Weekly systemic cisplatin plus locoregional hyperthermia: An effective treatment for patients with recurrent cervical carcinoma in a previously irradiated area

Franckena, Martine; Wit, Ronald de; Ansink, Anca C.; Notenboom, Annelise; Canters, R.; Fatehi, Daryoush; Rhoon, Gerard C. van; Zee, Jacoba van der

doi:10.1080/02656730701549359

Cited by 35 publications

(26 citation statements)

References 31 publications

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“…This provides a possible explanation for hyperthermia's sensitising effects towards irradiation and chemotherapeutic compounds that induce double strand breaks, such as cisplatin [34,35] and Trabectedin [36]. Moreover, attenuation of HR by hyperthermia sensitises cultured cells and mouse tumours to PARPinhibitors [19,[37][38][39], a class of therapeutics that specifically target cells deficient in HR.…”

Section: Discussionmentioning

confidence: 99%

Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies

Tempel

Odijk

Holthe

et al. 2017

International Journal of Hyperthermia

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Purpose: Hyperthermia (40-44 C) effectively sensitises tumours to radiotherapy by locally altering tumour biology. One of the effects of heat at the cellular level is inhibition of DNA repair by homologous recombination via degradation of the BRCA2-protein. This suggests that hyperthermia can expand the group of patients that benefit from PARP-inhibitors, a drug exploiting homologous recombination deficiency. Here, we explore whether the molecular mechanisms that cause heat-mediated degradation of BRCA2 are conserved in cell lines from various origins and, most importantly, whether, BRCA2 protein levels can be attenuated by heat in freshly biopted human tumours. Experimental design: Cells from four established cell lines and from freshly biopsied material of cervical (15), head-and neck (9) or bladder tumours (27) were heated to 42 C for 60 min ex vivo. In vivo hyperthermia was studied by taking two biopsies of the same breast or cervical tumour: one before and one after treatment. BRCA2 protein levels were measured by immunoblotting. Results: We found decreased BRCA2-levels after hyperthermia in all established cell lines and in 91% of all tumours treated ex vivo. For tumours treated with hyperthermia in vivo, technical issues and intra-tumour heterogeneity prevented obtaining interpretable results. Conclusions: This study demonstrates that heat-mediated degradation of BRCA2 occurs in tumour material directly derived from patients. Although BRCA2-degradation may not be a practical biomarker for heat deposition in situ, it does suggest that application of hyperthermia could be an effective method to expand the patient group that could benefit from PARP-inhibitors. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies

Tempel

Odijk

Holthe

et al. 2017

International Journal of Hyperthermia

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“…More recently, the cisplatin resistance reduction was also observed in several studies including phase I/II and III clinical trials. These studies concluded that the combination of cisplatin and hyperthermia, eventually accompanied by radiotherapy, has a great impact on the response rate and toxicity [159,[181][182][183][184].…”

Section: Biologic Rationale For Hyperthermia In Combination With Chemmentioning

confidence: 99%

In situ forming implants for local chemotherapy and hyperthermia of bone tumors

Mohamed

Borchard

Jordan

2012

Journal of Drug Delivery Science and Technology

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Hyperthermia, an established adjuvant in cancer treatment, potentiates the effects of anticancer drugs and synergetic combination can be obtained improving the therapeutic outcome. Bone metastases may benefit from this combination when treated through in situ forming implants. Once loaded with magnetizable (nano-) particles and antineoplastic agents, these implants allow for the local application of magnetically-induced hyperthermia and the release of an anticancer drug. The implant can be heated applying an external magnetic field, sensitizing the surrounding tumoral tissues, while releasing the chemotherapeutic agent.Moreover, bone implants provide mechanical support to the weakened bone and consequently relieve pain.This review gives an overview of the current knowledge as well as the rationale of combining locally both magnetic hyperthermia and chemotherapy using in situ forming implants in the field of bone metastases treatment. KeywordsInduced hyperthermia, chemotherapy, drug delivery systems, in situ forming implants, iron oxide nanoparticles, bone metastases, cementoplasty, vertebroplasty 3

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“…Clinical tests have shown that hyperthermia combined with chemotherapy has increased efficacy against tumors such as high-grade soft tissue sarcomas. 31 In our experiment, when combined with hyperthermia therapy, FA-DOX-BSA MNPs had a greater effect on cell viability and inhibited NPC cells significantly (a four-fold increase in cytotoxicity versus DOX-BSA MNPs). 2.…”

Section: Antitumor Effect Of Fa-dox-bsa Mnps In Vivomentioning

confidence: 85%

Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo

Yang¹,

Miao³

et al. 2014

IJN

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Background This study aimed to generate targeted folic acid-conjugated, doxorubicin-loaded, magnetic iron oxide bovine serum albumin nanospheres (FA-DOX-BSA MNPs) that lower the side effects and improve the therapeutic effect of antitumor drugs when combined with hyperthermia and targeting therapy. A new nanodrug using magnetic nanospheres for heating and addition of the folate receptor with cancer cell specificity was prepared. The characteristics of these nanospheres and their antitumor effects in nasopharyngeal carcinoma were explored. Methods FA-DOX-BSA MNPs comprising encapsulated magnetic iron oxide nanoparticles were prepared using a desolvation cross-linking method. Activated folic acid (N-hydroxysuccinimide ester of folic acid) was conjugated to the surface of albumin nanospheres via amino groups. Results Folic acid was successfully expressed on the surface of the nanospheres. Electron microscopy revealed that the FA-DOX-BSA MNPs were nearly spherical and uniform in size, with an average diameter of 180 nm. The nanomaterial could deliver doxorubicin at clinically relevant doses with an entrapment efficiency of 80%. An increasing temperature test revealed that incorporation of magnetic iron oxide into nanospheres could achieve a satisfactory heat treatment temperature at a significantly lower dose when placed in a high-frequency alternating magnetic field. FA-DOX-BSA MNPs showed greater inhibition of tumors than in the absence of folic acid in vitro and in vivo. Compared with chemotherapy alone, hyperthermia combined with chemotherapy was more effective against tumor cells. Conclusion Folic acid-conjugated bovine serum albumin nanospheres composed of mixed doxorubicin and magnetic iron oxide cores can enable controlled and targeted delivery of anticancer drugs and may offer a promising alternative to targeted doxorubicin therapy for nasopharyngeal carcinoma.

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Weekly systemic cisplatin plus locoregional hyperthermia: An effective treatment for patients with recurrent cervical carcinoma in a previously irradiated area

Abstract: CDDP + HT results in a high response rate and acceptable toxicity in patients with recurrent cervical cancer.

Cited by 35 publications

References 31 publications

Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies

Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies

In situ forming implants for local chemotherapy and hyperthermia of bone tumors

Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo

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