Immunological Aspects of Photodynamic Therapy of Liver Tumors in a Rat Model for Colorectal Cancer¶

Duijnhoven, Frederieke van; Aalbers, Remco I.J.M.; Rovers, Jeroen; Terpstra, Onno T.; Kuppen, Peter J.K.

doi:10.1562/0031-8655(2003)078<0235:iaopto>2.0.co;2

Cited by 22 publications

(11 citation statements)

References 13 publications

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“…The use of CC531 colon carcinoma cells in tumor metastasis models has been evaluated in several studies [19][20][21][22][23][24]. It has been shown that CC531 cells injected into the vena mesocolica are a reliable tumor metastasis model.…”

Section: Discussionmentioning

confidence: 99%

Chemoembolisation of rat colorectal liver metastases with drug eluting beads loaded with irinotecan or doxorubicin

Eyol

Boleij

Taylor

et al. 2008

Clin Exp Metastasis

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Systemic chemotherapy has limited success in treating liver metastasis of colorectal cancer. Alternative approaches such as hepatic arterial infusion or trans arterial chemoembolisation aim to deliver the chemotherapy locally to address the predominant liver disease. Chemoembolisation with drug eluting beads (DEB) designed to deliver drug at the target over a protracted period of time is a new strategy to reduce the tumor burden of liver metastases. To test this hypothesis, DEB possessing anionic groups capable of ionically complexing with cationic drugs were synthesised by a suspension polymerisation method and were fractionated to produce an average size of 75 microm. The DEB were loaded with the desired concentration of either doxorubicin hydrochloride or irinotecan hydrochloride prior to administration by immersion in the drug solution, yielding essentially 100% loading efficiency. To determine their effect in vivo, a transplantable orthotopic and isogenic rat liver metastasis model was used which is based on intraportal injection of 4 x 10(6) beta-galactosidase transfected CC531 rat colorectal cancer cells into male WAG/Rij rats. By MTT assay, the cells were shown to be sensitive to both drugs in vitro with the IC(50) being by two orders of magnitude lower for doxorubicin (110 nM after 72 h) compared to irinotecan (25 microM after 72 h). For the in vivo phase, a differential expression of the ERK MAP kinase between tumor cells cultured in vitro and those inoculated in vivo was noted using Western blotting techniques. This was considered to be indicative of passage-induced cell senescence that reduced the sensitivity of the tumor cells to DEB chemoembolisation. This notwithstanding, administration of DEB loaded with irinotecan or doxorubicin by single injection into the hepatic artery showed significant anticancer activity, as measured by a reduction in the tumor burden of the liver and a corresponding reduction in liver weight. Comparing the two agents, irinotecan appears more advantageous because of its significant activity and excellent tolerability following administration at two dosages of either 20 or 30 mg/kg. Doxorubicin showed a narrower window of activity, being effective at 4 mg/kg but ineffective at the lower dose of 2 mg/kg. We conclude that chemoembolisation with DEB with either agent may have potential for treating patients with colorectal liver metastasis, although irinotecan DEB appeared to have a more favourable safety profile.

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Section: Discussionmentioning

confidence: 99%

Chemoembolisation of rat colorectal liver metastases with drug eluting beads loaded with irinotecan or doxorubicin

Eyol

Boleij

Taylor

et al. 2008

Clin Exp Metastasis

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“…An earlier study by our group confirmed the absent effect of PDT on the growth of established tumours. In this study, we also treated one out of two CC531 liver tumours with PDT and found that however effective, this treatment did not affect growth of nearby, untreated tumours [23], nor was there influx of macrophages or lymphocytes in these tumours. Both RFA and PDT of liver tumours increased resistance to local or systemic administration of tumour cells in suspension, but did not affect established tumours.…”

Section: Discussionmentioning

confidence: 78%

“…We used a rat colon carcinoma liver metastases model, CC531. We have extensive experience with this model, which has proven to be adequately reproducible [9,[21][22][23]. RFA and PDT were applied as local therapies and for regional therapy we used HAI with melphalan [24,25].…”

Section: Introductionmentioning

confidence: 99%

Locoregional Therapies of Liver Metastases in a Rat CC531 Coloncarcinoma Model Results in Increased Resistance to Tumour Rechallenge

Duijnhoven

Tollenaar

Terpstra

et al. 2005

Clin Exp Metastasis

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“…The mechanisms by which PDT can destroy tumors include (i) direct tumor cell killing 256 ; (ii) ROS-induced damage to the vascular system and deprivation of nutrients and oxygen to tumors 257,258 and (iii) immunosuppressive effects on the tumor. 259,260 Some of the most commonly used photosensitizing agents include porphyrins, chlorins and phthalocyanines. 261 Many photosensitizers exhibit poor solubility in water, which limits their application.…”

Section: Light-sensitive Micellesmentioning

confidence: 99%

Micellar Nanopreparations for Medicine

Sawant¹,

Jhaveri²

2014

Frontiers in Nanobiomedical Research

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Polymeric micelles are association core-shell colloidal carriers formed in aqueous media from self-assembling amphiphilic block-co-polymers, which have been studied and developed as drug carriers for the targeting of solid tumors. In this chapter, the polymeric micelles used for passive and active tumor targeting, for stimuli-sensitivity and multifunctionality are summarized. In the fi nal section, polymeric micelle formulations in clinical trials are discussed.

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Immunological Aspects of Photodynamic Therapy of Liver Tumors in a Rat Model for Colorectal Cancer¶

Cited by 22 publications

References 13 publications

Chemoembolisation of rat colorectal liver metastases with drug eluting beads loaded with irinotecan or doxorubicin

Chemoembolisation of rat colorectal liver metastases with drug eluting beads loaded with irinotecan or doxorubicin

Locoregional Therapies of Liver Metastases in a Rat CC531 Coloncarcinoma Model Results in Increased Resistance to Tumour Rechallenge

Micellar Nanopreparations for Medicine

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