In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone.

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

Comparison of FDG and FDG-labeled leukocytes PET/CT in diagnosis of infection.

UNLABELLED: The aim of this study is to compare FDG and FDG-labeled leukocyte (WBC) PET/CT in the diagnosis of infection using different SUV and visual thresholds for interpretation. Patients, material, method: 49 consecutive patients (27 men, 22 women, mean age: 55.7 years, range: 16-89 years) with suspected musculoskeletal infection (n = 34), vascular graft infection (n = 5), aortitis (n =1 ), endocarditis (n = 1), mass lesion which is suspicious for infection or malignity (n = 6), and fever of unknown origin (n = 2) underwent both FDG and WBC-PET/CT. Images were evaluated by both visual analysis (grade 1-3) according to uptake intensity and quantitative grading (grade 1-3) based on lesion to background SUVmax values. Final diagnosis was made by histopathological, microbiological analysis or clinical-radiological work-up. RESULTS: The diagnosis of infection was made in total 24 patients, of whom 14 were diagnosed by histopathological and the rest by clinical-radiological work-up. WBC-PET/CT imaging with the visual threshold of 1b as infection positivity (for truncal lesions uptake equivalent to liver or lumbar vertebrae uptake; for extremity lesions uptake significantly higher than neighbouring soft tissue uptake or higher than neighbouring bone marrow uptake) was found to have the highest diagnostic accuracy (AUC: 0.874, CI: 0.771-0.997, p < 0.001). The optimal SUV threshold was found to be 8.8 (p = 0.006; sensitivity: 72.7%, specificity: 82.8) and 5.3 (p < 0.001; sensitivity: 81.8%, specificity: 79.3%) for FDG and WBC-PET/CT, respectively by ROC curve analysis. CONCLUSION: WBC-PET/CT is more valuable than FDG PET/CT in the imaging of infection. Visual threshold of >1b seems to be more suitable for detection of infection.

[Comparative analysis of two main prognostic classifications for predicting the locally advanced prostate cancer after radical prostatectomy].

OBJECTIVE: comparison of two main clinical classifications D'Amico and NCCN for predicting the locally advanced prostate cancer. In this study we evaluated the preoperative data of 150 patients who underwent the radical prostatectomy. All patients were divided in prognostic groups according to NCCN and D'Amico classification criteria based on preoperative PSA level, digital rectal examination (DRE) and Gleason score. For comparative analysis of two main models statistical calculation was performed. Clinical application of magnetic resonance tomography is mandatory for evaluation of local extension for patients with intermediate and high risk. Comparative analysis of two main methods revealed the superiority of NCCN over D'Amico classification (p=0,0032) in predicting locally advanced prostate cancer.

Extraction of a foreign body from the breast parenchyma using radioguided occult lesion localisation (ROLL) technique: a new approach.

The radioguided occult lesion localisation (ROLL) technique is used for the excision of non-palpable breast lesions. This technique has not been described previously for the extraction of foreign bodies from the breast parenchyma. We report here a female patient who was admitted to our hospital with a foreign body in her right breast. The ROLL technique was used for the extraction of the foreign body.

Surgical treatment of patients with the complicated clinical course of gastric cancer.

Research objective was to study the results of surgical treatment of gastric cancer with clinical diseases complicated by the concomitant pathology in patients of different age groups. The author analysed data on 98 patients men and women with gastric cancer who received surgical treatment in the Abdominal Oncology Department at the National Centre of Oncology (Azerbaijan Republic) in 2004-2007. Four patients with gastric cancer were under 40 years old; twenty patients were from 41 to 50 years old; twenty five patients were from 51 to 60 years old; forty three patients were from 61 to 70 years old; six patients were older than 70. Clinical stages of the malignant process were defined according to TNM classification. In 7 of 98 patients with gastric cancer, clinical stage I of the disease was determined. In 26 of 98 patients clinical stage II was determined. In 51 patients clinical stage III was determined. In 14 patients clinical stage IV was determined. 67 of 98 patients had complication of the disease. Prognostic value of cellular immunity in gastric cancer was determined. More than 80% patients with gastric cancer had increased levels of Cancer Embryonic Antigen in the blood serum. The data analysis of long-term treatment of patients with gastric cancer showed 16.7% recurrence rate and 22.8% metastasis rate in under 50 year old patients, 10.4% recurrence rate and 11.9% metastasis rate in 51-70 year old patients, 0% recurrence rate and 20% metastasis rate in 70 year old patients. Multivariate analysis revealed the factors for determining the gastric cancer prognosis. Detection of the tumor in an early stage, standardized surgical treatment, close follow-up schedules and better perioperative management are expected to increase survival time for patients with gastric cancer.

X-ray contrast media induce aortic endothelial damage, which can be prevented with prior heparin treatment.

X-ray contrast media induce damage to the endothelial layer of vessels and initiate the formation of thrombosis, which is a complication for clinical diagnostic procedures. The future determination of the mechanisms, which underlie the damaging effect of X-ray contrast medium on vascular wall cells, especially vascular endothelium and possible prevention of this damage by vasoprotector, will result in a larger application in diagnostic procedures. The aim of the present study is to analyze the effect of X-ray contrast media (Verographin, Iodamid and Iodolipol) on the arterial endothelium morphology by using ultrastructural techniques (scanning and transmission electron microscopy, SEM and TEM respectively). Experiments have been carried out on New Zealand white rabbits (6 month old) and Wistar rats (6-8 month old) after a single injection of X-ray contrast media with and without prior heparin treatment. Control groups of animals were exposed to the same procedure but without X-ray contrast media injection and only received isotonic saline solution. The following time points were selected: 1, 6, 24, 72 h and 7 days. At the end of the experiments, animals were anesthetized by pentobarbital and then perfused with a balanced buffer for 1 min and followed by perfusion fixation with Karnovsky's fixative containing buffered solution of 2.5% paraformaldehyde and 2.5% glutaraldehyde (pH 7.36) at least 30 min. The aortic tissue was removed and immediately placed into a fresh portion of the same fixative. Aortic samples were then prepared for scanning and transmission electron microscopy (SEM and TEM respectively). Immediately after the injection of X-ray contrast media, the number of microvilli and blebs on the luminal surface of the endothelial cells (EC) significantly increased. Very often, nuclear portions of the EC sharply protruded into the vessel lumen. Clusters of spindle-shaped EC were seen throughout the endothelial monolayer. These changes persist through the 72-h period after X-ray contrast media injection. Moreover, the desquamation and denudation of the EC from the monolayer is often observed and this is accompanied by the presence of a microthrombus on the vessel surface. Seven days after the post-injection period, endothelial monolayers still show severe damage, which often coexists with the presence of a different sized microthrombus on the vessel surface. However, the degree of lesion formation in most areas is substantially decreased as compared to the early period of post-injection (24 and 72 h). Heparin treated group shows intact morphology similar to the control experimental groups (saline injected group). Infrequently, minimal morphological changes of the endothelium, such as increased number of microblebs and microvilli, were seen with heparin treatment. We conclude that the negative side effects of the X-ray contrast media can be eliminated by a single injection of heparin or other vasoprotector prior to the diagnostic procedure.

Spectral filters in low-vision correction.

Coloured filters are used to protect the lens, retina and other ocular tissues against the hazard of light damage and to improve the quality of vision mainly in cases of ocular media opacities. Four types of yellow, amber and orange filters have been designed as tinted glasses, shields and colour covering of spectacles. They were tested on 15 adult patients with partial cataract and on 80 children with congenital pathology (i.e. macular hypoplasia, albinism, aphakia after congenital cataract). The majority of the children had nystagmus. The filters with particular spectral characteristics provide reduction of light intensity in the light-damaging range by at least a factor of five. Optimal filters were selected by examination of visual acuity, contrast frequency sensitivity, glare sensitivity and subjective selection by the patients. The effects of filters were: 11-43% increase in corrected visual acuity, 27-34% increase in contrast sensitivity function (CSF) for all frequencies and a marked reduction in glare sensitivity. All patients reported subjective improvement including reduction of photophobia, eye-strain and eye discomfort. It is concluded that coloured filters are able to contribute substantially to rehabilitation of low-vision patients.

Association between periodontal disease and acute myocardial infarction.

BACKGROUND: Coronary heart disease is the leading cause of morbidity and mortality throughout the world. Well-known risk factors independently or combined participate in both myocardial infarction and atherosclerosis. Recent data have shown that viral and bacterial infections may also contribute to the acute thromboembolic events. The aim of the present study was to investigate the possible association between periodontal health and coronary heart disease in patients with acute myocardial infarction and chronic coronary heart disease. METHODS: A total of 120 patients, 60 with acute myocardial infarction (AMI) and 60 with chronic coronary heart disease (CCHD) were included in this study. The patients in the AMI group (50 men and 10 women; mean age 53.8 +/- 9.5 years) were admitted to the Department of Cardiology, University Hospital of Ege because of AMI. The CCHD patients group (42 men and 18 women; mean age 58.5 +/- 11.6 years) had no documented history of recent acute coronary events. All patients were clinically examined and completed a medical questionnaire. Missing teeth, restorations, probing depth (PD) and bleeding on probing (BOP) were recorded. Blood samples were taken on admission for measurements of serum total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol), and fasting blood glucose level. Sample proportions were compared by chi square test, quantitative variables with Student t test. The relation of clinical parameters and conventional risk factors to AMI was assessed with logistic regression analysis. RESULTS: The number of sites with PD > or = 4 mm, the percentage of sites exhibiting BOP, smoking status, total cholesterol, LDL-cholesterol, and triglycerides were statistically different between AMI and CCHD groups (P <0.05). Logistic regression analysis showed that the percentage of sites exhibiting BOP, the number of sites with PD > or = 4, the number of restorations, smoking status, and triglycerides levels were significantly associated with AMI (P <0.05). CONCLUSIONS: The results of this study indicate that periodontal disease may be associated with acute myocardial infarction. To our knowledge, this is the first study that reports the importance of periodontal health in the occurrence of acute myocardial infarction in a Turkish population. We propose that prospective randomized studies are needed to determine whether periodontal disease is a risk factor in the occurrence of acute myocardial infarction.