Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy

Pusztai, Lajos; Mendoza, Tito R.; Reuben, James M.; Martinez, Monica M.; Willey, Jie; Lara, Jonathan F.; Syed, Abdul Rahman; Fritsche, Herbert A.; Bruera, Éduardo; Booser, Daniel J.; Valero, Vicente; Arun, Banu K.; Ibrahim, Nuhad K.; Rivera, Edgardo; Royce, Melanie; Cleeland, Charles S.; Hortobágyi, Gabriel N.

doi:10.1016/j.cyto.2003.10.004

Cited by 262 publications

(183 citation statements)

References 25 publications

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“…However, the finding of reduced levels of GM-CSF with increases in IL-8 in some patients and in IL-10 in others does support the hypothesis that some of the symptoms of CFS may be due to immune dysfunction within the central nervous system. A recent study showing elevations of IL-8 and IL-10 levels during chemotherapy-induced symptoms resembling some of those seen in CFS provides additional evidence for this hypothesis (19).…”

Section: Discussionmentioning

confidence: 81%

Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome

Natelson¹,

Weaver²,

Tseng

et al. 2005

Clin Vaccine Immunol

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Arguments exist as to the cause of chronic fatigue syndrome (CFS). Some think that it is an example of symptom amplification indicative of functional or psychogenic illness, while our group thinks that some CFS patients may have brain dysfunction. To further pursue our encephalopathy hypothesis, we did spinal taps on 31 women and 13 men fulfilling the 1994 case definition for CFS and on 8 women and 5 men serving as healthy controls. Our outcome measures were white blood cell count, protein concentration in spinal fluid, and cytokines detectable in spinal fluid. We found that significantly more CFS patients had elevations in either protein levels or number of cells than healthy controls (30 versus 0%), and 13 CFS patients had protein levels and cell numbers that were higher than laboratory norms; patients with abnormal fluid had a lower rate of having comorbid depression than those with normal fluid. In addition, of the 11 cytokines detectable in spinal fluid, (i) levels of granulocyte-macrophage colony-stimulating factor were lower in patients than controls, (ii) levels of interleukin-8 (IL-8) were higher in patients with sudden, influenza-like onset than in patients with gradual onset or in controls, and (iii) IL-10 levels were higher in the patients with abnormal spinal fluids than in those with normal fluid or controls. The results support two hypotheses: that some CFS patients have a neurological abnormality that may contribute to the clinical picture of the illness and that immune dysregulation within the central nervous system may be involved in this process.

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Section: Discussionmentioning

confidence: 81%

Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome

Natelson¹,

Weaver²,

Tseng

et al. 2005

Clin Vaccine Immunol

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“…Elucidation of the signaling networks that are differentially initiated by low concentrations or by high concentrations of paclitaxel and the verification of specific inhibitors against key molecules inside the networks may help us in developing a better chemotherapeutic strategy in treatment of ovarian cancer with paclitaxel. Practically, paclitaxel at doses higher than necessary may elicit unwanted upregulation of IL-6, which may induce adverse side effects of chemotherapy (Pusztai et al, 2004) and increase the chance of cancer cells developing drug resistances (Duan et al, 1999). Our understanding of the multiple paclitaxel dose-dependent signaling pathways involved in the upregulation of IL-6 is of clinical importance because these results suggest that fine-tuning the therapeutic concentrations of paclitaxel in patients may be crucial for avoiding undesired effects.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically for ovarian cancers, upregulation of IL-6 has been associated with pathogenesis (Hefler et al, 2003;Liu et al, 2004), tumor progression (Fang et al, 2004), antiapoptosis (Yusuf et al, 2003), drug resistance (Duan et al, 1999), patients' poor outcomes (Penson et al, 2000) and paclitaxel-related side effects (Pusztai et al, 2004). However, the regulatory mechanisms of IL-6 expression in ovarian cancer cells and paclitaxel activation of IL-6 remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathways

Chan

Chen

et al. 2006

Oncogene

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Paclitaxel (Taxol) is an antineoplastic agent that specifically targets microtubules and arrests cells at the G2/M phase of the cell cycle. In addition to mitotic arrest, the activation of c-Jun N-terminal kinase (JNK) signaling pathway has been demonstrated to be involved in the process leading to apoptosis. In an attempt to explore what genes are transcriptionally regulated by the activated JNK signaling pathway upon paclitaxel treatment, we used cDNA microarrays to analyse the changes of gene expression in human ovarian cancer cells that were treated with paclitaxel and/or the JNK inhibitor SP600125. Among 20 genes that were specifically regulated by the paclitaxel-activated JNK pathway, interleukin (IL)-6 was shown to elicit function through the JAK-STAT signaling pathway in an autocrine and/or paracrine fashion. Subsequently, we identified that 87.5% of eight tested ovarian cancer lines secreted detectable levels of IL-6, which could be further upregulated 2-3.2 fold by 1 lM paclitaxel. Dissection on regulatory pathways for IL-6 indicated that (i) when ovarian cancer cells were treated with paclitaxel at low but clinically achievable concentrations (exemplified by 1 lM in this study), the JNK signaling pathway was the major stimulator of IL-6 gene regulation and (ii) at suprapharmacologically high concentrations (exemplified by 50 lM), paclitaxel exerted lipopolysaccharide-like effects, most likely through the Toll-like receptor 4 signaling pathway. Collectively, these results suggest that paclitaxel upregulates functional IL-6 expression in human ovarian cancer cells through multiple signaling pathways.

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“…It is well known that chemotherapy induces activation of systemic inflammatory and immune responses [29][30][31]. Systemic inflammatory or immune response can be assessed by determining circulating cytokine concentrations, but sometimes marked fluctuations of cytokine concentrations may occur even within a short time frame.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant combination therapy with trastuzumab in a breast cancer patient with synchronous rectal carcinoma: a case report and biomarker study

et al. 2017

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Abstract:We report a patient who presented with synchronous second primary human epidermal growth factor receptor (HER)-2-positive breast cancer and rectal cancer that both required simultaneous neoadjuvant therapy. A modified regimen combining anti-HER-2 monoclonal antibody trastuzumab with chemotherapy and external beam radiation was selected. An organ-preserving surgical procedure was possible both in the breast and the rectum. Citrulline decreased rapidly after the start of the treatment, and then gradually returned to pre-treatment levels after the completion of chemoradiation. Urinary neopterin concentrations exhibited a fluctuating course. Both serum neopterin and C-reactive protein concentrations were more or less stable during the initial administration of trastuzumab, paclitaxel and carboplatin and then increased steeply during chemoradiation and subsequently declined to pre-treatment levels during the weekly trastuzumab administration. Changes were observed in the serum retinol concentrations. A decline in lymphocyte counts was accompanied by marked changes in peripheral blood cell count-derived ratios. The present case report demonstrates a successful combination of two neoadjuvant regimens in a patient with two synchronous different second primary tumors. Data from this case also illustrate the use of biomarkers for monitoring of intensive therapeutic regimens in medical and radiation oncology.

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Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy

Cited by 262 publications

References 25 publications

Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome

Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome

Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathways

Neoadjuvant combination therapy with trastuzumab in a breast cancer patient with synchronous rectal carcinoma: a case report and biomarker study

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