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.

RMS roughness-independent tuning of surface wettability by tailoring silver nanoparticles with a fluorocarbon plasma polymer.

A layer of 14 nm-sized Ag nanoparticles undergoes complex transformation when overcoated by thin films of a fluorocarbon plasma polymer. Two regimes of surface evolution are identified, both with invariable RMS roughness. In the early regime, the plasma polymer penetrates between and beneath the nanoparticles, raising them above the substrate and maintaining the multivalued character of the surface roughness. The growth (ß) and the dynamic (1/z) exponents are close to zero and the interface bears the features of self-affinity. The presence of inter-particle voids leads to heterogeneous wetting with an apparent water contact angle θa = 135°. The multivalued nanotopography results in two possible positions for the water droplet meniscus, yet strong water adhesion indicates that the meniscus is located at the lower part of the spherical nanofeatures. In the late regime, the inter-particle voids become filled and the interface acquires a single valued character. The plasma polymer proceeds to grow on the thus-roughened surface whereas the nanoparticles keep emerging away from the substrate. The RMS roughness remains invariable and lateral correlations propagate with 1/z = 0.27. The surface features multiaffinity which is given by different evolution of length scales associated with the nanoparticles and with the plasma polymer. The wettability turns to the homogeneous wetting state.

Anti-proliferative and anti-angiogenic effects of CB2R agonist (JWH-133) in non-small lung cancer cells (A549) and human umbilical vein endothelial cells: an in vitro investigation.

Non-small cell lung cancer has one of the highest mortality rates among cancer-suffering patients. It is well known that the unwanted psychotropic effects of cannabinoids (CBs) are mediated via the CB(1) receptor (R), and selective targeting of the CB(2)R would thus avoid side effects in cancer treatment. Therefore, the aim of our study was to evaluate the effect of selective CB(2)R agonist, JWH-133, on A549 cells (non-small lung cancer) and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assay and DNA fragmentation assay were employed to evaluate the influence of JWH-133 (3-(1,1-dimethylbutyl)- 1-deoxy-Δ8-tetrahydrocannabinol) on investigated cancer cells. In addition, migration assay and gelatinase zymography were performed in HUVECs to asses JWH-133 anti-angiogenic activity. Our study showed that JWH-133 exerted cytotoxic effect only at the highest concentration used (10(-4) mol/l), while inhibition of colony formation was also detected at the non-toxic concentrations (10(-5)-10(-8) mol/l). JWH-133 was also found to be able to induce weak DNA fragmentation in A549 cells. Furthermore, JWH-133 at non-toxic concentrations inhibited some steps in the process of angiogenesis. It significantly inhibited endothelial cell migration after 17 h of incubation at concentrations of 10(-4)-10(-6) mol/l. In addition, JWH-133 inhibited MMP-2 secretion as assessed by gelatinase zymography. The present study demonstrates the in vitro anti-proliferative and anti-angiogenic potential of CB(2)R agonist, JWH-133, in nonsmall lung cancer cells and HUVECs. Our results generate a rationale for further in vivo efficacy studies with this compound in preclinical cancer models.

Análisis de una experiencia de consultoría ético clínica en cuidado intensivo / Analysis of a clinical ethics consultation experience in intensive care

Background: Very few patients are presented to ethics committees, and individual ethics consultations are a response to this situation. At the intensive care unit (ICU) in Clínica Alemana, Santiago Chile, an ethics consultation system was organized coordinated with the ethics committee. Aim: To report an evaluation of this ethics consultation system. Material and Methods: Analysis of the frst 50 cases analyzed in the consultation system. Analysis of the responses of intensive care physicians to a questionnaire about the main ethical problems that they face in their work. Results: The consultation system is mainly required by the ICU staff, and reports to the ethics committee. Fifty four percent of patients subjected to consultation were aged over 80 years. The main diagnoses were neurological, oncological or cardiopulmonary problems. The ethical problems identifed were treatment limitation (62 percent), proportionality or futility (42 percent), need of a peaceful death (36 percent), lack of anticipated decisions (28 percent), disagreement between physicians and patient’s family (24 percent), undefined subrogation (14 percent), and abuse of public resources (14 percent). Twenty six of 31 ICU physicians answered the questionnaire, using a 1 (min) to 7 (max.) scale. They found that consultation is helpful for decision making (6.3), useful for improving ethical perception (6.0), supportive for staff (6.5), good for patients (6.3), supportive for families (6.7), and timely performed (5.2). Conclusions: As a complement for the ethics committee’s work, consultation is a valid alternative for ethics counselling and a support for physicians and patient’s families. Its implementation depends on the particularities of each health institution.

Tres factores que influyen en la actitud de las personas ante la donación de órganos: [revisión] / Three influencing factors in people's attitude towards organ donation: [revision]

Se analiza la donación de órganos de cadáver para trasplantes a partir de tres postulados: 1) la influencia de la religión en la donación, particularmente del catolicismo; 2) la organización del sistema de información y acercamiento al donante y su familia, y 3) la formación personal de los miembros del equipo de salud. En la religión se encuentra una disociación entre la norma moral propuesta y la visión de los fieles. España, con su modelo de la Organización Nacional de Trasplantes, es el referente con una alta tasa de donación de órganos y gran credibilidad social en el sistema. El último postulado hace referencia a la importancia de contar con profesionales especialmente capacitados en la materia y en habilidades de comunicación. Se plantea la necesidad de tomar medidas administrativas y educativas que abarquen los puntos discutidos, con el fin de promover eficazmente la donación y aumentar el éxito de los programas de trasplante.

Cadaver organ donation for transplants is analyzed based on three factors: 1) Religious influence. The Catholic Church, as well as other Christian churches, accept transplants and organ donation as a sign of generosity; 2) An efficient information system for donors and families is necessary for obtaining potential donors; 3) The training of all members of the health team, and their personal views are of great importance to donors and family's decisions. There is a dissociation between religious moral principies and believer's perceptions. Spain, with its National Transplant Organization, has become the main point of reference, having a high rate of organs donation and great credibility. The third factor emphasizes the importance of having well trained professionals with the highest communication skills. Educational and management measures are needed for more successful organ donation and transplant programs.

Gp96 and its different expression in breast carcinomas.

The aim of our work was to determine the expression of glycoprotein 96 (gp96; glucose-regulated protein 94 - GRP94) in 69 samples of breast carcinoma. Enzyme immunohistochemical method was chosen for the detection of gp96 protein and its expression was compared in breast cancer cells versus normal breast cells. We found higher expression of gp96 protein in breast carcinoma cells and low or no expression in normal breast cells. Furthermore, we demonstrate first time, that ductal invasive breast carcinomas showed higher expression of gp96 than lobular invasive breast carcinomas.

Multidrug resistance proteins in renal cell carcinoma.

A large number of renal cancer patients show poor or partial response to chemotherapy and the precise mechanism has not been understood yet. MDR is the principal mechanism by which many cancers develop resistance to chemotherapeutic drugs and is associated with the elevated expression of MDR proteins. These are divided into two groups: ABC transporters and non-ABC transporters. The aim of our study was to determine the expression of MDR1/Pgp, MRP1 and LRP in 47 samples of renal cell carcinomas using immunohistochemical assay. Our results were analysed in relation to nuclear grade and other clinical and pathological parameters to see the possible correlation between the expression of MDR proteins and factors mentioned above. The majority of renal carcinoma specimens showed positivity for MDR proteins. In this regard, 21 % of samples revealed positive results for MDR1, 62 % for MRP1 and 76.6 % for LRP protein. Furthermore, our study displayed significant differences between MDR1, LRP and nuclear grade. On the other hand, no association was found between MRP1 and nuclear grade, as well as between the expression of three MDR proteins and other clinically relevant parameters.

Hsp90 inhibitor geldanamycin increases the sensitivity of resistant ovarian adenocarcinoma cell line A2780cis to cisplatin.

Ovarian carcinoma is the leading cause of death among gynecological neoplasms in the world. The chemoresistance is a major obstacle in the effective treatment of ovarian and other cancers. We evaluated the effects of Hsp90 inhibitor geldanamycin (GEL) alone and in combination with cisplatin in cisplatin resistant ovarian adenocarcinoma cell line. Our results showed Akt depletion and S-phase arrest of A2780cis cells after GEL treatment. Combined exposure of A2780cis cells to GEL and cisplatin resulted in greater than additive cytotoxic effect.

Praziquantel and liposomized glucan-treatment modulated liver fibrogenesis and mastocytosis in mice infected with Mesocestoides vogae (M. corti, Cestoda) tetrathyridia.

Beta-glucans are immunomodulators able to activate innate immunity and to potentiate acquired immune reactions. We investigated the impact of co-administration of liposomized beta-glucan on the larvicidal effect of the anthelmintic praziquantel (PZQ) in the livers and peritoneal cavities in mice infected with Mesocestoides vogae (M. corti). Also, within 2 weeks following therapy (up to day 29 p.i.) we examined collagen synthesis in the livers of mice by means of biochemical determination of hydroxyproline concentration, total mast cell counts and cell proliferative capacity using immunohistochemical and radiometrical methods. After co-administration of liposomized glucan (LG) and PZQ efficacy (%) was significantly higher than after treatment with either compound alone, particularly in the peritoneal cavity compared to the liver. In comparison with the control, more intense collagenesis was found in the B-liver parts (high intensity of infection) and lowering of collagen content in the A-parts (very weak infection). This effect was strongest after LG treatment and co-administration of PZQ abolished the pro-fibrotic effect of LG. In all groups, mast cell counts were higher in the B-liver parts than in the A-parts and the dynamics of mastocytosis was profoundly modulated following therapy. Whereas the effect of PZQ was only moderate, early and very strong onset was seen after LG treatment. Administration of PZQ suppressed LG induced-elevation of mast cells counts in both liver parts. Using DNA S-phase markers (BrdU and 3H-thymidine) the proliferative capacity was shown to be associated with several kinds of liver cells. Therapy significantly stimulated [3H]-thymidine incorporation (cell proliferation) only in the A-parts over that in control, the most after LG administration. In summary (i) the anthelmintic effect of PZQ could be enhanced after simultaneous administration of the immunomodulator beta-glucan entrapped in a liposomal carrier, (ii) intense mastocytosis seen after treatment with LG seems to have a direct role in the glucan's pro-fibrotic activity and can be abolished after co-administration of PZQ in a time-dependent manner, (iii) the pattern of cell proliferation indicates that in the case of PZQ treatment, the reparative processes of liver parenchyma are enhanced in an inverse correlation with the intensity of infection.

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.

Síndrome de ovario poliquístico: la importancia de establecer su diagnóstico / Polycystic ovary syndrome: the importance of establishing diagnosis

Polycystic ovary syndrome (PCOS) is a very common disorder that occurs up to 10 percent of premenopausal women. Although PCOS is known to be associated with a higher reproductive morbility and increased risk of hormone dependent-cancer, its diagnosis is particularly important because PCOS is strongly linked to insulin resistance. This involves a major risk of early metabolic and cardiovascular complications. On the other hand, the prevalence of metabolic disorders associated with insulin resistance is higher in family members of patients with PCOS than in those of normal women, which suggests that the treatment of this syndrome should be preventive rather than symptomatic. For that reason, PCOS might be considered a signal of a family disorder, a route to diabetes and a public health problem

Detection of the mandibular canal via shaded surface display and multiplanar reconstruction of CT data.

The purpose of this study was to evaluate the sensitivity of conventional two-dimensional (2D) multisection images (multiplanar rendering, MPR) and registered three-dimensional (3D) shaded surface images (shaded surface display, SSD) of standard axial computed tomography (CT) data for detecting the mandibular canal (MC) in the lower jaw of 136 patients. The patients, who had different indications for mandibular CT, were examined using standard axial CT scanning. Two post-processing programs were used for 3D visualization of the data sets. The cross-sectional rendered images and the shaded surface 3D images were graded for detection of the MC, the presence of artefacts, overall quality and clinical relevance. A 3D display of the MC was achieved using the MPR technique in 100% with high image quality. The surface rendered display depicted the MC in 80%. Artefacts markedly degraded the 3D displays obtained using the surface rendering technique; thus, SSD is an inappropriate technique for imaging the entire MC without manual segmentation. MPR-CT improves the sensitivity of CT imaging in the detection of the MC with very little time needed for post-processing compared with the SSD method. This post-processing modality should, therefore, be considered for serial studies of patients undergoing dental CT. The sensitivity of the MPR method is even superior to the standard axial CT slices.

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.

Influence of age and K, Mg aspartate (Cardilan) on murine haemopoiesis.

We have studied the effect of age as well as the effect of short-term and long-term intake of K and Mg salts of aspartic acid (Cardilan) on haemopoiesis in ICR mice strain. The cellularity of the bone marrow does not change with aging, but the number of granulocyte-macrophage colony-forming cells (GM-CFC) and also the number of spleen colony-forming units (CFU-S) and erythroid burst-forming units (BFU-E) in two-year-old mice increased in the bone marrow. In two-year-old mice the number of leukocytes decreased in the peripheral blood with aging, mainly as a result of a decrease in mononuclear cells. Short-term drinking (STD) of Cardilan caused increased numbers of CFU-S and BFU-E in bone marrow and increased numbers of reticulocytes in the peripheral blood of one-year old animals (STD/12 months old). In the oldest mice (STD/24) increased weight and cellularity of the spleen and rapid increase of leukocytes and reticulocytes in the peripheral blood was recorded. After long-term drinking (LTD) of Cardilan the number of spleen GM-CFC rose markedly in one-year-old mice (LTD/12) and in two-year-old mice (LTD/24) the number of reticulocytes in the peripheral blood rose. Our results indicate that K and Mg salts of aspartic acid influence erythropoietic activity most widely.

Arterial blood supply of the maxillary sinus.

Knowledge of the arterial supply of the maxillary sinus region is essential for surgical treatment in this area (e.g., implantation of grafting materials, repair of injuries, sinus floor elevation). The goal of this study was to describe the arterial architecture of the maxillary sinus region in respect to sinus lift procedures. In 18 unfixed human cadavers, the arterial vessels of the head were injected with a mixture of latex and barium sulfate. Afterward, the arteries entering the maxilla were prepared. The number and calibers as well as anastomoses were carefully documented. In addition, we measured the distance between the alveolar ridge and the lower main branches. The arterial supply of the maxilla originated from the posterior superior alveolar artery as well as from the infraorbital artery. In all specimens we found an intraosseous anastomosis between these two vessels. The oral mucosa in the area of interest is supplied by the posterior superior alveolar artery and the infraorbital artery, and an extraosseous anastomosis was found in 44% of our cases. The two anastomoses build up a double arterial arcade, supplying the lateral wall of the antrum and parts of the alveolar process.

Daily rhythm in rat pineal catecholamines.

A daily rhythm in the oscillations of pineal dopamine, norepinephrine and epinephrine content was found in male Wistar: Han rats. The acrophases of the oscillations were localized in the first half of the dark period and generally higher values were found in the dark part of the day.

The incidence, location, and height of maxillary sinus septa in the edentulous and dentate maxilla.

PURPOSE: This study evaluated the incidence, location, and height of antral septa and demonstrates their clinical implications. MATERIALS AND METHODS: One hundred ninety-four maxillary posterior regions, subdivided into four groups (group 1, 61 clinically examined atrophic ridges; group 2, 41 anatomically examined atrophic ridges; group 3, 42 radiographically [CT] examined atrophic ridges; and group 4, 50 CT examined dentate maxillary ridges), were examined for the incidence, location, and height of antral septa. RESULTS: The incidence of antral septa was significantly greater (P<.01) in atrophic edentulous regions (groups 1, 2, and 3) than in dentate regions (group 4). However, the septa were much lower (P<.01). In atrophic maxillae, about 70% of antral septa were located in the anterior (premolar) region. CONCLUSIONS: Antral septa are more commonly found in edentulous atrophic maxillae than in dentate maxillae. The septae in edentulous atrophic maxillae are shorter than those found in dentate maxillae. When present, maxillary sinus septae are more common anteriorly than posteriorly. CT scanning is the preferred radiographic method for detecting the presence (or absence) of sinus septae. Panoramic radiography has less sensitivity and specificity than CT scanning for the detection of sinus septa.

[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.