scholarly journals Assessment of the antiproliferative potential of Cissampelos owariensis (P. Beauv) methanolic extract in Wistar rats

2021 ◽  
pp. 178-183
Author(s):  
Dayo Rotimi Omotoso ◽  
Uche Christiana Okwuonu ◽  
Olayinka Simbiat Lawal ◽  
Oluwasegun Davis Olatomide

Cissampelos owariensis is a medicinal plant with a wide range of therapeutic uses.  In this study, the objective was to further assess its antiproliferative potential using cell proliferation and tumor suppressor markers. Solvent extraction of C. owariensis leaves was done using methanol. Twenty (20) male albino Wistar rats were randomly divided into four groups 1–4 (n=5) and respectively administered with methanolic extracts of C. owariensis at 0, 100, 300 and 500 mg/kg for 30 days. After treatment, the hepatic tissues were processed and examined histologically and immunohistochemically for cell proliferation (Ki-67) and tumor suppressor (p53) proteins.  Immunoexpression of the proteins was quantified using image-J software, the data analyzed with SPSS version 20 and values compared using t-test and one-way analysis of variance. The histological results showed no significant variation in hepatic histomorphology of treated Groups 2–4 relative to non-treated Group 1. However, the immunohistochemical results showed significant (p< 0.05) down-regulation in Ki-67 protein expression and a concomitant significant (p< 0.05) up-regulation in p53 protein expression in hepatic tissues of treated Groups 2–4 relative to non-treated Group 1.These inverse expression patterns of cell proliferation and tumor suppressor proteins following exposure to methanolic extracts of C. owariensis may suggest the antiproliferative potential of the plant extracts.

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4306
Author(s):  
Diana Maržić ◽  
Blažen Marijić ◽  
Tamara Braut ◽  
Stefan Janik ◽  
Manuela Avirović ◽  
...  

Background: The aim of this study was to (i) determine IMP3 protein expression in benign and malignant laryngeal lesions, (ii) compare its expression to Ki-67, p53, cyclin D1, and (iii) finally, to examine the prognostic power of IMP3 in squamous cell carcinomas of the larynx (LSSC). Methods: IMP3 protein expression was evaluated in 145 patients, including 62 LSCC, 45 dysplasia (25 with low and 20 with high-grade dysplasia), and 38 benign lesions (vocal cord polyps and nodules). Results: IMP3 was significantly higher expressed in LSCC compared to dysplasia and benign lesions (p < 0.001; p < 0.001, respectively). Similarly, higher expression patterns were observed for Ki-67 and p53, whereas cyclin D1 was equally distributed in all three lesions. IMP3 (p = 0.04) and Ki-67 (p = 0.02) expressions were significantly linked to neck node positivity, and IMP3 overexpression to worse disease-specific survival (p = 0.027). Conclusion: Since IMP3 showed significantly higher expression in laryngeal carcinomas, but not in high- or low-grade dysplasia, it serves as a useful marker to differentiate between invasive and noninvasive lesions. Higher IMP3 expression represented a significantly worse prognosticator for clinical outcomes of patients with squamous cell carcinoma of the larynx.


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.


2013 ◽  
Vol 169 (2) ◽  
pp. 217-223 ◽  
Author(s):  
Leandro Kasuki ◽  
Luiz Eduardo Armondi Wildemberg ◽  
Leonardo Vieira Neto ◽  
Jorge Marcondes ◽  
Christina M Takiya ◽  
...  

IntroductionOnly one study has evaluated Ki-67 as a predictor of the response to somatostatin analog therapy in acromegaly; however, other predictors like somatostatin receptor type 2 (SSTR2) and cytokeratin pattern expressions were not considered.ObjectiveTo evaluate whether Ki-67 is a predictor of octreotide LAR (OCT-LAR) response in somatotropinomas independent of SSTR2 and cytokeratin expression patterns.MethodsProtein expression was analyzed by immunohistochemistry. The percentage of cell nuclei that were immunolabeled for Ki-67 and the percentage of cells with positive SSTR2 staining were calculated. SSTR2 expression was considered high when ≥25%, and a cutoff of 2.3% was designated for Ki-67. Tumors were classified as densely or sparsely granulated according to the cytokeratin pattern.ResultsThirty-one somatotropinomas were studied. Fourteen patients (45.2%) were controlled with OCT-LAR therapy. The median Ki-67 labeling index (LI) was higher in patients not controlled with OCT-LAR than in those controlled (1.63 and 0.15 respectively, P=0.002). Higher SSTR2 expression and densely granulated tumors were correlated with control as well (P=0.04 and 0.038 respectively). There was no difference in Ki-67 levels between patients with high and low SSTR2 expression (P=0.651). After multivariate analysis, both Ki-67 and SSTR2 remained statistically significant as predictors of OCT-LAR response (P=0.017 and 0.012 respectively). The Ki-67 LI was higher in sparsely than in densely granulated tumors (P=0.047).ConclusionsKi-67 is a predictor of response to OCT-LAR in acromegaly, independent of SSTR2 expression and relates to cytokeratin patterns.


2021 ◽  
Vol 57 (1) ◽  
pp. 20
Author(s):  
Puguh Setyo Nugroho ◽  
Muhtarum Yusuf ◽  
Titiek Ahadiyah Hidayati

Several studies showed that the index of nasopharyngeal carcinoma (NPC) cell growth could be used to assess the carcinogenesis interaction factor, development and prognosis of NPC. Cell proliferation index could always be assessed with Ki-67 protein expression test. This research was conducted to study the correlation between cell proliferation index with cervical lymphoid node status in NPC in clinical manifestation to asses the progressivity and prognosis on NPC patients. This study used cross sectional design. Biopsy tissue specimen were acquired from 35 NPC patients clinically divided into four criteria of cervical lymphoid node status (N0, N1, N2 and N3). Expression of Ki-67 protein was acquired by immunohistochemistry test using monoclonal rabbit antibody anti-human Ki-67 clone 901-325-091911 (Biocare Medical, LCC. 4040 Pike Line, CA 94520 USA). The measurement of Ki-67 protein was conducted by pathology consultant. Spearman statistic test was performed to asses the correlation between Ki-67 protein expression and cervical lymphoid node status. The statistical significance was defined as p<0.05. Positive expression of Ki-67 protein was found in 33 patients; 4 patients with N0 (11.43%), 5 patients with N1 (14.29%), 9 patients with N2 (25.71%), and 15 patients with N3. Negative expression of Ki-67 protein was found in 2 patients with N0 (5.71%). The Spearman test resulted at p=0.0001 with correlation coefficient of 0.758. The correlation between Ki-67 protein expression with cervical lymphoid node resulted in a significant correlation (p<0.05). In conclusion, cell proliferation index has correlation with cervical lymphoid node status in NPC patients.


2020 ◽  
Author(s):  
Xin Du ◽  
P. Todorov ◽  
Evgenia Isachenko ◽  
G Rahimi ◽  
P. Mallmann ◽  
...  

Abstract Background: Ovarian tissue cryopreservation has a wide range of cancerous indications. Avoiding relapse becomes a specific area of concern that clinicians frequently encounter. The data about the comparative viability of cancer cells after cryopreservation are limited. This study aimed to evaluate the effect of cryopreservation on breast cancer cells.Methods: Samples were prepared using ZR-75-1 and MDA-MB-231 cell lines and divided into cryopreserved and non-intervened groups, respectively. Biological properties and the related protein markers were investigated. Cell morphology was monitored under the microscope. Cell proliferation, migration, and invasion were characterized by CCK-8, wound-healing, and transmembrane assay, respectively. The expression of Ki-67, P53, GATA-3, E-cadherin, Vimentin, and F-Actin was measured by immunofluorescent staining and western blotting. Xenotransplantation was established on the chorioallantoic membrane (CAM) culture system to explore angiogenesis close to the grafts.Results: Lamellipodia and filopodia were observed in cryopreserved ZR-75-1 cells. Both cell lines demonstrated increased cell motility and invasive ability after cryopreservation. However, cell proliferation was invariable in accordance with a regular expression of Ki-67 and P53. In ZR-75-1 cells, data exhibited a downregulation of E-cadherin after the decreased expression of GATA3, indicating the loss of intercellular adhesion after cryopreservation. Vimentin and F-actin were both upregulated in cryopreserved sample cells. Angiogenesis in CAM was significantly activated by cryopreserved MDA-MB-231 cells.Conclusions: Cryopreservation causes an increasing malignancy of ZR-75-1 and MDA-MB-231 cells and thus raises the risk of metastasis.


2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Mingwei Jiang ◽  
Wenjia Lu ◽  
Xiaomin Ding ◽  
Xiaodong Liu ◽  
Zhen Guo ◽  
...  

AbstractDown-regulation of p16INK4a and miR-146b-5p contributes to tumorigenesis in osteosarcoma (OS). However, the correlation between p16INK4a and miR-146b-5p in OS proliferation remains largely unknown. In the present study, we demonstrated that miR-146b-5p expression was positively correlated with p16INK4a in OS, but inversely correlated with TNF receptor associated factor 6 (TRAF6) expression. Overexpression of miR-146b-5p dramatically suppressed OS cell proliferation. Mechanistically, we validated TRAF6 as a direct functional target of miR-146b-5p and found that miR-146b-5p overexpression significantly decreased the level of phosphorylated PI3k and Akt, which are the pivotal downstream effectors of TRAF6. Moreover, TRAF6 expression was positively correlated with Ki-67 but inversely correlated with miR-146b-5p expression. In OS cells, silencing of TRAF6 mimicked the anti-tumor effects of miR-146b-5p. p16INK4a is an important tumor suppressor gene frequently down-regulated in OS. We found that this inhibitory effect is associated with the suppression of the miR-146b-5p, and is mediated via up-regulating TRAF6 expression. Our findings identified p16INK4a and miR-146b-5p as tumor suppressors, and suggested p16INK4a, miR-146b-5p and TRAF6 as potential therapeutic candidates for malignant OS.


Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 109
Author(s):  
Mohammed A. Attia ◽  
Eman T. Enan ◽  
Abdullah A. Hashish ◽  
Sherif M. H. El-kannishy ◽  
Ahmed R. Gardouh ◽  
...  

The use of 5-fluorouracil (5FU) is associated with multifaceted challenges and poor pharmacokinetics. Poly(lactic-co-glycolic acid)-lipid hybrid nanoparticles (PLNs)-based therapy has received attention as efficient carriers for a diversity of drugs. This study evaluated the in vivo chemotherapeutic and anti-proliferative efficacy of 5FU-loaded PLNs against 1,2-dimethylhydrazine (Di-MH) prompted colon dysplasia in mice compared to free 5FU. 5FU PLNs were prepared. Male Swiss albino mice were distributed to six experimental groups. Group 1: Saline group. All the other groups were injected weekly with Di-MH [20 mg/kg, s.c.]. Group 2: Di-MH induced colon dysplasia control group. Groups 3 and 4: Di-MH + free 5FU treated group [2.5 and 5 mg/kg]. Groups 5 and 6: Di-MH + 5FU-PLNs treated group [2.5 and 5 mg/kg]. Free 5FU and 5FU-PLNs doses were administered orally, twice weekly. Treatment with 5FU-PLNs induced a higher cytoprotective effect compared to free 5FU as indicated by lower mucosal histopathologic score and reduction in number of Ki-67 immunpositive proliferating nuclei. Additionally, there was significant upregulation of p53 and caspase 3 genes in colon specimens. Our results support the validity of utilizing the PLNs technique to improve the chemopreventive action of 5FU in treating colon cancer.


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