Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas

Aridome, Kuniaki; Takao, Sonshin; Kaname, Tadashi; Kadomatsu, Kenji; Natsugoe, Shoji; Kijima, Fumio; Aikou, Takashi; Muramatsu, Takashi

doi:10.1038/bjc.1998.517

Cited by 39 publications

(25 citation statements)

References 22 publications

(22 reference statements)

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“…Expression of a truncated form of MK (t-MK) mRNA, which lacks exon 3 encoding the N terminus, has been well documented in various tumours, including colon (Miyashiro et al, 1996), breast (Miyashiro et al, 1997), gastric (Aridome et al, 1998), and liver and kidney (Tao et al, 2007). Therefore, we immunostained OSCC tissues with IP-14 antibody, which had an epitope in the C-terminus, and IP-10 antibody, which had an epitope in the N-terminus.…”

Section: Ip-10mentioning

confidence: 99%

Midkine as a prognostic biomarker in oral squamous cell carcinoma

et al. 2008

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The aim of this study was to evaluate serum midkine (S-MK) concentrations as a prognostic tumour marker in oral squamous cell carcinoma (OSCC). We measured S-MK concentrations in patients with OSCC and healthy volunteers. In addition, we performed real-time quantitative reverse transcription -PCR analysis and immunohistochemistry with fresh tumour samples. To determine whether S-MK concentrations have prognostic value, we performed survival analyses with clinical information by using the log-rank test. Serum midkine concentrations were significantly higher in patients with OSCC than in healthy controls (Po0.001). Serum midkine concentrations were also significantly increased in early-stage OSCC compared with those of healthy individuals (Po0.001). In addition, immunohistochemistry allowed identification of overexpressed MK protein in OSCC tissues. MK mRNA showed higher expression in OSCC samples compared with normal mucosal samples. Patients in high S-MK groups showed a significantly lower 5-year survival rate compared with patients in low S-MK groups (Po0.05). The increased S-MK concentrations in early-stage OSCC were strongly associated with poor survival. Serum midkine concentrations may thus be a useful marker not only for cancer screening but also for predicting prognosis of OSCC patients.

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Section: Ip-10mentioning

confidence: 99%

Midkine as a prognostic biomarker in oral squamous cell carcinoma

et al. 2008

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“…In the last few years, MK was found to be overexpressed in various human malignant tumours. Northern blot experiments revealed MK mRNA expression in gastric cancers (Aridome et al, 1995(Aridome et al, , 1998, colorectal cancers (Aridome et al, 1995(Aridome et al, , 1998Ye et al, 1999), urinary bladder cancer (O'Brien et al, 1996), neuroblastoma (Nakagawara et al, 1995), Wilm's tumour (Tsutsui et al, 1993), and astrocytoma (Mishima et al, 1997). Interestingly, MK mRNA was reported to be extensively expressed in the early stage of colon cancer carcinogenesis (Ye et al, 1999).…”

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confidence: 99%

Clinical significance of midkine expression in pancreatic head carcinoma

et al. 2007

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Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P ¼ 0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P ¼ 0.0073). Multivariate analysis revealed that MK expression was an independent prognostic factor (P ¼ 0.0033). This is the first report of an association between MK expression and pancreatic head carcinoma. Midkine may play an important role in the progression of pancreatic head carcinoma, and evaluation of MK expression is useful for predicting malignant properties of pancreatic head carcinoma.

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“…This conclusion agrees with reports about tMK expression in metastatic foci. 18 Our study showed that tMK expression is involved in tumor malignancy including resistance to anticancer agents. The expression of tMK may be a sign of malignancy and provide useful information for clinical chemotherapy.…”

Section: Discussionmentioning

confidence: 67%

Truncated midkine correlates with sensitivity to anticancer drugs and malignancy in human tumor cell line

Akuzawa

Nobata

Shinozawa

2006

Cell Biochemistry & Function

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Midkine (MK) is a heparin binding growth factor having functions of neurite-outgrowth, mitogenesis and tissue repair. This molecule is involved in tumor growth and metastasis. The MK molecule consists of five exons, but there is a truncated isoform, lacking exon 3. We established SW13 cells transfected with the human truncated MK cDNA. These cells were induced to undergo apoptosis by anticancer agents, cisplatin, etoposide (ETP), mitomycin C (MMC) and paclitaxel (PAX). Truncated midkine (tMK) suppressed cell death and helped the cells to be viable. When the cells were cultured on dishes coated with extracellular matrix molecules, spontaneous detachment occurred in the tMK expressing cells. Also tMK enhanced cell invasion. These results suggest that expression of tMK has cell-protective functions and plays important roles in carcinogenesis and malignancy. Furthermore, it is suggested that tMK has a greater ability of malignant transformation than full-length MK. Whether tMK is expressed or not will be useful information for improving cancer chemotherapy.

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Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas

Cited by 39 publications

References 22 publications

Midkine as a prognostic biomarker in oral squamous cell carcinoma

Midkine as a prognostic biomarker in oral squamous cell carcinoma

Clinical significance of midkine expression in pancreatic head carcinoma

Truncated midkine correlates with sensitivity to anticancer drugs and malignancy in human tumor cell line

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