scholarly journals Morphofunctional transformations during the morphogenesis of the thyroid gland of the offspring of Wistar rats after intrauterine exposure to dexamethasone

Morphologia ◽  
2021 ◽  
Vol 15 (3) ◽  
pp. 155-161
Author(s):  
O.V. Fedosieieva ◽  
V.S. Bushman ◽  
A.G. Necheporenko

Background. In recent years, the prevalence of thyroid pathologies of various origins among children in the world has reached a significantly high level. The use of glucocorticoids during pregnancy remains a debatable issue in obstetrics today, as they can both positively and negatively affect the processes of organ morphogenesis and be the cause of pathological conditions in the postnatal period. Objective: to establish the features of morphofunctional transformations during the morphogenesis of the thyroid gland of the offspring of rats at an early age in normal and after intrauterine action of dexamethasone. Methods. 108 thyroid glands of rats of 3 experimental groups were microscopically examined using histological and immunohistochemical methods, followed by statistical processing of the obtained results. Results. Against the background of high levels of total follicular thyrocytes per 1 day of life in animals that received prenatal dexamethasone, cytoplasmic expression of TgAb was expressed, which correlated with the indicators of nuclear and cytoplasmic Fox-1 expression. From the 7th to the 11th day, a decrease in the total number of thyrocytes per unit area was observed due to the accumulation of colloid in the follicles, an increase in Fox-1 cytoplasmic expression and a decrease in nuclear expression, against the background of increased proliferative activity. By day 21, Fox-1 cytoplasmic and nuclear expression were almost identical. There was a decrease in the intensity of TgAb expression in the cytoplasm of thyrocytes and its expression in the colloid, a decrease in the number of Ki-67 positive thyrocytes per conditional unit area compared with the previous observation period. Conclusion. It was found that prenatal exposure of dexamethasone causes the offspring accelerate the development of morphological structures of the thyroid gland, but functionally they are in a state of stress of both the synthesizing apparatus and the process of hormone excretion, which is expressed in the imbalance of immunohistochemical expression of Fox-1 and TgAb. Such thyrocytes with signs of disturbances in synthetic activity desquamate into the lumen of the follicles, while on the 11th day we compensatory increase in the proliferative activity of the thyroid epithelium.

2018 ◽  
Vol 14 (3) ◽  
pp. 10-14
Author(s):  
S. M. Demidov ◽  
D. A. Demidov ◽  
S. V. Sazonov ◽  
E. I. Churakova

Objective:an immunohistochemical analysis of the characteristics of a recurrent tumor in breast cancer.Materials and methods.The statistical processing of immunohistochemical analysis’ results was performed and the most frequently encountered molecular-genetic subtypes of breast cancer with the development of local relapses were formulated. The analysis used a standard immunohistochemical panel, which is the “gold standard” for diagnostic in Russia today, and includes the expression of receptors for sex hormones (estrogen and progesterone), expression of the human epidermal growth factor HER2/neu receptor gene, and the index of proliferative activity Ki-67. The 2nd stage of the work was the evaluation of the dynamics of changes in the immunohistochemical characteristics of a recurrent tumor in comparison with the primary one.Results and conclusion.The most common local recurrence provides by triple-negative subtype of breast cancer (42 %). The changes in the immunohistochemical characteristics of a recurrent tumor in comparison with the primary one affected only the index of proliferative activity Ki-67 in the direction of its increase by 12 %.


2019 ◽  
Vol 22 (6) ◽  
pp. 97-104
Author(s):  
S. N. Nagornii ◽  
Yu. S. Antsiferova ◽  
A. I. Malyshkina ◽  
D. N. Voronin ◽  
D. L. Voskresenskaya

Data of MRI have the great diagnostic value for the estimation of the character of uterine leiomyoma growth, but do not allow make the unambiguous conclusions about the tumor proliferative activity.Aim:to elucidate the relationship between MRI of uterine leiomyoma and level of tumor proliferation and assess the possibility of the using of MRI data for pre-operative diagnostic of proliferative tumor growth.Materials and methods.Observation of 29 women with uterine leiomyoma was carried out. Before surgical treatment of the patients the MRI investigation with the general pelvic examination and estimation of the quantity of leiomyomas, their position, size and structure was conducted. In leiomyoma tissue and normal myometrium the Ki-67, transforming growth factor β3 (TGF β3) collagen 1A1 (COL1A1) and β-actin (housekeeper gene) mRNAs expressions were estimated by real-time reverse-transcription polymerasechain reaction.Results.According MRI data the most significant differences between studied leiomyomas were connected with T2-weighted signal in comparison with unchanged myometrium: the low T2-weighted signal and preferentially homogenous tissue structure were observed in 58,5% cases, and the increased T2-weighted signal with some heterogeneous structure of tumor were found in 41.1% samples. MRI data were correlated with results of molecular-genetic investigation: the low T2-weighted signal was associated with high levels of TGFβ3, COL1A1 mRNAs expression and minimal level of Ki-67 mRNA expression, whereas in leiomyomas with high T2-weighted signal the high Ki-67 mRNA expression was noted.Conclusion.Leiomyomas with heterogeneous structure and high T2 W signal are characterized by the high level of proliferative activity and this observation must be taken into account during leiomyoma estimation and choice of patient’s treatment tactic.


2021 ◽  
Vol 3 (47) ◽  
pp. 58
Author(s):  
O. Fedosieieva

    Antigenic influence at critical terms of ontogenesis can cause significant changes in the child's immune system. It is known that the entry of antigens into the fetus causes premature release of T-lymphocytes from the thymus and their migration to various organs. The paper was aimed at the study of the folliclegenesis of the thyroid gland in postnatal period at norm and after prenatal influence of staphylococcal toxoid.  In the experimental research as a material were thyroid glands of Wistar rats aged 1 to 60 days of postnatal development (162 animals), about 6 animals in each group. Three animals groups were studied on 1, 3, 7, 11, 14, 21, 30, 45, 60 days after bith. I gr. - intact animals (norm); ІІ gr. - control, animals which were injected intrauterine 0.9% NaCl solution; III - experimental animals injected with staphylococcal toxoid liquid purified adsorbed (10-14 units of binding in 1 ml, diluted 10 portions) by operation intrauterinely on the 18th day of dated pregnancy. Histological sections 3-5 μm thick were stained by hematoxylin and eosin, histochemicaly by alcian blue and azan staining.  Immunohistochemical study was performed according to the protocol recommended for a particular antibody of the manufacturer. Used ki-67 (Ki-67), TTF-1 (8G7G3/1), Fox-1 (A-12) monoclonal antibodies by Santa Cruz Biotechnology, Inc. A set of morphometric studies was performed by microscope Carl Zeiss Primo Star equipped with the Axiocam digital microphoto attachment with using program complex Zeiss Zen 2011. The results were considered reliable at p≤0,05. For processing of statistical material was used the standard software package Microsoft Office Excel and Statistica 10.0.The results were obtained about morphogenesis of rat’s thyroid after intrauterine antigenic action of staphylococcal toxoid. Morphofunctional homeostasis and stromal-parenchymal proportional relationship to thyroid gland closely associated with the activity of immune cells, including special role of lymphocytes, macrophages, and mast cells. Prenatal influence of staphylococcal toxoid led to the formation of a more pronounced structure of the parenchyma and stroma, but they showed signs of functional immaturity after birth. During the sucking period, the simultaneous presence of intra-, extrafollicular, septal and intramural types of folliculogesis is determined, which is a local reaction to systemic antigenic irritation with activation of compensatory-adaptive reactive folliclegenesis. The revealed changes in the process of folliclegenesis, accompanied by venous plethora, the formation of intraorgan diffuse lymphoid tissue and nodules, desquamation of the follicular epithelium, redistribution of the follicle diameter is a reaction to the systemic antigenic effect on the body during the critical period of prenatal development and normalizes by 45 days.Keywords: morphogenesis, thyroid gland, antigen, staphylococcal toxoid, experiment.


1993 ◽  
Vol 3 (6) ◽  
pp. 363-368 ◽  
Author(s):  
T. Hachisuga ◽  
K. Fukuda ◽  
M. Uchiyama ◽  
N. Matsuo ◽  
T. Iwasaka ◽  
...  

Using anti-p53 (PAb1801 and PAb240), anti-DNA polymerase α and Ki-67 monoclonal antibodies, the expression of p53 was studied in 11 normal endometria, 14 endometrial hyperplasias and 27 endometrial carcinomas and its relationship to the proliferative activity of the tumors was examined. Normal endometria and simple hyperplasias were completely negative for p53. The PAb1801 indices of complex hyperplasias and complex atypical hyperplasias were 2.5±1.8% and 5.0±3.2%, respectively. The PAb1801 indices of grade 1, grade 2 and grade 3 endometrial carcinomas were 10.2±14.2%, 44.4±29/0% and 45.0±32.5%, respectively. These results indicate a progressively enhanced p53 expression in the sequence from normal endometrium, through hyperplasia to carcinoma. A significant correlation between p53 expression and labeling indices of Ki-67 and DNA polymerase α was observed in endometrial carcinomas. The endo-metrial carcinomas with p53 overexpression developed mainly in post-menopausal patients and were frequently high-grade tumors with deep myometrial invasion. These findings may indicate that overexpression of p53 protein contributes to the proliferative activity of the tumor cells.


2016 ◽  
Vol 70 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Carla Thomas ◽  
Cleo Robinson ◽  
Ben Dessauvagie ◽  
Benjamin Wood ◽  
Greg Sterrett ◽  
...  

AimBreast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.MethodsExpression of five proliferation gene mRNAs; Ki-67, STK 15, CCNB1, CCND1 and MYBL2, was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score.ResultsExpression of Ki-67, STK15 and MYBL2 mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), but CCND1 and CCNB1 showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007).ConclusionsThis study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marcin Dobaczewski ◽  
Marcin Bujak ◽  
Carlos Gonzalez ◽  
Na Li ◽  
Xiao-Fan Wang ◽  
...  

We have recently demonstrated that the Transforming Growth Factor (TGF)-β/Smad3 pathway is activated in healing infarcts and plays an essential role in the pathogenesis of cardiac remodeling. Smad3 −/− mice were protected from the development of ventricular dilation following infarction and exhibited markedly reduced fibrosis of the peri-infarct area and the remodeling non-infarcted heart. Accordingly, we hypothesized that Smad3 signaling plays an essential role in regulating cardiac fibroblast function and gene expression in myocardial infarction. Surprisingly, Smad3 −/− infarcts exhibited increased peak infiltration with myofibroblasts, associated with evidence of enhanced proliferative activity. Smad3 −/− mice had a higher density of Ki-67-positive proliferating myofibroblasts in the infarcted myocardium in comparison with wildtype (WT) animals (Smad3−/− 917±291 cells/mm 2 vs. WT 614±115 cells/mm 2 , p<0.05). In vitro experiments suggested that TGF-β inhibits murine cardiac fibroblast proliferation in a concentration-dependent manner and that the antiproliferative effects of TGF-β are abrogated in Smad3 −/− fibroblasts. On the other hand Smad3 signaling was essential for extracellular matrix protein synthesis by cardiac fibroblasts. TGF-β-mediated induction of procollagen type III and of the matricellular protein tenascin-C in cardiac fibroblasts was dependent on Smad3. In addition, TGF-β-induced Tissue Inhibitor of Metalloproteinases (TIMP)-1 and -2 upregulation was also abrogated in Smad3 −/− fibroblasts, suggesting that Smad3 signaling regulates matrix metabolism. In vivo, Smad3 −/− infarcts exhibited attenuated tenascin-C and collagen deposition in the infarct and in the remodeling non-infarcted heart. Our findings suggest that the Smad3 pathway critically regulates fibroblast function in healing myocardial infarction. In Smad3 −/− mice, the healing infarct contains abundant myofibroblasts that exhibit enhanced proliferative activity, but have markedly decreased ability to synthesize extracellular matrix proteins and to produce TIMPs. In the absence of Smad3, attenuated matrix deposition in the remodeling non-infarcted heart results in decreased dilation and ameliorated diastolic dysfunction. This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).


2018 ◽  
Vol 46 (4) ◽  
pp. 314-322
Author(s):  
V. V. Delektorskaya ◽  
O. N. Solov'eva ◽  
G. Yu. Chemeris ◽  
Yu. I. Patyutko

Background:Well-differentiated pancreatic neuroendocrine tumors (pNETs) represent a group of rare epithelial neoplasms with a highly variable clinical course. AKT1 is one of the most frequently activated protein kinases in pNETs, which promotes the tumor growth and is of interest as a prognostic factor and a target for new treatment approaches.Aim:To study the expression of the phosphorylated variant of AKT1-kinase (p-AKT1) in primary pNETs and their liver metastases and to correlate the results with various clinical and pathological parameters and the disease prognosis.Materials and methods:P-AKT1 expression was studied by the immunohistochemical analysis of the primary lesions and liver metastases in 52 pNETs patients.Results:A high level of cytoplasmic and/or nuclear immunoreactivity was detected in 24/52 of the primary pNETs (46.2%) and in 16/27 of their liver metastases (59.3%). p-AKT1 expression was observed in 3 (21.4%) of NET grade (G) 1, in 14 (46.7%) of NET G2, and in 7 (87.5%) of NET G3. p-AKT1 expression was more frequently identified in pNET G3 category and increased during the tumor progression in metachronous liver metastases, as compared to the corresponding primary tumor. In addition, p-AKT1 positivity was significantly associated with an increase of grade from G1 to G3 (p = 0.004), the Ki-67 index (p = 0.029), the pTNM stage (p = 0.0008), perineural invasion (p = 0.031) and a decrease in disease-free survival (p = 0.05).Conclusion:The results suggest that p-АКТ1 plays an important role in the pathogenesis of pNETs and may be an additional criterion for assessment of the prognosis and treatment effectiveness in this type of tumors.


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