Redox Biomarkers and Matrix Remodeling Molecules in Ovarian Cancer.

Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress intensity can determine the degree of cellular injury and often the severity of redox-mediated chemoresistance. The study group comprised 27 patients with serous OC of which 18% were classified as Federation of Gynecology and Obstetrics (FIGO) stages I/II, while the rest were diagnosed grades III/IV. The control group comprised of 15 ovarian tissue samples. The results were compared with genetic data from The Cancer Genome Atlas. Nitro-oxidative stress, inflammation and apoptosis biomarkers were measured colorimetrically/fluorometrically or via real-time PCR in the primary ovarian tumor and healthy tissue. Stratification of patients according to FIGO stages revealed that high-grade carcinoma exhibited substantial alterations in redox balance, including the accumulation of protein glycoxidation and lipid peroxidation products. TCGA data demonstrated only limited prognostic usefulness of the studied genes. In conclusion, high-grade serous OC is associated with enhanced tissue oxidative/nitrosative stress and macromolecule damage that could not be overridden by the simultaneously augmented measures of antioxidant defense. Therefore, it can be assumed that tumor cells acquire adaptive mechanisms that enable them to withstand the potential toxic effects of elevated reactive oxygen species.

Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications.

Ovarian cancer is a non-homogenous malignancy. High-grade serous carcinoma (HGSC) is the most common subtype, and its drug resistance mechanisms remain unclear. Despite the advantages of modern pharmacotherapy, high-grade ovarian cancer is associated with a poor prognosis and research into targeted therapies is in progress. The aim of the study was to assess the dominant energy substrate transport mechanism in ovarian cancer cells and to verify whether genomic aberrations could predict clinical outcomes using the Cancer Genome Atlas (TCGA) dataset. Total RNA was extracted from HGSC frozen tissues, and the expression of selected genes was compared to respective controls. GLUT1, FABPpm, MCT4 and SNAT1 genes were significantly overexpressed in carcinomas compared with controls, while expression of CD36/SR-B2, FATP1, FABP4, GLUT4, ASCT2 and LPL was decreased. No differences were found in FATP4, LAT1, MCT1 and FASN. The transcript content of mitochondrial genes such as PGC-1α, TFAM and COX4/1 was similar between groups, while the ß-HAD level declined in ovarian cancer. Additionally, the MCT4 level was reduced and PGC-1α was elevated in cancer tissue from patients with 'small' primary tumor and omental invasion accompanied by ascites as compared to patients that exhibited greater tendencies to metastasize to lymph nodes with clear omentum. Based on TCGA, higher FABP4 and LPL and lower TFAM expression indicated poorer overall survival in patients with ovarian cancer. In conclusion, the presented data show that there is no exclusive energy substrate in HGSC. However, this study indicates the advantage of glucose and lactate transport over fatty acids, thereby suggesting potential therapeutic intervention targets to impede ovarian cancer growth.

The Exploration of Chemokines Importance in the Pathogenesis and Development of Endometrial Cancer.

Endometrial cancer (EC) is one of the most frequent female malignancies. Because of a characteristic symptom, vaginal bleeding, EC is often diagnosed in an early stage. Despite that, some EC cases present an atypical course with rapid progression and poor prognosis. There have been multiple studies conducted on molecular profiling of EC in order to improve diagnostics and introduce personalized treatment. Chemokines-a protein family that contributes to inflammatory processes that may promote carcinogenesis-constitute an area of interest. Some chemokines and their receptors present alterations in expression in tumor microenvironment. CXCL12, which binds the receptors CXCR4 and CXCR7, is known for its impact on neoplastic cell proliferation, neovascularization and promotion of epidermal-mesenchymal transition. The CCL2-CCR2 axis additionally plays a pivotal role in EC with mutations in the LKB1 gene and activates tumor-associated macrophages. CCL20 and CCR6 are influenced by the RANK/RANKL pathway and alter the function of lymphocytes and dendritic cells. Another axis, CXCL10-CXCR3, affects the function of NK-cells and, interestingly, presents different roles in various types of tumors. This review article consists of analysis of studies that included the roles of the aforementioned chemokines in EC pathogenesis. Alterations in chemokine expression are described, and possible applications of drugs targeting chemokines are reviewed.

Factors Predisposing to Burnout Syndrome among Medical Staff Participating in Complex Surgical Processes.

BACKGROUND: Burnout syndrome is a serious manifestation of distress among health-care professionals. OBJECTIVE: Due to the specific nature of work in operating theaters, factors that affect the staff performance and therefore predispose to burnout syndrome were assessed. METHODS: Based on the original questionnaire, 254 respondents working in the operating theaters of the university hospital, appraised levels of work satisfaction, sources of stress, and psychosocial burden. Work-related mental stress was assessed using the Meister's questionnaire. Burnout levels were evaluated in the group extended to 316 employees with Maslach Burnout Inventory. RESULTS: Work satisfaction analysis indicated unsatisfactory management and remuneration as the negative agents. The majority of the respondents emphasized the maintenance of medical records as a prominent stress factor. A large number of participants (n = 221; 87%) described work as emotionally burdensome. The results showed that the highest burden was related to the following variables: time pressure, responsibility, problems, and conflicts. The examined group was qualified to the second degree of mental load related to the work. Similarly, the entire group reached a high level of emotional exhaustion. CONCLUSIONS: Presented data indicate the need of evaluation to minimize occupational burnout problem.

Obesity and Energy Substrate Transporters in Ovarian Cancer-Review.

Ovarian cancer is the seventh most common cancer in women. It is characterized by a high mortality rate because of its aggressiveness and advanced stage at the time of diagnosis. It is a nonhomogenous group of neoplasms and, of which the molecular basics are still being investigated. Nowadays, the golden standard in the treatment is debulking cytoreductive surgery combined with platinum-based chemotherapy. We have presented the interactions and the resulting perspectives between fatty acid transporters, glucose transporters and ovarian cancer cells. Studies have shown the association between a lipid-rich environment and cancer progression, which suggests the use of correspondent transporter inhibitors as promising chemotherapeutic agents. This review summarizes preclinical and clinical studies highlighting the role of fatty acid transport proteins and glucose transporters in development, growth, metastasizing and its potential use in targeted therapies of ovarian cancer.

Two Concurrent Cancers in a 19-Year-Old Patient: Yolk Sac Ovarian Tumor and Metastatic Gastrointestinal Tract Malignancy-Case Report.

BACKGROUND: Two concurrent malignancies present in a young person is an extremely rare condition. Diagnoses of gastric cancer primarily concern older patients. There are very few reports of concomitant Krukenberg tumor and germ-cell ovarian malignancy. CASE: A 19-year-old girl was admitted to the gynecologic oncology department with symptoms of advanced malignancy. Radiological imaging revealed disseminated neoplastic disease with bulky adnexal tumors. Cytoreductive surgery was performed, achieving no visible disease (T = 0 cm). The final pathology report confirmed metastatic mixed adenoneuroendocrine carcinoma (MANEC) in both ovaries, originating from the gastrointestinal tract. Moreover, the primary germ cell yolk sac tumor was found in the left ovary. CONCLUSION: In cases of concomitant gastric and ovarian tumors, metastatic disease (Krukenberg tumor) should be considered in the differential diagnosis. This concerns even adolescent patients. In particular cases, including tumors with germ cell components, primary debulking surgery is crucial for prognosis.