scholarly journals Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer

Author(s):  
Mariana Seabra ◽  
Eduardo Cândido ◽  
Paula Vidigal ◽  
Rivia Lamaita ◽  
Angélica Rodrigues ◽  
...  

Objective The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association. Methods Women with IB stage-ICSCC (n = 20) and women with uterine leiomyoma (n = 20) were prospectively evaluated. Patients with ICSCC were submitted to type B-C1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies. Results The WWOX expression was significantly lower in the tumor compared with the expression in the benign cervix (p = 0.019). The WWOX expression was inversely associated with the CD31 expression in the tumor samples (p = 0.018). There was no association between the WWOX expression with the p53 expression (p = 0.464) or the Ki-67 expression (p = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p = 0.156), grade of differentiation (p = 0.914), presence of lymphatic vascular invasion (p = 0.155), parametrium involvement (p = 0.421) or pelvic lymph node metastasis (p = 0.310) in ICSCC tissue samples. Conclusion The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.

2020 ◽  
Vol 30 (6) ◽  
pp. 1232-1237
Author(s):  
Meydan Turan ◽  
Gulay Turan

Purpose: Pterygium is a common lesion of the ocular surface, and its etiology and pathogenesis are still uncertain. This study aimed to investigate the role of apoptosis and proliferation in pterygium formation and recurrence. Materials and methods: In this study, p53, Bcl-2, and Ki-67 expression levels were evaluated in primary pterygium ( n = 35) and recurrent pterygium ( n = 32) tissue samples and compared with normal conjunctiva ( n = 30) tissue samples. In addition, recurrent pterygiums were divided into three groups based on recurrence time, and their p53, Bcl-2, and Ki-67 expression levels were compared. Results: The results show that p53, Bcl-2, and Ki-67 expression levels were significantly higher in the pterygium tissue samples as compared to the control group ( p < 0.001, p < 0.001, and p < 0.001, respectively). When primary and recurrent pterygium tissues were compared, bcl-2 expression was higher in recurrent pterygium tissue samples ( p = 0.003). However, when Ki-67 and p53 expression levels were evaluated, no significant difference was found between primary and recurrent pterygium ( p = 0.215, p = 0.321, respectively). Also, p53 and Ki-67 expression were correlated in pterygium tissue samples, and Bcl-2 expression was significantly higher in pterygium that recurrence in the first 6 months after surgery. There was no difference between groups 1, 2, and 3 in terms of p53 and Ki-67 expression. Conclusion: Antiapoptotic mechanisms and proliferation play an important role in the etiopathogenesis of pterygium. Furthermore, Bcl-2 expression may be important in pterygium recurrence.


2019 ◽  
Vol 17 (5) ◽  
pp. 265-275
Author(s):  
Y. Peristiowati ◽  
Y. Puspitasari ◽  
Indasah

This study is aimed at analyzing the anticancer properties of papaya leaf extract, specifically the inhibition of cell proliferation and apoptotic induction through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 pathways. Twenty-five mice (Mus musculus), aged 2 months and weighing 20–30 g, was injected with 0.5 mg dexamethasone for 7 days. The mice were then injected intracutaneously with 1 ml of HeLa cells (8 × 106 HeLa cells/microliter). The mice were divided into five groups (5 each): negative control (P1) (5% CMC-Na, sodium carboxymethyl cellulose), treatment II (225 mg/kg BW (body weight) papaya leaves methanol extract), treatment III (450 mg/kg BW), treatment IV (750 mg/kg BW), and treatment PV (2 mg alcohol anticancer drug). Papaya leaf extract treatments were applied for 2 weeks. Then, the tumor tissue was isolated for hematoxylin and eosin staining. Immunohistochemical imaging was used to detect Ki-67, caspase-3, NF-κB, and p53 expression. Further analysis was undertaken using the ImmunoRatio software program. The results indicated that administration of papaya leaf methanol extract significantly increased the expression of NF-κB and p53 at a dose of 450 mg/kg BW. Our results also showed that the mice treated with 450 mg of papaya leaf extract per kg of BW (P3) had the largest increase of caspase-3 expression compared to the negative control group. Papaya leaf ethanol extract decreased the cancer cell proliferation index and increased apoptosis of cancer cells in animal models of cervical cancer; it may also work to increase NF-kB expression and expression of the p53 gene.


2015 ◽  
Vol 59 (2) ◽  
pp. 255-261
Author(s):  
Gulbin Sennazli ◽  
Funda Yildirim ◽  
Seckin Serdar Arun ◽  
Aydin Gurel ◽  
Kivilcim Sonmez

Abstract The objective of this study was to investigate the correlation between different histological types and grades of canine malignant mammary tumours, tumour cell proliferation and their angiogenic activity using immunohistochemical markers. Mammary tissue samples from 47 bitches with mammary cancer were evaluated. The expression of cellular proliferation marker Ki-67 and endothelial marker Von Willebrand’s factor (vWF) were immunohistochemically demonstrated. The tumours with the highest Ki-67 and vWF expressions were found to share similar histomorphological features. Simple solid carcinoma had the highest levels of Ki-67, vWF, and higher histological grade while complex carcinomas, osteosarcomas, and carcinosarcomas had the lowest ones. The differences between the expressions of Ki-67 and vWF in different tumour types were considered to be of great importance in determination of biological behaviour and prognosis of these tumours. This study is one of the few studies that evaluate these differences among the subtypes of malignant canine mammary tumours


2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094379
Author(s):  
Yanshan Li ◽  
Yunxiuxiu Xu ◽  
Ruomei Wang ◽  
Wenxin Li ◽  
Wenguang He ◽  
...  

Objective To investigate whether the Notch–Hif-1α signaling pathway is involved in liver regeneration. Methods Rats were divided into two groups and treated with daily intraperitoneal injections of saline (control) or the gamma-secretase inhibitor, Fli-06, for 2 days. Two-thirds of the rat livers were resected and rats were later euthanized at specific time points post-resection to analyze the remnant livers. Each group's liver/body weight ratio was calculated, and immunostaining and western blotting were used to determine the cell proliferation marker, PCNA and Ki-67 expression. Real-time PCR and western blotting were used to compare the mRNA expression of Notch homolog-1 ( Notch1), hairy and enhancer of split-1 ( Hes1), and vascular endothelial growth factor ( Vegf), and the protein expression of NICD and HIF-1α, respectively. Results The liver/body weight ratios and number of Ki-67- and PCNA-positive cells were significantly lower in the experimental group than the control group, indicating lower levels of liver regeneration following the disruption of Notch signaling by Fli-06. The Hes1 and Vegf mRNA levels and NICD and HIF-1α protein expression levels were all down-regulated by Fli-06 treatment. Conclusion Notch–Hif-α signaling pathway activation plays an important role in liver regeneration, where it may contribute toward liver cell proliferation.


2012 ◽  
Vol 92 (9) ◽  
pp. 1208-1219 ◽  
Author(s):  
Cheng Zhong ◽  
Xin Zhang ◽  
Zhengjian Xu ◽  
Rongxin He

Background Electromagnetic fields (EMFs) used in stem-cell tissue engineering can help elucidate their biological principles. Objective The aim of this study was to investigate the effects of low-intensity EMFs on cell proliferation, differentiation, and cycle in mouse bone marrow stromal cells (BMSCs) and the in vivo effects of EMFs on BMSC. Methods Harvested BMSCs were cultured for 3 generations and divided into 4 groups. The methylthiotetrazole (MTT) assay was used to evaluate cell proliferation, and alkaline phosphatase activity was measured via a colorimetric assay on the 3rd, 7th, and 10th days. Changes in cell cycle also were analyzed on the 7th day, and bone nodule formation was analyzed on the 12th day. Additionally, the expression of the collagen I gene was examined by reverse transcription-polymerase chain reaction (RT-PCR) on the 10th day. The BMSCs of the irradiated group and the control group were transplanted into cortical bone of different mice femurs separately, with poly(lactic-co-glycolic acid) (PLGA) serving as a scaffold. After 4 and 8 weeks, bone the bone specimens of mice were sliced and stained by hematoxylin and eosin separately. Results The results showed that EMFs (0.5 mT, 50 Hz) accelerated cellular proliferation, enhanced cellular differentiation, and increased the percentage of cells in the G2/M+S (postsynthetic gap 2 period/mitotic phase + S phase) of the stimulation. The EMF-exposed groups had significantly higher collagen I messenger RNA levels than the control group. The EMF + osteogenic medium–treated group readily formed bone nodules. Hematoxylin and eosin staining showed a clear flaking of bone tissue in the irradiated group. Conclusion Irradiation of BMSCs with low-intensity EMFs (0.5 mT, 50 Hz) increased cell proliferation and induced cell differentiation. The results of this study did not establish a stricter animal model for studying osteogenesis, and only short-term results were investigated. Further study of the mechanism of EMF is needed.


2011 ◽  
Vol 126 (5) ◽  
pp. 460-463 ◽  
Author(s):  
K Sikka ◽  
S C Sharma ◽  
A Thakar ◽  
S Dattagupta

AbstractIntroduction:The aggressiveness of cholesteatoma in children compared with adults is well known. However, the factors influencing the poorer prognosis of paediatric cholesteatoma are not well understood. This study compared the proliferative potential of paediatric cholesteatoma with that of adult cholesteatoma, using Ki-67 as a proliferation marker.Methods:A prospective study of 67 patients with aural cholesteatoma was performed. Thirty-eight adult and 29 paediatric cases were evaluated using clinical parameters including bone erosion, complications and extent of disease. A surgical specimen underwent histological evaluation and measurement of the proliferation index using Ki-67 labelling. Normal epithelium from a control group was also examined.Results:Cholesteatoma epithelium has a greater rate of proliferation than normal skin. There were however no statistical differences between the paediatric and adult cholesteatoma groups in terms of clinical behaviour or proliferation potential. Paediatric cholesteatoma was similar to adult cholesteatoma in terms of complications, bone erosion and disease spread.Conclusion:Cholesteatoma is a disorder of epithelial proliferation. Although postulated to be more aggressive in children than adults, this study found no clinicopathological differences between paediatric and adult cases.


1997 ◽  
Vol 86 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Julie M. Cunningham ◽  
David W. Kimmel ◽  
Bernd W. Scheithauer ◽  
Judith R. O'Fallon ◽  
Paul J. Novotny

✓ Consecutive paraffin sections of 105 astrocytomas and 15 oligoastrocytomas were examined for expression of p53, MIB-1 (Ki-67), and proliferating cell nuclear antigen (PCNA). The tumors had been examined previously for genetic abnormalities and by flow cytometry. Regardless of the tumor's stage and grade and the patient's age and gender, p53 expression was found in 40% of tumors. Although p53 expression was associated with a loss on chromosome 17p and was more frequent in aneuploid tumors, it had no association with survival time. The MIB-1 and PCNA labeling indices increased with increasing tumor grade but showed no association with other clinicopathological parameters. In individual tumors, there was poor concordance between any of the variables (MIB-1, PCNA, and p53). Results for p53 and MIB-1 were similar for both astrocytomas and oligoastrocytomas. The MIB-1 and PCNA values appeared to have prognostic utility in univariate analysis but not after adjusting for patient age and tumor grade. The poor concordance between MIB-1 and PCNA in individual tumors indicates that any one means of assessing proliferative potential in gliomas may not be reliable.


2016 ◽  
Vol 3 (2) ◽  
pp. 87-91
Author(s):  
Evgeniya A. Kogan ◽  
O. E Ushakova ◽  
Yu. N Kur’yanova ◽  
N. M Fayzullina ◽  
O. K Stupko

The aim of the work - the study of the morphological and immunophenotypic variants of the structure gonads in gonadal dysgenesis (GD) and karyotypic characteristics of patients with the Shereshevsky-Turner syndrome (SHTS). There were investigated the tissue samples of the removed gonads and ovaries from 16 SHTS patients with GD and 11 patients from the control group without SSHT whose ovaries had been removed due to parovarian cysts. The morphological study was executed with immunohistochemical typing of gonadal tissue with the detection of expression: Ki-67, Vimentin, Desmin, Inhibin A, ER ( «DAKO»), AR ( «SpringBioscience»). The karyotype was investigated by means of cytogenetic method, whereas the presence of the SRY-gene - with aid of PCR-reaction in blood lymphocytes. As a result, there were established morphological variants of GD in SHTS: streak-gonads (8 patients), GD with ovarian stroma (6 patients), GD with the formation of the gonadoblastoma (2 patients). At that in the blood lymphocytes of SHTS patients there were discovered following karyotypes: 45Х, 45X/46XY, 45X/46XX, 45, Х, t (4, 19) (р14, q13.3), 45, Х[5]/46, Xi(X)(q10)[20], 45, Х[31]/46, Xi(X)(q10)[19], 46Xpsui(Y)(q10)[6]/45, Х[3]/46 XY[20]. There were revealed statistically significant correlations between karyotypes of blood lymphocytes and immunophenotypes of cell of the genital cord stroma, fibroblasts and GD germinal cells. Markers directly relating to the survival of follicles: inhibin-a, AR, ER were of the greatest importance for the development of someone or other morphological variant. GD in patients with ovarian stroma were differed in the greatest expression of ER (p < 0.05). SRY-gene was detected in the 1 patient with the lack of Y-chromosome. In two patients gonadoblastoma was found in GD without the presence of the SRY-gene in blood lymphocytes. The data obtained testify to a variety of morphologic and immunophenotypic variants of GD in SHTS, which are not always correlated with the karyotype of blood lymphocytes ofpatients that may partly reflect a possible discrepancy between the karyotypeofblood lymphocytes and DG tissue due to gene mosaicism.


2021 ◽  
Author(s):  
Hu Zhao ◽  
Yuan Chen ◽  
You-Ping Liao ◽  
Hai-Mei Chen ◽  
Qiu-Hong Yang ◽  
...  

Abstract Tumor cells often exhibit the Warburg effect, wherein, they preferentially undergo glycolysis over oxidative phosphorylation for energy production. Monocarboxylate transporter 1 (MCT1) and 4 (MCT4) are critical symporters mediating lactate efflux and preventing intracellular acidification during tumor growth. Numerous studies have focused on inhibiting MCT1 or MCT4 in various cancers. However, its role in T-cell lymphoma (TCL) is not yet investigated owing to the low incidence of TCL. This study was designed to investigate the expression of MCT1/MCT4 in patients with TCL and determine their prognostic value in this cancer. We performed immunohistochemistry to evaluate the expression level of MCT1/MCT4 in 38 TCL tissue samples and then compared their expression among different TCL subgroups, which were formed based on different clinical characteristics. Survival analysis was performed to evaluate the relationship between MCT1/MCT4 expression and both overall survival (OS) and progression-free survival (PFS). Our results revealed that MCT1 and MCT4 expression was significantly increased in TCL tissues compared to the control group. In addition, increased MCT1 expression associated with the female sex, advanced disease stage, increased serum LDH, Ki-67 at ≥50%, and intermediate or high-risk groups as categorized by the International Prognostic Index (IPI) score. We also found that increased MCT1 expression may be associated with reduced OS and PFS. In conclusion, MCT1 and MCT4 are overexpressed in patients with TCL, and may predict poor prognosis. MCT1 inhibition might be a novel treatment strategy for TCL, and further preclinical trials are required.


2020 ◽  
Author(s):  
Shi Wu ◽  
Dan Lu ◽  
Xinkai Zheng ◽  
Jin Xu ◽  
Zhen Li ◽  
...  

Abstract Objectives This study was designed to investigate the miRNAs that regulate the cell proliferation of condyloma acuminatum (CA) lesions and their targets.Methods The expression of Ki-67 in 26 CA patients compared with 10 healthy controls was assessed by immunohistochemistry. And the different miRNAs in 4 CA patients and 4 control cases were analyzed by bioinformatics. PCR was used to validate the expression of screened miRNA and its corresponding target genes.Results The expression of Ki-67 was abnormally increased in CA compared with healthy controls ( P <0.05). The comparison of the control group with the CA group revealed 81 differentially expressed miRNAs, of which 56 were downregulated and 25 were upregulated. Two of the differentially expressed miRNAs, miR-30a-5p and miR-514a-3p, are associated with cell proliferation and their target genes are autophagy-related protein (Atg) 5 and Atg12, and Atg3 and Atg12, respectively. PCR results showed that the expression levels of miR-30a-5p and miR-514a-3p were decreased in CA patients compared with healthy controls ( P <0.05), whereas the expression of Atg5, Atg12 and Atg3 was increased ( P <0.05). The expression of the autophagy proteins microtubule-associated protein 1 light chain 3 (LC3) and P62/SQSTM1 (P62) was abnormally increased in the local lesion tissue of the 26 patients with CA compared with the 10 healthy controls, as assessed by immunohistochemistry ( P <0.05).Conclusions Our results suggest that autophagy levels may be modulated by has-miRNA30a-5p and has-miRNA514a-3p in CA patients, leading to dysregulated cell proliferation.


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