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01-04-2013 | Regional Cancer Therapies

Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis: Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia

Authors: Joerg O. W. Pelz, MD, Malte Vetterlein, MD, Tanja Grimmig, MSc, Alexander G. Kerscher, MD, Eva Moll, BSc, Maria Lazariotou, PhD, Niels Matthes, MD, Marc Faber, BSc, Christoph-Thomas Germer, MD, Ana Maria Waaga-Gasser, PhD, Martin Gasser, MD

Published in: Annals of Surgical Oncology | Issue 4/2013

Abstract

Background

In patients with isolated peritoneal carcinomatosis (PC) of gastrointestinal cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment option integrated into multimodal concepts. Heat shock proteins (HSP) seem to play a major role in cellular stress during HIPEC therapy. We analyzed differentially hyperthermic conditions and HSPs responsible for cell stress–mediated repair mechanisms in tumor tissues from patients who underwent HIPEC therapy and in an in vitro hyperthermic model.

Methods

Tumor tissues from our patient cohort with isolated PC were selected for further analysis when representative material was available before and after HIPEC therapy. To further dissect the role of HSPs under conditions of hyperthermia, gene and protein expression was additionally determined, together with cellular apoptosis and proliferation in human HT-29 colon cancer cells.

Results

Differently up-regulated HSP70/72 and HSP90 gene and protein expression was found in all investigated patient tumors. In vitro studies confirmed observations from clinical tumor analysis as underlying HSP-mediated cell stress mechanisms. Moreover, results from proliferation and apoptosis assays combined with differentiated HSP expression analysis demonstrated the relevance of preselecting specific target temperatures to achieve optimal toxic effects on remaining tumor cells in vivo.

Conclusions

Therapeutic approaches like HIPEC to achieve antiproliferative and apoptosis-inducing cellular effects in patients with PC are negatively influenced by highly conserved HSP mechanisms in tumor cells. This study shows for the first time that specific hyperthermic conditions are necessary to be established to achieve optimal toxic effects on tumor cells during HIPEC therapy, a finding that opens potentially new therapeutic strategies.

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Title: Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis: Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia
Authors: Joerg O. W. Pelz, MD
Malte Vetterlein, MD
Tanja Grimmig, MSc
Alexander G. Kerscher, MD
Eva Moll, BSc
Maria Lazariotou, PhD
Niels Matthes, MD
Marc Faber, BSc
Christoph-Thomas Germer, MD
Ana Maria Waaga-Gasser, PhD
Martin Gasser, MD
Publication date: 01-04-2013
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 4/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-012-2784-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis: Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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