Histamine combined with melphalan in isolated limb perfusion for the treatment of locally advanced soft tissue sarcomas: preclinical studies in rats

Brunstein, Flávia; Santos, Ivan Dunshee de Abranches Oliveira; Ferreira, Lydia Masako; Tiel, Sandra T. van; Eggermont, Alexander; Hagen, Timo L.M. ten

doi:10.1590/s0102-86502005000400003

Cited by 4 publications

(2 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Limiting the distribution volume from the whole body to a leg or an arm, as is accomplished in isolated limb perfusion, could significantly improve tumor response and avoidance of amputation in patients with advanced melanoma or sarcoma, when melphalan was administered in combination with TNF-α, compared to treatment with melphalan alone [ 61 , 62 , 63 ]. Investigating the potential of TNF in isolated limb perfusion and the mechanisms behind this increased antitumor effect, we observed that the addition of TNF, as well as other vaso-active agents such as histamine or interleukin-2, caused local edema and hemorrhage, and by doing so caused more drug to accumulate in the tumor [ 64 , 65 , 66 , 67 , 68 ]. Angiograms taken before and after TNF-based ILP showed that tumor-associated vessels were specifically affected, while normal vessels remained intact [ 69 ].…”

Section: Augmentation Of Vascular Permeability By Tumor Necrosis Fact...mentioning

confidence: 99%

Liposomal Drug Delivery Systems for Cancer Therapy: The Rotterdam Experience

et al. 2022

View full text Add to dashboard Cite

At the Nanomedicine Innovation Center (NICE) at the Erasmus MC in Rotterdam, we have approached the treatment of cancer by starting with a vision of first establishing a platform that enables us to overcome the low levels of drugs delivered to tumors and the issue of dose-limiting toxicity. Showing that a reduction of the volume of distribution, and a lowering of toxicity and side-effects, accompanied by augmented intratumoral drug delivery, could change outcomes in patients, paved the way to target, not only localized disease, but also systemic and metastasized cancers. In particular, the detailed studies with intravital microscopy we performed at NICE provided us with the necessary insights and affected to a large extent our program on liposome-based cancer therapy. Together with our experience with the loco-regional treatment of cancer, this helped us to develop a program that focused on the subsequent aspects discussed here. We recognized that passive accumulation of nanoparticles was not as effective as previously believed and undertook to improve the local accumulation by changing the tumor pathophysiology and, in particular, the vascular permeability. We added the targeting of liposomes using vascular and tumor directed moieties, to improve cellular drug delivery. To improve payload delivery, we studied the modification of liposomes with phospholipids that help passive drug release and augment cellular accumulation. Second, and importantly, modification of liposomes was undertaken, to enable triggered drug release. The capability for modifying liposomes to respond to a trigger, and the ability to now apply an external trigger (e.g., hyperthermia) and specifically reach the tumor volume, resulted in the current smart drug delivery systems. Our experience at NICE, after a few decades of research on lipid-based nanoparticles, shows that, after the first liposomal formulation registered for clinical application in cancer therapy, further developments quickly followed, while further clinical applications lagged behind. Now we need to focus on and make the next steps towards the clinic, to fulfil the promise that is found there.

show abstract

Section: Augmentation Of Vascular Permeability By Tumor Necrosis Fact...mentioning

confidence: 99%

Liposomal Drug Delivery Systems for Cancer Therapy: The Rotterdam Experience

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Since systemic administration of TNF is highly toxic, Lejeune et al established a technique referred to as ILP, which facilitates local TNF administration [59]. ILP with TNF in combination with chemotherapeutic drugs led to complete response rates in patients [60] and showed improved penetrance of the cytostatic drugs melphalan and doxorubicin into tumours in animal models [61]. Interestingly, TNF specifically disrupts tumour supporting blood vessels while sparing normal blood vessels.…”

Section: Targeting Tnf‐r1mentioning

confidence: 99%

Death receptors as targets for anti‐cancer therapy

Papenfuss

Cordier

Walczak

2008

J Cellular Molecular Medi

View full text Add to dashboard Cite

Human tumour cells are characterized by their ability to avoid the normal regulatory mechanisms of cell growth, division and death. The classical chemotherapy aims to kill tumour cells by causing DNA damage-induced apoptosis. However, as many tumour cells posses mutations in intracellular apoptosis-sensing molecules like p53, they are not capable of inducing apoptosis on their own and are therefore resistant to chemotherapy. With the discovery of the death receptors the opportunity arose to directly trigger apoptosis from the outside of tumour cells, thereby circumventing chemotherapeutic resistance. Death receptors belong to the tumour necrosis factor receptor superfamily, with tumour necrosis factor (TNF) receptor-1, CD95 and TNF-related apoptosis-inducing ligand-R1 and -R2 being the most prominent members. This review covers the current knowledge about these four death receptors, summarizes pre-clinical approaches engaging these death receptors in anti-cancer therapy and also gives an overview about their application in clinical trials conducted to date.

show abstract