Ki67 targeted strategies for cancer therapy

Yang, Chunsheng; Zhang, J.; Ding, Manhua; Xu, Kailin; Li, Leping; Mao, Lijun; Zheng, Junnian

doi:10.1007/s12094-017-1774-3

Cited by 182 publications

(129 citation statements)

References 90 publications

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“…Combined with the results of the current study, it can be concluded that the loss of appetite in patients with early GC may be associated with the high expression of nesfatin-1 in GC tissues. The expression of Ki67 varies greatly during the cell cycle and is increased in a variety of tumor types (35). It has also been reported that Ki67 protein expression in GC tissues was significantly higher compared with that in normal gastric mucous tissues (36).…”

Section: Discussionmentioning

confidence: 93%

Nesfatin‑1 is a potential diagnostic biomarker for gastric cancer

et al. 2019

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The lack of reliable plasma biomarkers limits their use in the diagnosis of gastric cancer (GC). The current study aimed to determine whether plasma nesfatin-1 can be used as a novel non-invasive biomarker for the diagnosis of GC. The levels of nesfatin-1 in 40 patients with GC and 40 healthy individuals, who were selected from the Chaohu Hospital Affiliated to Anhui Medical University, were assessed. ELISA was used for the measurement of plasma nesfatin-1 levels, while immunohistochemistry was applied to determine Ki67 protein expression in GC and normal gastric tissues. The diagnostic value of plasma nesfatin-1 for GC was further assessed using receiver operating characteristic (ROC) curve analysis. The results revealed that, compared with the controls, the mean nesfatin-1 levels in patients with GC were significantly increased. Furthermore, the protein expression of Ki67 in GC tissue was significantly upregulated compared with that in normal gastric tissue. Plasma nesfatin-1 levels were also demonstrated to be correlated with Ki67 protein expression in GC tissues. Additionally, ROC curve analysis indicated the potential diagnostic value of nesfatin-1, and the area under the ROC curve (AUC) for nesfatin-1 was 0.857 (95% confidence interval, 0.769-0.946). At a threshold nesfatin-1 level of 1.075 ng/ml, the optimal sensitivity and specificity were 70.0 and 95.0%, respectively, in discriminating patients with GC from healthy controls. These results indicated that plasma nesfatin-1 may serve as a novel biomarker for the diagnosis of GC and determination of GC cell proliferation.

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Section: Discussionmentioning

confidence: 93%

Nesfatin‑1 is a potential diagnostic biomarker for gastric cancer

et al. 2019

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“…47 The expression of Ki67 is strongly associated with tumor-cell proliferation. 48,49 Our findings suggested that sustained release of EPI from the mMWCNTs-EPI system promoted mitochondria-dependent apoptosis and inhibited proliferation (Figures 8 and 9). mMWCNTs increased residence time of EPI in the bladder via an external magnet, but this study does have some limitations.…”

Section: Discussionmentioning

confidence: 78%

<p>Magnetic multiwalled carbon nanotubes with controlled release of epirubicin: an intravesical instillation system for bladder cancer</p>

Suo¹,

Wang²,

Jin³

et al. 2019

IJN

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Background: Traditional intravesical instillation treatment in bladder cancer has limited efficacy, which results in a high frequency of recurrence. Purpose: The aim of this study was to report on an epirubicin (EPI)-loaded magnetic multiwalled carbon nanotube (mMWCNTs-EPI) system for intravesical instillation in place of the current formulation. Methods: The mMWCNTs-EPI system was formulated with carboxylated MWCNTs, Fe 3 O 4 magnetic nanoparticles, and EPI. Features and antitumor activity of the system were investigated. Results: Under the effect of external magnets, the mMWCNTs-EPI system showed sustained release and prolonged retention behavior and better antitumor activity than free EPI. The mMWCNTs-EPI system had higher efficiency in enhancing cytotoxicity and inhibiting proliferation in vitro and in vivo than free EPI. Our studies also revealed the atoxic nature of mMWCNTs. Conclusion: These findings suggested that mMWCNTs are effective intravesical instillation agents with great potential for clinical application.

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“…Currently, the development of targeted cancer therapies against KIAA0101/p15PAF [20], p53 [38,39], Ki-67 [40], and PCNA [41] are being actively investigated. These attempts might translate into the novel therapeutics for HCC in the near future.…”

Section: Discussionmentioning

confidence: 99%

PCNA-associated Factor (KIAA0101/p15PAF) over expression and Gene Copy Number Alterations in Hepatocellular Carcinoma Tissues

Tantiwetrueangdet

Panvichian

Sornmayura

et al. 2020

Preprint

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Abstract Background PCNA-associated factor (KIAA0101/p15PAF) is a cell-cycle regulated oncoprotein that regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass, through the interaction with the human sliding clamp PCNA. KIAA0101 is overexpressed in various cancers, including hepatocellular carcinoma (HCC). However, it remains unknown whether KIAA0101 gene amplification occurs and causally correlates with the KIAA0101 overexpression in HCC. This question is relevant to the development of the optimal test(s) for KIAA0101 and the strategies to target KIAA0101 in HCC. Methods In this study, we validated KIAA0101 mRNA expression levels by quantitative real-time PCR in 40 pairs of snap-frozen HCC and matched-non-cancerous tissues; we then evaluated KIAA0101 gene copy numbers by droplet digital PCR (ddPCR) in 36 pairs of the tissues. Besides, KIAA0101 protein expression was detected by immunohistochemistry (IHC) in 81 pairs of formalin-fixed paraffin-embedded (FFPE) tissues. We determined the correlation between KIAA0101 gene copy numbers and KIAA0101 RNA expression by Spearman correlation, and between KIAA0101 protein expression and other clinicopathological variables by Chi-square test. Results Our results confirmed KIAA0101 mRNA overexpression in HCC; KIAA0101 mRNA levels were significantly higher in HCC than in the matched-non-cancerous tissues (p < 0.0001). We found no amplification of KIAA0101 gene in HCC and no correlation between KIAA0101 gene copy numbers and KIAA0101 RNA expression. KIAA0101 protein was overexpressed in the majority of HCC tissues (77.8%) but was not be detectable in all of the matched-non-cancerous tissues. Significant correlations between the expression of KIAA0101 protein and p53 tumor suppressor protein, and Ki-67 proliferation marker protein were found (p = 0.002 and 0.017, respectively), but no correlations between the expression of KIAA0101 and age, tumor size, and expression of AFP and HBsAg. Conclusions KIAA0101 overexpression, at mRNA and protein levels, frequently occurs in HCC without concurrent KIAA0101 gene amplification. Significant correlations between the expression of KIAA0101 protein and p53 and Ki-67 proteins were observed in this study. Thus, detection of KIAA0101 mRNA/protein might be used, along with the detection of p53 and Ki-67 proteins, as potential biomarkers to select candidate patients for further studies of novel HCC treatment related to these targets.

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Ki67 targeted strategies for cancer therapy

Cited by 182 publications

References 90 publications

Nesfatin‑1 is a potential diagnostic biomarker for gastric cancer

Nesfatin‑1 is a potential diagnostic biomarker for gastric cancer

<p>Magnetic multiwalled carbon nanotubes with controlled release of epirubicin: an intravesical instillation system for bladder cancer</p>

PCNA-associated Factor (KIAA0101/p15PAF) over expression and Gene Copy Number Alterations in Hepatocellular Carcinoma Tissues

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