A Recipe for Successful Metastasis: Transition and Migratory Modes of Ovarian Cancer Cells.

One of the characteristic features of ovarian cancer is its early dissemination. Metastasis and the invasiveness of ovarian cancer are strongly dependent on the phenotypical and molecular determinants of cancer cells. Invasive cancer cells, circulating tumor cells, and cancer stem cells, which are responsible for the metastatic process, may all undergo different modes of transition, giving rise to mesenchymal, amoeboid, and redifferentiated epithelial cells. Such variability is the result of the changing needs of cancer cells, which strive to survive and colonize new organs. This would not be possible if not for the variety of migration modes adopted by the transformed cells. The most common type of metastasis in ovarian cancer is dissemination through the transcoelomic route, but transitions in ovarian cancer cells contribute greatly to hematogenous and lymphatic dissemination. This review aims to outline the transition modes of ovarian cancer cells and discuss the migratory capabilities of those cells in light of the known ovarian cancer metastasis routes.

Serum Proteomic Profiles of Patients with High and Low Risk of Endometrial Cancer Recurrence.

Endometrial cancer is the most common gynecological cancer worldwide. Classifying endometrial cancer into low- or high-risk groups based on the following features is recommended: tumor grade, lymphovascular space invasion, myometrial involvement, and non-endometrioid histology. Despite the recent progress in molecular profiling of endometrial cancer, a substantial group of patients are misclassified based on the current criteria. This study aimed to identify proteins that could be used as biomarkers for the stratification of endometrial cancer patients into low- or high-risk groups. The proteomic analysis of serum samples from endometrial cancer patients was performed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The data were then analyzed using chemometric algorithms to identify potential biomarkers. Nineteen precursor ions were identified as fragments of eighteen proteins which included (1) connective tissue matrix proteins, (2) cytoskeletal proteins, and (3) innate immune system molecules and stress proteins. These biomarkers could be used to stratify the high- and low-risk patients, thus enabling more precise treatment decisions.

Choriocarcinoma complicated with intra-abdominal and intrapleural hemorrhage in pregnancy - case report.

Background: Choriocarcinoma is a rare neoplasm, exceptionally uncommon during an ongoing pregnancy. The disease often has a metastatic character, causing severe symptoms from various anatomic sites like the lungs, central nervous system, vagina, pelvis, or liver. Due to the condition's rarity, evidence on how to treat the choriocarcinoma originating during pregnancy remains scarce. Case presentation: Here, we present a case of a patient who developed choriocarcinoma before the 29th week of gestation. The neoplasm had a metastatic character, resulting in hemorrhage complicated by a hypovolemic shock. The patient underwent an emergency cesarean section and several surgeries to stop the massive hemorrhage. The treatment of the choriocarcinoma included chemotherapy with methotrexate followed by an EMA-CO regimen. The patient had a complete response to the therapy. The neonate suffered from complications related to prematurity. Conclusion: Metastatic choriocarcinoma can be a diagnostic and therapeutic challenge during ongoing pregnancy. Treatment of the disease can be associated with severe complications, but a complete response to chemotherapy is possible with a favorable long-term prognosis.

Cancer Stem Cell Markers-Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis.

Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients' clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10-3; p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10-3). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response.

The Prognostic Value of Cancer Stem Cell Markers (CSCs) Expression-ALDH1A1, CD133, CD44-For Survival and Long-Term Follow-Up of Ovarian Cancer Patients.

Recurrent disease and treatment-associated chemoresistance are the two main factors accounting for poor clinical outcomes of ovarian cancer (OC) patients. Both can be associated with cancer stem cells (CSCs), which contribute to cancer formation, progression, chemoresistance, and recurrence. Hence, this study investigated whether the expression of known CSC-associated markers ALDH1A, CD44, and CD133 may predict OC patient prognosis. We analyzed their expression in primary epithelial ovarian cancer (EOC) patients using immunohistochemistry and related them to clinicopathological data, including overall survival (OS) and progression-free survival (PFS). Expression of ALDH1A1 was detected in 32%, CD133 in 28%, and CD44 in 33% of cases. While Kaplan-Meier analysis revealed no association of the expression of CD133 and CD44 with PFS and OS, ALDH1A1-positive patients were characterized with both significantly shorter OS (p = 0.00022) and PFS (p = 0.027). Multivariate analysis demonstrated that the expression of ALDH1A1, FIGO stage III-IV, and residual disease after suboptimal debulking or neoadjuvant chemotherapy correlated with shorter OS. The results of this study identify ALDH1A1 as a potential independent prognostic factor of shorter OS and PFS in EOC patients. Therefore, targeting ALDH1A1-positive cancer cells may be a promising therapeutic strategy to influence the disease course and treatment response.

Extracellular Matrix Modulates Outgrowth Dynamics in Ovarian Cancer.

Ovarian carcinoma (OC) forms outgrowths that extend from the outer surface of an afflicted organ into the peritoneum. OC outgrowth formation is poorly understood due to the limited availability of cell culture models examining the behavior of cells that form outgrowths. Prompted by immunochemical evaluation of extracellular matrix (ECM) components in human tissues, laminin and collagen-rich ECM-reconstituted cell culture models amenable to studies of cell clusters that can form outgrowths are developed. It is demonstrated that ECM promotes outgrowth formation in fallopian tube non-ciliated epithelial cells (FNE) expressing mutant p53 and various OC cell lines. Outgrowths are initiated by cells that underwent outward translocation and retained the ability to intercalate into mesothelial cell monolayers. Electron microscopy, optical coherence tomography, and small amplitude oscillatory shear experiments reveal that increased ECM levels led to increased fibrous network thickness and high shear elasticity of the microenvironment. These physical characteristics are associated with outgrowth suppression. The low ECM microenvironment mimicks the viscoelasticity of malignant peritoneal fluid (ascites) and supports cell proliferation, cell translocation, and outgrowth formation. These results highlight the importance of the ECM microenvironment in modulating OC growth and can provide additional insights into the mode of dissemination of primary and recurrent ovarian tumors.

Phoenixin as a New Target in the Development of Strategies for Endometriosis Diagnosis and Treatment.

Small integral membrane protein 20/phoenixin (SMIM20/PNX) and its receptor GPR173 (G Protein-Coupled Receptor 173) play a role in the regulation of the hypothalamic-pituitary-gonadal axis (HPG). The aim of the study was to determine PNX, FSH, LH, and 17ß-estradiol association in women with endometriosis, and the expression of SMIM20/PNX signaling via GPR173. Serum PNX, FSH, LH, and 17ß-estradiol concentrations were measured by enzyme and electrochemiluminescence immunoassay. SMIM20/PNX and GPR173 expression in the eutopic and ectopic endometrium was assessed by qPCR and immunohistochemistry. Reduced PNX level, increased LH/FSH ratio and elevated 17ß-estradiol concentration were found in patients with endometriosis. No differences in SMIM20 expression were observed between the studied endometria. GPR173 expression was lower in ectopic than in eutopic endometria. SMIM20 expression was mainly restricted to stroma. GPR173 was detected in some eutopic and ectopic stromal cells and in eutopic glandular epithelial cells. Discriminant analysis indicates the diagnostic relevance of PNX and LH/FSH ratio in patients with endometriosis. In women with endometriosis, reduced PNX levels and GPR173 expression may be responsible for HPG axis dysregulation. These new insights may contribute to a better understanding of the pathophysiology of endometriosis and provide the basis for a new strategy for diagnosis and treatment of endometriosis.

Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review.

Gynecological and breast cancers still remain a significant health problem worldwide. Diagnostic methods are not sensitive and specific enough to detect the disease at an early stage. During carcinogenesis and tumor progression, the cellular need for DNA and protein synthesis increases leading to changes in the levels of amino acids. An important role of amino acids in many biological pathways, including biosynthesis of proteins, nucleic acids, enzymes, etc., which serve as an energy source and maintain redox balance, has been highlighted in many research articles. The aim of this review is a detailed analysis of the literature on metabolomic studies of gynecology and breast cancers with particular emphasis on alterations in free amino acid profiles. The work includes a brief overview of the metabolomic methodology and types of biological samples used in the studies. Special attention was paid to the possible role of selected amino acids in the carcinogenesis, especially proline and amino acids related to its metabolism. There is a clear need for further research and multiple external validation studies to establish the role of amino acid profiling in diagnosing gynecological and breast cancers.

Serum Free Amino Acid Profiling in Differential Diagnosis of Ovarian Tumors-A Comparative Study with Review of the Literature.

Proper preoperative ovarian cancer (OC) diagnosis remains challenging. Serum free amino acid (SFAA) profiles were investigated to identify potential novel biomarkers of OC and assess their performance in ovarian tumor differential diagnosis. Serum samples were divided based on the histopathological result: epithelial OC (n = 38), borderline ovarian tumors (n = 6), and benign ovarian tumors (BOTs) (n = 62). SFAA profiles were evaluated using aTRAQ methodology based on high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Levels of eleven amino acids significantly differed between OC+borderline and BOTs. The highest area under the receiver operating characteristic curve (AUC of ROC) (0.787) was obtained for histidine. Cystine and histidine were identified as best single markers for early stage OC/BOT and type I OC. For advanced stage OC, seven amino acids differed significantly between the groups and citrulline obtained the best AUC of 0.807. Between type II OC and BOTs, eight amino acids differed significantly and the highest AUC of 0.798 was achieved by histidine and citrulline (AUC of 0.778). Histidine was identified as a potential new biomarker in differential diagnosis of ovarian tumors. Adding histidine to a multimarker panel together with CA125 and HE4 improved the differential diagnosis between OC and BOTs.

Granzyme B in peripheral blood mononuclear cells as a measure of cell-mediated immune response in paraneoplastic neurological syndromes and malignancy.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) may coexist with ovarian or lung cancers. Some tumors coexisting with PNS are smaller and have a better prognosis than tumors without PNS. PNS may constitute an opportunity to observe a natural immune antitumor response. We aimed to investigate a cytotoxic immune response by measuring granzyme B (GrB) in peripheral blood mononuclear cells (PBMC) in patients affected with ovarian or lung malignancy, with and without accompanying PNS. METHODS: We enrolled patients with: nonmalignant lesions (n = 21), ovarian cancer (n = 19), lung cancer (n = 57), and PNS (n = 30). PBMC were isolated by density gradient centrifugation with Ficoll-Paque. We evaluated the expression of GrB in PBMC lysates by ELISA and normalized to protein content as measured by the Lowry method. RESULTS: GrB levels in PBMC in the group with malignant tumors-median 1650 pg/mg protein (interquartile range 663-3260 pg/mg) and in patients with PNS-median 1890 pg/mg protein (range 1290-2640 pg/mg) was lower than in control group with nonmalignant lesions-median 5240 pg/mg protein (range 2160-7440 pg/mg), p = 0.0003 and p = 0.0038, respectively. The differences in GrB levels in PBMC between these groups were independent of epidemiological factors-age, sex, body mass index (BMI), and the number of immune cells, as confirmed by multiple regression analysis. Within the group of patients with malignancy and PNS, GrB levels in PBMC were elevated if onconeural antibodies were detected (2610; 2390-3700 pg/mg protein) as compared to patients without antibodies (1680; 970-1880 pg/mg protein, p = 0.035). GrB in PBMC was higher if the malignancy was diagnosed at the low (3060; 2120-5220 pg/mg protein) as compared to the high stage (1330; 348-2140, p = 0.00048). In patients with lung cancer, the expression of GrB in PBMC was lower (1430; 635-2660 pg/mg protein) than in the group with ovarian cancer (2580; 1730-3730, p = 0.02). CONCLUSION: The cytotoxic response measured in peripheral blood by GrB in PBMC is impaired both in the course of malignancy and PNS. Levels of GrB in PBMC were higher if onconeural antibodies were detected. Tracking reactive immune responses, such as GrB in PBMC may have diagnostic and monitoring value in malignancy and PNS.

Assessment of gynecological and lifestyle-related risk factors of ovarian cancer.

INTRODUCTION: Ovarian cancer remains the most lethal gynecological cancer. Assessment of gynecological and lifestyle-related risk factors is essential to reduce the occurrence and the mortality rate of the disease. MATERIAL AND METHODS: Surveys were collected among 71 patients with ovarian cancer and 76 women without gynecological cancer. Questionnaires included questions about medical history and lifestyle in the past. RESULTS: The control group had breastfed longer (p = 0.034) and used hormonal contraception more often (p = 0.00037) than the study group. The patients in FIGO (French. Fédération internationale de gynécologie et d'obstétrique) stage III or IV had a higher number of lifetime ovulatory cycles (p = 0.001) than the control group. Women at FIGO stage IV slept significantly less than patients at other stages (p = 0.0026). Oncological patients reporting sedentary work more often were diagnosed at advanced stages (p = 0.00328). The risk of ovarian cancer was 0.046 times smaller for women who had given birth (p = 0.025), 0.94 times smaller for every one month longer breastfeeding (p = 0.0428), 0.677 times smaller for every one year older age at menarche (p = 0.0152), 0.106 times smaller for women who had used hormonal contraception (p = 0.0019), and 5.46 times higher for women who ever worked night shifts (p = 0.0128). CONCLUSIONS: Our study proves the importance of both gynecological and lifestyle-related risk factors of ovarian cancer and their impact on its prevalence. Lifestyle-related risk factors cannot be ignored, as they might have a direct influence on the aggravation of the risk of this type of cancer. Promoting an adequate amount of physical activity and sleep, breastfeeding, and having children could improve the detection and treatment of ovarian cancer in general.

MALDI-MSI-A Step Forward in Overcoming the Diagnostic Challenges in Ovarian Tumors.

This study presents the use of matrix-assisted laser desorption and ionization mass spectrometry imaging (MALDI-MSI) directly on the tissue of two ovarian tumors that often present a diagnostic challenge, a low-grade serous borderline ovarian tumor and ovarian fibrothecoma. Different spatial distribution of m/z values within the tissue samples was observed, and regiospecific peaks were identified. Among the 106 peaks in the borderline ovarian tumor five, regiospecific peaks (m/z: 2861.35; 2775.79; 3368.34; 3438.43; 4936.37) were selected using FlexImaging software. Subsequently, the distribution of those selected peaks was visualized on the fibrothecoma tissue section, which demonstrated the differences in the tissue homo-/heterogeneous structure of both tumors. The comparison with the histopathological staining of the ovarian borderline tumor tissue section, obtained during serial sectioning, showed a close correlation of the molecular map with the morphological and histopathological features of the tissue and allowed the identification of different tissue types within the sample. This study highlights the potential significance of MSI in enabling morphological characterization of ovarian tumors as well as correct diagnosis and further prognosis than thus far seen in the literature. Osteopontin, tropomyosin and orosomucoid are only a couple of the molecules investigated using MALDI-MSI in ovarian cancer research. This study, in line with the available literature, proves the potential of MALDI-MSI to overcome the current limitations of classic histopathological examination giving a more in-depth insight into the tissue structure and thus lead to the more accurate differential diagnosis of ovarian tumors, especially in the most challenging cases.

Human Epididymis Protein 4 (HE4) Reference Limits in Polish Population of Healthy Women, Pregnant Women, and Women with Benign Ovarian Tumors.

OBJECTIVES: Defining precisely the normal range of HE4 protein is crucial for the proper interpretation of tumor marker results and for a more efficient diagnosis of ovarian malignancy. The aim of our study was to evaluate a reference limit of HE4 protein in a population to promote and facilitate the common use of HE4 protein assays. We also tried to identify potential association of HE4 levels with other conditions such as smoking, age, BMI, and creatinine levels. METHODS: Blood samples were collected from 617 patients divided into three groups: healthy, pregnant, and with benign ovarian tumors. Serum HE4 concentrations were measured following a standard procedure. HE4 reference ranges for each group and association of HE4 levels with BMI, creatinine, and smoking were investigated. RESULTS: HE4 reference limit for healthy patients equals 85 pmol/l, which becomes 73 pmol/l and 93 pmol/l for pre and postmenopausal subgroups, respectively. There is a statistically significant correlation between HE4 serum level and smoking (p = 0.000001) and there is no correlation with creatinine. But if we take into account age and smoking, in multivariate analysis, there is a correlation. For pregnant, the upper limit values of normal HE4 levels are 55 pmol/l (median = 40 pmol/l), 80 pmol/l (median = 43 pmol/l), and 106 pmol/l (median = 53 pmol/l) for the first, second, and third trimesters, respectively. CONCLUSIONS: HE4 protein value strongly depends on the patient's age and smoking. The serum concentration of HE4 marker increases with the duration of pregnancy. Understanding the normal range of HE4 protein enables the correct interpretation of marker measurements. This may result in an earlier and more effective diagnosis of ovarian cancer.

Regulation of human chorionic gonadotropin beta subunit expression in ovarian cancer.

PURPOSE: Expression of human chorionic gonadotropin beta subunit by cancers is extensively documented, yet regulation of the multiple genes that can code for this protein is poorly understood. The aim of the study was to examine the mechanisms regulating CGB gene expression in ovarian cancer. METHODS: Expression of CGB genes and SP1, SP3, TFAP2A transcription factor genes was evaluated by RT-qPCR. The methylation status of CGB genes promoter regions was examined by methylation-specific PCR. RESULTS: mRNA arising from multiple CGB genes was detected in both ovarian control and malignant tissues. However, expression of CGB3-9 genes was shown to be significantly higher in malignant than healthy ovarian tissues. CGB1 and CGB2 transcripts were shown to be present in 20% of ovarian cancers, but were not detected in any of the control samples. Malignant tissues were characterized by DNA demethylation of CGB promoter regions. In ovarian cancer CGB expression positively correlated with TFAP2A transcripts level and expression of TFAP2A transcription factor was significantly higher in cancer than in control tissues. In contrast SP3 expression level was significantly lower in ovarian tumours than in control ovarian tissue. CONCLUSIONS: In ovarian cancers increased expression of human chorionic gonadotropin beta subunit is associated with demethylation of CGB promoter regions. CGB3-9 expression level strongly correlates with expression of the TFAP2A transcription factor. Presence of mRNA arising from CGB1 and CGB2 genes appears to be a unique feature of a subset of ovarian cancers.

Semaphorin 3A (SEMA3A), protocadherin 9 (PCdh9), and S100 calcium binding protein A3 (S100A3) as potential biomarkers of carcinogenesis and chemoresistance of different neoplasms, including ovarian cancer - review of literature.

Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Its high mortality rate results from lack of adequate and sensitive methods allowing for the detection of the early stages of the disease, as well as low efficiency of the treatment, caused by the cytotoxic drug resistance of cancer cells. Unfortunately, tumours are able to develop new pathways and protective mechanisms that allow them to survive toxic conditions of chemotherapy. Therefore, intensive search for new genes and proteins involved in resistance to cytotoxic drugs is still needed, especially from a clinical point of view. The article presents an overview of the available literature on the role of semaphorin 3A (SEMA3A), protocadherin 9 (PCDH9), and S100 calcium binding protein A3 (S100A3) in carcinogenesis and chemoresistance of various tumors including ovarian cancer. As it turns out, the role of described genes/proteins is not limited only to their native biological activity but they function also as an oncogenic or suppressor factors in the tumor development. Moreover, they can also play an important role in development of drug resistance, as it was shown in ovarian cancer cell lines.

The value of an initial drop in human Chorionic gonadotropin levels in predicting a response to methotrexate in women with low-risk gestational trophoblastic neoplasia.

OBJECTIVES: The early identification of patients who are being treated for low-risk gestational trophoblastic neoplasia (LRGTN) with single-agent chemotherapy, who are at high risk of developing chemoresistance, is of crucial importance. The aim of our research was to evaluate the pretreatment beta subunit of human chorionic gonadotropin (ßhCG) concentration and its decrease after the administration of the first course of methotrexate (MTX) in predicting later chemo-resistance to single-agent chemotherapy. MATERIAL AND METHODS: A total of 46 patients diagnosed with LRGTN treated with a 5-day methotrexate (MTX) regimen were retrospectively studied. 24 of the patients were successfully cured with only MTX therapy (MTX group). The disease was considered resistant in the remaining 22 patients who, after MTX therapy, required further chemotherapy with an EMA/CO regimen (EMA/CO group). To compare changes in the ßhCG concentrations between the two courses of treatment (and the two groups), we calculated the percentage of decline. We determined the specificity and sensitivity of the initial ßhCG level and its percentage decline, as a potential predictor of the need for a future EMA/CO regimen. For diagnostic purposes, ßhCG levels were measured before the first and second administrations of MTX with a commercial ELISA kit. RESULTS: In the EMA/CO group, we found the initial ßhCG level before the first MTX dose was higher (median = 6275 mIU/mL, range: 21.53-192.610.0 mIU/mL) than in the MTX group (median = 532 mIU/mL, range: 56.5 mIU/mL-360.397.0 mIU/mL) (p = 0.034, Mann-Whitney test). The percentage decreases in the ßhCG values relative to the initial concentrations were higher in the MTX group (median decrease = 82.7%, range: from 13.3% to 99.9%) than in the EMA/CO group (median de- crease = 71.1%, range: from an increase of 56.1% to a decrease of 97.1%) (p = 0.0079, Mann-Whitney test). An analysis of the ROC curves implied optimal cutoff values for the initial ßHCG (6054 IU, sensitivity = 55%, specificity = 86%) and the percentage change in ßhCG levels (decrease by 76.5%, sensitivity = 72%, specificity = 71%). CONCLUSIONS: Women with initially higher ßhCG levels have a greater risk of developing MTX chemo resistance. It would be advantageous to consider administering an EMA/CO regimen in women with LRGTN when their initial ßhCG levels are greater than 6000.

The role of artificial nutrition in gynecological cancer therapy.

Cancer patients are at risk of developing malnutrition from underlying disease as well as from cancer treatment. Moreover, weight loss is considered as a predictive factor for disease progression and shorter survival time. As many as 10-20% of patients with cancer die from the results of malnutrition, instead of from the cancer itself. In the case of cancer-related malnutrition, it is necessary to quickly implement individualized nutritional support depending on the type and stage of the disease, metabolic changes, the patient's condition, expected survival and the function of the gastrointestinal tract. Artificial nutrition reduces the side effects of chemotherapy and improves immunity. Perioperatively it reduces the risk of infection, facilitates wound healing and shortens the length of hospitalization, thereby reducing the costs of the treat- ment. Initially, a malnourished patient, without gastrointestinal dysfunction, qualifies for nutritional counseling. When the energy needs cannot be met by normal feeding, nutritional supplements, taken orally, are recommended. The next step is to feed the patient by nasogastric tube or percutaneous endoscopic gastrostomy. Parenteral nutrition, which results in more side effects, is only started when enteral nutrition is insufficient to ensure adequate nutritional status or in cases of gastrointestinal tract obstruction. The benefit of parenteral nutrition is that it especially provides for those patients with gynaecological cancer who have radiation-induced intestinal damage and post-surgical complications such as short bowel syndrome. Palliative nutrition must to relieve hunger and thirst. Nutritional interventions should be individualized and focused on the changing nutrient needs of the patient and should be supported by physical activity. Regular assessment of the nutritional status of the patient should be an inherent element of the oncological treatment.

Significance of BRCA1 expression in breast and ovarian cancer patients with brain metastasis - A multicentre study.

PURPOSE: Cerebral metastases develop in 10-30% of patients with breast cancer (BC) and in around 3.3 to 4% of patients with ovarian cancer (OC). The aim of the multicenter study is to investigate the correlation between the expression of estrogen alpha receptors (ERα), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), stromal cell-derived factor 1 (SDF1) and its receptor C-X-C chemokine receptor type 4 (CXCR4), breast cancer metastasis suppressor 1 (BRMS1), astrocyte elevated gene 1 (AEG1), depending on the status of BRCA1 protein, in patients suffering from OC and BC with brain metastases. PATIENTS AND METHODS: The analysis included 51 patients: 29 with BC and 22 with OC, in whom brain metastases were disclosed. RESULTS: In most patients (65.5% of BC patients and 68.2% of patients with OC tumors) BRCA1 protein loss was found. No correlation was disclosed between the levels of ERα, PR receptors, HER2, SDF1, CXCR4, AEG1, BRMS1 and BRCA1 status, patient age, stage of disease advancement, grade of histological maturity of the cells, presence of metastases to lymph nodes. A statistically significant correlation was disclosed between the negative expression of PR receptors and a high expression of CXCR4 in patients with BC. High values of the AEG1 protein (linked to metastases) were detected alongside a high expression of BRMS1 (a suppressor of metastases). CONCLUSIONS: Patients with BC and OC and brain metastases have a frequent loss of BRCA1 expression. The role of ERα, PR, HER2, SDF1, CXCR4, AEG1, BRMS1 in metastatic process needs further studies.

Wide spectrum targeted metabolomics identifies potential ovarian cancer biomarkers.

AIMS: Despite of almost a hundred years of research on cancer metabolism, the biological background of cancerogenesis and cancer-related reprogramming of metabolism remains not fully understood. In order to comprehensively and effectively diagnose and treat the deadliest diseases, the mechanisms underlying these diseases have to be discovered urgently. Among the gynecological malignancies, ovarian cancer is the most common cause of death. The aim of the study was to search for potential cancer-related differences in concentrations of metabolites and interactions between them in serum of women with ovarian cancer and benign ovarian tumor in comparison with healthy controls using targeted metabolomics. These metabolites might serve as biomarkers in the future. MAIN METHODS: We used wide spectrum targeted metabolomics to evaluate serum concentrations of metabolites related to ovarian cancer and compared them against benign ovarian tumors and healthy controls. The measurements were performed using high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry technique in highly-selective multiple reaction monitoring mode. KEY FINDINGS: In this study we confirmed our previous findings about the role of histidine and citrulline in ovarian cancer as well as we indicated new lipid compounds (lysoPC a C16:1, PC aa C32:2, PC aa C34:4 and PC aa C 36:6) potentially involved in cancer metabolism. SIGNIFICANCES: We indicated interesting interactions between metabolites for further in-depth research which could potentially serve as clinically useful biomarkers in future. Moreover, the presented work attempts to visualize a possible 3D-network of relationships between the molecules found to be related to ovarian malignancy.

MALDI-TOF-MS Analysis in the Identification of Urine Proteomic Patterns of Gestational Trophoblastic Disease.

Gestational trophoblastic disease (GTD) is a group of highly aggressive, rare tumors. Human chorionic gonadotropin is a common biomarker used in the diagnosis and monitoring of GTD. To improve our knowledge of the pathology of GTD, we performed protein-peptide profiling on the urine of patients affected with gestational trophoblastic neoplasm (GTN). We analyzed urine samples from patients diagnosed with GTN (n = 26) and from healthy pregnant and non-pregnant controls (n = 17) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Ions were examined in a linear mode over a m/z range of 1000⁻10,000. All GTN urine samples were analyzed before and after treatment and compared with those of the controls. The statistical analyses included multivariate classification algorithms as well as ROC curves. Urine sample analyses revealed there were significant differences in the composition of the ions between the evaluated groups. Comparing the pre-treatment and group with the pregnant controls, we identified two discriminatory proteins: hemoglobin subunit α (m/z = 1951.81) and complement C4A (m/z = 1895.43). Then, comparing urine samples from the post-treatment cases with those from the non-pregnant controls, we identified the peptides uromodulin fragments (m/z = 1682.34 and 1913.54) and complement C4A (m/z = 1895.43).