Exosomes in breast cancer management: Where do we stand? A literature review.

BACKGROUND: Exosomes constitute cellular molecular fingertips that participate in intercellular communication both in health and disease states. Hence, exosomes emerge as critical mediators of cancer development and progression, as well as potential biomarkers and novel therapeutic targets. OBJECTIVE: To review literature data regarding applications of circulating exosomes in breast cancer management. METHODS: This is a literature review of relevant published studies until April 2020 in PubMed and Google Scholar databases. Original papers in the English language concerning exosome related studies were included. RESULTS: Exosomes represent molecular miniatures of their parent cells. Several homeostatic mechanisms control exosomal secretion and synthesis. Exosomal exchange among cells creates an intricate intercellular crosstalk orchestrating almost every tissue process, as well as carcinogenesis. Available data highlight exosomes as major mediators of cancer development and progression. The secretion of specific exosomal molecules, particularly miRNAs, correlates with the underlying processes and can be used as a means of tumor detection and prognostic assessment. CONCLUSIONS: Exosomal miRNAs expression profiles and levels closely relate to cancer extent, type and prognosis. Deep comprehension of such correlations and systematization of experimental outcomes will offer a novel approach in cancer detection and management.

A Strict Patient Selection Protocol Could Be the Key to Success for Transanal Minimally Invasive Surgery (TAMIS).

OBJECTIVES: In recent years, the local excision of benign rectal lesions or early-stage rectal cancers using minimally invasive surgical techniques has replaced radical interventions that caused impairment in patients' quality of life. The aim of the present study was to investigate the feasibility of transanal minimally invasive surgery (TAMIS), as well as its excision quality, its oncologic outcomes, and its impact on anorectal function. METHODS: Patients who underwent TAMIS at a single colorectal unit of a tertiary university hospital from 2015 until 2020 for benign rectal lesions or early-stage malignant rectal lesions, along with unsuitable patients for radical interventions, were included in the present study. RESULTS: Twenty-five patients underwent TAMIS for rectal lesions. Their median distance from the anal verge was 7 cm (range 4-12 cm) and their median size was 3.8 cm (range 2-6 cm). The median operative duration was 75 minutes (range 30-150 minutes) and the median hospitalization interval was 2 days (range 1-6 days). In addition, the negative resection rate was 100% and the recurrence rate was 4% during an average follow-up period of 30 months (range 3-36 months). Two patients (8%) presented short-term complications, and in 1 patient (4%) a hybrid technique was required. Seventeen patients (68%) reported moderate incontinence symptoms 6 weeks postoperatively that subsided in all patients 3 months postoperatively. CONCLUSIONS: TAMIS seemed to be a feasible technique with adequate oncologic outcomes and high excision quality, which preserved patients' quality of life. The impact of TAMIS on anorectal function after neoadjuvant chemoradiotherapy for rectal cancer should be further investigated, however.

Complex refractive index of freshly excised human breast tissue as a marker of disease.

We report differences in the refractive index of healthy and tumorous freshly excised human breast tissue as determined from reflectance profile measurements at five wavelengths (432 nm, 532 nm, 633 nm, 964 nm, 1551 nm) in the visible and near-infrared using a standard prism-coupling refractometer. These refractive index differences, particularly in the near-infrared, can be used to distinguish fibroadenomas and cancerous growths not only from normal breast tissue but also from each other.

A novel way of hook wire placement for surgical resection of suspicious breast lesions using the stereotactic vacuum assisted breast biopsy table.

Preoperative hook localization is a necessary procedure for targeting impalpable breast lesions. The aim of the current study is to introduce an alternative technique of wire placement by using the stereotactic biopsy device instead of the conventionally used mammography device. Fifty-one patients with impalpable mammographic lesions, graded BIRADS 4 or 5, were prospectively enrolled. Mean duration was 7 ± 1.5 minutes. Lesion-to-wire distance was <1 cm in 96% (51/53). Hook wire placement using the stereotactic biopsy device is considered as a safe, accurate, fast, and well-tolerable for the patient procedure.

Predictive factors for breast lesion excision system (BLES) accuracy and safety in stereotactic biopsy of suspicious calcifications.

AIM: To retrospectively assess the effectiveness and safety of BLES stereotactic biopsy of suspicious calcifications and investigate possible predictive factors for underestimation. METHODS AND MATERIALS: Between January 2014 and January 2016, 400 biopsies of suspicious calcifications were performed in our Department using the BLES stereotactic device. The mean age of our population was 58.5 years (range 39-78 years). The final surgical results were used as gold standard. The effectiveness of the method was statistically evaluated. Mammographic size, grade, molecular type, and presence of comedo type/necrosis were assessed as predictive factors. RESULTS: 90/400 (22.5%) cases were cancers (20% invasive cancers, 80% non-invasive cancers). 38/400 cases were atypical lesions (9.5%). No underestimation was found in atypical lesions that underwent surgery (29/38 cases). Downgrade was achieved in 45.5% of cases (with complete removal in 34.4%), concordance in 43.3%, and upgrade was found in 15.5% of the cases; the initial mammographic size and the grade of the cancers were found to be statistically significant predictive factors. The total complication rate was 8.75%. CONCLUSIONS: Breast lesion excision system is a highly accurate and safe stereotactic biopsy technique of suspicious calcifications with low underestimations and high downgrade/removal rates with the potential to alter the final surgical decision in selected cases.

Role of one-pass breast lesion excision system in complete excision of high-risk breast lesions with atypia expressed as clusters of microcalcifications.

PURPOSE: To assess the role of the breast lesion excision system (BLES) in complete removal of clusters of microcalcifications found on mammogram proved histologically to be high-risk lesions with cell atypia. METHODS AND MATERIALS: Three hundred ninety-four consecutive women (mean age 58.5 years, range 39-78 years) with 400 clusters of suspicious microcalcifications underwent stereotactic biopsy using the intact BLES device between January 2014 and January 2016. All cases proved histologically to be high-risk lesions were subsequently assessed for complete removal. The underestimation rate was also assessed. RESULTS: Thirty-eight out of 400 (9.5%) lesions were high-risk lesions with atypia with mean size 7.63 mm (st. dev. = 4.03 mm) which was within the size that the BLES needle can excise (20 mm). Four (10.5%) papillomas with atypia, 14 (36.8%) cases with flat epithelial atypia (FEA), 10 (26.3%) cases with lobular intraepithelial neoplasia (LIN-LIN 1, LIN 2), 8 (21.2%) with atypical ductal hyperplasia (ADH) and 2 (5.3%) cases with mucocele-like lesions (MLL) with atypia were found. Twenty-nine out of 38 lesions had subsequent surgery. Complete excision was achieved in 23/29 lesions (79.3%). No underestimation was found. Two-year mammographic stability was found in all lesions. Non-parametric statistical analysis showed no other significant predictive factor for complete excision apart from the distance of the lesions from the specimen margins (p = 0.031 Mann-Whitney test). CONCLUSION: One-pass BLES intact biopsy technique is a safe method of complete removal of high-risk atypical lesions with high accuracy rates for certain histologies and could be potentially used as an alternative excision method to diagnostic surgery in selected cases. KEY POINTS: • Breast lesion excision system (BLES) is an image-guided biopsy technique that uses radiofrequency to remove an intact piece of tissue including the target breast neoplasm. • Breast lesion excision system (BLES) under stereotactic guidance is able to accurately biopsy high-risk breast lesions expressed mammographically as clusters of suspicious microcalcifications. • BLES under stereotactic guidance is an accurate technique for en bloc excision of selected cases of small clusters of suspicious microcalcifications proved to be high-risk lesions with histopathologically disease-free margins of excision.

RANKL, OPG, TRAIL, KRas, and c-Fos expression in relation to central lymph node metastases in papillary thyroid carcinoma.

PURPOSE: RANKL, OPG and TRAIL have long been pursued in cancer. Mutated KRas proteins and c-Fos overexpression - well-recognized oncogenic events - have been conceived as coordinators of RANKL, OPG and TRAIL pathways. Considering the paucity in the relevant literature, the purpose of the present study was to investigate whether the expression of these molecules configures a distinct papillary thyroid carcinoma (PTC) subgroup with adverse clinicopathological characteristics. METHODS: RANKL, OPG, TRAIL, KRas, and c-Fos immunohistochemical expression in relation to clinicopathological characteristics of PTC was assessed retrospectively in paraffin-embedded PTC specimens from 114 patients who underwent total thyroidectomy with simultaneous central lymph node dissection (CLND). RESULTS: Expression of RANKL, OPG, TRAIL, Kras and c- Fos was revealed in 78.6, 63.2, 61.4, 47.4, and 73.7% of PTC, respectively. As predominant KRas-expressing PTC histotype emerged the classical PTC (cPTC), comprising 66.7% of PTC. A significant correlation was demonstrated of RANKL, OPG, and TRAIL expression with central lymph node metastasis CLNM (p=0.007, p<0.001, and p=0.002, respectively), concerning especially cPTC as regards to RANKL (p=0.027) and OPG (p=0.006), and both cPTC (p=0.043) and follicular variant of PTC (FVPTC) (p=0.049) with regard to TRAIL. OPG expression associated significantly with multifocality (p=0.045). Multivariable-adjusted logistic regression models characterized TRAIL as independent predictor of CLNM (OR=10.335, 95% CI: 1.23-86.87). CLNM correlated significantly with six pairs of coexpressions: TRAIL-KRas (p=0.011), TRAIL-c-Fos (p=0.006), OPG-c-Fos (p=0.024), RANKL-TRAIL (p<0.001), RANKL-OPG (p<0.001), TRAIL- OPG (p<0.001). CONCLUSION: The present study suggested for the first time that OPG, RANKL, TRAIL expressions, either alone or in concert involving c-Fos and KRas expression, are related to CLNM. Further research is warranted to elucidate whether the examined molecules can be endorsed as indicators of aggressive PTC behavior and guide a personalized therapeutic intervention.

The value of stereotactic vacuum assisted breast biopsy in the investigation of microcalcifications. A six-year experience with 853 patients.

PURPOSE: Vacuum Assisted Breast Biopsy (VABB) is a minimal invasive technique, in the diagnostic approach for non palpable lesions. The aim of this study was to evaluate the efficacy and accuracy of VABB in the investigation of breast microcalcifications, a significant mammographic sign of early breast cancer. The rate of histological underestimation and the false negative rate were assessed based on the follow up data and the histological examination of the surgical specimens. METHODS: From January 2005 to November 2011, 853 women with mammographically detected microcalcifications, classified as BI-RADS 3-5, were referred to our Breast Unit for evaluation. During this 6-year period, 825 vacuum-assisted breast biopsies were performed, while 28 women (3.3%) were not submitted to VABB due to superficial location of microcalcifications. RESULTS: VABB histology revealed 594 benign (69.6%), 66 high risk (7.7%) and 164 malignant (19.2%) lesions. Twenty- nine cases were classified as non diagnostic, as in one case (0.1%) the sample of the biopsy was maladjusted and not suitable to undergo histopathological examination due to mechanical alterations and in 28 (3.3%) cases microcalcifications were located in proximity to the skin and open surgical excision was performed. The overall documented underestimation rate was 4.6%, the false negative rate was 2.4%. The sensitivity of the method was 98.2%, specificity 100%, positive predictive value 100% and negative predictive value 97.6%. CONCLUSIONS: VABB is a safe and accurate method for the evaluation of suspicious microcalcifications and diagnosis of early breast cancer.

Ocular Surface Disease in Breast Cancer Patients Using Aromatase Inhibitors.

Aromatase inhibitors (AIs) are widely used as adjuvant hormonal therapy in postmenopausal women with hormone receptor-positive breast cancer. The purpose of this study was to investigate the potential impact of AIs on the anterior segment of the eye and especially the ocular surface. Participants in our study were 41 hormone receptor-positive early stage breast cancer patients (80 eyes), treated with AIs, while 80 eyes of 40 age- and gender-matched healthy controls, not previously used AIs for any purpose, were also evaluated. All participants underwent a complete ophthalmological examination, including best corrected visual acuity (BCVA) assessment, slit-lamp biomicroscopy, and dilated fundus examination. Ocular surface disease-related symptoms and signs were also recorded. The most common symptom was found to be blurred vision, while other symptoms included foreign body sensation, tearing, redness, and photophobia. Slit-lamp examination revealed blepharitis and meibomian gland dysfunction in 75% and 42.5% of patients, respectively. Superficial punctate keratitis and conjunctival injection were also present. Our results demonstrated a high prevalence of ocular surface disease-related symptoms and signs in patients receiving AIs compared to healthy controls. This study may raise a flag regarding the use of AIs. However, further and larger prospective longitudinal studies are needed to examine the possible effect of AIs alone or in combination with chemotherapy in the eyes of breast cancer patients.

Serum irisin levels are lower in patients with breast cancer: association with disease diagnosis and tumor characteristics.

BACKGROUND: Irisin is a recently discovered myokine, involved in the browning of white adipose tissue. To date, its function has been mainly associated with energy homeostasis and metabolism, and it has been proposed as a promising therapeutic target for obesity and metabolic diseases. This is the first study investigating the role of irisin in human breast cancer. METHODS: Participants included one hundred and one (101) female patients with invasive ductal breast cancer and fifty one (51) healthy women. Serum levels of irisin, leptin, adiponectin and resistin were quantified in duplicates by ELISA. Serum levels of CEA, CA 15-3 and Her-2/neu were measured on an immunology analyzer. The association between irisin and breast cancer was examined by logistic regression analysis. The feasibility of serum irisin in discriminating breast cancer patients was assessed by ROC curve analysis. Potential correlations with demographic, anthropometric and clinical parameters, with markers of adiposity and with breast tumor characteristics were also investigated. RESULTS: Serum levels of irisin were significantly lower in breast cancer patients compared to controls (2.47 ± 0.57 and 3.24 ± 0.66 µg/ml, respectively, p < 0.001). A significant independent association between irisin and breast cancer was observed by univariate and multivariate analysis (p < 0.001). It was estimated that a 1 unit increase in irisin levels leads to a reduction in the probability of breast cancer by almost 90%. Irisin could effectively discriminate breast cancer patients at a cut-off point of 3.21 µg/ml, with 62.7% sensitivity and 91.1% specificity. A positive association with tumor stage and marginal associations with tumor size and lymph node metastasis were observed (p < 0.05, p < 0.01, p < 0.01, respectively). CONCLUSIONS: Our novel findings implicate irisin in breast cancer and suggest its potential application as a new diagnostic indicator of the presence of disease.

Effectiveness of sildenafil and U-74389G in a rat model of colitis.

BACKGROUND: Crohn disease is still incurable. Compounds with anti-inflammatory and/or antioxidative effects are tested in various preclinical models of the disease. Our aim was to investigate the effects of sildenafil and lazaroid U-74389G in an experimental rat model of trinitrobenzenesulfonic acid-induced colitis. MATERIALS AND METHODS: Trinitrobenzenesulfonic acid was instilled into the colon of all male Wistar rats except for the rats belonging to the first group. For 6 days, the animals in group 3 were administered daily sildenafil orally, the rats in group 4 were administered daily U-74389G intravenously, and the rats in group 5 were coadministered daily sildenafil orally and intravenous U-74389G. The rats in groups 1 and 2 were not administered any treatment. During the study, the weights were recorded as a marker of clinical condition. The colon damage was evaluated using macroscopic colon mucosal damage index (CMDI), microscopic (Geboes score), and biochemical methods (tissue tumor necrosis factor [TNF]-α and malondialdehyde [MDA]). RESULTS: Sildenafil reduced TNF-α tissue levels and increased body weight. U-74389G reduced TNF-α, the macroscopic index of mucosal damage score (CMDI) and increased body weight. The combined treatment with sildenafil and U-74389G reduced tissue levels of both TNF-α and MDA, lowered CMDI and microscopic Geboes score, and increased body weight. CONCLUSIONS: U-74389G demonstrated a significant anti-inflammatory activity related to its ability to reduce colonic TNF-α, CMDI score, and improve weight change. We confirmed that sildenafil has anti-inflammatory capacity by reducing colonic TNF-α and by improving body weight. Finally, the combined treatment showed superior effects by reducing colonic TNF-α, colonic MDA, CMDI score, Geboes score, and by improving weight.

The effect of U-74389G on pancreas ischemia-reperfusion injury in a swine model.

BACKGROUND: Oxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack. The aim of our study was to evaluate the therapeutic potential of 21-aminosteroid U-74389G in pancreatic injury after ischemia and reperfusion of the organ in a swine model. MATERIALS AND METHODS: Twelve pigs (weighing 28-35 kg) were randomized into the following two experimental groups: group A (control group, n = 6): ischemia of pancreas (30 min) followed by reperfusion for 120 min; and group B (n = 6): ischemia of pancreas (30 min), U-74389G intravenous injection (10 mg/kg) in the inferior vena cava, and reperfusion for 120 min. Tissue and blood sampling was conducted at 0, 30, 60, 90 and 120 min after reperfusion. Repeated measures analysis of variance was performed for the evaluation of differences between the two groups. RESULTS: Histopathologic evaluation did not reveal a statistically significant difference concerning hemorrhage (P = 0.193), leukocyte infiltration (P = 0.838), acinar necrosis (P = 0.183), and vacuolization (P = 0.185) in the pancreatic tissue between the two groups; nevertheless, edema seemed to be more pronounced in the U-74389G group (P = 0.020). Serum metabolic data in the control and therapy groups were not significantly different; accordingly, tissue malondialdehyde levels (P = 0.705) and tumor necrosis factor α values (P = 0.863) did not differ between the two groups. CONCLUSIONS: On the basis of the histologic data and the absence of reduction in the malondialdehyde and tumor necrosis factor α levels, it is concluded that the administration of U-74389G does not seem to exert a sizable therapeutic effect in attenuating pancreatic damage from ischemia-reperfusion injury.

Mesenchymal Stem Cell Transplantation Has a Regenerative Effect in Ischemic Myocardium: An Experimental Rat Model Evaluated by SPECT-CT Assessment.

Translational perspective: Ischemic heart disease remains a major medical problem with high mortality rates. Beside the great efforts devoted to research worldwide and the use of numerous experimental models, an absolute understanding of myocardial infarction and tissue loss has not yet been achieved. Furthermore, the regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in the medical (and especially cardiovascular) community. In a novel experimental rat model, the beneficial effect of mesenchymal stem cell transplantation (MSCT) in a surgically induced ischemic myocardium was documented. From a clinical perspective, this work supports the surgical administration of MSCT in the infarcted area during coronary artery bypass surgery. AIMS: The regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in cardiovascular research. We developed a novel experimental rat model and used it to examine the effect of mesenchymal stem cell transplantation (MSCT) on myocardial ischemia evaluated by SPECT-CT and immunohistochemistry. METHODS AND RESULTS: An open thoracotomy took place for forty adult female Wistar rats with (n = 30) or without (n = 10) surgical ligation of the left anterior descending coronary artery (LAD) in order to cause myocardial ischemia. Myocardial viability was evaluated via SPECT/CT 7 days before surgery, as well as at 7 and 14 days post-surgery. At day 0, 15 animals received homologous stem cells injected at the ischemic myocardium area. A SPECT/CT evaluation showed decreased activity of the myocardial cells in the left ventricle one week post-infarction. Regeneration of the ischemic myocardium fifteen days post-infarction was recorded only in animals subjected to stem cell transplantation. These findings were also confirmed by histology and immunohistochemical analysis, with the significantly higher expression of GATA4 and Nkx2.5. CONCLUSIONS: The positive effect of mesenchymal stem cell transplantation in the ischemic myocardium was recorded. The application of SPECT-CT allowed a clear evaluation of both the quality and quantity of the living myocardium post-infarction, leading to a new approach in the research of cardiovascular diseases. From a clinical perspective, MSCT may be beneficial when accompanied by myocardial revascularization procedures.

Clinical, Histopathological, and Immunohistochemical Characteristics of Predictive Biomarkers of Breast Cancer: A Retrospective Study.

Background/Aim: Breast cancer is a complex disease with variability in clinical manifestation, response to current therapy, and biochemical and histological features among various subgroups. Histologic grading and immuno-histochemical evaluation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index play a crucial role in increasing the differential diagnostic value among various types of breast carcinoma. The aim of this study was to determine the histopathological and immuno-histochemical characteristics of breast tumors from a University Laboratory of Pathology in Greece. Patients and Methods: The study included female patients over 18 years of age, whose histopathological and immunohistochemical reports were stored in the archives of the First Department of Pathology of National and Kapodistrian University of Athens. The study involved 197 female patients with a median age of 70 years and median tumor size of 2.6 cm. Results: Most tumors were located at the left breast and ductal carcinoma was the most common histologic type (35.5%). Most tumors had histologic grade 2 (106, 53.8%), and were classified as TNM stage IIA (65, 33%). Most grade 1 and 2 tumors exhibited high expression of PR, whereas most grade 3 tumors had no PR expression. Moreover, patients with triple-negative cancer presented with grades 2 and 3 at a lower percentage compared to patients without a triple-negative phenotype (p=0.001). Conclusion: The study provided valuable insights into the histopathological and immuno-histochemical characteristics involved in the development and progression of breast cancer.

The impact of the stromal cell-derived factor-1-3'A and E-selectin S128R polymorphisms on breast cancer.

Breast cancer is prone to metastasis even in early stage disease. Stromal cell-derived factor-1 (SDF-1) is a chemokine that has been associated with the egress of cancer cells from the primary focus and homing to distant sites, while E-selectin has been implicated in their trans-endothelial migration. This study was performed to evaluate the association between SDF-1-3'A and E-selectin S128R-two polymorphisms associated with enhanced function-and the risk of breast cancer, as well as their influence on breast cancer outcome. A retrospective analysis was conducted on 261 patients and 480 healthy controls using PCR-RFLP. The frequencies for the wild-type (GG), GA and AA genotypes of SDF-1 were 43.7, 45.2, and 11.1 % in patients, and 51.5, 41.3, and 7.3 % in healthy controls, respectively, while the SDF-1-3'A allelic frequency was 33.7 % at patients and 27.9 % at controls. The SDF-1-3'A carrier group of patients and the A allele of SDF-1 were overrepresented among the breast cancer cases (p = 0.04 and 0.02, respectively). For the E-selectin S128R polymorphism, the frequencies for the wild-type (AA), AC and CC genotypes were 58.6, 38.3, and 3.1 % in patients and 63.8, 31.4, and 3.8 % in controls, respectively, while the C allelic frequency was 22.2 % for patients and 19.5 % for controls. The CC genotype was associated with poorer survival. Otherwise, no significant association was detected between examined genotypes and tumor characteristics. Overall, our findings support that the SDF-1-3'A confers increased susceptibility to breast cancer and that the E-selectin S128R CC genotype may be related to poorer prognosis. Investigation in bigger cohorts of patients is warranted.

MMP-2 -1306C>T polymorphism in breast cancer: a case-control study in a South European population.

This case control study aims to investigate the role of MMP-2 -1306C>T polymorphism as a potential risk factor and possible prognostic marker for breast cancer in a South European population. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. MMP-2 -1306C>T polymorphism was genotyped; multivariate logistic regression as well as Cox regression analysis were performed. MMP-2 -1306C>T status was not associated with breast cancer risk either at the total sample or at the subanalyses on premenopausal and postmenopausal women. At the survival analysis, a trend towards a favorable association between MMP-2 -1306C>T allele and disease-free survival as well as overall survival was observed. Regarding subanalyses on ER-negative and ER-positive cases, the favorable association implicating MMP-2 -1306C>T allele was particularly evident among ER-positive cases; no significant associations emerged among ER-negative cases. MMP-2 -1306C>T polymorphism does not seem to be a risk factor for breast cancer in South European population; however, a trend towards a favorable association with survival has been observed.

The effect of synbiotics on acute radiation-induced diarrhea and its association with mucosal inflammatory and adaptive responses in rats.

BACKGROUND: Previous clinical studies advocated that probiotics beneficially affect acute radiation-induced diarrhea. These encouraging results were attributed to the restoration of the intestinal flora; however, there is lack of evidence if and how probiotics influence the underlying pathophysiological mechanisms. AIMS: The present study was conducted to investigate the potential supporting role of a synbiotic preparation (combination of pro- and pre-biotics) on experimentally-induced acute radiation diarrhea from the perspective of mucosal inflammation and histological injury. METHODS: Ninety adult Wistar rats were randomly assigned into six groups. Group A (non-irradiated), group B (non-irradiated/synbiotic supplemented), group C (irradiated), and group D (irradiated/synbiotic supplemented) were followed up to a week after the beginning of the experiment. Group E (irradiated) and group F (irradiated/synbiotic supplemented) were followed up for four days. On the last day of the experiments tissues were harvested for structural and molecular assessments. RESULTS: Synbiotic administration could not avert the occurrence of diarrhea, but significantly attenuated its severity. This effect was associated with the significant downregulation of neutrophil accumulation and lipid peroxidation during the acute phase. During the subacute phase, synbiotic treatment significantly improved both the histological profile and radiation mucositis. These mechanisms significantly contributed to the rehabilitation of the intestinal absorptive function as further indicated from the significantly reduced weight loss. CONCLUSIONS: Given the optimization of the intestinal flora exerted by synbiotics, the resolution of diarrhea relies on the suppression of the "reactive" and the augmentation of "regenerative" components of acute radiation-induced intestinal response.

A Novel Experimental Rat Model for the In Vivo Assessment of Myocardial Ischemia Based on Single Photon Emission Computed Tomography.

BACKGROUND/AIM: Myocardial infarction, an acute medical situation with a high mortality rate worldwide, has been extensively studied in modern cardiovascular research, using different experimental models. However, a deep understanding of myocardial activity loss has not been fully investigated. We have developed a novel experimental rat model for noninvasive assessment of myocardial ischemia based on single photon emission computed tomography (SPECT/CT), in order to further understand and evaluate myocardial activity before and after surgical induction of myocardial ischemia. MATERIALS AND METHODS: Thirty adult female Wistar rats underwent open thoracotomy with (n=20) or without (n=10) surgical ligation of the left anterior descending coronary artery (LAD). The myocardial ischemia was confirmed with ECG and myocardial viability was evaluated via SPECT/CT at 7 days before as well as at 7 and 14 days post-surgery, after which animals were sacrificed and myocardial ischemic injury was further assessed histologically. RESULTS: All animals were evaluated with anatomical and functional criteria based on the SPECT/CT imaging results. A successful surgical technique causing ischemia and loss of myocardial function in all animals undergoing a LAD ligation was established. Furthermore, evaluation of the viable myocardium with SPECT/CT confirmed the reduction of functional myocardial cells of the left ventricle post-infarction, which was also documented histologically. CONCLUSION: Using our technique, the validity of this animal model to induce and evaluate myocardial ischemia was demonstrated. Our choice to apply SPECT-CT qualitative and quantitative evaluation of myocardial function leads to a new approach in experimentation with an anticipated significant impact in the ongoing cardiovascular laboratory research.

Circulating levels of endothelin-1 (ET-1) and its precursor (Big ET-1) in breast cancer early diagnosis.

Deregulation of the endothelin system, comprised of endothelin-1 (ET-1), its isoforms (ET-2 and ET-3) and their receptors (ET(A)R and ET(B)R), is under investigation in various types of human cancer. ET-1 has been suggested to participate in breast cancer development and progression, while Big ET-1, its biological precursor, has also been found elevated in breast cancer patients. In the present study, we investigated plasma ET-1 and Big ET-1 levels in patients with suspicious mammographic lesions, in order to assess their potential application as diagnostic biomarkers in the early estimation of breast disease. The study consisted of 94 patients (Group A to 30 patients with invasive ductal carcinoma: Group B, 30 with ductal carcinoma in situ; and group C, 34 with papilloma or ductal hyperplasia), who underwent an image-guided vacuum-assisted breast biopsy, and 30 healthy controls (group D). ET-1 and Big ET-1 plasma levels were measured with enzyme-linked immunosorbent assay. ET-1 levels did not exhibit significant differences between patients and healthy controls (Group A to 0.92 fmol/mL; Group B: 0.90 fmol/mL; Group C: 0.66 fmol/mL; and Group D: 0.86 fmol/mL). In contrast, Big ET-1 levels were significantly higher in patients with invasive or in situ carcinoma compared to healthy controls (Group A: 0.69 fmol/mL; Group B, 0.62 fmol/mL; and group D: 0.39 fmol/mL; p < 0.001 and p < 0.01). Plasma Big ET-1 may provide a useful tool for the early detection of invasive or noninvasive ductal breast cancer. The utilization of such a diagnostic tool would greatly assist in the modern management of breast cancer.