Correlation Between Akt and p53 Protein Expression and Chemoradiotherapy Response in Cervical Cancer Patients

Kurnia, Iin; Siregar, Budiningsih; Soetopo, Setiawan; Ramli, Irwan; Kurjana, Tjahya; Andriono,; Tobing, Maringan Diapari Lumban; Suryawathi, Bethy; Kisnanto, Teja; Tetriana, Devita

doi:10.4308/hjb.21.4.173

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…[57][58][59][60][61][62][63][64][65][66][67][68][69][70] The overexpression of Akt1 and EGFR is associated with the poor survival and clinical outcomes of patients with CC. 69,71 The oncogene JUN is upregulated in the CC tumor tissues compared to normal tissues, and lower JUN expression is related to higher survival among patients with CC. 72 The estrogen receptor α (encoded by ESR1) is associated with the tumorigenesis, development, and persistence of CC.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Understanding of the Anticancer Mechanisms of FDY2004 Against Cervical Cancer Based on Network Pharmacology

Lee¹,

Kang²,

Park³

et al. 2021

Natural Product Communications

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Herbal drugs are continuously being developed and used as effective therapeutics for various cancers, such as cervical cancer (CC); however, their mechanisms of action at a systemic level have not been explored fully. To study such mechanisms, we conducted a network pharmacological investigation of the anti-CC mechanisms of FDY2004, an herbal drug consisting of Moutan Radicis Cortex, Persicae Semen , and Rhei Radix et Rhizoma. We found that FDY2004 inhibited the viability of human CC cells. By performing pharmacokinetic evaluation and network analysis of the phytochemical components of FDY2004, we identified 29 bioactive components and their 116 CC-associated pharmacological targets. Gene ontology enrichment analysis showed that the modulation of cellular functions, such as apoptosis, growth, proliferation, and survival, might be mediated through the FDY2004 targets. The therapeutic targets were also key components of CC-associated oncogenic and tumor-suppressive pathways, including PI3K-Akt, human papillomavirus infection, IL-17, MAPK, TNF, focal adhesion, and viral carcinogenesis pathways. In conclusion, our data present a comprehensive insight for the mechanisms of the anti-CC properties of FDY2004.

show abstract

Section: Discussionmentioning

confidence: 99%

A Comprehensive Understanding of the Anticancer Mechanisms of FDY2004 Against Cervical Cancer Based on Network Pharmacology

Lee¹,

Kang²,

Park³

et al. 2021

Natural Product Communications

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show abstract

“…Some studies indicated that PI3K/AKT activity was elevated in the cells harboring high levels of tP53 mutant protein [28][29][30], and more than half of the solid tumors harbor mutated tP53 protein that suppresses autophagy and ceases cancer cell apoptosis [31][32][33]. On the other side, it has been reported that suppression of autophagy by PI3K/AKT activation accelerates tumor growth due to inflammation [34,35].…”

Section: Introductionmentioning

confidence: 99%

Strategy of Hepatic Metabolic Defects Induced by beclin1 Heterozygosity in Adult Zebrafish

Mawed

Zhang

et al. 2020

IJMS

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Hepatic disorders have been increasing in recent years because of high carbohydrate diets. Hepatocytes depend mainly on the basal autophagy to maintain hepatic glucose/lipid homeostasis in mammals. However, the regulatory mechanisms of autophagy in hepatic energy metabolism are still unknown in fish species. Accordingly, mutant zebrafish lines of autophagy-related genes beclin1 and atg7 were generated by CRISPR/Cas9 gene-editing technology. Interestingly, unlike atg7+/−, male beclin1+/− zebrafish displayed liver defects in the morphology and histology, including abnormal hepatocyte proliferation, hemorrhagic and inflammatory phenotypes. A significant decrease in hepatocyte glycogen and an increase in hepatocyte lipids were detected in the histological assay that coincidence with the hepatic gene expression. Meanwhile, loss of heterozygosity for beclin1 creates a suitable microenvironment for hepatic tumorigenesis via phosphorylation of Akt kinase, which in turn affects liver autophagy. The reduction in autophagy activity in male beclin1+/− liver leads to a disturbance in the glucose/lipid metabolism and negatively regulates apoptosis accompanied by the induction of cellular proliferation and acute inflammatory response. Our findings highlight an important role of beclin1 in zebrafish liver development and energy metabolism, suggesting the crucial role of autophagy in maintaining homeostasis of the nutrient metabolism in fish species.

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“…However, the high level of Akt indicated poor radiotherapy response, and there were no association between some proliferation markers like AgNOR, MIB-1, and p53 with radiotherapy response [13,14]. The aim of the present study is to investigate the relationship between p70s6k as biomarker and radiotherapy response in cervical cancer.…”

mentioning

confidence: 99%

The Relationship between Expression of p70s6k with Radiotherapy Response in Cervical Cancer

et al. 2016

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There are many important prognostic factors in advanced stage cervical cancer primary treated with radiotherapy. Besides clinical factors, many biomarkers have been studied in relation with radiotherapy response. The p70s6k is a biomarker which plays a significant role in cell proliferation. Increased levels of p70s6k are also associated with drug resistance in cancer. In the present study, the relationship between the expression level of p70s6k before treatment and the radiotherapy response in cervical cancer was determined. Immunohistochemical staining of p70s6k, MIB-1, and p53 was conducted in microscopic slide from 21 cancer tissue biopsies before treatment with radiotherapy. After the treatment had completed early radiotherapy response was observed by pelvic control method. The results showed that p70s6k is partly highly expressed (61.9%, 13/21) and partly low expressed (38.1%, 8/21) in the cancer cells. They also show that there is no statistically significant differences on AgNOR mean, MIB-1, and p53 indices in the different degrees of p70s6k expression (p≥0.05). Higher expression levels of p70s6k is more strongly associated with good radiotherapy response compared to lower ones (p=0.05). In conclusion, the level of p70s6k expression before treatment has an association with radiotherapy response.

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Correlation Between Akt and p53 Protein Expression and Chemoradiotherapy Response in Cervical Cancer Patients

Cited by 4 publications

References 40 publications

A Comprehensive Understanding of the Anticancer Mechanisms of FDY2004 Against Cervical Cancer Based on Network Pharmacology

A Comprehensive Understanding of the Anticancer Mechanisms of FDY2004 Against Cervical Cancer Based on Network Pharmacology

Strategy of Hepatic Metabolic Defects Induced by beclin1 Heterozygosity in Adult Zebrafish

The Relationship between Expression of p70s6k with Radiotherapy Response in Cervical Cancer

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