Overexpression of Forkhead Box M1 Transcription Factor (FOXM1) is a Potential Prognostic Marker and Enhances Chemoresistance for Docetaxel in Gastric Cancer

Okada, Kaoru; Fujiwara, Yoshiyuki; Takahashi, Tsuyoshi; Nakamura, Yurika; Takiguchi, Shuji; Nakajima, Kiyokazu; Miyata, Hiroshi; Yamasaki, Makoto; Kurokawa, Yukinori; Mori, Masaki; Doki, Yuichiro

doi:10.1245/s10434-012-2680-0

Cited by 89 publications

(68 citation statements)

References 29 publications

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“…Conversely, silencing of NPM expression sensitized hepatoma cells to doxorubicin, cisplatin, lapatinib, sorafenib and UV-B (16); thus suggesting that the inhibition of NPM may be considered a novel therapeutic strategy for cancer treatment. Human epidermal growth factor receptor-2 (Her-2) is a member of the epidermal growth factor receptor family of receptor tyrosine kinases, which have vital roles in the development and progression of various solid tumors, including gastric cancer (17). Since the downregulation of Her-2 was shown to promote the apoptosis of tumor cells (18), Her-2 is regarded as a potential target in breast and gastric cancer therapy.…”

Section: Downregulation Of Npm Expression By Her-2 Reduces Resistancementioning

confidence: 99%

Downregulation of NPM expression by Her-2 reduces resistance of gastric cancer to oxaliplatin

Sun

Shen

et al. 2017

Oncology Letters

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Abstract. Nucleophosmin (NPM) and human epidermal growth factor receptor-2 (Her-2) are abnormally expressed in various types of human malignant tumors, including gastric cancer, and have been closely associated with cancer chemoresistance. However, their interaction and roles in oxaliplatin resistance are not fully understood. Therefore, the present study aimed to elucidate the relationship between NPM and Her-2 in gastric cancer cell lines and clinical samples, and further investigated their role in the resistance of gastric cancer to oxaliplatin. Western blotting and reverse transcription-quantitative polymerase chain reaction confirmed that NPM and Her-2 expression were significantly upregulated in gastric cancer cells and clinical samples, and that their expression levels were strongly correlated. However, Her-2 expression was not affected by upregulation or downregulation of NPM expression in gastric cancer cells. Cell counting kit-8 assays demonstrated that the cell sensitivity to oxaliplatin decreased simultaneously with an increase in NPM expression. Furthermore, inhibition of Her-2 expression using trastuzumab significantly increased the sensitivity of the cells to oxaliplatin, which occurred simultaneously with the downregulation of NPM. These results indicated that inhibition of NPM, as a Her-2 downstream signal, may be a novel strategy to overcome oxaliplatin-resistant gastric cancer, and that trastuzumab and oxaliplatin may exhibit a synergistic antitumor effect in Her-2-positive gastric cancer cells.

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Section: Downregulation Of Npm Expression By Her-2 Reduces Resistancementioning

confidence: 99%

Downregulation of NPM expression by Her-2 reduces resistance of gastric cancer to oxaliplatin

Sun

Shen

et al. 2017

Oncology Letters

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“…Cellular proteins: Serum level of alpha-1-microglobulin/bikunin precursor (AMBP) protein, as well as increased expression of β-tubulin III protein, was demonstrated to predict lower chemotherapeutic response to paclitaxel-capecitabine schemes [91,92]; regenerating gene family member 4 (Reg IV or REG4) predicted resistance to 5-FU-based regimens [93]; forkhead box M1 (FOXM1) transcription factor seems to predict resistance to docetaxel [94]; and dysregulated ribosomal proteins were found to enhance vincristine, adriamycin, and 5-FU resistance [95].…”

Section: Protein Markersmentioning

confidence: 99%

Molecular Prognostic Factors in Gastric Cancer

Lazăr¹,

Tăban²,

Cornianu³

et al. 2017

Gastric Cancer

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Gastric cancer represents a major health problem worldwide. Literature data have demonstrated that gastric tumors present a high molecular heterogeneity, responsible for the process of carcinogenesis and dissemination. By revealing the molecular subtype of the tumor, it is possible to assess its behavior, the outcome of the patient, and the treatment approach, according to its genetic and epigenetic proile. This chapter aims to highlight some of the many diferent genetic mutations, epigenetic alterations, as well as aberrant signaling pathways involved in the pathogenesis of stomach cancers, each of these molecular abnormalities acting in a speciic stage of the disease. Moreover, the manuscript describes the novel therapeutic agents that target some of these aberrant molecular signaling pathways. Unfortunately, only a few agents are currently part of the standard treatment of gastric cancer, while most of the others remain to prove their therapeutic eicacy in the seting of clinical trials. By discovering the diferent molecular subtypes of gastric cancer, as well as numerous classes of targeted molecular agents, in the future, we would be able to perform an individualized treatment, associated with maximum eiciency and less costs.Keywords: gastric cancer, molecular classiication, gene expressions-based prognostic scoring system, molecular biomarkers, molecular targeted treatment IntroductionDespite a decline in the incidence in past decades, gastric cancer remains a major health problem globally [1,2], being the ifth most common type of cancer worldwide, with almost one million new cases estimated to have occurred in 2012, according to Globocan [3]. Furthermore, stomach cancer represents the third leading cause of cancer death in both sexes worldwide (723,000 deaths) [3].© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.According to the World Health Organization classiication, the vast majority of gastric cancers are adenocarcinomas, divided into papillary, tubular, mucinous (colloid), and poorly cohesive carcinomas (including signet-ring cell carcinoma and other variants) [4]. Although it was proposed a long time ago (1965), the Lauren classiication is still widely used in clinical practice and subdivides gastric carcinomas into intestinal and difuse types, associated with diferent pathogenesis, ways of spreading, and outcome [5]. Unfortunately, these two classiication systems have litle clinical impact, making the development of classiiers that can deine prognosis and guide patient's treatment as an urgent need.Literature data have demonstrated that the development of gastric cancer is associated in the majority of cases with infectious agents such as the Gram-negative spiral bacterium Helicobacter pylori (most often) [6] and Epstein-Barr virus (EBV) (about 9% o...

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“…We summarized the eligible studies that focused on the FoxM1 expression and prognosis by cox regression, the details of which were listed in Table 2 (Bektas et al, 2008;Li et al, 2009;Yang et al, 2009;Jiang et al, 2011;Priller et al, 2011;Sun et al, 2011a;2011b;Yu et al, 2011;Chu et al, 2012;He et al, 2012;Xia et al, 2012a;2012b;Xue et al, 2012;Li et al, 2013a;2013b;Okada et al, 2013;Wang et al, 2013a;2013b;Wu et al, 2013;Xu et al, 2013). Studies were eligible if they reported a risk estimate [e.g., hazard ratio (HR) or relative risk (RR) relating FoxM1 expression to subsequent death using survival analysis regression models], and they reported an estimate of precision, such as a standard error or 95%CI.…”

Section: Correlation Between Foxm1 Expression and Clinicopathologicalmentioning

confidence: 99%

FoxM1 as a Novel Therapeutic Target for Cancer Drug Therapy

Xu¹,

Miao²,

Wan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Overexpression of Forkhead Box M1 Transcription Factor (FOXM1) is a Potential Prognostic Marker and Enhances Chemoresistance for Docetaxel in Gastric Cancer

Cited by 89 publications

References 29 publications

Downregulation of NPM expression by Her-2 reduces resistance of gastric cancer to oxaliplatin

Downregulation of NPM expression by Her-2 reduces resistance of gastric cancer to oxaliplatin

Molecular Prognostic Factors in Gastric Cancer

FoxM1 as a Novel Therapeutic Target for Cancer Drug Therapy

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