The Effect of Acetylsalicylic Acid, as a Representative Non-Steroidal Anti-Inflammatory Drug, on the Activity of Myeloperoxidase.

BACKGROUND: Acetylsalicylic acid (ASA or aspirin) is one of the world's most widely used non-steroidal anti-inflammatory drug (NSAID). Numerous studies have shown that the long-term use of aspirin may contribute to longer survival among patients with various types of cancer, including ovarian cancer. AIM: The aim of this study was to investigate the effect of ASA on myeloperoxidase (MPO), which is found at an elevated level in women with ovarian cancer, among others. METHODS: The influence of different concentrations of ASA on the chlorinating and peroxidase activity of MPO was analysed. The relationship between the concentration of ASA and the degree of inhibition of MPO activity was determined based on the results. CONCLUSIONS: Aspirin has a significant effect on MPO activity. The use of 50 mM ASA resulted in the enzyme activity being inhibited by more than 90%.

Prognostic Significance of Survivin Expression in Patients with Ovarian Carcinoma: A Meta-Analysis.

BACKGROUND: Survivin belongs to the protein family of inhibitors of apoptosis (IAP) and is a regulator of the cell cycle and apoptosis. The aim of this study was to assess the clinical and prognostic significance of expression survivin in patients with ovarian cancer. METHODS: We systematically searched for articles in PubMed, the American Chemical Society (Publications), Medline, the Royal Society of Chemistry, Scopus and the Web of Science. Patient clinical data, overall survival (OS), disease-free survival (DFS), and survivin expression were extracted from individual studies. We performed statistical analysis using the STATA 16 package. Eighteen publications containing data from 2233 patients with ovarian cancer were included in this meta-analysis. RESULTS: We found an adverse effect of survivin expression on OS (risk ratio (HR): 1.60; 95% confidence interval (CI): 1.33-1.93, p = 0.00) but this was not observed on DFS (HR: 1.06; 95% CI: 0.55-2.05, p = 0.87). The analysis of clinicopathological parameters showed that survivin expression was associated with the histological grades (G1-2 vs. G3) (odds ratio (OR) = 0.53, 95% CI: 0.34-0.83, p = 0.01) and: International Federation Gynecology and Obstetrics (FIGO) stage (I-II vs. III-IV) (OR = 0.22, 95% CI: 0.09-0.55, p = 0.00), but it was not significantly correlated with the histological subtype (OR = 1.14, 95% CI: 0.83-1.58, p = 0.42). CONCLUSIONS: Our meta-analysis suggests that survivin expression may be a marker of poor prognosis in ovarian cancer. Survivin expression was associated with parameters of greater aggressiveness of ovarian cancer. Prospective studies are needed to confirm our results indicating that survivin expression can be used as an ovarian cancer biomarker.

[Screening for ovarian cancer in BRCA1/BRCA2 mutations carriers]. / Badania przesiewowe w kierunku raka jajnika u nosicielek mutacji genów BRCA1/BRCA2.

Worldwide screening for early detection of ovarian cancer in both, the general population and the group of women at high risk for ovarian cancer including BRCA genes mutations carriers, has proven to be ineffective. The recommended screening methods, including a pelvic examination, transvaginal ultrasound, and CA125 performed biannually continue to fail due to their relatively low sensitivity specificity and positive predictive value tests, as well as the fact that cancer is still detected in advanced stages (FIGO III/IV). However proteomic techniques and the ongoing search for more sensitive and specific biomarkers to increase effectiveness of screening tests for ovarian cancer bring new hope. We reviewed the current literature on screening for ovarian cancer in BRCA genes mutations carriers.

Survivin expression as a prognostic factor in patients with epithelial ovarian cancer or primary peritoneal cancer treated with neoadjuvant chemotherapy.

BACKGROUND: The aim of this study was to evaluate association of expression of survivin and p53 with the effects of neoadjuvant chemotherapy (NAC) in patients with advanced ovarian cancer (AOC). METHODS: We retrospectively evaluated 60 consecutive patients with AOC (International Federation of Gynecology and Obstetrics stage IIIC-IV) treated with NAC. The expression of p53 and survivin was assessed immunohistochemically. The median of expression total score survivin equals 2 was adopted to dichotomize the group. The positive and negative expression of p53 was used to dichotomize the group. RESULTS: The expression of survivin in tumor tissue taken before and after NAC was a significant difference in the percentage of stained nuclei (P = 0.0002), the intensity of staining (P = 0.0003), and total score (P = 0.0001). There was a significant difference in p53 expression in tumor tissue before and after NAC in the percentage of stained nuclei (P = 0.0424). Survivin expression, in contrast to p53 expression, was a prognostic factor in patients with AOC treated with NAC (P = 0.0484). The expression of survivin and p53 was not a predictive factor. Independent adverse predictor factors were as follows: lack of optimal interval debulking surgery and the lack of an objective response (the respective hazard ratio was 3.93 [95% confidence interval, 2.07-7.46; P < 0.0001] and 2.36 [95% confidence interval,1.25-4.47; P = 0.0080]). The suboptimal range of interval debulking surgery, resistance to platinum, and the lack of paclitaxel in the NAC were adverse prognostic factors (the respective hazard ratio was 2.61 [95% confidence interval, 1.17-5.83], 2.72 [95% confidence interval, 1.07-6.89], and 2.56 [95% confidence interval, 1.06-6.18]; P < 0.05]). CONCLUSIONS: High expression of survivin could be a prognostic factor in patients treated with NAC for AOC.

Cystatin C as a parameter of glomerular filtration rate in patients with ovarian cancer.

AIMS: To evaluate the potential role of serum cystatin C as a marker of renal function in patients with ovarian cancer. METHODS: Treatment of consecutive ovarian cancer patients who were eligible for chemotherapy with paclitaxel (135 mg/m²/24 h) and cisplatin (75 mg/m²) every 3 weeks in 6 cycles. Glomerular filtration rate (GFR) markers, i.e. serum levels of creatinine and cystatin C, estimated by the Cockcroft-Gault and Modification of Diet in Renal Disease formulas, were recorded before each cycle and 3 weeks after the 6th course. RESULTS: The median age of 34 patients was 54 years. In the initial stage of treatment, we did not observe any correlation between cystatin C and other GFR markers. We noted a significant association between cystatin C and tumor extent on spiral CT scans (diameter: >1 cm) performed at baseline (p = 0.004), and after the 1st (p = 0.03) and 2nd cycle (p = 0.026). We observed a correlation between cystatin C and CA-125 level before chemotherapy (R = 0.4; p = 0.02) and after the 1st cycle (R = 0.43; p = 0.04). CONCLUSION: The results of our study suggest that cystatin C is not a reliable marker of the GFR in ovarian cancer patients, probably due to its nature as a cysteine protease inhibitor.

Serous peritoneal psammocarcinoma with an aggressive course: a case and review of the literature.

BACKGROUND: Primary serous peritoneal psammocarcinoma (PSPP) is a rare variant of serous carcinoma characterized by massive psammoma body formation and low-grade cytological features. Patients with serous psammocarcinoma have a protracted clinical course and relatively favourable prognosis, although a more aggressive course of PSPP may occur. CASE PRESENTATION: A 52-year-old woman suffering from abdominal pain with ascites and serum CA-125 level substantially elevated underwent an exploratory laparoscopy which revealed bulk disease. The pathology report detected PPSP at the FIGO stage IIIC. The patient received neoadjuvant chemotherapy (3 courses of paclitaxel/pegylated liposomal doxorubicin/carboplatin). Optimal interval debulking surgery was performed as the next step, followed by three courses of adjuvant chemotherapy (paclitaxel/carboplatin). Due to the fact that the patient had residual disease, at the second-look surgery she received consolidation therapy with intraperitoneal and intravenous chemotherapy carboplatin. Eight months after the completion of treatment the patient developed disease recurrence in the peritoneum. Palliative surgery (enterostomy) was performed. Furthermore, the patient received two lines of chemotherapy consisting of cyclophosphamide/cisplatin and then gemcitabine. After twenty five months she developed brain metastases, treated with palliative radiotherapy. The patient died twenty-eight months since her primary presentation of PSPP. CONCLUSION: PSPP is an infrequent variant of epithelial cancer with favourable prognosis. The disease may however, take a more aggressive course. Thus, an aggressive therapy is required to postpone the progression.

Salvage therapy with topotecan in heavily pretreated ovarian cancer patients.

BACKGROUND: We showed feasibility and efficacy of topotecan in third or a higher line of chemotherapy in heavily pretreated ovarian cancer (HPOC) patients. METHODS: Between January 2004 and June 2007, 25 cases of HPOC were treated with topotecan as 30-min infusion at the dose of 1.5 mg/m2 through 5 consecutive days every 21 days. We assessed toxicity profile using NCI CTC and the response was measured according to RECIST and CA-125 criteria described by Rustin. RESULTS: Heavily pretreated ovarian cancer received at least two cycles of topotecan (median 6, range 2-6) with prior chemotherapy lines (median 3, range 3-7). In 20 HPOC who met RECIST criteria results were as follows: PR, 6/20 (30%); NC, 7/20 (35%); PD, 7/20 (35%). Biochemical response was noted in 20 patients having ?15% (3/20) of 75% and 20% (4/20) of 50% decline of CA-125. Time to progression was median 6 months (95% CI: 4.06-6.18) and overall survival was median 9 months (95% CI: 8.69-16.27). In multivariate analysis, primary optimal debulking and response to primary chemotherapy (HR = 0.24, 95% CI: 0.08-0.69, P = 0.0084; HR = 0.38, 95% CI: 0.14-0.98, P = 0.0448, respectively) were independent prognostic factors when assessed in relation to salvage therapy with topotecan. We did not observe difference in side effects after topotecan treatment among patients in relation to the higher number of previously used chemotherapy line (3 vs. >3). CONCLUSIONS: We state that topotecan is able to offer a control of ovarian cancer, despite previous treatment, but reliable management is needed to alleviate hematologic toxicity.

Renal protection with magnesium subcarbonate and magnesium sulphate in patients with epithelial ovarian cancer after cisplatin and paclitaxel chemotherapy: a randomised phase II study.

BACKGROUND: The aim of this study was to examine the effect of magnesium supplementation on nephrotoxicity accompanying standard cisplatin-based chemotherapy in patients with epithelial ovarian cancer (EOC). PATIENTS AND METHODS: A double-blind, placebo-controlled, randomised study was conducted in which study arm magnesium sulphate (5 g) was administered before each course of standard chemotherapy with paclitaxel (135 mg/m(2)/24 h) plus cisplatin (75 mg/m(2)) every 3 weeks in patients with EOC. Magnesium subcarbonate (500 mg), three times per day orally, was administered during the treatment intervals. The control arm was administered a placebo instead of both magnesium salts. Magnesium serum levels (sMg) and GFR markers: serum levels of creatinine (sCr), Cockroft-Gault (ClCG) and Modification Diet of Renal Disease (MDRD) formulae were recorded before each cycle, and 3 weeks after the sixth course. RESULTS: 41 EOC patients were randomised and 40 were eligible. sMg varied significantly between the supplemented and placebo groups (p<0.0001). The control group showed a significantly greater decrease of GFR assessed by: sCr (p=0.0069), ClCG (p=0.0077) and MDRD (p=0.032) formulae compared with the magnesium supplemented group. CONCLUSIONS: These results demonstrate the nephroprotective effect of magnesium supplementation during chemotherapy with cisplatin.

[CA 125 regression after two cycles of neoadjuvant chemotherapy as prognostic factor in patients with advanced ovarian cancer and primary peritoneal serous cancer who underwent interval surgical cytoreduction]. / Regresja markera CA 125 po dwóch kursach neoadjuwantowej chemioterapii jako czynnik prognostyczny u chorych na raka jajnika i pierwotnego surowiczego raka otrzewnej poddawanych interwalowej operacji cytoredukcyjnej.

OBJECTIVES: The aim of our study was to assess the prognostic role of CA 125 regression during neoadjuvant chemotherapy (NAC) in patients with ovarian cancer (OC) or primary peritoneal serous carcinoma (PPSC) that underwent interval debulking surgery (IOC). MATERIAL AND METHODS: Thirty one patients with advanced OC or PPSC (FIGO stage IIIC and IV) who underwent initial exploratory surgery, followed by NAC containing platinum analogs, have been analyzed, retrospectively. We have used a regression coefficient (RCA 125), which was calculated as following: log10 (CA 125 level measured after two cycles of NAC/baseline CA 125) for statistical analysis. The median value of RCA 125 reached -0.788 and has been used to dichotomize. Optimal IOC has been performed in 67.74% (21/31) patients, suboptimal in 25.81% (8/31) patients and 6.45% (2/31) of patients did not undergo IOC due to the progression of the disease. RESULTS: We have noted significant correspondence between time to progression and RCA 125 in univariate analysis, which we have also confirmed in multivariate analysis (HR 0.27; 95% CI, 0.15-0.96; p = 0.0178). Similarly, we have observed significant relationship between overall survival, RCA 125 and extension IOC in univariate analysis. Multivariate analysis confirmed that RCA 125 was independent prognostic factor, HR-0.18 (95% CI, 0.07-0.56; p = 0.004). In case of patients with high RCA 125, a greater rate of optimal debulking cytoreduction (p = 0.0278, U = 50.0) has been observed. CONCLUSIONS: RCA 125 after two courses of NAC appears to be an important prognostic factor in patients with OC or PPSC, who underwent IOC High RCA 125 during NAC seems to be a good predictive factor in order to achieve optimal IOC.