Weekly epirubicin plus lonidamine in advanced breast carcinoma

: Lonidamine has been demonstrated to potentiate the cytotoxic activity of several antineoplastic drugs, for example anthracyclines. Moreover, epirubicin is considered one of the most active drugs in advanced breast cancer, although optimal dose and schedule remains to be defined. In the present study we have treated 51 patients with advanced breast cancer with a combination of lonidamine (450 mg/day orally from day 1 throughout treatment) and epirubicin (25 mg/m2 i.v.) administered according to a weekly schedule for 24 weeks. Objective responses were observed in 29 out of 51 patients (57%; CR 16%, PR 41%). Liver metastases responded in eight out of 12 evaluable patients (67%). Average response duration was 12.4 months and median overall survival was 23 months (range 1-90+). Toxicity was negligible. The combination of weekly epirubicin and lonidamine is feasible and active in advanced breast cancer patients

Survival of Listeria monocytogenes in uncooked Italian dry sausage (salami).

This study was undertaken to supplement existing information on the survival of Listeria monocytogenes in Italian salami. The fact that Italian salami is frequently consumed by a large number of people poses some serious health implications. Some raw materials have been found to be microbiologically contaminated, for their production occurs without any thermic treatment, and these are in circulation throughout Italy all year round. We selected the product for its microbiological, technological, and commercial characteristics. We analyzed 1,020 samples taken during the autumn and winter 2002 and spring and summer 2003 periods and immediately before selling. The samples were collected from 17 plants with an annual production of between 1 and 2,000 metric tons and with a distribution of products in over 80% of Italy in geographic terms. To detect and enumerate L. monocytogenes, we followed International Organization for Standardization (ISO) 11290 part 1 and 2: 1996 (modified using chromogenic medium Agar Listeria according to Ottarviani and Agosti [ALOA]). L. monocytogenes was found in 22.7% of samples, but the contamination level was less than 10 CFU/g. Contamination prevalence ranged from 1.6 to 58.3% and was lower than 10% in 5 of the 17 plants checked. The most frequently isolated serotypes were 1/2c, 1/2a, 1/2b, and 4b. Additional studies are necessary to establish if the exposure to a small number of L. monocytogenes cells through the consumption of salami represents a significant health risk and, in light of the future introduction of the SANCO/4198/2001 revision 21 "Commission Regulation on Microbiological Criteria for Foodstuffs," is a necessary investigation

The mir-133a, tpm4 and tap63γ role in myocyte differentiation microfilament remodelling and colon cancer progression

MicroRNAs (miRNAs) play an essential role in the regulation of a number of physiologi-cal functions. miR-133a and other muscular miRs (myomiRs) play a key role in muscle cell growth and in some type of cancers. Here, we show that miR133a is upregulated in individuals that under-take physical exercise. We used a skeletal muscle differentiation model to dissect miR-133a’s role and to identify new targets, identifying Tropomyosin-4 (TPM4). This protein is expressed during muscle differentiation, but importantly it is an essential component of microfilament cytoskeleton and stress fibres formation. The microfilament scaffold remodelling is an essential step in cell transformation and tumour progression. Using the muscle system, we obtained valuable information about the microfilament proteins, and the knowledge on these molecular players can be transferred to the cytoskeleton rearrangement observed in cancer cells. Further investigations showed a role of TPM4 in cancer physiology, specifically, we found that miR-133a downregulation leads to TPM4 upregulation in colon carcinoma (CRC), and this correlates with a lower patient survival. At molecular level, we demonstrated in myocyte differentiation that TPM4 is positively regulated by the TA isoform of the p63 transcription factor. In muscles, miR-133a generates a myogenic stimulus, reduc-ing the differentiation by downregulating TPM4. In this system, miR-133a counteracts the differen-tiative TAp63 activity. Interestingly, in CRC cell lines and in patient biopsies, miR-133a is able to regulate TPM4 activity, while TAp63 is not active. The downregulation of the miR leads to TPM4 overexpression, this modifies the architecture of the cell cytoskeleton contributing to increase the invasiveness of the tumour and associating with a poor prognosis. These results add data to the interesting question about the link between physical activity, muscle physiology and protection against colorectal cancer. The two phenomena have in common the cytoskeleton remodelling, due to the TPM4 activity, that is involved in stress fibres formation

Breast cancer and timing of surgery during menstrual cycle: a 5-year analysis of 248 premenopausal women

: In the present report, we retrospectively analyzed the impact of the timing of surgery during menstrual cycle on disease-free and overall survival of 248 premenopausal patients with stage I/II breast cancer who underwent surgery followed by anthracycline-containing adjuvant chemotherapy. With a median follow-up of 5 years, no statistically significant differences were observed in disease-free or overall survival between women operated upon during the follicular (days 0-14) and the luteal (days 15-32) phase of the menstrual cycle. The impact on disease-free and overall survival of lymph-node status, tumor size and hormone receptor expression, but not of the phase of the menstrual cycle at the time of surgery, was confirmed by univariate and multivariate analysis. However, when combined with hormone receptor status, the phase of the menstrual cycle at the time of surgery proved useful to better define the prognosis of primary breast cancer patients, with significantly longer disease-free and overall survival for patients operated upon during the follicular phase and with positive hormone receptors

Intrauterine versus post-mortem magnetic resonance in second trimester termination of pregnancy for central nervous system abnormalities

Objective: To evaluate if limiting factors of intrauterine magnetic resonance imaging (iuMRI) performed in the early second trimester of pregnancy (19\u201323 weeks) affect its accuracy in comparison to post-mortem MRI (pmMRI) in fetuses that underwent termination of pregnancy (TOP) for central nervous system (CNS) defects. Study design: This is a secondary analysis of a 10 years prospective observational study. Cases of TOP < 23 weeks for CNS malformation that had undergone neurosonography (NSG), iuMRI, pmMRI and autopsy were included. The agreement between iuMRI and pmMRI was calculated. The autopsy represented the gold-standard. Results: Overall, 143 TOPs for fetal congenital anomaly underwent the post-mortem diagnostic protocol. Of these, 31 cases underwent iuMRI and pmMRI for CNS abnormality. Three cases were excluded due to brain autolysis at autopsy. Corpus callosum defects were the most represented (16/28; 57 %). In only one case of posterior fossa defect, pmMRI identified the presence of vermian hypoplasia not diagnosed at iuMRI. In 2 cases (7%), iuMRI added clinically relevant additional findings to NSG, that were posteriorly confirmed by pmMRI. Conclusions: The study shows that, at 19\u201323 weeks and for CNS defects, limiting factors that might influence the performance of iuMRI have little influence on iuMRI accuracy. This finding is particularly important for professionals who work in countries with legal bound for TOP in the early second trimester

Toxicity and activity of docetaxel in anthracycline-pretreated breast cancer patients: a phase II study

: Docetaxel has proven effective in advanced breast cancer. Myelosuppression and cumulative fluid retention syndrome are troublesome, potentially avoidable toxicities. In this consecutive cohort study, docetaxel (100 mg/m2 by 1 hour i.v. infusion, q3 weeks) activity and toxicity was explored in 56 anthracycline-pretreated patients (eligible: 55: median age: 51 years [range: 28-68 years]; median performance status: 0 [range: 0-3]) with metastatic breast cancer, using two different granulocyte colony-stimulating factor and steroid pre- and postmedication schedules. Twenty-nine patients (group A) received a 5-day oral prednisone premedication, and 26 (group B) received 4-day low-dose i.m. dexamethasone; group B patients also received prophylactic granulocyte colony-stimulating factor. All patients were evaluable for toxicity and 53 for response. Prophylactic granulocyte colony-stimulating factor significantly lowered the incidence of grade III-IV neutropenia and neutropenic fever (p = 0.0001 and 0.01, respectively). The incidence of moderate-severe fluid retention syndrome was lower in patients receiving i.m. dexamethasone (p = 0.08). Overall response rate was 53% (4 complete responses/24 partial responses, 95% confidence interval 39.4-66.2%); 32% have stable disease and 15% progressive disease. In 21 anthracycline-refractory/resistant patients, as well as in 10 paclitaxel-pretreated patients, the overall response rate was 50%. Docetaxel is highly active in anthracycline- and paclitaxel-pretreated metastatic breast cancer, with manageable toxicity. Optimal use of both granulocyte colony-stimulating factor support and steroid premedication deserves further investigation

Weekly schedule of vinorelbine in pretreated breast cancer patients

Purpose: In this phase II study, we explored tolerability and activity of vinorelbine administered according to a dose-dense weekly schedule with hematopoietic growth factor support in pretreated, advanced breast cancer patients. Patients and methods: From January 1994 to March 1996, 40 patients with metastatic breast cancer, pretreated with at least one prior anthracycline-containing regimen, were entered into the study. Patient characteristics: median age 53 years (range 32-70); ECOG performance status 0-1: 34 patients, 2: 6 patients; dominant visceral metastatic disease: 15 patients, dominant non-visceral: 25; anthracycline-refractory/resistant: 2 patients, sensitive: 38 patients. Six patients were treated as first-line therapy for metastatic disease and 34 in second- or subsequent lines. All patients received vinorelbine at the dose of 25 mg/m2/week as a short intravenous infusion, together with routine antiemetic medication. Granulocyte-colony stimulating factor (Lenograstim) at the dose of 150 microg/m2 subcutaneously on day 3 was included in the treatment schedule. Results: The median number of treatment weeks was 23 (range: 4-24), with a delivered dose-intensity (DDI) of 23.8 mg/m2/week (range: 18.7-25, 95.2% of projected dose-intensity). Toxicity was mild, with non-complicated neutropenia being the main toxicity observed (grade 3-4 in 25% of the patients but only 2% of treatment weeks). Overall response rate was 52.5%, with complete responses in 12.5% of patients. Median duration of the response and median time to progression were 10 and 9 months, respectively. Median overall survival was 19 months. Conclusion: Dose-dense weekly vinorelbine is safe and effective with minimal toxicity in pretreated advanced breast cancer patients

Activity profile of top-class association football referees in relation to fitness test performance and match standard

The aim of this study was to examine the kinematic activity profiles, cardiovascular responses and physical fitness of top-class football referees (n=11) during the FIFA Confederations Cup 2005. Computerised match-analyses (n=9) were performed with a two-dimensional photogrammetric video system, and the cardiovascular demand imposed on the referees (n=12) was measured using heart rate recordings. Total distance covered was 10,218, s=643 m of which 3531, s=510 m was covered at high intensities (>3.6 m.s(-1)). Both total distance covered (r2=0.59; P=0.02) and high-intensity activities (r2=0.44; P=0.05) were related to the distance covered by the ball in the same match. The referees ran at high speed 37% further (P=0.01) in the actual tournament than during under-17 top-level officiating. After the 5-min interval during which high-speed running peaked, in the following 5 min the performance was reduced by 19% (P=0.01) in relation to the mean of the game. Mean heart rate was 161, s=9 b.min(-1) (86, s=3% of maximal heart rate (HRmax)). Mean heart rate (expressed as percentage of HRmax) was related in part (r2=0.36; P5 m.s(-1)) best describes the physical performance of referees; (3) heart rate recording can be a useful tool to determine the most intense periods of a match and (4) the new fitness tests adopted by FIFA were poor predictors of match activities

Position statement and updated international guideline for safe and effective whole-body electromyostimulation training-the need for common sense in WB-EMS application

Whole-Body Electromyostimulation (WB-EMS) is a training technology that enables simultaneous stimulation of all the main muscle groups with a specific impulse intensity for each electrode. The corresponding time-efficiency and joint-friendliness of WB-EMS may be particularly attractive for people unable or unmotivated to conduct (intense) conventional training protocols. However, due to the enormous metabolic and musculoskeletal impact of WB-EMS, particular attention must be paid to the application of this technology. In the past, several scientific and newspaper articles reported severe adverse effects of WB-EMS. To increase the safety of commercial non-medical WB-EMS application, recommendations "for safe and effective whole-body electromyostimulation" were launched in 2016. However, new developments and trends require an update of these recommendations to incorporate more international expertise with demonstrated experience in the application of WB-EMS. The new version of these consensus-based recommendations has been structured into 1) "general aspects of WB-EMS", 2) "preparation for training", recommendations for the 3) "WB-EMS application" itself and 4) "safety aspects during and after training". Key topics particularly addressed are 1) consistent and close supervision of WB-EMS application, 2) mandatory qualification of WB-EMS trainers, 3) anamnesis and corresponding consideration of contraindications prior to WB-EMS, 4) the participant's proper preparation for the session, 5) careful preparation of the WB-EMS novice, 6) appropriate regeneration periods between WB-EMS sessions and 7) continuous interaction between trainer and participant at a close physical distance. In summary, we are convinced that the present guideline will contribute to greater safety and effectiveness in the area of non-medical commercial WB-EMS application

Experience with low-energy gold-gold operations in RHIC during FY 2010

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