Hyaluronic acid–paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts

Stefano, Ilaria De; Battaglia, Alessandra; Zannoni, Gian Franco; Prisco, Maria Grazia; Fattorossi, Andrea; Travaglia, Daniele; Baroni, Silvia; Renier, Davide; Scambia, Giovanni; Ferlini, Cristiano; Gallo, Daniela

doi:10.1007/s00280-010-1462-2

Cited by 51 publications

(33 citation statements)

References 34 publications

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“…Also in ovarian cancer, increased density of CD44 positive cells was associated with chemotherapy resistance [87], [88]. Interestingly, conjugates of Paclitaxel with the CD44 ligand hyaluronic acid were shown to be more effective in reducing tumour burden in implanted CD44 positive human ovarian carcinoma mouse models compared to free Paclitaxel [89], [90]. These data might suggest that by adding these conjugates to platinum-based chemotherapy, the CD44 positive (CIC) cells might be specifically targeted thereby decreasing CIC initiated relapses.…”

Section: Discussionmentioning

confidence: 99%

Ovarian Cancer Cell Line Panel (OCCP): Clinical Importance of In Vitro Morphological Subtypes

et al. 2014

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Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21), Round (n = 7) and Spindle (n = 12) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop specific treatment approaches for histological and molecular subtypes of ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Ovarian Cancer Cell Line Panel (OCCP): Clinical Importance of In Vitro Morphological Subtypes

et al. 2014

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“…Future experiments should therefore be aimed at improving the efficacy of the system by prolonging the residence time of NK105 in the peritoneal cavity, with the expectation that this will increase drug penetration into the nodules. Controlling drug release and absorption by hydrogel conjugation, (11,46) regulating peritoneal permeability by combination with bevacizumab, (47) molecular targeting or pH control release. (48)(49)(50) and other new strategies are promising methods that could be combined with intraperitoneal NK105.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effect and pharmacokinetics of intraperitoneal NK105, a nanomicellar paclitaxel formulation for peritoneal dissemination

et al. 2012

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The intraperitoneal administration of paclitaxel has been shown to be a promising treatment strategy for peritoneal malignancy. The present study evaluated the effects of intraperitoneal administration of NK105, a paclitaxel-incorporating micellar nanoparticle, which has been shown to have a remarkable effect in a mouse model of gastric cancer. Intraperitoneal NK105 significantly reduced peritoneal tumors in vivo compared with the conventional paclitaxel formulation of paclitaxel solubilized in Cremophor EL and ethanol (PTX-Cre). Moreover, intraperitoneal NK105 significantly reduced the size of subcutaneously inoculated tumors, whereas no such effect was seen with PTX-Cre. Similar systemic toxic effects were observed following the intraperitoneal administration of both NK105 and PTX-Cre. Although NK105 disappeared rapidly almost within a day from the peritoneal cavity, the paclitaxel concentration in peritoneal nodules 4 h after intraperitoneal administration was significantly higher in the NK105 group than in the PTX-Cre group (P < 0.05), whereas there were no significant differences in liver paclitaxel concentrations between the two groups. We also evaluated the pharmacokinetics following intraperitoneal administration of NK105 and PTX-Cre. Serum paclitaxel concentrations 6, 12, 24, and 48 h after the intraperitoneal administration of the drugs were significantly higher in the NK105 than the PTX-Cre group. Furthermore, the peak serum concentration was higher in the NK105 than PTX-Cre group (24 100 ± 3560 vs 108 ± 25 ng/mL, respectively; P < 0.001), as was the area under the concentration-time curve from 0 to 48 h (191 000 ± 32 100 vs 1500 ± 108 ngÁh/mL, respectively; P < 0.001). Therefore, intraperitoneal chemotherapy with nanoparticulate paclitaxel NK105 may offer a novel treatment strategy for improving drug delivery in gastric cancer with peritoneal dissemination because of enhanced drug penetration into peritoneal nodules and its prolonged presence in the systemic circulation. (Cancer Sci 2012; 103: 1304-1310 G astric cancer is the fourth leading cause of cancer-related deaths worldwide, and peritoneal dissemination is the most frequent and life-threatening form of metastasis and recurrence in patients with gastric cancer.(1,2) The current systemic chemotherapy regimens for gastric cancer have not achieved satisfactory results, particularly in the treatment of peritoneal dissemination.(3) One of the problems with this type of therapy is the limited delivery of systemically administered drugs to the peritoneal cavity.(4) Intraperitoneal chemotherapy has been shown to be safe and effective in ovarian cancer (5)(6)(7) and is expected to provide a breakthrough in the treatment of gastric cancer with peritoneal dissemination.(8-10) However, in addition to the intraperitoneal administration of drugs, it is necessary to develop new strategies for the treatment of gastric cancer to achieve better results. Research into drug delivery systems (DDS) is ongoing and is mostly aimed at improving the penetration of drugs...

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“…Finally, therapeutic agents or imaging agents can be rapidly released from HA-based nanomedicines into the tumor cell cytosol. mRNA levels or the enzymatic activity of HYALs have been elevated in ovarian and endometrial cancers, [34] prostate cancer, [35] bladder cancer, [36] colorectal carcinoma [37] and metastatic breast cancer. [38] Therefore, HYALs can be used as target enzymes to improve the drug delivery efficiency of HANPs.…”

Section: Tumor-targeting Mechanism Of Ha Nanoparticlesmentioning

confidence: 99%

Recent developments in hyaluronic acid-based nanomedicine for targeted cancer treatment

Rao

Yoon

Han

et al. 2015

Expert Opinion on Drug Delivery

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To develop a successful HA-based nanomedicine, it has to be prepared without significant deterioration of intrinsic property of HA. The chemical modification of HA with drugs or hydrophobic moieties may reduce the binding affinity of HA to the receptors. In addition, since the HA-based nanomedicines tend to accumulate in the liver after their systemic administration, new strategies to overcome this issue have to be developed.

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Hyaluronic acid–paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts

Cited by 51 publications

References 34 publications

Ovarian Cancer Cell Line Panel (OCCP): Clinical Importance of In Vitro Morphological Subtypes

Ovarian Cancer Cell Line Panel (OCCP): Clinical Importance of In Vitro Morphological Subtypes

Antitumor effect and pharmacokinetics of intraperitoneal NK105, a nanomicellar paclitaxel formulation for peritoneal dissemination

Recent developments in hyaluronic acid-based nanomedicine for targeted cancer treatment

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