Quantity of mutant K-ras gene in pancreatic secretions for diagnosis of pancreatic carcinoma with different assays: analysis of 100 patients

Tada, Minoru; Tateishi, Keisuke; Kawabe, Takao; Sasahira, Naoki; Isayama, Hiroyuki; Komatsu, Yutaka; Shiratori, Yasushi; Omata, Masao

doi:10.1016/s0009-8981(02)00237-1

Cited by 17 publications

(8 citation statements)

References 19 publications

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“…However, qualitative analyses of DNA mutations are problematic because of the frequent presence of K-ras or p53 mutations in pancreatic intraepithelial neoplasias or hyperplastic duct (40 -42). It has been reported that quantitative analysis of Ras mutations is a useful strategy for diagnosis of pancreatic carcinoma (43). However, quantitation of DNA mutations merely reflects the component ratio of cells with mutations against cells without mutations, meaning that this is not a , and siRNA-K2 against S100A6 (c).…”

Section: Discussionmentioning

confidence: 99%

The Role of S100A6 in Pancreatic Cancer Development and Its Clinical Implication as a Diagnostic Marker and Therapeutic Target

Ohuchida¹,

Mizumoto²,

Ishikawa³

et al. 2005

Clinical Cancer Research

147

128

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Recent microarray analyses showed that the S100 family contains members that are candidate diagnostic markers or therapeutic targets. In the present study, to evaluate the involvement of S100A6 in pancreatic cancer and its clinical usefulness for diagnosis, we examined S100A6 mRNA expression in pancreatic tissues and pancreatic juice from patients with different pancreatic diseases. To investigate the role of S100A6 in carcinogenesis of pancreatic cancer and the potential of S100A6 as a diagnostic marker for early detection of pancreatic cancer, we did immunohistochemistry and microdissection-based mRNA analysis of pancreatic normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. We also used in vitro experiments and microarray analysis with RNA interference to evaluate the functional role of S100A6 and its potential as a therapeutic target for pancreatic cancer. S100A6 mRNA levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. In pancreatic juice, there was a significant difference in S100A6 expression between patients with carcinoma and those with nonneoplastic disease. Receiver operating characteristic curves revealed that S100A6 might be a useful marker for diagnosis of pancreatic cancer. Immunohistochemistry and microdissection-based analysis showed differential expression of S100A6 among normal ducts, pancreatic intraepithelial neoplasias, andinvasive ductal carcinomas. In vitro data showed that inhibition of S100A6 decreased proliferation and invasiveness of cancer cells, and these findings were supported by microarray data. Our present results suggest that quantitation of S100A6 mRNA is a promising tool for diagnosis of pancreatic cancer, and that S100A6 may be a promising therapeutic target for pancreatic cancer.Pancreatic cancer is the fifth most common cause of tumor-related deaths in the industrialized world (1, 2). Fewer than 10% to 20% of patients are candidates for surgery at the time of presentation, and <20% of patients who undergo curative resection are alive after 5 years (3, 4). Despite recent progress, there is no modality for early detection of pancreatic cancer. With the exception of a recent report describing successful use of adjuvant chemotherapy in the ESPAC-1 trial (5), there has been no report of effective treatment of advanced pancreatic cancer, including local and metastatic disease. To improve the prognosis of patients with pancreatic cancer, we need effective screening strategies and effective treatments for the disease once it has been detected.Microarray analysis allows simultaneous monitoring of the expression of thousands of genes and is a powerful tool for identifying genes associated with pancreatic carcinoma. Microarray analyses recently showed expression of S100A2 and S100A6 to be up-regulated in pancreatic cancer (6 -8). S100 family proteins are small Ca 2+ , Zn 2+ , and Cu 2+ binding proteins of the EF-hand type and have been implicated in regulation of a variety of intracellular and extracellular p...

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Section: Discussionmentioning

confidence: 99%

The Role of S100A6 in Pancreatic Cancer Development and Its Clinical Implication as a Diagnostic Marker and Therapeutic Target

Ohuchida¹,

Mizumoto²,

Ishikawa³

et al. 2005

Clinical Cancer Research

147

128

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“…Recently, a kit to quantitatively detect K-ras mutations, combining enriched PCR and ELMA, has been developed. The successful detection of K-ras mutations from pancreatic juice of patients with pancreatic cancer has been reported using this kit (Tada et al, 2002b). One of the technical problems with cytologic sampling from the uterine cavity using an endocyte device is the difficulty of completely avoiding any contamination by the uterine cervical cells.…”

Section: Discussionmentioning

confidence: 99%

K-ras mutation in the endometrium of tamoxifen-treated breast cancer patients, with a comparison of tamoxifen and toremifene

et al. 2005

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The putative presence of a mutation in codon 12 of the K-ras gene was investigated in the endometrium of tamoxifen (TAM) and toremifene (TOR)-treated breast cancer patients. DNA was extracted from fresh cytologic samples of the endometrium in 86 TAM and 21 TOR-treated breast cancer patients. Mutations were detected by enriched PCR and an enzyme-linked mini-sequence assay (ELMA). K-ras mutation was found in 35 TAM-treated endometrial samples, and in only one TOR-treated endometrium (Po0.003). In 24 premenopausal patients, K-ras mutation was found in seven (43.8%) of 16 patients with less than 47 months of TAM treatment, while none was found in eight patients with more than 48 months of TAM treatment (Po0.03). In 62 postmenopausal-amenorrheic patients, K-ras mutation was found in three (15.8%) of 19 patients with less than 23 months of TAM treatment, while it was found in 16 (61.5%) of 26 patients with 24 -47 months of TAM treatment and nine (52.9%) of 17 patients with more than 48 months of TAM treatment (P ¼ 0.002). The presence of K-ras mutation is significantly influenced by the duration of TAM treatment and menstrual status of the patients. TOR may have a lower potential genotoxicity than TAM.

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“…As shown in previous reports, both a pancreas harboring IPMN and a non-IPMN cyst can develop into a pancreatic ductal carcinoma distinct from the cystic lesions [4,7,13]. Additionally, a pancreatic cyst which is currently identified as a non-IPMN may develop into an IPMN in the future [4,[17][18][19][20]; therefore, both IPMNs and non-IPMN cysts should be followed up periodically even if they cannot be distinguished from each other.…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic curable pancreatic ductal carcinoma detected during the follow-up of pancreatic cysts distinct from carcinoma

Kawada

Uehara

Katayama

et al. 2011

Clin J Gastroenterol

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Recent studies have reported that pancreatic ductal carcinomas are frequently found during the follow-up of pancreatic cysts distinct from carcinoma; however, the majority of them are detected in advanced stages. Therefore, the early detection of metachronous ductal carcinomas is one of the issues in the management of pancreatic cysts. A 25-mm pancreatic cyst in the pancreatic head was found during an annual check-up in a 70-year-old woman. She was followed up every 6 months by abdominal ultrasound (US) and blood tests, and every 12 months by an additional magnetic resonance imaging scan. Twelve months later, abdominal US revealed a suspicious low-echoic area of 17 mm diameter in the pancreatic body. Eighteen months later, her serum carbohydrate antigen 19-9 level rose to 92 U/ml. Endoscopic retrograde pancreatography demonstrated a strictured main pancreatic duct (MPD) of 15 mm in length in the pancreatic body. A cytological examination of the brushed MPD revealed adenocarcinoma. The patient underwent distal pancreatectomy and splenectomy after chemoradiotherapy. An histological examination revealed a ductal carcinoma of 26 mm diameter in the pancreatic body, which was successfully resected. This case might help to establish an optimal surveillance method to detect metachronous ductal carcinomas arising from the pancreas harboring cystic lesions.

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Quantity of mutant K-ras gene in pancreatic secretions for diagnosis of pancreatic carcinoma with different assays: analysis of 100 patients

Cited by 17 publications

References 19 publications

The Role of S100A6 in Pancreatic Cancer Development and Its Clinical Implication as a Diagnostic Marker and Therapeutic Target

The Role of S100A6 in Pancreatic Cancer Development and Its Clinical Implication as a Diagnostic Marker and Therapeutic Target

K-ras mutation in the endometrium of tamoxifen-treated breast cancer patients, with a comparison of tamoxifen and toremifene

Asymptomatic curable pancreatic ductal carcinoma detected during the follow-up of pancreatic cysts distinct from carcinoma

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