized cohort. Immunohistochemistry was performed in 96 mammary carcinomas with antibodies against CD44 and CD24. Expression of CD44+ and CD44+/CD24– phenotype was detected in 75 of 96 (78%) and 63 of 96 (65.6%) carcinomas, respectively. Their expression was associated with tumor type, occurring more often in tubular complex carcinomas than in solid carcinomas. CD44+/CD24– phenotype was associated with a better overall survival ( P = .001). CD24+ expression was detected in 52 of 96 tumors (54%) and CD44–/CD24+ phenotype in 39 of 96 tumors (40.6%). Both were associated with poor clinicopathological parameters (high grade, and emboli). No correlation with overall survival was observed. CD44+/CD24– expression was associated with a better prognosis and occurred at high frequency and high level, indicating that this phenotype is not suitable to detect cancer stem cells in canine mammary carcinomas. Although further studies are needed, our results suggest that CD24 may constitute a valuable marker of poor prognosis for canine mammary carcinomas.

scholarly journals Clinical Relevance of Circulating Tumor Cells in Esophageal Cancer Detected by a Combined MACS Enrichment Method

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 718 ◽  
Author(s):  
Anna Woestemeier ◽  
Katharina Harms-Effenberger ◽  
Karl-F. Karstens ◽  
Leonie Konczalla ◽  
Tarik Ghadban ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Clinical Relevance ◽  
Univariate Analysis ◽  
Immunocytochemical Staining ◽  
Clinicopathological Parameters ◽  
Advanced Tumor

Introduction. Current modalities to predict tumor recurrence and survival in esophageal cancer are insufficient. Even in lymph node-negative patients, a locoregional and distant relapse is common. Hence, more precise staging methods are needed. So far, only the CellSearch system was used to detect circulating tumor cells (CTC) with clinical relevance in esophageal cancer patients. Studies analyzing different CTC detection assays using advanced enrichment techniques to potentially increase the sensitivity are missing. Methods. In this single-center, prospective study, peripheral blood samples from 90 esophageal cancer patients were obtained preoperatively and analyzed for the presence of CTCs by Magnetic Cell Separation (MACS) enrichment (combined anti-cytokeratin and anti-epithelial cell adhesion molecules (EpCAM)), with subsequent immunocytochemical staining. Data were correlated with clinicopathological parameters and patient outcomes. Results. CTCs were detected in 25.6% (23/90) of the patients by combined cytokeratin/EpCAM enrichment (0–150 CTCs/7.5 mL). No significant correlation between histopathological parameters and CTC detection was found. Survival analysis revealed that the presence of more than two CTCs correlated with significantly shorter overall survival (OS) and progression-free survival (PFS). Conclusion. With the use of cytokeratin as an additional enrichment target, the CTC detection rate in esophageal cancer patients can be elevated and displays the heterogeneity of cytokeratin (CK) and EpCAM expression. The presence of >2CTCs correlated with a shorter relapse-free and overall survival in a univariate analysis, but not in a multivariate setting. Moreover, our results suggest that the CK7/8+/EpCAM+ or CK7/8+/EpCAM− CTC subtype does not lead to an advanced tumor staging tool in non-metastatic esophageal cancer (EC) patients.

scholarly journals Prognostic value of preoperative circulating tumor cells counts in patients with UICC stage I-IV colorectal cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252897
Author(s):  
Thaer S. A. Abdalla ◽  
Jan Meiners ◽  
Sabine Riethdorf ◽  
Alexandra König ◽  
Nathaniel Melling ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Stage I ◽  
Clinicopathological Parameters ◽  
Curative Intent ◽  
High Risk Patients ◽  
Risk Patients

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. There is an urgent need to identify prognostic markers for patients undergoing curative resection of CRC. The detection of circulating tumor cells in peripheral blood is a promising approach to identify high-risk patients with disseminated disease in colorectal cancer. This study aims to evaluate the prognostic relevance of preoperative CTCs using the Cellsearch® system (CS) in patients, who underwent resection with curative intent of different stages (UICC I-IV) of colorectal cancer. Out of 91 Patients who underwent colorectal resection, 68 patients were included in this study. CTC analysis was performed in patients with CRC UICC stages I-IV immediately before surgery. Data were correlated with clinicopathological parameters and patient outcomes. One or more CTCs/7.5 mL were detected in 45.6% (31/68) of patients. CTCs were detected in all stages of the Union of International Cancer Control (UICC), in stage I (1/4, 25%), in stage II (4/12, 33.3%), in stage III (5/19, 26.3%) and in stage IV (21/33, 63.6%). The detection of ≥ 1 CTCs/ 7.5ml correlated to the presence of distant overt metastases (p = 0.014) as well as with shorter progression-free (p = 0.008) and overall survival (p = 0.008). Multivariate analyses showed that the detection of ≥ 1 CTCs/ 7.5ml is an independent prognostic indicator for overall survival (HR, 3.14; 95% CI, 1.18–8.32; p = 0.021). The detection of CTCs is an independent and strong prognostic factor in CRC, which might improve the identification of high-risk patients in future clinical trials.

scholarly journals Prognostic and clinical significance of long non-coding RNA SNHG12 expression in various cancers

2020 ◽  
Author(s):  
Chenghao Zhang ◽  
Chao Tu ◽  
Xiaolei Ren ◽  
Wenchao Zhang ◽  
Lile He ◽  
...  
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Clinical Stage ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Tumor Type ◽  
Advanced Clinical Stage ◽  
Non Coding Rna ◽  
Tcga Dataset ◽  
Stratified Analysis

Abstract Background: Recently, dysregulation of lncRNA SNHG12 has been determined in kinds of cancers. However, definite prognostic value of SNHG12 remains unclear. We conducted this meta-analysis to evaluate the association between SNHG12 expression levels and caner prognosis.Methods: A literature retrieval was conducted by searching kinds of databases. The meta-analysis of prognostic and clinicopathological parameters was performed by using Revman 5.2 and Stata 12.0 software. Besides, The Cancer Genome Atlas dataset was analyzed to validate the results in our meta-analysis via using Gene Expression Profiling Interactive Analysis.Results: High SNHG12 expression significantly predicted worse overall survival (HR=1.97, 95%CI 1.56-2.48, P<0.01) and recurrence-free survival (HR=1.71, 95%CI 1.05-2.78, P<0.01). Tumor type, sample size, survival analysis method, and cut-off value did not alter SNHG12 prognosis value according to stratified analysis results. Additionally, patients with elevated SNHG12 expression were more prone to unfavorable clinicopathological outcomes, including larger tumor size, lymph node metastasis, distant metastasis, advanced clinical stage. Online cross-validation in TCGA dataset further proved that cancer patients with upregulated SNHG12 expression had worse overall survival and disease-free survival.Conclusion: Elevated SNHG12 expression was associated with poor survival and unfavorable clinicopathological features in various cancers, and therefore might be a potential prognostic biomarker in human cancers.

scholarly journals Design, Synthesis, and Evaluation of Novel 2-Methoxyestradiol Derivatives as Apoptotic Inducers through an Intrinsic Apoptosis Pathway

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 123
Author(s):  
Li-Xin Sheng ◽  
Jiang-Yu Zhang ◽  
Li Li ◽  
Xiao Xie ◽  
Xiao-An Wen ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cell Lines ◽  
Proliferative Activity ◽  
Inhibitory Concentration ◽  
Dependent Manner ◽  
Human Breast ◽  
Apoptosis Pathway ◽  
Single Access ◽  
Intrinsic Apoptosis Pathway ◽  
Mcf 7

In order to discover novel derivatives in the anti-tumor field, reported anti-tumor pharmacophores (uridine, uracil, and thymine) were combined with 2-methoxyestradiol, which has been characterized as having excellent biological properties in terms of anti-tumor activity. Thus, 20 hybrids were synthesized through etherification at the 17β-OH or 3-phenolic hydroxyl group of 2-methoxyestradiol, and evaluated for their biological activities against the human breast adenocarcinoma MCF-7 cell lines, human breast cancer MDA-MB-231 cell lines, and the normal human liver L-O2 cell lines. As a result, all the uridine derivatives and single-access derivatives of uracil/thymine possessed good anti-proliferative activity against tested tumor cells (half maximal inhibitory concentration values from 3.89 to 19.32 µM), while only one dual-access derivative (21b) of thymine possessed good anti-proliferative activity (half maximal inhibitory concentration ≈ 25 µM). Among them, the uridine derivative 11 and the single-access derivative of uracil 12a possessed good anti-proliferative selectivity against tested tumor cells. Furthermore, basic mechanism studies revealed that hybrids 11 and 12a could induce apoptosis in MCF-7 cells through mitochondrial pathway. These hybrids induced morphological changes in MCF-7 cells, causing mitochondrial depolarization. These two hybrids also had the following effects: arrest of the cell cycle at the G2 phase; up regulation of Apaf-1, Bax, and cytochrome c; down regulation of Bcl-2 and Bcl-xL for both mRNA and protein; and increase of the expression for caspase-8 and -9. Finally, apoptotic effector caspase-3 was increased, which eventually caused nuclear apoptosis at least through an intrinsic pathway in the mitochondria. Additionally, hybrids 11 and 12a could specifically bind to estradiol receptor alpha in a dose-dependent manner.

scholarly journals 80 Cancer testis antigen burden: A novel predictive biomarker for immunotherapy in solid tumors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A89-A89
Author(s):  
Sarabjot Pabla ◽  
RJ Seager ◽  
Yong Hee Lee ◽  
Erik Van Roey ◽  
Shuang Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Regression Model ◽  
Tumor Cells ◽  
Immune Cell ◽  
Tumor Type ◽  
Cancer Testis Antigen ◽  
Rna Seq ◽  
Tumor Types ◽  
Cancer Testis

BackgroundWhen expressed in cancer cells, cancer testis antigens (CTAs) are highly immunogenic and have the capacity to elicit cancer-specific immune responses in diverse malignancies. With their expression limited to tumor cells, CTAs have become a prime target of natural T cell response, immune cell-based therapy, and cancer vaccines. In this study, we investigated CTA burden in real-world clinical tumors spanning multiple histologies, revealing a novel prognostic gene expression-based biomarker.MethodsTargeted RNA-seq was performed on 5450 FFPE tumors representing 39 histologic types, predominantly composed of lung cancer (40.4%) followed by colorectal cancer (10.6%) and breast cancer (8.6%). Using an amplicon-based NGS approach, expression levels of 17 CTA genes were ranked against a reference population. Cancer Testis Antigen Burden (CTAB) was calculated as the sum of the gene expression rank for each CTA gene. The median CTAB of ≥171 was used as cutoff for CTAB High versus Low classification. We estimated Pearson’s correlation for all CTA genes to discover co-expression patterns between CTAs and histologies. Overall survival (OS) analysis was performed using CoxPh regression model whereas response analysis was performed using logistic regression model with p-values reported.ResultsWithin the tumor samples, CTAB values ranged from 0–1700, with kidney cancer demonstrating overall lowest mean CTAB (110) and melanoma the highest (550). NSCLC had an average CTAB of 283. In an immune checkpoint blockade treated retrospective cohort of 110 NSCLC patients, High CTAB showed better OS compared to Low CTA (HR: 0.55, p=0.07). Additionally, when combined with tumor inflammation and cell proliferation biomarkers, highly inflamed but poorly proliferative tumors with High CTAB had improved OS (HR: 0.27, p=0.05). No significant association with response was detectedConclusionsOur studies show that co-expression of multiple CTA genes occurs in many tumor types and can be reliably detected using a targeted RNA-seq approach. Utilization of this co-expression pattern to calculate CTAB reveals tumor-type associated signatures, which in a small NSCLC cohort is associated with the overall survival. The findings suggest that these immunogenic antigens expose the tumor cells to natural or immunotherapy augmented cell-based immune response, and that CTAB is a potential predictive marker for therapeutic response to checkpoint inhibitors. Further studies are needed to establish the predictive value in other tumor types, as well as the role of CTAB in immune cell therapies and vaccinations.

scholarly journals Mevalonate Cascade Inhibition by Simvastatin Induces the Intrinsic Apoptosis Pathway via Depletion of Isoprenoids in Tumor Cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Javad Alizadeh ◽  
Amir A. Zeki ◽  
Nima Mirzaei ◽  
Sandipan Tewary ◽  
Adel Rezaei Moghadam ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Intrinsic Apoptosis ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway

scholarly journals The Expression of Programmed Death Ligand-1 within Stages of Oral Squamous Cell Carcinoma: Immunohistochemical Analysis

2020 ◽  
pp. 59-68
Author(s):  
Moomal Aslam Khan ◽  
Serajuddaula Syed ◽  
Noor Ul Wahab ◽  
Saima Akram Butt ◽  
Jabbar Ahmed Qureshi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Statistical Significance ◽  
Clinicopathological Parameters ◽  
Immunohistochemical Expression ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Incidence And Mortality

Background: Oral squamous cell carcinoma is prevalent in South Asian countries with rising cases of its incidence and mortality. Despite advancements in treatment, survival and recurrence rates are poor. Immunotherapy is a novel therapeutic modality in immunooncology. Immune checkpoint proteins are under investigation for clinical implications amongst which Programmed Death Ligand-1 has shown valuable results in certain malignancies. Aims: To determine the immunohistochemical expression of Programmed Death Ligand-1(PD-L1) in oral squamous cell carcinoma and to find an association of Programmed Death Ligand-1 with stage and clinicopathological parameters of oral squamous cell carcinoma. Study Design: Cross-sectional study. Place and Duration of Study: Ziauddin Medical University, Karachi, 1 Year duration during 2018-2019. Methods: A total number of 140 biopsy confirmed cases of oral squamous cell carcinoma were recruited in the study. Immunohistochemical expression of Programmed Death Ligand-1 was evaluated and associated with the clinicopathological parameters of oral squamous cell carcinoma (OSCC). The data was statistically analyzed through Descriptive statistics and Chi square test by using SPSS v.20. Results: Out of 140 participants, 74% were males (n=103) and 26% were females (n=37). Programmed Death Ligand-1 positivity was observed in 62.1% of cases (n=87). The Mean age of the participants was 48.91 ± 11.7 years.  The most common site of cancer involvement was buccal mucosa and majority of participants were habitual of consuming chewable products i.e. Pan, Gutka and betel nut (89; 64%). Stage III and IV tumours comprised a major portion of cases in our study. (52; 37%), (56; 40%). A statistically significant p-value was noted for the association of Programmed Death Ligand-1 with stage II and IV tumours. (P-values: 0.029, 0.001)The association of Programmed Death Ligand-1 with other variables such as age, gender, ethnicity, sites or habits was not statistically significant. Conclusion: This study concludes that the statistical significance of Programmed Death Ligand-1 expression with tumour stage is suggestive of worsening prognosis and might have detrimental effects as tumour progresses in advanced stage. Programmed Death Ligand-1 positivity in patients having oral squamous cell carcinoma could be useful in future research in the light of cancer immunotherapy which has shown success in oncology.

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