scholarly journals HYPOXIA-DEPENDANT MECHANISMS OF REGULATING NEOANGIOGENESIS AND APOPTOSIS IN PATIENTS WITH EARLY RECURRENT LOCALIZED PROSTATE CANCER

2018 ◽  
Vol 14 (3) ◽  
pp. 37-42
Author(s):  
O. I. Kit ◽  
F. S. Bova ◽  
A. Yu. Maksimov
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Tumor Tissue ◽  
Prostate Gland ◽  
Early Recurrence ◽  
Localized Prostate Cancer ◽  
Control Group ◽  
Expression Of Genes ◽  
Comparative Group

Objective. Examination of the expression of genes responsible for hypoxia-dependent control of transcription, neoangiogenesis, and apoptosis in tumor tissue of the prostate, in patients with localized prostate cancer (РС) with biochemical recurrence (BR) and without recurrences after radical prostatectomy (RPE).Materials and methods. The main group included 56 patients with localized PC who had been diagnosed with BR within two years after RP. 60 patients with localized PC who did not relapse had a comparative group. 55 patients in whom operative biopsy specimens of the prostate gland were taken within healthy tissues with the removal of benign prostatic hyperplasia were combined into a control group. Determination of the expression level of the BAX, BCL2, VEGFA and HIF1α genes in tumor tissue was performed by real-time polymerase chain reaction.Results. In patients with localized PC after RPE, development of BR is associated with an increase in the expression of BCL2, VEGFA and HIF1α genes and a decrease in the expression of the BAX gene. In patients with localized PC and early recurrence of tumor tissue through a hypoxia-dependent factor that enhances transcritical processes in tumor cells, neoangiogenesis is activated, which is associated with inhibition of apoptosis of tumor cells by enhancing the expression of the antiapoptotic gene BCL2.Conclusion. Determination of the expression of BAX, BCL2, VEGFA and HIF1α genes in tumor tissue with localized PC allows further assessment of the risk of disease progression after surgical treatment.

scholarly journals ASSOCIATION OF EXPRESSION OF NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2 GENES WITH BIOCHEMICAL REMEDIATION IN PATIENTS WITH LOCALIZED PROSTATE CANCER

2019 ◽  
Vol 6 (3) ◽  
pp. 10-19
Author(s):  
Ph. S. Bova ◽  
O. I. Kit ◽  
A. Yu. Maksimov
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Main Group ◽  
Localized Prostate Cancer ◽  
Control Group ◽  
Cancer Tissue ◽  
Expression Of Genes ◽  
Experimental Group ◽  
Bcl2 Gene

Aim. To identify the association of NFKB1, HIF1, VEGFA, VEGFB, BAX, BCL2 gene expression in prostate adenocarcinoma cells with biochemical recurrence of localized prostate cancer. Patients and methods. Three groups of patients were formed in the study – the main one, the comparison group and the control group. In patients with prostate cancer (PC) in the main group (n = 56) with biochemical recurrence (BR) for two years after radical surgery, as well as in 60 patients without BR (experimental group) by real-time PCR in prostate cancer tissue the expression of genes NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2 was determined. The control group consisted of 55 patients in whom, when performing diagnostic punctures for benign prostate tumors, biopsy specimens were taken in healthy tissues. The age of patients in the three groups ranged from 57 to 74 years (median 63 years). When quantifying expression of genes NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2, the difference in the values of reaction threshold cycles (Ct) fixed for the studied and reference genes was determined. The relative level (Expr) was the ratio of Ct medians for each gene in two compared groups of the studied three ones: in the main group to the indicator in the control group, in the experimental group to the indicator in the control group, and also between the main group and the experimental group. Results. A comparative analysis of gene expression in prostate cancer tissue in the main group compared with the experimental group showed a statistically significant increase (p < 0,05) in the relative index for the HIF1 gene (2,7 times), the VEGFA gene (2,4 times ) and the NFKB1 gene (2 times). Consequently, in patients with localized early recurrence prostate cancer, initially in the prostate tissue, a higher level of expression of the NFKB1, HIF1 and VEGFA genes was established. In the experimental group relative to the control group, the expression of the proapoptic gene BAX was 1,6 times higher (p < 0,05), and for the antiapoptic gene BCL2 no changes were detected (p = 0,09). Thus, in patients with localized prostate cancer in the absence of BR, after radical prostatectomy, an initial increase in the expression of the BAX gene promoted the activation of apoptosis. In patients with localized prostate cancer, subsequent biochemical recurrence initially in the tissue of prostate adenocarcinoma inhibition of apoptosis due to increased expression of the BCL2 gene was observed. Conclusion. Enhancement of NFKB1, VEGFA, HIF1 and BCL2 gene expression in prostate tissue is associated with the development of BR in patients with localized prostate cancer.

scholarly journals The Assessment of IL-21 and IL-22 at the mRNA Level in Tumor Tissue and Protein Concentration in Serum and Peritoneal Fluid in Patients with Ovarian Cancer

2021 ◽  
Vol 10 (14) ◽  
pp. 3058
Author(s):  
Aleksandra Mielczarek-Palacz ◽  
Celina Kruszniewska-Rajs ◽  
Marta Smycz-Kubańska ◽  
Jarosław Strzelczyk ◽  
Wojciech Szanecki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Fluid ◽  
Tumor Tissue ◽  
Mrna Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
First Time ◽  
Ovarian Serous Cancer

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research.

Cell-Free DNA Detection of Tumor Mutations in Heterogeneous, Localized Prostate Cancer Via Targeted, Multiregion Sequencing

2021 ◽  
pp. 710-725
Author(s):  
Emmalyn Chen ◽  
Clinton L. Cario ◽  
Lancelote Leong ◽  
Karen Lopez ◽  
César P. Márquez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Tissue ◽  
Somatic Tissue ◽  
Localized Prostate Cancer ◽  
Genomic Alterations ◽  
Cell Free Dna ◽  
Free Dna ◽  
Multiple Regions ◽  
Localized Disease ◽  
Tissue Alterations

PURPOSE Cell-free DNA (cfDNA) may allow for minimally invasive identification of biologically relevant genomic alterations and genetically distinct tumor subclones. Although existing biomarkers may detect localized prostate cancer, additional strategies interrogating genomic heterogeneity are necessary for identifying and monitoring aggressive disease. In this study, we aimed to evaluate whether circulating tumor DNA can detect genomic alterations present in multiple regions of localized prostate tumor tissue. METHODS Low-pass whole-genome and targeted sequencing with a machine-learning guided 2.5-Mb targeted panel were used to identify single nucleotide variants, small insertions and deletions (indels), and copy-number alterations in cfDNA. The majority of this study focuses on the subset of 21 patients with localized disease, although 45 total individuals were evaluated, including 15 healthy controls and nine men with metastatic castration-resistant prostate cancer. Plasma cfDNA was barcoded with duplex unique molecular identifiers. For localized cases, matched tumor tissue was collected from multiple regions (one to nine samples per patient) for comparison. RESULTS Somatic tumor variants present in heterogeneous tumor foci from patients with localized disease were detected in cfDNA, and cfDNA mutational burden was found to track with disease severity. Somatic tissue alterations were identified in cfDNA, including nonsynonymous variants in FOXA1, PTEN, MED12, and ATM. Detection of these overlapping variants was associated with seminal vesicle invasion ( P = .019) and with the number of variants initially found in the matched tumor tissue samples ( P = .0005). CONCLUSION Our findings demonstrate the potential of targeted cfDNA sequencing to detect somatic tissue alterations in heterogeneous, localized prostate cancer, especially in a setting where matched tumor tissue may be unavailable (ie, active surveillance or treatment monitoring).

scholarly journals Effect of immunoadjuvants on the disease course in patients with operable breast cancer

2019 ◽  
Vol 14 (4) ◽  
pp. 20-23
Author(s):  
M. M. Vasilyeva ◽  
I. P. Moshurov ◽  
L. Yu. Grivtsova ◽  
N. N. Tupitsyn ◽  
N. A. Kozlov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Tissue ◽  
Radical Mastectomy ◽  
Control Group ◽  
Cancer Management ◽  
New Strategy ◽  
Breast Cancer Management ◽  
Grade Ii ◽  
And Control

Background. A new strategy of breast cancer management is required for effective disease prevention and control. Immunotherapy is one of promising options.Objective: to evaluate the effect of immunoadjuvant polyoxidonium on pathmorphological changes in breast tumors.Materials and methods. The study was performed in 75 patients with breast cancer: 50 patients received polyoxidonium in a neoadjuvant regimen (main group), 25 patients did not receive polyoxidonium (control group). Polyoxidonium at a dose of 12 mg was administered intramuscularly 1 time per day on the days 1, 2, 3, 5 and 7 before surgery; on the day 8, radical mastectomy was performed in patients of both groups, followed by histological examination and determination of the grade of therapeutic pathomorphosis of the tumor.Results. The proportion of cases with grade I therapeutic pathomorphosis was 58 %, grade II therapeutic pathomorphosis – 6 %. Pathomorphosis in metastatic lymph nodes was observed in 22.7 % of cases.Conclusion. The anti-tumor effect of polyoxidonium was confirmed on the basis of the induction of pathomorphosis of the tumor tissue of breast cancer.

scholarly journals Detection and isolation of disseminated tumor cells in bone marrow of patients with clinically localized prostate cancer

The Prostate ◽  
2019 ◽  
Vol 79 (14) ◽  
pp. 1715-1727 ◽  
Author(s):  
Frank C. Cackowski ◽  
Yugang Wang ◽  
Joseph T. Decker ◽  
Christopher Sifuentes ◽  
Steven Weindorf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
Localized Prostate Cancer

scholarly journals Clinical Impact of Circulating Tumor Cells in Patients with Localized Prostate Cancer

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 676 ◽  
Author(s):  
Broncy ◽  
Paterlini-Bréchot
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Early Stage ◽  
Clinical Impact ◽  
Localized Prostate Cancer ◽  
Aggressive Cancer ◽  
Highly Sensitive ◽  
Prostate Cancers ◽  
Suitable Marker

The main issue concerning localized prostate cancers is the lack of a suitable marker which could help patients’ stratification at diagnosis and distinguish those with a benign disease from patients with a more aggressive cancer. Circulating Tumor Cells (CTC) are spread in the blood by invasive tumors and could be the ideal marker in this setting. Therefore, we have compiled data from the literature in order to obtain clues about the clinical impact of CTC in patients with localized prostate cancer. Forty-three publications have been found reporting analyses of CTC in patients with non-metastatic prostate cancer. Of these, we have made a further selection of 11 studies targeting patients with clinical or pathological stages T1 and T2 and reporting the clinical impact of CTC. The results of this search show encouraging data toward the use of CTC in patients with early-stage cancer. However, they also highlight the lack of standardized methods providing a highly sensitive and specific approach for the detection of prostate-derived CTC.

2138 CIRCULATING TUMOR CELLS (CTCS) ARE DETECTABLE IN PATIENTS WITH HIGH-RISK, LOCALIZED PROSTATE CANCER THROUGH USE OF THE CELLSEARCH PLATFORM

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
Sumanta Pal ◽  
Clayton Lau ◽  
Miaoling He ◽  
Jennifer Linehan ◽  
Timothy Wilson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Localized Prostate Cancer

Determination of Soluble MICA in Serum as a Novel Marker for Tumor Stage and Metastasis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1344-1344
Author(s):  
Helmut R. Salih ◽  
Petra Stieber ◽  
Andrea Peterfi ◽  
Dorothea Nagel ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
T Cells ◽  
Differential Diagnosis ◽  
Nk Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Control Group ◽  
Healthy Individuals ◽  
Benign Disorders

Abstract The human NKG2D ligands (NKG2DL) MICA and MICB have been shown to be expressed on tumors of epithelial and hematopoietic origin in vivo. Recently we reported that MICA is shed from the cell surface of tumor cells and is present in sera of tumor patients (J Immunol169:4098 (2002), Blood102:1389 (2003)). Since the strength of an anti-tumor response by NK cells and CD8 T cells is critically depending on NKG2DL expression levels, down-regulation of MICA-expression on tumor cells represents an immune escape mechanism that diminishes anti-tumor reactivity of NKG2D-bearing lymphocytes. However, no data are yet available regarding the correlation of soluble MICA (sMICA) levels with specific tumor entities, aggressiveness of the disease, and hence the potential implementation of sMICA as novel marker in differential diagnosis and prognosis of cancer. In this study, we determined sMICA levels in sera of 512 individuals including 296 patients with various cancers, 154 patients with benign disorders and 62 healthy individuals. Healthy individuals revealed significantly lower sMICA values (median<30pg/mL) than patients with benign diseases (84pg/mL; p=0.005) and cancer patients (161pg/mL; p<0.0001). In addition, sMICA levels differed significantly between cancer patients and patients with benign disorders (p<0.0001) that represent the most relevant control group for differential diagnosis. In cancer patients, while there was no association between sMICA levels and tumor size (p=0.456), cell differentiation (p=0.271), or lymph node involvement (p=0.674), sMICA correlated significantly with cancer stage and metastasis (p=0.015 and p=0.007, respectively). Our data indicate that release of MICA might play a role in late stages of tumor progression by overcoming the confining effect of NK cells and CD8 T cells. Thus, determination of sMICA levels provides valuable information for cancer staging, and sMICA in serum seems to be an indicator for systemic manifestation of malignancy rather than for local tumor extent.

Radiation Treatment for Localized Prostate Cancer and the Risk of Developing Myelodysplastic Syndromes (MDS)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 120-120
Author(s):  
Sudipto Mukherjee ◽  
Chandana Reddy ◽  
Jay Ciezki ◽  
Ramon V. Tiu ◽  
Edward A. Copelan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Treatment ◽  
Previous History ◽  
World Health ◽  
Localized Prostate Cancer ◽  
Control Group ◽  
Surgery Group ◽  
Increased Risk ◽  
Secondary Mds

Abstract Abstract 120 Background: Both environmental radiation exposure and use of therapeutic radiation (XRT) in primary solid tumor malignancies increase the risk of secondary MDS. No data exist on the risk of developing secondary MDS in prostate cancer patients (pts) being treated with radiotherapy. Establishing this risk has important clinical implications, as prostate cancer is the leading cancer in men and radiation therapy has increasingly become the preferred modality for treatment of localized prostate cancer. Methods: We performed a prospective case control study of 11,015 pts with localized prostate adenocarcinoma newly diagnosed between 1986 and 2011 at Cleveland Clinic who underwent treatment with either radical prostatectomy (control group) or definitive radiotherapy (external beam radiotherapy [EBRT] or prostate interstitial brachytherapy [PI] – case group), to investigate the risk of radiation-related MDS. Data on demographics, surgery, radiation treatment, and follow-up were collected from merged prostate cancer and MDS databases. Cytogenetic risk groups were per International Prognostic Scoring System (IPSS) for MDS. Univariate and multivariate analyses were performed using the Fine and Gray competing risk model with MDS as a time-dependent endpoint (which incorporates differences in duration of follow-up) and death from any cause as the competing event, comparing radiotherapy groups to the surgical cohort as the reference group, controlling for age and follow-up frequency. Hazard ratios (HR) with 95% confidence intervals (CIs) are reported. Results: For all pts, median age was 64 years (yrs, range, 37 – 88) at the time of prostate cancer diagnosis: 69 yrs in EBRT, 67 yrs in PI, and 60 yrs in surgery pts, respectively (p<0.0001); 5119 (46%) were treated with XRT, 5896 (54%) with prostatectomy. None of the pts had a previous history of another malignancy. Among XRT pts, 2183 (43%) were treated with EBRT, 2936 (57%) with PI. Median follow-up was 3.0 yrs [(range, 0.0 – 25.2): 6.8 yrs in the EBRT group, 2.5 yrs in the PI group and 1.8 yrs in the surgery group, (p<0.0001)] following prostate intervention, longer (4.6 yrs) in pts treated since 1996, when PI was first performed [6.6 yrs in the EBRT group, 3.8 yrs in the PI group and 4.3 yrs in the surgery group, (p<0.0001)]. In the entire cohort, 30 pts developed MDS: 24 in the XRT group and 6 in the surgery group. MDS World Health Organization classification was: RA/RARS (n=12), RCMD (n=3), RAEB-1 (n=3), RAEB-2 (n=3), CMML (n=2), MDS-U (n=3) and unknown (n=4). IPSS cytogenetic risk classification was: good risk (n=17), intermediate risk (n=5), poor risk (n= 4) and unknown (n = 4). For MDS pts within the XRT group, median age at MDS diagnosis was 79 yrs (range, 74 – 89) for EBRT, 80 yrs (range, 64 – 100) for PI. The median time to develop MDS was 8.9 yrs (range, 0.9 – 20.2): 9.1 for EBRT, 8.2 for PI, and 13.0 for prostatectomy pts, respectively (p=0.05). In univariate analyses, older pts (HR=1.14; CI, 1.09 – 1.2; p<0.0001), and those treated with XRT (HR=3.3; CI, 1.35 – 8.08; p=0.009): EBRT (HR=2.6; CI, 1.0 – 6.9; p=0.05), PI (HR=5.87; CI, 2.1 – 16.3; p=0.0007) were significantly more likely to develop MDS. In multivariate analysis though, while advanced age (HR=1.13; CI, 1.0 – 1.2; p < 0.0001) remained significantly associated with MDS development, XRT did not (HR=1.56; CI, 0.56 – 4.38; p=0.4), though a trend remained for PI (HR=2.85; CI, 0.9 – 8.8; p = 0.07). Conclusions: Pts who underwent definitive radiation treatment for localized prostate cancer did not appear to have a significantly increased risk of subsequent MDS, in analyses that controlled for age and incorporated length of follow-up. A trend for MDS development was present for those undergoing XRT with PI. These findings are encouraging for both patients and providers who have concerns about the potential effects of XRT on development of MDS. Disclosures: Maciejewski: Celgene: Membership on an entity's Board of Directors or advisory committees. Sekeres:Celgene: Consultancy, Honoraria, Speakers Bureau.

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