Notch3 Overexpression as Potential Therapeutic Target in Advanced Stage Chemoresistant Ovarian Cancer

Rahman, Mohammed Tanjimur; Nakayama, Kentaro; Rahman, Munmun; Katagiri, Hiroshi; Katagiri, Atsuko; Ishibashi, Tatsuro; Ishikawa, Masatoshi; Iida, Kouji; Nakayama, Shinichi; Otsuki, Yoshiro; Miyazaki, Kohji

doi:10.1309/ajcpkdlrq8f3ewns

Cited by 62 publications

(52 citation statements)

References 19 publications

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“…It has also been reported that expression levels of Notch3 were increased in rat tracheal epithelial cells after treatment with 5-FU (20). NOTCH3 knockdown enhanced the sensitivity of nasopharyngeal carcinoma cells to CDDP treatment (21), and NOTCH3 overexpression correlated with shorter progressionfree/overall survival in patients with advanced stage ovarian carcinoma treated with platinum and taxane (22). In our data, NOTCH3 was upregulated in drug-resistant cells.…”

Section: Discussionsupporting

confidence: 80%

Alteration of gene expression and DNA methylation in drug-resistant gastric cancer

et al. 2014

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Abstract. The mechanisms of drug resistance in cancer are not fully elucidated. To study the drug resistance of gastric cancer, we analyzed gene expression and DNA methylation profiles of 5-fluorouracil (5-FU)-and cisplatin (CDDP)-resistant gastric cancer cells and biopsy specimens. Drug-resistant gastric cancer cells were established with culture for >10 months in a medium containing 5-FU or CDDP. Endoscopic biopsy specimens were obtained from gastric cancer patients who underwent chemotherapy with oral fluoropyrimidine S-1 and CDDP. Gene expression and DNA methylation analyses were performed using microarray, and validated using real-time PCR and pyrosequencing, respectively. Out of 17,933 genes, 541 genes commonly increased and 569 genes decreased in both 5-FU-and CDDP-resistant AGS cells. Genes with expression changed by drugs were related to GO term 'extracellular region' and 'p53 signaling pathway' in both 5-FU-and CDDP-treated cells. Expression of 15 genes including KLK13 increased and 12 genes including ETV7 decreased, in both drug-resistant cells and biopsy specimens of two patients after chemotherapy. Out of 10,365 genes evaluated with both expression microarray and methylation microarray, 74 genes were hypermethylated and downregulated, or hypomethylated and upregulated in either 5-FU-resistant or CDDP-resistant cells. Of these genes, expression of 21 genes including FSCN1, CPT1C and NOTCH3, increased from treatment with a demethylating agent. There are alterations of gene expression and DNA methylation in drug-resistant gastric cancer; they may be related to mechanisms of drug resistance and may be useful as biomarkers of gastric cancer drug sensitivity.

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Section: Discussionsupporting

confidence: 80%

Alteration of gene expression and DNA methylation in drug-resistant gastric cancer

et al. 2014

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“…The activation of Notch 1 signaling appears to sustain the motility, migration and invasion of tumor cells in esophagus squamous cell carcinomas, lingual squamous cell carcinoma, endometrial carcinoma and breast cancer (11)(12)(13)(14)(15). Almost all cases of T cell acute lymphoblastic leukemia (T-ALL), and colorectal, pancreatic and ovarian cancer have been reported to exhibit aberrant Notch 3 expression (6,8,16,17). Our previous study also reported that Notch 3 overexpression was associated with a poor prognosis in NSCLC patients (18).…”

Section: Introductionmentioning

confidence: 91%

“…In hematological malignancies, the role for Notch is well established, while more recent studies have demonstrated the significance of Notch activity in the initiation and progression of solid tumors (5)(6)(7)(8)(9). The mammalian Notch receptor family consists of four type I transmembrane receptors (known as Notch 1-4), all of which have been implicated in human cancer.…”

Section: Introductionmentioning

confidence: 99%

Notch signaling molecules as prognostic biomarkers for non-small cell lung cancer

Jin

Qian³

et al. 2015

Oncology Letters

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“…[62] Inactivation of Notch-3 by -secretase inhibitor (GSI) or short interference RNA (siRNA) decreased cell proliferation and induced apoptosis in the chemoresistant ovarian cancer cells. [63] Finally, Lu et al [64] have showed that the Notch-3 was positively correlated with Jagged-1 at the mRNA and protein levels. Therefore, they concluded that Notch-3 and Jagged-1 may play an important role in the initiation and proliferation of human nonfunctioning adenomas.…”

Section: Notch In Carcinogenesismentioning

confidence: 99%

Notch signaling in hepatocellular carcinoma: molecular targeting in an advanced disease

Sokolowski¹,

Balamurugan²,

Kunnimalaiyaan³

et al. 2015

Hepatoma Res

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The use of alternative therapeutic approaches in advanced carcinogenesis is a growing investigative base. One such cancer, primary liver cancer, is one of the most commonly occurring cancers worldwide and often presents in late stage disease consequently preventing traditional curative modalities. As a result, hepatocellular carcinoma (HCC), representing the majority of primary liver cancer, is the third most common cause of cancer-related deaths globally. Survival rates are linked to stage of presentation as well as concomitant cirrhosis limiting the 5-year survival in these patients to < 20%. Alternative strategies are in dire need as patients in this cohort have limited palliative options. Currently, sorafenib is the only approved systemic therapy; however, it has a limited survival advantage and low effi cacy prompting the empirical need for further evaluation. Understanding of cancer therapy has led to an enhanced focus on the Notch pathway as a potential target for advanced HCC. Notch signaling is a critical component of development and cell fate and has been linked to various modalities including liver regeneration and as a key driver in carcinogenesis. In this review, we will provide a review of the current status of the Notch signaling in liver cancer and of Notch as an alternative potential strategy for advanced HCC.

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Notch3 Overexpression as Potential Therapeutic Target in Advanced Stage Chemoresistant Ovarian Cancer

Cited by 62 publications

References 19 publications

Alteration of gene expression and DNA methylation in drug-resistant gastric cancer

Alteration of gene expression and DNA methylation in drug-resistant gastric cancer

Notch signaling molecules as prognostic biomarkers for non-small cell lung cancer

Notch signaling in hepatocellular carcinoma: molecular targeting in an advanced disease

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