Vagotomy enhances experimental metastases of 4THMpc breast cancer cells and alters Substance P level

Erin, Nuray; Barkan, Gueliz Akdas; Harms, John F.; Clawson, Gary A.

doi:10.1016/j.regpep.2008.03.012

Cited by 58 publications

(48 citation statements)

References 40 publications

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“…Thus, because this region responds to peripheral inflammation, it may also respond to tumor-associated inflammation. A recent study has described a relationship between vagotomy and breast cancer metastases to the lungs and other regions (10). The increase in substance P associated with the presence of a malignant tumor and with vagotomy may reflect an increase in tumor-associated inflammation, with inflammation and pain being strongly linked.…”

Section: Discussionmentioning

confidence: 99%

“…However, chemical and surgical vagotomy prevents tumorassociated anorexia in mice (9) and enhances the metastasizing rate of peripheral malignant tumors (10). In view of these studies, it has been hypothesized that the vagus (and potentially other neural routes) may provide signals about the presence of malignancy-related inflammation to the brain with possible subsequent modulation of tumorigenesis (2,11).…”

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confidence: 99%

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Brain Mapping of Patients with Lung Cancer and Controls: Inquiry into Tumor-to-Brain Communication: FIGURE 1.

Golan¹,

Kennedy²,

Frenkel³

et al. 2009

J Nucl Med

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Recent converging evidence suggests that the brain may receive stimuli and possibly modulate tumor progression via the vagus nerve. The present study aimed to compare brain metabolism in patients with and without lung cancer and to assess if significant differences exist in regions associated with the vagus nerve. Methods: Eighteen patients with lung malignancy and 19 controls underwent 18 F-FDG PET of the brain. Brain metabolism was compared using statistical parametric mapping. Results: Patients with lung malignancy showed a statistically significantly higher right cerebellar metabolism. Conclusion: This finding may be related to the role of the cerebellum in immune regulation, because of its proximity to the nucleus tractus solitarius innervated by the vagus and its connections with the hypothalamus. This higher metabolism in the right cerebellum may reflect an attempt to reinstate homeostasis in functions such as respiration and immunity pertinent to lung malignancy. Cancer research has shifted from solely focusing on genetic aspects and defining the intracellular etiology of tumorigenesis to also assessing interactions between tumors and their microenvironment (1). Furthermore, there is increasing interest in assessing the potential presence of bidirectional links between peripheral malignant tumors and the brain, in the form of tumor-to-brain communication and modulation (2).The inflammatory microenvironment plays a crucial role early during tumorigenesis (3,4) and later for angiogenesis and tumor invasion (5). The brain receives signals from peripheral inflammatory processes by several routes, including the vagus (6), through interleukin-1 receptors on its paraganglia. There are conflicting reports on the rate of cancer-related death in vagotomized ulcer patients (7,8). However, chemical and surgical vagotomy prevents tumorassociated anorexia in mice (9) and enhances the metastasizing rate of peripheral malignant tumors (10). In view of these studies, it has been hypothesized that the vagus (and potentially other neural routes) may provide signals about the presence of malignancy-related inflammation to the brain with possible subsequent modulation of tumorigenesis (2,11).The present study aimed to examine brain metabolism in patients with lung malignancy, addressing most of the limitations of prior studies (12-15). Most patients included in the study were evaluated because of pulmonary nodules detected on CT. Both patients and physicians were unaware of the final diagnosis with respect to the presence of active malignancy at the time of imaging, which was performed before any treatment. MATERIALS AND METHODS Patients and Control SubjectsEighteen patients with lung malignancy and 19 controls were included. The malignancy group consisted only of newly diagnosed, histologically proven cases of cancer and included 16 patients with non-small cell lung cancer ( The control group comprised a subgroup of 8 patients with lymphoma in remission for at least 4 y (the LymC group), including Hodgkin lymphoma (n 5 2, s...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Brain Mapping of Patients with Lung Cancer and Controls: Inquiry into Tumor-to-Brain Communication: FIGURE 1.

Golan¹,

Kennedy²,

Frenkel³

et al. 2009

J Nucl Med

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show abstract

“…It may be that vagal nerve activity is also affected by cancer (De Couck and Gidron, unpublished data). However, two experimental studies in mice showed that vagotomy or capsaicin-induced denervation enhanced cancer metastasis (47,48), demonstrating experimentally the protective effects of the vagus nerve on cancer progression. Furthermore, a recent study found an anti-inflammatory drug that activates the vagus nerve (CNI-1493) to reduce tumor burden in a breast cancer murine model (49).…”

Section: Discussionmentioning

confidence: 99%

The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients

Couck¹,

Brummelen²,

Schallier³

et al. 2013

Oncology Reports

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Abstract. Recent studies suggest that vagal nerve activity, indexed by heart rate variability (HRV), could have a prognostic role in cancer. However, most studies did not control adequately for confounders and included cardiac patients. Furthermore, the validity of this prognostic role needs to be tested in different types of cancer. The present study tested the prognostic role of HRV in prostate cancer (PC) and non-small cell lung cancer (NSCLC) patients, using a historical prospective design. HRV was derived from brief 10 sec ECGs obtained at approximately the time of diagnosis in 113 PC patients and 133 NSCLC patients. Outcomes included prostate-specific antigen (PSA) at 6 and 24 months in PC, and overall survival (OS) (for the full sample) and survival time (for the deceased patients) in NSCLC. Furthermore, the possible mediating role of C-reactive protein (CRP) was tested (in NSCLC), as well as whether age and stage moderated the relationship between HRV and prognosis in both types of cancer. In the PC patients, HRV significantly inversely predicted PSA levels at 6 and 24 months, independent of confounders. Furthermore, this was particularly significant in metastatic PC patients, indicating moderation by stage. In NSCLC patients, HRV did not predict OS and survival time, but it did positively predict survival time in patients under the age of 65, independent of confounders. Additionally, CRP was not found to mediate the relationship between HRV and OS or survival time in NSCLC. The present results partly support previous studies and extend them to two additional common types of cancer, using a more rigorous control over confounders. Together with recent experimental findings, these results propose a modulatory role of vagal nerve activity in cancer. Therefore, routine measurement of HRV in estimating prognosis in cancer may be considered.

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“…However, the literature shows conflicting results. Although some studies have shown that NK1 antagonists or inhibition of SP decrease tumour growth [49][50][51], almost an equal number of studies have shown that SP inhibits tumour growth through its stimulatory effects on the immune system [52][53][54][55].…”

Section: Introductionmentioning

confidence: 99%

NK1 receptor antagonists and dexamethasone as anticancer agents in vitro and in a model of brain tumours secondary to breast cancer

et al. 2013

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Emend, an NK1 antagonist, and dexamethasone are used to treat complications associated with metastatic brain tumours and their treatment. It has been suggested that these agents exert anticancer effects apart from their current use. The effects of the NK1 antagonists, Emend and N-acetyl-L-tryptophan, and dexamethasone on tumour growth were investigated in vitro and in vivo at clinically relevant doses. For animal experiments, a stereotaxic injection model of Walker 256 rat breast carcinoma cells into the striatum of Wistar rats was used. Emend treatment led to a decrease in tumour cell viability in vitro, although this effect was not replicated by N-acetyl-L-tryptophan. Dexamethasone did not decrease tumour cell viability in vitro but decreased tumour volume in vivo, likely to be through a reduction in tumour oedema, as indicated by the increase in tumour cell density. None of the agents investigated altered tumour cell replication or apoptosis in vivo. Inoculated animals showed increased glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 immunoreactivity indicative of astrocytes and microglia in the peritumoral area, whereas treatment with Emend and dexamethasone reduced the labelling for both glial cells. These results do not support the hypothesis that NK1 antagonists or dexamethasone exert a cytotoxic action on tumour cells, although these conclusions may be specific to this model and cell line.

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Vagotomy enhances experimental metastases of 4THMpc breast cancer cells and alters Substance P level

Cited by 58 publications

References 40 publications

Brain Mapping of Patients with Lung Cancer and Controls: Inquiry into Tumor-to-Brain Communication: FIGURE 1.

Brain Mapping of Patients with Lung Cancer and Controls: Inquiry into Tumor-to-Brain Communication: FIGURE 1.

The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients

NK1 receptor antagonists and dexamethasone as anticancer agents in vitro and in a model of brain tumours secondary to breast cancer

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