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.

scholarly journals Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2418
Author(s):  
Xuezhen Zeng ◽  
Simon E. Ward ◽  
Jingying Zhou ◽  
Alfred S. L. Cheng
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Cancer Patients ◽  
High Recurrence Rate ◽  
Immune Microenvironment ◽  
Liver Sinusoidal Endothelial Cells ◽  
Premetastatic Niche ◽  
Cancer Pathogenesis ◽  
Colorectal Cancer Patients ◽  
The Impact

A drastic difference exists between the 5-year survival rates of colorectal cancer patients with localized cancer and distal organ metastasis. The liver is the most favorable organ for cancer metastases from the colorectum. Beyond the liver-colon anatomic relationship, emerging evidence highlights the impact of liver immune microenvironment on colorectal liver metastasis. Prior to cancer cell dissemination, hepatocytes secrete multiple factors to recruit or activate immune cells and stromal cells in the liver to form a favorable premetastatic niche. The liver-resident cells including Kupffer cells, hepatic stellate cells, and liver-sinusoidal endothelial cells are co-opted by the recruited cells, such as myeloid-derived suppressor cells and tumor-associated macrophages, to establish an immunosuppressive liver microenvironment suitable for tumor cell colonization and outgrowth. Current treatments including radical surgery, systemic therapy, and localized therapy have only achieved good clinical outcomes in a minority of colorectal cancer patients with liver metastasis, which is further hampered by high recurrence rate. Better understanding of the mechanisms governing the metastasis-prone liver immune microenvironment should open new immuno-oncology avenues for liver metastasis intervention.

scholarly journals Sphingosine-kinase-1 expression is associated with improved overall survival in high-grade serous ovarian cancer

2021 ◽  
Vol 147 (5) ◽  
pp. 1421-1430
Author(s):  
L. C. Hanker ◽  
A. El-Balat ◽  
Z. Drosos ◽  
S. Kommoss ◽  
T. Karn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tumor Resection ◽  
Sphingosine Kinase ◽  
Sphingolipid Metabolism ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Sphingosine Kinase 1 ◽  
Cancer Pathogenesis

Abstract Purpose Sphingosine-kinase-1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in ovarian cancer pathogenesis, progression and mechanisms of drug resistance. It is overexpressed in a variety of cancer subtypes. We investigated SPHK1 expression as a prognostic factor in epithelial ovarian cancer patients. Methods Expression analysis of SPHK1 was performed on formalin-fixed paraffin-embedded tissue from 1005 ovarian cancer patients with different histological subtypes using immunohistochemistry. Staining intensity of positive tumor cells was assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. Results In our ovarian cancer collective, high levels of SPHK1 expression correlated significantly with complete surgical tumor resection (p = 0.002) and lower FIGO stage (p = 0.04). Progression-free and overall survival were further significantly longer in patients with high-grade serous ovarian cancer and overexpression of SPHK1 (p = 0.002 and p = 0.006, respectively). Conclusion Our data identify high levels of SPHK1 expression as a potential favorable prognostic marker in ovarian cancer patients.

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 Review: Targeting the Transforming Growth Factor-Beta Pathway in Ovarian Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 668 ◽  
Author(s):  
Brandon M. Roane ◽  
Rebecca C. Arend ◽  
Michael J. Birrer
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
High Response Rate ◽  
Cellular Growth ◽  
Tumor Dissemination ◽  
Mesenchymal Transformation

Despite extensive efforts, there has been limited progress in optimizing treatment of ovarian cancer patients. The vast majority of patients experience recurrence within a few years despite a high response rate to upfront therapy. The minimal improvement in overall survival of ovarian cancer patients in recent decades has directed research towards identifying specific biomarkers that serve both as prognostic factors and targets for therapy. Transforming Growth Factor-β (TGF-β) is a superfamily of proteins that have been well studied and implicated in a wide variety of cellular processes, both in normal physiologic development and malignant cellular growth. Hypersignaling via the TGF-β pathway is associated with increased tumor dissemination through various processes including immune evasion, promotion of angiogenesis, and increased epithelial to mesenchymal transformation. This pathway has been studied in various malignancies, including ovarian cancer. As targeted therapy has become increasingly prominent in drug development and clinical research, biomarkers such as TGF-β are being studied to improve outcomes in the ovarian cancer patient population. This review article discusses the role of TGF-β in ovarian cancer progression, the mechanisms of TGF-β signaling, and the targeted therapies aimed at the TGF-β pathway that are currently being studied.

Immunoreactive score of Ep-CAM might predict survival in early ovarian cancer patients

2011 ◽  
Vol 71 (08) ◽  
Author(s):  
MJ Battista ◽  
J Steetskamp ◽  
N Mantai ◽  
S Gebhard ◽  
C Cotarelo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Early Ovarian Cancer

ROLE OF LIPID PROFILE IN OVARIAN CARCINOMA PATIENTS

2019 ◽  
Vol 3 (8) ◽  
Author(s):  
Dr. Manisha ◽  
Dr. Ruchi Jindal
Keyword(s):  
Ovarian Cancer ◽  
Lipid Profile ◽  
Cancer Patients ◽  
Ovarian Tumor ◽  
Ovarian Cancer Risk ◽  
Low Level ◽  
Medical College ◽  
Group I ◽  
History Of

Background: The term "ovarian cancer" includes several different types of cancer that  arise from cells of the ovary, most commonly, tumors arise from the epithelium or lining cells of the ovary.  Ovarian cancer risk is positively associated with higher consumption of dietary cholesterol and eggs, and inversely associated with a higher intake of vegetables. High consumption of fats may increase circulating estrogen levels, thus increasing the possibility of cell damage and proliferation that is responsible for cancerous growth. Material & Methods: The present study was conducted at Geetanjali Medical College and Hospital, Udaipur (Rajasthan). Total  100 cases (females) attending the obstetrics and gynecology department for some gynecological and other problem  were selected for this study between the age of 40-60 years, who were attending cancer centre at GEETANJALI MEDICAL COLLEGE AND  HOSPITAL, Udaipur (Rajasthan).                GROUP I: - It consisted of healthy females control subjects (n=50) .By routine examination and tests, we ensured that all the subjects were healthy and there were no signs and symptoms or history of ovarian tumor and diseases GROUP II: - It consisted of ovarian cancer females subjects (n=50) with a history of ovarian tumor. Results:   Higher level of cholesterol, LDL, VLDL and low level of HDL are found in ovarian cancer patients. Conclusion: The present study we highlights the importance and role of serum lipid profile in diagnosis, prognosis and recurrence of the disease. The study shows that serum level of cholesterol, LDL, VLDL was elevated in  patients of ovarian cancer while low level of HDL are found in ovarian cancer patients. Key words: lipid profile, ovarian cancer.

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