Dietary phytochemicals in breast cancer research: anticancer effects and potential utility for effective chemoprevention.

Cancerous tissue transformation developing usually over years or even decades of life is a highly complex process involving strong stressors damaging DNA, chronic inflammation, comprehensive interaction between relevant molecular pathways, and cellular cross-talk within the neighboring tissues. Only the minor part of all cancer cases are caused by inborn predisposition; the absolute majority carry a sporadic character based on modifiable risk factors which play a central role in cancer prevention. Amongst most promising candidates for dietary supplements are bioactive phytochemicals demonstrating strong anticancer effects. Abundant evidence has been collected for beneficial effects of flavonoids, carotenoids, phenolic acids, and organosulfur compounds affecting a number of cancer-related pathways. Phytochemicals may positively affect processes of cell signaling, cell cycle regulation, oxidative stress response, and inflammation. They can modulate non-coding RNAs, upregulate tumor suppressive miRNAs, and downregulate oncogenic miRNAs that synergically inhibits cancer cell growth and cancer stem cell self-renewal. Potential clinical utility of the phytochemicals is discussed providing examples for chemoprevention against and therapy for human breast cancer. Expert recommendations are provided in the context of preventive medicine.

Photodynamic therapy of murine fibrosarcoma with topical and systemic administration of hypericin.

The in vivo antitumour activity of the natural photosensitizer hypericin was evaluated. C3H/DiSn mice inoculated with fibrosarcoma G5:1:13 cells were intraperitoneally or intratumourally injected with hypericin (5 mg/kg) and 2 hours later the mice were locally irradiated with laser light (488 nm, 150 mW/cm2, 180 J/cm2) when the tumour reached volume of 40-80 mm3 (approximately 17 days after inoculation). Tumours treated with hypericin alone as well as those irradiated with laser light alone have similar growth rates and none of these tumours regressed spontaneously. The mean tumour volume in hypericin-PDT treated groups was significantly lower in comparison to that found in the control group 3-5 weeks after the therapy. A higher proportion of animals with tumour volume less than 5-fold of the initial volume has been observed in both hypericin-PDT treated groups. Complete response to PDT has been observed for 44.4% of the animals with intraperitoneally administered hypericin and for 33.3% of the animals with intratumourally administered hypericin. Complete remission occurred in treated lesions with 3 mm or less in height. Hypericin-PDT significantly increased survival. However, no statistically significant difference in survival rate of animals has been found between the intratumoural and the intraperitoneal schedule of administration of hypericin.

In-vitro assessment of a registration protocol for image guided implant dentistry.

In this study a computer aided navigation technique for accurate positioning of oral implants was assessed. An optical tracking system with specially designed tools for monitoring the position of surgical instruments relative to the patient was used to register 5 partially or completely edentulous jaw models. Besides the accuracy of the tracking system, the precision of localizing a specific position on 3-dimensional preoperative imagery is governed by the registration algorithm which conveys the coordinate system of the preoperative computed tomography (CT) scan to the actual patient position. Two different point-to-point registration algorithms were compared for their suitability for this application. The accuracy was determined separately for the localization error of the position measurement hardware (fiducial localization error-FLE) and the error as reported by the registration algorithm (fiducial registration error-FRE). The overall error of the navigation procedure was determined as the localization error of additional landmarks (steel spheres, 0.5 mm diameter) after registration (target registration error-TRE). Images of the jaw models were obtained using a high resolution CT scan (1.5 mm slice thickness, 1 mm table feed, incremental scanning, 120 kV, 150 mAs, 512 x 512 matrix, FOV 120 mm). The accuracy of the position measurement probes was 0.69 +/- 0.15 mm (FLE). Using 3 implanted fiducial markers, FRE was 0.71 +/- 0.12 mm on average and 1.00 +/- 0.13 mm maximum. TRE was found to be 1.23 +/- 0.28 mm average and 1.87 +/- 0.47 mm maximum. Increasing the number of fiducial markers to a total of 5 did not significantly improve precision. Furthermore it was found that a registration algorithm based on solving an eigenvalue problem is the superior approach for point-to-point matching in terms of mathematical stability. The experimental results indicate that positioning accuracy of oral implants may benefit from computer aided intraoperative navigation. The accuracy achieved compares well to the resolution of the CT scan used. Further development of point-to-point/point-to-surface registration methods and tracking hardware has the potential to improve the precision of the method even further. Our system has potential to reduce the intraoperative risk of causing damage to critical anatomic structures, to minimize the efforts in prosthetic modelling, and to simplify the task of transferring preoperative planning data precisely to the operating room in general.

[Melatonin and its wide-spectrum effects: use of melatonin in the treatment of tumors]. / Melatonín a jeho sirokospektrálne úcinky: vyuzitie melatonínu v nádorovej terapii.

One of the major physiological roles of melatonin is its synchronizative influence on circadian rhythmicity and the induction of seasonal responses to changes in day length. In seasonally reproductive animals like the hamster, melatonin has been established as antigonadotrophic on the gonadal axis. Melatonin has been used successfully to treat jet lag and some circadian-based sleep disorders. It has the immunomodulatory role, which can be supported by the existence of specific binding sites in lymphoid cells, thymus and spleen. Not negligible is the antioxidative effect of melatonin and the ability to scavenge some reactive forms of oxygen. Melatonin has potentially important influence on the neoplastic growth and direct and indirect oncostatic effect in some forms of neoplasia. The beneficial influence of melatonin alone or its combination with immunotherapy, radiotherapy or chemotherapy in many clinical studies in patients with tumors was demonstrated.