Degree Of Proliferative Activity Research Articles

Prognostic Factors After Surgical Treatment of Liver Metastases from Breast Cancer - 19 Years of Experience.

The aim of this study was to determine the importance of surgical treatment, utility of hormone receptor status and selected biomarkers in the prognosis of patients with liver metastases from breast cancer (BCLM). Thirty female underwent surgery for BCLM between 1/2000 and 1/2019. The type of surgery (resection/radiofrequency ablation) had no impact on overall survival (OS) - (p=0.894). Having more than one BCLM (p=0.003), expression of human epidermal receptor 2 in metastases (p=0.034), as well as an elevated presurgical level of carbohydrate antigen 19-9 (p=0.017) and postsurgical thymidine kinase (p=0.034) were negative prognostics factor for recurrence-free survival. The factors affecting OS included the number of liver procedures (p=0.021), the degree of proliferative activity (p=0.008) and elevated postsurgical carcinoembryonic antigen level (p=0.038). The type of surgery had no impact on OS. Markers and hormonal status of liver metastases are important factors affecting prognosis.

Immunohistochemical Study of Tumor Cells Proliferative Activity at Different Graduations of Prostate Cancer

Prostate cancer is one of the leading causes of men death in developed countries. Modern diagnostic methods, including a puncture biopsy of the prostate gland, make it possible to verify oncology in the early stages, however, routine studies do not always allow to predict the course of the disease and outcome. The aim of our study was to analyze the clinical, morphological and immunohistochemical features of the proliferative activity of adenocarcinoma cells using the Ki-67 marker, to compare the degree of proliferative activity in tumors of various degrees of malignancy (according to Gleason’s classification), as well as to compare this indicator with the clinical stage of the disease, the level of prostate-specific antigen in the blood, the size of the prostate gland. Materials and Methods: On the basis of the City Clinical Hospital No. 31 and the Veteran Hospital No. 2, paraffin blocks with material obtained as a result of prostate biopsy, transurethral resection, and radical prostatectomy were selected. A morphological and immunohistochemical study of the material with the Ki-67 marker and a quantitative assessment of the degree of proliferative activity were carried out. Data were analyzed using the STATISTICA 10.0 program using estimates of the normality of the data distribution according to the Shapiro-Wilk W-test, the significance of differences was estimated using the Mann-Whitney U-test, and correlation relationships using Spearman’s correlation coefficient. Results: Statistically significant differences in the degree of proliferative activity in groups differing in the degree of differentiation were revealed. A statistically significant direct correlation of moderate severity was revealed when comparing proliferative activity with the degree of differentiation according to the Gleason system (rs = 0.523) and the clinical stage of the disease (rs = 0.646). No statistically significant correlation was found between indicators such as prostate-specific antigen level, age, prostate volume, and proliferative activity index. Conclusion: taking into account the proliferative activity index in addition to clinical and morphological studies helps to diagnose and subsequently predict the course of prostate cancer.

Prognostic aspects of immunohistochemical assessment of cellular renewal and transcription factor SOX2 with precancerous changes in the gastric mucosa depending on the genotype of Helicobacter pylori in patients with various types of chronic gastritis

The precancerous potential of chronic gastritis (CG) associated with H. pylori is discussed in numerous writings, and today, CG is central to precancerous conditions of the stomach. A convincing theoretical basis for such an assessment of chronic gastritis is its characteristic feature — an interruption of cell renewal with the proliferation phase predominating over the differentiation phase. However, the determination of the degree of proliferative activity and impaired differentiation of the epithelium of the gastric mucosa (GM) remains not fully understood. The goal of our study was the immunohistochemical evaluation of the expression of Ki-67, Cyclin D1, p53, CPP32, HER2 and the Sox2 transcription factor in GM epithelial cells in patients with H. pylori-associated chronic gastritis.. To accomplish this goal, histological, cytological, immunohistochemical, molecular genetic, morphometric and statistical research methods were used. We found that in chronic H. pylori-associated non-atrophic gastritis (CNG) compared with H. pylori (-), the GM epithelium renewal rate increased, characterized by a significant increase in the expression of caspase-3 and Ki-67 proliferation markers, cyclin D1 (p <0.001) with expansion of the proliferative compartment and apoptosis zones. Ki-67, Cyclin D1, and p53 expression in severe dysplasia (SD) of GM was significantly (p <0.05) higher than the mild in patients with chronic non-atrophic and atrophic H. pylori-associated gastritis, despite a decrease in the expression of the transcription factor Sox2 and caspase-3 in cases of SD. The most specific marker for determining SD in patients with H. pylori-associated chronic gastritis was marker p53 (sensitivity 98.73%; specificity 83.38%, confidence interval 95%, p <0.05). Considering the immunohistochemical markers of H. pylori, a screening system has been developed for the early diagnosis of precancerous changes in the GM that will help optimize the treatment tactics of patients with chronic gastritis and increase the efficiency of detecting dysplastic and atrophic changes in the GM at their early stages of development.

Прогностичні маркери проліферації та апоптозу в пацієнтів на вузлові форми зоба на фоні автоіму-нного тиреоїдиту

Мета роботи: вивчити процеси апоптозу та проліферації в пункційному матеріалі щитоподібної залози (ЩЗ) при вузловому зобі на фоні автоімунного тиреоїдиту ВЗАІТ з використанням імуногістохімічного методу дослідження, а також визначити індекс проліферативної активності.Матеріали і методи. На пункційному матеріалі ЩЗ, отриманому від 75 хворих із гістологічно верифікованим діагнозом ВЗАІТ, проведено імуногістохімічне дослідження шляхом використання моноклональних антитіл проти Fas, FasL, Bcl-2, P53 та Ki67 антигенів.Результати досліджень та їх обговорення. Результати показали ступінь проліферативної активності тканини ЩЗ при ВЗАІТ. Виявлено високу проліферативну активність лімфоїдної тканини, помірну проліферативну активність тиреоцитів у ділянці лімфоїдної інфільтрації і низьку – поза нею. Виражена експресія Fas та FasL на тиреоцитах, у ділянках лімфоїдної інфільтрації побічно свідчить про те, що при ВЗАІТ відбуваються імунологічно зумовлені процеси апоптозу тиреоцитів. Збільшення кількості імунореактивних клітин, що експресують Ki67 у ділянці лімфоїдної інфільтрації і деструкції тиреоцитів, свідчить про регенерацію фолікулярного епітелію як компенсаторно-пристосувальну реакцію органа. Виражена експресія bsl-2 у лімфоцитах запобігає вхід клітин в апоптоз і подовжує час виживання клітин. Спостерігалася висока експресія протеїну р53 в ядрах тиреоцитів та фолікулярних просвітах, яку можна пояснити мутаціями гена р53, що дозволяє клітинам знайти толерантність до апоптичної дії ефекторів імунної системи.

Loss of Trp53 promotes medulloblastoma development but not skin tumorigenesis in Sufu heterozygous mutant mice

Basal cell carcinoma of the skin typically carries genetic alterations in components of the hedgehog (HH) signaling pathway. Previously, we generated a knockout mouse with a loss-of-function mutation in suppressor of fused (Sufu), an essential repressor of the pathway downstream of Hh ligand cell surface reception. Mice heterozygous for the mutated Sufu allele develop a skin phenotype that includes lesions similar to basaloid follicular hamartomas. The purpose of the current study was to test the possibility that the simultaneous loss of the tumor suppressor gene, transformation related protein 53 (Trp53), would aggravate the Sufu skin phenotype since Trp53 loss is known to enhance the growth of other Hh-driven tumors. Consistent with previous reports, medulloblastomas and rhabdomyosarcomas developed in Sufu(+/-) ;Trp53(-/-) mice. However, the characteristic Sufu(+/-) skin phenotype was not altered in the absence of Trp53, and showed no changes in latency, multiplicity, cellular phenotype, or proliferative capacity of the basaloid lesions. This finding was both novel and intriguing and demonstrated a differential, tissue-specific sensitivity to Sufu and Trp53 tumor suppressor gene loss, which may be linked to developmental stage and the degree of proliferative activity in specific cell types.

Proliferation and functional changes of pancreatic gastrin cells in neonatal rat.

Although gastrin cells are not found in the adult pancreas, they are found transiently in the neonatal pancreas. It has been suggested that gastrin may play a role in pancreatic development. However, cell kinetics as well as the fate and the role of gastrin cells are not clear. Proliferation and functional changes of pancreatic gastrin cells in neonatal Wister rats were studied by immunohistochemistry and [(3)H]thymidine autoradiography. Numbers of pancreatic gastrin cells in neonatal rats showed a peak immediately after birth and then decreased rapidly. Gastrin cells were observed within approximately 2 weeks after birth in islets and within approximately 4 weeks after birth among exocrine cells. In contrast with the decrease of gastrin cell numbers, numbers of duodenal cholecystokinin cells increased remarkably after 7 days of age. Proliferative activity of acinar cells showed two peaks at age 2 days and 9 days. Despite a decrease in gastrin cell numbers, gastrin cells maintained a certain degree of proliferative activity. The "re-staining method" for gastrin and insulin revealed that immunoreactive cells for both gastrin and insulin were rarely found a few days after birth. These results suggest that pancreatic gastrin cells do not die off or change to another type of endocrine cell and that some gastrin cells change to insulin cells.

AgNOR Counts in Preneoplastic Lesions of the Bronchus

Silver staining of argyrophil nucleolar organizer regions (AgNORs) has become a valuable method to assess cell kinetics in paraffin sections and separate benign from malignant lesions. As a putative technique for the distinction between regenerative and preneoplastic alterations of the bronchial mucosa we employed the Ag-staining method, evaluating the number of dots/nucleus and shape of the dots. Dots/nucleus were counted by by standardized methods, and mean and standard deviation were calculated. Comparative investigations were performed in bioptically obtained specimens of normal bronchial epithelium (1.94 +/- 0.1 dots/nucleus, n = 12), basal cell hyperplasia (2.22 +/- 0.13 dots/nucleus, n = 15), goblet cell hyperplasia (2.38 +/- 0.16 dots/nucleus, n = 17), squamous cell metaplasia (2.58 +/- 0.17 dots/nucleus, n = 25), squamous cell metaplasia with mild and moderate dysplasia (2.50 +/- 0.5 dots/nucleus, n = 15), squamous cell metaplasia with severe dysplasia and carcinoma in situ (3.10 +/- 0.47 dots/nucleus, n = 17), micropapillomatosis (2.20 +/- 0.21 dots/nucleus, n = 13) and early squamous cell carcinoma of the bronchus (4.40 +/- 0.74, n = 13). In preneoplastic lesions a variability in form and size of the dots was found. Though showing an increase in the number of dots/nucleus coincidentally with the degree of proliferative activity, the AgNOR method cannot be considered as a statistically significant tool in the evaluation of regenerative and preneoplastic lesions in bioptically obtained specimens.

Growth factors in liver development, regeneration and carcinogenesis

Liver growth during regeneration is controlled by several growth factors which may be involved in the triggering, progression and termination of hepatocyte replication. It is likely that liver regeneration involves both circulating factors and those produced in hepatic tissue during the growth response. TGFα is an autocrine stimulator of hepatocyte proliferation which increases transiently in replicating hepatocytes both in vivo and in vitro. Constitutive TGFα overexpression in young transgenic mice causes liver hypertrophy and enhanced proliferation that progress to hepatic tumor development in the great majority of animals after 12 months of age. In contrast, HGF is present in normal blood in humans and animals and plasma concentrations increase after partial hepatectomy, liver injury and fulminant hepatic failure. In liver tissue, levels of HGF and its mRNA correlate better with the extent of injury than with the degree of proliferative activity. The factor is produced by nonparenchymal cells and presumably acts on hepatocytes through paracrine or endocrine mechanisms. A transient increase of TGFβ1 in regenerating liver may promote the formation of extracellular matrix components and signal the end of hepatocyte proliferation. Prolonged overexpression of the factor in nonparenchymal cells causes liver fibrosis both in humans and experimental animals. The liver contains TGFβ1,2 and 3, all of which inhibit hepatocyte DNA synthesis. Their mRNAs increase in the regenerating liver but with very different kinetics. Despite the enormous progress achieved in understanding the mechanisms that regulate liver regeneration, it is not known whether HGF, TGFα and TGFβ interact with each other or with other factors or hormones during the growth process. Further, it remains to be established how the effect of these factors may relate to the sequential changes in proto-oncogene expression that occur after partial hepatectomy.

T-lymphocyte activation by a gluten fraction, glyc-gli. Studies of adult coeliac patients and healthy controls.

A gluten fraction (glyc-gli) induced proliferation of T lymphocytes obtained from coeliac patients or healthy controls. Glyc-gli acted as an antigen, and T-cell activation was strongly dependent on antigen-presenting monocytes in the cultures. The lymphocyte response was similar for HLA-B8/DR3-positive and HLA-B8/DR3-negative healthy controls, and coeliac patients in remission on a gluten-free diet could not be distinguished from the controls by the degree of proliferative activity in this test. Conversely, untreated coeliac patients showed a significantly lower lymphocyte response to glyc-gli than both coeliac patients in remission and controls. This result may reflect sequestration of gluten-specific cells into the mucosal lesion or mesenteric lymph nodes in patients with active coeliac disease.

Stages of transformation in the development of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced transitional cell carcinomas in the urinary bladder of rats.

The histogenesis of papillary and nonpapillary transitional cell carcinomas were studied morphologically and autoradiographically in 177 female Wistar rats after oral application of N-butyl-N-(4-hydroxybutyl)-nitrosamine with varying exposure and induction times. By far the largest proportion of carcinomas developed by a malignant transformation of preexisting papillomas or their precursors, the papillary hyperplasias. The transition into a focally malignant growth did not take place abruptly, but occurred stepwise through different successive stages of transformation, each having its own distinct morphological character. The first stage consisted of a focal, sharpely defined cellular atypia. In a further stage carcinomata in situ developed out of the atypical foci and progressed finally in a last stage of transformation into a circumscript infiltrative growth. The successive development of each stage occurred independent of any further carcinogen application after transformation was initiated at the molecular level. The number of papillomas with transformation stages increased with a lengthening of the exposure and induction time. 74.4% of all the registered papillomas had been transformed. Consequently papillomas must be considered potentially highly malignant. The 3H-TdR index was 4.2 times higher in atypical urothelial areas (7.6%) and 7.5 times higher in carcinomata in situ (14.3%) than in the surrounding papillomatous structures which appeared light microscopically benign. The latter demonstrated a rather constant 3H-TdR index, whether they bordered on atypical foci (1.8%) or carcinomata in situ (1.9%). The length of exposure and induction time exercised no significant influence on the degree of proliferative activity. The development of transitional cell carcinomas from a primary carcinoma in situ (intraurothelial carcinoma) played a much less significant role.