An In Vivo Evaluation of Docetaxel Delivered Intratumorally in Head and Neck Squamous Cell Carcinoma

Yoo, George H.; Subramanian, Geetha; Boinpally, Ramesh; Iskander, Andrew; Shehadeh, N. J.; Oliver, Jeffrey W.; Ezzat, Waleed H.; Piechocki, Marie P.; Ensley, John F.; Lin, Ho Sheng; Shibuya, Terry Y.; Polin, Lisa; Parchment, Ralph E.

doi:10.1001/archotol.131.5.418

Cited by 10 publications

(11 citation statements)

References 46 publications

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“…However, it does not rule out the possibility of paracrine contribution of T cells and other leukocytes. Until now, in vivo docetaxel treatment is thought to reduce tumor burden through direct cytotoxicity (41); however, in this study, we show an indirect immunomodulatory mechanism as well. As previously mentioned, MDSC accumulation has been correlated directly with tumor burden (8).…”

Section: Discussioncontrasting

confidence: 47%

A Novel Chemoimmunomodulating Property of Docetaxel: Suppression of Myeloid-Derived Suppressor Cells in Tumor Bearers

Kodumudi

Woan

Gilvary

et al. 2010

Clinical Cancer Research

442

304

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Purpose Myeloid-derived suppressor cells (MDSC) accumulate in tumor-bearing hosts and are associated with immune suppression. To date, there have only been few studies that evaluate the direct effect of chemotherapeutic agents on MDSCs. Agents that inhibit MDSCs may be useful in the treatment of patients with various cancers. Experimental Design We investigated the in vivo effects of docetaxel on immune function in 4T1-Neu mammary tumor-bearing mice to examine if a favorable immunomodulatory effect accompanies tumor suppression. Primary focus was on the differentiation status of MDSCs and their ability to modulate T-cell responses. Results Docetaxel administration significantly inhibited tumor growth in 4T1-Neu tumor-bearing mice and considerably decreased MDSC proportion in the spleen. The treatment also selectively increased CTL responses. Docetaxel-pretreated MDSCs cocultured with OT-II splenocytes in the presence of OVA323–339 showed OT-II–specific CD4 activation and expansion in vitro. In characterizing the phenotype of MDSCs for M1 (CCR7) and M2 [mannose receptor (CD206)] markers, MDSCs from untreated tumor bearers were primarily MR+ with few CCR7+ cells. Docetaxel treatment polarized MDSCs toward an M1-like phenotype, resulting in 40% of MDSCs expressing CCR7 in vivo and in vitro, and macrophage differentiation markers such as MHC class II, CD11c, and CD86 were upregulated. Interestingly, docetaxel induced cell death selectively in MR+ MDSCs while sparing the M1-like phenotype. Finally, inhibition of signal transducer and activator of transcription 3 may in part be responsible for the observed results. Conclusions These findings suggest potential clinical benefit for the addition of docetaxel to current immunotherapeutic protocols.

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Section: Discussioncontrasting

confidence: 47%

A Novel Chemoimmunomodulating Property of Docetaxel: Suppression of Myeloid-Derived Suppressor Cells in Tumor Bearers

Kodumudi

Woan

Gilvary

et al. 2010

Clinical Cancer Research

442

304

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“…Intratumoral chemotherapy focuses high drug concentrations in solid tumors and limits total body exposure to the cytotoxic agent, resulting in increased dose‐related killing of tumor cells at reduced, or at least equivalent, systemic toxic effects [Jackson et al, 2000]. Yoo et al [2005] found that intratumoral injection of taxol (15 mg/kg) inhibited growth of tumor by inducing apoptosis. Here, we found that intratumoral injection with 50 mg/kg of taxol not only prolonged life span without obvious side effect (Fig.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral injection of taxol in vivo suppresses A549 tumor showing cytoplasmic vacuolization

Wang

Chen

2012

J of Cellular Biochemistry

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Based on our recent in vitro studies, this report was designed to explore the mechanism by which high concentration of taxol (70 µM) induced paraptosis-like cell death in human lung carcinoma (A549) cells, and to evaluate the therapeutic efficacy of taxol using A549 tumor-bearing mice in vivo. Exposure of cells to taxol induced time-dependent cytotoxicity and cytoplasmic vacuolization without the involvement of Bax, Bak, Mcl-1, Bcl-XL, and caspase-3. Although taxol treatment induced activating transcription factor 6 (ATF6) cleavage indicative of endoplasmic reticulum (ER) stress, silencing ATF6 by shATF6 did not prevent taxol-induced both cytotoxcity and cytoplasmic vacuolization, suggesting that taxol-induced cytoplasmic vacuolization and cell death were not due to ER stress. Moreover, taxol-treated cells did not show DNA fragmentation and loss of mitochondrial membrane potential, the typical characteristics of apoptosis. In addition, taxol-induced cytoplasmic vacuolization did not show the cellular lysis, the characteristics of oncosis, and positive of β-galactosidase, the characteristic of senescence, indicating that taxol induced paraptosis-like cell death is neither oncosis nor senescence. Moreover, our in vivo data showed that intratumoral injection of taxol (50 mg/kg) in A549 tumor xenograft mice on day 1 and day 19 potently suppressed tumor growth showing significant ER vacuolization without toxicity. In conclusion, high concentration of taxol exhibits a significant anticancer activity by inducing paraptosis-like cell death in vitro and in vivo, without significant toxicity, suggesting a promising therapeutic strategy for apoptosis-resistance cancer by inducing ER vacuolization.

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“…Accordingly, the criterion of the efficient regimen of docetaxel treatment can be determined by comparing the tumor t D intraday to the time period from initiating therapy on time of dose delivery in the studied regimen. As described and conducted by several authors, Table 1 shows growth inhibition in tumors of different cell lines in murine experiments by docetaxel in different regimens [27][28][29][30][31][32][33][34].…”

Section: Effectiveness Of Docetaxel Treatment Assaymentioning

confidence: 99%

Optimal standard regimen and predicting response to docetaxel therapy

Moawad

2014

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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An In Vivo Evaluation of Docetaxel Delivered Intratumorally in Head and Neck Squamous Cell Carcinoma

Cited by 10 publications

References 46 publications

A Novel Chemoimmunomodulating Property of Docetaxel: Suppression of Myeloid-Derived Suppressor Cells in Tumor Bearers

A Novel Chemoimmunomodulating Property of Docetaxel: Suppression of Myeloid-Derived Suppressor Cells in Tumor Bearers

Intratumoral injection of taxol in vivo suppresses A549 tumor showing cytoplasmic vacuolization

Optimal standard regimen and predicting response to docetaxel therapy

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