Gao M, Sun J, Jin W, Qian Y [6]

Th1 and Th2 cells, levels of INF-γ, IL-2, IL-4 and T-bet and GATA3 activities increased significantly after incubation with PMA and ionomycin. However, the number of Th₁, Th₁/Th₂ cells, INF-γ and INF-γ/IL-4 levels and activities/levels of T-bet and GATA3 were decreased after incubation with PMA and ionomycin in the presence of morphine. Naloxone can abolish the suppressive effect of morphine in the differentiation of Th cells. Morphine has a negative effect in the Th cell balance induced by PMA and ionomycin, the mechanism is related to T-bet and GATA3.

Shakhar G, Ben-Eliyahu S [7]

Minimizing postoperative immunosuppression seems feasible, it can limit tumor recurrence and should be considered when planning oncologic surgeries. In the short term, doctors could try to avoid immunosuppressive anesthetic approaches, inadvertent hypothermia, excessive blood transfusions and untreated postoperative pain. When possible, minimally invasive surgery should be considered. Long term clinical trials should evaluate prophylactic measures, including perioperative immunostimulation and various antagonists of cytokines and hormones specified herein.

Page G, Ben-Eliyahu S, Yirmiya R, Liebeskind J [8]

The results support the hypothesis that activity suppression of NK cells mediates increasing surgically induced metastatic colonization. Besides, an analgesic dose of morphine blocked the surgery-induced increase in metastasis without affect metastasis in unoperated animals. These findings suggest that postoperative pain is a critical factor in promoting metastatic spread. If a similar relationship between pain and metastasis occurs in humans, pain control must be considered a vital component of postoperative care.

Forget P, Collet V, Lavand'homme P, De Kock M [9]

Surgery, analgesics and coexisting conditions influence cellular immunity significantly. The importance of these changes varies with time. Fentanyl had a worse influence than clonidine and ketamine, but it seemed equally protective against the development of metastases.

Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S [10]

This study in a mouse model of lung metastasis demonstrates that some anesthetics increase the tumor metastasis susceptibility, apparently by suppressing the natural killer cell activity. Ketamine was more deleterious and its effects were prevented by peripheral blockade of the beta-adrenoceptors combined with low levels of immunostimulation.

Kim R [11]

Local anesthetics such as lidocaine increase the activity of NK cells. Anesthetics such as propofol and locoregional anesthesia, which decrease neuroendocrine responses induced by surgery through the HPA axis and the suppression of the SNS, can cause less immunosuppression and recurrence of certain types of cancer compared to volatile anesthetics and opioids.

De Kock M, Loix S, Lavand'homme P [12]

Ketamine appears as a unique "homeostatic regulator" of acute inflammatory reaction and stress induced immune disorders. This is of some interest at a time when short- and long-term deleterious consequences of inappropriate inflammatory disorders reactions are increasingly reported. However, large scale studies showing improvement in patient outcome, are needed before definitively asserting the clinical reality of this positive effect.

Chang Y, Chen TL, Sheu JR, Chen RM [13]

This study shows that a clinically relevant concentration of ketamine [100 microM] may suppress macrophage function of phagocytosis, its oxidative capacity and inflammatory cytokine production, possibly by reducing the mitochondrial membrane potential rather than direct cell toxicity.

Blandino-Rosano M, Barbaresso R, Jimenez-Palomares M, Bozadjieva N, Werneck-de-Castro JP [14]

Rapamycin treatment decreases CPE expression and Insulin secretion in mice and human pancreatic islets. We suggest an important role of mTORC1 in β-cells and we have identified the downstream pathways that lead to β-cell mass, the function and processing of insulin.

 Shapiro J, Jersky J, Katzav S, Feldman M, Segal S [15]

Current experiences indicate that the anesthetic drugs used during surgical excision of two tumors from different mice can cause a significant increase in metastatic propagation and progression. These drugs also caused the dissemination of metastases to organs in which metastases were not found. The possibility of similar phenomena of metastatic acceleration occurring in other mice tumor systems or in other mammals, or with other anesthetics, requires further study.

 Kim R, Emi M, Tanabe K [16]

In fact, not just the modulation of cell death induced by anticancer drugs, but also the activation of antitumor immune responses using molecularly targeted drugs such as antibodies and small molecules, may provide a remarkable increase of chemotherapeutic effects in cancer therapy. More studies are needed on cellular and molecular mechanisms to contribute to anti-tumor immune responses.

 Bar-Yosef S, Melamed R, Page GG, Shakhar G, Shakhar K, et al. [17]

Adding spinal block to general anesthesia with halothane markedly attenuates the promotion of metastases by surgery.

 Melamed R, Rosenne E, Shakhar K, Schwartz Y, Abudarham N, et al. [18]

The findings point to possible prophylactic measures in cancer patients undergoing surgery and suggest a role for MP-NK cells in resistance to metastasis of apparently insensitive tumors.

Shakhar G, Abudarham N, Melamed R, Schwartz Y, Rosenne E, et al. [19]

MP-NK cells are unique in their ability to kill apparently immunoresistant tumor. Low doses of synthetic ds-RNA and potentially Th₁ cytokines may expand this MP-NK population and protect it from immunosuppression. The news of such a prophylactic approach is to direct the immediate postoperative period, which is characterized by high vulnerability to residual disease, and to protect critical anti-metastatic immunity against postoperative suppression. The use of such an intervention potentially innocuous in cancer patients who are preparing for surgery might reduce metastatic recurrence.

Le Cras AE, Galley HF, Webster NR [20]

Spinal anesthesia may result in less immunosuppression after surgery. The study found that the proportion of T help cells 1 for T help cells 2 was higher in patients undergoing prostate surgery under spinal anesthesia instead of general anesthesia. Th₁ cells promote protective immune responses that may result in fewer postoperative infections.

 Angele MK, Faist E [21]

Although significant advances have been made, it is important to better define the pathophysiology and identify the mechanisms responsible for cell mediated immunity depression using experimental animal models. The effective treatments regimen may be developed only when injury models begin to consider them as factors.

Ben-Eliyahu S, Page GG, Yirmiya R, Shakhar G [22]

The results indicate that the stress-induced suppression of NKA is enough to cause tumor intensified development. Under certain stressful conditions, the suppression of NKA is the primary mediator increasing the tumor, while in other conditions, additional factors play a significant role. The clinical circumstances in which surgical stress can induce increased metastatic growth are discussed.

 Staudt LM [23]

Various oncogenic abnormalities in epithelial cancers, including mutant K-ras, involve non conventional IkappaB kinases to activate NF-kappaB. The inhibition of constitutive NF-kappaB signaling in each of these cancers induces apoptosis, justifying the development of NF-kappaB pathway inhibitors for cancer treatment.

 He H, Chen J, Xie WP, Cao S, Hu HY, et al. [24]

The findings provide new insight into the effects of ketamine in cancer treatment; we suggest that ketamine, which has been widely used in cancer surgeries and for pain relief in patients with chronic cancer, may not be the best choice because it may worsen cancer through anti-apoptosis promotion.