Role of cancer stem cells and microRNA in resistance to chemotherapy in patients with ovarian cancer.

Despite the introduction of "the golden standard" in chemotherapy for ovarian cancer (taxanes/platinum), a relapse of the disease is noted in 80% of women treated in this manner. Studies on ovarian cancer stem cells (CSCs) and attempts at treatment using salinomycin, isolated from Streptonzyces albus and endotoxin of Clostridium peifringens, are promising, in particular because CSC markers have been identified. Resistence of ovarian cancer cells to paclitaxel and cisplatin is associated with a reduced expression of miR-30c, miR-130, and miR335, which results in activation of M-CSF, the known factor of resistance to cytostatic drugs. In clear cell ovarian cancer, a reduced expression of miR-449 was detected, which may lead to overexpression of MET phenotype, typical for chemoresistant ovarian cancer. MicroRNAs remain in investigations, but their involvement in the control of genes linked to the development of the cancer and its progression seems to offer the promise of a targeted therapy.

The role of overweight and obesity in selected gynecological malignancies.

A review of literature data related to the effects of overweight and obesity on the development and course of selected gynecological malignancies: endometrial, breast and ovarian cancer is presented. Three hypotheses are included in an attempt to explain this rela- tionship: the adipokinine hypothesis, a hypothesis involving the effects of excessive estrogen levels, and the insulin hypothesis.

Multiple primary cancers in BRCA 1/2 carriers - A review of literature and our observations.

An increasing number of patients with diagnosed synchronous or metachronous neoplasms that arc gene as well as non-gene dependent which are associated with the development of new oncological treatment, and environmental factors, prompted the authors of this study to conduct an analysis in a narrow group of patients with multiple cancers and simultaneous BRCA1I mutations (confirmed by genetic analysis). BRCA1 mutation, as well as multiple cancers were found in seven patients treated between 2007 and 2013. The patients diagnosed with a second cancer shared a uniquely common trait - a 5382insC mutation. The study describes four patients that did not carry a BRCA 1/2 mutation, yet were diagnosed with multiple cancers. A brief review of literature was performed concerning multiple cancers in women.

Evaluation of residual tumor locations in advanced ovarian cancer patients after incomplete primary cytoreduction.

BACKGROUND: Nowadays complete primary cytoreduction can be achieved in a large number of patients suffering from advanced ovarian cancer. However, there is a group of patients in whom complete tumor resection remains impossible. The authors analyzed the intraoperative limiting factors in patients with residual tumor after primary surgery treated in the present institution. MATERIALS AND METHODS: Patients with advanced epithelial ovarian cancer (FIGO Stage IIIB-IV), who underwent primary incomplete surgery in the present institution between 2006 and 2008 were included in this study. Patients' records were evaluated regarding to intraoperative findings and final surgical results. RESULTS: The authors identified 39 eligible patients in their registry. Twenty-six (66.7%) patients underwent surgery with residual tumor < 1 cm and 13 (33.3%) ≥ 1 cm. The most frequent location of residual tumor limiting complete surgery was disseminated bowel carcinomatosis in 34 (87.2%) patients. Moreover significant differences in tumor residuals locations and operative time between patients with residuals < 1 cm and ≥ 1 cm were reported (p < 0.05). CONCLUSIONS: The most frequent reason for incomplete primary cytoreduction remains disseminated carcinomatosis. However, in patients with residuals under one cm, its frequency is significantly higher. The complication rate is comparable in patients independently of residual tumor < 1 cm and ≥ 1 cm. Therefore the cytoreductive efforts should be made even in primarily not completely operated patients in order to achieve residuals under one cm.

Late recurrence of ovarian cancer: a literature review and description of two cases.

Ovarian cancer is not the most frequent malignancy of female reproductive system, but it causes many deaths in women with this diagnosis. Mostly of the patients with ovarian cancer will have recurrence after first-line standard treatment containing surgery and chemotherapy. This article presents two cases with late recurrence in women with ovarian cancer; both were nine years after the first diagnosis and both were operated and received second-line chemotherapy. The authors reviewed medical literature with late recurrence of ovarian cancer.

Small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT)--case report.

Small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT) is a very rare malignant disease, seen mostly in young women, with a very poor prognosis. There is no standard treatment for patients with this disease and most literature is limited to short series or case reports. This report describes the case of a 34-year-old woman with aggressive course of SCCOHT and poor outcome. What proved difficult was the process of establishing the diagnosis due to non-specific first symptoms of disease and consequently the combined treatment of surgery and chemotherapy with concurrent side effects.

Oxidative stress markers in uterine fibroids tissue in pre- and postmenopausal women.

UNLABELLED: Uterine fibroids are common benign tumors of the reproductive organ and occur in approximately 50-80% of women of reproductive age. The pathogenesis of uterine fibroids is multifactorial and includes: sex hormones, genetic factors, cytokines, and oxidative stress. OBJECTIVE: The aim of this study was to investigate the oxidative stress markers in tissue samples of women with uterine fibroids, with further analysis on size and menopausal status. MATERIALS AND METHODS: Fifty-nine patients with the mean age 50.6 (35 premenopausal and 24 postmenopausal) who underwent standard gynecological procedures were recruited in the study. All women had histologically proven uterine leiomyoma. Samples were collected ex vivo immediately after resection. Glutathione peroxidase (GPX), catalase (CAT), and the ferric reducing ability of plasma (FRAP) were measured. RESULTS: The activity of GPX was significantly higher in fibroid samples than in myometrium (0.070 +/- 0.042 vs. 0.057 +/- 0.027 U/mg of protein, p < 0.05), activity of CAT did not differ between samples (1.13 +/- 0.86 vs. 1.23 +/- 0.51 U/mg of protein, p > 0.05), and FRAP presented higher values in fibroid samples than in myometrium (4.58 +/- 6.29 vs. 3.04 +/- 3.81 mM Fe(+2)/mg of protein), but the difference was not statistically significant (p = 0.06). In the subgroups analyses, there were no statistically significant differences when comparing the activity of GPX, CAT, and FRAP in fibroid samples from pre- and postmenopausal women, as well as when comparing fibroid samples of small size (< 50 mm) and large size (≥ 50 mm) tumors. CONCLUSION: Oxidative stress markers are changed in fibroid tissue samples showing that oxidative stress may play an important role in this tumor formation, although without influencing menopausal status nor tumor size.

Effects of dinuclear berenil-platinum(II) complexes on fibroblasts redox status.

PURPOSE: Platinum(II) complex anticarcinogenic mechanisms are associated with changes in the cellular redox status of cancer as well as healthy cells. Therefore, the goal of the present study was to investigate oxidative modifications in cellular components following fibroblast exposure to novel dinuclear berenil-platinum(II) complexes. MATERIAL AND METHOD: ROS levels, antioxidant parameters level/activity, and damage to DNA, lipids, and proteins, including pro-apoptotic and anti-apoptotic factors in human skin fibroblasts following berenil-platinum(II) complex treatments i.e. Pt2(isopropylamine)4(berenil)2, Pt2(piperazine)4(berenil)4, Pt2(2-picoline)4(berenil)2, Pt2(3-picoline)4(berenil)2, and Pt2(4- picoline)4(berenil)2 were examined. RESULTS: Treatment of fibroblasts with platinum(II) complexes has shown that all compounds enhance total ROS and superoxide anion generation as well as change the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase and decrease in the level of non-enzymatic antioxidants (GSH, vitamin C, E and A). Such a situation is conducive to oxidative stress formation and oxidative modifications of cellular macromolecules and to increase in the expression of proapoptotic proteins. Pt2(isopropylamine)4(berenil)2 elicited the most damage, which resulted in oxidative modification of cellular components. The therapeutic use of this complex would cause considerable side effects in patients, therefore the agent lacks drug potential; however Pt2(piperazine)4(berenil)2 and Pt2(2-picoline)4(berenil)2 exhibited reduced redox and increased apoptotic profiles compared to cisplatin. CONCLUSION: Results of this paper and preliminary data show that Pt2(2-picoline)4(berenil)2 is less dangers than cisplatin to fibroblasts and more disruptive than cisplatin to breast cancer cell metabolism, and therefore it is a promising candidate for use in future anticancer drug strategies.

Development of antiangiogenic therapies for ovarian cancer.

Angiogenesis is a dynamic process which leads to a development of cancer and metastases. The most recognized and dominant prognostic factor is vascular endothelial growth factor (VEGF) and its receptors. VEGF was identyfied in 1989. There are three receptors for VEGF: VEGFR1 (VEGF receptor 1) and VEGFR2 that play the role in angiogenesis and development of ascites, and VEGFR3 is critical for lymphangiogenesis. There is bevacizumab--a new drug, monoclonal antibody that can block connection VEGF to its receptors. The first notification of activity of bevacizumab in ovarian cancer was in 2005. The aim of the article is to show some clinical trials in ovarian cancer and their results. The bevacizumab was registered in November 2011 in first line with standard chemotherapy in ovarian cancer. There is a new weapon against this disease.

Factors affecting response of chemotherapy in women with ovarian cancer.

Chemotherapy plays an important role in the treatment of ovarian cancer. Patients' response to chemotherapy is determined by a variety of acknowledged factors, but one might expect that many of them are yet to be described. The aim of this paper was to present the most essential yet still to be generally assessed in clinical practice, factors, which include: E-cadhedrin, hypoxia inducible factor alpha, survivin, COX-2, clusterin, BRCA1 protein, TP53 protein, YY1 protein, multidrug resistance protein, and interleukin-8.

The effect of ε-aminocaproyl-S-benzyl-L-cysteine on the t-PA activity of human saliva.

PURPOSE: The aim of this work was to study the effect of the synthetic antifibrinolytics: ε-aminocaproic acid (EACA), tranexamic acid (AMCHA) and ε-aminocaproyl-S-benzyl-L-cysteine (H-EACA-S-Bzl-L-Cys-OH) on the fibrinolytic activity of saliva in order to obtain new data on the activity of saliva tissue plasminogen activator (t-PA). MATERIAL AND METHODS: Saliva samples were obtained from healthy volunteers. Saliva, precipitate and supernatant were tested 1hr, 4 hrs and 6hrs after collection. The effect of the synthetic antifibrinolytics was examined with the use of the clot lysis time determination. RESULTS: All examined compounds inhibited the fibrinolytic activity of saliva 1hr after collection. H-EACA-S-Bzl-L-Cys-OH was the most active inhibitor. After 6 hours in room temperature only this compound showed a certain possibility to prolong the clot lysis time. CONCLUSIONS: The obtained results may indicate the possibility of the difference in specificity between the activities of t-PA of saliva and recombinant tissue plasminogen activator activities. It may explain the unexpected high inhibitory activity of H-EACA-S-Bzl-L-Cys-OH in our study.

The effect of hyaluronic acid (Cicatridine) on healing and regeneration of the uterine cervix and vagina and vulvar dystrophy therapy.

Procedures aimed at the treatment of precancerous lesions and ectopia on the uterine cervix are frequently linked to lesions of anatomical structures. The application of hyaluronic acid (Cicatridine vaginal ovules) promotes accelerated healing of the uterine cervix and acquisition of a normal shape in the uterine cervix canal. Local application of hyaluronic acid in the vagina following radiotherapy due to cancer in the uterine cervix or endometrium favourably affects the healing of post-irradiation lesions in the vagina and improves quality of life. Over 90% of patients responded positively to the application of hyaluronic acid in the form of a cream on dystrophic lesions in the vulva. Hyaluronic acid aids the healing process of post-procedural wounds in the uterine cervix, following radiotherapy applied due to cancer of the uterine cervix, endometrium and in vulvar dystrophy.

Elevated blood plasma concentrations of active ghrelin and obestatin in benign ovarian neoplasms and ovarian cancers.

Both ghrelin and obestatin are derived from preproghrelin by post-translational processing. The two peptides are secreted into the blood but circulating levels of these peptides have not been assessed in women with ovarian tumours. Therefore, the purpose of this study was to evaluate peripheral blood concentrations of active and total ghrelin and obestatin in patients with benign ovarian tumours and those with ovarian cancer. The studies were conducted on 22 patients operated due to benign ovarian tumours, and 31 patients operated due to ovarian cancer. A control group consisted of 32 women, 24 to 65 years of age. Both in women with benign ovarian tumours and those with ovarian cancer blood concentrations of active ghrelin and obestatin were higher than in the control group (active ghrelin: 90 +/- 4, 84 +/- 4 and 56 +/- 9 pg/ml, respectively, obestatin: 660 +/- 36; 630 +/- 30 and 538 +/- 31 ng/ml (x +/- SE), respectively). In contrast, total ghrelin concentrations in blood were similar in the studied groups. The alterations resulted in increased values of active to total ghrelin concentration ratio in the peripheral blood of patients with benign ovarian tumours or with ovarian cancer (0.79 +/- 0.02 and 0.93 +/- 0.05, respectively vs 0.58 +/- 0.02 in the control group). Due to the absence of any convincing proof for the presence of a functional GHS-R-1a receptor for ghrelin in human ovaries it did not seem probable that the observed elevated levels of active ghrelin and obestatin were directly linked to development of ovarian tumours.

Two cases of metachronic tumours: cancers of the ovary and endometrium in young women. Case presentation and review.

Ovarian and endometrial cancers seldom develop in females under 40 years of age. Manifestation of metachronic cancers before the age of 40 is of casuistic interest. Two cases are presented in whom metachronic cancers were detected: the first localisation involved the ovary, and the second the endometrium. One of the patients had earlier delivered a baby with multiple hereditary defects and was diagnosed with secondary infertility. The second patient was diagnosed with primary infertility. Immunohistochemical tests disclosed the presence of alpha and beta type estrogen receptors and progesterone receptors in the tumour cells of the ovary and endometrium. Neither of the patients carried mutations in the BRCA 1 or NOD 2 genes.

Elevated blood active ghrelin and normal total ghrelin and obestatin concentrations in uterine leiomyoma.

Ghrelin and obestatin originate from the same peptide precursor, preproghrelin. Both peptides are secreted in the blood. We investigated serum active and total ghrelin and obestatin concentrations in women with uterine myomatosis. Serum concentrations of active ghrelin in uterine leiomyoma were significantly higher compared to women in the control group (86 +/- 3 vs 56 +/- 9 pg/ml, respectively; p < 0.02). On the other hand, serum concentrations of total ghrelin and obestatin in uterine leiomyoma did not differ from those in the control group. In the control group the ratio of active to total ghrelin concentrations amounted to 0.62, while in women with uterine myoma it was 0.95, pointing to a prevalence of the active form of ghrelin in women with uterine myoma. Also the ratio of active ghrelin concentration to obestatin concentration was higher in the latter group while the ratio of total circulating ghrelin to obestatin concentrations was similar in the two groups. The data may suggest a role of active ghrelin in the development of a myoma. Moreover, the results indicate that increased blood ratios of active to total ghrelin and to obestatin concentrations are not specific for cachexia.

Activity of telomerase in ovarian cancer cells. Clinical implications.

Estimation of telomerase activity in cell nuclei of ovarian malignant tumours may provide an independent prognostic index. The test for telomerase activity in tumour cell nuclei may be accepted as a useful diagnostic test with application for differential diagnoses of benign ovarian tumours vs tumours of a borderline or malignant character.

New cytokine: stromal derived factor-1.

Cytokines are proteins which regulate and control the basic functions of cells, including proliferation, differentiation and migration by auto- and paracrine communication. Chemokines are a family of proinflammatory chemotactic cytokines. Chemokines play a significant role in many physiological and pathological processes. Chemokines usually join many receptors, and the same receptors can join many different chemokines. SDF-1 works by its receptor CXCR4. The SDF-1+CXCR4 complex plays a significant role in the creation of metastases of neoplasms and as a response to cytostatic treatment. Identification of this complex may be a useful prognostic factor in the therapy of many types of carcinoma. The ability to block CXCR4 indicates the existence of new targets in breast or ovarian carcinoma treatment as well as in cases of cervical adenocarcinoma.

Short peptides containing L-lysine and epsilon-aminocaproic acid as potential plasmin inhibitors.

Eight short peptides containing L-lysine and epsilon-aminocaproic acid were obtained and their effect on the amidolytic activities of plasmin, thrombin and trypsin was examined. Tripeptide amide Boc-EACA-L-Lys-EACA-NH2 was the most effective and specific plasmin inhibitor.

Studies on leptin and leptin receptor gene expression in myometrium and uterine myomas of gnRH analogue-treated women.

AIM: To test if treatment with GnRH analogue, which leads to a significant reduction in myoma volume, changes expression of leptin genes and gene coding leptin receptor isoforms in uterine myomas and in the surrounding unaltered myometrium. METHODS: Using RT-PCR, expression of leptin genes and leptin receptor genes was studied in myomas and in the surrounding myometrium in women with uterine myomas, untreated or treated with GnRH analogue. In the randomly selected cases presence of leptin protein and of leptin receptor proteins was examined also by Western blotting. RESULTS: Expression of leptin genes was demonstrated both in myomas and in the surrounding myometrium, and a similar pattern of expression was found for leptin receptor isoforms. The results of RT-PCR were confirmed by Western blotting, which documented the identical distribution of leptin proteins and leptin receptor proteins in studied tissues. Treatment with GnRH analogue had no effect on the expression pattern of studied genes. CONCLUSION: The results of the present study on the administration of GnRH analogue to females with myomas suggest that no direct or immediate inter-relationship exists between expression of leptin genes in uterine myomas on one hand and estrogen, progesterone and leptin levels in the blood on the other. Expression seems to be of a more durable nature but factors that induce such expression remain unknown.