scholarly journals Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6965
Author(s):  
Natalia Yunusova ◽  
Elena Kolegova ◽  
Elena Sereda ◽  
Larisa Kolomiets ◽  
Alisa Villert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Enzymatic Activity ◽  
Cancer Patients ◽  
Ovarian Tumors ◽  
Target Cells ◽  
Cancer Tissue ◽  
20S Proteasome ◽  
Tumor Dissemination ◽  
Healthy Females

Exosomes are directly involved in governing of physiological and pathological conditions of an organism through the transfer of information from producing to receiving cells. It can be assumed that exosomes are one of the key players of tumor dissemination since they are very stable and small enough to penetrate from various tissues into biological fluids and then back, thus interacting with tissue target cells. We evaluated the enzymatic activity and the level of 20S proteasome in tissue and exosomes of healthy females (n = 39) and patients with ovarian (n = 50) and breast (n = 108) tumors to reveal the critical role of exosomal cargo in the mediation of different types of metastases. Exosomes from plasma and ascites were isolated and characterized in according to International Society for Extracellular Vesicles guidelines. The level of 20S proteasome in tissue and exosomes was determined using Western blot analysis. Chymotrypsin- and caspase-like (ChTL and CL, respectively) peptidase activities of the proteasomes were determined using fluorogenic Suc-LLVY-AMC and Cbz-LLG-AMC substrates, respectively. We observed increased levels of 20S proteasome in ovarian cancer tissue and luminal B subtype breast cancer tissue as well as in plasma exosomes from cancer patients. Moreover, the level of the 20S proteasome in plasma exosomes and ascites exosomes in patients with ovarian tumors is comparable and higher in ovarian cancer patients with low volume ascites than in patients with moderate and high-volume ascites. We also found increased ChTL and CL activities in breast cancer and ovarian cancer tissues, as well as in peritoneal metastases in ovarian cancer, while proteasomal activity in exosomes from plasma of healthy females and all patients, as well as from ascites of ovarian tumor patients were lower than detection limit of assay. Thus, regardless of the type of tumor metastasis (lymphogenous or peritoneal), the exosomes of cancer patients were characterized by an increased level of 20S proteasome, which do not exhibit enzymatic activity.

scholarly journals Selection of aptamers against triple negative breast cancer cells using high throughput sequencing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Débora Ferreira ◽  
Joaquim Barbosa ◽  
Diana A. Sousa ◽  
Cátia Silva ◽  
Luís D. R. Melo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Throughput ◽  
Triple Negative Breast Cancer ◽  
High Throughput Sequencing ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Target Cells ◽  
Cancer Tissue ◽  
Surface Receptors

AbstractTriple-negative breast cancer is the most aggressive subtype of invasive breast cancer with a poor prognosis and no approved targeted therapy. Hence, the identification of new and specific ligands is essential to develop novel targeted therapies. In this study, we aimed to identify new aptamers that bind to highly metastatic breast cancer MDA-MB-231 cells using the cell-SELEX technology aided by high throughput sequencing. After 8 cycles of selection, the aptamer pool was sequenced and the 25 most frequent sequences were aligned for homology within their variable core region, plotted according to their free energy and the key nucleotides possibly involved in the target binding site were analyzed. Two aptamer candidates, Apt1 and Apt2, binding specifically to the target cells with $$K_{d}$$ K d values of 44.3 ± 13.3 nM and 17.7 ± 2.7 nM, respectively, were further validated. The binding analysis clearly showed their specificity to MDA-MB-231 cells and suggested the targeting of cell surface receptors. Additionally, Apt2 revealed no toxicity in vitro and showed potential translational application due to its affinity to breast cancer tissue sections. Overall, the results suggest that Apt2 is a promising candidate to be used in triple-negative breast cancer treatment and/or diagnosis.

scholarly journals A MOLECULAR-BASED APPROACH TO INVESTIGATE BREAST CANCER 1 AND BREAST CANCER 2 STATUS IN OVARIAN CANCER AMONG IRAQI WOMEN

2018 ◽  
Vol 11 (7) ◽  
pp. 199
Author(s):  
Muhannad Shweash ◽  
Saddam Jumaa Naseer ◽  
Maisam Khider Al-anii ◽  
Thulfiqar Fawwaz Mutar
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Gene Mutations ◽  
Healthy Controls ◽  
Brca1 And Brca2 ◽  
First Degree Relatives ◽  
Brca Gene ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

Objective: Cancer ovary is one of the fatal gynecologic malignancies worldwide. Since breast cancer (BRCA) genes are considered tumor suppressor genes and play important roles in cancer by repairing of chromosomal damage with the error repair of DNA breaks. Therefore, breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations strongly enhance the development of ovarian cancer risk among women. Here, we report that both genes are an essential mediator of progress ovarian cancer, to determine the influence of BRCA1 and BRCA2 mutations in the improvement of ovarian cancer.Methods: A total of 25 subjects were chosen for the genetic studies, and three groups were recruited: fifteen ovarian cancer patients group, five healthy controls, and five first-degree relatives to a known case of ovarian cancer patients.Results: A genetic analysis revealed that a strong correlation exists between both gene mutations’ status in ovarian cancer, and BRCA gene mutations (185delAG, 5382insC, and 4153delA in BRCA1 and 6174delT in BRCA2) remained to establish to have a relatively high frequency among people in this study among ovarian cancer patients. Furthermore, seven patients with ovarian cancer carried all of the four investigated mutations, and five had three mutations.Conclusion: Otherwise, BRCA gene frequency showed low prevalence among first-degree relatives, and to a lesser extent among healthy controls, with only a few had all of the mutations combined. These data demonstrate for the first time a molecular link between BRCA1 and BRCA2 mutations in ovarian cancer progression in Iraq.

Factors of VEGF, IGF, and TGF-β1 families in omentum tissues to mark premetastatic niches in ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17535-e17535
Author(s):  
Anna P. Menshenina ◽  
Elena M. Frantsiyants ◽  
Tatiana I. Moiseenko ◽  
Ekaterina V. Verenikina ◽  
Natalia D. Cheryarina ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Elisa Test ◽  
Premetastatic Niche ◽  
Treatment And Prevention ◽  
Cancer Pathogenesis ◽  
Tumor Dissemination ◽  
Cell Release ◽  
Mesenchymal Epithelial Transition ◽  
Tgf Β1

e17535 Background: Analysis of the nature of cancer cell release and interaction with the microenvironment determines the fundamental basis of ovarian cancer pathogenesis, which is necessary for the development of new methods for peritoneal dissemination treatment and prevention. The purpose of the study was to analyze levels of VEGF-A, VEGFR1, VEGF-C, VEGFR3, TGF-β, IGF-1, IGF-2 and IGFBP3 in omental tissues (O) with and without metastasis (Mts) in ovarian cancer patients. Methods: Samples of O tissues were obtained from 51 ovarian cancer patients aged 60±1.9 years (G2-G3 serous cystadenocarcinoma – AC, Т2-3NxM0-1). 17 non-cancer patients of similar age were controls (C). Levels of VEGF-A, VEGFR1, VEGF-C, VEGFR3, IGF-1, IGF-2, IGFBP3 and TGF-β1 were measured in Mts and O tissues by standard ELISA test systems. Results: VEGF-A levels in O of AC patients were 2.6 times higher than in C. In Mts, VEGF-A and VEGFR1 exceeded the levels in C (by 6.3 and 3.1 times) and O (by 2.5 and 2.8 times, respectively). VEGF-C in O was lower than in C by 5.5 times, while VEGFR3 was 2.2 times higher. In Mts, VEGF-C and VEGFR3 exceeded the levels in C (by 7.8 and 3.6 times) and O (by 43.3 and 1.6 times, respectively, p<0.05). Levels of IGF-2 and IGFBP3 in O were similar to the levels in C, while IGF-1 was twice higher. In Mts, IGF-1, IGF-2 and IGFBP3 exceeded the levels in C (by 4.9, 2.8 and 3.4 times) and O (by 2.5, 2.2 and 3.6 times, respectively). Levels of TGF-β1 were higher in O by 2.9 times and in Mts – by 2.3 times. Conclusions: The interaction between VEGF-A, IGF-1, and TGF-β can serve as a regulator of the metabolic state of the “soil” for tumor dissemination, marking the premetastatic niche and providing mesenchymal-epithelial transition of circulating tumor cells.

Ca 15.3 as a Tumour Marker in Breast Cancer

1987 ◽  
Vol 2 (3) ◽  
pp. 135-142 ◽  
Author(s):  
Peter Schmidt-Rhode ◽  
Klaus-Dieter Schulz ◽  
Gerhard Sturm ◽  
Anette Raab-Frick ◽  
Helge Prinz
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Tumour Marker ◽  
Primary Treatment ◽  
Breast Diseases ◽  
Breast Cancer Patients ◽  
Ca 15.3 ◽  
Healthy Females

CA 15.3 is an antigenic determinant associated with human mammary carcinomas. Two murine monoclonal antibodies have been raised against the determinants, and an immunoradiometric assay (IRMA-Kit, Centocor, USA) has been developed to determine the antigen levels in plasma of cancer patients. Based on the 99% confidence limit of healthy women, plasma values above 30 U/ml are considered abnormal. Plasma samples from 357 women were examined in the present study. Healthy females (n = 84) ranged below the cut-off level between < 10 and 29 U/ml. Higher values were found in 12.5% of benign breast diseases and in 23.6% of breast cancer patients, including all stages. Depending on the stage of the disease, there were elevated levels in 11% of operable breast cancer patients preoperatively, in 7% of the cases with no evidence of disease after primary treatment and in 63.5% ofpatients with disseminated mammary carcinoma. In metastasized breast cancer the frequency and the degree of abnormal titers were closely related to the extent of the metastatic disease. Follow-up examinations of 63 patients under cytotoxic therapy showed CA 15.3 changes correlating well with the clinical course in up to 90% of the antigen positive cases. The present data indicate that CA 15.3 may be useful in the surveillance of breast cancer patients. However in our study one third of the patients with metastatic breast cancer did not show any increase in CA 15.3 and must be regarded as antigen negative.

scholarly journals Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

2020 ◽  
Vol 21 (19) ◽  
pp. 7341
Author(s):  
Maria Konoshenko ◽  
Georgy Sagaradze ◽  
Evgeniya Orlova ◽  
Tatiana Shtam ◽  
Ksenia Proskura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Surface ◽  
Blood Cell ◽  
Cancer Patients ◽  
Path Length ◽  
Total Blood ◽  
Migration Path ◽  
Mesenchymal Transition ◽  
Tumor Dissemination ◽  
Total Migration

Exosomes are crucial players in cell-to-cell communication and are involved in tumorigenesis. There are two fractions of blood circulating exosomes: free and cell-surface-associated. Here, we compared the effect of total blood exosomes (contain plasma exosomes and blood cell-surface-associated exosomes) and plasma exosomes from breast cancer patients (BCPs, n = 43) and healthy females (HFs, n = 35) on crucial steps of tumor progression. Exosomes were isolated by ultrafiltration, followed by ultracentrifugation, and characterized by cryo-electron microscopy (cryo-EM), nanoparticle tracking analysis, and flow cytometry. Cryo-EM revealed a wider spectrum of exosome morphology with lipid bilayers and vesicular internal structures in the HF total blood in comparison with plasma. No differences in the morphology of both exosomes fractions were detected in BCP blood. The plasma exosomes and total blood exosomes of BCPs had different expression levels of tumor-associated miR-92a and miR-25-3p, induced angiogenesis and epithelial-to-mesenchymal transition (EMT), and increased the number of migrating pseudo-normal breast cells and the total migration path length of cancer cells. The multidirectional effects of HF total blood exosomes on tumor dissemination were revealed; they suppress the angiogenesis and total migration path length of MCF10A, but stimulate EMT and increase the number of migrating MCF10A and the total path length of SKBR3 cells. In addition, HF plasma exosomes enhance the metastasis-promoting properties of SKBR3 cells and stimulate angiogenesis. Both cell-free and blood cell-surface-associated exosomes are involved in the crucial stages of carcinogenesis: the initiation of EMT and the stimulation of proliferation, cell migration, and angiogenesis. Thus, for the estimation of the diagnostic/prognostic significance of circulating exosomes in the blood of cancer patients more correctly, the total blood exosomes, which consist of plasma exosomes and blood cell-surface-associated exosomes should be used.

Evaluation of the Specificity of the Leukocyte Migration Inhibition Test against Histologically Homologous and Heterologous Neoplastic Antigens in Cancer Patients

1981 ◽  
Vol 67 (3) ◽  
pp. 169-175 ◽  
Author(s):  
Giovanni Mantovani ◽  
Maria A. Manca ◽  
Francesco Cossu ◽  
Ernesto Proto ◽  
Guglielmo Taglieri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Digestive Tract ◽  
Laryngeal Cancer ◽  
Cancer Tissue ◽  
Migration Inhibition ◽  
Cancer Antigens ◽  
Homologous Antigen ◽  
Wide Range ◽  
Heterologous Antigens

The aim of the present study was to verify whether the CMI response of the host's lymphocytes is directed towards tumor-associated antigens (TAA) specific for each histological type of tumor. The leucocyte migration inhibition (LMI) test was selected for this purpose, utilizing the cancer patients' leucocytes and, as neoplastic antigens, formalin-fixed cells of surgically removed cancer tissue. Two hundred and eighteen patients were studied, 110 of whom were affected by breast cancer, 48 by digestive tract and 60 by laryngeal cancer. The total amount of tests performed was 278. The leucocytes of 93 normal subjects were tested against the different tissues' cancer antigens, as were the leucocytes of 41 patients with cancer of different organs tested against the corresponding normal tissues' antigens. The breast cancer patients (122 tests performed) showed 82.35 % positive tests against homologous antigen, 72.72 % and 95.24 % against heterologous (digestive tract and laryngeal cancer, respectively) antigens. The digestive tract cancer patients (69 tests performed) showed 70.27 % positive tests against homologous, 66.66 % and 43.48 % against heterologous antigens (breast and laryngeal cancer, respectively). The laryngeal cancer patients (87 tests performed) showed 74.29 % positive tests against homologous, 38.10 % and 80.65 % against heterologous antigens (breast and digestive tract, respectively). The results led to the conclusion that the LMI test response of cancer patients was not « tissue specific »: the test did not discriminate between the homologous and the heterologous cancer antigens, and it seems that the response was not directed towards specific TAA but only towards wide-range or « group » TAA, shared by several types of tumors.

Gonadotropin Levels in Ovarian Cyst Fluids: A Predictor of Malignancy?

1998 ◽  
Vol 13 (3) ◽  
pp. 165-168 ◽  
Author(s):  
S. Krämer ◽  
M. Leeker ◽  
W. Jäger
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Elevated Serum ◽  
Serum Levels ◽  
Ovarian Tumors ◽  
Surgical Removal ◽  
Serum Samples ◽  
Benign Ovarian Tumors ◽  
Surprising Finding ◽  
Cyst Fluids

Gonadotropins can stimulate ovarian cancer growth in cell cultures. Corresponding LH/hCG receptors have been demonstrated in ovarian cancer. However, reduction of elevated serum gonadotropins by GnRH analogs in ovarian cancer patients did not lead to growth restriction, which means that serum levels of gonadotropins may not play the most important role in ovarian cancer. We therefore analyzed the LH and FSH concentrations in cyst fluids of ovarian cancer. Patients with preoperatively diagnosed cystic ovarian tumors were eligible for the study. Serum samples of the patients were obtained during surgery, while the fluids within the cysts were aspirated after surgical removal of the tumor. FSH and LH levels in serum and cyst fluids were measured using single antibody EIA (Boehringer Mannheim GmbH, Germany). Cyst fluids and sera of 108 patients were evaluated. While there were no significant differences in the FSH and LH serum concentrations, highly significant differences in the FSH and LH levels in cyst fluids were found. Only cancer cysts contained FSH and LH, while the corresponding concentrations in benign cysts were always below the measuring range of the assays. This clear division between high gonadotropin levels in cysts of serous ovarian cancer and low or absent concentrations in benign ovarian tumors further supports the hypothesis that FSH and LH may play a role in ovarian cancer; however, explanations for this surprising finding are still lacking.

scholarly journals Clinical significance of serum PSA in breast cancer patients

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Toru Hanamura ◽  
Koichi Ohno ◽  
Shinya Hokibara ◽  
Hideki Murasawa ◽  
Toshitsugu Nakamura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Biology ◽  
Specific Antigen ◽  
Metastatic Breast ◽  
Serum Testosterone ◽  
Biological Properties ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Post Menopausal

Abstract Background Recent preclinical data suggest that androgen receptor (AR) signaling plays a significant role in subsets of breast cancer. Clinical trials testing AR-targeting therapies in breast cancer have been conducted. Assessment of AR-signal in breast cancer tissue maybe useful for treatment selections. Prostate specific antigen (PSA) is the product of an androgen-responsive gene. Serum PSA (sPSA) can be detected in women by a highly sensitive assay although the concentration is much lower than that observed in males. We investigated if sPSA reflects tumor biology, including AR signaling in breast cancer patients. Methods In this study, 132 healthy controls and 144 breast cancer patients were enrolled. sPSA was evaluated by the chemiluminescent enzyme immunoassay (CLEIA) method. Correlations between sPSA and the various clinicopathological factors were analyzed. Results In post-menopausal state, sPSA detection rate was significantly higher in breast cancer patients compared with controls (27.4% vs 11.3%: p = 0.0090), but not in the whole cohort (29.2% vs 25.8%: p = 0.5265) or pre-menopausal subgroup (37.0% vs 42.6%: p = 0.6231). In post-menopausal breast cancer cases, higher sPSA value was associated with clinic-pathological factors including the expression of AR protein in primary legion. In a correlation analysis of quantitative data limited to post-menopausal metastatic breast cancer (MBC), sPSA was positively, albeit weakly correlated with clinic-pathological features including serum testosterone levels and AR positivity. Conclusions Our data suggest that sPSA may reflect tumor biological properties including AR activity in post-menopausal breast cancer.

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