BC-miR: Monitoring Breast Cancer-Related miRNA Profile in Blood Sera—A Prosperous Approach for Tumor Detection

Breast cancer is the most frequent cancer with a high fatality rate amongst women worldwide. Diagnosing at an early stage is challenging, and due to the limitations of the currently used techniques, including mammography and imaging diagnostics, it still remains unascertained. Serum biomarkers can be a solution for this as they can be isolated in a less painful, more cost-effective, and minimally invasive manner. In this study, we shed light on the relevant role of multiple microRNAs (miRNAs) as potential biomarkers in breast cancer diagnosis. We monitored the expressional changes of 15 pre-selected miRNAs in a large cohort, including 65 patients with breast cancer and 42 healthy individuals. We performed thorough statistical analyses on the cohort sample set and determined the diagnostic accuracy of individual and multiple miRNAs. Our study reveals a potential improvement in diagnostics by implicating the monitoring of miR-15a+miR-16+miR-221 expression in breast cancer management

BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness

, László Tordai 4 , Rozália Tóth 4 , Zsuzsanna Kahán 4 and Lajos Haracska 5,

Regional differences in the neuronal expression of cyclooxygenase-2 (COX-2) in the newborn pig brain

Cycoxygene (COX-2 is the major costitutively expressed COX isoform in the newborn brain. COX-2 derived prostanoids and reactive oxygen species appear to play a major role in the mechanism of perinatal hypoxic-ischemic injury in the newborn piglet, an accepted animal model of the human term neonate. The study aimed to quantitatively determine COX-2 immunopositive neurons in different brain regions in piglets under normoxic conditions (n=15), and 4 hours after 10 min asphyxia (n=11). Asphyxia did not induce significant changes in neuronal COX-2 expression of any studied brain areas. In contrast, there was a marked regional difference in all experimental groups. Thus, significant difference was observed between fronto-parietal and temporo-occipital regions: 59±4% and 67±3% versus 41±2%* and 31±3%* respectively (mean±SEM, data are pooled from all subjects, n=26, *p<0.05, vs. fronto-parietal region). In the hippocampus, COX-2 immunopositivity was rare (highest expression in CA1 region: 14±2%). The studied subcortical areas showed negligible COX-2 staining. Our findings suggest that asphyxia does not significantly alter the pattern of neuronal COX-2 expression in the early reventilation period. Furthermore, based on the striking differences observed in cortical neuronal COX-2 distribution, the contribution of COX-2 mediated neuronal injury after asphyxia may also show region-specific differences. © 2012 The Japan Society of Histochemistry and Cytochemistry

Comparison of cerebrocortical microvascular effects of different hypoxic-ischemic insults in piglets: A laser-speckle imaging study

The newborn pig is a widely accepted large animal model of hypoxic/ischemic (H/I) encephalopathy (HIE) of the term neonate appropriate for translational research. The methodology of the induction of H/I stress shows extensive variability of the literature, and little is known how these affect study outcome. The purpose of the present study was to determine the cerebrocortical microvascular effects of different H/I insults used in current HIE piglet models. For the semiquantitative study of cerebrocortical blood flow, we developed a methodological innovation: an operating microscope was converted into a custom-designed laser-speckle imager. Anesthetized, air-ventilated newborn pigs (n=7) were fitted with a closed cranial window. Speckle image series (2 ms, 1 Hz) were collected during baseline conditions, during transient bilateral carotid artery occlusion (BCAO), hypoxic (FiO2=0.1) hypoxia, hypoxia + BCAO, and asphyxia induced by suspending ventilation. Laser-speckle contrast analysis was performed off-line over parenchymal and arteriolar regions of interests, and pial arteriolar diameters were also determined for detailed analysis of cortical perfusion changes. Under normoxic conditions, transient BCAO did not affect parenchymal perfusion or pial arteriolar diameters. Hypoxia induced marked cortical hyperemia in 5 out of 7 piglets, with simultaneous increases in pial arteriolar diameters and arteriolar flow velocity, however, BCAO could not even affect these hypoxia-induced perfusion changes. In contrast to hypoxia or hypoxia + BCAO, asphyxia inevitably led also to severe cerebrocortical ischemia. In summary, acute reversible BCAO does not reduce cerebrocortical blood flow in the piglet, and thus it likely does not exacerbate the effect of hypoxic ventilation. Asphyxia elicits not only severe hypoxia, but also severe brain ischemia. These microcirculatory effects must be taken into consideration when assessing results obtained in the various HIE piglet models

Good practice: The experiences with the utilization of residual cancer burden—A single institution study

Abstract Introduction The use of neoadjuvant therapy (NAT) has been showing an incraesing tendency in the treatment of locally advanced breast cancer. The evaluation of residual cancer could be performed by Residual Cancer Burden (RCB) calculator. The prognostic system takes the two largest diameters of the tumor, the cellularity, the amount of in situ carcinoma, the number of metastatic lymph nodes, and the size of the largest metastatic deposit into account. The aim of our study was to examine the reproducibility of RCB in NAT treated patients. Methods Patients who were treated with NAT and had resection specimens between 2018 and 2021 were selected. Histological examination was performed by five pathologists. After assessment of the examined variables, RCB points and RCB classes were defined. For statistical analysis, interclass correlation was used (SPSS Statistics V.22.0 software). Results Altogether 100 patients were included in our retrospective, cohort study (average age: 57 years). In two‐thirds of the cases, third generation chemotherapy was used, and mastectomy was performed. Significant concordance was found in the two largest diameters of the tumor (coefficients, 0.984 and 0.973), the cellularity (coefficient, 0.970), and the largest metastatic deposit (coefficient, 0.998). Although the amount of in situ carcinoma proved to be the least reproducible factor, it resulted in almost 90% of agreement (coefficient, 0.873). Regarding RCB points and classes, similar results were observed (coefficients, 0.989 and 0.960). Conclusions Significant agreement was observed between examiners based on almost all RCB parameters, points, and classes, reflecting the optimal reproducibility of RCB. Therefore, we recommend the use of the calculator in routine histopathological reports in NAT cases

Molecular hydrogen alleviates asphyxia-induced neuronal cyclooxygenase-2 expression in newborn pigs

Cyclooxygenase-2 (COX-2) has an established role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE). In this study we sought to determine whether COX-2 was induced by asphyxia in newborn pigs, and whether neuronal COX-2 levels were affected by H2 treatment. Piglets were subjected to either 8 min of asphyxia or a more severe 20 min of asphyxia followed by H2 treatment (inhaling room air containing 2.1% H2 for 4 h). COX-2 immunohistochemistry was performed on brain samples from surviving piglets 24 h after asphyxia. The percentages of COX-2-immunopositive neurons were determined in cortical and subcortical areas. Only in piglets with more severe HIE, we observed significant, region-specific increases in neuronal COX-2 expression within the parietal and occipital cortices and in the CA3 hippocampal subfield. H2 treatment essentially prevented the increases in COX-2-immunopositive neurons. In the parietal cortex, the attenuation of COX-2 induction was associated with reduced 8'-hydroxy-2'-deoxyguanozine immunoreactivity and retained microglial ramifcation index, which are markers of oxidative stress and neuroin fl ammation, respectively. This study demonstrates for the first time that asphyxia elevates neuronal COX-2 expression in a piglet HIE model. Neuronal COX-2 induction may play region-specific roles in brain lesion progression during HIE development, and inhibition of this response may contribute to the antioxidant/anti-in fl ammatory neuroprotective effects of H2 treatment