Katarzyna M. Terlikowska

Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies.

Serum levels of IL-6, IL-8 and CRP as prognostic factors in epithelial ovarian cancer.

In the present study, associations between pretreatment interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) serum levels and epithelial ovarian cancer (EOC) were analyzed using commercially available, enzyme-linked immunosorbent assay (ELISA) in 118 patients and 64 control subjects. Values were correlated with clinicopathological characteristics and outcomes. Control variables included age, stage, grade, histological type and residual tumor size. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to study the associations between IL-6, IL-8 and CRP levels, control variables, overall survival and disease-free survival. The median IL-6, IL-8 and CRP serum levels in EOC were significantly higher than in the normal control group; 11.5 pg/mL (range, 3.4-62.6) versus 2.9 (1.1-12.3) pg/mL (p<0.001) and 21.8 pg/mL (range, 16.4-105.3) versus 9.3 (4.3-32.4) pg/mL (p<0.001) and 9.51 mg/L (range, 0.3-129.2) versus 1.2 (0.1-11.5) mg/L (p = 0.001), respectively. High levels of IL-6, IL-8 and CRP were associated with reduced overall survival (P = 0.003, P = 0.035, P = 0.046) and disease-free survival (P<0.001, P = 0.026, P = 0.043), respectively. Multivariate analyses showed that IL-6, IL-8 and CRP serum levels independently predicted disease-free survival (P = 0.011, P = 0.001 and P = 0.021), and overall survival (P = 0.004, P = 0.014 and P = 0.016), respectively. EOC is associated with extensive changes in the serum cytokine environment, highlighting the importance of further investigations of relative cytokine level changes. Preoperative serum IL-6, IL-8, and CRP levels seem promising for distinguishing EOC patients from healthy controls; however, their clinical value is still to be confirmed. High levels of IL-6, IL-8, and CRP in EOC patients have been suggested to be a poor prognostic factor for OS and DFS.

Comparison of Various Databases for Estimation of Dietary Polyphenol Intake in the Population of Polish Adults

The primary aim of the study was to estimate the consumption of polyphenols in a population of 6661 subjects aged between 20 and 74 years representing a cross-section of the Polish society, and the second objective was to compare the intakes of flavonoids calculated on the basis of the two commonly used databases. Daily food consumption data were collected in 2003–2005 using a single 24-hour dietary recall. Intake of total polyphenols was estimated using an online Phenol-Explorer database, and flavonoid intake was determined using following data sources: the United States Department of Agriculture (USDA) database combined of flavonoid and isoflavone databases, and the Phenol-Explorer database. Total polyphenol intake, which was calculated with the Phenol-Explorer database, was 989 mg/day with the major contributions of phenolic acids 556 mg/day and flavonoids 403.5 mg/day. The flavonoid intake calculated on the basis of the USDA databases was 525 mg/day. This study found that tea is the primary source of polyphenols and flavonoids for the studied population, including mainly flavanols, while coffee is the most important contributor of phenolic acids, mostly hydroxycinnamic acids. Our study also demonstrated that flavonoid intakes estimated according to various databases may substantially differ. Further work should be undertaken to expand polyphenol databases to better reflect their food contents.

Curcumin in chemoprevention of breast cancer

Breast cancer is the most common malignant cancer among women, both in Poland and worldwide. Due to the constantly increasing number of breast cancer cases, it is vital to develop effective activities in primary and secondary prevention. One of the promising methods of best value, connecting both types of cancer prevention, appears to be chemoprevention. Chemoprevention uses natural or synthetic compounds to inhibit, delay or reverse the process of carcinogenesis. Among ingredients of natural origin, great attention is paid to curcumin - a broad-spectrum anti-cancer polyphenol derivative, extracted from the rhizome of Curcuma longa L. Curcumin has a number of chemopreventive properties such as anti-inflammatory activity, induction of apoptosis, inhibition of angiogenesis as well as tumor metastasis. Numerous in vitro and in vivo studies have demonstrated the mentioned anti-cancer effect in the epithelial breast cell line MCF-10A and in the epithelial breast cell lines MCF-7, BT-474, SK-BR-3-hr and MDA-MB-231. The main problem associated with the use of curcumin as a chemopreventive agent in humans is its low absorption from the gastrointestinal tract, poor solubility in body fluids and low bioavailability. Current studies are underway to increase the bioavailability and effectiveness of curcumin in vivo. Good results in the prevention and the treatment of breast cancer could be ensured by curcumin nanoparticles coated with albumin, known as nanocurcumin. The studies using nanocurcumin, however, are still in the preclinical stage, which is why there is a need to conduct extensive long-term randomized clinical trials to determine its effectiveness.

Utility of HE4 to identify patients with endometrioid endometrial cancer who may require lymphadenectomy

PURPOSE The aim of the study was to establish whether preoperative serum levels of HE4 and CA125 could be a good predictor for lymphadenectomy in the early stage of endometrioid adenocarcinoma of the uterus. MATERIAL AND METHODS Preoperative serum HE4 and CA125 were measured in 78 postmenopausal patients treated surgically. The ROC curves were generated to determine the optimal cutoff values of HE4 and CA125 levels with optimum sensitivity and specificity for the prediction of lymphadenectomy. RESULTS Based on ROC curve, we found that the HE4 value of 78pmol/l is the best cutoff to identify candidates who may require lymphadenectomy with the sensitivity of 86.6% and the specificity of 67.2% (NPV=88.4% and PPV=51.2%). The area under the curve (AUC) equals 0.814 (95% CI=0.721-0.886). The cutoff level of CA125 that shows the prognostic indices is 26U/ml, with the sensitivity of 66.6% and the specificity of 61.2% (NPV=69.4% and PPV=44.3%). For CA125 the AUC amounts to 0.671 (95% CI=0.568-0.764). We also found a statistically significant difference, comparing HE4 and CA125 AUC (0.814 vs. 0.671, respectively, p<0.001). The combination of HE4 and CA125 established in our study as the cutoff point has the sensitivity of 81.2% and the specificity of 65.9% with NPV=83.4% and PPV=47.9%. CONCLUSIONS Our findings indicate that in the early stage of endometrioid endometrial cancer, HE4 can serve as a preoperative tool that can help to identify postmenopausal women who may require lymphadenectomy.

Sprouts as potential sources of dietary antioxidants in human nutrition

__________________________________________________________________________________________ Purpose: The present study evaluates antioxidant activity, as well as polyphenol and flavonoid contents in common sprouts, available on the Polish market. The aim of this study was to extend our already published food databases. Materials and methods: Ten seed species from four plant families were analysed. Total polyphenol content of sprout extracts was determined using the Folin-Ciocalteau method. Total flavonoid content was assessed by the aluminium chloride colorimetric method. Total antioxidant status was measured using FRAP and ABTS methods. Results: The FRAP antioxidant potential was 0.602.53 mmol TE (trolox equivalents)/100 g FM (fresh mass), and arranged in descending order it was: white mustard>cress>radish>broccoli>chickpea> sunflower>mung bean>wheat>green lentil>alfalfa), while the ABTS potential was 3.92-16.19 mmol TE/100 g FM (according to decreasing value: white mustard>green lentil>chickpea>sunflower>mung bean>cress> alfalfa>wheat> broccoli> radish). The polyphenol content was 160-774 mg GAE (gallic acid equivalents)/100 g FM, and flavonoid content 15-53 mg QE (quercetin equivalents)/100 g FM. Conclusion: Our results suggest that sprouts in comparison to other foods, despite small weight can be powerful sources of antioxidants. Special attention in human nutrition should be paid to white mustard sprouts as they are excellent source of polyphenol and flavonoid and are characterized by tremendous antioxidant activity.