Fever-range whole body hyperthermia increases the number of perfused tumor blood vessels and therapeutic efficacy of liposomally encapsulated doxorubicin

Xu, Ye; Choi, Jong‐Soo; Hylander, Bonnie L.; Sen, Arindam; Evans, Sharon S.; Kraybill, William G.; Repasky, Elizabeth A.

doi:10.1080/02656730701666112

Cited by 33 publications

(34 citation statements)

References 61 publications

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“…Hyperthermia can potentially rapidly and significantly alter the tumor microenvironment-alterations in hypoxia [90,91], perfusion [92], and immunological function (as summarized in this review) likely play a role in the enhance survival noted in patients who receive combination treatments that include hyperthermia [93]. There are several known beneficial effects of hyperthermia in augmenting perfusion and oxygenation within tumors which very likely mediate positive responses to radiotherapy and chemotherapy [11,90,93]. As discussed earlier, the temperatures achieved in these studies can affect many normal cells in the tumor microenvironment, including cells of the immune system.…”

Section: Discussionmentioning

confidence: 94%

“…Classical paradigms suggest that hyperthermia (and in particular, temperatures over 42°C) has the ability to sensitize radioresistant tumor cells to apoptosis [9]. Hyperthermia also interferes with DNA damage repair [10], augments drug uptake into tumor cells and can reverse drug resistance [11,12]. However, there has long been appreciation in this field of the potential similarity between exogenously induced hyperthermia used in the clinic and natural hyperthermic states which occur during fever.…”

Section: Introductionmentioning

confidence: 97%

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Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

et al. 2009

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There is increasing documentation of significant survival benefits achieved in cancer patients treated with hyperthermia in combination with radiation and/or chemotherapy. Most evidence collected regarding the mechanisms by which hyperthermia positively influences tumor control has centered on in vitro data showing the ability of heat shock temperatures (usually above 42 degrees C) to result in radio- or chemosensitization. However, these high temperatures are difficult to achieve in vivo, and new thermometry data in patients reveal that much of the tumor and surrounding region is only heated to 40-41 degrees C or less as a result of vascular drainage from the target zone of the heated tumor. Thus, there is now a growing appreciation of a role for mild hyperthermia in the stimulation of various arms of the immune system in contributing to long term protection from tumor growth. Indeed, a review of recent literature suggests the existence of an array of thermally sensitive functions which may exist naturally to help the organism to establish a new "set point" of immune responsiveness during fever. This review summarizes recent literature identifying complex effects of temperature on immune cells and potential cellular mechanisms by which increased temperature may enhance immune surveillance.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 97%

Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

et al. 2009

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“…These include approaches that use tumor-priming agents that alter tumor vascular perfusion/permeability, interstitial pressure, or stromal properties to enhance deposition and efficacy of subsequently administered agents. Effectors of tumor-priming include cytotoxic drugs (GriffonEtienne et al, 1999;Lu et al, 2007), physical modulation of the tumor stromal matrix with enzymes such as collagenase or hyaluronidase (Eikenes et al, 2004(Eikenes et al, , 2005Provenzano et al, 2012), inhibitors of select signaling pathways (Tong et al, 2004;Olive et al, 2009), hyperthermia (Kong et al, 2000;Xu et al, 2007;Choe et al, 2011;Sen et al, 2011), and drug delivery vehicles (Zhou et al, 2002;Arnold et al, 2005;Baker et al, 2008;Cho and Kwon, 2011).…”

Section: Introductionmentioning

confidence: 99%

Systems Pharmacological Analysis of Paclitaxel-Mediated Tumor Priming That Enhances Nanocarrier Deposition and Efficacy

Ait‐Oudhia

Straubinger

Mager

2012

J Pharmacol Exp Ther

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Paclitaxel (PAC)-mediated apoptosis decompresses and primes tumors for enhanced deposition of nanoparticulate agents such as pegylated liposomal doxorubicin (DXR). A quantitative pharmacokinetic/pharmacodynamic (PK/PD) approach was developed to analyze efficacy and identify optima for PAC combined with sterically stabilized liposome (SSL)-DXR. Using data extracted from diverse literature sources, Cremophor-paclitaxel (Taxol ® ) PK was described by a carriermediated dispositional model and SSL-DXR PK was described by a two-compartment model with first-order drug release. A hybrid-physiologic, well-stirred model with partition coefficients (Kp) captured intratumor concentrations. Apoptotic responses driving tumor priming were modeled using nonlinear, time-dependent transduction functions. The tumor growth model used net first-order growth and death rate constants, and two transit compartments that captured the temporal displacement of tumor exposure versus effect, and apoptotic signals from each agent were used to drive cytotoxic effects of the combination. The final model captured plasma and intratumor PK data, apoptosis induction profiles, and tumor growth for all treatments/sequences. A feedback loop representing PAC-induced apoptosis effects on Kp _DXR enabled the model to capture tumor-priming effects. Simulations to explore time-and sequence-dependent effects of priming indicated that PAC priming increased K p_DXR 3-fold. The intratumor concentrations producing maximal and halfmaximal effects were 18 and 7.2 mg/ml for PAC, and 17.6 and 14.3 mg/ml for SSL-DXR. The duration of drug-induced apoptosis was 27.4 h for PAC and 15.8 h for SSL-DXR. Simulations suggested that PAC administered 24 h before peak priming could increase efficacy 2.5-fold over experimentally reported results. The quantitative approach developed in this article is applicable for evaluating tumor-priming strategies using diverse agents.

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“…While increases in vascular endothelial adhesion were obligatory for trafficking of cytotoxic T cells, this does not exclude the possibility that additional changes in vessel function or T cell fate occur as a consequence of thermal preconditioning of the tumor microenvironment. In this regard, STT reportedly increases tumor vessel permeability and reduces intratumoral interstitial fluid pressure, both of which could facilitate CD8 + T cell extravasation (41)(42)(43). Moreover, STT acting via IL-6 could theoretically influence T cell survival (known to be sensitive to IL-6/STAT3 signaling; ref.…”

Section: Discussionmentioning

confidence: 99%

IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells

Fisher¹,

Chen²,

Skitzki³

et al. 2011

J. Clin. Invest.

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Fever-range whole body hyperthermia increases the number of perfused tumor blood vessels and therapeutic efficacy of liposomally encapsulated doxorubicin

Cited by 33 publications

References 61 publications

Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

Systems Pharmacological Analysis of Paclitaxel-Mediated Tumor Priming That Enhances Nanocarrier Deposition and Efficacy

IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells

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