scholarly journals Age Dependent Switching Role of Cyclin D1 in Breast Cancer

2012 ◽  
Vol 35 (3) ◽  
pp. 179-185
Author(s):  
Carmela Rinaldi ◽  
Natalia Maria Malara ◽  
Rosalia D’Angelo ◽  
Antonina Sidoti ◽  
Attilio Leotta ◽  
...  

Background: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. The aim of this study was to better understand the molecular dynamics of ductal carcinomas with regard to proliferation and the ageing process.Methods: 130 cases of ductal breast cancer in postmenopausal women, aged 52–96 in 3 age classes were selected. Tumoral tissues preserved in formaldehyde solution and subsequently embedded in paraffin were subjected to analysis Fluorescencein situHybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT- PCR) and immuno-histochemical tests. The molecular variables studied were estimated in relation to the patients’ age.Results: The results obtained suggest that the increment of the levels of cyclin D1 in intra-ductal breast tumors in older woman that we have examined is significantly associated with a lower proliferation rate.Conclusion: Cyclin D1, which characterizes tumor in young women as molecular director involved in strengthening tumoral proliferation mechanisms, may be seen as a potential blocking molecular switch in corresponding tumours in old women.

Author(s):  
Vikash Kumar Gupta ◽  
Buthaina Mohammad Alkandari ◽  
Wasif Mohammed ◽  
Mohsen Ahmed Abdelmohsen ◽  
Mohammad Gaber Abdullah Mohammad

AbstractStudies available in the literature have shown alterations in blood coagulation tests in severe cases of COVID-19 pneumonia, with a significant risk of venous thromboembolism (VTE). Since microvascular thrombosis is a well-known fact in COVID-19 disease, requiring therapeutic anticoagulation, low-molecular weight heparin (LMWH) in prophylactic dose is a part of the clinical management of hospitalized COVID-19 patients. In this scenario, we describe three cases of abdominal spontaneous retroperitoneal hematoma (SRH) in hospitalized reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients.


2021 ◽  
Vol 9 (2) ◽  
pp. 454
Author(s):  
Esther Viedma ◽  
Elias Dahdouh ◽  
José González-Alba ◽  
Sara González-Bodi ◽  
Laura Martínez-García ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Madrid, Spain, on 25 February 2020. It increased in frequency very fast and by the end of May more than 70,000 cases had been confirmed by reverse transcription-polymerase chain reaction (RT-PCR). To study the lineages and the diversity of the viral population during this first epidemic wave in Madrid we sequenced 224 SARS-CoV-2 viral genomes collected from three hospitals from February to May 2020. All the known major lineages were found in this set of samples, though B.1 and B.1.5 were the most frequent ones, accounting for more than 60% of the sequences. In parallel with the B lineages and sublineages, the D614G mutation in the Spike protein sequence was detected soon after the detection of the first coronavirus disease 19 (COVID-19) case in Madrid and in two weeks became dominant, being found in 80% of the samples and remaining at this level during all the study periods. The lineage composition of the viral population found in Madrid was more similar to the European population than to the publicly available Spanish data, underlining the role of Madrid as a national and international transport hub. In agreement with this, phylodynamic analysis suggested multiple independent entries before the national lockdown and air transportation restrictions.


Author(s):  
Damiano Caruso ◽  
Francesco Pucciarelli ◽  
Marta Zerunian ◽  
Balaji Ganeshan ◽  
Domenico De Santis ◽  
...  

Abstract Purpose To evaluate the potential role of texture-based radiomics analysis in differentiating Coronavirus Disease-19 (COVID-19) pneumonia from pneumonia of other etiology on Chest CT. Materials and methods One hundred and twenty consecutive patients admitted to Emergency Department, from March 8, 2020, to April 25, 2020, with suspicious of COVID-19 that underwent Chest CT, were retrospectively analyzed. All patients presented CT findings indicative for interstitial pneumonia. Sixty patients with positive COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) and 60 patients with negative COVID-19 RT-PCR were enrolled. CT texture analysis (CTTA) was manually performed using dedicated software by two radiologists in consensus and textural features on filtered and unfiltered images were extracted as follows: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPP), skewness, and kurtosis. Nonparametric Mann–Whitney test assessed CTTA ability to differentiate positive from negative COVID-19 patients. Diagnostic criteria were obtained from receiver operating characteristic (ROC) curves. Results Unfiltered CTTA showed lower values of mean intensity, MPP, and kurtosis in COVID-19 positive patients compared to negative patients (p = 0.041, 0.004, and 0.002, respectively). On filtered images, fine and medium texture scales were significant differentiators; fine texture scale being most significant where COVID-19 positive patients had lower SD (p = 0.004) and MPP (p = 0.004) compared to COVID-19 negative patients. A combination of the significant texture features could identify the patients with positive COVID-19 from negative COVID-19 with a sensitivity of 60% and specificity of 80% (p = 0.001). Conclusions Preliminary evaluation suggests potential role of CTTA in distinguishing COVID-19 pneumonia from other interstitial pneumonia on Chest CT.


2016 ◽  
Vol 38 (3) ◽  
pp. 1003-1014 ◽  
Author(s):  
Aiyu Zhu ◽  
Yan Li ◽  
Wei Song ◽  
Yumei Xu ◽  
Fang Yang ◽  
...  

Background/Aims: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.


2007 ◽  
Vol 85 (8) ◽  
pp. 909-915 ◽  
Author(s):  
Ismene Serino ◽  
Gaia Izzo ◽  
Diana Ferrara ◽  
Michela d’Istria ◽  
Sergio Minucci

The Harderian gland (Hg), the only gland found in the orbit of the frog Rana esculenta L., 1758, probably plays a role in orbital lubrication. The secretory activity of the Hg is seasonal, showing the highest activity in summer. There is little information on Hg gene expression; previously, we identified a mRNA named harderin, whose deduced protein has no homology with other proteins. Differential expression of the harderin transcript between the sexes expressed during the annual cycle implies sexual dimorphism. RT–PCR (reverse transcription – polymerase chain reaction) analysis, revealed that harderin is expressed during the entire year in the Hg of both sexes. It shows a higher level of expression in the female glands than that of male glands. Two peaks of expression, in February and in June, were observed in the female glands, while only the February peak was observed in those of males. These observations were supported by in situ hybridization. Experiments involving gonadectomy and (or) hormonal replacement therapy showed a significant decrease in harderin in the Hg of females; this effect is prevented by estradiol (testosterone had no effect), while ICI (antiestrogen) counteracts the hormonal prevention, suggesting that this sexual dimorphism is under estradiol control. The constant expression of harderin mRNA during the year suggests a probable constitutive role for this molecule.


1997 ◽  
Vol 45 (1) ◽  
pp. 107-118 ◽  
Author(s):  
André Nadeau ◽  
Gilles Grondin ◽  
Richard Blouin

ZPK is a recently described protein serine/threonine kinase that has been originally identified from a human teratocarcinoma cell line by the polymerase chain reaction and whose function in signal transduction has not yet been elucidated. To investigate the potential role of this protein kinase in developmental processes, we have analyzed the spatial and temporal patterns of expression of the ZPK gene in mouse embryos of different gestational ages. Northern blot analysis revealed a single mRNA species of about 3.5 KB from Day 11 of gestation onwards. In situ hybridization studies demonstrated strong expression of ZPK mRNA in brain and in a variety of embryonic organs that rely on epithelio-mesenchymal interactions for their development, including skin, intestine, pancreas, and kidney. In these tissues, the ZPK mRNA was localized primarily in areas composed of specific types of differentiating cells, and this expression appeared to be upregulated at a time concomitant with the onset of terminal differentiation. Taken together, these observations raise the possibility that the ZPK gene product is involved in the establishment and/or maintenance of a fully cytodifferentiated state in a variety of cell lineages.


2017 ◽  
Vol 16 (4) ◽  
pp. 38-45
Author(s):  
D. A. Ryabchikov ◽  
I. K. Vorotnikov ◽  
T. P. Kazubskaya ◽  
S. S. Lukina ◽  
E. A. Filippova ◽  
...  

Background. Epigenetic changes of TSG are supposed as the most fine and active genes regulation mechanism in particular breast cancer (BC) genes pathway development. The most valuable results are awaited for methylation role of genes located on the short arm of chromosome 3 with also MGMT gene (10q26) in BC pathogenesis because of their ambiguous data for methylation status in tumors. Objective: to illustrate the specific methylation role of the RASSF1A, SEMA3B, RARß2, RHOA, GPX1, USP4, DAG1, NKIRAS1 and MGMT genes promoter regions in BC pathogenesis. Materials and methods. Sample set of 174 BC patients consists of tumor and surrounding histologically normal tissue that were collected and clinically characterized in the N.N. Blokhin National Medical Research Center of Oncology. Two substantive methods were used to evaluate DNA methylation status. To analyse RASSF1A, SEMA3B, RARß2 and MGMT genes methylation we used polymerase chain reaction specific for the methylated allele. Whereas for analyses RHOA, GPX1, USP4, DAG1, NKIRAS1 promoter regions genes methylation status was used methyl sensitive restriction analyses with 2 methyl sensitive endonuclaeses HpaII and HhaI with subsequent polymerase chain reaction. Results. A statistically significant high frequency of RASSF1A, SEMA3B, RARß2, and MGMT genes methylation in epithelial breast tumors compared with histologically normal tissue from the same patients was shown. Significant correlation of RARß2 and MGMT genes methylation frequency considering the different clinical and morphological characteristics of the malignant process was revealed. The statistically significant relationship between methylation of RASSF1A, RARß2 and MGMT genes and patient survival is shown for the first time. Conclusion. The findings of epigenetic changes in the luminal BC supplement the “molecular picture” of this cancer and contribute to an understanding of its pathogenesis. The revealed features of investigated genes methylation can find clinical application for the development of modern approaches to prognosis, prevention and choice of tactics for treatment of BC in females of the Moscow region.


Medicinus ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 31
Author(s):  
Aziza Ghanie Icksan ◽  
Muhammad Hafiz ◽  
Annisa Dian Harlivasari

<p><strong>Background : </strong>The first case of COVID-19 in Indonesia was recorded in March 2020. Limitation of reverse-transcription polymerase chain reaction (RT-PCR) has put chest CT as an essential complementary tool in the diagnosis and follow up treatment for COVID-19. Literatures strongly suggested that High-Resolution Computed Tomography (HRCT) is essential in diagnosing typical symptoms of COVID-19 at the early phase of disease due to its superior sensitivity  (97%) compared to chest x-ray (CXR).</p><p>The two cases presented in this case study showed the crucial role of chest CT with HRCT to establish the working diagnosis and follow up COVID-19 patients as a complement to RT-PCR, currently deemed a gold standard.<strong></strong></p>


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