Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis

Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia

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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1105-1113
Number of pages9
JournalAnnals of Surgical Oncology
Volume20
Issue number4
Early online date2 Mar 2013
DOIs
Publication statusPublished - Apr 2013

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Heat-Shock Proteins
Fever
Carcinoma
Drug Therapy
Neoplasms
Poisons
Apoptosis
Therapeutics
Gene Expression
Gastrointestinal Neoplasms
Colonic Neoplasms
Proteins
Cell Proliferation
Temperature

Cite this

Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis : Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia. / Pelz, Joerg O. W. ; Vetterlein, Malte; Grimmig, Tanja; Kerscher, Alexander G.; Moll, Eva; Lazariotou, Maria; Matthes, Niels; Faber, Marc Nicolas; Germer, Christoph-Thomas; Waaga-Gasser, Ana Maria; Gasser, Martin.

In: Annals of Surgical Oncology, Vol. 20, No. 4, 04.2013, p. 1105-1113.

Research output: Contribution to journalArticle

Pelz, JOW, Vetterlein, M, Grimmig, T, Kerscher, AG, Moll, E, Lazariotou, M, Matthes, N, Faber, MN, Germer, C-T, Waaga-Gasser, AM & Gasser, M 2013, 'Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis: Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia', Annals of Surgical Oncology, vol. 20, no. 4, pp. 1105-1113. https://doi.org/10.1245/s10434-012-2784-6
Pelz, Joerg O. W. ; Vetterlein, Malte ; Grimmig, Tanja ; Kerscher, Alexander G. ; Moll, Eva ; Lazariotou, Maria ; Matthes, Niels ; Faber, Marc Nicolas ; Germer, Christoph-Thomas ; Waaga-Gasser, Ana Maria ; Gasser, Martin. / Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis : Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia. In: Annals of Surgical Oncology. 2013 ; Vol. 20, No. 4. pp. 1105-1113.
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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.",
author = "Pelz, {Joerg O. W.} and Malte Vetterlein, and Tanja Grimmig, and Kerscher, {Alexander G.} and Eva Moll, and Maria Lazariotou, and Niels Matthes, and Faber, {Marc Nicolas} and Christoph-Thomas Germer, and Waaga-Gasser,, {Ana Maria} and Martin Gasser,",
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T1 - Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis

T2 - Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia

AU - Pelz, Joerg O. W.

AU - Vetterlein,, Malte

AU - Grimmig,, Tanja

AU - Kerscher, Alexander G.

AU - Moll,, Eva

AU - Lazariotou,, Maria

AU - Matthes,, Niels

AU - Faber, Marc Nicolas

AU - Germer,, Christoph-Thomas

AU - Waaga-Gasser,, Ana Maria

AU - Gasser,, Martin

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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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