Combination of inositol and alpha lipoic acid in metabolic syndrome-affected women: a randomized placebo-controlled trial

Inositol has been reported to improve insulin sensitivity since it works as a second messenger achieving insulin-like effects on metabolic enzymes. The aim of this study was to evaluate the inositol and alpha lipoic acid combination effectiveness on metabolic syndrome features in postmenopausal women at risk of breast cancer

Metabolic syndrome-breast cancer link varies by intrinsic molecular subtype

Metabolic syndrome (MS) has been shown to increase the risk of breast cancer. Existing data suggest that the strength of metabolic syndrome-breast cancer link varies by intrinsic molecular subtype, but results from worldwide literature are controversial. Primary endpoint of the study was to assess whether MS is a predictor of specific breast cancer (BC) subtype. Secondary endpoint was to determine whether components of MS can individually increase the risk of specific breast cancer subtype

Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit

Combined effect of obesity and diabetes on early breast cancer outcome: A prospective observational study

Background: Previous studies suggested that obesity and diabetes were correlated with breast cancer outcome. The aim of the present study was to investigate the prognostic effect of obesity and diabetes on the outcome of early breast cancer patients. Materials and Methods: Overall, 841 early breast cancer patients were prospectively enrolled between January 2009 and December 2013. Study population was divided into four groups: (1) patients without obesity or diabetes; (2) patients with only diabetes; (3) patients with only obesity; and (4) patients with both diabetes and obesity. Categorical variables were analyzed by the chi-square test and survival data by the log-rank test. Results: At diagnosis, obese and diabetic patients were more likely to be older (p < 0.0001) and post-menopausal (p < 0.0001) and to have a tumor larger than 2 cm (p < 0.0001) than patients in groups 1–3. At univariate analyses, obese and diabetic patients had a worse disease-free survival (p = 0.01) and overall survival (p = 0.001) than did patients without obesity and diabetes. At multivariate analyses, the co-presence of obesity and diabetes was an independent prognostic factor for diseasefree survival (hazard ratio=2.62, 95% CI 1.23–5.60) but not for overall survival. Conclusions: At diagnosis, patients with obesity and diabetes were older, had larger tumors and a worse outcome compared to patients without obesity or diabetes. These data suggest that metabolic health influences the prognosis of patients affected by early breast cance

Association between mode of breast cancer detection and diagnosis delay

abstract We investigated the association between mode of breast cancer (Bca) detection and diagnosis delay in a case-series of primary, histologically confirmed Bca patients from Southern Italy. Nine hundred and fifty nine women diagnosed with incident, primary Bca were recruited in two southern Italian regions. We grouped the mode of detection into two categories: Self-Detection (S-D) and Mammography (MG). Diagnosis delay was defined as the time between detection and a histologically confirmed diagnosis of invasive Bca. 20.9% detected Bca with MG while 79.1% had S-D Bca. Women who detected Bca themselves (S-D) were more likely to delay breast cancer diagnosis than women who were diagnosed by a mammography (MG) (OR: 2.0; 95% CI: 1.39–2.87); when considering the model adjusted for health system-related characteristics, the risk increased (OR: 2.13; 95% CI: 1.47–3.09). Our study indicates a disadvantage in terms of diagnostic delay for women who were admitted and treated in community hospitals compared to women admitted and treated in breast health services

The Dynamic Optical Breast Imaging in the Preoperative Workflow of Women with Suspicious or Malignant Breast Lesions: Development of a New Comprehensive Score

Purpose. To determine the diagnostic accuracy of DOBIComfortScan in patients with Breast Imaging Reporting suspect breast lesions (BI-RADS) 4-5 breast lesions. Materials and Methods. One-hundred and thirteen patients underwent DOBIComfortScan examination before surgery. Twelve parameters were taken into consideration to define DOBI findings. Results. Twenty-seven radical mastectomies, 47 quadrantectomies and 39 wide excisions, were performed. Overall, 65 invasive cancer, 9 in situ carcinoma and 39 nonmalignant lesions, were observed. Ten out of 12 considered parameters resulted significantly in association with histology at discriminant analysis. A summation score of 30.5 resulted to be the best cut off at ROC analysis, giving a sensitivity and specificity of 80% and 87%, respectively, and a positive predictive value of 92.2%. Finally the following DOBI-BI-RADS model was developed: malignant B5≥38 score); possibly malignant (B4=25-37 score); benign but the possibility of malignancy cannot be excluded (B3=20-24 score); benign (B2&lt;20 score). Conclusion. definition of other parameters permits to improve the accuracy of this procedure. Further studies are warranted to define the potential role of DOBIComfortScan in breast cancer imaging.</jats:p

Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial

BACKGROUND: After two studies reporting response rates higher than 70% in HER2-positive metastatic breast cancer with weekly trastuzumab and vinorelbine, we planned a phase 2 study to test activity of the same combination, with trastuzumab given every 3 weeks. METHODS: Patients with HER2-positive metastatic breast cancer (3+ at immunohistochemistry or positive at fluorescence in situ hybridization), PS ≤2, normal left-ventricular ejection fraction (LVEF) and no more than one chemotherapy line for metastatic disease were eligible. Vinorelbine (30 mg/m(2)) was given on days 1&8 every 21 and trastuzumab (8 mg/kg day 1, then 6 mg/kg) every 21 days). A single-stage phase 2 design, with p(0 )= 0.45, p(1 )= 0.65, type I and II error = 0.10, was applied; 22 objective responses were required in 39 patients. RESULTS: From Nov 2002 to May 2005, 50 patients were enrolled, with a median age of 54 years (range 31–81). Among 40 patients eligible for response assessment, there were 7 complete and 13 partial responses (overall response rate 50%; 95% exact CI 33.8–66.2); 11 patients had disease stabilization, lasting more than 6 months in 10 cases. Response rate did not vary according to patients and tumor characteristics, type and amount of previous chemotherapy. Within the whole series, median progression-free survival was 9.6 months (95% CI 7.3–12.3), median overall survival 22.7 months (95% CI 19.5-NA). Fifteen patients (30%) developed brain metastases at a median time of 12 months (range 1–25). There was one toxic death due to renal failure in a patient receiving concomitant pamidronate. Twenty-three patients (46%) had grade 3–4 neutropenia, 2 (4%) grade 3 anemia, 4 (8%) febrile neutropenia. Two patients stopped treatment because of grade 2 decline of LVEF and one patient because of grade 2 liver toxicity concomitant with a grade 1 decline of LVEF. One patient stopped trastuzumab after 50 cycles because of grade 1 decline of LVEF. CONCLUSION: Although lower than in initial studies, activity of 3-weekly trastuzumab plus vinorelbine fell within the range of results reported with weekly schedules. Toxicity was prevalently manageable. This combination is safe and active for metastatic breast cancer patients who received adjuvant taxanes with anthracyclines

FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders

BACKGROUND: Fos-related antigen 1 (FRA-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases. METHODS: We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis. RESULTS: FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB) samples. CONCLUSION: The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative breast disorders

Endogenous Urotensin II Selectively Modulates Erectile Function through eNOS

Urotensin II (U-II) is a cyclic peptide originally isolated from the neurosecretory system of the teleost fish and subsequently found in other species, including man. U-II was identified as the natural ligand of a G-protein coupled receptor, namely UT receptor. U-II and UT receptor are expressed in a variety of peripheral organs and especially in cardiovascular tissue. Recent evidence indicates the involvement of U-II/UT pathway in penile function in human, but the molecular mechanism is still unclear. On these bases the aim of this study is to investigate the mechanism(s) of U-II-induced relaxation in human corpus cavernosum and its relationship with L-arginine/Nitric oxide (NO) pathway.Human corpus cavernosum tissue was obtained following in male-to-female transsexuals undergoing surgical procedure for sex reassignment. Quantitative RT-PCR clearly demonstrated the U-II expression in human corpus cavernosum. U-II (0.1 nM-10 µM) challenge in human corpus cavernosum induced a significant increase in NO production as revealed by fluorometric analysis. NO generation was coupled to a marked increase in the ratio eNOS phosphorilated/eNOS as determined by western blot analysis. A functional study in human corpus cavernosum strips was performed to asses eNOS involvement in U-II-induced relaxation by using a pharmacological modulation. Pre-treatment with both wortmannin or geldanamycinin (inhibitors of eNOS phosphorylation and heath shock protein 90 recruitment, respectively) significantly reduced U-II-induced relaxation (0.1 nM-10 µM) in human corpus cavernosum strips. Finally, a co-immunoprecipitation study demonstrated that UT receptor and eNOS co-immunoprecipitate following U-II challenge of human corpus cavernosum tissue.U-II is endogenously synthesized and locally released in human corpus cavernosum. U-II elicited penile erection through eNOS activation. Thus, U-II/UT pathway may represent a novel therapeutical target in erectile dysfunction