Efficacy of gemcitabine conjugated and miRNA-205 complexed micelles for treatment of advanced pancreatic cancer

Mittal, Anupama; Chitkara, Deepak; Behrman, Stephan W.; Mahato, Ram I.

doi:10.1016/j.biomaterials.2014.04.053

Cited by 141 publications

(122 citation statements)

References 57 publications

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“…The authors proposed that reduced miR-23b levels increase levels of its target AGT12 and autophagy to promote radioresistance [98]. Treatment of cells with a combination of the tumor suppressor miR-205 and gemcitabine micelles reduced cell invasion and restored the gemcitabine chemosensitivity, while intratumoral injection of the combinatorial treatment in mice bearing gemcitabine-resistant xenografts potently arrested tumor growth [99].…”

Section: Mirnas Relate To Chemotherapy Treatment In Pdacmentioning

confidence: 99%

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

2016

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Pancreatic cancer is a devastating malignancy that ranks as the fourth leading cause of cancerrelated deaths worldwide. Dismal prognosis is mainly attributable to limited knowledge of the molecular pathogenesis of the disease. miRNAs have been found to be deregulated in pancreatic cancer, affecting several steps of initiation and aggressiveness of the disease by regulating important signaling pathways, such as the KRAS and Notch pathways. Moreover, the effect of miRNAs on regulating cell cycle events and expression of transcription factors has gained a lot of attention. Recent studies have highlighted the application of miRNAs as biomarkers and therapeutic tools. The current review focuses on latest advances with respect to the roles of miRNAs in pancreatic ductal adenocarcinoma associated signaling pathways and miRNA-based therapeutics. KEYWORDS• antisense oligonucleotides • miRNAs • pancreatic cancer Pancreatic cancer overview Pancreatic ductal adenocarcinoma (PDAC) is the predominant form of pancreatic neoplasms and accounts for greater than 85% of the clinical cases [1]. The disease develops via acinar-ductal metaplasia and neoplastic precursor lesions [2]. In the USA alone, 48,960 new cases of pancreatic cancer were expected to occur in 2015, with an estimated 40,560 deaths, about the same number in women (19,850) as in men (20,710). Over 96% are cancers arising from exocrine pancreas. Endocrine carcinomas are often diagnosed at a younger age and exhibit a better prognosis. From 2007 to 2011, mortality rates increased slightly by 0.3% per year. For all stages combined, the 1-and 5-year relative survival rates are 28 and 7%, respectively. For the small percentage of people diagnosed with local disease (9%), the 5-year survival is 26%, while more than half of patients (53%) are diagnosed at a late stage for which 1-and 5-year survival rates reach 15 and 2%, respectively [3]. These numbers are a staggering example of the poor prognosis associated with PDAC.While new therapeutic options are emerging for nonhematologic malignancies, molecular-targeted therapies for pancreatic cancer have failed to make any positive impact on patient survival. In 1993, the Nobel Prize-winning discovery of small interference RNAs (siRNAs) led to an outburst of knowledge on RNA interference and gene regulation [4]. Since then, thousands of research studies have described the functional role of small noncoding RNAs, named miRNAs, in a vast panel of human pathologies. In 2002, a small genomic region in chromosome 13q14 comprising miR-15a and miR-16-1 genes was found to be commonly deleted in chronic lymphocytic leukemia, For reprint orders, please contact: reprints@futuremedicine.com

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Section: Mirnas Relate To Chemotherapy Treatment In Pdacmentioning

confidence: 99%

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

2016

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“…Nanomedicines have unique advantages in overcoming tumor cell resistance to gemcitabine, and various types of gemcitabine nanomedicine formulations, such as micelles, 156 liposomes, 157 supramolecular vesicular aggregates, and nanovesicles, [158][159][160] have been shown to circumvent gemcitabine resistance. The general mechanisms by which gemcitabine nanomedicines overcome gemcitabine chemoresistance are discussed below.…”

Section: 155mentioning

confidence: 99%

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Chen¹,

Zheng²,

Shi³

et al. 2018

IJN

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Despite recent advances in targeted therapies and immunotherapies, chemotherapy using cytotoxic agents remains an indispensable modality in cancer treatment. Recently, there has been a growing emphasis in using nanomedicine in cancer chemotherapy, and several nanomedicines have already been used clinically to treat cancers. There is evidence that formulating small molecular cancer chemotherapeutic agents into nanomedicines significantly modifies their pharmacokinetics and often improves their efficacy. Importantly, cancer cells often develop resistance to chemotherapy, and formulating anticancer drugs into nanomedicines also helps overcome chemoresistance. In this review, we briefly describe the different classes of cancer chemotherapeutic agents, their mechanisms of action and resistance, and evidence of overcoming the resistance using nanomedicines. We then emphasize on gemcitabine and our experience in discovering the unique (stearoyl) gemcitabine solid lipid nanoparticles that are effective against tumor cells resistant to gemcitabine and elucidate the underlying mechanisms. It seems that lysosomes, which are an obstacle in the delivery of many drugs, are actually beneficial for our (stearoyl) gemcitabine solid lipid nanoparticles to overcome tumor cell resistance to gemcitabine.

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“…[101][102][103] Intratumoral administration of these polyplexes in xenografted mice resulted in a significant reduction in the growth rate and weight of tumors compared with that in the control groups and showed a high biocompatibility of the micelles in vivo. 104 Qian et al have synthesized new amphiphilic star-branched copolymers (PLA-PDMAEMA) for co-channeling of an inhibitor of miR-21 and doxorubicin into xenografts of glioma cells, leading to a significant synergistic inhibition of tumor growth 105 and demonstrating the potential of the therapeutic combination.…”

Section: Mirna and Chemoresistancementioning

confidence: 99%

Emerging role of microRNAs in the treatment of hepatocellular carcinoma

Callegari¹,

Domenicali²,

Gramantieri³

et al. 2015

GICTT

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Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide. Currently available curative options, such as surgery and transplantation, are not available to patients with advanced stages of disease. Among the potential new treatments being investigated are microRNA (miRNA)-based therapies. A number of preclinical studies have reported antitumor activities of miRNA mimics or anti-miRNA molecules. Optimal in vivo delivery of miRNA molecules is crucial to their action. To this end, significant progress has been made in the development of nanoparticles for in vivo delivery of miRNA molecules. Delivery of these molecules, alone or in combination with other drugs, promises to open new possibilities for therapeutic approaches to hepatocellular carcinoma.

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Efficacy of gemcitabine conjugated and miRNA-205 complexed micelles for treatment of advanced pancreatic cancer

Cited by 141 publications

References 57 publications

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Emerging role of microRNAs in the treatment of hepatocellular carcinoma

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