The clinical utility of miR-215 as a potential biomarker in colon cancer was investigated. The levels of miR-215 were quantified by real-time qRT-PCR in 34 paired normal and tumor specimens. The expression levels of miR-215 were decreased in colon tumors, and were associated with patient survival. Thus, miR-215 is a potential prognostic biomarker in colon cancer. Background We have previously shown that miR-215 suppressed the expression of key targets such as thymidylate synthase (TS), dihydrofolate reductase, and denticleless protein homolog (DTL) in colon cancer. miR-215 is a tumor suppressor candidate due to the upregulation of p53 and p21 by targeting DTL. However, high levels of miR-215 conferred chemoresistance due to cell cycle arrest and reduced cell proliferation by suppressing DTL. In this study, the clinical significance of miR-215 was further investigated as a potential prognostic biomarker in colon cancer patients. Methods Total RNAs were extracted from 34 paired normal and colon (stage II and III) tumor specimens using the Trizol-based approach. The levels of miR-215 and a closely related miR-192 were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) expression analysis. The expression of DTL mRNA and protein were quantified by real time qRT-PCR and immunohistochemistry. Results The expression levels of miR-192 (P = .0008) and miR-215 (P < .0001) were significantly decreased in colon tumors compared with normal tissues. DTL was significantly over-expressed and was inversely correlated with miR-215, further suggesting an in vivo physiologic relevance of miR-215 mediated DTL suppression. Kaplan-Meier survival analysis by Cox regression revealed that high levels of miR-215 expression (hazard ratio, 3.516; 95% confidence interval, 1.007–12.28, P = .025) are closely associated with poor patient’s overall survival. Furthermore, an elevated expression of a miR-215 target protein DTL was detected in colon cancer tissues whereas no expression was present in normal tissues. Conclusion miR-215 has a unique potential as a prognostic biomarker in stage II and III colon cancer.

PurposemicroRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Experimental DesignTotal RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.ResultsThe expression levels of miR-200c (P<0.0001) and miR-205 (P<0.0001) were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028). Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.ConclusionmiR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

Sharks and skates represent the earliest vertebrates with an adaptive immune system based on lymphocyte antigen receptors generated by V(D)J recombination. Shark B cells express two classical immunoglobulins (Ig), IgM and IgW, encoded by an early, alternative gene organization consisting of numerous autonomous miniloci, where the individual gene cluster carries a few rearranging gene segments and one constant region, μ or ω. We have characterized eight distinct Ig miniloci encoding the nurse shark omega heavy (H) chain. Each cluster consists of VH, D and JH segments and six to eight constant (C) domain exons. Two interspersed secretory exons, in addition to the 3’-most C exon with tailpiece, provide the gene cluster with the ability to generate at least six secreted isoforms that differ as to polypeptide length and C domain combination. All clusters appear to be functional, as judged by the capability for rearrangement and absence of defects in the deduced amino acid sequence. We previously showed that IgW VDJ can perform isotype switching to μ C regions; in this study we found that switching also occurs between ω clusters. Thus C region diversification for any IgW VDJ can take place at the DNA level, by switching to other ω or μ C regions, as well as by RNA processing to generate different C isoforms. The wide array of pathogens recognized by antibodies require different disposal pathways, and our findings demonstrate complex and unique pathways for C effector function diversity that evolved independently in cartilaginous fishes.

Background Until today, assessment of renal function has remained a challenge for modern medicine. In many cases, kidney diseases accompanied by a decrease in renal function remain undetected and unsolved, since neither laboratory tests nor imaging diagnostics provide adequate information on kidney status. In recent years, developments in the field of functional magnetic resonance imaging with application to abdominal organs have opened new possibilities combining anatomic imaging with multiparametric functional information. The multiparametric approach enables the measurement of perfusion, diffusion, oxygenation, and tissue characterization in one examination, thus providing more comprehensive insight into pathophysiological processes of diseases as well as effects of therapeutic interventions. However, application of multiparametric fMRI in the kidneys is still restricted mainly to research areas and transfer to the clinical routine is still outstanding. One of the major challenges is the lack of a standardized protocol for acquisition and postprocessing including efficient strategies for data analysis. This article provides an overview of the most common fMRI techniques with application to the kidney together with new approaches regarding data analysis with deep learning. Methods This article implies a selective literature review using the literature database PubMed in May 2021 supplemented by our own experiences in this field. Results and Conclusion Functional multiparametric MRI is a promising technique for assessing renal function in a more comprehensive approach by combining multiple parameters such as perfusion, diffusion, and BOLD imaging. New approaches with the application of deep learning techniques could substantially contribute to overcoming the challenge of handling the quantity of data and developing more efficient data postprocessing and analysis protocols. Thus, it can be hoped that multiparametric fMRI protocols can be sufficiently optimized to be used for routine renal examination and to assist clinicians in the diagnostics, monitoring, and treatment of kidney diseases in the future. Key Points:  Citation Format

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Gender discrimination which refers to the bias based on people's gender, exist in most patriarchal societies and have been presented in many forms during people's life in different stages. With the deeply reviewing of relative sources, the presenting of gender discrimination within workplace has been proofed as a serious problem globally since some regions considered the problem as 'solved' or 'common' phenomenon instead of a serious social problem. Corporate culture has struggled people by presenting gender discrimination, especially for women during the work time. Female workers are suffering under the pressure of discriminatory corporate culture within workplace from various aspects like the sexual harassment, hidden rules for promotion, the existence of glass-ceiling and special stipulations particularly set for females like dressing code. Although both male and female workers can be limited by the discriminated corporate culture, females are the main victims who directly suffer from both written and invisible rules. The paper deeply talking about how the discrimination exist in workplace and how it affects workers especially female workers.

Purpose: The consideration of radiation exposure is becoming more important in metastatic melanoma due to improved prognoses. The aim of this prospective study was to investigate the diagnostic performance of whole-body (WB) magnetic resonance imaging (MRI) in comparison to computed tomography (CT) with 18F-FDG positron emission tomography (PET)/CT and 18F-PET/MRI together with a follow-up as the reference standard. Methods: Between April 2014 and April 2018, a total of 57 patients (25 females, mean age of 64 ± 12 years) underwent WB-PET/CT and WB-PET/MRI on the same day. The CT and MRI scans were independently evaluated by two radiologists who were blinded to the patients’ information. The reference standard was evaluated by two nuclear medicine specialists. The findings were categorized into different regions: lymph nodes/soft tissue (I), lungs (II), abdomen/pelvis (III), and bone (IV). A comparative analysis was conducted for all the documented findings. Inter-reader reliability was assessed using Bland–Altman procedures, and McNemar’s test was utilized to determine the differences between the readers and the methods. Results: Out of the 57 patients, 50 were diagnosed with metastases in two or more regions, with the majority being found in region I. The accuracies of CT and MRI did not show significant differences, except in region II where CT detected more metastases compared to MRI (0.90 vs. 0.68, p = 0.008). On the other hand, MRI had a higher detection rate in region IV compared to CT (0.89 vs. 0.61, p > 0.05). The level of agreement between the readers varied depending on the number of metastases and the specific region, with the highest agreement observed in region III and the lowest observed in region I. Conclusions: In patients with advanced melanoma, WB-MRI has the potential to serve as an alternative to CT with comparable diagnostic accuracy and confidence across most regions. The observed limited sensitivity for the detection of pulmonary lesions might be improved through dedicated lung imaging sequences.

Background: microRNAs (miRNAs) have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. As a result, miRNAs represent important diagnostic biomarkers for the advancement of cancer and potential therapeutic approaches. They may be up-regulated or down-regulated in various tumor types, thus act as oncogenes or tumor suppressors. Although accumulating evidence suggests the role of aberrant miRNA expression in endometrial carcinogenesis, there is still limited data available about the endrometrial miRNAs. Endometrial cancer is characterized by frequently infiltrating tumors, and one of the most important molecular alterations in this process is through epithelial-mesencymal transition (EMT). Several studies implicated the role of miRNAs targeting the critical players during EMT. The goal of this study is to investigate the clinical utility of selected key miRNAs in archival FFPE tissue samples of patients with endometrial cancer. In this study, the expression of miR-26a, miR-205, miR-200c, miR-192, miR-215, let-7g, miR-21, miR-181b were quantified from 20 stage I, 2 stage II, 5 stage III, 8 stage IV endometrial cancer patients (endometrioid-type endometrial cancer (EEC), endometrial serous carcinoma(ESC), clear cell carcinoma(CCC) undifferentiated carcinoma (UDC), malignant mullerian mixed tumor (MMMT)) with up to 15 years clinical follow up information. Methods: Using archival FFPE tissues, areas of tumor and normal tissues were identified according to the corresponding hematoxylin and eosin stained sections, and cores of 1.5 mm in diameter were extracted. Total RNAs were isolated from 35 paired endometrial tumor and adjacent normal tissue specimens by using Trizol based approach. The expression levels of miRNAs were quantified by using real-time qRT-PCR analysis. Results: The expression of miR-205 (p=0.0002) and miR-200c (p&lt;0.0001) were significantly elevated in endometrial cancer tissue specimens when compared to adjacent normal tissues. Kaplan-Meier survival analysis indicated that low levels of miR-205 expression (hazard ratio, 0.309; log rank test, p=0.018) is closely associated with better patient's overall survival. Conclusions: miR-205 holds a great potential as a prognostic biomarker in endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 158. doi:10.1158/1538-7445.AM2011-158