Enhanced therapeutic effects for human pancreatic cancer by application K-ras and IGF-IR antisense oligodeoxynucleotides

Shen, Yongmei; Yang, Xiaochun; Chen, Yang; Shen, Junkang

doi:10.3748/wjg.14.5176

Cited by 14 publications

(9 citation statements)

References 21 publications

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“…These results suggest that a correlation exists between the expression status of IGFR1 and EGFR signaling, including the K-ras pathway (20,21). Shen et al reported that the combination of both K-ras and IGFR1 antisense oligodeoxynucleotide cooperatively inhibited the growth of pancreatic cancer cell lines in vitro, and induced their apoptosis in vivo (22). Furthermore, combined IGF-1 and K-ras analyses have been shown to be beneficial for the better selection of colorectal cancer patients that may respond to therapy (23).…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor receptor-1 expression predicts postoperative recurrence in adenocarcinoma of the lung

Nakagawa

Uramoto

Shimokawa

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers exist for either selecting appropriate candidates or for predicting clinical recurrence. The purpose of the present study was to clarify the clinical role of insulin-like growth factor receptor-1 (IGFR1) in lung adenocarcinoma. Tumor specimens were collected from 182 patients who underwent a complete resection for adenocarcinoma of the lung. The expression of IGFR1 was evaluated by immunohistochemistry. The genetic status of the epidermal growth factor receptor (EGFR) and K-ras genes was also investigated by PCR-based analyses. Immunohistochemistry and real-time PCR assays were used to evaluate the MET gene association with tyrosine phosphorylation and hepatocyte growth factor (HGF) status, and amplification, respectively. Positive expression of IGFR1 was detected in 43 (23.6%) of the 182 cases. A positive IGFR1 expression was also identified in 12 (42.9%) and 31 (20.1%) of the patients with and without recurrence, respectively (p=0.009). Logistic regression models indicated that positive staining for IGFR1 expression was an independent factor associated with tumor recurrence. IGFR1 expression was associated with a poorer disease-free survival (DFS). Multivariate analysis demonstrated positive IGFR1 expression to be independently associated with an increased risk for poor DFS. The tumors appearing positive for IGFR1 were more frequent among those with K-ras mutations when compared with the wild-type group. IGFR1 expression was associated with reduced DFS correlating with postoperative recurrence. Therefore, the expression status of IGFR1 can be a candidate surrogate marker to select patients who may benefit from adjuvant chemotherapy. IntroductionLung cancer is the leading cause of cancer-related death in the world (1). The incidence of adenocarcinoma, one of the major histological subtypes of non-small cell lung cancer (NSCLC), is increasing (2). The prognosis is dismal as the 5-year survival is only approximately 50%, even in patients who achieve complete surgical resection (3). This suggests that occult metastases are present at the time of surgical intervention. As a consequence, adjuvant chemotherapy is required (4). However, the 5-year survival rate of patients with resected stage IB NSCLC is 74% without adjuvant chemotherapy, suggesting that not all patients require chemotherapy after a complete resection (5). Therefore, it is necessary to identify patients who may benefit the most from post-operative adjuvant chemotherapy to, not only precisely select the patients who require additional treatment, but also to prevent the occurrence of adverse events in patients who do not require treatment (4). Therefore, it is important to evaluate the biological and molecular characteristics of lung adenocarcinoma to identify the factors related to recurrence following surgery. However, there are currently no useful markers that predict clinical recurrence.Insulin-like growth fa...

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Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor receptor-1 expression predicts postoperative recurrence in adenocarcinoma of the lung

Nakagawa

Uramoto

Shimokawa

et al. 2011

Experimental and Therapeutic Medicine

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“…KRAS codons 12 and 13 are also mutated in colorectal cancer (Cejas et al, 2009) and pancreatic cancer (Shen et al, 2008), among others. In targeted therapy for lung cancer, mutations in the KRAS gene arealso closely associated with clinical outcomes (Sung and Cho, 2008).…”

Section: Discussionmentioning

confidence: 99%

Expression of c-myc and mutation of the KRAS gene in patients with ovarian mucinous tumors

Li¹,

Sun²,

He³

2015

Genet. Mol. Res.

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ABSTRACT. We examined the expression of c-myc and mutations in the KRAS gene in ovarian mucinous tumors to explore the pathogenesis of these tumors and the feasibility of targeted gene therapy. Expression of c-myc protein and mutations in the KRAS gene in 24 cases of ovarian mucinous cystadenoma, 46 cases of ovarian borderline mucinous cystadenoma, and 46 cases of ovarian mucinous cystadenocarcinoma were detected using the immunohistochemistry PV-9000 2-step method and polymerase chain reaction-restriction fragment length polymorphism. The positive expression rates of c-myc in ovarian mucinous cystadenoma, borderline mucinous cystadenoma, and cystadenocarcinoma were 0, 39.1, and 65.2%, respectively (P < 0.01), while the mutation rates in KRAS were 0, 39.1 and 13.0%, respectively. The mutation rate of the borderline group was significantly higher, while rates in the other 2 groups were similar (P > 0.05). c-myc was not correlated with clinical stage, pathological grade, or age of patients with ovarian mucinous cystadenocarcinoma or borderline mucinous cystadenoma (P > 0.05), but was correlated with tumor size (P < 0.05). Mutations in KRAS were not correlated with clinical stage or tumor size in patients with borderline mucinous cystadenoma (P > 0.05), whereas it 10753 c-myc expression and KRAS mutation ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 10752-10759 (2015) was correlated with age (P < 0.05). In borderline mucinous cystadenoma, c-myc expression and KRAS mutations were not correlated (P > 0.05). c-myc is involved in the formation of ovarian borderline mucinous cystadenoma and mucinous cystadenocarcinoma, and the KRAS gene may contribute to the formation of borderline mucinous cystadenoma.

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“…Some researchers had reported that K-Ras gene mutation was usually identified in some endodermal tissues, such as pancreas, lung, colon and rectum (Quinlan et al, 2008;Li et al, 2009;Pu et al, 2011). Shen et al (2008) had identified a point mutation at codon 12 (GGTGTT) in the K-Ras gene. K-Ras antisense oligonucleotide could prevent proliferation and induce apoptosis of Patu8988 cells.…”

Section: Discussionmentioning

confidence: 99%

RNAi-induced K-Ras Gene Silencing Suppresses Growth of EC9706 Cells and Enhances Chemotherapy Sensitivity of Esophageal Cancer

Wang

Zheng²,

Fan³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Enhanced therapeutic effects for human pancreatic cancer by application K-ras and IGF-IR antisense oligodeoxynucleotides

Abstract: Abstract

Cited by 14 publications

References 21 publications

Insulin-like growth factor receptor-1 expression predicts postoperative recurrence in adenocarcinoma of the lung

Insulin-like growth factor receptor-1 expression predicts postoperative recurrence in adenocarcinoma of the lung

Expression of c-myc and mutation of the KRAS gene in patients with ovarian mucinous tumors

RNAi-induced K-Ras Gene Silencing Suppresses Growth of EC9706 Cells and Enhances Chemotherapy Sensitivity of Esophageal Cancer

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