Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion

Sakaguchi, Hirozo; Ishida, Hideyuki; Nitanda, Hiroyuki; Yamazaki, Nobuhiro; Kaneko, Koji; Kobayashi, Kunihiko

doi:10.1016/j.lungcan.2016.12.015

Cited by 18 publications

(18 citation statements)

References 13 publications

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“…On the basis of these preliminary results, we believe that nanoparticles represent a promising approach for the development of a highly effective local treatment for MPM, because they allow us to directly address malignant cells and deliver high level of drugs over a sustained period of time, while sparing normal cells. Approaches of intrapleural drug delivery have been described in the literature, [37][38][39] including Pe loaded nanoparticles 40 but, to our knowledge, we have shown for the first time that specific targeting of MPM cells by nanoparticles is feasible and effective. Furthermore, CD146 targeting offers the possibility of new approaches that could be translated to the treatment of other cancers or metastasis affecting the pleural or peritoneal space.…”

Section: Discussionmentioning

confidence: 88%

Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: In-vitro study

Stella¹,

Cova²,

Inghilleri³

et al. 2015

11.2 Pleural and Mediastinal Malignancies

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Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth. Methods: MPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry). Results: GNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization. Conclusion: GNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.

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Section: Discussionmentioning

confidence: 88%

Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: In-vitro study

Stella¹,

Cova²,

Inghilleri³

et al. 2015

11.2 Pleural and Mediastinal Malignancies

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show abstract

“…In this respect it has been shown the existence of inactivated T lymphocytes in the peritoneal cavity that can be induced to become [36,37]. Finally we think that this technique can also be useful in other serous membranes tumors like those in the pericardial and pleural cavities that in general have poor prognosis [38,39].…”

Section: Discussionmentioning

confidence: 89%

Preclinical studies for a cationic liposome formulation containing Il-2 Intended for the treatment of Human Tumors

Corona-Ortega¹

2018

Arch Pharm Pharma Sci

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Human cervical cancer tumours expressing the IL-2 receptor (IL-2R) were induced in the peritoneal cavity of nude mice. The tumours were signifi cantly reduced by the i.p. administration of either free IL-2 or liposomes containing this growth factor. No toxicity was observed in the mice even at the highest doses of IL-2 in liposomes. We did not detect any IL-2 in the blood plasma pointing to a strong retention of the liposomes on the cavity. We concluded that this preclinical study for the treatment of tumours expressing IL-2R in the peritoneal cavity is effective and safe. The liposomes were stable and their IL-2 active for up to one year when kept at-14 o C in a cryopreservation media approved by the FDA for human use.

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Section: Discussionmentioning

confidence: 90%

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

Cova

Pandolfi

Colombo

et al. 2019

IJN

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PurposeMalignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.MethodsMPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).ResultsGNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.ConclusionGNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.

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Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion

Abstract: IPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion.

Cited by 18 publications

References 13 publications

Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: In-vitro study

Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: In-vitro study

Preclinical studies for a cationic liposome formulation containing Il-2 Intended for the treatment of Human Tumors

<p>Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study</p>

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