Morpholino antisense oligomer targeting human midkine: Its application for cancer therapy

Takei, Yoshiyuki; Kadomatsu, Kenji; Yuasa, Kanako; Sato, Waichi; Muramatsu, Takashi

doi:10.1002/ijc.20781

Cited by 33 publications

(21 citation statements)

References 36 publications

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“…In fact, various growth factors are reported to be overexpressed in many human tumours. Like other growth factors, MK is known to promote cell survival (Qi et al, 2000), cell growth (Takei et al, 2001(Takei et al, , 2005, and cell migration (Sato et al, 2001). These biological activities support the hypothesis that MK may involve in oncogenesis and tumour progression.…”

Section: Discussionmentioning

confidence: 80%

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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Section: Discussionmentioning

confidence: 80%

Clinical significance of midkine expression in pancreatic head carcinoma

et al. 2007

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“…10,11 In this study, to establish a new cancer therapy system based on blockading of the human MK gene, we adopted RNAi strategies. For the in vivo therapy study, we used atelocollagen as a carrier of siRNAs.…”

Section: Methodsmentioning

confidence: 99%

“…11,13 Cells were transfected with siRNAs in serum-free medium using LipofectAMINE PLUS (Invitrogen, Carlsbad, CA) as described previously. 13 Each conditioned medium was examined by Western blot analysis.…”

Section: Analysis Of Rnai Effectmentioning

confidence: 99%

Combinational antitumor effect of siRNA against midkine and paclitaxel on growth of human prostate cancer xenografts

Takei

Kadomatsu

Goto

et al. 2006

Cancer

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Background Many professional emergency responders (ERs) who belong to the Korean National Emergency Management Agency (NEMA) have been cross‐trained and serve multiple roles. As such, firefighters and other ERs in Korea are exposed to similar occupational hazards. This study was conducted to estimate cancer morbidity in male ERs and compare that with Korean men. Methods The cohort was comprised of 33,416 male ERs working between 1980 and 2007, who were alive on December 31, 1995. Work histories were merged with the Korea National Central Cancer Registry (KNCCR) to assess cancer morbidity between 1996 and 2007. Standardized incidence ratios (SIRs) with reference to Korean men were analyzed. Results SIRs with reference to national cancer rates were not significantly decreased for overall cancer (SIR = 0.97, 95% CI = 0.90–1.08) in all ERs. However, colorectal (SIR = 1.35, 95% CI = 1.07–1.67), kidney (SIR = 1.59, 95% CI = 1.00–2.41), and bladder (SIR = 1.77, 95% CI = 1.08–2.73) cancer, and non‐Hodgkin's lymphoma (SIR = 1.81, 95% CI = 1.12–2.76) morbidities were significantly increased among all ERs. In firefighters, significantly increased cancer types were as same as those of all ERs. In non‐firefighter ERs, colorectal (SIR = 2.51, 95% CI = 1.20–4.61) and bone and articular cartilage cancers (SIR = 9.53, 95% CI = 1.07–34.41) were significantly higher than those of Korean men. Conclusions Korean firefighters showed excess morbidity in several cancer types, including colorectal and urologic cancers, and non‐Hodgkin's lymphoma, demonstrating similar trends to previous studies for firefighters conducted in other countries. Increased incidence in these cancer types suggests occupational exposure to carcinogens and shift work. Am. J. Ind. Med. 55:768–778, 2012. © 2012 Wiley Periodicals, Inc.

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“…We and Ochiya's group previously showed the efficacy of atelocollagen for delivering nucleic acid compounds such as antisense oligodeoxynucleotides, [10][11][12] morpholino antisense oligomers, 13 and siRNAs, [14][15][16] especially in vivo. Atelocollagen, which is prepared from bovine dermis, 17,18 contributes to increases in cellular uptake, nuclease resistance and the prolonged release of siRNA, 14,[19][20][21] as well as plasmid DNA, 17 and antisense oligonucleotide compounds, 10,11,13,22 administered to tumors.…”

mentioning

confidence: 99%

“…Atelocollagen, which is prepared from bovine dermis, 17,18 contributes to increases in cellular uptake, nuclease resistance and the prolonged release of siRNA, 14,[19][20][21] as well as plasmid DNA, 17 and antisense oligonucleotide compounds, 10,11,13,22 administered to tumors. An siRNAatelocollagen complex also can be delivered via an intravenous injection route as nanoparticles, enabling systemic delivery of siRNAs.…”

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confidence: 99%

Systemic delivery of siRNA specific to tumor mediated by atelocollagen: Combined therapy using siRNA targeting Bcl‐xL and cisplatin against prostate cancer

Nagahara

Makita

et al. 2009

Intl Journal of Cancer

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The largest obstacle to the effective use of short interfering RNA (siRNA) in an animal body is the ability to deliver it to the target tissue. Here we showed a systemic delivery method of siRNA specific to pregrown solid tumors via atelocollagen. Atelocollagen facilitated the selective uptake of siRNA into the tumors when an siRNA/atelocollagen complex was administered intravenously to mice. We chose a Bcl‐xL protein as a model target to prove the therapeutic efficacy of the atelocollagen‐mediated method. Bcl‐xL acts as an anti‐apoptotic factor, which is overexpressed in many cancers, including prostate cancer. One of the four designed siRNAs to human Bcl‐xL potently inhibited the expression of Bcl‐xL by the PC‐3 human prostate cancer cell line in vitro, leading to cell apoptosis. Intravenous injections for3 consecutive days (siRNA, 100 μg/injection per day as a complex with atelocollagen) effectively downregulated Bcl‐xL expression in the PC‐3 xenograft. We administered four series of 3 consecutive days of intravenous injections each, for a total of 12 injections, which significantly inhibited tumor growth when the treatment was combined with cisplatin (2 mg/kg). Local injection of Bcl‐xL siRNA also potently inhibited tumor growth. All of the tumors treated with Bcl‐xL siRNA/atelocollagen complex via both intravenous and intratumoral injection showed terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling‐positive apoptosis. There were no severe side effects such as interferon‐α induction and liver or renal damage in mice. Our results indicate that systemic delivery of siRNA via atelocollagen, which specifically targets tumors, is safe and feasible for cancer therapy. © 2009 UICC

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Morpholino antisense oligomer targeting human midkine: Its application for cancer therapy

Cited by 33 publications

References 36 publications

Clinical significance of midkine expression in pancreatic head carcinoma

Clinical significance of midkine expression in pancreatic head carcinoma

Combinational antitumor effect of siRNA against midkine and paclitaxel on growth of human prostate cancer xenografts

Systemic delivery of siRNA specific to tumor mediated by atelocollagen: Combined therapy using siRNA targeting Bcl‐xL and cisplatin against prostate cancer

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