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. 2012:2012:351750.
doi: 10.5402/2012/351750. Epub 2012 Jun 3.

H19-promoter-targeted therapy combined with gemcitabine in the treatment of pancreatic cancer

Vladimir Sorin  1 , Patricia Ohana, Jennifer Gallula, Tatiana Birman, Imad Matouk, Ayala Hubert, Michal Gilon, Avraham Hochberg, Abraham Czerniak
Affiliations

H19-promoter-targeted therapy combined with gemcitabine in the treatment of pancreatic cancer

Vladimir Sorin (V体育平台登录) et al. ISRN Oncol. 2012.

"VSports最新版本" Abstract

Pancreatic cancer is the eighth cancer leading cause of cancer-related death in the world and has a 5-year survival rate of 1-4% only. Gemcitabine is a first line agent for advanced pancreatic therapy; however, its efficacy is limited by its poor intracellular metabolism and chemoresistance. Studies have been conducted in an effort to improve gemcitabine treatment results by adding other chemotherapeutic agents, but none of them showed any significant advantage over gemcitabine monotherapy. We found that 85% of human pancreatic tumors analyzed by in situ hybridization analyses showed moderated to strong expression of the H19 gene. We designed a preclinical study combining gemcitabine treatment and a DNA-based therapy for pancreatic cancer using a non viral vector BC-819 (also known as DTA-H19), expressing the diphtheria toxin A chain under the control of the H19 gene regulatory sequences VSports手机版. The experiments conducted either in an orthotopic and heterotopic pancreatic carcinoma animal model showed better antitumor activity following the sequential administration of the vector BC-819 and gemcitabine as compared to the effect of each of them alone. The results presented in the current study indicate that treatment with BC-819 in combination with gemcitabine might be a viable new therapeutic option for patients with advanced pancreatic cancer. .

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Figures

Figure 1
Figure 1
Sequential administration of BC-819 and gemcitabine in a hamster orthotopic pancreatic carcinoma model. (a) Average of ex vivo tumor volume of the nontreated, gemcitabine, and BC-819 + gemcitabine treated groups measured after sacrifice (day 18). Asterisks indicate significant difference after BC-819 + gemcitabine compared with no treatment or gemcitabine alone (*P < 0.05, **P < 0.01, and ***P < 0.001). (b) Average of tumor growth progression of the nontreated, gemcitabine, and BC-819 + gemcitabine treated groups calculated as the ratio of tumor size at the end of the experiment (day 18) compared to the size before treatment (day 7).
Figure 2
Figure 2
Histopathology analyses in orthotopically induced tumors in the pancreas of hamsters treated either with Luc-H19 + gemcitabine (a) or BC-819 + gemcitabine. (b) The arrows in pictures (a) and (b) mark the necrotic area (X10 original magnification for picture). An extensive area of necrotic tissue it is clearly shown in the BC-819-gemcitabine-treated tumor only. Slides were prepared from paraffin block sections and stained with hematoxylin eosin.
Figure 3
Figure 3
Sequential administration of BC-819 and gemcitabine in a subcutaneous human pancreatic tumor in nude mouse model. and Confluent CRL-1469 human pancreatic carcinoma cells were injected subcutaneously into the back of athymic nude mice. After tumor development (30 days), three BC-819 administrations were performed, with a 2-day interval between each treatment, by direct injection into the tumor at days 0, 2, and 4. Mice were randomly divided into one of the following groups: control (glucose 5%), BC-819 alone, gemcitabine alone and BC-819 + gemcitabine. Average tumor growth progression of control (N = 7), BC-819 (N = 7), gemcitabine (N = 7), and BC-819 + gemcitabine (N = 7) groups comparing the tumor volume measured at the end of the experiment to the volume measured at the beginning.
Figure 4
Figure 4
The effect of sequential administration of BC-819 and gemcitabine on tumor progression and on the survival of a nude mice heterotopic pancreatic carcinoma model. Pancreatic carcinoma cells from hamster (PC1-0 cells) were injected subcutaneously into the back of athymic nude mice. After tumor development, 3 treatments of plasmid vectors were given, with a 2-day interval between each treatment, by direct injection into the tumor. Mice were randomly divided into 4 groups of 4 animals each and received the following treatments: Luc-H19 (control vector), BC-819, Luc-H19 + gemcitabine, BC-819 + gemcitabine. Mice were sacrificed when tumor reached a diameter larger than 13 mm. (a) Average tumor growth progression comparing the tumor volume measured after the last treatment to the volume measured before the first treatment. (b) Percentage of mice with a tumor diameter <13 mm as a function of time after the start of the treatment. The days or treatment are marked by arrows.
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References

    1. Rosewicz S, Wiedenmann B. Pancreatic carcinoma. Lancet. 1997;349(9050):485–489. - "VSports注册入口" PubMed
    1. Sanchez SE, Trevino JG. Current adjuvant and targeted therapies for pancreatic adenocarcinoma. Current Medicinal Chemistry. 2008;15(17):1674–1683. - PubMed
    1. Ohana P, Bibi O, Matouk I, et al. Use of H19 regulatory sequences for targeted gene therapy in cancer. International Journal of Cancer. 2002;98(5):645–650. - PubMed
    1. Ohana P, Schachter P, Ayesh B, et al. Regulatory sequences of H19 and IGF2 genes in DNA-based therapy of colorectal rat liver metastases. Journal of Gene Medicine. 2005;7(3):366–374. - PubMed
    1. Mizrahi A, Czerniak A, Levy T, et al. Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. Journal of Translational Medicine. 2009;7, article 69 - PMC - PubMed

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