Proliferative activity (Ki-67) and level of VEGF gene expression in gemistocytic astrocytomas

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.

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Clinical significance of Notch and VEGF gene expression in serious ovarian carcinoma

10.26226/morressier.5770e29cd462b80290b4c15c ◽

2016 ◽

Author(s):

SANG GEUN JUNG

Keyword(s):

Gene Expression ◽

Ovarian Carcinoma ◽

Clinical Significance ◽

Vegf Gene

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Survivin Gene Expression Positively Correlates with Proliferative Activity of Cancer Cells in Esophageal Cancer

Tumor Biology ◽

10.1159/000070659 ◽

2003 ◽

Vol 24 (1) ◽

pp. 40-45 ◽

Cited By ~ 26

Author(s):

Masahide Ikeguchi ◽

Ken-ichi Yamaguchi ◽

Nobuaki Kaibara

Keyword(s):

Gene Expression ◽

Esophageal Cancer ◽

Cancer Cells ◽

Proliferative Activity ◽

Survivin Gene

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Regional Heterogeneity in the Proliferative Activity of Human Gliomas as Measured by the Ki-67 Labeling Index

Journal of Neuropathology & Experimental Neurology ◽

10.1097/00005072-199311000-00008 ◽

1993 ◽

Vol 52 (6) ◽

pp. 609-618 ◽

Cited By ~ 77

Author(s):

STEPHEN W. COONS ◽

PETER C. JOHNSON

Keyword(s):

Proliferative Activity ◽

Labeling Index ◽

Human Gliomas ◽

Regional Heterogeneity ◽

Ki 67

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Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals

Biomolecules ◽

10.3390/biom11060834 ◽

2021 ◽

Vol 11 (6) ◽

pp. 834

Author(s):

Ekaterina Blinova ◽

Dmitry Pakhomov ◽

Denis Shimanovsky ◽

Marina Kilmyashkina ◽

Yan Mazov ◽

...

Keyword(s):

Gene Expression ◽

Wound Healing ◽

Topical Therapy ◽

Skin Defect ◽

Ki 67 ◽

Fgfr3 Gene ◽

White Rats ◽

Tnf Α ◽

Acid Formulation ◽

Healing Property

Background: The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals. Methods: Cerium N-acetyl-6-aminohexanoate (laboratory name LHT-8-17) as a 10 mg/mL aquatic spray was used as wound experimental topical therapy. LHT-8-17 toxicity was assessed in human skin epidermal cell culture using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A linear wound was reproduced in 18 outbred white rats with streptozotocin-induced (60 mg/kg i.p.) diabetes; planar cutaneous defect was modelled in 60 C57Bl6 mice with streptozotocin-induced (200 mg/kg i.p.) diabetes and 90 diabetic db/db mice. Firmness of the forming scar was assessed mechanically. Skin defect covering was histologically evaluated on days 5, 10, 15, and 20. Tissue TNF-α, IL-1β and IL-10 levels were determined by quantitative ELISA. Oxidative stress activity was detected by Fe-induced chemiluminescence. Ki-67 expression and CD34 cell positivity were assessed using immunohistochemistry. FGFR3 gene expression was detected by real-time PCR. LHT-8-17 anti-microbial potency was assessed in wound tissues contaminated by MRSA. Results: LHT-8-17 4 mg twice daily accelerated linear and planar wound healing in animals with type 1 and type 2 diabetes. The formulated topical application depressed tissue TNF-α, IL-1β, and oxidative reaction activity along with sustaining both the IL-10 concentration and antioxidant capacity. LHT-8-17 induced Ki-67 positivity of fibroblasts and pro-keratinocytes, upregulated FGFR3 gene expression, and increased tissue vascularization. The formulation possessed anti-microbial properties. Conclusions: The obtained results allow us to consider the formulation as a promising pharmacological agent for diabetic wound topical treatment.

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Immunohistochemical study of p53 expression in endometrial carcinomas: correlation with markers of proliferating cells and clinicopathologic features

International Journal of Gynecological Cancer ◽

10.1046/j.1525-1438.1993.03060363.x ◽

1993 ◽

Vol 3 (6) ◽

pp. 363-368 ◽

Cited By ~ 10

Author(s):

T. Hachisuga ◽

K. Fukuda ◽

M. Uchiyama ◽

N. Matsuo ◽

T. Iwasaka ◽

...

Keyword(s):

Dna Polymerase ◽

Proliferative Activity ◽

P53 Protein ◽

Myometrial Invasion ◽

Proliferating Cells ◽

Ki 67 ◽

Normal Endometrium ◽

P53 Expression ◽

Dna Polymerase Α ◽

Endometrial Carcinomas

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.

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Endocrine gland-derived vascular endothelial growth factor in rat pancreas: genetic expression and testosterone regulation

Journal of Endocrinology ◽

10.1677/joe-07-0567 ◽

2008 ◽

Vol 197 (2) ◽

pp. 309-314 ◽

Cited By ~ 7

Author(s):

Angélica Morales ◽

Sumiko Morimoto ◽

Lorenza Díaz ◽

Guillermo Robles ◽

Vicente Díaz-Sánchez

Keyword(s):

Gene Expression ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Pancreatic Tissue ◽

Endocrine Gland ◽

Vascular Endothelial ◽

Rinm5f Cells ◽

Vegf Gene ◽

Rat Pancreas ◽

Endothelial Growth Factor

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an endothelial cell mitogen, expressed essentially in steroidogenic cells. Recently, the expression of EG-VEGF in normal human pancreas and pancreatic adenocarcinoma has been demonstrated. Epidemiologically, pancreatic carcinogenesis is more frequent in males than females, and given that androgen receptors and testosterone biotransformation have been described in pancreas, we hypothesized that testosterone could participate in the regulation of EG-VEGF expression. In this study, we investigated the regulation of EG-VEGF gene expression by testosterone in normal rat pancreatic tissue and rat insulinoma cells (RINm5F). Total RNA was extracted from rat pancreas and cultured cells. Gene expression was studied by real-time PCR and protein detection by immunohistochemistry. Serum testosterone was quantified by RIA. Results showed that EG-VEGF is expressed predominantly in pancreatic islets and vascular endothelium, as well as in RINm5F cells. EG-VEGF gene expression was lower in the pancreas of rats with higher testosterone serum levels. A similar effect that was reverted by flutamide was observed in testosterone-treated RINm5F cells. In summary, testosterone down-regulated EG-VEGF gene expression in rat pancreatic tissue and RINm5F cells. This effect could be mediated by the androgen receptor. To our knowledge, this is the first time that a direct effect of testosterone on EG-VEGF gene expression in rat pancreas and RINm5F cells is demonstrated.

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Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

The Scientific World JOURNAL ◽

10.1100/tsw.2009.36 ◽

2009 ◽

Vol 9 ◽

pp. 313-319 ◽

Cited By ~ 4

Author(s):

Markus D. Schofer ◽

S. Fuchs-Winkelmann ◽

C. Wack ◽

M. Rudisile ◽

R. Dersch ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Time Course ◽

Negative Impact ◽

Fracture Repair ◽

Bone Morphogenetic Protein 2 ◽

Vegf Gene ◽

Down Regulation ◽

Artificial Graft ◽

The Impact

Growth factors like bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid) (PLLA) nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC) differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2–enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers.

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